The Color Atlas of Internal Medicine [1st ed.] 0071772383, 9780071772389, 9780071772396

Table of contents :
Title
......Page 4
Copyright......Page 5
Contents
......Page 8
Preface
......Page 16
Part 1 Learning with Images and Digital Photography
......Page 20
1 An Atlas to Enhance Patient Care, Learning, and Teaching
......Page 21
Part 2 Issues in Internal Medicine
......Page 24
2 Doctor-Patient Relationship
......Page 25
3 Family Planning
......Page 29
4 End of
Life......Page 33
5 Social Justice
......Page 42
6 Global Health......Page 51
Part 3 Physical and Sexual Abuse
......Page 68
7 Intimate Partner Violence......Page 69
8 Sexual Assault
......Page 74
Part 4 Ophthalmology
......Page 80
9 Pterygium......Page 81
10 Hordeolum and Chalazion......Page 84
11 Scleral and Conjunctival Pigmentation......Page 87
12 Corneal Foreign Body and Corneal Abrasion
......Page 91
13 Conjunctivitis......Page 94
14 Scleritis and Episcleritis......Page 99
15 Uveitis and Iritis......Page 103
16 Glaucoma......Page 106
17 Diabetic Retinopathy......Page 109
18 Hypertensive Retinopathy......Page 112
19 Papilledema......Page 115
20 Age-Related Macular Degeneration......Page 118
21 Eye Trauma—Hyphema......Page 122
22 Differential Diagnosis of the Red Eye
......Page 125
Part 5 Ear, Nose, and Throat
......Page 130
23 Otitis Media: Acute Otitis and Otitis
Media with Effusion......Page 131
24 Otitis Externa
......Page 138
25 Ear: Foreign Body
......Page 142
26 Chondrodermatitis Nodularis Helicis and
Preauricular Tags......Page 145
27 Nasal Polyps
......Page 149
28 Sinusitis......Page 152
29 Angular Cheilitis
......Page 157
30 Torus Palatinus......Page 160
31 Pharyngitis......Page 162
32 The Larynx (Hoarseness)
......Page 168
Part 6 Oral Health
......Page 174
33 Black Hairy Tongue......Page 175
34 Geographic Tongue......Page 178
35 Gingivitis and Periodontal Disease......Page 181
36 Gingival Overgrowth
......Page 185
37 Aphthous Ulcer......Page 188
38 Leukoplakia......Page 193
39 Oropharyngeal Cancer
......Page 196
40 Adult Dental Caries......Page 200
Part 7 Cardiovascular
......Page 204
41 Aortic Aneurysm......Page 205
42 Atrial Fibrillation......Page 212
43 Clubbing......Page 225
44 Heart Failure
......Page 228
45 Coronary Artery Disease......Page 231
46 Deep Venous Thrombosis......Page 234
47 Bacterial Endocarditis
......Page 239
48 Hypertension......Page 244
49 Pericarditis and Pericardial Effusion
......Page 247
50 Peripheral Arterial Disease......Page 251
51 Venous Insufficiency
......Page 258
Part 8 Hematology
......Page 262
52 Iron Deficiency Anemia
......Page 263
53 B12 Deficiency
......Page 267
54 Sickle Cell Disease......Page 273
Part 9 Pulmonary
......Page 278
55 Asthma and Pulmonary Function Testing......Page 279
56 Chronic Obstructive Pulmonary Disease......Page 288
57 Lung Cancer......Page 297
58 Pleural Effusion
......Page 305
59 Community-Acquired Pneumonia
......Page 309
60 Pneumothorax......Page 315
61 Pulmonary Embolism......Page 318
62 Pulmonary Fibrosis......Page 325
63 Sarcoidosis......Page 329
64 Tuberculosis......Page 335
Part 10 Gastrointestinal
......Page 344
65 Clostridium Difficile Infection
......Page 345
66 Colon Cancer......Page 348
67 Colon Polyps......Page 354
68 Diverticulitis......Page 359
69
Gallstones......Page 363
70 Gastric Cancer......Page 368
71 Gastroesophageal Reflux Disease (GERD)
......Page 373
72 Hemorrhoids......Page 377
73 Ischemic Colitis......Page 381
74 Liver Disease......Page 384
75 Acute Pancreatitis......Page 392
76 Peptic Ulcer Disease......Page 396
77 Inflammatory Bowel Disease
......Page 400
Part 11 Genitourinary/Renal
......Page 408
78 Bladder Cancer......Page 409
79 Hydronephrosis......Page 414
80 Kidney Stones......Page 417
81 Nephrotic Syndrome......Page 421
82 Polycystic Kidneys......Page 425
83 Prostate Cancer......Page 429
84 Renovascular Hypertension......Page 434
85 Renal Cell Carcinoma......Page 9
86 Chronic Kidney Disease......Page 445
87 Urinary Sediment......Page 448
Part 12 Women's Health
......Page 452
88 Overview of
Vaginitis......Page 453
89 Atrophic Vaginitis......Page 456
90 Bacterial Vaginosis......Page 460
91 Candida Vulvovaginitis......Page 464
92 Trichomonas Vaginitis......Page 469
93 Chlamydia Cervicitis......Page 473
94 Mastitis and Breast Abscess......Page 477
95 Breast Cancer......Page 480
96 Paget Disease of
the Breast......Page 486
Part 13 Musculoskeletal/Rheumatologic
......Page 490
97 Arthritis Overview......Page 491
98
Osteoarthritis......Page 497
99 Rheumatoid Arthritis......Page 501
100 Psoriatic Arthritis......Page 505
101 Ankylosing Spondylitis......Page 511
102 Back Pain......Page 514
103 Lumbar Spinal Stenosis......Page 518
104 Compression Fractures......Page 520
105 Gout......Page 523
106 Olecranon Bursitis......Page 527
107 Clavicular Fracture......Page 530
108 Distal Radius Fracture......Page 533
109 Metatarsal Fracture......Page 538
110 Hip Fracture......Page 541
111 The Knee......Page 544
112 Dupuytren Disease......Page 549
113 Polymyalgia Rheumatica and Temporal Arteritis......Page 552
Part 14 Dermatology
......Page 558
114 Acne Vulgaris......Page 559
115 Rosacea......Page 567
116 Pseudofolliculitis and Acne Keloidalis Nuchae
......Page 573
117 Hidradenitis Suppurativa......Page 577
118 Impetigo......Page 581
119 Folliculitis......Page 585
120 Pitted Keratolysis......Page 591
121 Erythrasma
......Page 594
122 Cellulitis......Page 599
123 Abscess......Page 603
124 Necrotizing Fasciitis......Page 607
125 Chickenpox......Page 611
126 Zoster......Page 615
127 Zoster Ophthalmicus......Page 620
128 Herpes Simplex......Page 625
129 Molluscum Contagiosum......Page 632
130 Common Warts......Page 636
131 Flat Warts......Page 642
132 Genital Warts......Page 646
133 Plantar Warts......Page 652
134 Fungal Overview......Page 657
135 Candidiasis......Page 663
136 Tinea Corporis......Page 667
137 Tinea Cruris......Page 673
138 Tinea Pedis......Page 677
139 Tinea Versicolor......Page 683
140 Lice......Page 687
141 Scabies......Page 692
142 Cutaneous Larva Migrans......Page 699
143 Atopic Dermatitis......Page 702
144 Contact Dermatitis......Page 710
145 Hand Eczema......Page 718
146 Nummular Eczema......Page 725
147 Psychocutaneous Disorders......Page 729
148 Urticaria and Angioedema......Page 735
149 Seborrheic Dermatitis......Page 742
150 Psoriasis......Page 748
151 Pityriasis Rosea......Page 764
152 Lichen Planus......Page 769
153 Reactive Arthritis......Page 776
154 Erythroderma......Page 780
155 Skin Tag
......Page 786
156 Seborrheic Keratosis
......Page 789
157 Sebaceous Hyperplasia
......Page 794
158 Dermatofibroma
......Page 797
159 Pyogenic Granuloma
......Page 801
160 Benign Nevi
......Page 805
161 Congenital Nevi
......Page 812
162 Epidermal Nevus and Nevus Sebaceous
......Page 817
163 Dysplastic Nevus
......Page 821
164 Actinic Keratosis and Bowen Disease
......Page 826
165
Keratoacanthoma......Page 832
166 Lentigo Maligna
......Page 836
167 Cutaneous Horn
......Page 840
168 Basal Cell Carcinoma
......Page 844
169 Squamous Cell Carcinoma
......Page 853
170 Melanoma
......Page 861
171 Granuloma Annulare
......Page 874
172 Pyoderma Gangrenosum
......Page 880
173 Sarcoidosis
......Page 886
174 Cutaneous T-Cell Lymphoma
......Page 892
175 Erythema Multiforme, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis
......Page 898
176 Erythema Nodosum
......Page 905
177 Vasculitis
......Page 910
178 Lupus: Systemic and Cutaneous
......Page 918
179 Dermatomyositis
......Page 927
180 Scleroderma and Morphea
......Page 935
181 Overview of Bullous Diseases
......Page 942
182 Bullous Pemphigoid
......Page 948
183 Pemphigus
......Page 953
184 Other Bullous Diseases
......Page 961
185 Alopecia Areata
......Page 968
186 Traction Alopecia and Trichotillomania
......Page 973
187 Scarring Alopecia
......Page 977
188 Normal Nail Variants
......Page 983
189 Pigmented Nail Disorders
......Page 989
190 Ingrown Toenail
......Page 994
191 Onychomycosis
......Page 998
192 Paronychia
......Page 1004
193 Psoriatic Nails
......Page 1008
194 Subungual Hematoma
......Page 1012
195 Melasma
......Page 1015
196 Vitiligo and Hypopigmentation
......Page 1019
197 Photosensitivity
......Page 1025
198 Erythema Ab Igne
......Page 1031
199 Acquired Vascular Skin Lesions
......Page 1035
200 Hereditary and Congenital Vascular Lesions
......Page 1039
201 Cutaneous Drug Reactions
......Page 1043
202 Keloids
......Page 1053
203 Genodermatoses
......Page 1058
204 Erythema Annulare Centrifugum
......Page 1064
Part 15
Podiatry......Page 1068
205 Corn and Callus
......Page 1069
206 Bunion Deformity
......Page 1073
207 Hammer Toe
......Page 1076
208 Ischemic Ulcer
......Page 1080
209
Neuropathic Ulcer......Page 1082
210 Charcot Arthropathy
......Page 1084
211 Dry Gangrene
......Page 1087
Part 16 Infectious Diseases
......Page 1090
212 AIDS and Kaposi Sarcoma
......Page 1091
213 Urethritis in Men......Page 1096
214 Intestinal Worms and Parasites......Page 1099
215 Lyme Disease......Page 1104
216 Meningitis......Page 1110
217 Osteomyelitis......Page 1115
218 Syphilis......Page 1121
Part 17 Endocrine
......Page 1128
219 Diabetes Overview......Page 1129
220 Acanthosis Nigricans......Page 1137
221 Diabetic Dermopathy......Page 1141
222 Necrobiosis Lipoidica......Page 1144
223 Hyperlipidemia and Xanthomas......Page 1148
224 Obesity......Page 1154
225 Osteoporosis and Osteopenia......Page 1160
226 Hypothyroidism......Page 1167
227 Hyperthyroidism......Page 1172
228 Acromegaly......Page 1179
229 Cushing Syndrome......Page 1183
Part 18 Neurology
......Page 1192
230 Headache......Page 1193
231 Cerebral Vascular Accident......Page 1197
232 Subdural Hematoma......Page 1201
233 Normal Pressure Hydrocephalus......Page 1204
234 Bell’s Palsy......Page 1207
235 Neurofibromatosis
......Page 1210
Part 19 Substance Abuse
......Page 1214
236 Substance Abuse Disorder......Page 1215
237 Tobacco Addiction......Page 1220
238 Alcoholism (Alcohol Use Disorder)
......Page 1232
239 Methamphetamine......Page 1242
240 Cocaine......Page 1247
241 Injection-Drug Use......Page 1254
Appendices
......Page 1260
A Interpreting Evidence-Based Medicine......Page 1261
B Guide for the Use of Topical and Intralesional
Corticosteroids......Page 1264
C Dermoscopy......Page 1267
A
......Page 1280
B
......Page 1284
C
......Page 1286
D
......Page 1291
E
......Page 1293
F
......Page 1296
G
......Page 1297
H
......Page 1298
I
......Page 1302
K
......Page 1303
L
......Page 1304
M
......Page 1306
N
......Page 1308
O
......Page 1310
P
......Page 1312
R
......Page 1317
S
......Page 1319
T
......Page 1323
V
......Page 1326
W
......Page 1328
Z
......Page 1329
Topic Index
......Page 1330

Citation preview

THE CO LO R ATLAS O F INTERNAL MEDICINE

NO TICE Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The authors and the publisher o this work have checked with sources believed to be reliable in their e orts to provide in ormation that is complete and generally in accord with the standards accepted at the time o publication. However, in view o the possibility o human error or changes in medical sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or publication o this work warrants that the in ormation contained herein is in every respect accurate or complete, and they disclaim all responsibility or any errors or omissions or or the results obtained rom use o the in ormation contained in this work. Readers are encouraged to con rm the in ormation contained herein with other sources. For example and in particular, readers are advised to check the product in ormation sheet included in the package o each drug they plan to administer to be certain that the in ormation contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications or administration. This recommendation is o particular importance in connection with new or in requently used drugs.

THE CO LO R ATLAS O F INTERNAL MEDICINE Ed it o r s Richard P. Usat ine , MD Pro essor, Family and Community Medicine Pro essor, Dermatology and Cutaneous Surgery Assistant Director, Medical Humanities Education University o Texas Health Science Center at San Antonio Medical Director, Skin Clinic, University Health System San Antonio, Texas

Gary Fe re nchick, MD, MS Pro essor o Internal Medicine Division Chie , General Medicine Internal Medicine Clerkship Director Michigan State University, College o Human Medicine East Lansing, Michigan

Mind y A. Smit h, MD, MS Clinical Pro essor Department o Family Medicine Michigan State University East, Lansing, Michigan

E.J . Maye aux, J r., MD Pro essor and Chairman, Department o Family and Preventive Medicine Pro essor o Obstetrics and Gynecology University o South Carolina School o Medicine Columbia, South Carolina

He id i S. Chumle y, MD Executive Dean and Chie Academic O cer American University o the Caribbean

New York Chicago San Francisco Athens London Madrid Mexico City Milan New Delhi Singapore Sydney Toronto

Copyright © 2015 by McGraw-Hill Education. All rights reserved. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher, with the exception that the program listings may be entered, stored, and executed in a computer system, but they may not be reproduced for publication. ISBN: 978-0-07-177239-6 MHID: 0-07-177239-1 The material in this eBook also appears in the print version of this title: ISBN: 978-0-07-177238-9, MHID: 0-07-177238-3. eBook conversion by codeMantra Version 1.0 All trademarks are trademarks of their respective owners. Rather than put a trademark symbol after every occurrence of a trademarked name, we use names in an editorial fashion only, and to the bene t of the trademark owner, with no intention of infringement of the trademark. Where such designations appear in this book, they have been printed with initial caps. McGraw-Hill Education eBooks are available at special quantity discounts to use as premiums and sales promotions or for use in corporate training programs. To contact a representative, please visit the Contact Us page at www.mhprofessional.com. TERMS OF USE This is a copyrighted work and McGraw-Hill Education and its licensors reserve all rights in and to the work. Use of this work is subject to these terms. Except as permitted under the Copyright Act of 1976 and the right to store and retrieve one copy of the work, you may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works based upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it without McGraw-Hill Education’s prior consent. You may use the work for your own noncommercial and personal use; any other use of the work is strictly prohibited. Your right to use the work may be terminated if you fail to comply with these terms. THE WORK IS PROVIDED “AS IS.” McGRAW-HILL EDUCATION AND ITS LICENSORS MAKE NO GUARANTEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. McGraw-Hill Education and its licensors do not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free. Neither McGraw-Hill Education nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom. McGraw-Hill Education has no responsibility for the content of any information accessed through the work. Under no circumstances shall McGraw-Hill Education and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise.

DEDICATIO N

To our patients who unsel shly agreed to let us display their diseases and a f ictions to the world to enhance the study and practice o medicine. We are honored by this trust. We have learned much rom our patients as they continue to help us teach the next generation o health care providers.

Co VEr iMAGEs

v

Fr o Nt Co VEr TO P RO w Left: Nonproli erative diabetic retinopathy, with scattered intradot-blot, f ame hemorrhages, and also macular exudates (Figure 219-2; Reproduced with permission from Andrew Sanchez, COA). Middle: Sarcoidosis causing a lupus pernio pattern on the ace o an A rican American woman (Figure 63-3; Reproduced with permission from Richard P. Usatine, MD). Right: Rheumatoid arthritis with rheumatoid nodules over the PCP joints along with de ormities o the digits (Figure 97-7; Reproduced with permission from Ricardo Zuniga-Montes, MD).

BO TTO M RO w Left: Palmar patches and plaques in a young man with secondary syphilis and HIV/ AIDS (Figure 218-18B; Reproduced with permission from Jonathan B. Karnes, MD). Middle: Frontal chest radiograph o a primary pulmonary TB in ection in a 20-year-old man, showing mediastinal and right hilar lymphadenopathy (black arrows) and right upper lobe consolidation (white arrow) (Figure 64-1A; Reproduced with permission from Carlos Santiago Restrepo, MD). Right: Asymptomatic diverticulosis (Figure 68-4; Reproduced with permission from John Rodney, MD).

BACK Co VEr Top: Multiple so t neuro bromas on the neck o a patient with neuro bromatosis (Reproduced with permission from Richard P. Usatine, MD.) Middle: Localized bullous pemphigoid with large bulla on the thigh o a 91-year-old woman (Figure 182-2; Reproduced with permission from Richard P. Usatine, MD). Bottom: Dactylitis (sausage ngers) in a woman with plaque psoriasis and psoriatic arthritis (Figure 100-3; Reproduced with permission from Richard P. Usatine, MD).

Co Nt ENt s Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi Pre ace . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii

PART 1 LEARNING WITH IMAGES AND DIGITAL PHO TO GRAPHY 1

An Atlas to Enhance Patient Care, Learning, and Teaching . . . 2

Se ct io n 2: No se and Sinus 27 Nasal Polyps. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Sinusitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Se ct io n 3: Mo ut h and Thro at 29 Angular Cheilitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 Torus Palatinus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Pharyngitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 The Larynx (Hoarseness) . . . . . . . . . . . . . . . . . . . . . . . .

PART 2

PART 6

ISSUES IN INTERNAL MEDICINE

O RAL HEALTH

2 3 4 5 6

Doctor–Patient Relationship . . . . . . . . . . . . . . . . . . . . . . . 6 Family Planning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 End o Li e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Social Justice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 Global Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

PART 3 PHYSICAL AND SEXUAL ABUSE 7 8

Intimate Partner Violence . . . . . . . . . . . . . . . . . . . . . . . . 50 Sexual Assault. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

PART 4 O PHTHALMO LO GY 9 10 11 12 13 14 15 16 17 18 19 20 21 22

Pterygium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 Hordeolum and Chalazion . . . . . . . . . . . . . . . . . . . . . . . . 65 Scleral and Conjunctival Pigmentation . . . . . . . . . . . . . . . . 68 Corneal Foreign Body and Corneal Abrasion. . . . . . . . . . . . 72 Conjunctivitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Scleritis and Episcleritis . . . . . . . . . . . . . . . . . . . . . . . . . . 80 Uveitis and Iritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 Glaucoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 Diabetic Retinopathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 Hypertensive Retinopathy . . . . . . . . . . . . . . . . . . . . . . . . 93 Papilledema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 Age-Related Macular Degeneration . . . . . . . . . . . . . . . . . . 99 Eye Trauma—Hyphema . . . . . . . . . . . . . . . . . . . . . . . . 103 Di erential Diagnosis o the Red Eye . . . . . . . . . . . . . . . . 106

PART 5

Black Hairy Tongue. . . . . . . . . . . . . . . . . . . . . . . . . . . . Geographic Tongue . . . . . . . . . . . . . . . . . . . . . . . . . . . . Gingivitis and Periodontal Disease. . . . . . . . . . . . . . . . . . Gingival Overgrowth . . . . . . . . . . . . . . . . . . . . . . . . . . Aphthous Ulcer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Leukoplakia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Oropharyngeal Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . Adult Dental Caries. . . . . . . . . . . . . . . . . . . . . . . . . . . .

130 133 138 141 143 149

156 159 162 166 169 174 177 181

PART 7 CARDIO VASCULAR 41 42 43 44 45 46 47 48 49 50 51

Aortic Aneurysm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Atrial Fibrillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clubbing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Coronary Artery Disease . . . . . . . . . . . . . . . . . . . . . . . . Deep Venous Thrombosis . . . . . . . . . . . . . . . . . . . . . . . Bacterial Endocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pericarditis and Pericardial E usion. . . . . . . . . . . . . . . . . Peripheral Arterial Disease . . . . . . . . . . . . . . . . . . . . . . . Venous Insu ciency . . . . . . . . . . . . . . . . . . . . . . . . . . .

186 193 206 209 212 215 220 225 228 232 239

PART 8 HEMATO LO GY 52 53 54

Iron De ciency Anemia . . . . . . . . . . . . . . . . . . . . . . . . . 244 B12 De ciency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248 Sickle Cell Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254

PART 9

EAR, NO SE, AND THRO AT Se ct io n 1: Ear 23 Otitis Media: Acute Otitis and Otitis Media with E usion . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Otitis Externa. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Ear: Foreign Body. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 Chondrodermatitis Nodularis Helicis and Preauricular Tags . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

33 34 35 36 37 38 39 40

v

PULMO NARY 112 119 123 126

55 56 57 58 59 60

Asthma and Pulmonary Function Testing. . . . . . . . . . . . . . Chronic Obstructive Pulmonary Disease . . . . . . . . . . . . . Lung Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pleural E usion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Community-Acquired Pneumonia. . . . . . . . . . . . . . . . . . Pneumothorax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

260 269 278 286 290 296

Co Nt ENt s

v

61 62 63 64

Pulmonary Embolism . . . . . . . . . . . . . . . . . . . . . . . . . . Pulmonary Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Tuberculosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

299 306 310 316

PART 10 GASTRO INTESTINAL 65 66 67 68 69 70 71 72 73 74 75 76 77

Clostridium Di cile In ection . . . . . . . . . . . . . . . . . . . . Colon Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Colon Polyps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Diverticulitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Gallstones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Gastric Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Gastroesophageal Ref ux Disease (GERD) . . . . . . . . . . . . Hemorrhoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ischemic Colitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Liver Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acute Pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Peptic Ulcer Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . Inf ammatory Bowel Disease. . . . . . . . . . . . . . . . . . . . . .

326 329 335 340 344 349 354 358 362 365 373 377 381

390 395 398 402 406 410 415 421 426 429

PART 12 WO MEN’S HEALTH Se ct io n 1: Vag init is/ Ce rvicit is 88 Overview o Vaginitis . . . . . . . . . . . . . . . . . . . . . . . . . . 89 Atrophic Vaginitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 Bacterial Vaginosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 Candida Vulvovaginitis . . . . . . . . . . . . . . . . . . . . . . . . . 92 Trichomonas Vaginitis . . . . . . . . . . . . . . . . . . . . . . . . . . 93 Chlamydia Cervicitis . . . . . . . . . . . . . . . . . . . . . . . . . . . Se ct io n 2: Bre ast 94 Mastitis and Breast Abscess. . . . . . . . . . . . . . . . . . . . . . . 95 Breast Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 Paget Disease o the Breast . . . . . . . . . . . . . . . . . . . . . . .

97 99 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113

Arthritis Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . Osteoarthritis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Rheumatoid Arthritis. . . . . . . . . . . . . . . . . . . . . . . . . . . Psoriatic Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ankylosing Spondylitis. . . . . . . . . . . . . . . . . . . . . . . . . . Back Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Lumbar Spinal Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . Compression Fractures . . . . . . . . . . . . . . . . . . . . . . . . . Gout . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Olecranon Bursitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clavicular Fracture . . . . . . . . . . . . . . . . . . . . . . . . . . . . Distal Radius Fracture . . . . . . . . . . . . . . . . . . . . . . . . . . Metatarsal Fracture . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hip Fracture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Knee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Dupuytren Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . Polymyalgia Rheumatica and Temporal Arteritis . . . . . . . .

472 478 482 486 492 495 499 501 504 508 511 514 519 522 525 530 533

DERMATO LO GY

GENITO URINARY/RENAL Bladder Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hydronephrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Kidney Stones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nephrotic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . Polycystic Kidneys . . . . . . . . . . . . . . . . . . . . . . . . . . . . Prostate Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Renovascular Hypertension . . . . . . . . . . . . . . . . . . . . . . Renal Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . Chronic Kidney Disease . . . . . . . . . . . . . . . . . . . . . . . . . Urinary Sediment . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

MUSCULO SKELETAL/RHEUMATO LO GIC

PART 14

PART 11 78 79 80 81 82 83 84 85 86 87

PART 13

434 437 441 445 450 454 458 461 467

Se ct io n 1: Acne i o rm Diso rd e rs 114 Acne Vulgaris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 Rosacea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 Pseudo olliculitis and Acne Keloidalis Nuchae. . . . . . . . . . 117 Hidradenitis Suppurativa . . . . . . . . . . . . . . . . . . . . . . . . Se ct io n 2: Bact e rial 118 Impetigo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 Folliculitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 Pitted Keratolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 Erythrasma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 Cellulitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 Abscess . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 Necrotizing Fasciitis . . . . . . . . . . . . . . . . . . . . . . . . . . . Se ct io n 3: Viral 125 Chickenpox . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 Zoster . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127 Zoster Ophthalmicus. . . . . . . . . . . . . . . . . . . . . . . . . . . 128 Herpes Simplex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 Molluscum Contagiosum . . . . . . . . . . . . . . . . . . . . . . . . 130 Common Warts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 Flat Warts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 Genital Warts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 Plantar Warts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Se ct io n 4: Fung al 134 Fungal Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 Candidiasis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

540 548 554 558 562 566 572 575 580 584 588 592 596 601 606 613 617 623 627 633 638 644

Co Nt ENt s 136 Tinea Corporis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 Tinea Cruris. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 Tinea Pedis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 Tinea Versicolor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Se ct io n 5: In e st at io ns 140 Lice. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 Scabies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142 Cutaneous Larva Migrans . . . . . . . . . . . . . . . . . . . . . . . . Se ct io n 6: De rmat it is/ Alle rg ic 143 Atopic Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 Contact Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 Hand Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146 Nummular Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 Psychocutaneous Disorders . . . . . . . . . . . . . . . . . . . . . . 148 Urticaria and Angioedema . . . . . . . . . . . . . . . . . . . . . . . Se ct io n 7: Pap ulo sq amo us Co nd it io ns 149 Seborrheic Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . 150 Psoriasis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 Pityriasis Rosea. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152 Lichen Planus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 Reactive Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154 Erythroderma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Se ct io n 8: Be nig n Ne o p lasms 155 Skin Tag . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156 Seborrheic Keratosis . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 Sebaceous Hyperplasia. . . . . . . . . . . . . . . . . . . . . . . . . . 158 Dermato broma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 Pyogenic Granuloma . . . . . . . . . . . . . . . . . . . . . . . . . . . Se ct io n 9: Ne vi 160 Benign Nevi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 Congenital Nevi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162 Epidermal Nevus and Nevus Sebaceous . . . . . . . . . . . . . . 163 Dysplastic Nevus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Se ct io n 10: Pre cance r/ Early Cance r 164 Actinic Keratosis and Bowen Disease . . . . . . . . . . . . . . . . 165 Keratoacanthoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166 Lentigo Maligna . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167 Cutaneous Horn . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Se ct io n 11: Skin Cance r 168 Basal Cell Carcinoma. . . . . . . . . . . . . . . . . . . . . . . . . . . 169 Squamous Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . 170 Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Se ct io n 12: Inf lt rat ive / Immuno lo g ic 171 Granuloma Annulare . . . . . . . . . . . . . . . . . . . . . . . . . . 172 Pyoderma Gangrenosum . . . . . . . . . . . . . . . . . . . . . . . . 173 Sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174 Cutaneous T-Cell Lymphoma. . . . . . . . . . . . . . . . . . . . .

648 654 658 664 668 673 680 683 691 699 706 710 716 723 729 745 750 757 761 767 770 775 778 782 786 793 798 802 807 813 817 821

x

Se ct io n 13: Hyp e rse nsit ivit y Synd ro me s 175 Erythema Multi orme, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis. . . . . . . . . . . . . . . . . . . . . . . . . . . 879 176 Erythema Nodosum . . . . . . . . . . . . . . . . . . . . . . . . . . . 886 177 Vasculitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 891 Se ct io n 14: Co nne ct ive Tissue Dise ase 178 Lupus: Systemic and Cutaneous . . . . . . . . . . . . . . . . . . . 899 179 Dermatomyositis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 908 180 Scleroderma and Morphea . . . . . . . . . . . . . . . . . . . . . . . 916 Se ct io n 15: Bullo us Dise ase 181 Overview o Bullous Diseases . . . . . . . . . . . . . . . . . . . . . 923 182 Bullous Pemphigoid. . . . . . . . . . . . . . . . . . . . . . . . . . . . 929 183 Pemphigus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 934 184 Other Bullous Diseases . . . . . . . . . . . . . . . . . . . . . . . . . 942 Se ct io n 16: Hair and Nail Co nd it io ns 185 Alopecia Areata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 949 186 Traction Alopecia and Trichotillomania . . . . . . . . . . . . . . 954 187 Scarring Alopecia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 958 188 Normal Nail Variants. . . . . . . . . . . . . . . . . . . . . . . . . . . 964 189 Pigmented Nail Disorders . . . . . . . . . . . . . . . . . . . . . . . 970 190 Ingrown Toenail . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 975 191 Onychomycosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 979 192 Paronychia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 985 193 Psoriatic Nails . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 989 194 Subungual Hematoma . . . . . . . . . . . . . . . . . . . . . . . . . . 993 Se ct io n 17: Pig me nt ary and Lig ht -Re lat e d Co nd it io ns 195 Melasma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 996 196 Vitiligo and Hypopigmentation . . . . . . . . . . . . . . . . . . . 1000 197 Photosensitivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1006 198 Erythema Ab Igne . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1012 Se ct io n 18: Vascular Skin Diso rd e rs 199 Acquired Vascular Skin Lesions. . . . . . . . . . . . . . . . . . . 1016 200 Hereditary and Congenital Vascular Lesions . . . . . . . . . . 1020 Se ct io n 19: O t he r Skin Diso rd e rs 201 Cutaneous Drug Reactions . . . . . . . . . . . . . . . . . . . . . . 1024 202 Keloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1034 203 Genodermatoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1039 204 Erythema Annulare Centri ugum . . . . . . . . . . . . . . . . . 1045

PART 15 825 834 842 855 861 867 873

PO DIATRY 205 206 207 208 209 210 211

Corn and Callus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Bunion De ormity . . . . . . . . . . . . . . . . . . . . . . . . . . . Hammer Toe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ischemic Ulcer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Neuropathic Ulcer . . . . . . . . . . . . . . . . . . . . . . . . . . . Charcot Arthropathy . . . . . . . . . . . . . . . . . . . . . . . . . Dry Gangrene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1050 1054 1057 1061 1063 1065 1068

Co Nt ENt s

x

PART 16

PART 18

INFECTIO US DISEASES

NEURO LO GY

212 213 214 215 216 217 218

AIDS and Kaposi Sarcoma . . . . . . . . . . . . . . . . . . . . . . Urethritis in Men . . . . . . . . . . . . . . . . . . . . . . . . . . . . Intestinal Worms and Parasites . . . . . . . . . . . . . . . . . . . Lyme Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Meningitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Osteomyelitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Syphilis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1072 1077 1080 1085 1091 1096 1102

230 231 232 233 234 235

Headache . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cerebral Vascular Accident . . . . . . . . . . . . . . . . . . . . . Subdural Hematoma . . . . . . . . . . . . . . . . . . . . . . . . . . Normal Pressure Hydrocephalus . . . . . . . . . . . . . . . . . . Bell’s Palsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Neuro bromatosis . . . . . . . . . . . . . . . . . . . . . . . . . . .

1174 1178 1182 1185 1188 1191

PART 19 PART 17

SUBSTANCE ABUSE

ENDO CRINE 219 220 221 222 223 224 225 226 227 228 229

Diabetes Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . Acanthosis Nigricans . . . . . . . . . . . . . . . . . . . . . . . . . . Diabetic Dermopathy . . . . . . . . . . . . . . . . . . . . . . . . . Necrobiosis Lipoidica . . . . . . . . . . . . . . . . . . . . . . . . . Hyperlipidemia and Xanthomas . . . . . . . . . . . . . . . . . . Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Osteoporosis and Osteopenia . . . . . . . . . . . . . . . . . . . . Hypothyroidism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hyperthyroidism . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acromegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cushing Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . .

1110 1118 1122 1125 1129 1135 1141 1148 1153 1160 1164

236 237 238 239 240 241

Substance Abuse Disorder . . . . . . . . . . . . . . . . . . . . . . Tobacco Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . Alcoholism (Alcohol Use Disorder) . . . . . . . . . . . . . . . . Methamphetamine . . . . . . . . . . . . . . . . . . . . . . . . . . . Cocaine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Injection-Drug Use . . . . . . . . . . . . . . . . . . . . . . . . . . .

1196 1201 1213 1223 1228 1235

APPENDICES A B C

Interpreting Evidence-Based Medicine . . . . . . . . . . . . . . 1242 Guide or the Use o Topical and Intralesional Corticosteroids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1245 Dermoscopy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1248

Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1261

Co Nt r iBu t o r s Cat hy Ab b o t t , MD

Gina R. Chaco n, MD

Assistant Pro essor Department o Family Medicine Michigan State University College o Human Medicine East Lansing, Michigan

Dermatology Resident Marsh eld Clinic - Marsh eld Center Marsh eld, Wisconsin

O live r Ab e la, MD

Family Practitioner Sutter East Bay Medical Foundation Albany, Cali ornia

Cardiovascular Fellow University o Nevada School o Medicine Las Vegas, Nevada

Anna Allre d , MD Resident Physician Department o Neurological Surgery University o Texas South Western Medical Center Dallas, Texas

O sama Alsara, MD Chie Resident Internal medicine program Michigan State University East Lansing, Michigan

He nd Azhary, MD Assistant Pro essor Department o Family Medicine Michigan State University College o Human Medicine East Lansing, Michigan

Me lissa M. Chan, MD

Sat ish Chand o lu, MD Hospitalist, Sparrow Hospital Clinical Instructor Michigan State University East Lansing, Michigan

Pie rre Chano ine , MD Drexel University School o Medicine Philadelphia, Pennsylvania St. Christopher’s Hospital or Children Philadelphia, Pennsylvania

Tho mas J . Co rso n, DO Emergency Medicine Banner Health Mckee Medical Center Loveland, Colorado

J o hn E. De lze ll, J r., MD, MSPH

Dermatologist Colorado Springs Dermatology Clinic Colorado Springs, Colorado

Director, Medical Student Education Associate Pro essor in Division o Family Medicine Department o Humanities, Health, and Society Herbert Wertheim College o Medicine Florida International University Miami, Florida

Yo o n-So o Cind y Bae -Harb o e , MD

Ro e na A. De So uza, MD

Boston University Hospital Medical Center Department o Dermatology Boston, Massachusetts

Assistant Pro essor Division o Urology University o Texas Medical School at Houston Houston, Texas

Michae l Bab co ck, MD

J ame s C. Barro , MD Clinical Assistant Pro essor Department o Obstetrics and Gynecology Louisiana State University Health Center Shreveport, Louisiana

Rut h E. Be rg g re n, MD Pro essor o Medicine Division o In ectious Diseases University o Texas Health Science Center San Antonio, Texas

Marg are t L. Burks, MD

Lucia Diaz, MD Chie Resident Dermatology Department University o Texas Medical School at Houston MD Anderson Cancer Center Houston, Texas

Hannah Fe re nchick, MD Resident, Emergency Medicine Detroit Receiving Hospital Detroit, Michigan

Internal Medicine Resident Vanderbilt University Medical Center Nashville, Tennessee

Lind se y B. Finkle a, MD

Ke vin J . Cart e r, MD

J avie r LaFo nt aine , DPM, MS

Assistant Pro essor Department o Family Medicine Louisiana State University Health Center Shreveport, Louisiana

Chie , Podiatry Section Central Texas Veterans Health Care System Temple, Texas

Dermatologist San Antonio, Texas

x

x

Co Nt r iBu t o r s Ke lli He jl Fo ulkro d , MS

Nat han Hit ze man, MD

Psychotherapist/ Yoga Teacher Psychology Center o Austin Austin, Texas

Faculty, Sutter Health Family Medicine Residency Program Sacramento, Cali ornia

J e re my A. Franklin, MD

Associate Pro essor Oral Medicine Subject Expert Department o Comprehensive Dentistry University o Texas at San Antonio Health Science Center Dental School San Antonio, Texas

Director, Medical Sciences MedImmune LLC Lubbock, Texas

Rad ha Raman Murt hy Go kula, MD, CMD Geriatrician & Palliative Medicine Consultant University o Toledo Medical Center Assistant Pro essor Department o Family Medicine University o Toledo Toledo, Ohio

w and a C. Go nsalve s, MD Pro essor and Vice Chair Department o Family and Community Medicine University o Kentucky College o Medicine Lexington, Kentucky

Ve nu Go urine ni, MD Cardiology ellow Rush University Medical Center Chicago, Illinois

Ke lly Gre e n, MD Ophthalmology, Private Practice Marble Falls, Texas Clinical Assistant Pro essor Department o Ophthalmology University o Texas Health Science Center San Antonio, Texas

Alfo nso Guzman, MD Family Physician San Antonio, Texas

Churlso n Han, MD Assistant Pro essor o Internal Medicine Michigan State University East Lansing, Michigan

Me re d it h Hanco ck, MD Preliminary Resident Internal Medicine Loyola University Medical Center Maywood, Illinois

J immy H. Hara, MD, FAAFP Pro essor o Clinical Family Medicine David Ge en School o Medicine at UCLA Los Angeles, Cali ornia

David He nd e rso n, MD Associate Pro essor, Department o Family Medicine Associate Dean, Medical Student A airs University o Connecticut School o Medicine Farmington, Connecticut

Michae ll A. Hub e r, DDS

Kare n A. Hug he s, MD, FAAFP Associate Director North Mississippi Center Family Medicine Residency Program Tupelo, Mississippi

Khalilah Hunt e r-And e rso n, MD Assistant Pro essor Department o Traumatology & Emergency Medicine University o Connecticut Health Center Farmington, Connecticut

Carlo s Ro b e rt o J aé n, MD, PhD, MS Pro essor and Chair o Family and Community Medicine Pro essor o Epidemiology and Biostatistics The Dr. and Mrs. James L. Holly Distinguished Pro essor Scholar, ReACH (Research to Advance Community Health) Center University o Texas Health Science Center at San Antonio San Antonio, Texas

Nat alia J aime s, MD Assistant Pro essor Department o Dermatology Universidad Ponti cia Bolivariana Attending Physician Aurora Skin Cancer Center Medellin, Colombia

Ad e liza J ime ne z, MD Sta Physician Southern Cali ornia Permanente Medical Group Downey, Cali ornia

Anne E. J o hnso n, MD Psychiatry Resident University o Texas Southwestern Dallas, Texas

Rajil M. Karnani, MD, MME Assistant Pro essor o Internal Medicine Michigan State University East Lansing, Michigan

J o nat han B. Karne s, MD Faculty MDFMR Dermatology Services, Main Dartmouth Family Medicine Residency Augusta, Maine

Co Nt r iBu t o r s J e nnife r A. Ke e hb auch, MD, FAAFP

Caro lyn Milana, MD

Director o Research, Graduate Medical Education Florida Hospital Assistant Director, Family Medicine, Residency, Florida Hospital Director, Women’s Medicine Fellowship, Florida Hospital Orlando, Florida

Assistant Pro essor o Pediatrics Stony Brook Long Island Children’s Hospital Stony Brook, New York

Me lanie Ke t chand ji, MD Urology Resident University o Texas Health Science Center Houston, Texas

Amo r Khache mo une , MD Attending Physician, Dermatologist Mohs Surgeon and Dermatopathologist Veterans A airs Medical Center Brooklyn, New York

J o o nse o k Kim, MD Fellow, Division o Cardiovascular Health and Disease University o Cincinnati Medical Center Cincinnati, Ohio

J . Michae l King , MD Otolaryngology, Head and Neck Surgery Peak ENT and Voice Center Boulder, Colorado

Ro b e rt Kraft , MD Clinical Assistant Pro essor Department o Family and Community Medicine University o Kansas School o Medicine Wichita, Kansas

Mad hab Lamichhane , MD Cardiovascular Diseases Fellow Michigan State University East Lansing, Michigan

J uanit a Lo zano -Pine d a, DDS, MPH

Shashi Mit t al, MD Family Physician MedFirst Northeast Primary Care Clinic San Antonio, Texas

Asad K. Mo hmand , MD, FACP VCU Pauley Heart Center Medical College o Virginia Virginia Commonwealth University Richmond, Virginia

Me lissa Muszynski, MD Resident, Department o Dermatology Georgetown University Hospital Washington Hospital Center Washington DC

Anje li Nayar, MD Assistant Pro essor o Medicine Uni ormed Services University o the Health Sciences Medical School Sta Physician, Internal Medicine Department o San Antonio Military Medical Center San Antonio, Texas

Priyank Pat e l, MD Hematology Oncology Fellow, Roswell Park Cancer Institute, University at Bu alo, Bu alo, New York

Richard Paulis, MD Emergency Medicine Rochester General Hospital Atlanta, Georgia

Assistant Pro essor Department o Comprehensive Dentistry University o Texas at San Antonio Health Science Center Dental School San Antonio, Texas

De e p t hi Rao , MD

Ashfaq A. Marg ho o b , MD

Brian Z. Rayala, MD

Associate Pro essor Director, Skin Cancer Clinic, Hauppauge, Long Island Memorial Sloan-Kettering Cancer Center New York, New York

Assistant Pro essor Department o Family Medicine University o North Carolina School o Medicine Chapel Hill, North Carolina

Ang ie Mat hai, MD

Sup rat ik Rayamajhi, MD

Assistant Clinical Pro essor East Carolina University Greenville, North Carolina

Assistant Pro essor o Internal Medicine Director, Advanced Medicine Clerkship Michigan State University East Lansing, Michigan

Laura Mat rka, MD Assistant Pro essor Department o Otolaryngology – Head and Neck Surgery The Ohio State University Wexner Medical Center Columbus, Ohio

Fellow Division o Endocrinology Michigan State University East Lansing, Michigan

Suraj Re d d y, MD Dermatology Albuquerque Dermatology Associates Albuquerque, New Mexico

x

Co Nt r iBu t o r s

xv

Kat ie Re p p a, MD

C. Blake Simp so n, MD

Resident University o Pittsburgh Pittsburgh, Pennsylvania

Pro essor, Department o Otolaryngology, Head and Neck Surgery University o Texas Health Science Center San Antonio, Texas

Karl T. Re , MD

Lind a Sp e e r, MD

Assistant Pro essor o Family Medicine and Urology University o Michigan Medical School Ann Arbor, Michigan

Pro essor and Chair Department o Family Medicine University o Toledo College o Medicine and Li e Sciences Toledo, Ohio

Miche lle Ro e , DO Family Medicine San Joaquin General Hospital French Camp, Cali ornia

Khashayar Sarab i, MD Internal & Integrative Medicine Irvine, Cali ornia

She hnaz Zaman Sarmast , MD Dermatologist, Skin Specialist Allen/ Addison, Texas

Ana Tre viño Sauce d a, MD Assistant Clinical Pro essor Dermatology and Cutaneous Surgery University o Texas Health Science Center San Antonio San Antonio, Texas

And re

D. Sche cht man, MD, FAAFP

Adjunct Clinical Assistant Pro essor Stan ord University School o Medicine Division o General Medical Disciplines Faculty, San Jose-O’Connor Hospital Family Medicine Residency Program San Jose, Cali ornia

Ang e la She d d , MD Dermatopathology Fellow ProPath Dallas, Texas

Maure e n K. She e han, MD, MHA Associate Pro essor, Division o Vascular Surgery University o Texas Health Science Center San Antonio, San Antonio, Texas

Nao hiro Shib uya, DPM, MS, FACFAS Associate Pro essor o Surgery Texas A&M Health and Science Center College o Medicine Bryan, Texas

Erne st Vald e z, DDS Assistant Pro essor Department o Oral and Maxillo acial Surgery University o Texas Health Science Center at San Antonio San Antonio, Texas

Yu w ah, MD Assistant Pro essor Department o Family and Community Medicine University o Texas Health Science Center at Houston Houston, Texas

Mark L. w ille nb ring , MD Founder and CEO, ALLTYR Saint Paul, Minnesota

Brian w illiams, MD Brian J. Williams Dermatology, Private Practice Midvale, Utah

Bo nnie w o ng , MD Assistant Pro essor o Clinical Family Medicine Indiana University, School o Medicine Indianapolis, Indiana

J ana K. Zaud ke , MD Assistant Pro essor Department o Family Medicine University o Kansas School o Medicine Kansas City, Kansas

pr EFACE Internists see a wide variety o diseases and conditions including cardiovascular, dermatologic, endocrine, gastrointestinal, and rheumatologic disorders. This comprehensive atlas that aids in diagnosis, using visible signs and internal imaging, can be o tremendous value. We have assembled more than 2000 outstanding clinical images or this very purpose, and are proud to present the rst edition o a modern comprehensive atlas o Internal Medicine. Some photographs will amaze you; all will in orm you about the various conditions that be all our patients. It took a number o people many years to create the rst edition o The Color Atlas of Internal Medicine. For me (Dr. Usatine) as the lead editor, it is a li elong work that started with little notebooks I kept in my white coat pocket to take notes during my residency. It then took on color when I began keeping a camera at work and taking photographs with my patient’s permission o any interesting clinical nding that I might use to teach medical students and residents the art and science o medicine. I was inspired by many great physicians, including Dr. Jimmy Hara, who had the most amazing 35-mm slide collection o clinical images. His knowledge o medicine is encyclopedic and I thought that his taking photographs might have something to do with that. Also, I realized that these photographs would greatly enhance my teaching o others. As I began to expand my practice to see more dermatology cases, my photograph collection skyrocketed. Digital photography made it more a ordable and practical to take and catalogue many new images. The Color Atlas of Internal Medicine is written or internists and all health care providers involved in caring or adults. It can also be invaluable to medical students, residents, and dermatologists.

The Color Atlas of Internal Medicine is also available electronically or iPad, iPhone, iPod touch, all Android devices, Kindle, and on the web through Access Medicine. These electronic versions will allow health care providers to access the images and content rapidly at the point-o -care. The Color Atlas of Internal Medicine is or anyone who loves to look at clinical photographs or learning, teaching, and practicing medicine. The rst chapter begins with an introduction to learning with images and digital photography. The core o the book ocuses on medical conditions organized by anatomic and physiologic systems. There are special sections devoted to the essence o Internal Medicine, physical/ sexual abuse, women’s health, and substance abuse. The collection o clinical images is supported by evidence-based in ormation that will help the health care provider to diagnose and manage common medical problems. The text is concisely presented with many easy-to-access bullets as a quick point-o -care re erence. Each chapter begins with a patient story that ties the photographs to the real li e stories o our patients. The photographic legends are also designed to connect the images to the people and their human conditions. Strength o recommendation ratings are cited throughout so that the science o medicine can be blended with the art o medicine or optimal patient care. Because knowledge continues to advance a ter any book is written, use the online resources presented in many o the chapters to keep up with the newest changes in medicine. Care deeply about your patients and enjoy your practice, as it is a privilege to be a health care provider and healer.

xv

This page intentionally left blank

ACKNo w l Ed GMENt s This book could not have been completed without the contributions o many talented physicians, health care pro essionals, and photographers. We received photographs rom people who live and work across the globe. Each photograph is labeled and acknowledges the photographer and contributor. There are some people who contributed so many photographs; it is appropriate to acknowledge them up ront in the book. Paul Comeau was the pro essional ophthalmology photographer at University o Texas Health Science Center San Antonio (UTHSCSA). His beauti ul photographs o the external and internal eye make the ophthalmology section o this book so rich and valuable. The dermatology division at UTHSCSA contributed much o their expertise in photography, writing, and reviewing the extensive dermatology section. During the last ew years, I was ortunate to work closely with the dermatology aculty and residents and they contributed generously to our book. Dr. Eric Kraus, the program director, gave us many wonder ul photographs, especially or the section on bullous diseases. He also gave us open access to the 35-mm slides collected by the Division o Dermatology. Dr. Je Me ert also contributed photographs to many chapters. Dr. Jack Resneck, Sr., rom Louisiana, scanned his slides rom more than 40 years o practice and gave them to Dr. E.J. Mayeaux, Jr., or use. Dr. Resneck’s vast dermatologic experiences add to our atlas. The UTHSCSA Head and Neck Department contributed many photographs or this book. We especially thank Dr. Frank Miller and Dr. Blake Simpson or their contributions. Dr. Dan Stulberg, a physician rom New Mexico, with a passion or photography and dermatology, contributed many photographs throughout our book. We thank our trainees, many o whom coauthored chapters with us. UTHSCSA medical students and residents and ellows rom Michigan State University’s Primary Care Faculty Development Fellowship program coauthored chapters and contributed photographs with great enthusiasm to the creation o this work. It was a pleasure to mentor these young writers and experience with them the rewards o authorship. Dr. Usatine is thank ul or the contributions o his “Underserved Dermatology Fellows.” Working closely with such brilliant and caring doctors in our Skin Clinic and ree outreach clinics allowed me to learn rom them while doing my best to advance their academic and humanistic careers. O course, we would have no book without the talented writing and editing o my coeditors, Drs. Gary Ferenchick, Mindy A. Smith, E.J. Mayeaux, and Heidi S. Chumley. They each bring years o clinical and educational experience to the writing o the Atlas. Dr. Mayeaux contributed many o his own photographs, especially in women’s health care, to our Atlas. Most o all we need to thank our patients who generously gave their permission or their photographs to be taken and published in this book. While some photos are not recognizable, we have many photos o the ull ace that are very recognizable and were generously given to us by our patients with ull written permission to be published as is. For photographs that were taken decades ago in which written consents were no longer available, we have used bars across

the eyes to make the photos less recognizable—verbal consent was always obtained or these images. The last section o this book is dedicated to understanding substance abuse (chemical dependency) and its treatment. This could not have been done without the generous contributions o the dedicated sta and the women residents at Alpha Home, a nonpro t alcohol and drug treatment program in San Antonio. The medical students and aculty rom UTHSCSA spend 2 to 3 evenings a week providing ree health care to these women who are bravely acing their addictions and ghting to stay sober 1 day at a time. Their pictures have been generously added to our book with their permission. I (Dr. Richard Usatine) thank my amily or giving me the support to see this book through. It has taken much time rom my amily li e and my amily has supported me through the long nights and weekends it takes to write a book while continuing to practice and teach medicine. I am ortunate to have a loving wi e, success ul son, wonder ul daughter, great son-in-law, and one very cute grandson who add meaning to my li e and allowed me to work hard on the creation o this Color Atlas. Dr Gary Ferenchick adds, “I want to acknowledge and thank my children Hannah Ferenchick, MD who contributed to this atlas and my son Jesse, both o whom are embarking on writing their own li e stories. Also, I am grate ul to my lovely wi e Carol, whose support makes my li e much easier and who is one o my li e’s bedrocks.” Dr. Mindy Smith adds, “I thank my late husband, Gary Crakes, and daughter, Jenny, or their support and willingness to listen when I struggle with phrasing and wording in my writing and editing. I also thank several colleagues who have helped me to establish mysel as an editor and supported my continued growth in this eld—Drs. Barry Weiss, Mark Ebell, Richard Usatine, Suzanne Sorkin, and Leslie Shimp.” Dr. E.J. Mayeaux adds, “I thank my wi e and amily or understanding the many hours o work and computer time it takes to produce this work. I would like to dedicate this work to Mr. Bob (Papa Bob) Mitchell who can always nd the unny angle to any situation and who gave me my partner and love o my li e. I would also like to thank my new work amily at the Department o Family and Preventive Medicine at the University o South Carolina School o Medicine in Columbia. We are going to do great things!” Dr. Heidi Chumley adds, “I want to thank my husband, John Delzell, who has brought love and peace to my o ten chaotic li e, and my children, Cullen, Sierra, David, Selene, and Jack, who give me joy and provide the incentive to stay on task. Each one, in turn, has cheer ully pitched in to help a grumpy and tired mom who stayed up most o the night working on one o many chapters. I have been very blessed.” Finally, we all thank James Shanahan and Harriet Lebowitz rom McGraw-Hill or believing in this project and guiding us through to completion. Our gratitude also extends to Hardik Popli or his dedicated work on this book.

xv

This page intentionally left blank

PART 1

LEARNING WITH IMAGES AND DIGITAL PHO TO GRAPHY

*

St re ng t h o Re co mme nd at io n (SO R)

De f nit io n

A

Re comme nd ation b ase d on consiste nt and g ood -q uality p atie nt-orie nte d e vid e nce .*

B

Re comme nd ation b ase d on inconsiste nt or limite d -q uality p atie nt-orie nte d e vid e nce .*

C

Re comme nd ation b ase d on conse nsus, usual p ractice , op inion, d ise ase -orie nte d e vid e nce , or case se rie s or stud ie s o d iag nosis, tre atme nt, p re ve ntion, or scre e ning .*

Se e Ap p e nd ix A on p ag e s 1241-1244 or urthe r in ormation.

PART 1

2

LEARNING WITH IMAGES AND DIGITAL PHO TO GRAPHY

Ch a pt e r 1

1 AN ATLAS TO ENHANCE PATIENT CARE, LEARNING, AND TEACHING Richard P. Usatine , MD People only see what they are prepared to see. —Ralph Waldo Emerson Whether you are viewing Figure 1-1 in a book, in an aquarium, or in the sea, you immediately recognize the image as a f sh. Those o you who are more schooled in the classif cation o f sh might recognize that this is an angelf sh with the tail resembling the head o the angel and the posterior f ns representing the wings. I you are truly prepared to see this f sh in all its splendor, you would see the blue circle above its eye as the crown o the queen angelf sh. Making a diagnosis in medicine o ten involves the kind o pattern recognition needed to identi y a queen angelf sh. This is much the same as recognizing a beauti ul bird or the painting o a avorite artist. I you are prepared to look or the clues that lead to the identif cation (diagnosis), you will see what needs to be seen. How can we be best prepared to see these clues? There is nothing more valuable than seeing an image or a patient who has the condition in question at least once be ore you encounter it on your own. The memory o a power ul visual image can become hardwired into your brain or ready recall. In medicine, it also helps to know where and how to look to f nd the clues you may need when the diagnosis cannot be made at a single glance. For example, a patient with inverse psoriasis may present with a rash under the breast that has been repeatedly and unsuccess ully treated with anti ungal agents or candidiasis or tinea (Figures 1-2 and 1-3). The prepared clinician knows that not all erythematous plaques under the breast are ungal and looks or clues such as nail changes (Figures 1-2 and 1-4) or scaling erythematous plaques around the elbows, knees, or umbilicus (see Figure 1-3). Knowing where to look and what to look or is how an experienced clinician makes the diagnosis o psoriasis.

FIGURE 1-1 Q ue e n ang e lf sh (Holacanthus ciliaris). (Re p rod uce d with p e rmission rom Sam The kke thil. http ://www.f ickr.com/p hotos/nature loving .)

FIGURE 1-2 Inve rse p soriasis und e r the b re ast that mig ht ap p e ar to b e a ung al in e ction to the untraine d e ye . Note the sp linte r he morrhag e s in the nail o the third d ig it that p rovid e a clue that the p atie nt has p soriasis. (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

USING O UR SENSES As physicians we collect clinical data through sight, sound, touch, and smell. Although physicians in the past used taste to collect data, such as tasting the sweet urine o a patient with diabetes, this sense is rarely, i ever, used in modern medicine. We listen to heart sounds, lung sounds, bruits, and percussion notes to collect in ormation or diagnoses. We touch our patients to eel lumps, bumps, thrills, and masses. We occasionally use smell or diagnosis. Un ortunately, the odors o disease are rarely pleasant. Even the ruity odors o Pseudomonas are not like the sweet ruits o a armers’ market. O course, we also use the patient’s history, laboratory data, and more advanced imaging techniques to diagnose and manage patients’ illnesses. It was our belie in the value o visual imagery that led to the development o The Color Atlas of Internal Medicine. We are pleased to provide more than 2000 images to you and doctors around the world as a large, color textbook and as an interactive electronic application or easy use on the iPhone, iPod Touch, iPad, and all android devices.

FIGURE 1-3 The p atie nt in Fig ure 1-2 with inve rse psoriasis had a typ ical psoriatic plaq ue in the umb ilicus. This was the only othe r are a involve d be sid e s the b re asts and the nails b ut e asily could have b e e n misse d without the knowle d g e o whe re to look or the clue s ne e d e d to make the diag nosis. (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

PART 1

a N a t La S t O e Nh a NCe pa t Ie Nt Ca r e , Le a r NING, a ND t e a Ch ING

LEARNING WITH IMAGES AND DIGITAL PHO TO GRAPHY USING IMAGES TO MAKE A DIAGNO SIS

FIGURE 1-4 Whe n the d iag nosis o p soriasis is b e ing consid e re d , look at the nails or p itting or othe r nail chang e s such as sp linte r he morrhag e s, onycholysis, or o il sp ots. This is a g ood e xamp le o nail p itting in a p atie nt with p soriasis. (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

We all see visible clinical f ndings on patients that we do not recognize. When this happens, open this book and look or a close match. Use the appendix, index, or table o contents to direct you to the section with the highest-yield photos. I you f nd a direct match, you may have ound the diagnosis. Read the text and see i the history and physical examination match your patient. Per orm or order tests to conf rm the diagnosis, i needed. I you cannot f nd the image in our book try the Internet and the Google search engine. Try a Google image search and ollow the leads. O course this is easiest to do i you have a good di erential diagnosis and want to conf rm your impression. I you do not have a diagnosis in mind, you may try entering descriptive words and looking or an image that matches what you are seeing. I the Google image search does not work, try a Web search and look at the links or other clues. Finally, there are dedicated atlases on the Internet or organ systems that can help you f nd the needed image. Most o these atlases have their own search engines, which can help direct you to the right diagnosis. Table 1-1 lists some o the best resources currently available online.

EXPANDING O UR INTERNAL IMAGE BANKS The larger our saved image bank in our brain, the better clinicians and diagnosticians we can become. The expert clinician has a large image bank stored in memory to call on or rapid pattern recognition. Our image banks begin to develop in medical school when we view pictures in lectures and textbooks. We then begin to develop our own clinical image bank through our clinical experiences. Our re erences are printed color atlases, as well as those available on the Internet and electronically. Studying and learning the patterns rom any atlas can enhance your expertise by enlarging the image bank stored in your memory. An atlas takes the clinical experiences o clinicians over decades and gives it to you as a single re erence. We o er you, or the f rst time in the United States, a modern, comprehensive internal medicine color atlas, which includes areas such as oral health, dermatology, podiatry, and the eye.

USING IMAGES TO BUILD TRUST IN THE PATIENT–PHYSICIAN RELATIO NSHIP I you are seeing a patient with a mysterious illness that remains undiagnosed and you f gure out the diagnosis, you can o ten bridge the issues o mistrust and anxiety by showing the patient the picture o another person with the diagnosis. Use our atlas or that purpose and supplement it with the Internet. This is especially important or a patient who has gone undiagnosed or misdiagnosed or some time. “Seeing is believing” or many patients. Ask f rst i they would want to see some pictures o other persons with a similar condition; most will be very interested. The patient can see the similarities between their condition and the other images and eel reassured that your diagnosis is correct. Write down the name o the diagnosis or your patient and use your patient education skills.

TABLE 1-1 Exce lle nt Clinical Imag e Colle ctions on the Inte rne t

De rm Atlas

www.d e rmatlas.org

Johns Hop kins Unive rsity

De rmIS

www.d e rmis.ne t

De rm In ormation Syste ms rom Ge rmany

De rmne t

www.d e rmne t.com

Skin Dise ase Imag e Atlas

Inte ractive De rm Atlas

www.d e rmatlas.ne t

From Richard P. Usatine , MD

ENT

www.e ntusa.com

From an ENT p hysician

Eye

www.e ye round s.org

Unive rsity o Iowa

Fig ure Se arch

http ://f g ure se arch.askhe rme s.org

Unive rsity o Wisconsin

Imag e s o all typ e s

http ://commons.wikime d ia.org

Wikime d ia Commons

In e ctious Dise ase s

www.p hil.cd c.g ov

CDC Pub lic He alth Imag e Lib rary

Rad iolog y

http ://rad .usuhs.e d u/me d p ix/

Me d Pix

Skinsig ht

http ://www.skinsig ht.com/html

Log ical Imag e s

3

PART 1

4

LEARNING WITH IMAGES AND DIGITAL PHO TO GRAPHY Do be care ul when searching or images on the Web in the presence o patients. Sometimes what pops up is not pretty (or, or that matter, G- or PG-rated). I turn the screen away rom the patient be ore initiating the search and then censor what I will show them. I you teach, model this behavior in ront o your students. Show them how re erence books and the Internet at the point o care can help with the care o patients.

TAKING YO UR O WN PHO TO GRAPHS Images taken by you with your own camera o your own patients complete with their own stories are more likely to be retained and retrievable in your memory because they have a context and a story to go with them. We encourage our readers to use a digital camera (within a smartphone or a stand-alone camera) and consider taking your own photos. O course, always ask permission be ore taking any photograph o a patient. Explain how the photographs can be used to teach other doctors and to create a record o the patient’s condition at this point in time. I the photograph will be identif able, ask or written consent; or patients younger than age 18 years, ask the parent to sign. Store the photos in a manner that avoids any Health Insurance Portability and Accountability Act (HIPAA) privacy violations, such as on a secure server or on your own computer with password protection and data encryption. These photographs can directly benef t the patient when, or example, ollowing nevi or changes. Digital photography is a wonder ul method or practicing, teaching, and learning medicine. You can show patients pictures o conditions on parts o their bodies that they could not see without multiple mirrors and some unusual body contortions. You can also use the zoom view eature on the camera or smartphone to view or show a segment o the image in greater detail. Children generally love to have their photos taken and will be delighted to see themselves on the screen o your camera.

CHAPTER 1

The advent o digital photography makes the recording o photographic images less expensive, easier to do, and easier to maintain. Digital photography also gives you immediate eedback and a sense o immediate gratif cation. No longer do you have to wait or a roll o f lm to be completed and processed be ore f nding out the results o your photography. Not only does this give you immediate gratif cation to see your image displayed instantaneously in the camera, but also alerts you to poor-quality photographs that can be retaken while the patient is still in the o f ce. This speeds up the learning curve o the beginning photographer in a way that could not happen with f lm photography.

O UR GO ALS Many o the images in this atlas are rom my collected works over the past 27 years o my practice in medicine. My patients have generously allowed me to photograph them so that their photographs would help the physicians and patients o the uture. To these photos, we have added images that represent decades o experiences by other physicians and specialists. Physicians who have submitted their images to “Photo Rounds” in the Journal of Family Practice are also sharing their photos with you. Finally, 12 years o providing students with cameras during their clerkships at the University o Cali ornia at Los Angeles (UCLA) and the University o Texas Health Sciences Center at San Antonio (UTHSCSA) have allowed our students to add their experiences to our atlas. It is the goal o this atlas to provide you with a wide range o images o common and uncommon conditions and provide you with the knowledge you need to make the diagnosis and initiate treatment. We want to help you to be the best diagnostician you can be. We may aspire to be a clinician like Sir William Osler and have the detective acumen o Sherlock Holmes. The images collected or this atlas can help move you in that direction by making you prepared to see what you need to see.

PART 2

ISSUES IN INTERNAL MEDICINE

*

St re ng t h o Re co mme nd at io n (SO R)

De f nit io n

A

Re comme nd ation b ase d on consiste nt and g ood -q uality p atie nt-orie nte d e vid e nce .*

B

Re comme nd ation b ase d on inconsiste nt or limite d -q uality p atie nt-orie nte d e vid e nce .*

C

Re comme nd ation b ase d on conse nsus, usual p ractice , op inion, d ise ase -orie nte d e vid e nce , or case se rie s or stud ie s o d iag nosis, tre atme nt, p re ve ntion, or scre e ning .*

Se e Ap p e nd ix A on p ag e s 1241-1244 or urthe r in ormation.

6

PART 2

ISSUES IN INTERNAL MEDICINE

2 DO CTO R–PATIENT RELATIO NSHIP Mind y A. Smith, MD, MS

Ch a pt e r 2

their physicians to treat a wide variety o medical problems but re er to a specialist when necessary (88% and 84%), and they wanted a physician who looks at the whole person—emotional, psychological, and physical (73% and 74%). In addition, o 39 possible attributes o physicians, most patients (68-97% stated extremely or very important) viewed the ollowing as the most important attributes or services that drive overall satis action with their physician: • Does not judge; understands and supports.

Humor is one way through which patients and physicians relate to each other on a human level. Even politics is not o -limits in the doctor– patient relationship.

PATIENT STO RY Patient stories, particularly i we listen attentively and nonjudgmentally, provide us with a window into their lives and experiences. These stories help us to know our patients in power ul ways, and that knowledge about the patient, as someone special, provides the context, meaning, and clues about their symptoms and illnesses that can lead to healing. At our best, we serve as witness to their struggles and triumphs, supporter o their e orts to change and grow, and guide through the medical maze o diagnostic and therapeutic options. Sometimes, their stories become our own stories—those patients who we will never orget because their stories have changed our lives and the way we practice medicine (Figure 2-1).

WHAT PATIENTS WANT FRO M THEIR PHYSICIAN Based on 2002 telephone interviews o the general public (N = 1031), 1 most patients strongly agreed that they wanted to take an active role in their health care (82% and 91%, patients with amily physicians and patients with general internists, respectively), they wanted

• Always honest, direct. • Acts as partner in maintaining health. • Treats both serious and nonserious conditions. • Attends to emotional and physical health. • Listens to me. • Encourages healthier li estyle. • Tries to get to know me. • Can help with any problem. • Someone I can stay with as I get older.

WHAT PHYSICIANS WANT FRO M AND FO R PATIENTS Although the types and intensity o relationships with patients di er, our positive and negative experiences with patients shape us as clinicians, in uence us in our personal relationships, and shape the character o our practices. Arthur Kleinman, in his prologue to Patients and Doctors: LifeChanging Stories from Primary Care, wrote, “We all seem to want (or demand) experiences that matter, but maybe what is oremost is that we want experiences in which we matter.” There is perhaps no greater satis action than the belie that what we do and who we are matters to those we care or in both our personal and pro essional lives. 2 A positive relationship with a patient is one o mutual growth. This concept o doctor–patient reciprocity is not new and can be ound in the writings o Erasmus, more than 500 years ago, arising rom a classical conception o riendship. 3 As clinicians we want patients to be healthier and improved in some meaning ul way a ter our encounter with them. Meaning ul elements common to healing practices across cultures include the ollowing4: • Providing a meaning ul explanation or the sickness • Expressing care and concern • O ering the possibility o mastery and control over the illness or its symptoms Family physicians (n = 300) who were interviewed as part o the uture o amily medicine (FFM) initiative stated that the ollowing things completely captured the essence o what they ound as most satis ying about being a amily physician1: • The strong relationships developed with patients over the years (54%). • The variety—no day is ever the same (54%).

FIGURE 2-1 Dr. Je rry Winakur and Lyd ia Guild are e njoying a re ce nt visit, one o many in the ir 30-ye ar re lationship as d o ctor and p atie nt. The y have e ach had the ir trials and jo ys ove r the d e cad e s and now f nd that the y have grown old together. (Reproduced with permission from Jeffrey M. Levine, MD)

• O ers me a strong sense o purpose because I can make a real di erence in people’s lives (48%). • Don’t spend their days taking care o illness, but take care o the whole patient (Figure 2-2) (46%).

DO Ct O r –pa t Ie Nt r e La t IO NSh Ip

PART 2

ISSUES IN INTERNAL MEDICINE were signif cantly more likely to have good control based on hemoglobin A1C than were patients o physicians with low empathy scores (56% and 40%, respectively). 7 • Patients who reported an established relationship with a primary care provider (PCP) were less likely to currently smoke than those who lacked a PCP relationship (26.5% and 62.3%, respectively). 8 • There is a direct link between patient satis action and the amount o in ormation that physicians provide. 9,10 • There is also a strong positive correlation between patient satis action, recall, and understanding and physician’s partnership building (eg, enlisting patient input). 10 • Provision o health in ormation to patients in uences patient decision making in important ways.

FIGURE 2-2 Dr. Alan Blum is a p hysician who has b e e n d oing ske tche s o his p atie nts or d e cad e s now. Whe n he p re se nts his d rawing s, he re ad s his p oe tic storie s that g o with the d rawing s. Some o his d rawing s have b e e n p ub lishe d in JAMA. He re is the p oe m that g oe s with this man’s story: “Gov’me nt g ave me a chance to g e t a he arin’ aid or re e . But whe n I we nt to th’ d octor, he say, ’We ll, cap ’n, the re g onna b e a lot o’ thing s you d on’t want to he ar!’”

LEARNING FRO M PATIENTS To learn rom patients, clinicians must do the ollowing: • Move outside o their worldview and accept the patient’s point o view and belie system.

ESSENTIALS O F GO O D DO CTO R–PATIENT RELATIO NSHIP Although the doctor–patient relationship may be viewed as a contract or providing services, Dr. Candib argues that this view does not f t well with developing a healing relationship that must be based on “unconditional positive regard,” benef cence, caring, and a moral basis o conduct. 11 Furthermore, contracts ail to deal with the unpredictable and ail to acknowledge the power inequality between physicians and patients. To counter this power imbalance, Candib emphasizes the need or clinicians to use that power to empower the patient. Following are the requirements o empowerment o patients12: • Recognition o oppression—Acknowledging the patient’s contextual problems (eg, poverty, race, religion, sexual pre erence) and the sources o inequality and oppression that contribute to their health status or the purpose o naming and supporting the patient’s reality.

• Let go o stereotypes, biases, and dogma.

• Expressing empathy—A characteristic o being with the patient that leads to empowerment by conf rming the worthiness o the other.

• Use active empathic listening, see the patient in context, and adopt re ective and re exive practices. 5

• Respecting the patient as a person (particularly those who are cognitively or otherwise impaired).

• Emphasize patient dignity and control within a supportive team, which may include amily, riends, aides, and community resources.

• Responding to the changing abilities o the patient—Using exibility, timing, and a shi ting o skills to advance the movement o the patient in a positive direction.

• Accept di erences o opinion or patient re usal graciously without abandoning the patient. 4

• Look at each patient encounter as a cross-cultural event. Western medical training acculturates clinicians into a world seen in large part as one o problems and solutions; this is o ten at odds with patients’ need to f nd meaning in the illness episode, be heard and acknowledged, and learn to live a quality li e with chronic illness.

BENEFITS O F A GO O D DO CTO R–PATIENT RELATIO NSHIP Beyond the benef t o enhancing the medical experience or both clinicians and patients, data that support developing a good doctor–patient relationship include the ollowing: • Patients who are satisf ed with their physicians are 3 times more likely to ollow a prescribed medical regimen. 6 • Patients with diabetes cared or by physicians with high empathy scores (based on the physician’s sel -administered Je erson Scale o Empathy)

• Using language that increases patient’s power—Solicit and legitimize the patient’s explanations and experience. This may include using questions about what patients want rom the encounter, what they think about their problem, what they think the clinician should do about the problem, and what they have tried that has worked or them in the past. • Taking the patient seriously—This includes respecting the patients’ ears, not trivializing their concerns, and allowing the truth to un old over time to prevent harm or embarrassment to the patient. • Supporting choice and control—Accepting patients’ priorities, even i health is not the top one, and allowing patients to choose, even i their choice is to relinquish control. • Eliciting the patient’s story, o ten over time, to be able to put the illness experience into historical and social context. • Providing patient education in a context in which the clinician asks what the patient already knows, what they want and need to know, and whether they have any questions. Health educators should discuss risks and benef ts o a proposed diagnostic or treatment plan

7

8

PART 2

ISSUES IN INTERNAL MEDICINE that are meaning ul to the patient and provide patients with the tools and in ormation to make their own decisions. Some patients pre er to delegate authority to the physician to make medical decisions; the challenge then is or the physician to f nd out the patient’s pre erences and values. Caring is also an essential eature o a good doctor–patient relationship. Caring, as connectedness with a patient, evolves rom the relationship. Within the context o this relationship, the clinician makes the patient eel known, pays attention to the meaning that a symptom or illness has in the patient’s li e, expresses real eeling (separate rom re ecting back the patient’s eelings), and practices devotion (eg, a willingness at times to do something extra or the patient). 13 To provide care to patients, clinicians must take care o themselves.

SKILLS FO R BUILDING GO O D DO CTO R–PATIENT RELATIO NSHIPS • One strategy or improving communication with patients is using the patient-centered interview. 14 This technique ocuses on eliciting the patient’s agenda in order to address their concerns more promptly. • Incorporating the BATHE (Background, A ect, Trouble and Handling o their current situation, and Empathy) method into the standard patient interview was ound to increase 8 o 11 measures o patient satis action. 15 • Using sel -disclosure or the purposes o role modeling and guiding, showing empathy, building trust, and developing a stronger relationship in the context o shared assumptions about the relationship are some o the other strategies. Sel -disclosure, however, must be balanced with the obligation o not to take advantage o patients by using such disclosure as an appeal or help or intimacy. 16 In addition, it may be prudent to avoid disclosure o unresolved issues and to avoid repetitiousness (as when disclosure predominates over inquiry).

MAXIMIZING THE EFFECTIVENESS O F PATIENT EDUCATIO N

Ch a pt e r 2

Despite lack o clinical outcomes rom this research, authors o a systematic review ound the ollowing18: • Methods or communicating clinical evidence to patients include nonquantitative general terms, numerical translation o clinical evidence, graphical representations, and decision-making aids. • Focus-group data suggested that clinicians present options and/ or equipoise be ore asking patients about pre erred decision-making roles or ormats or in ormation. • Absolute risk reduction is pre erred. • The order o in ormation presented and the time rame o outcomes can bias patient understanding. • Limited evidence supports use o human stick f gure graphics or aces or single probabilities and vertical bar graphs or comparative in ormation. • Less-educated and older patients pre erred proportions to percentages and did not appreciate conf dence intervals. REFERENCES 1. American Academy o Family Physicians. Future of Family Medicine Project. http:/ / www.aa p.org/ online/ en/ home/ membership/ initiatives/ uture amilymed.html. Accessed March 2012. 2. Kleinman A. Prologue. In: Borkan J, Reis S, Steinmetz D, Medalie JH, eds. Patients and Doctors: Life-Changing Stories from Primary Care. Madison, WI: University o Wisconsin Press; 1999:ix. 3. Albury WR, Weisz GM. The medical ethics o Erasmus and the physician-patient relationship. Med Humanit. 2001;27(1):35-41. 4. Brody H. Family and community—re ections. In: Borkan J, Reis S, Steinmetz D, Medalie JH, eds. Patients and Doctors: Life-Changing Stories from Primary Care. Madison, WI: University o Wisconsin Press; 1999:67-72. 5. Medalie JH. Learning rom patients—re ections. In: Borkan J, Reis S, Steinmetz D, Medalie JH, eds. Patients and Doctors: Life-changing Stories from Primary Care. Madison, WI: University o Wisconsin Press; 1999:50. 6. Rosenberg EE, Lussier MT, Beaudoin C. Lessons or clinicians rom physician-patient communication literature. Arch Fam Med. 1997;6(3):279-283.

Steps or maximizing patient education or behavior change include the ollowing17:

7. Hojat M, Louis DZ, Markham FW, et al. Physicians’ empathy and clinical outcomes or diabetic patients. Acad Med. 2011;86(3):359-364.

• Understanding the power o the clinician’s expertise as a motivator toward behavior change.

8. DePew Z, Gossman W, Morrow LE. Association o primary care physician relationship and insurance status with reduced rates o tobacco smoking. Chest. 2010;138(5):1278-1279.

• Being patient centered and patient responsive (eg, assess readiness to change, patient wishes or autonomy or assistance in decision making). • Encouraging the patient to choose one or at most 2 behavior goals at a time. • Being specif c in the advice given.

9. Blanchard CG, Labrecque MS, Ruckdeschel JC, Blanchard EB. Physician behaviors, patient perceptions, and patient characteristics as predictors o satis action o hospitalized adult cancer patients. Cancer. 1991;65(1):186-192.

• Obtaining commitment rom the patient or change.

10. Hall JA, Roter KL, Katz NR. Meta-analysis o correlates o provider behavior in medical encounters. Med Care. 1988;26(7):657-675.

• Using multiple educational strategies, o ten over time and rom a team o providers.

11. Candib LM. Medicine and the Family—A Feminist Perspective. New York, NY: Basic Books; 1995:119-145.

• Using social support when possible. • Assuring appropriate ollow-up.

12. Candib LM. Medicine and the Family—A Feminist Perspective. New York, NY: Basic Books; 1995:246-273.

Some guidance can be ound in the literature or discussing clinical evidence with patients in the process o making medical decisions.

13. Candib LM. Medicine and the Family—A Feminist Perspective. New York, NY: Basic Books; 1995:206-239.

DO Ct O r –pa t Ie Nt r e La t IO NSh Ip

14. Brown J, Stewart M, McCracken E, McWhinney IR, Levenstein J. The patient-centered clinical method. 2. Def nition and application. Fam Pract. 1986;3(2):75-79. 15. Leiblum SR, Schnall E, Seehuus M, DeMaria A. To BATHE or not to BATHE: patient satis action with visits to their amily physician. Fam Med. 2008;40(6):407-411. 16. Candib LM. Medicine and the Family—A Feminist Perspective. New York, NY: Basic Books; 1995:181-205.

PART 2

ISSUES IN INTERNAL MEDICINE 17. Jaques LB, Curtis P, Goldstein AO. Helping your patients stay healthy. In: Sloane PD, Slatt LM, Ebell MH, Jacques LB, eds. Essentials of Family Medicine. Baltimore, MD: Lippincott Williams & Wilkins; 2002:117-125. 18. Epstein RM, Alper BS, Quill TE. Communicating evidence or participatory decision making. JAMA. 2004;291(19):2359-2366.

9

10

PART 2

ISSUES IN INTERNAL MEDICINE

Ch a pt e r 3

3 FAMILY PLANNING E.J. Maye aux Jr., MD Jame s Barrow, MD

PATIENT STO RY Your patient is a 25-year-old married woman who wants to postpone having children for another 2 years while she nishes graduate school. She and her husband are currently using condoms, but would like to change to something different. She is in good health and does not smoke. It is now your opportunity to discuss with her all the methods available to prevent pregnancy. First, you determine what she knows about the methods and if she has any preferences. She tells you that she is speci cally interested in either the hormonal vaginal ring (NuvaRing) (Figure 3-1) or the newest intrauterine device (IUD) that releases a hormone (Figure 3-2). Then you participate in shared decision making as she comes up with the method that best ts her lifestyle and health issues.

INTRO DUCTIO N Contraception is like many other treatments in medicine. Each method has its risks and bene ts. Each method has its barriers to use, such as compliance, cost, and social stigmas. By educating patients appropriately and letting them know beforehand of the potential side effects, we can greatly increase compliance and satisfaction.

FIGURE 3-2 Mire na (le vonorg e stre l-re le asing intraute rine syste m) p rovid e s e e ctive contrace p tion or at le ast 5 ye ars. (Re p rod uce d with p e rmissio n from Baye r He althCare Pharmace uticals Inc.)

EPIDEMIO LO GY • Approximately one-half of pregnancies in the United States are unintended1 and approximately one-half of these occurred in women using reversible contraception. 2 • The most commonly used contraceptive methods in the United States are oral contraceptive pills (OCPs), male condoms, and female sterilization. 3 • Long-acting reversible forms of contraception are increasingly popular. Encouraging these methods may help lower the unintended pregnancy rate. Gaps or discontinuation of use of short-acting methods lead to unintended pregnancy.4 • Newer contraceptives often have improved side-effect pro les or have more convenient delivery systems that may not require daily patient adherence. Having a wide range of contraceptive options helps patients nd a method that will work best for them. • This chapter focuses on contraceptive methods available in the United States and the considerations one must address when counseling patients on their choice of method.

CO NSIDERATIO NS • No contraception method is perfect. Each individual or couple must balance the advantages and disadvantages of each method and decide which offers the best choice. As the physician, one must help the patient make the appropriate decision based on many factors that are unrelated to their medical history or to the side-effect pro le of the method, such as the likelihood of compliance and access to follow-up. FIGURE 3-1 NuvaRing is a comb ine d ho rmonal intravag inal contrace p tive ring . The e xib le mate rial o the ring allows or e asy inse rtion and re moval. Note the size in comp arison to a q uarte r. (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

• Some important considerations in choosing a contraceptive method are its potential side effects, failure rates, and noncontraceptive bene ts. See Table 3-1.

PART 2

Fa MILY pLa NNING

ISSUES IN INTERNAL MEDICINE

TABLE 3-1 Contrace p tive O p tions Availab le in the Unite d State s in 2012

Unint e nd e d Pre g nancie s Wit h 1 Ye ar o Use (%) Me t ho d

Typ ical Use

The o re t ical

No nco nt race p t ive Be ne f t s

Use Wit h Bre ast e e d ing

None

85

85

—

—

Sp e rmicid e

29

18

None

Ye s

Withd rawal

27

4

None

Ye s

Pe riod ic ab stine nce ( e rtility aware ne ss)

25

3-5

None

Ye s

Diap hrag m with sp e rmicid e

16

6

None

Ye s

Fe male cond om

21

5

Pre ve nts STDs

Ye s

Male cond om

15

2

Pre ve nts STDs

Ye s

O CPs—comb ine d and p rog e stin-only

8

0.3

Re g ulation o me nstrual cycle and d ysme norrhe a, p ossib le d e cre ase in ovarian and e nd ome trial cance r risk, d e cre ase acne

No

Contrace p tive p atch

8

0.3

Same as O CPs

No

Vag inal ring

8

0.3

Same as O CPs

No

De p o-Prove ra

3

0.3

Same as O CPs

Ye s

Cop p e r-containing IUD

0.8

0.6

None

Ye s

Le vonorg e stre l IUD

0.2

0.2

Re g ulation o me nstrual cycle s and d ysme norrhe a

Ye s

Fe male ste rilization

0.5

0.5

None

Ye s

Male ste rilization

0.15

0.10

None

Ye s

Etonog e stre l imp lant

0.05

0.05

Same as O CPs

Sa e ty cond itional

IUD, intraute rine d e vice ; O CP, oral contrace p tive p ill; STD, se xually transmitte d d ise ase . Data rom Trusse ll J. Contrace p tive e f cacy. In: Hatche r RA, Trusse ll J, Ne lson AL, e t al, e d s. Contrace p tive Te chnolog y, 20th re v e d . Ne w York, NY: Ard e nt Me d ia; 2011:827-1010; He rnd on EJ, Zie man M. Ne w contrace p tive op tions. Am Fam Physician. 2004;69:853-860; He rnd on EJ, Zie man M. Imp roving Acce ss to Q uality Care in Family Planning : Me d ical Elig ib ility Crite ria for Contrace p tive Use . 2nd e d . Ge ne va, Switze rland : Re p rod uctive He alth and Re se arch, World He alth O rg anization; 2000. http ://whq lib d oc.who.int/p ub lications/2004/9241562668. p d . Acce sse d July 4, 2006; Sp e ro L, Fritz MA. Clinical Gyne colog ic End ocrinolog y and Infe rtility. 7th e d . Philad e lp hia, PA: Lip p incott Williams & Wilkins; 2005.

• Smoking increases the risks of the most dangerous side effects of estrogencontaining contraceptives. This is an important issue in helping a patient choose the safest and the best method. Encouraging smoking cessation is always a good intervention, but one might avoid prescribing an estrogencontaining contraceptive until the patient can truly quit smoking. • Avoid estrogen-containing contraceptives in women with hypertension or migraine with aura. In both cases, the theoretical or proven risk of stroke outweighs the advantages.

NEWER CO NTRACEPTIVE CHO ICES • In addition to the traditional 20 to 35 µg ethinyl estradiol (EE) OCPs, 30 and 20 µg EE in combination with the new progestogen drospirenone (Yasmin, YAZ) are available. Drospirenone has some

antimineralocorticoid activity and has been shown to decrease the water retention, negative affect, and appetite changes that are commonly associated with menstrual cycle changes. 4 Serum potassium levels should be monitored when women are at a risk for hyperkalemia. The progesterone in these pills often helps in decreasing the severity of acne. Beyaz is a newer formulation of the above with the addition of folate. If a patient becomes pregnant while taking this pill, her folate levels would be adequate to prevent neural tube defects. • Extended OCPregimens with 84 days of levonorgestrel-EE pills and 7 days of nonhormonal pills (Seasonale) are available. Seasonique has the same pills for the rst 84 days but uses 10 µg EE pills for the last 7 days to make up the 91-day cycle. They have similar advantages to other OCPs except that the patient has only 4 periods a year. Another extended OCP regimen combining levonorgestrel and EE has been released in which there are no nonhormonal pills at all (Lybrel).

11

12

PART 2

ISSUES IN INTERNAL MEDICINE

Ch a pt e r 3

• The hormonal vaginal ring (NuvaRing) has similar active ingredients of OCPs, but it does not require daily attention (see Figure 3-1). It is placed in the vagina for 3 weeks at a time (with 1 week off) and releases EE and etonogestrel. Withdrawal bleeding occurs during the ring-free week. The vaginal ring is associated with a lower incidence of breakthrough bleeding than standard OCPs. • There is a newer form of Depo-Provera given every 3 months, but is given subcutaneously (SQ) instead of intramuscularly (IM). The SQ version provides 30% less hormone, 104 versus 150 mg per injection. It works at least as well as Depo-Provera IM as a contraceptive, and also works as well as Lupron Depot for endometriosis pain with fewer hot ashes and less bone loss. If long-term use is considered, it may be prudent to select another contraceptive, discuss the risk of possible bone loss, or consider monitoring bone density in women using either version of Depo-Provera for more than 2 years. These medications can increase the incidence of acne and weight gain in some women as a result of the androgenic effects of the progesterone. • The Mirena IUD releases levonorgestrel and provides effective contraception for at least 5 years (see Figure 3-2). Pregnancy rates are comparable with those occurring with surgical sterilization. Coppercontaining IUDs are another long-term option lasting up to 10 years; however, it may be associated with dysmenorrhea and irregular vaginal bleeding some of the time. Twenty percent of women have amenorrhea after 1 year of use with Mirena, and as with the coppercontaining IUDs, there is a risk of expulsion. The absolute risk of ectopic pregnancy with IUD use is extremely low because of the high effectiveness of IUDs. However, if a woman becomes pregnant during IUD use, the relative likelihood of ectopic pregnancy is greatly increased. 5 • Nexplanon (etonogestrel implant) is an etonogestrel-containing single rod implant for subdermal use (Figure 3-3). It is a long-acting (up to 3 years), reversible, contraceptive method. It must be removed or replaced by the end of the third year. The implant is 4 cm in length with a diameter of 2 mm and contains 68 mg of the synthetic progestin etonogestrel (ENG). It does not contain estrogen or latex and is not radiopaque. The contraceptive effect of the ENG implant involves suppression of ovulation, increased viscosity of the cervical mucus, and alterations in the endometrium. In the rst year of use, it had the lowest failure rate of any form of contraception, including tubal ligation. 7 The effectiveness of Nexplanon in women who weigh more than 130% of

FIGURE 3-3 Ne xp lanon imp lantab le sub cutane ous contrace p tive syste m. The inse rtion d e vice is a sharp trochar and the imp lant is mad e o a so t silastic tub e . (Re p rod uce d with p e rmission from E.J. Maye aux Jr., MD.)

FIGURE 3-4 Essure tub al o cclusion d e vice or p e rmane nt ste rilization. It is p lace d within the allop ian tub e s using a vag inal ap p roach and a hyste roscop e . (Re p rod uce d with p e rmission from Jay Be rman, MD.)

their ideal body weight has not been studied. Problems with Nexplanon are similar to other progestin-only contraceptives (acne and gaining weight). • Nexplanon sterilization is a common and very effective form of contraception that should be considered permanent. • Hysteroscopic tubal occlusion (Essure) is a newer technique (Figures 3-4 to 3-6). The device is a exible microcoil designed to promote tissue growth in the fallopian tubes. It does not require any incisions and can be performed without general anesthesia, typically in less than 30 minutes. There is a 3-month waiting period after the device is placed when an alternative birth control must be used. On the 3-month follow-up visit, a hysterosalpingogram (HSG) is performed to document that the tubes have been blocked. • The combination contraceptive patch (Ortho Evra) releases EE and norelgestromin and has the same mechanism of action as OCPs (Figure 3-7). It is applied weekly for 3 weeks, followed by a patchfree week during which menses occur. Recommended application sites include the upper arm, buttocks, and torso (excluding the back and breasts). It has similar ef cacy to OCPs but may be less effective in women weighing more than 90 kg (198 lb). In a rare instance of patch detachment, it must be replaced. The progesterone in the patch may decrease the severity of acne.

FIGURE 3-5 Hyste roscop ic vie w showing the coile d Essure d e vice within a allop ian tub e imme d iate ly a te r it was imp lante d . (Re p rod uce d with p e rmission from Jay Be rman, MD.)

Fa MILY pLa NNING

PART 2

ISSUES IN INTERNAL MEDICINE FO LLO W-UP Monitor for side effects, level of usage, and tolerability. The contraceptive choice should be periodically reexamined as the patient may want to switch to a different method of contraception as needs and circumstances change.

PATIENT RESO URCES

• Managing Contraception Web site has a choices section that is good for patients—http:/ / managingcontraception.com/ . • NuvaRing Web site—http:/ / www.nuvaring.com/ . • Mirena Web site—http:/ / www.mirena-us.com/ . • Essure Web site—http:/ / www.essure.com/ . • Nexplanon Web site—http:/ / www.nexplanon-usa.com/ . • CDC Web site—http:/ / www.cdc.gov/ reproductivehealth/ UnintendedPregnancy/ Contraception.htm. • ACOG Web site—http:/ / www.acog.org/ publications/ patient_education/ ab020.cfm. FIGURE 3-6 Hyste rosalp ing og ram (HSG) with b ilate ral Essure d e vice s within the allop ian tub e s (arrows). Contrast mate rial d iste nd s the ute rine cavity b ut d oe s not e nte r the cornua, allop ian tub e s or p e ritone al cavity, ind icating succe ss ul occlusion. The b lack/g ray b ub b le in the white -ap p e aring ute rus is the HSG cathe te r b alloon. (Re p rod uce d with p e rmission from E.J. Maye aux Jr., MD.)

PATIENT EDUCATIO N For some contraceptive methods to be effective, the patient must be willing to use them consistently and correctly. Other methods do not require any action on the part of the patient. Patients will need to understand the bene ts and risks of the method they choose and how to be best assured that the method is working for them. If patients are aware of the possible side effects, they can address any such effect with their physician if an adverse effect occurs.

PRO VIDER RESO URCES

• Contraceptive Technology Table of Contraceptive Ef cacy— http:/ / www.contraceptivetechnology.org/ table.html. • American Family Physician. New Contraceptive Options— http:/ / www.aafp.org/ afp/ 20040215/ 853.html. • World Health Organization. Medical Eligibility Criteria for Contraceptive Use. 4th ed. 2009—http:/ / www.who.int/ reproductivehealth/ topics/ en/ .

REFERENCES 1. Henshaw SK. Unintended pregnancy in the United States. Fam Plann Perspect. 1998;30:24-29, 46. 2. Kost K, Singh S, Vaughan B, et al. Estimates of contraceptive failure from the 2002 National Survey of Family Growth. Contraception. 2008;77:10. 3. Piccinino LJ, Mosher WD. Trends in contraceptive use in the United States: 1982-1995. Fam Plann Perspect. 1998;30:4-10, 46. 4. Raine TR, Foster-Rosales A, Upadhyay UD, et al. One-year contraceptive continuation and pregnancy in adolescent girls and women initiating hormonal contraceptives. Obstet Gynecol. 2011; 117(2 pt 1):363-371. 5. Herndon EJ, Zieman M. New contraceptive options. Am Fam Physician. 2004;69:853-860. 6. World Health Organization. Medical Eligibility Criteria for Contraceptive Use. 4th ed. 2009. http:/ / www.who.int/ reproductivehealth/ topics/ en/ . Accessed May 21, 2012. 7. Trussell J. Contraceptive failure in the United States. Contraception. 2011;83;397-404.

FIGURE 3-7 The O rtho Evra comb ine d hormonal contrace p tive p atch. The p atch is chang e d we e kly or 3 we e ks and the n le t o or 1 we e k p e r cycle . (Re p rod uce d with p e rmission from E.J. Maye aux, Jr., MD.)

13

14

PART 2

ISSUES IN INTERNAL MEDICINE

Ch a pt e r 4

4 END O F LIFE

• Physical and emotional symptom management

Rad ha Ramana Murthy Gokula, MD Mind y A. Smith, MD, MS

• Advanced care planning

• Support of function, autonomy, personal dignity, and self-respect • Aggressive symptom control near death • Patient and family satisfaction • Patient’s assessment of overall quality of life and well-being

PATIENT STO RY An 89-year-old frail woman presents with Alzheimer disease, dementia, hypothyroidism, depression, congestive heart failure, and macular degeneration. Her functional status was gradually declining. It was dif cult for her family to provide 24-hour care and she was admitted to a nursing facility. Her dementia worsened over a period of 2 years in the nursing facility and she became incontinent of urine and feces while developing limitations in speech and ambulation. She could not sit up without assistance and lost her ability to smile and hold her head up independently. The facility was very supportive and a hospice consult was initiated. Figure 4-1 shows Dr. Gokula along with the hospice nurse visiting the patient for admission to hospice care.

INTRO DUCTIO N End-of-life care is care that is delivered to patients of all ages who have a very short life expectancy. This care is focused on meeting the patient’s emotional and physical needs for symptom relief and general comfort care, and offering patient and family support. Following are the 5 basic principles of palliative care1: • Respect the goals, preferences, and choices of the person. • Look after the medical, emotional, social, and spiritual needs. • Support the needs of family members. • Help patients and their families access needed health care providers and appropriate care settings. • Provide excellence in care at the end of life (see Figure 4-1). Following are the quality-of-care domains for a person at the end of life2:

• Family burden—emotional and nancial • Survival time • Provider continuity and skill • Bereavement services

EPIDEMIO LO GY • According to National Health Center statistics, there were approximately 2.42 million deaths in the United States in 2009, most were attributed to cardiovascular disease and cancer. 3 • The major causes of death in the population aged 25 to 44 years were accidents, cancer, heart disease, suicide, homicide, and other causes. • Among those aged 45 to 64 years, leading causes of death were cancer, heart disease, accidents, chronic respiratory diseases, and liver disease. The common causes of death in persons above age 65 years were heart disease, cancer, chronic lower respiratory disease, stroke, and Alzheimer disease. • In 2009, heart disease, cancer, chronic lower respiratory diseases, stroke, and accidents accounted for almost 64% of all deaths in the United States.4 • Thirty-two percent of all deaths in the United States in 2007 were inpatient hospital deaths. 5 Average hospital costs for a stay ending in death were $23,000, about 2.7 times higher than for a patient discharged alive. Hospice services were involved for approximately 20% of dying patients. 6 More than 70% of hospice patients had cancer and 90% of hospice patients died outside the hospital. The use of hospice and other endof-life services varies among different racial groups in the United States7: • Caucasians are more aware of advanced directives when compared to the non-white racial or ethnic groups. • The use of life-sustaining treatments is more common among African Americans when compared to other racial groups. • Cultural differences are also seen for disclosure of information about a terminal illness. Korean, Mexican, Japanese, and Native American populations are more likely to discourage discussion of terminal illness and patient prognosis and prefer families to be informed. • The involvement of family in the decision-making process with end-oflife care was seen among all racial groups, but Asian and Hispanic Americans prefer family-centered decision making when compared to other racial and ethnic groups.

ETIO LO GY AND PATHO PHYSIO LO GY Causes of death are multifactorial. Following are the major modi able contributors: FIGURE 4-1 Family p hysician D . Mu hy Gokula and hosp ice nu se Ch is Emch a e comfo ing and e xamining a e minally ill p a ie n ne a ing he e nd of life in He a land Hosp ice .

• Tobacco use—20.6% of all the adults in the United States smoke cigarettes; the highest rates are among men (23.5%) and American Indians/ Alaska Natives (23.2%).8 It is estimated that nearly 1 of every 5 deaths

e ND O F LIFe

each year in the United States is attributed to smoking. 9 Smoking increases the risk of developing emphysema (10- to 13-fold), heart and cardiovascular disease (2- to 4-fold), and many cancers (1.4- to 3-fold). • Poor diet—Diets that are high in fat (>40% of calories consumed) are associated with increased risk of breast, colon, endometrial, and prostate cancer. Diet is important in controlling diabetes, heart disease, obesity, and chronic renal disease. • Physical inactivity—Those who exercise regularly live longer and are healthier; exercise reduces the risk of cardiovascular disease and hypertension and improves function in those with depression, osteoarthritis, and bromyalgia. Unfortunately less than 20% of adults met the 2008 federal guidelines for aerobic activity and muscle-strengthening. 10

PART 2

ISSUES IN INTERNAL MEDICINE majority was unintentional.16 Opioid pain medications were involved in over 40%. Poisoning was the third leading method of suicide from 2005 to 2007, with 75% owing to alcohol and/ or drug overdose. The most commonly used drugs identi ed in drug-related suicides were prescription drugs in the opioid, benzodiazepine, and antidepressant classes.17

DIAGNO SIS It is estimated that approximately 70% of all deaths are preceded by a disease or condition such that it is reasonable to plan for dying in the near future. 6 These diseases or conditions are as follows:

• Alcohol consumption—Alcohol is consumed by 80% of the population, and 10% to 15% of men and 5% to 8% of women are alcohol dependent. Excess alcohol consumption (> 3 drinks per day) is associated with mood disorders (10-40%), cirrhosis (15-20%), and neuropathy (5-15%); it increases the risk of pancreatitis (3-fold) as well as cancers of the breast (1.4-fold), esophagus (3-fold), and rectum (1.5-fold). 11 In addition, based on data from 2009, an estimated 30.2 million people (12%) aged 12 years or older reported driving under the in uence of alcohol at least once in the past year. 12

• Cancer that is widespread, aggressive or metastatic and for patients who no longer seek curative care. Other clues include a decline in performance status and/ or signi cant unintentional weight loss.

• Injury—In 2004, 167,184 people died as a result of injury, accounting for 7% of all deaths. 13 The majority of injury-related deaths are unintentional. Falls are the leading mechanism of injury death for elderly people while for adults of 35 to 53 years, poisoning is the leading mechanism of injury death. Motor vehicles in traf c are the leading mechanism of injury death for all other age groups, except for children under age 2 years. Many of these deaths are preventable.

• Patients con ned to bed or who require assistance with all the basic activities of daily living.

• Sexual behaviors—Sexually transmitted infections (STIs) are among the most common infectious diseases and affect approximately 13 million people in the United States each year; most of these people are younger than age 25 years. Sexually transmitted diseases (STDs) are associated with increased risk of HIV/ AIDS; in 2007, there were approximately 455,636 persons living with AIDS in the United States.14 Causes of death from AIDS include infections (especially, pulmonary and central nervous system), cancer (especially, Kaposi sarcoma and non-Hodgkin lymphoma), cardiomyopathy, and nephropathy. • Illicit use of drugs—Drug addiction remains a major problem in the United States. According to data from the National Institute on Drug Abuse Monitoring the Future Survey of over 46,000 8th- to 12th-grade students, increases were seen in daily marijuana use (21.4% of high school seniors in the past 30 days) and lifetime ecstasy use in 8th graders (from 2.2% in 2009 to 3.3% in 2010) while decreases were noted in methamphetamine use (from 6.5% in 1999 to 2.2% in 2010) and current cocaine use (from 2.3 million in 2003 to 1.6 million in 2009). 12 Cocaine is associated with death from respiratory depression, cardiac arrhythmias, and convulsions; methamphetamine use is associated with life-threatening hypertension, cardiac arrhythmia, subarachnoid and intracerebral hemorrhage, ischemic stroke, convulsions, and coma. • Microbial agents—Microbial agents remain a major cause of death and disability with continued discovery of new agents and increasing drug resistance. Although it is dif cult to ascertain whether an infectious agent caused death or was incidental to death, the expert panel of investigators in New Mexico, on the basis of autopsy data, found that 85% (106/ 125) of the deaths (late 1994-mid 1996) were identi ed as infectious disease-related. 15 • Toxic agents—Toxic agents include poisons and environmental toxins. In the United States in 2008, there were 36,500 poisoning deaths; the vast

• Dementia with an inability to ambulate, bathe, or dress without assistance; associated urinary or fecal incontinence; inability to meaningfully communicate; or associated with life-threatening infections, multiple stage 3 or 4 skin ulcers, inability to maintain suf cient uid and calorie intake, or failure to thrive (including a temporal decline in functional status).

• Patients with a body mass index less than 22 and/ or those who refuse or do not respond to enteral or parenteral nutritional support. • Heart disease that is poorly responsive to optimal medical treatment, NYHA class IV, or congestive heart failure with poor ejection fraction (≤20%). Based on data from multiple studies including SUPPORT, Framingham, and IMPROVEMENT, 1-year mortality estimates are as follows: class II (mild symptoms), 5% to 10%; class III (moderate symptoms), 10% to 15%; class IV (severe symptoms), 30% to 40%. Independent predictors of poor prognosis in patients with heart failure include recent cardiac hospitalization, renal insuf ciency (creatinine ≥1.4 mg/ dL), systolic blood pressure less than 100 mm Hg and/ or pulse greater than 100 bpm, treatment-resistant ventricular dysrhythmias, treatment-resistant anemia, hyponatremia, cachexia, reduced functional capacity, and comorbidities (eg, diabetes). 18 • HIV/ AIDS with CD4 count less than 25 or persistent viral load more than 100,000 copies/ mL plus at least one of the following: wasting (loss of 33% of lean body mass), major AIDS-de ning refractory infection (eg, cryptosporidium infection) or malignancy (eg, central nervous system or systemic lymphoma), progressive multifocal leukoencephalopathy, renal failure, Karnofsky performance status (KPS) less than 50%, advanced AIDS dementia complex, or signi cant functional decline in the activities of daily living. • Neurologic disease (eg, Parkinson disease, amyotrophic lateral sclerosis, multiple sclerosis, muscular dystrophy, and myasthenia gravis) that is associated with rapid progression and/ or critical nutritional state, lifethreatening infections in the preceding 12 months, stage 3 or 4 skin ulcers, critically impaired breathing capacity and declined ventilator support, or life-threatening complication (eg, recurrent aspiration, sepsis). • Pulmonary disease including disabling dyspnea at rest or with minimal exertion, increased emergency department visits and/ or hospitalizations, hypoxemia on room air (oxygen saturation < 88%), cor pulmonale, unintentional progressive weight loss, or resting tachycardia greater than 100 bpm. • End-stage renal disease with progressive decline in those not seeking dialysis (or not a candidate), with a calculated creatinine clearance less

15

16

PART 2

ISSUES IN INTERNAL MEDICINE

Ch a pt e r 4

than 10 ( 6 mg/ dL for patients with diabetes).

A population-based survey of family members, friends, and caregivers in 6 US communities found the following21:

• End-stage liver disease with progressive decline in those with refractory ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, or recurrent variceal bleeding despite treatment.

• Seventy-one percent of terminally ill patients had shortness of breath.

• Stroke associated with coma in the acute phase; coma with abnormal brain stem response, absent verbal response, absent withdrawal response to pain, or serum creatinine greater than 1.5 mg/ dL at day 3; dysphagia and insuf cient intake of uids and calories; poor functional status; or poststroke dementia. • Nonspeci c terminal illness characterized by a rapid decline, disease progression, or progressive weight loss; dysphasia with aspiration; increase in emergency department visits and/ or hospitalizations; worsening pressure ulcers despite optimum care; or a decline in systolic blood pressure below 90 mm Hg. Unfortunately, physicians are often reluctant to make this determination, resulting in palliative and hospice care not being offered until very late in the course of the illness. In addition, physicians often feel that they must be able to predict a life expectancy of less than 6 months with certainty to institute hospice care. The National Hospice and Palliative Care Organization has evidencebased guidelines on determining prognosis for a number of noncancer conditions. 19 This information can assist clinicians in working with patients at the end of life on advanced care decisions and planning. Two validated instruments that may help clinicians estimate prognosis are the palliative performance scale (PPS) and the KPS. • The PPS (http:/ / meds.queensu.ca/ palliativecare/ assets/ pps_scale_tool. pdf) rates information on ambulation, activity and evidence of disease, self-care, intake, and consciousness level. The PPS was found to be a strong predictor of survival when applied at admission to patients in palliative care.20 In this retrospective cohort study, median survival time at PPS of 10% was 1 day, survival with PPS of 20% was 2 days, at PPS of 30% survival was 9 days, while at PPS of 60% median survival was 40 days. • The KPS (http:/ / www.hospicepatients.org/ karnofsky.html) is often used to follow the course of illness and is based on performance status ranging from normal (100%) to dead (0%). CLINICAL FEATURES Common physical symptoms reported by dying patients are as below6: • Constipation (90%) • Fatigue and weakness (90%) • Dyspnea (75%) and other cardiopulmonary symptoms such as cough

• Fify percent had moderate-to-severe pain. • Thirty-six percent were incontinent of urine or feces. • Eighteen percent were fatigued enough to spend more than 50% of their waking hours in bed.

MANAGEMENT Management often begins with communicating bad news to patients and families about likely or imminent death. This task can be extremely difcult. In cases where the patient is not deemed legally competent, make sure that the legal decision maker is present. In addition, if the patient is a non-English speaker, consider obtaining a skilled medical interpreter rather than relying on a family member. Providers may nd the following P-SPIKES approach useful22: • Preparation—Review information to be presented and practice. • Setting—Arrange time and place, ensure privacy, and include important support persons. • Perception of patient—Inquire about the patient’s and the family’s understanding of the illness. • Information needs—Find out about what the patient and family need to be told and in how much detail. • Knowledge of the condition—Provide bad news sensitively and slowly, warning them that bad news is imminent and checking to see whether there is understanding. • Empathy and exploration—Acknowledge the feelings expressed, give the patient and family time to react, and remind them that you are not abandoning them. • Summary/ strategic planning—Discuss next steps or schedule followups to do this if more time is needed. Roles for the primary care provider include consultation, providing anticipatory guidance, providing support and comfort, and assisting with identifying and managing symptoms (including pain control) (Figure 4-2). In assisting dying patients and their families or caregivers with making decisions about their care, clinicians should be prepared to discuss the following:

• Pain (36-90%)

• Realistic treatment options for cure or palliation of the primary disease process.

• Insomnia

• Advance directives and withholding of life-sustaining treatment.

• Other gastrointestinal symptoms, including dry mouth, anorexia, nausea, vomiting, constipation, diarrhea, and dysphagia

• Cultural beliefs and preferences (eg, truth-telling vs protecting the patient, religious beliefs).

• Fecal and urinary incontinence

• Preferences for place of care for those dying, involvement of others, and symptom management.

• Dizziness • Swelling and numbness of the extremities Following are the common mental and psychological symptoms reported by dying patients6: • Depression (75% symptomatic; < 25% with major depression) and feelings of hopelessness, anxiety, and/ or irritability • Confusion and delirium (up to 85% at the end stage)

A number of factors are important in providing optimal care to the dying patient. In a study of factors considered important to seriously ill patients, recently bereaved family members, and physicians involved in end-of-life care, investigators found the following23: • There was a general agreement on the items relating to having preferences in writing, symptom control, being kept clean, experiencing physical touch, good communication and knowing what to expect,

e ND O F LIFe

PART 2

ISSUES IN INTERNAL MEDICINE completed them. 6 Speci c forms do not have to be used and oral directives may be enforceable. 24 ° Proxy designations—Appointing an individual or individuals to make medical decisions (ie, durable power of attorney for health care). Legal aspects—The US Supreme Court has ruled that patients have a right to decide about refusing or terminating medical interventions. Many states have their own statutory forms for living wills. • The American College of Physicians and the American Society of Internal Medicine End-of-Life Care Consensus Panel note that life-sustaining treatment may be withheld for patients unable to speak for themselves if it is believed to be the patient’s wish, the surrogate decision maker states that it is the patient’s wish, and/ or it is in the patient’s best interests to do so. 25 • The prescription of high-dose opioids to relieve pain in terminally ill patients that result in death will not lead to criminal prosecution provided it was the physician’s intent to relieve suffering. 25 HO SPICE CARE AND SERVICES Hospice care refers to care when curative interventions have been judged to be no longer bene cial. This type of care can be delivered in many settings including home, hospital, or special residential facilities.

FIGURE 4-2 Pho og ap h of Ma jo ie Cla ke ake n b y he g and son. She suffe e d f om Alzhe ime d ise ase ha le f he d e p e sse d and f us a e d . In his p ic u e , ake n in 1996, Ma jo ie lis e ns o he nu se d e sc ib e he sce ne and e xp lain ha he y a e on he f on p o ch of he home . She d ie d in Janua y, 1997. (Re p rod uce d with p e rmission from Marshall Clarke .)

getting one’s affairs in order and achieving a sense of completion, and maintaining dignity and a sense of humor. • Patients reported wanting to remain mentally aware, not be a burden, and noted the importance of prayer and being at peace with God. They were not as concerned about dying at home. • Family members reported wanting to use all the treatment options and to help patients avoid pain, shortness of breath, and suffering. ADVANCED DIRECTIVES

• The types of hospice services include physician and nursing care, home health aides, pastoral care, counseling, respite care, and bereavement programs (Figure 4-3). • Hospice eligibility general guidelines include ful lling the criteria for end-stage disease as outlined above and documenting both the patient’s and family’s decision on palliative care rather than curative care and rapid disease progression. In addition, documentation of signi cant functional decline is important using validated instruments like Functional Assessment Staging (FAST), PPS, basic activities of daily living (BADLs), and/ or NYHA class IV heart disease. Other criteria include weight loss of 7.5% or 10% in the preceding 3 to 6 months, respectively, or serum albumin less than 2.5 g/ dL. Physicians should be aware of the Medicare hospice bene t (MHB) covered under Medicare Part A (physician services are billed under Medicare Part B). 25 In the United States, the MHB pays for 80% of all

Advance directives and advance care planning continue to be poorly utilized. Clinicians should consider outpatient and inpatient opportunities to introduce these concepts with the goals of empowering the patient and understanding the patient’s preferences if they are too sick to speak for themselves. Possible scenarios can be discussed such as recovery from an acute event (specifying acceptable interventions) and persistent vegetative state (preferences for life-sustaining interventions). • The National POLST (physician orders for life-sustaining treatment) Paradigm task force is a new program designed to improve the quality of end-of-life care based on effective communication of patient wishes, documentation of medical orders, and a commitment by health care professionals to honor these wishes. Information can be found at http:/ / closure.org and includes Web-based resources for patients and health providers. • Advance directive documents are of 2 broad types—instructional directives and proxy designations. ° Instructional directives such as living wills that describe decisions about care and health care. These can be general or speci c. Although 80% of Americans endorse completing living wills, only 20% (and less than one-third of health care providers) have

FIGURE 4-3 D . Alan Blum is a family p hysician who has b e e n d oing ske che s of his p a ie n s fo d e cad e s now. Whe n he p e se n s his d awing s, he e ad s his p oe ic s o ie s ha g o wi h he d awing s. Some o f his d awing s have b e e n p ub lishe d in JAMA.

17

18

PART 2

ISSUES IN INTERNAL MEDICINE

Ch a pt e r 4

hospice care including medical, nursing, counseling, and bereavement services to terminally ill patients and their families. Medicare bene ciaries who choose hospice care receive noncurative medical and support services for their terminal illness. Home care may be provided along with inpatient care if needed and a variety of other services that are not covered by Medicare. Eligibility criteria are listed below:

therapy. Many hospitals now have inpatient palliative care services to assist patients, families, and primary care providers in delivering this type of care. General approach to palliative care focuses on 4 broad domains— managing physical symptoms, managing psychological symptoms, addressing social needs, and understanding spiritual needs.

• Patient is eligible for Medicare Part A or Medicaid.

• Needs assessment—Clinicians should focus on the 4 domains and try to understand the degree of dif culty and how much the identi ed problem interferes with the patient’s life.

• Patient is terminally ill, that is, patient’s physician and medical director of hospice certify that the patient is terminally ill and has a life expectancy of 6 months or less if the disease runs its normal course. If the medical director is the patient’s physician only one signature is required. • Patient chooses hospice care and signs a Medicare hospice bene ts form. This process is reversible and patients may at a future time elect to return to Medicare Part A. • Hospice care is provided by a Medicare-certi ed hospice program. • Under Medicare, DNR status cannot be used as a requirement for admission. Length of bene ts • Entitled to receive hospice care as long as he or she meets the eligibility criteria. • Hospice bene t consists of two 90-day bene t periods, followed by an unlimited number of 60-day bene t periods. • Bene t periods may be used consecutively or at intervals. • Patient needs to be certi ed terminally ill at the beginning of each period. • No life time limit to hospice care for Medicare bene ciaries. • If patient experiences remission of the disease and is discharged from hospice, he or she can be eligible for hospice care in the future without any regard to the previous use of hospice services. • The same rules apply for Medicaid patients. Services covered include physician, nurse, dietician, and medical social services, medical supplies and equipment, outpatient drugs for symptom management and pain relief, and home care (eg, aids, physical, occupational, and speech therapy). Other services included are as follows: • Short-term general inpatient care for problems that cannot be managed at home—most commonly intractable pain or delirium. • Short-term respite care—up to 5 days to permit family caregivers to take a break (can incur a 5% copayment). • Counseling in home for patient and family. • Bereavement, pastoral, and spiritual support for patient and family. • Payment of consulting physician fees at 100% of Medicare allowance. • Physician, nurse, social worker, and counselor on-call availability 24 hours a day, 7 days a week. Services not covered include active treatment of terminal illness (except for symptom management and pain control of the terminal illness), care provided by a physician or facility that has not contracted with the patient’s hospice agency, and continuous nursing assistant or nursing home room and board charges. PALLIATIVE CARE Palliative care is care focused on preventing, relieving, reducing, or soothing symptoms of disease without affecting a cure. 26 As such, it is not restricted to patients who are dying but can be used along with a curative

• Setting goals and continuous reassessment—Goals for care include improving symptoms, delaying disability, nding peace, and providing for the loved ones. Plan times to review these goals as the course of the illness changes or progresses. • Pain management—There is no reason that patients need to suffer, particularly at the end of life. Barriers to managing pain successfully include limited ability of providers to assess pain severity, fear of sanction/ prosecution, and lack of knowledge (including awareness of guidelines). ° Assessment of pain—Important aspects include periodicity (eg, continuous), location, intensity, modifying factors, effects of treatments, and impact on the patient. ° Intervention—This includes nonpharmacologic treatment (eg, massage, positioning, transcutaneous electrical nerve stimulation [TENS], physical therapy), pain medications, and other palliative procedures (eg, nerve blocks, radiotherapy, acupuncture). ° Pain medications may be approached in a stepwise fashion from nonopioids (eg, acetaminophen [4 g/ d], ibuprofen [1600 mg/ d]), to mild opioids (eg, codeine [30 mg every 4 hours] or hydrocodone [5 mg every 4 hours]) to stronger opioids (eg, morphine 5-10 mg every 4 hours). Doses should be titrated as needed. Side effects (eg, constipation, nausea, and drowsiness) should be anticipated and prevented (eg, laxatives and antiemetic) or treated. Patients may become tolerant to these side effects after approximately 1 week. Speci c pain syndromes may require additional consideration. These include the following: Continuous pain, which requires round-the-clock dosing, rescue medication, and regular assessment and readjustment. If rescue medication has been needed, increase the daily opioid dose by the total dose of rescue medication the next day. For longer duration of action, transdermal fentanyl may be considered (100 µg/ h is equianalgesic to morphine 4 mg/ h and has a duration of 48-72 hours). Neuropathic pain (arising from disordered, ectopic nerve signals) is typically shock-like or burning. Medications to consider in addition to opioids are gabapentin (100-300 mg daily or up to 3 times daily), 5% lidocaine patch (3 patches daily for a maximum of 12 hours), tramadol (50-100 mg 1-3 times daily), and tricyclic antidepressants (10-25 mg at bedtime titrated to 75-150 mg). 28 Adjunctive analgesic medications are those that potentiate the effects of opioids. These include the above treatments for neuropathic pain, glucocorticoids (eg, dexamethasone once daily), clonidine, and baclofen. Legal concerns—Physicians may be unwilling or uncomfortable providing high-dose opioids out of fear that they would be hastening the patient’s death. However, the assumption that opioids appropriately titrated to control pain hasten death is not supported by medical evidence. In addition, as noted above, the physician’s intent to relieve suffering, despite the risk of death, is ethical and unlikely to result in prosecution.

e ND O F LIFe

CO NTRO L O F CO m m O N Sy m PTO m S 6

• Constipation —Occurs due to medications, inactivity, and poor nutritional/ hydration, limited ber intake, confusion, and intestinal obstruction comorbidities such as diabetes mellitus, hypothyroidism, or hypercalcemia. The goal of treatment should be one bowel movement every 1 to 2 days. Constipation prophylaxis should be started for all patients taking regular opiate regimens. Options include increasing ber, stool softeners (eg, sodium docusate [Colace] 300-600 mg/ d oral), stimulant laxatives (eg, prune juice 1/ 2-1 glass/ d, senna [Senokot] 2-4 tablet/ d, bisacodyl 5-15 mg/ d orally or per rectum), and osmotic laxatives (eg, lactulose 15-30 mL every 4-8 hours, magnesium hydroxide [milk or magnesia] 15-30 mL/ d). • Dyspnea—When possible, treat reversible causes (eg, infection, hypoxia). Options include opioids (eg, codeine 30 mg every 4 hours, morphine 5-10 mg every 4 hours) and anxiolytics (eg, lorazepam 0.5-2 mg oral/ sublingual/ intravenous [IV], diazepam 5-10 mg oral/ IV). A parenteral infusion or long-acting opiate can also be tried, with bolus dosing for breakthrough pain; nebulized opiates are ineffective for dyspnea. 29 For patients with a history of respiratory disease consider bronchodilators and/ or glucocorticoids. For those with excessive secretions, scopolamine may be considered, starting with a low dose every 2 hours or with worsening dyspnea, as needed. Oxygen is commonly prescribed although data do not support effectiveness in improving the sensation of breathlessness;30 one crossover trial found ambient air delivered by nasal cannula was as effective as oxygen for dyspnea. 30 The inexpensive and simple practice of blowing ambient air on the patient’s face may help relieve dyspnea. • Fatigue—Occurs due to disease factors (eg, heart failure, tumor necrosis factor), cachexia, dehydration, anemia, hypothyroidism, and medications. Options include decreasing activity, increasing exercise as tolerated, changing medications, glucocorticoids (eg, dexamethasone once daily), or stimulants (eg, dextroamphetamine 5-10 mg oral). Moda nil, an analeptic drug, may also be considered (initial dose 200 mg). • Depression—Because many of the somatic symptoms used to diagnose depression in healthy individuals are present in patients who are dying, psychological criteria become more important in making treatment decisions. Options include counseling, exercise, and medications (eg, selective serotonin reuptake inhibitor); low doses should be used initially (eg, uoxetine 10 mg/ d) and increased as needed. Psychostimulants (eg, dextroamphetamine or methylphenidate 2.5-5 mg twice daily) may be considered if rapid onset of action is needed; these may be used in conjunction with traditional antidepressants. • Delirium—Occurs due to metabolic abnormalities (liver failure, electrolyte disturbance, vitamin B12 de ciency), infection, brain tumors, medications, and multiple other causes. Options include treating reversible causes and medications including neuroleptics (eg, haloperidol 0.5-5 mg oral/ subcutaneous/ intramuscular [IM]/ IV every 1-4 hours, risperidone 1-3 mg every 12 hours), anxiolytics (eg, lorazepam 0.5-2 mg oral/ IM/ IV), and anesthetics (propofol 0.3-2 mg/ h continuous infusion). ADDRESSINg SO CIAL NEEDS Considerations include economic burden and caregivers: ° The US health insurance system is neither universal nor comprehensive and many patients and their families nd themselves under tremendous nancial strain. ° Twenty percent of terminally ill patients spend more than 10% of 6 the family income on health care costs beyond insurance premiums.

PART 2

ISSUES IN INTERNAL MEDICINE ° Ten percent to thirty percent of families need to secure additional

monies by means such as selling assets or taking out a second mortgage to cover health care costs. 6 stop work to provide care for a termi° Twenty percent of caregivers nally ill family member. 6 ° Families/ caregivers often need outside help such as providing personal care for the patient such as bathing, psychological or spiritual counseling, respite care, or making arrangements for the body after death. ° Primary care providers can facilitate encounters with family and friends by offering their presence and suggestions about easing the visits (eg, reading to the patient, sharing music, or creating a videotape, audiotape, or scrapbook). ° Hospice and social workers can offer great assistance to patients and families in addressing these needs. Understanding spiritual needs ° Approximately 70% of dying patients become more religious or spiritual at the end of life. noted the importance of ° As noted by Steinhauser et al., patients prayer and being at peace with God. 24 ° Physicians should ask about and support patient and family expressions of spirituality and consider encouraging pastoral care, as desired.

PATIENT AND FAMILY EDUCATIO N It is very important to involve patients and their families in discussion at an early stage as most want to know their diagnosis and prognosis. • The role of the primary care physician should be discussed, particularly if other providers are involved in the care of the patient. Possible roles include consultation about care needs, anticipatory guidance on prognosis and expected symptoms, provision of support and comfort, and assistance with managing symptoms. • Families usually suffer emotionally, spiritually, and nancially as they care for the patient. 21 Family members often experience a sense of hopelessness, anger, guilt, and powerlessness when they cannot relieve the suffering of their terminally ill family member. • Families who need to provide care for a terminally ill patient should be made aware of community resources and the provisions in the Family Medical Leave Act. 31 • It is not unusual to see hidden family con icts resurface in the face of a terminal illness and any emotional tension that exists between the caregivers and patient can impede care. Physicians should be sensitive to the con icts and cultural in uences and closely observe how patients and their families are communicating so that they can better support them, allowing them to express their emotions and concerns and referring them to appropriate counselors or support groups when needed. 32,33 • Children should not be excluded from this process and the physician, with permission, can help in determining what children already know about the illness and in providing accurate information about the diagnosis, prognosis, and treatment expectations for the dying family member. Also advise caregivers to try to maintain the children’s daily schedule and routines of the family as much as possible, monitor for problems at school, encourage questions, and plan activities (eg, reading a story) when visiting ill family members. It may be helpful to inform teachers and counselors at school about the family situation and request that the teachers let the parent know if the child is having any dif culty or talks about worries.

19

20

PART 2

ISSUES IN INTERNAL MEDICINE • Consider counseling for the child if the child requests help or displays symptoms of depression or anxiety that interfere with school, home, or peers, risk-taking behavior, or signi cant discord with others. The following are the processes that many dying people go through: • Social withdrawal—Initial withdrawal is from the surroundings and then worldly interests decline and nally withdrawal from family, ultimately leading to loss of communication. • Decreasing nutritional requirements—There is a decreased need for uids and solids; uids are usually preferred and should follow what the patient wants rather than force-feeding. • Disorientation—There is increased confusion with time, place, and person. Usually patients talk about seeing people who have already died or state that their death is nearing. Redirecting the patient is necessary only if asked for or if the patient is distressed. • Decreased senses—Hearing and vision decrease. Use soft lights that help with decreasing visual hallucinations. Speak softly and gently as patients hear even at the end of life. Hearing is the last of the 5 senses to be lost. • Restlessness—Also called “terminal restlessness” is caused by the change in the body’s metabolism. Reassurance is important and appropriate symptom management with medications may be helpful. • Sleep—There is increased time spent in sleep that may be a result of changes in the body’s metabolism or natural to the underlying disease process. Spending time at the bedside can help capture the time when the patient is most alert. • Incontinence of urine and bowel movements is often not a problem until death is very near. Absorbent pads can be placed under the patient for greater comfort and cleanliness or a urinary catheter may be used for comfort care. The amount of urine will decrease and becomes darker at the end of life. Expected physical changes include the following: • Skin color changes include ushing, bluish hue to the skin, and cold sensation of the skin. Skin may have a jaundiced look when the patient is approaching death. The arms and legs of the body may become cool to the touch. The hands and feet become purplish. The knees, ankles, and elbows are blotchy. These symptoms are a result of decreased circulation. • Blood pressure decreases; the pulse may increase or decrease. • Body temperature can uctuate; fever is common. • Increased perspiration along with clamminess. • Respirations may increase, decrease, or become irregular; there may be periods of cessation of breathing (apnea). • Congestion can present as a rattling sound in the lungs and/ or upper throat. This occurs because the patient is too weak to clear the throat or cough. The congestion can be affected by positioning, may be very loud, and sometimes just comes and goes. Elevating the head of the bed and swabbing the mouth with oral swabs may be helpful. • The patient may enter a coma before death and not respond to verbal or tactile stimuli.

FO LLO W-UP WITHDRAWAL O F LIFE-SUSTAININg TREATm ENT • Evidence-based criteria for guiding physicians through this process is lacking; however, general consensus exists based on ethical and clinical principles in the care of these patients. 34,35

Ch a pt e r 4

• Withdrawal of life-sustaining treatment can be considered when curative care is not possible and supportive or other treatment is no longer desired and does not provide comfort to the patient. • Withholding life-sustaining treatment is morally, ethically, and legally equivalent to withdrawing life support. Any kind of treatment that is given to the patient can be withdrawn or withheld. In conducting these discussions with patients and their families, the physician needs to consider a patient’s information-sharing preferences (eg, a preference for limited information), minimum acceptable quality of life and functional status, whether the patient is able to understand consequences of life-sustaining treatment, whether procedures offered con ict with the patient’s values, and the patient’s need for advice and guidance. 36 • Treat withdrawal of life-sustaining treatment equivalent to a medical procedure and all formalities (eg, informed consent) should be ful lled prior to the procedure. • If withdrawal of one life-sustaining treatment is indicated, then consider withdrawing all existing treatments for the patient. • A general consensus should be reached with the health care team and family members that is in the best interest of the patient. Following are the steps that should be taken for withdrawal of life support36: ° Informed consent. ° Appropriate setting and monitoring. ° Sedation and analgesia. ° Having a plan for withdrawal (information about the protocol can be found in fast facts at www.eperc.mcw.edu). ° Pastoral, nursing, and emotional support. ° Documentation. ° Interventions to improve care during withdrawal of life-sustaining treatment that can be considered are consultation with an ethics committee, palliative care team, family conferences, and a standardized order form for withdrawing life-sustaining therapies. 37 g RIEF AND b EREAVEm ENT FO LLO W-UP • Manifestations of grief consist of both psychological symptoms (eg, sadness, anxiety, emotional lability, apathy, impaired concentration) and physical symptoms (anorexia, change in weight, trouble initiating or maintaining sleep, fatigue, headache). In the rst month following death, it is important to reassure surviving family members and friends that these manifestations of grief are normal and to offer support, suggestions for symptom management, and coping resources. • Subsequent follow-up visits should be used to assess the progress of mourning and to identify depression; if the latter is identi ed, consider pharmacotherapy and counseling. • Usually, the primary physician is noti ed of the death and may be required to make the pronouncement (based on lack of vital signs and lack of response to noxious stimulus) and complete the death certi cate (noting cause of death and contributing medical conditions). • Following the death of the patient, personal expressions of condolence from the primary care provider(s) and staff should be encouraged and range from cards to attending visitation and the funeral; based on personal experience, the latter can assist with grieving and closure for the physician. SUg g ESTED READINg S • Callanan M, Kely P. Final Gifts: Understanding the Special Awareness, Needs and Communications of the Dying. Bantam Books; 1992. • Ray MC. I Am Here to Help: A Hospice Workers Guide to Communicating with Dying People and Their Loved Ones. Hospice Handouts, McRay Company.

e ND O F LIFe

• Lattanzi-Licht M, Mahoney JJ, Miller GW. The National Hospice Organization Guide to Hospice Care: The Hospice Choice: In Pursuit of A Peaceful Death. Simon & Schuster. • Hanson W. The Next Place. Waldman House Press; 1997. • Baugher R, Calija M. A Guide to the Bereaved Survivor. Caring People Press. Newcastle, WA; 1998. • Brown LK, Brown M. When Dinosaurs Die: A Guide to Understanding Death. Little Brown & Company. Boston; 1998. PATIENT RESO URCES

• Caring Connections—http:/ / www.caringinfo.org. • Get Palliative Care—www.getpalliativecare.org. • National Family Caregivers Association—http:/ / www .nfcacares.org/ . • National Hospice and Palliative Care Organization—http:/ / www.nhpco.org. PRO VIDER RESO URCES

• American Academy of Hospice and Palliative Medicine—http:/ / www.aahpm.org/ . • National Hospice and Palliative Care Organization—http:/ / www.nhpco.org. • American Pain Society—http:/ / www.ampainsoc.org. • American Society for Bioethics and Humanities—http:/ / www .asbh.org. • American Society of Law, Medicine and Ethics—http:/ / www .aslme.org. • End-of-Life Care Consensus Panel—American College of Physicians-American Society of Internal Medicine—http:/ / www .acponline.org/ running_practice/ ethics/ . • The EPEC Project (Education resource online)—http:/ / www .epec.net. • Palliative Care Matters—http:/ / www.pallcare.info.

REFERENCES

PART 2

ISSUES IN INTERNAL MEDICINE Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill Companies Inc.; 2005:53-66. 7. Kwak J, Healy WE. Current research findings on end-of-life decision making among racially or ethnically diverse groups. Gerontologist. 2005;45(5):634-641. 8. Centers for Disease Control and Prevention. Vital signs: current cigarette smoking among adults aged ≥18 years—United States, 2009. MMWR Morb MortalWkly Rep. 2010;59(35):1135-1140. 9. Centers for Disease Control and Prevention. State-speci c smokingattributable mortality and years of potential life lost—United States, 2000-2004. MMWR Morb MortalWkly Rep. 2009;58(02):29-33. 10. National Center for Health Statistics. Health, United States, 2010: in brief. Hyattsville, MD. 2011. 11. Schuckit MA. Alcohol and alcoholism. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds. Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill Companies Inc.; 2005:2562-2566. 12. National Institute on Drug Abuse. InfoFacts: nationwide trends. http:/ / www.drugabuse.gov/ publications/ infofacts/ nationwidetrends. Accessed May 2013. 13. United States Department of Health and Human Services. Injury in the United States: 2007 Chartbook. http:/ / www.cdc.gov/ nchs/ data/ misc/ injury2007.pdf. Accessed May 2013. 14. Centers for Disease Control and Prevention. AIDS in the United States by geographic distribution. http:/ / www.cdc.gov/ hiv/ resources/ factsheets/ geographic.htm. Accessed May 2013. 15. Wolfe MI, Nolte KB, Yoon SS. Fatal infectious disease surveillance in a medical examiner database. http:/ / www.cdc.gov/ ncidod/ eid/ vol10no1/ 02-0764.htm. Accessed May 2013. 16. Centers for Disease Control and Prevention. Drug poisoning deaths in the United States, 1980-2008. http:/ / www.cdc.gov/ nchs/ data/ databriefs/ db81.htm. Accessed May 2013. 17. Centers for Disease Control and Prevention. Suicides due to alcohol and/ or drug overdose. http:/ / www.cdc.gov/ ViolencePrevention/ pdf/ NVDRS_Data_Brief-a.pdf. Accessed May 2013. 18. Reis eld GM, Wilson GR. Prognostication in heart failure. Fast facts and concepts. October 2005:143. http:/ / www.eperc.mcw.edu/ EPERC/ FastFactsIndex/ ff_143.htm. Accessed May 2013.

1. Von Gunten CF. Interventions to manage symptoms at the end of life. J Palliat Med. 2005;8(suppl 1):S88-S94.

19. National Hospice and Palliative Care Organization. http:/ / www. nhpco.org (for members). Accessed March 2012.

2. Lynn J. Measuring quality of care at the end of life: a statement of principles. JAm Geriatr Soc. 1997;45:526-527.

20. Lau F, Downing GM, Lesperance M, et al. Use of palliative performance scale in end-of-life prognostication. J Palliative Med. 2006;9(5): 1066-1075.

3. Xu J, Kochanek KD, Tejada-Vera B. Deaths: preliminary data for 2007. NationalVital Statistics Reports. Hyattsville, MD: National Center for Health Statistics; 2009:58(1). 4. Kochanek KD, Xu JQ, Murphy SL, et al. Deaths: preliminary data for 2009. NationalVital Statistics Reports. Hyattsville, MD: National Center for Health Statistics; 2011:59(4). 5. Zhao Y, Encinosa W. The cost of end-of-life hospitalizations, 2007. HCUP Statistical Brief # 81. November 2009, revised April 2010. Rockville, MD: Agency for Healthcare Research and Quality. http:/ / www.hcup-us.ahrq.gov/ reports/ statbriefs/ sb81.pdf. Accessed March 2012. 6. Emanuel EJ, Emanuel LL. Palliative and end-of-life care. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds.

21. Emanuel EJ, Fairclough DL, Slutsman J, et al. Assistance from family members, friends, paid care givers, and volunteers in the care of terminally ill patients. N Engl J Med. 1999;341(13):956-963. 22. Buckman R. How to Break Bad News:A Guide for Health Care Professionals. Baltimore, MD: Johns Hopkins University Press; 1992. 23. Steinhauser KE, Christakis NA, Clipp EC, et al. Factors considered important at the end of life by patients, family physicians, and other care providers. JAMA. 2000;284(19):1476-1482. 24. Meisel A, Snyder L, Quill T; American College of Physicians— American Society of Internal Medicine End-of-Life Care Consensus Panel. Seven legal barriers to end-of-life care: myths, realities and grains of truth. JAMA. 2000;284(19):2495-2501.

21

22

PART 2

ISSUES IN INTERNAL MEDICINE 25. Turner R. Fast facts and concepts No. 82 and 83. Medicare hospice bene t Part 1. January 2003. End-of-Life Physician Education Resource Center. http:/ / www.eperc.mcw.edu. Accessed March 2012. 26. Field MJ, Cassel CK, eds. Approaching Death: Improving Care at the End of Life. Washington, DC: National Academy Press; 1997.

CHAPt Er 4

31. Department of Labor. Wage and hour division. Family and Medical Leave Act. http:/ / www.dol.gov/ whd/ fmla/ . Accessed May 2013. 32. Larson DG, Tobin DR. End of life conversations: evolving practice and theory. JAMA. 2000;284:1573-1578.

27. World Health Organization. Pain ladder. http:/ / www.who.int/ entity/ cancer/ palliative/ painladder/ en/ . Accessed March 1, 2007.

33. Della Santina C, Bernstein RH. Whole patient assessment, goal planning, and in ection points: their role in achieving quality end-of life care. Clin Geriatr Med. 2004;20:595-620.

28. Dworkin RH, Backonja M, Rowbotham MC, et al. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol. 2003;60:1524-1534.

34. Jonsen AR, Seigler M, Winslade WJ. Clinical Ethics:A Practical Approach to Ethical Decisions in Clinical Medicine. 4th ed. New York, NY: McGraw-Hill; 1998.

29. Clemens KE, Quednau I, Klaschik E. Use of oxygen and opioids in the palliation of dyspnea in hypoxic and non-hypoxic palliative care patients: a prospective study. Support Care Cancer. 2009;17:367-377.

35. Gordon DR. Principles and practice of withdrawing life-sustaining treatments. Crit Care Clin. 2004;20:435-451.

30. Philip J, Gold M, Milner A, et al. A randomized, double-blind, crossover trial of the effect of oxygen on dyspnea in patients with advanced cancer. J Pain Symptom Manage. 2006;32:541-550.

36. Billings JA, Krakauer EL. On patient autonomy and physician responsibility in end-of-life care. Arch Intern Med. 2011;171(9):849-853. 37. Curtis JR. Interventions to improve care during withdrawal of lifesustaining treatments. J Palliat Med. 2005;8(suppl 1):S116-S131.

SO CIAL JUSTICE

5 SO CIAL JUSTICE

PART 2

ISSUES IN INTERNAL MEDICINE O UR STO RIES AS CARING CLINICIANS

Mind y A. Smith, MD, MS Richard P. Usatine , MD

O all the orms o inequality, injustice in health care is the most shocking and inhumane. —Martin Luther King, Jr.

The f rst question which the priest and the Levite asked was“I I stop to help this man, what will happen to me?”But ... the Good Samaritan reversed the question: “I I do not stop to help this man, what will happen to him?” —Martin Luther King, Jr.

PATIENT STO RIES At only 5.5 lb (10 lb less than the th percentile or weight on the World Health Organization’s growth chart), an 8-month-old in ant boy su ered rom severe malnutrition. In the summer o 2003, amid the height o Liberia’s civil war, his aunt brought him to the Médecins sans Frontières/ Doctors Without Borders hospital or treatment. Because o the war, his amily had been orced to f ee rom their home, leaving behind their usual methods o getting ood. Dr. Andrew Schechtman was there to help the day the child was brought to the clinic in Liberia (Figure 5-1). Despite the best available treatment or the malnutrition and concurrent pneumonia, the boy died on his third hospital day.

Those o us who become physicians or other health care providers do so or many reasons. One reason is because o a desire to help someone else. Along the way, we sometimes lose ourselves in the day-to-day struggles, the disappointments, the obligations, the atigue, and the proound helplessness that descends upon us a ter a particularly bad day. But we are still here and, i we listen with our hearts, we are still capable o great and small things. We are privileged in so many ways and we must recognize our power over ourselves and over the communities that we serve. It is easy to become overwhelmed by the problems that we ace as clinicians and as ellow human beings. Our health care system is in shambles, our natural world is being poisoned, our nations are continually at war, and yet, as this chapter highlights, there is so much that we can do—we can listen, we can observe, we can witness, we can bring aid, we can touch, we can love, and we can lead. The text that ollows highlights just a ew examples o the ways in which our colleagues are challenging themselves to nd creative solutions to the many problems aced by those who are underserved, displaced, or su ering.

DO CTO RS WITHO UT BO RDERS (ANDREW SCHECHTMAN, MD) EPIDEMIO LO GY The UN High Commissioner or Re ugees reported that in 2011 there were 10.9 million re ugees (those displaced across an international border) and 27.5 million internally displaced persons (IDPs, those displaced within their own country). 1 At the end o 2010, the UN re ugee agency was caring or an estimated 14.7 million o these IDPs. During times o a complex humanitarian emergency (de ned as a humanitarian crisis in a country, region, or society where there is a breakdown o authority resulting rom internal or external conf ict and which requires an international response that goes beyond the mandate or capacity o any single agency and/ or the ongoing UN country program), the ollowing usually occur2: • Civilian casualties • Populations besieged or displaced • Serious political or conf ict-related impediments to delivery o assistance • Inability o people to pursue normal social, political, or economic activities • High security risks or relie workers

ETIO LO GY

FIGURE 5-1 Dr. And re w Sche chtman was the re to he lp the d ay a se ve re ly malnourishe d child was b roug ht to the clinic in war-torn Lib e ria. De sp ite the b e st availab le tre atme nt that could b e p rovid e d in the Doctors Without Bord e rs hosp ital, the child d ie d o comp lications o malnutrition and p ne umonia—a casualty o war and p ove rty. (Re p rod uce d with p e rmission from And re w Sche chtman, MD.)

People can be displaced rom their homes by man-made (war, persecution) or natural disasters (tsunami, earthquake, or hurricane). War is responsible or most o the displacement. Some o the source countries accounting or the most re ugees are A ghanistan, Sudan, Somalia, the Palestinian territories, and Iraq. • Communicable diseases usually cause the most illness and deaths in humanitarian emergencies in less-developed countries. Children younger than 5 years o age are the most vulnerable. 2 Other priority

23

24

PART 2

ISSUES IN INTERNAL MEDICINE

Ch a pt e r 5

areas include provision o adequate sa e water, ood, shelter, and protection rom violence. • In addition to the usual causes o illness and death in emergencya ected populations in less-developed countries (measles, malaria, pneumonia, and diarrhea), crowded settlements may be prone to outbreaks o cholera, meningitis, and other diseases, which can be rapidly spread. Such outbreaks may be explosive and cause many deaths in a relatively short period o time.

PRO BLEM IDENTIFIED In times o stability, writes Dr. Andrew Schechtman, many o the poorest people in the world succeed in their struggle to meet basic needs or shelter, ood, and water. When displaced rom their homes by manmade or natural disaster, communities and extended amilies are disrupted, access to ood and water are lost, and marginal circumstances become desperate. Displaced people are o ten dependent on the support o the international aid community to meet their basic needs.

BEING PART O F THE SO LUTIO N When in rastructure collapses as a result o man-made or natural disasters, access to health care can be limited or nonexistent. Serving as a volunteer physician with Médecins sans Frontières (Doctors Without Borders) allowed Dr. Schechtman to provide medical care to people in desperate circumstances who had nowhere else to turn or assistance. Bearing witness to tragedies such as the case described in Figure 5-1 gave him another means to help, that is, the authority to speak out on behal o victims like this child, ocus public attention on the situation, and encourage political pressure to bring the ghting to an end.

DISASTER RELIEF (RICHARD USATINE, MD)

FIGURE 5-2 A husb and and wi e d isp laying the b anne r the y mad e while b e ing strand e d on the ir roo d uring hurricane Katrina in Ne w O rle ans. The husb and , who had an ab ove -the -kne e amp utation, manag e d to climb with his crutche s on to the roo o the ir oo d e d home . A te r 2 d ays the y we re save d rom the ood wate rs. In a she lte r in San Antonio the y d isp laye d the sig n that he lp e d save the ir live s. (Re p ro d uce d with p e rmission fro m Richard P. Usatine , MD.)

• O the 25 deaths occurring in this period (0.2%), 23 occurred in patients who were seen or an illness (92%) and 2 occurred in patients seen or an injury (8%). • About 1235 (9.1%) visits or injuries and illnesses were reported among relie workers (eg, paid military, paid civilian, sel -employed, or volunteer).

ETIO LO GY When hurricanes move onto land, the resulting storm surges, violent winds, heavy rains, and f ooding can cause extensive damage. Hurricanes Katrina and Rita caused devastating storm-surge conditions or coastal

EPIDEMIO LO GY Hurricane Katrina was the deadliest hurricane to strike the United States since 1928. Katrina made initial land all on August 25, 2005, in south Florida as a category 1 hurricane increasing rapidly in strength to category 5 upon reaching the Gul o Mexico. On September 24, 2005, a second category 3 hurricane, Rita, orced the cessation o response activities in New Orleans and prompted the evacuation o Louisiana and Texas cities near the Gul . In the days a ter the hurricane struck, displacement o people living in these areas resulted in more than 200,000 in evacuation centers in at least 18 states (Figures 5-2 to 5-4). There were more than 1800 deaths reported in Louisiana, Mississippi, Florida, Alabama, and Georgia. • Eight hospitals and 9 acute care acilities in New Orleans reported on 17,446 visits (including 8997 [51.6%] or illness; 4579 [26.2%] or injury) during the days a ter hurricane Rita and during repopulation o the city. 3 • Approximately 1500 people (10.9%) were admitted to a hospital. The most common reasons or hospital admission were heart disease (26.6%), gastrointestinal illness (12.3%), mental health condition (6.7%), and heat-related illness (6.1%).

FIGURE 5-3 Dr. Usatine with a young man who was e vacuate d rom Ne w O rle ans a te r hurricane Katrina. The y are in a she lte r in San Antonio and Dr. Usatine has just f nishe d an incision and d rainag e o an ab sce ss close to the e ye (se e Fig ure 123-1 or an imag e o the ab sce ss p rior to d rainag e ). The San Antonio me d ical community mo b ilize d q uickly to p rovid e me d ical care to the Katrina e vacue e s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

SO CIa L JUSt ICe

PART 2

ISSUES IN INTERNAL MEDICINE stabilized and taken to a local hospital with EMT transport. The physical a f ictions were the tip o the iceberg o the psychological trauma that the evacuees had su ered.

BEING PART O F THE SO LUTIO N

FIGURE 5-4 Thousand s o p e op le sle e p ing in a she lte r in San Antonio a te r b e ing e vacuate d rom Ne w O rle ans and the Gul Coast in 2005. The Katrina e vacue e s e xp e rie nce d the horro rs o the hurricane , the ood , and the Sup e r Dome . Some e vacue e s we re ad d e d as hurricane Rita thre ate ne d the Gul Coast. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Mississippi, Louisiana, and Alabama and damage as ar east as the Florida panhandle. Storm-induced breaches in the New Orleans levee system resulted in the catastrophic f ooding o approximately 80% o that city. 4 Hurricane Katrina disrupted basic utilities, ood-distribution systems, health care services, and communications in large portions o Louisiana and Mississippi. Be ore 1990, the majority o hurricane-related deaths in the United States resulted rom drowning caused by sudden storm surges. 5 Since 1990, advances in warning technology and timely evacuation have increased the proportion o indirect causes o death and injury rom hurricanes, such as electrocutions, cleanup injuries, and carbon monoxide poisonings. During and a ter hurricane Katrina, the majority o deaths resulted rom storm surges along the Mississippi and Louisiana coastlines and f ooding in the New Orleans area.

PRO BLEM IDENTIFIED Dr. Usatine, a pro essor o medicine at the University o Texas Health Science Center San Antonio watched the horror o hurricane Katrina com ortably rom the sa ety o his home and work in San Antonio. On September 3, 2005 the rst re ugees (evacuees) rom hurricane Katrina were brought to San Antonio. Dr. Usatine joined hundreds o other health care volunteers to provide ree health care in the shelters that received these rst evacuees (see Figure 5-2). Medical students also mobilized to be there to assist the local doctors in caring or these patients. Thousands o evacuees rom New Orleans were transported directly to Kelly Air Force Base or ood, shelter, social services, and medical care. Medications were donated rom local pharmacies and doctors and nurses rom the community and the universities came to provide services. Many medical problems were identi ed and treated including skin in ections rom the unsanitary f oodwaters. Common skin problems included cellulitis, skin abscesses, and impetigo (see Figure 5-3). Furthermore li e-threatening conditions included patients with diabetes and hypertension out o control because they were evacuated without their medications, their medications were lost or their prescriptions ran out. One man began seizing in ront o Dr. Usatine’s eyes because he had been without his antiepileptic medicines or 1 week. Fortunately, he was

Every evacuee had a rightening story to tell and some were looking or amily members and children rom whom they had been separated. Providing shelter, ood, medical and social services to thousands o people at once was a great challenge but with all the agencies and volunteers that could be mustered in San Antonio most would say that the e ort was a success. The work o providing services and ultimately resettlement or these evacuees went on or months. Hurricane Rita threatened the Gul Coast only 4 weeks a ter hurricane Katrina and this added additional evacuees to the people in San Antonio needing services (see Figure 5-4). As a physician, Dr. Usatine ound it rewarding to be there at the time o need or his ellow human beings who had su ered immeasurably due to the natural disasters and the lack o preparedness or these disasters. To this day he nds it incredible that such a wealthy nation neglected the known risks o f ooding in New Orleans and let the levees go unrepaired until the city o New Orleans had to pay the price o the disaster brought on by hurricane Katrina. He was proud to be part o the relie e ort that was mounted in his hometown o San Antonio.

INTERNATIO NAL HUMANITARIAN EFFO RTS: ETHIO PIA (RICK HO DES, MD) EPIDEMIO LO GY Chronic ood de cits a ect about 792 million people in the world, including 20% o the population in developing countries. Malnutrition greatly increases the risk o disease and early death, particularly in young children where protein-energy malnutrition plays a major role in hal o all deaths o children under age 5 years annually in developing countries. 6 Worldwide, malnutrition a ects 1 in 3 people and is especially common among the poor and those with inadequate access to health education, clean water, and good sanitation. About 26% o children with proteinenergy malnutrition live in A rica. Severe orms o malnutrition include marasmus, iodine de ciency which can result in cretinism and irreversible brain damage, and vitamin A de ciency which can result in blindness and increased risk o in ection and death. 6 Worldwide, 2.4 billion people will remain without improved sanitation in 2015 and in 2011, 768 million people relied on unimproved drinking water sources. In most o A rica, sanitation coverage is less than 50%. 7 Ethiopia and its neighbor Somalia are among the ew remaining countries in A rica with less than 50% o the population using improved sources o drinking water.7 Piped drinking water supplies, associated with the best health outcomes, are present only or 1% to 10% o Ethiopia’s population.

ETIO LO GY Ethiopia has a population o over 91 million people. The gross national income per capita is $1100, making it one o the poorest nations in the world. The probability o dying under age 5 years is 68/ 1000 live births,

25

26

PART 2

ISSUES IN INTERNAL MEDICINE

Ch a pt e r 5

in part due to the low percentage o women attending antenatal care and only 10% o births being attended by skilled health personnel. 8 The health work orce is nearly nonexistent with 0.3 physicians per 10,000 population and 2.5 nurses and midwives per 10,000 population. Health problems in Ethiopia include maternal mortality, malaria, tuberculosis (TB), and HIV/ AIDS compounded by malnutrition and lack o access to clean water and sanitation.

PRO BLEM IDENTIFIED Rick Hodes is an internist who has lived and worked in Ethiopia or over 20 years. As an orthodox Jew, he always aspired to serve others and even as a child, his avorite books were about doctors who went to remote places to help people. He rst went to Ethiopia in 1984 to do amine relie work. His experience o working at a mission in Ethiopia run by Mother Teresa changed his li e. He returned to Ethiopia on a Fulbright Fellowship and in 1990 was hired by the American Jewish Joint Distribution Committee (JDC) as the medical adviser or the country. His original position was to care or 25,000 potential immigrants to Israel but he is continually drawn back to Ethiopia to provide care to patients. When asked once why he wouldn’t pre er to work in the United States than A rica with its poverty and lack o resources, Hodes said, “It would be less rustrating—but it would also be less inspiring.”

BEING PART O F THE SO LUTIO N FIGURE 5-6 A p atie nt o Dr. Hod e s with se ve re kyp hoscoliosis se cond ary to tub e rculosis o the sp ine . (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

As senior consultant at a Catholic mission, Dr. Hodes helps patients with heart disease (rheumatic and congenital) (Figure 5-5), spinal disease (TB and scoliosis) (Figure 5-6), in ectious disease and cancer. He has worked with re ugees in Rwanda, Zaire, Tanzania, Somalia, and Albania in addition to Ethiopia. Dr. Hodes is part o a team at the American Jewish JDC, a Jewish humanitarian assistance organization ounded in 1914 that provides needed services in more than 70 countries. One among his JDC duties has been providing medical care or thousands o Ethiopian Jews preparing to immigrate to Israel. In addition to its assistance to the Ethiopian Jewish community, the JDC has served tens o thousands o Ethiopians, Jews and non-Jews, through clinics, immunization, nutrition programs, amily planning, and community health. Dr. Hodes has worked primarily in Ethiopia or the JDC since 1990. In addition to providing direct patient care, he has arranged specialized

care or hundreds o children in need with neurosurgeons and orthopedic surgeons in the United States and Ghana. He has ostered numerous orphaned children and adopted 4 children, providing needed medical care with his own insurance. Some o these children are now attending schools and colleges around the United States. He has also led teams o doctors, who come to work with him as volunteers (Figure 5-7). In one interview, Hodes said, “Getting ree medical care in a Catholic hospital by a Jewish doctor is like the whole world coming together. It’s the way the world should work.”

FIGURE 5-5 Examining an Ethiop ian orthod ox p rie st with rhe umatic he art d ise ase who has incre asing cong e stive he art ailure . (Re p rod uce d with p e rmission from Rick Hod e s, MD.)

FIGURE 5-7 Dr. Hod e s with Ame rican me d ical stud e nts and d octors visiting him at his clinic at Mothe r Te re sa’s mission in Ad d is Ab ab a, Ethiop ia. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

SO CIa L JUSt ICe

CARING FO R THO SE WITH DISABILITIES (LAURIE WO O DARD, MD) EPIDEMIO LO GY Approximately 54 million Americans currently live with at least one disability and the vast majority (52 million) live in their communities (Figure 5-8).9 • According to data rom 1999, the prevalence rate o disability was 24% among women and 20% among men. 10 Approximately 32 million adults had di culty with one or more unctional activities, and approximately 16.7 million adults had a limitation in the ability to work around the house. Two million adults used a wheelchair and 7 million used a cane, crutches, or a walker. • O children aged 3 to 17 years, 4.9 million were told that they had some type o learning disability and 12.8% (9.4 million) had special health care needs. 9 • Racial and ethnic minorities have higher rates o disabilities than whites or Asian Americans; 7.3 million individuals (ages 15 to 65 years) with disabilities are o racial or ethnic minorities. • In 2005, the surgeon general issued a Call to Action to improve the health and wellness o persons with disabilities underscoring the need in this population. 9

PART 2

ISSUES IN INTERNAL MEDICINE ETIO LO GY Challenges to a person’s health can happen at any age and at any time. Disabilities are not illnesses, rather they are limitations related to a medical condition that have an inf uence on essential li e unctions such as walking, seeing, or working. 9 Furthermore, disabilities do not a ect all people in the same way. • O all the adults with disabilities, 41.2 million (93.4%) reported that their disability was associated with a health condition including arthritis and rheumatism (17.5%), back or spine problems (16.5%), heart trouble or hardening o the arteries (7.8%), lung or respiratory problems (4.7%), dea ness or hearing problems (4.2%), mental or emotional problems (3.7%), blindness or visual problems (3.4%), and intellectual disability (2%). 10 • Rates o disability are increasing in part because o the aging population, better survival o catastrophic illnesses and trauma, and advances in preventing in ant and child mortality.

PRO BLEM IDENTIFIED As a mother o a child with pro ound disabilities, Dr. Laurie Woodard ound that her medical training did little to prepare her or caring or her child or nding help (see Figure 5-8). She became acutely aware that people with disabilities had great di culty in nding physicians and those who provided care o ten seemed a raid o them. She said, “I couldn’t imagine someone not wanting to care or her because she had a disability.” Physicians tend to ocus on the medical condition and not the whole person and their amilies; when con ronted with the patient’s health care needs and unctional issues, the eeling o acting more like a social worker than a physician caused them to all back into medical model ramework. In addition, societal support or those with disabilities, particularly disabilities acquired as an adult, are ragmented and the primary care physician needs to become the link.

BEING PART O F THE SO LUTIO N Dr. Woodard began to care or increasing numbers o patients with disabilities, training hersel through reading, experience, and asking patients what worked. As she worked with individual students she planned or a time when she could break into the medical student curriculum to provide this training. Eight years ago, when the curriculum or third-year students underwent major re orm, she saw her opportunity. Within the primary care 12-week experience, a curriculum on special populations was planned and Laurie made sure that it included teaching about people with disabilities. Her curriculum, implemented in 2005 with goals ranging rom sensitivity training to understanding both the capabilities and needs o individuals with disabilities, contains the ollowing components:

FIGURE 5-8 Dr. Laurie Wood ard and he r d aug hte r Anika share a g ood laug h ollowing b re ak ast while on vacation in Ne w Me xico. Altho ug h Anika is d e p e nd e nt or all he r activitie s o d aily living and is nonve rb al b e cause o sp astic q uad rip are tic ce re b ral p alsy, she love s to trave l and has a wond e r ul se nse o humor.

• Clinic-like experience with 8 to 10 patients with physical disabilities (eg, cerebral palsy, communication issues, wheelchair users) where pairs o students complete brie interview and physical examination under video monitoring. The session ends with a debrie ng circle wrap up with students and patients. • Panel discussion involves patients with varying abilities who usually represent an advocacy agency or organization. Special emphasis is placed on community services and opportunities including the arts and sports.

27

28

PART 2

ISSUES IN INTERNAL MEDICINE

Ch a pt e r 5

• Home visits where student pairs (2 medical students or a medical student and physical therapy student) receive a preparation sheet and checklist and learn how disability a ects individuals and their amily. Following the visit, students prepare ref ection plus research reports that are posted on blackboard; part o the assignment is to read and comment on all the papers.

Dr. Woodard’s daughter graduated rom high school in June 2011. The amily is working on helping her structure her day and move beyond the interminable wait list or services to which she is entitled. She is happy and healthy and the amily members consider themselves lucky to have good, a ordable caregivers, and companions to assist her.

• Service learning project where students give presentations on health topics (eg, rst aid, inf uenza) selected by sta at an adult daycare acility or individuals with intellectual disabilities or the high school group noted above, or assist in the recreational activities or individuals with disabilities (eg, ree physicals or riders in therapeutic horseback riding program).

CARING FO R THE HO MELESS (J IM WITHERS, MD)

• An objective structured clinical examination (OSCE) case involving a manual wheelchair user with shoulder pain; the standardized patients are individuals who are wheelchair users. • Sensitivity training session, run by Parks and Recreation where students are randomly assigned a disability (eg, using a wheelchair or other assistive device or blind old) and complete tasks ollowed by watching the movie Murderball (an in ormative and proactive documentary about the Paralympics sport, quadriplegic rugby, and its players). A speech pathologist also provides a hands-on assistive/ augment communication device tutorial. “The students learn to see the patient rst,” she says, “that caring or these individuals requires recognizing the patient’s expertise about their disability and problem solving together. For most students, even the most jaded, this is simply an eye-opening experience as the patients are usually quite physically impaired but lead ull and active lives.” (Figure 5-9) Dr. Woodard has expanded this program and is coteaching with aculty rom the School o Physical Therapy (PT) so that medical and PT students interview and examine patients together. In addition, she will begin providing training within the courses Doctoring 1 and Doctoring 2 to rstand second-year medical students (the home visit and panel discussion will be moved to the rst year) allowing more complex and challenging issues to be addressed during the clerkship. Finally, she is also involved with Alliance or Disability in Health Education, a group mainly out o the Northeast whose mission is to get the American Association o Medical Colleges (AAMC) to require the topic o disability in the curriculum.

FIGURE 5-9 Dr. Wood ard , d aug hte r Anika, and d og Nikki are p art o a te am o Unive rsity o South Florid a (USF) me d ical stud e nts, aculty, and amily who p articip ate d in a “whe e l-a-thon” to raise mone y or Tamp a’s f rst ully acce ssib le p layg round . Te aching me d ical stud e nts the the rap e utic value o sp orts and re cre ation or p e op le with d isab ilitie s is an imp ortant asp e ct o the USF curriculum.

EPIDEMIO LO GY Throughout the United States and abroad there are growing numbers o people who are orced to sleep on the streets. In 2009, at least 643,000 people were homeless on any given night and 1 in every 200 Americans (approximately 1.56 million people) spent at least one night in a shelter during that year. 11 Even within homeless populations, the unsheltered homeless (or “rough sleepers”), have much greater challenges in terms o health, discrimination, environmental stress, and mental illness. The characteristics o the street homeless and the larger community conspire to create a disa ected, highly vulnerable subgroup or whom very little success ul intervention is available. In many cases, even homeless health agencies view this population as either hopeless or “not ready” or services. Coincident with the nancial, moral, and social crisis associated with the growing street homeless population, systems o medical education are called upon to educate uture clinicians that are capable o “bridging the reality gap” between the complex needs o individuals and the airly rigid structure o modern health care. A classroom is needed in which we can “learn to learn” rom those who are the most alienated and underserved (Figure 5-10). Indeed, the skills thus learned have signi cant implications or how we approach health care that will meet the needs o all uture populations. Creating a workable model or e ectively including those living under the bridges, in the alleys, and along the rivers o our own communities can provide a template or bridging other such “reality gaps.”

FIGURE 5-10 “Classroom o the stre e ts.” Dr. Withe rs with 2 me d ical stud e nts and 1 outre ach g uid e (with b lack cap ) working with home le ss youth und e r a b rid g e on the north sid e o Pittsb urg h. (Re p rod uce d with permission from Pittsburgh Mercy Health System and Operation Safety Net.)

SO CIa L JUSt ICe

PART 2

ISSUES IN INTERNAL MEDICINE

FIGURE 5-12 Dr. Withe rs is washing the e e t o an old e r home le ss man at Marke t Sq uare , d owntown Pittsb urg h. A p sychiatry nurse with the b e ard is watching . The man’s e e t ne e d e d care or mod e rate tre nch oot. Most imp ortantly, this imag e d e monstrate s the conce p t o se rvice . (Re p rod uce d with p e rmission from Pittsb urg h Me rcy He alth Syste m and O p e ration Safe ty Ne t.)

FIGURE 5-11 Volunte e r nurse Carole trying to e stab lish a re lationship with a me ntally ill home le ss man in d owntown Pittsb urg h. This p hoto shows the imp ortance o re sp e ct and me e ting p e op le whe re the y are . (Re p rod uce d with p e rmission from Sand y Marlin. © 2013 Pittsb urg h Me rcy He alth Syste m and O p e ration Safe ty Ne t.)

ETIO LO GY The street homeless are a heterogeneous group, each with their own story that must be understood. However, there are a number o common actors that lead to street homelessness. These include mental illness, addiction, abuse, prejudice, and legal issues (Figure 5-11). They are paradoxically among the highest utilizers o costly emergency services and present or care only when orced to do so by crisis. By de nition they do not engage preventive or primary care services, being largely alienated rom mainstream society. As such, they present a unique challenge, but also an opportunity to learn how to recreate the health care response to meet the reality o those who have been excluded. In the nal analysis, it is the health system itsel that must be improved.

provide much needed direct medical service and also act as a learning opportunity to explore the principles o e ective medical-social connection. Experiences making “house calls” with his ather as a child, international health work, and ocused attention to the eld o domestic violence stimulated his search or a suitable classroom that would orce clinicians to work with people almost completely on their terms. In order to make this cognitive leap complete, he elt he needed to take a dramatic course o action. In 1992, Dr. Withers began to dress as a homeless person and make nighttime visits to the street homeless o Pittsburgh. He was accompanied by a “street guide” who had been ormerly homeless and was trusted by the street homeless community. His intention was to start as much as possible with no preconceptions or agenda in terms o medical solutions, but rather develop relationships with the street homeless that might lead to a shared path o healing (Figure 5-12). O the rst 119 unsheltered homeless he encountered, virtually none had any orm o primary care despite the act that there was a high prevalence o serious medical and mental health disease.

BEING PART O F THE SO LUTIO N PRO BLEM IDENTIFIED Although there are notable models or health care delivery that “Go To The People,” the vast majority o health care requires people to seek care on the terms o the system. Unable to do so, rough sleepers throughout the world are growing urther alienated and resented by existing systems o care. This impasse is not only ine cient, but also results in mutual resentments—especially when the street homeless population contains disproportionate numbers o ethnic minorities. The ultimate cost o this situation is a lack o wholeness as a community leading to deeper ragmentation and ear. Early in his career, Dr. Jim Withers (an Internal Medicine teaching physician or the Pittsburgh Mercy Health System in Pittsburgh) realized that a new approach to the care o disconnected populations could both

Dr. Withers began to bring medications in a backpack and then seek higher levels o care as each individual desired. Soon there were other medical volunteers and medical students working on the streets with their own ormerly homeless guides (Figure 5-10). An electronic health record was created, an o ce established or ollow-up issues and, by January o 1993, Operation Sa ety Net (OSN) was established as a part o the Pittsburgh Mercy Health System at Mercy Hospital. Since the establishment o OSN (www.operationsa etynet.net), the program has had a signi cant impact on both health care delivery and medical education in Pittsburgh. Approximately 1200 individuals are seen each year on the streets. Most are now insured through targeted bene ts counseling and are directed to a primary care o ce speci cally tailored to their care. Street patients are managed within a “medical home” type model with a 24-hour on-call answering service and ollow-up care.

29

30

PART 2

ISSUES IN INTERNAL MEDICINE Any homeless person, emergency department, or vested party can contact OSN as the “home care service or the streets.” A city-wide hospital consult service serves to improve patient care and provide better discharge planning. With success ul collaborations and grant support, OSN has housed over 900 chronically homeless individuals rom 2004 to 2013. An increasingly comprehensive care system meets the speci c needs o the recovering street homeless population and ollows them at whatever stage o engagement they chose to participate. Over 100 students are trained within the OSN model each year and many go on to establish their own service-oriented programs throughout the world (see Figure 5-10). Dr. Withers visited India in 1993 at which time he heard about the work o Dr. Jack Preger in Calcutta. Dr. Preger established the Calcutta Rescue program in 1979 which delivers medical care directly to the street homeless o that vast city (Figure 5-13). At that meeting, Dr. Withers had an epiphany and realized that a new eld o medicine was being practiced in both their cities involving the same basic principles o care delivery. A ter many journeys to communities throughout the United States and abroad, Dr. Withers developed a network o grassroots organizations practicing what is now known as “street medicine.” A number o established e orts in cities like Boston, Santiago Chile, and Dublin were linked and an even larger number o new programs have emerged being inspired by the street medicine movement. In order to galvanize the street medicine movement, Dr. Withers established the rst annual International Street Medicine Symposium in Pittsburgh in 2005. The symposium, held in a di erent city each year, has grown rom the original meeting o 27 pioneers to 199 registrants rom all over the United States and 12 other countries, spanning 5 continents, who came to the ninth International Street Medicine Symposium in Boston in 2013. Students also presented updates on their growing network and displayed 19 academic posters. The Street Medicine Institute (www.streetmedicine.org) was established by Dr. Withers and other key partners in 2009 to be the global “home” o the street medicine movement. The vision is that one day every person orced to live on the streets will have direct access to medical care that is sensitive to their particular need. Also, it is envisioned that every possible health science school will have an elective “classroom

Ch a pt e r 5

o the streets” in which uture clinicians can develop their service-oriented skills within their own communities (see Figure 5-10). The Street Medicine Institute is dedicated to assisting the development o new street medicine programs, improving the practice o street medicine, ostering the trans ormational value o the street medicine movement, and to create learning opportunities within the street medicine context. Dr. Withers believes that by serving the most vulnerable o our own communities, we learn to make health care an agent o positive change in ourselves and society at large. PRO VIDER RESO URCES

International Humanitarian Efforts • Doctors Without Borders—http:/ / www .doctorswithoutborders.org. • http:/ / www.globalcorps.com/ jobs/ ngolist.doc. • http:/ / www.exploringabroad.com/ humanitarian-org.htm. • http:/ / www.internationalhealthvolunteers.org/ . • Rick Hodes Web site—http:/ / rickhodes.org. • Calcutta Rescue—http:/ / www.calcuttarescue.org/ Disabled Persons • US Department o Justice—http:/ / www.usdoj.gov/ crt/ ada/ cguide.htm. • Social Security Administration—http:/ / www.ssa.gov/ disability/ (in ormation on bene ts). • In ormation on Sports Events or the Disabled— http:/ / www .dsusa.org. • http:/ / www.disabilityinfo.gov. Homeless • National Coalition or the Homeless—http:/ / www .nationalhomeless.org/ . • National Alliance to End Homelessness—http:/ / www.naeh .org/ . • US Department o Housing and Urban Development—http:/ / www.hud.gov/ homeless/ index.cfm. • Veterans A airs—http:/ / www1.va.gov/ homeless/ . • The Society o Student-Run Free Clinics—http:/ / www .studentrunfreeclinics.org/ . • Haven or Hope—http:/ / www.havenforhope.org/ . REFERENCES 1. United Nations High Commissioner or Re ugees (UNHCR). http:/ / www.unhcr.org/ pages/ 49c3646c11.html. Accessed November 2013. 2. Center or Disease Control (CDC). Frequently Asked Questions About International Emergency and Re ugee Health. http:/ / www.cdc.gov/ globalhealth/ gdder/ ierh/ FAQ.htm. Accessed November 2013. 3. Daley WR. Public Health Response to Hurricanes Katrina and Rita— Louisiana, 2005. http:/ / www.cdc.gov/ mmwr/ preview/ mmwrhtml/ mm5502a1.htm. CDC. Accessed November 2013.

FIGURE 5-13 Dr. Jack Pre g e r e stab lishe d the Calcutta Re scue p rog ram in 1979 which d e live rs me d ical care d ire ctly to the stre e t home le ss o that vast city. Dr. Pre g e r is working und e r a b rid g e in Calcutta b ring ing me d ical care to a home le ss man.

4. Injury and Illness Surveillance in Hospitals and Acute-Care Facilities A ter Hurricanes Katrina and Rita— New Orleans Area, Louisiana, Sept 25 to Oct 15, 2005. http:/ / www.cdc.gov/ mmwr/ preview/ mmwrhtml/ mm5502a4.htm. Accessed November 2013.

SO CIa L JUSt ICe

5. Hanzlick R. O ce o the Fulton County Medical Examiner. Surveillance and Programs Br, Div o Environmental Hazards and Health E ects, Center or Environmental Health, CDC. MMWR Morb MortalWkly Rep. 1987;36(19):297-299. 6. World Health Organization. Water-related diseases. Malnutrition. http:/ / www.who.int/ water_sanitation_health/ diseases/ malnutrition/ en/ . Accessed October 2013. 7. World Health Organization. Progress on Sanitation and DrinkingWater: 2013 Update. http:/ / apps.who.int/ iris/ bitstream/ 10665/ 81245/ 1/ 9789241505390_eng.pd . Accessed October 2013. 8. World Health Organization A rican Region: Ethiopia. http:/ / www.who. int/ countries/ eth/ en/ . Accessed November 2013.

PART 2

ISSUES IN INTERNAL MEDICINE 9. Department o Health and Human Services. The Surgeon General’s Call to Action to Improve the Health andWellness o Persons with Disabilities. Rockville, MD: Public Health Service; 2005. http:/ / www. surgeongeneral.gov/ library/ disabilities/ calltoaction/ calltoaction. pd . Accessed April 25, 2007. 10. Prevalence o disabilities and associated health conditions among adults—United States, 1999. MMWR Morb MortalWkly Rep. 2001;50(07):120-125. 11 Centers or Disease Control and Prevention. National Prevention In ormation Network. http:/ / www.cdcnpin.org/ scripts/ population/ homeless.asp. Accessed May 1, 2012.

31

PART 2

32

ISSUES IN INTERNAL MEDICINE

Ch a pt e r 6

6 GLO BAL HEALTH Ruth E. Be rg g re n, MD Richard P. Usatine , MD

CO MMUNITY STO RY Common River is a US-based nongovernmental organization (NGO) implementing a community development program in Aleta Wondo, Ethiopia. This NGO is ounded on the principle o positive deviance, in which local best practices are identi ed and replicated to maximize agricultural production (organically grown co ee is produced in this region), as well as to improve the nutritional status, health, and education o orphaned and vulnerable children. Since 2009, a group rom the University o Texas School o Medicine in San Antonio has traveled annually to Aleta Wondo to provide school health screening and ree health care, including treatment o endemic helminth in ections, trachoma, and skin diseases, while collaborating with and supporting the local governmentsponsored health clinic (Figure 6-1A). In Figure 6-1B, a University o Texas medical student helps an elderly man to a chair where he will be seen by the medical team working in Aleta Wondo. The people o Aleta Wondo will receive oral albendazole or the treatment o intestinal parasites and will undergo complete physical examinations or the detection and treatment o other common conditions, such as head lice, tinea capitis, trachoma, and oot in ections. In Figure 6-1C, a group o women has just completed their woman’s literacy class or the day. Improving women’s literacy can improve the health o the entire community.

B

C FIGURE 6-1 (Continue d ) B. A Unive rsity o Te xas me d ical stud e nt he lp s an e ld e rly man to a chair whe re he will b e se e n b y the me d ical te am working in Ale ta Wond o. O ne o the local nursing stud e nts is ob se rving the clinical activity. (Re p rod uce d with p e rmission from Le ste r Rose b rock.) C. Smiling wome n who have just comp le te d the ir woman’s lite racy class or the d ay. Imp roving woman’s lite racy is a g re at way to raise the he alth status o the community. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

A FIGURE 6-1 A. Many p e op le still live in e xtre me p ove rty with no running wate r and e le ctricity. This is a typ ical hut in Ethiop ia. This one is inhab ite d b y a g rand mothe r, he r g rand child , and a cow. The p hotog rap h was take n a te r a home visit to p rovid e IM ce triaxone to the child a te r he r re le ase rom the local hosp ital whe re she was tre ate d or a ne ck ab sce ss and ce llulitis. The me d ical te am was staying at Common Rive r and orig inate d rom the Unive rsity o Te xas. (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

WHAT IS GLO BAL HEALTH? For years, the term international health has described health work in resource-limited settings with an emphasis on tropical diseases, communicable diseases, and illness caused by poor nutrition and inadequate access to water, sanitation, and maternal care. 1 More recently, global health is commonly used to emphasize mutual sharing o experience and

GLO Ba L h e a Lt h

knowledge, in a bilateral exchange between industrialized nations and resource-limited countries, and the emphasis is expanding to include noncommunicable diseases and chronic illness. 2 One de nition o global health, proposed by the Consortium o Universities or Global Health Executive Board, is “an area or study, research, and practice that places priority on improving health and achieving equity in health or all people worldwide.”1 This chapter ocuses on a ew conditions commonly encountered in developing nations, emphasizing communicable diseases and malnutrition. Ethical dilemmas abound when pro essionals rom resource-rich settings leave their amiliar environment and apply their practices in a severely resource-limited setting. Consider, or example, breast eeding guidelines in the setting o maternal-to-child HIV prevention. National protocols di er depending on resource availability. In some settings, telling an HIV-positive mother not to breast- eed (because breast-milk can transmit HIV) may sentence her in ant to near-certain death rom diarrhea. I a program overturns local teaching about exclusive breasteeding, it must ensure a sa e and sustainable alternative orm o in ant eeding. Imposing the standards o industrialized nations in a community that cannot a ord to continue to provide these standards can undo years o program development. Care must be taken not to undermine the trust a community has placed in local health providers, as this can ultimately increase morbidity rather than relieve su ering. Working with local health providers is essential so that a short trip can result in extended bene ts to the community. This chapter brief y introduces some o the relevant subject areas with which global health providers should amiliarize themselves when preparing or international work. Statistics that aid in understanding the state o a nation’s health relative to other countries are the mortality rate o children younger than age 5 years and adult li e expectancy. Least-developed countries report that as many as 112 o 1000 children die be ore age 5 years, compared to 8 per 1000 in developed countries, 3 and adult li e expectancy ranges rom 48 or 49 years at birth (Chad, Swaziland) to 88 or 89 years (Japan, Monaco). 3 Another important parameter by which to compare the health status o countries is that o maternal mortality, de ned as the number o maternal deaths per 100,000 live births. These gures, together with basic epidemiology o disease, provide important insights into public health priorities or populations. What statistics do not provide, however, is the level o importance ascribed to a particular health issue by a community. It is necessary to acknowledge and address the needs expressed by communities themselves, in order o their own priorities, so as to achieve sustained improvements in health outcomes. All health improvements ultimately rely on long-term behavioral changes, whether dietary, pill taking, physical activity, or hygiene related. Group behavioral change requires buy-in rom the population with the approbation and inf uence o local leadership. A use ul method o creating a positive impact is to make use o ongoing peer-to-peer adult education techniques through the introduction o community health clubs. This can be e ective or empowering resource-limited communities to develop their priorities, and to advocate their community health and development needs.4 It is best to learn about and collaborate with the local and governmental community health activities be ore launching any intervention, be it clinical, in rastructural, or preventive. WATER AND SANITATIO N Many diseases in resource-poor settings are traceable to de cits in clean water supply and storage, lack o soap or bathing, and lack o unctioning in rastructure to manage human waste (garbage collection, latrines)5 (Figure 6-2). Some o the most important ones include typhoid ever, cholera, and intestinal parasites.

PART 2

ISSUES IN INTERNAL MEDICINE

FIGURE 6-2 An Ethiop ian p it latrine , which o e rs no mitig ation or ie s and is situate d in p roximity to the wate r tab le b e low. He avy rains will le ad to contamination o the wate r sup p ly with e cal p athog e ns. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Lack o government and public health in rastructure in the developing world leads to large populations living without clean running water. The World Health Organization (WHO) and UNICEF estimate that 780 million people are without access to improved water sources and 2.5 billion (37% o the world’s population) people are without access to improved sanitation sources. 6 Water and sanitation de ciencies are responsible or most o the global burden o diarrheal disease. The most common diarrheal disease o returning travelers is caused by enterotoxigenic Escherichia coli. All over the world, young and malnourished children die o preventable diarrhea caused by rotavirus, E. coli, Salmonella, Shigella, and Campylobacter. Diseases that are particularly deadly as a result o lack o access to clean water include typhoid ever and cholera. Intestinal parasites, while usually not deadly, do lead to chronic problems with malnutrition and anemia, which themselves contribute to cyclical poverty and disease because they lead to impaired learning, reduced productivity, and vulnerability to other in ectious diseases.

TYPHO ID FEVER Typhoid ever, also known as enteric ever, is an acute systemic illness caused by the invasive bacterial pathogen, Salmonella typhi. S. typhi is ingested in contaminated water or ood, invades the mucosal sur ace o the small intestine, and causes bacteremia, with seeding o the liver, spleen, and lymph nodes. EPIDEMIO LO GY Typhoid ever is mainly ound in countries with poor sanitary conditions. Because most such countries do not routinely con rm the diagnosis with blood cultures, the disease is highly underreported. Outbreaks o typhoid are o ten seen in the rainy season, and in areas where human ecal material washes into sources o drinking water. Shallow water tables and improperly placed latrines are environmental risk actors or typhoid. Globally there are 16 to 33 million cases annually, with up to hal a million deaths every year. 7 CLINICAL PRESENTATIO N Patients develop an acute systemic illness with prolonged ever, malaise, and abdominal pain a ter ingesting contaminated ood or water. This

33

34

PART 2

ISSUES IN INTERNAL MEDICINE truly nonspeci c syndrome may include headache, mild cough, and constipation, with nausea and vomiting. Diarrhea may be present but it is not the rule. A ter a 10- to 20-day incubation period, there is a stepwise progression o ever over a period o 3 weeks, and the patient may display a transient rash described as rose spots (2- to 4-mm pink macules on the torso, which ade on pressure). Temperature pulse dissociation with relative bradycardia despite high ever may be noted in ewer than 25% o patients. In the second week, the patient becomes more toxic and may develop hepatosplenomegaly. Untreated, typhoid can progress to include delirium, neurologic complications, and intestinal per oration caused by a proli eration o Salmonella in the Peyer patches (lymphoid tissue) o the intestinal mucosa. Although the mortality rate or untreated typhoid is 20%, early antibiotic therapy can decrease mortality. Approximately 1% to 4% o those who recover rom acute typhoid ever become carriers o the disease and continue to shed Salmonella in their stool despite not being ill. 7

Ch a pt e r 6

or sanitation. Although the in ection is o ten mild or asymptomatic, in 5% to 10% o patients it can be severe and li e threatening. 11 EPIDEMIO LO GY

Culture o blood, stool, rectal swab, or bone marrow. 8

V. cholerae reservoirs occur in brackish and salt water, as well as estuaries. Although the organism occurs in association with copepods and zooplankton, its largest reservoir is in humans. Cholera pandemics have been reported in South Asia, A rica, and Latin America. Characteristically, cholera outbreaks occur in countries that have su ered destruction o public health in rastructure (collapse o water supplies, sanitation, and garbage collection systems). The 2010 outbreak in post-earthquake Haiti has been traced to UN peacekeeping soldiers, whose waste contaminated a major Haitian river used or bathing, irrigation, and drinking water. In just 10 months, 300,000 cases were reported, o whom 4500 died, and the outbreak has continued to wax and wane with the rainy seasons or years. 12 A large in ective dose is necessary or in ection, and although approximately only 10% o those in ected all ill, the in ection can be atal or young children, elderly, and malnourished individuals.

DIFFERENTIAL DIAGNO SIS

PATHO PHYSIO LO GY

• Malaria (o ten clinically indistinguishable rom typhoid; empiric therapy or both malaria and typhoid may be warranted i diagnostic testing9 is unavailable)

V. cholerae is a motile, gram-negative rod. A ter ingestion via contaminated water or ood, it must survive the acid environment o the stomach be ore colonizing the mucosal sur ace o the small intestine. The organism is noninvasive, and not associated with bloody diarrhea. Rather, it makes a potent toxin causing massive secretion o electrolyte-rich f uid into the gut lumen. Human-to-human contact spread virtually never occurs. Transmission through contaminated ood or water is the rule. 13 Clinical presentation ranges rom mild watery diarrhea to acute, ulminant watery diarrhea that looks like rice water. A ter an incubation period o 18 to 40 hours, patients may lose up to 30 L o f uid daily, resulting in metabolic acidosis and electrolyte disturbances. Severe dehydration can lead to death in a matter o hours. Vomiting, when present, starts a ter the onset o diarrhea. Pro oundly dehydrated patients present with decreased skin turgor, sunken eyes, and lethargy. Children, but not adults, may have mild ever. Cramping caused by loss o calcium and potassium is common. 13

DIAGNO SIS

• Enteroinvasive E. coli • Campylobacter • Paratyphoid ever (Salmonella para typhi, other less virulent Salmonellae) • Dengue ever (mosquito-borne arbovirus in ection spread by Aedes aegypti) • Rickettsial diseases (typhus, spotted ever, Q ever) • Brucellosis • Leptospirosis • Heat stroke MANAGEMENT Prompt diagnosis and initiation o antibiotic therapy is essential and li esaving. Oral rehydration therapy should be initiated rst, ollowed by IV f uids i vomiting cannot be controlled and or patients with altered mental status or hypovolemic shock. Antibiotic resistance patterns di er with geographic location. For A rica and resource-limited settings in the Americas, the rst choice is chloramphenicol 1 g PO daily or 10 to 14 days, or ciprof oxacin. Historically, trimethoprim-sul amethoxazole 960 mg PO twice daily or 10 to 14 days has been used, 8 but there has been increasing drug resistance to sul a in these areas. In Asia, where multidrug resistant S. typhi strains are well described, ciprof oxacin (500-750 mg twice daily), ce triaxone (60 mg/ kg IV daily) or azithromycin (500 mg daily) may be used or 7 to 14 days. 8-10 Azithromycin should be used only in mild disease. Some guidelines advocate the use o dexamethasone 3 mg/ kg IV ollowed by 1 mg/ kg every 6 hours or 2 days in the setting o shock or altered mental status. 8 See vaccine in ormation at the end o this chapter.

CHO LERA Cholera is an acute, diarrheal disease caused by Vibrio cholerae. It is usually transmitted by contaminated water or ood, and is associated with pandemics in countries that lack public health in rastructure and resources

DIFFERENTIAL DIAGNO SIS AND LABO RATO RY TESTS Early presentation may resemble enterotoxigenic E. coli; however, the syndrome is quickly distinguishable because o the extreme volume o “rice water” secretory diarrhea that is the result o the cholera toxin. V. cholerae may be con rmed by stool culture, polymerase chain reaction (PCR) or toxin genes, or dark- eld microscopy with speci c antisera, which will immobilize the V. cholerae. 14 The Centers or Disease Control and Prevention (CDC) recommends con rmation o cholera by stool specimen culture or rectal swab. For transport, Cary Blair media is used, and or identi cation, thiosul ate-citrate-bile-salts (TCBS) agar is recommended. 11 MANAGEMENT Water, sanitation, and hygiene education is essential, as is education about recognizing the symptoms and immediately seeking medical attention while initiating oral rehydration. Optimally, rehydration should commence with reconstitution o WHO-distributed oral rehydration salts (ORS), which is available in all but the most remote areas o the world. Hydration is the mainstay o therapy, and replacement o f uids should be calibrated to match losses. ORS should be prepared with previously boiled water and consumed within 24 hours o reconstitution.

GLO Ba L h e a Lt h

FIGURE 6-3 In this Ethiop ian community without running wate r, wate r is colle cte d in je rry cans. Thousand s o wome n carry the se he avy, f lle d cans or mile s a te r f lling the m up rom this sing le p ip e . The local town has p rovid e d one sing le p ip e as the wate r source or the community. Althoug h the re is mud d y wate r b e low, the wate r coming rom the p ip e ap p e ars cle ar, althoug h it is like ly to harb or b acte ria and p arasite s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

IV or intraosseous hydration with Ringer lactate solution should be initiated i the patient is vomiting or in danger o hypovolemic shock. The volume needed to rehydrate a cholera patient is o ten underestimated; or this reason, collection and measurement o the watery stool in a bucket placed under the cholera cot is recommended. Antibiotics are recommended or severe cases o cholera; the ollowing are the options15: 1. Doxycycline 300 mg orally as single dose (contraindicated in pregnancy) 2. Azithromycin 1 g orally as single dose (more e ective than either erythromycin or ciprof oxacin; appropriate rst-line therapy or children and in pregnancy) 3. Ciprof oxacin 4. Furazolidone 100 mg orally In pregnancy, erythromycin 250 mg PO daily or 3 days may also be used. PREVENTIO N O F DISEASES SECO NDARY TO CO NTAMINATED WATER Drinking puri ed or treated water, good handwashing practices, and avoidance o contaminated ood are essential. Travelers should be reminded not to brush their teeth with tap water and to avoid having potentially contaminated ice added to their beverages. Carbonated beverages are sa e as the carbonation process is bactericidal. Community education about handwashing and treatment o water is essential. In communities lacking running water (Figure 6-3), home storage o drinking water should be in containers with protective lids. Local guidelines regarding addition o chlorine to home-stored water containers should be ollowed.

INTESTINAL PARASITES EPIDEMIO LO GY AND GEO GRAPHIC DISTRIBUTIO N One-third o the world’s population is in ected with intestinal parasites, and although many parasitic in ections are asymptomatic, some have serious health consequences. Especially a ected are pregnant women and

PART 2

ISSUES IN INTERNAL MEDICINE

FIGURE 6-4 Ascaris e g g ound in the stool o a p atie nt with inte stinal p arasite s. In most d e ve lop ing countrie s Ascaris is tre ate d e mp irically with alb e nd azole ; stool stud ie s are not always availab le or may not b e cost-e e ctive . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

children, or whom hookworm-associated anemia results in maternal mortality, low-birth-weight babies, growth stunting, and impaired learning. The CDC recommends predeparture albendazole treatment as a single 600-mg dose or all re ugees rom sub-Saharan A rica and South Asia. While this treatment will eradicate most o the nematodes, it is insu cient or Strongyloides stercoralis and schistosomiasis. 16 CLINICAL PRESENTATIO N Abdominal pain, cramps, bloating, anorexia, anemia, atigue, growth stunting o children, hepatomegaly (schistosomiasis) DIAGNO SIS Stool or ova and parasite studies (Figure 6-4) will not reliably detect Strongyloides or schistosomiasis; serologic testing is available or the latter. Eosinophilia is an important diagnostic clue or the presence o parasites; the nding o persistent eosinophilia warrants a care ul diagnostic evaluation or parasitic in ection. TREATMENT Ad ult s Albendazole 400 mg orally as single dose will eradicate hookworm, and Ascaris, but not Trichuris in most people.17 Eradication o Trichuris trichiura requires 3 daily doses o albendazole or adding ivermectin to mebendazole.18 PREVENTIO N Preventative measures include proper management o human waste, handwashing a ter de ecation and be ore cooking, and wearing shoes (prevents hookworm and Strongyloides). WHO guidelines recommend mass treatment o school children in endemic areas with single-dose albendazole therapy once in every 6 months.

MALNUTRITIO N A global shi t is underway, rom diseases o undernutrition to overnutrition in tandem with industrialization and advances in transportation and technology. In spite o this global shi t, about a quarter o the world’s

35

36

PART 2

ISSUES IN INTERNAL MEDICINE preschool children demonstrate growth stunting caused by nutritional de ciencies. In resource-poor countries, adult obesity and childhood undernutrition may coexist within the same amilies. The causes o this seeming paradox include many actors associated with poverty: the vulnerability o preschool children to in ection when sanitation is inadequate, lack o nutrition education, decreased physical activity with increasing availability o technology and transportation, and mass marketing o inexpensive, calorie-rich oods.

THE NUTRITIO N TRANSITIO N AND MICRO NUTRIENT DEFICIENCIES Obesity has become a leading global cause o death and disability, 19 and the term “nutrition transition” is used to describe the associated dietary change rom one dominated by carbohydrates and ber to a diet rich in sugar and animal ats. 20 Despite the sur eit o energy associated with the nutrition transition, global micronutrient de ciencies contribute importantly to developmental delays, reduced cognitive unction, impaired immunity, obesity, and hypertension. 21 There are 4 micronutrient de ciencies o global importance, each with associated clinical syndromes that should be recognized. All can be associated with growth stunting in children, who may present with abnormally short stature but relatively normal weight or height. Growth stunting rom micronutrient de ciency is associated with adult obesity, 22 and obese adults also demonstrate micronutrient de ciencies despite the act that they appear overnourished. 23 Although many o the guidelines regarding micronutrient de ciencies are speci c to children, the de ciencies persist and contribute to disease vulnerability and decreased productivity in adulthood, which in turn leads to the amiliar cycle o disease and poverty. VITAMIN A DEFICIENCY Vitamin A is a critical regulator o immune unction, which is required or maintaining the integrity o mucosal sur aces. Vitamin A supplementation in countries with malnutrition reduces blindness ( rom xerophthalmia) as well as the morbidity o in ectious diseases (especially measles, diarrhea, and respiratory in ections). In 2009, the WHO estimated that clinical vitamin A de ciency (night blindness) and biochemical vitamin A de ciency (serum retinol concentration < 0.70 µmol/ L) a ected 5.2 and 190 million preschool-age children, respectively. 24 About 250,000 children develop blindness caused by vitamin A de ciency every year, and hal o them die within 12 months o losing sight. 25 Clinical Pre se nt at io n Pregnant women in vitamin A de cient communities may be among the rst to signal the problem when they complain o night blindness. The earliest presentation o vitamin A de ciency is poor night vision, which may progress to night blindness, xerophthalmia, ulceration, and scarring o the cornea, with ultimate blindness. Vitamin A de ciency is also associated with anemia, and has been suggested as a preventable cause o maternal mortality. 26 However, a recent trial in Ghana involving more than hal a million woman-years and over 2500 deaths concluded that weekly vitamin A administration did not reduce mortality in women o childbearing age. 27 Manag e me nt While meta-analyses o large trials giving vitamin A supplements to hundreds o thousands o children under age 5 years reveal striking

Ch a pt e r 6

reductions in mortality and morbidity, the bene t o programmatic vitamin A supplementation or adults has not been demonstrated. In children, vitamin A reduces diarrhea and measles incidence as well as morbidity, mortality, and eye disease. In countries where vitamin A de ciency is problematic, pregnant women o ten report symptomatic night blindness. The most recent guidelines do not recommend vitamin A supplementation during pregnancy as part o routine antenatal care or preventing maternal mortality. WHO does state that or countries with signi cant public health problems rom de ciency, vitamin A should be given to prevent night blindness. Pregnant women in these settings should get up to 10,000 IU vitamin A daily or 25,000 IU vitamin A weekly as an oral liquid, oil-based preparation. A single dose o vitamin A should never exceed 25,000 units, especially during the rst trimester o pregnancy, to avoid teratogenicity. Supplementation is continued or 12 weeks during pregnancy until delivery. The WHO de nes at-risk populations as those where the prevalence o night blindness is greater than or equal to 5% in pregnant women or greater than or equal to 5% in children aged 2 to 5 years. 28 Treatment o active xerophthalmia is considered an emergency and management should include oral vitamin A. Current recommendations or xerophthalmia (night blindness and/ or Bitot spots) are 10,000 units daily or 25,000 units weekly or 3 months. Active corneal lesions rom vitamin A de ciency are rare, but should be treated with 200,000 units o vitamin A on days 1, 2, and 14. 29 ZINC DEFICIENCY Zinc plays a central role in cellular growth, di erentiation, and metabolism. It is necessary or physical growth, gastrointestinal (GI), and immune unction. Many zinc studies show improved growth o children and decreased in ections when supplements are given to vulnerable populations. Studies suggest that the global prevalence o zinc de ciency approaches 31%, especially in A rica, the eastern Mediterranean, and South Asia. 30 Clinical Pre se nt at io n The most common presentation o zinc de ciency is nonspeci c and may include growth stunting, delayed sexual maturation, dermatitis, and de ective immunity. Zinc de ciency is associated with decreased macrophage chemotaxis, decreased neutrophil activity, and decreased T-cell responses. 31 It is widely acknowledged that zinc de ciency contributes signi cantly to mortality rom pneumonia, diarrhea, and malaria. Diag no sis Because there is no good biomarker or zinc de ciency, diagnosis must rest on clinical suspicion and documentation o therapeutic response to supplementation. Manag e me nt WHO guidelines or diarrhea recommend use o low concentration ORS together with routine zinc supplementation or 10 to 14 days. While care ully studied in children, data regarding zinc supplementation or diarrhea in adults are lacking. 32 In children, zinc supplementation decreases the duration and volume o diarrheal stools by 25% and 30%, respectively, and brings an approximate 50% reduction in noninjury deaths in the year ollowing the treatment. 33 Un ortunately, zinc supplementation bene ts are still not widely known by health care workers in developing countries. 34

GLO Ba L h e a Lt h

IRO N DEFICIENCY Iron de ciency is the most common micronutrient de ciency in the world, and 2 billion people (nearly one-third o the global population) are anemic. In resource-limited countries, iron de ciency anemia is either caused or aggravated by malaria, intestinal parasites such as hookworm, and other chronic in ections such as HIV, tuberculosis, or schistosomiasis. Iron de ciency causes enormous morbidity and contributes to 20% o global maternal mortality. Because the consequences include impaired cognition and physical development, increased risk o illness in children and reduced work productivity, iron de ciency is a real barrier to economic development in resource-poor countries. 35 As with zinc and vitamin A, iron de ciency can be detrimental to host immunity, causing decreased neutrophil chemotaxis. 31

PART 2

ISSUES IN INTERNAL MEDICINE iodine de ciency results in a orm o pro ound cognitive impairment known as cretinism. Other consequences include stillbirths, dea mutism, subclinical hyper- or hypothyroidism, impaired mental unction, and retarded physical development. 37 Int e rve nt io ns Iodine may be supplied in tablets or liquid orm and taken daily; in adults, 150 µg/ d is su cient or thyroid unction and an adult multivitamin typically contains 150 µg o iodine per tablet, but this is impractical. Population-based interventions should include iodization o salt, and in some developing countries, eradication o iodine de ciency has been accomplished by adding iodine drops to well water. VITAMIN B3 (NIACIN) DEFICIENCY

Int e rve nt io ns The WHO has developed a 3-pronged strategy or addressing global iron de ciency: increasing iron uptake through dietary diversi cation and supplementation, improvement o nutritional status, and controlling in ections, especially worms. In countries with signi cant iron de ciency anemia, malaria, and helminth in ections, these interventions can restore individual health as well as raise national productivity levels, thereby interrupting the cycle o poverty and disease. 35 IO DINE DEFICIENCY Insu cient dietary iodine can signi cantly lower the IQ o whole populations and is the leading preventable cause o brain damage. Although iodine de ciency is easily solved through ood orti cation costing 2 cents per person annually, prevalences o 60% to 90% iodine de ciency among school children are observed in multiple A rican, Asian, and eastern Mediterranean countries. There is tremendous variance o iodine de ciency within individual countries and de ciency is not linked to poor or disadvantaged districts. 36 Iodine de ciency occurs where the soil has low iodine content because o past glaciation or repeated leaching e ects o precipitation. Food crops grown in iodine-de cient soil provide inadequate dietary iodine. 37 Clinical Pre se nt at io n Because iodine is required or thyroid hormone synthesis, iodine de ciency results in hypothyroidism and goiter (Figure 6-5). Congenital

FIGURE 6-5 Massive g oite r cause d b y iod ine d e f cie ncy. This woman is rom a country in A rica whe re iod ine is not routine ly sup p le me nte d in the d ie t and g oite r is e nd e mic. (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

Clinical niacin de ciency is a problem in severely resource-limited settings where diets rely heavily on corn or sorghum. Pellagra re ers to a nutritional wasting disease that occurs when there is de ciency o nicotinic acid and/ or tryptophan. 38 Clinical Pre se nt at io n The term “pellagra” re ers to a symptom complex o 4 Ds: diarrhea, dermatitis, dementia, and (sometimes) death, which is seen in niacin de ciency states. The dermatitis is a phototoxic rash, occurring primarily on sun-exposed skin o the neck and chest in a necklace-like distribution (Figure 6-6), as well as on the hands and orearms, or in a boot-like distribution sparing the heel. The rash is initially erythematous, and may be blistering or scaling with progression to hyperkeratosis and hyperpigmentation over bony prominences. Accompanying neurologic problems include disorientation, myoclonic jerks, tremors, depression, and in severe cases, central pontine myelinolysis. 39 Diag no sis Diagnosis requires clinical suspicion, recognition o the 4 Ds, and understanding o risk actors. In addition to poverty and maize diet, risk actors or pellagra include eating disorders, alcohol abuse, malabsorption, medications (especially INH, PZA, and phenytoin or phenobarbital), Crohn disease, and hypothyroidism. Oral niacin supplementation should ameliorate symptoms in 1 to 2 days, and can con rm the diagnosis.

FIGURE 6-6 Pe llag ra rom niacin d e f cie ncy causing the typ ical rash around the ne ck known as Casal ne cklace . (Re p rod uce d with p e rmission from Rick Hod e s, MD.)

37

38

PART 2

ISSUES IN INTERNAL MEDICINE Manag e me nt On a population level, orti cation o maize f our with niacin can be very e ective. Patients should be educated about nutritional sources o niacin, which include eggs, peanuts, meat, poultry, sh, legumes, and beans. For clinical therapy in a symptomatic individual, niacin is dosed at 100 to 500 mg PO divided 2 to 3 times daily until complete recovery (3-4 weeks). 40 Because nutrient de ciencies generally do not occur in isolation, consider treating or other common de ciencies including protein, zinc, thiamine, and vitamin B12. Although the dermatitis rarely leaves scars, residual hyperpigmentation may last or months. Hot f ashes and headache rom niacin may be diminished by pretreatment with aspirin, 325 mg about 30 minutes be ore the dose. 41

Ch a pt e r 6

These patients may also develop acute respiratory distress syndrome (ARDS), hypoglycemia, acidosis, and shock in the setting o hyperparasitemia. Untreated patients with cerebral malaria ultimately progress to coma, respiratory ailure, and death. 44 Diffe re nt ial Diag no sis The initial presentation o malaria is so nonspeci c that it mimics inf uenza (without the respiratory symptoms), enteric ever (see section on typhoid), dengue ever, rickettsial in ections, brucellosis, and leishmaniasis. I hemolysis has been extensive, the patient may present with jaundice, and viral hepatitis or leptospirosis may also be on the di erential diagnosis. 42 Lab o rat o ry Diag no sis

VECTO R-BO RNE DISEASES MALARIA

Malaria is usually diagnosed by light microscopy o peripheral blood smears prepared with a Giemsa, Field, or modi ed Wright stain (Figure 6-7A and B). A thick-and-thin smear should be obtained

Malaria is a protozoan in ection spread by the Anopheles mosquito vector in endemic areas. O the 4 species o malaria (Plasmodium alciparum, Plasmodium ovale, Plasmodium malariae, and Plasmodium vivax), P. alciparum is the most important to address, because i unrecognized and untreated, it can be rapidly atal. Only P. alciparum exhibits high levels o parasitemia in blood, and it is the only type o malaria that causes sequestration o parasitized erythrocytes in microvasculature. This unique eature o P. alciparum is responsible or the severe end-organ damage, including renal ailure, acute respiratory distress syndrome, and coma that is seen with untreated disease. 42 Ep id e mio lo g y and Ge o g rap hic Dist rib ut io n There are more than 200 million cases o malaria in the world every year. According to the WHO, up to 1 million people worldwide die annually rom malaria, with 89% o these deaths occurring in A rica. Most o the deaths caused by malaria occur in children younger than age 5 years. P. alciparum, P. vivax, P. malariae, and P. ovale are globally distributed in the tropics. P. vivax is more common in Asia, South America, Oceania, and India. P. ovale is ound mainly in West A rica, and P. malariae is much less common than P. vivax or P. alciparum. The risk or malaria varies greatly within a given country, and depends on altitude (higher altitudes have lower risk), season (greatest risk in rainy season), and urbanization (rural areas have greater risk than urban areas). Thus, travelers should be aware o these di erences and plan or prophylaxis accordingly. The CDC publication, Health In ormation or International Travel, is available online at http:/ / www.cdc.gov/ travel/ and should be consulted or updates about regional patterns o malaria risk, as well as drug resistance and guidelines, which are subject to requent changes. 43

A

Clinical Pre se nt at io n A ter a 1- to 3-week incubation period ollowing the bite o an in ected emale mosquito, patients develop a nonspeci c syndrome o high ever, headache, myalgia, and shaking chills. This syndrome is requently accompanied by nausea, vomiting, and back pain, and occasional diarrhea. Splenomegaly and anemia (related to hemolysis) are common in all 4 types o malaria. As untreated P. alciparum progresses, there is a risk o cerebral malaria, which is caused by parasitized erythrocytes sequestered in the capillaries o the brain, with secondary metabolic consequences. Cerebral malaria is characterized by severe headache and altered consciousness.

B FIGURE 6-7 A. Plasmod ium falcip arum with a b anana-shap e d g ame tocyte . O all the sp e cie s o malaria, P. falcip arum is most like ly to cause se ve re morb id ity and mortality. B. P. falcip arum with chromatin in ring s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

GLO Ba L h e a Lt h

whenever possible or every ebrile patient in whom malaria is suspected, especially rom ebrile travelers returning rom malaria endemic areas. Thin smears allow relative quanti cation and speciation o parasites when the parasitemia is high; thick smears are use ul to rule in malaria, especially when parasitemia is low. Because a single negative smear does not rule out malaria, the test must be repeated on at least 3 occasions at 12- to 24-hour intervals. 45 Patients with high levels o parasitemia (>5%) have a worse prognosis, and should be considered or inpatient care. Other diagnostic modalities include the f uorochrome acridine orange stain or f uorescence microscopy and PCR (not yet widely available but help ul or very low levels o parasitemia). Rapid antigen assays using ngerstick blood samples on cards impregnated with speci c antibodies are alternative methods or laboratory diagnosis o malaria. In the United States, the US Food and Drug Administration has approved the BinaxNOW Malaria test, which, although costly, is convenient or rapid eld use. Un ortunately, this and other immunochromatographic strip assays are not able to determine parasite load. 43 Tre at me nt Many cases o malaria can be treated e ectively with oral medication, and parenteral therapy is reserved or severe disease or or patients who are vomiting. Be ore prescribing therapy, determine which species is most likely involved based on microscopy or rapid diagnostic test; consider the geographic area and local drug resistance patterns. A ter the patient has been given the rst dose o medication, the patient should be observed or an hour. Vomiting can be managed with metoclopramide, 10 mg orally, and i vomiting occurs within 30 minutes, the ull initial dose can be repeated. The WHO recommends artemisininbased combination treatments as rst line or uncomplicated P. alciparum: artemether-lume antrine 1 dose at hours 1, 8, 24, 36, 48, and 60 based on body weight: 5 to 14 kg: 1 tablet per dose; 15 to 24 kg: 2 tablets per dose; 25 to 34 kg: 3 tablets per dose; greater than 34 kg: 4 tablets per dose. Other artemisinin combinations can be used as ollows: artesunate plus amodiaquine, artesunate plus mef oquine, and artesunate plus sul adoxine-pyrimethamine. The combination o choice depends on the level o resistance o the partner medication in a given region. Artemisinin and derivatives should not be given as monotherapy. For US-returning travelers • Quinine + doxycycline: quinine 10 mg/ kg 3 times daily or 7 days and doxycycline twice daily or 7 days or • Atovaquone-proguanil: atovaquone 20 mg/ kg/ d, proguanil 8 mg/ kg/ d or 3 days.

PART 2

ISSUES IN INTERNAL MEDICINE Care ul hemodynamic monitoring and management o seizures (with intravenous benzodiazepines) are essential. Pre ve nt io n Prevention measures are a public health priority and should include mosquito control, elimination o standing water in households and gardens, insect repellant containing at least 10% to 50% diethyltoluamide (DEET; 30% DEET provides 6-8 hours o protection), and permethrinimpregnated bed nets. Since 2000, prevention and control measures have reduced malaria mortality by more than 25% globally and by 33% in A rica. 46 Pre ve nt on for Trave le rs Choice o chemoprophylaxis depends on drug-resistance patterns or P. alciparum in the country being visited. Generally, prophylaxis should start 1 week be ore arrival and should continue through 4 weeks a ter leaving the endemic area. In the case o atovaquone-proguanil, prophylaxis may start the day be ore arrival and end 7 days a ter departure. Drugs commonly used in prophylaxis include atovaquone-proguanil (Malarone, which is expensive in the United States), mef oquine (may cause central nervous system side e ects), and doxycycline (causes photosensitivity). Chloroquine can be used only in a ew areas; chloroquinesusceptible malaria is restricted to the Caribbean, Central America, and parts o the Middle East.

RESO URCES

• Centers or Disease Control and Prevention. Malaria— http:/ / www.cdc.gov/ malaria. • World Health Organization. Malaria—http:/ / www.who.int/ malaria/ en/ .

LEISHMANIASIS Leishmaniasis is a vector-borne disease transmitted by the sandf y. It can be divided into 2 major orms, a cutaneous orm, which is the most common, and the visceral orm. There is also a more rare mucocutaneous orm that can cause signi cant acial dis gurement around the nose and mouth. Syno nyms Kala-azar is another name or visceral leishmaniasis. Ep id e mio lo g y

Tre atme nt of Se ve re P. falcip arum All cases o severe malaria should be managed as medical emergencies. Give intravenous (IV) or intramuscular (IM) artesunate, artemether, or quinine dihydrochloride (not available in the United States). In the United States give quinidine gluconate, 10 mg base/ kg (up to 600 mg) in 0.9% saline by rate-controlled IV in usion over 1 to 2 hours, ollowed by a maintenance dose o 0.02 mg base/ kg/ min with electrocardiogram (ECG) monitoring until patient can take oral drugs. Quinine and quinidine must never be given by IV bolus because o the potential or atal hypotension. Patients with cerebral malaria should undergo lumbar puncture to rule out bacterial meningitis and their blood glucose should be checked every 4 hours because o the signi cant risk o hypoglycemia in severe malaria.

• New World leishmaniasis is ound in Mexico, Central America, and South America. Old World leishmaniasis is ound in India, A rica, the Middle East, southern Europe, and parts o Asia. • Most leishmaniasis diagnosed in the United States occurs in travelers returning rom endemic areas including military personnel who served in Iraq or A ghanistan. • Some cutaneous leishmaniasis cases acquired in the United States have been reported in Texas and Oklahoma. 47 • Ninety percent o cutaneous leishmaniasis occurs in A ghanistan, Algeria, Iran, Saudi Arabia, Syria, Brazil, Colombia, Peru, and Bolivia. 47 • Ninety percent o visceral leishmaniasis cases occur in parts o India, Bangladesh, Nepal, Sudan, Ethiopia, and Brazil. 47

39

40

PART 2

ISSUES IN INTERNAL MEDICINE

Ch a pt e r 6

Et io lo g y and Pat ho p hysio lo g y • Leishmaniasis is caused by more than 20 species o the protozoan genus Leishmania. • Leishmaniasis is transmitted to people through the bite o the sandf y. • The intracellular amastigotes o Leishmania replicate within macrophages. • The disease can also be transmitted like any blood-borne in ection, but human-to-human transmission is rare. Risk Fact o rs • Living in and traveling to endemic countries. • Rural areas have a higher prevalence o disease in the endemic countries. • Not protecting the skin rom sandf y bites during the time rom dusk to dawn. • Blood trans usions, needle sharing in injection-drug users, needlestick injuries, and congenital transmission also are all reported risk actors or visceral leishmaniasis. 48

A

Diag no sis Cl n cal Fe ature s • Six weeks a ter a sandf y bite, the cutaneous orm may be localized to a single ulcer or nodule (Figure 6-8) or may be disseminated widely (Figure 6-9). • A ter a 2- to 6-month incubation period, the visceral orm can involve the liver, spleen, and bone marrow and causes systemic illness. The patient may present with ever, anemia, night sweats, weight loss, and an enlarged abdomen because o hepatosplenomegaly. 49 • Mucocutaneous leishmaniasis a ects the nose and mouth and may a ect the nasal septum and palate (Figure 6-10). This orm may occur months to years a ter what appears to be healing o cutaneous leishmaniasis. D str b ut on • A cutaneous orm o leishmaniasis has a predilection or the nose and ace (see Figure 6-8). • Cutaneous leishmaniasis is also commonly seen on the extremities. Note that the sandf y would generally have more access to bite the ace and extremities where clothing is less likely to be a protective barrier. • Disseminated cutaneous leishmaniasis can be seen rom the head to the toes (see Figure 6-9). Lab oratory Te st ng • Cutaneous leishmaniasis may be diagnosed by clinical appearance and a biopsy or a scraping o the ulcer. A Giemsa stain will demonstrate parasites in the skin smears taken rom the edge o an active ulcer.49 In some centers, PCR is available and is considered as the method o choice. 50 • Visceral leishmaniasis is diagnosed rom a blood sample or a bone marrow biopsy. Several serologic agglutination tests (direct agglutination test [DAT] or f uorescent allergosorbent test [FAST]) are highly sensitive or the detection o Leishmania antibodies. Culture o a bone marrow aspirate or PCR improves diagnostic yield. 49 Diffe re nt ial Diag no sis • The di erential diagnosis o cutaneous leishmaniasis includes leprosy, sarcoidosis, pyoderma gangrenosum, primary syphilis, and venous stasis ulcers. • The di erential diagnosis o visceral leishmaniasis includes malaria, typhoid ever, and lymphoma.

B FIGURE 6-8 Examp le s o le ishmaniasis on the ace . Le sions e me rg e at the site o the sand y b ite ; the nose is commonly a e cte d as se e n in the wome n in Fig ure s A and B rom A rica. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Manag e me nt Nonp harmacolog c Wound care or ulcers Me d cat ons The main drugs used to treat leishmaniasis include sodium stibogluconate (available rom the CDC) and meglumine antimonate. 51,52 Other medications used include milte osine (the only oral drug or leishmaniasis) f uconazole and liposomal amphotericin b (this is the only drug with FDA approval or visceral leishmaniasis in the United States). 51,52 Amphotericin b is the standard o care in India because o antimonial resistance. 50 Surg e ry Plastic surgery may be used to treat the dis gurement o mucocutaneous or cutaneous leishmaniasis.

GLO Ba L h e a Lt h

PART 2

ISSUES IN INTERNAL MEDICINE PRO GNO SIS • Cutaneous leishmaniasis does resolve spontaneously in some cases and in other cases it may persist and resist treatments. The prognosis is related to the severity o the case and the community o the host. Even in cases that resolve, scarring is requent. • Visceral leishmaniasis is atal i not diagnosed and treated. RESO URCES

• PubMed Health. Leishmaniasis—http:/ / www.ncbi.nlm.nih .gov/ pubmedhealth/ PMH0002362/ . • Centers or Disease Control and Prevention. Parasites– Leishmaniasis—http:/ / www.cdc.gov/ parasites/ leishmaniasis/ .

EYES—TRACHO MA EPIDEMIO LO GY AND GEO GRAPHIC DISTRIBUTIO N

FIGURE 6-9 Di use le ishmaniasis in an A rican man with involve me nt rom the ace to the toe s. The multip le nod ule s look like le p romatous le p rosy b ut b y skin snip te sting , the d iag nosis o le ishmaniasis was conf rme d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PREVENTIO N O F VECTO R-BO RNE DISEASES Prevention is a public health priority that must include vector (mosquito and sandf y) control, elimination o standing water in households and gardens, insect repellant containing 20% to 30% DEET, and permethrincoated bednets. Sandf ies and Anopheles mosquitoes bite rom dusk to dawn, but the A. aegypti vector o dengue ever bites any time during the day making daytime use o mosquito repellant especially important in dengue-endemic areas.

FIGURE 6-10 Se ve re mucocutane o us le ishmaniasis causing d e struction o the nose . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Chlamydia trachomatis is the leading in ectious cause o blindness, accounting or 3% o the world’s blindness. Globally, 21.4 million people have trachoma, and o these, 1.2 million are blind. 53 Trachoma is associated with poor sanitation, inadequate water supply, and lack o personal hygiene. It is transmitted rom person to person via unwashed ngers, f ies, and close amily contact (sharing o ace towels and bedclothes). Trachoma is endemic in A rica (especially in the driest regions), India, South Asia, Australia, and parts o South America. CLINICAL PRESENTATIO N Patients experience inf ammation o the eye with watery discharge, itching, burning, and blurry vision. Examination o the tarsal conjunctiva reveals ollicles (round swellings that are paler than the surrounding conjunctiva, at least 0.5 mm in diameter). With progression, intense trachomatous inf ammation develops, producing inf ammatory thickening o the tarsal conjunctiva, which appears red and thickened with numerous ollicles (Figure 6-11). Eventually, trachoma causes scarring, with white lines or bands in the tarsal conjunctiva as well as trichiasis, in which eyelashes turn inward and

FIGURE 6-11 Trachoma causing p romine nt ollicle s on the up p e r e ye lid in a p e rson in e cte d with C. trachomatis. Note how ip p ing the e ye lid is ne e d e d to se e the ollicle s und e r the up p e r e ye lid . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

41

42

PART 2

ISSUES IN INTERNAL MEDICINE

Ch a pt e r 6

Sk IN INFECTIO US SKIN DISEASES

FIGURE 6-12 Blind ne ss cause d b y untre ate d trachoma. Althoug h this is one o the most common cause s o b lind ne ss world wid e , trachoma is e asily tre atab le with a sing le d ose o o ral azithromycin. Pre ve ntion is achie ve d throug h b e tte r acce ss to wate r and soap , to g e the r with e d ucation ab out the thre e “Fs”: ie s, f ng e rs, acial hyg ie ne . (Re p ro d uce d with p e rmission from P. Usatine , MD.)

begin to rub against the cornea, and entropion, or inward turning o the eyelid itsel . With time, this chronic rubbing causes corneal opacity and blindness (Figure 6-12). DIAGNO SIS Although laboratory diagnostic testing is available or staining C. trachomatis in scrapings rom the tarsal plate, most settings where trachoma is endemic do not o er this resource, and visual inspection o the everted upper eyelid must su ce. Each eye should be examined or trichiasis and corneal opacities. The upper eyelid is everted by asking the patient to look down, holding eyelashes between thumb and nger, and everting the lid using a cotton-tipped applicator. The everted lid is then checked or ollicles, inf ammation, and scarring. The di erential diagnosis o trachoma includes allergic conjunctivitis (which can also produce ollicles o the tarsal plate), and bacterial or viral conjunctivitis.

Many o the skin diseases encountered in resource-limited countries are secondary to crowded living conditions and lack o clean water and soap. Scabies mites and human lice are endemic in many populations that are unable to wash requently. I clean water is scarce it is more likely to be used or drinking and cooking than bathing. In developed countries, we take clean running water (hot and cold), soap, and shampoo or granted. In developing countries, even i water is available, it may not be accessible as warm running water or showers or baths. When an intervention as simple as mass distribution o ree soap or personal hygiene draws enormous crowds to a mobile clinic, the vastness o inequality in access to basic health measures around the world becomes pain ully obvious. Although people recognize the importance o access to soap and clean water, the absence o this luxury results in skin in ections and in estations that are highly prevalent and spread rom person to person. We can divide skin diseases into in estations, bacterial, viral, and ungal in ections. All o these skin in ections are covered in the dermatology section o this book. Here we highlight some cases seen in developing countries. Scabies (see Chapter 141, Scabies) is caused by a human mite that burrows under the skin causing itching and leading to scratching. The itching and scratching may keep the person awake at night and may lead to bacterial superin ections. Scabies is spread by direct skin contact (Figure 6-13), shared bedding and clothing, and occasionally by omites. Human lice (see Chapter 140, Lice) exist as 3 separate species that are known as head lice, body lice, and pubic lice. Schoolchildren are particularly at risk or head lice, and in areas with limited head washing, the majority o kids may be in ested. Body lice live on clothing and eed on the blood o their host. Body lice are more prevalent in adults who bathe rarely and wear the same unwashed clothing day a ter day. Pubic lice are transmitted through sexual contact and are not known to be more prevalent in developing countries. Water and hygiene issues do predispose to increased head and body lice in developing countries.

MANAGEMENT • Azithromycin, 1 g single oral dose or adults and 20 mg/ kg or children in a single dose. • In pregnancy: erythromycin 500 mg twice daily or 7 days. • Less e ective: topical erythromycin and tetracycline. 10 • In some settings, surgery is available to correct entropion and trichiasis. PREVENTIO N Preventive measures include community hygiene education, use o soap and water or washing hands and aces, and control o f ies through use o ventilated improved pit (VIP) latrines. The WHO has developed the acronym “SAFE” or the global elimination o trachoma: S Surgery or entropion and trichiasis A Antibiotics or in ectious trachoma F Facial cleanliness to reduce transmission E Environmental improvements such as control o disease-spreading f ies and access to clean water54

FIGURE 6-13 Scab ie s in e station co ve ring the mothe r’s b re ast and he r b ab y’s hand . With p oor acce ss to he alth care , this in e station would like ly re main untre ate d , and could le ad to b acte rial sup e rin e ction and imp e tig o. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

GLO Ba L h e a Lt h

FIGURE 6-14 Imp e tig o cause d b y a b acte rial in e ction on the ne ck with hone y crusting . Imp e tig o is more p re vale nt whe n the re is inad e q uate hyg ie ne and lack o acce ss to he alth care . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 2

ISSUES IN INTERNAL MEDICINE

FIGURE 6-15 Le p romatous le p rosy with le onine acie s in a woman. Note the loss o e ye b rows calle d mad arosis and the p romine nt e ar involve me nt. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Int ro d uct io n Bacterial in ections o the skin (see Chapter 118, Impetigo) are ubiquitous throughout the world. Impetigo is a super cial bacterial in ection that presents with honey crusts (Figure 6-14) or bullae. Good hygiene can prevent impetigo and there ore it is not surprising that many cases o impetigo are seen in countries that lack access to soap and clean water. Impetigo is o ten secondary to other skin diseases such as scabies or ungal in ections that create breaks in the skin barrier unction. Cases o secondary in ected scabies and tinea are seen commonly in developing countries. Viral in ections o the skin include herpes simplex, varicella zoster, molluscum contagiosum, and human papilloma virus in ections. These in ections are seen commonly in HIV-in ected persons who are not receiving optimal antiretroviral therapy. In countries with a high prevalence o HIV-in ected people, a severe case o molluscum, warts, or shingles in a young person should prompt a clinician to consider HIV testing, i possible. Molluscum in ections and warts are so ubiquitous throughout the world that it is important to realize that healthy people with healthy immune systems can get these in ections too. Viral exanthems caused by diseases such as varicella and measles may be more prevalent in countries where vaccinations are less available. Fungal in ections o the skin can occur rom the head down to the toes. Heat, humidity, and lack o bathing are predisposing actors to ungal skin in ections. There ore, tropical developing countries provide good environments or tinea capitis, tinea corporis, and tinea pedis.

MYCO BACTERIUM (LEPRO SY AND TUBERCULO SIS-HIV CO INFECTIO N) LEPRO SY Pat ie nt St o ry A woman presents with signi cant changes to her ace (Figure 6-15). A slit-skin examination is per ormed on the ear lobe o the woman and many acid- ast bacilli, characteristic o Mycobacterium leprae, are ound. The woman is started on the WHO-standard multidrug therapy using ri ampin, clo azimine, and dapsone.

Leprosy (Hansen disease) is caused by M. leprae and is still endemic in many parts o the developing world where there is poverty and poor access to clean water. At one time, persons with leprosy were called “lepers” and isolated to leper colonies because the disease was dis guring and the communities were a raid that it was highly contagious. Current science and epidemiology tell us that leprosy is transmitted via droplets rom the nose and mouth during close and requent contact over a period o years, and not by casual contact. Thus doctors working with patients who have leprosy are at no real risk o becoming in ected. Issues related to stigma and discrimination still exist. Ep id e mio lo g y • There were 219,075 new cases reported in the world by 105 countries in 2011. 55 • The United States reported 173 new cases in 2011. 55 • Since 1990, more than 14 million leprosy patients have been cured, about 4 million rom 2000 to 2010. 56 Et io lo g y and Pat ho p hysio lo g y • The clinical mani estations o leprosy depend on the immunologic reaction to the in ection. The 2 opposite ends o the spectrum consist o the ollowing: ° Lepromatous leprosy in which there is a strong antibody response and a poor cell-mediated community resulting in larger amounts o M. leprae in the tissues (see Figure 6-15). ° Tuberculoid leprosy in which there is a strong cell-mediated immunity and a poor antibody response resulting in less M. leprae in the tissues. This tends to present with hypopigmented anesthetic patches (Figure 6-16). • There is also borderline leprosy in which there is a mixed cell-mediated immunity and antibody response showing eatures o both lepromatous leprosy and tuberculoid leprosy. • Treatment regimens di er depending on whether the patient has paucibacillary ( ewer organisms) or multibacillary leprosy. Lepromatous leprosy and borderline lepromatous leprosy are most likely to be multibacillary.

43

44

PART 2

ISSUES IN INTERNAL MEDICINE

FIGURE 6-16 Multibacillary lep rosy with hypop ig me nte d patche s. These patches are commonly numb due to cutaneous nerve damage rom mycobacterial in ection. (Re produced with p ermission from Richard P. Usatine, MD.)

Risk Fact o rs • Poverty and living in an endemic area. • Inadequate access to clean water and poor hygiene. • Living in the household o an in ected person. • Eating or handling armadillos as these animals are natural hosts or M. leprae. Diag no sis Cl n cal Fe ature s • Facial eatures include leonine acies, madarosis (loss o eyebrows as seen in Figure 6-15), elongated and dysmorphic earlobes, and saddlenose de ormities rom destruction o the nasal cartilage and bone. • Visible skin changes include nodules in lepromatous leprosy, hypopigmented patches in tuberculoid (see Figure 6-16) and borderline leprosy, and annular saucer-like lesions in borderline leprosy. • Nerve involvement can cause a clawhand (f exion contractures o the ngers as seen in Figure 6-17), wristdrop, ootdrop, Bell palsy, hammertoes, and sensory neuropathy leading to neurotropic ulcers and traumatic blisters.

Ch a pt e r 6

FIGURE 6-18 Le p rosy has cause d this old man to lose his f ng e rs b ut he continue s to le ad a p rod uctive li e we aving rug s or sale at a le p rosy hosp ital. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

D str b ut on The nodules o lepromatous leprosy are mostly seen on the ace and ears but can be seen in other areas. Hypopigmented patches can be seen anywhere on the body including the ace. Lab oratory Te st ng • In obvious cases o leprosy, the slit-skin examination done on the ear lobe or bacillary index is the most important test to determine i the patient has multibacillary or paucibacillary leprosy. • In cases that are suspicious or leprosy (especially outside o endemic areas), a skin punch biopsy o a suspicious lesion is use ul or nding M. leprae in the tissues. Diffe re nt ial Diag no sis Super cial mycoses, vitiligo, and cutaneous lariasis all cause changes in pigmentation similar to leprosy. In ltrated lesions that resemble leprosy include those o leishmaniasis, psoriasis, and sarcoidosis. 57 Manag e me nt

• Eye involvement can cause corneal anesthesia, keratitis, episcleritis, lagophthalmos (the inability to close the eyelid completely), and blindness.

Early diagnosis and multidrug therapy are essential or reducing the disease burden o leprosy worldwide. The WHO has supplied multidrug therapy ree o cost to leprosy patients in all endemic countries. 58

• Advanced untreated leprosy can lead to shortening and/ or loss o ngers as a result o bone resorption in hands that have become anesthetic and not protected rom repeated trauma (Figure 6-18).

• Leprosy is curable and treatment at an early stage can prevent disability. • Multidrug therapy is a combination o ri ampin, dapsone, and clo azimine or multibacillary leprosy patients, and ri ampin and dapsone or paucibacillary patients. • Duration o multidrug therapy is 12 to 24 months or multibacillary and 6 months or paucibacillary patients. 57 • Treatment with a single antileprosy drug will always result in development o drug resistance to that drug and is there ore an unethical practice. • Strategies to increase early access to care and to provide easy-to-obtain ree multidrug treatment are essential or eliminating leprosy in the world. Research on a preventive vaccine continues in tandem with Mycobacterium tuberculosis vaccine research. 59

FIGURE 6-17 Clawhand cause d b y the ne urolog ic d amag e o le p rosy. This cond ition may b e ame nab le to surg ical inte rve ntion involving te nd on trans e r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Comprehensive treatment o advanced cases with neuropathy should include oot and hand care to prevent urther damage to these insensitive limbs. 57

GLO Ba L h e a Lt h

• Surgical management or some leprosy-associated problems, such as tendon trans er to correct the clawhand, may be available in some centers. 60 TUBERCULO SIS AND HIV Ep id e mio lo g y Tuberculosis (TB) is a very common HIV-associated in ection, and causes at least 13% o HIV-associated deaths worldwide. 61 In 2010 alone, the WHO estimated that there were 1.1 million HIV-associated new cases o TB, the majority o whom live in sub-Saharan A rica. Globally, about one-third o HIV-in ected people are coin ected with TB (at least 11 million people). 62 Pat ho g e ne sis TBis transmitted by aerosolized respiratory droplet nuclei (see Chapter 64, Tuberculosis). Weakened cell-mediated immunity in HIV-in ected individuals allows more rapid disease progression and causes higher mortality rates rom TB. At the same time, untreated TB in ection accelerates toward immunologic decline in HIV in ection. Because these 2 diseases pre erentially a f ict populations with reduced access to medications and supportive care, the emergence o multidrug-resistant TB has become an increasing threat.

PART 2

ISSUES IN INTERNAL MEDICINE Patients with low CD4 cell counts (< 200 cells/ µL) commonly have poorly reactive skin tests or TB, and thus need a care ul history o exposures, review o symptoms, and monitoring o the chest x-ray or evidence o active disease, with repeat TB screening when the CD4 cell count rises above 200 cells/ µL. Manag e me nt Late nt TB infe ct on HIV-positive patients with latent tuberculosis in ection (LTBI) should have a chest x-ray and 3 sputum smears or acid- ast bacilli to rule out active disease. Once active TB is ruled out, isoniazid prophylaxis should be initiated regardless o age or any HIV-positive person with the ollowing characteristics: (a) a positive diagnostic test or LTBI, or (b) a negative LTBI test but with evidence o old or poorly healed brotic lesions on chest x-ray, or (c) negative LTBI diagnostic test in a close contact o a person with in ectious pulmonary TB. Duration o LTBI prophylaxis: isoniazid 300 mg daily or twice weekly or 9 months given with vitamin B6 (pyridoxine 25 mg daily). An alternative regimen o 12 doses o once weekly isoniazid-ri apentine has recently been validated. Pyridoxine prevents isoniazid-associated peripheral neuropathy. 63 Act ve M. Tub e rculosis D se ase

Clinical Pre se nt at io n The clinical presentation o TB in an HIV-in ected person with a relatively preserved immune system (CD4+ T-cell count >350 cells/ µL), is identical to that seen in HIV-negative patients. With increasing immunode ciency, however, TB o ten presents atypically. Chest radiographs may not demonstrate classic ndings o upper lobe bronodular or cavitary disease, and extrapulmonary presentations (lymphadenitis, pleuritis, pericarditis, meningitis) are seen. Tuberculous lymphadenitis and cutaneous TB (designated scro ula when it a ects the neck) are illustrated in Figure 6-19. Diag no sis HIV screening should be per ormed in all patients diagnosed with TB, and HIV-in ected patients should be screened annually or M. tuberculosis with puri ed protein derivative (PPD) skin testing, chest x-ray, and/ or blood test or inter eron-γ release assay (IGRA) depending on availability.

Any HIV-positive patient with cough and pulmonary in ltrates should be placed in respiratory isolation until TB is ruled out by 3 separately obtained sputum smears (Ziehl-Neelsen) with cultures sent or acid- ast bacilli. This rule applies even when the chest radiograph does not demonstrate cavitary or upper lobe in ltrates. Smear-negative, culture-positive M. tuberculosis is not uncommon. Treatment regimens or HIV-TB coin ected patients are largely identical to those o TB monoin ected patients. It is important not to start antiretroviral therapy (ART) and TB therapy simultaneously, to avoid con usion about drug allergies and side e ects. In addition, there is a risk o immune reconstitution syndrome (immune reconstitution inf ammatory reaction [IRIS]: inf ammatory response that worsens mani estations o any opportunistic in ection) when ART is started too soon a ter initiating TB medication. Guidelines or ART in TB coin ection are speci c. I the CD4 cell count is less than 50, ART should start within 2 weeks o TB therapy. I the CD4 count is greater than 50, ART should start within 8 to 12 weeks o TB therapy. I IRIS does occur, both ART and TB treatment should be continued while managing the IRIS. 64 Directly observed therapy (DOT) or TB is strongly recommended or HIV-TB coin ected patients.

PRO VIDER AND PATIENT RESO URCES

• Traveler’s Health from the Centers for Disease Control and Prevention is a comprehensive site that includes in ormation on more than 200 international destinations, travel vaccinations, diseases related to travel, illness and injury abroad, nding travel health specialists, insect protection, sa e ood and water, and a survival guide—http:/ / wwwnc.cdc.gov/ travel/ .

FIGURE 6-19 Scro ula o the ne ck cause d b y M. tub e rculosis in an ad ult who d id not comp le te his tub e rculosis tre atme nt. The long d uration o the rap y le ad s to challe ng e s or ad he re nce , and d rug -re sistant tub e rculosis commonly re sults. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• The Yellow Book 2012 is available online as a re erence or those who advised international travelers about health risks—http:/ / wwwnc.cdc.gov/ travel/ page/ yellowbook-2012-home .htm.

45

46

PART 2

ISSUES IN INTERNAL MEDICINE • Detailed vaccine information for travel can be obtained at the CDC website on vaccinations. This includes in ormation on yellow ever vaccine, typhoid vaccine, and routine vaccines—http:/ / wwwnc .cdc.gov/ travel/ page/ vaccinations.htm. • Vaccine information can be looked up by speci c destination on the traveler’s health website—http:/ / wwwnc.cdc.gov/ travel/ . • US Department of State International Travel Site, including country speci c in ormation, travel alerts and travel warnings—http:/ / travel.state.gov/ travel/ travel_1744.html.

CO NCLUSIO N Medical students and health pro essionals are being increasingly drawn to global health or reasons ranging rom the desire or enhanced cultural understanding, to the mission to work or global health equity, to alleviate su ering, or to broaden medical experience beyond geographic boundaries. Whatever one’s personal motivation, such experiences should never be undertaken without disciplined preparation. Medical pro essionals should learn in advance o their travels about the culture, language, and expressed needs and priorities o the local government and health providers and their service populations. In addition, they need to learn about the diagnoses and locally appropriate management o prevalent diseases in the population they plan to serve. Equally important, they should take appropriate preventive measures (vaccines, malaria prophylaxis) to protect their own health. Lack o personal and pro essional preparation can easily turn the tide rom net bene t to major burdens or host country organizations. Ultimately, well-prepared medical educators and clinicians, wherever they may come rom, are uniquely positioned to share knowledge that saves lives and leads to a more equitable world. REFERENCES 1. Kaplan JP, Bond TC, Merson MH, et al. Towards a common de nition o global health. Lancet. 2009;373:1993-1995. 2. Brown TM, Cueto M, Fee E. The World Health Organization and the transition rom “international” to global” public health. Am J Public Health. 2006;96:62-72. 3. Central Intelligence Agency. TheWorld Factbook. http:/ / www.cia. gov/ library/ publications/ the-world- actbood/ geos/ cy.html. Accessed September 20, 2012. 4. Waterkeyn J, Carincross S. Creating demand or sanitation and hygiene through community health clubs: a cost-e ective intervention in two districts in Zimbabwe. Soc Sci Med. 2005;61(9): 1958-1970.

Ch a pt e r 6

eds. Ox ord Handbook o Tropical Medicine. 3rd ed. New York, NY: Ox ord University Press; 2008:665-739. 9. Boggild AK, Van Voorhis WC, Liles WC. Travel-acquired illnesses associated with ever. In: Jong E, San ord E, eds. Travel andTropical Medicine Manual. 4th ed. Philadelphia, PA: Saunders Elsevier; 2008. 10. Gilbert D, Moellering R, Eliopoulos G, Chambers H, Saag M. The San ord Guide to Antimicrobial Therapy. 41st ed. Sperryville, VA: Antimicrobial Therapy; 2011. 11. Cravioto A, Lanata CF, Lantagne DS, Nair GB. Final Report o the Independent Panel o Experts on the Cholera Outbreak in Haiti 2011. http:/ / www.un.org/ News/ dh/ in ocus/ haiti/ UN-cholera-reportnal.pd . Accessed September 21, 2012. 12. Levine MM, Gotuzzo E, Sow SO. Cholera in ections. In: Guerrant RL, Walker DH, Weller PF, eds. Tropical In ectious Diseases: Principles, Pathogens &Practice. 2nd ed. Philadelphia, PA: Elsevier; 2006: 273-282. 13. Penny ME. Diarrhoeal diseases. In: Eddleston M, Davidson R, Brent A, Wilkinson R, eds. Ox ord Handbook o Tropical Medicine. 3rd ed. New York, NY: Ox ord University Press; 2008:213-267. 14. Centers or Disease Control and Prevention. Cholera Diagnosis and Testing. http:/ / www.cdc.gov/ cholera/ diagnosis.html. Accessed September 21, 2012. 15. Centers or Disease Control and Prevention. Recommendations or the Use o Antibiotics or theTreatment o Cholera. http:/ / www.cdc.gov/ cholera/ treatment/ antibiotic-treatment.html. Accessed September 21, 2012. 16. Centers or Disease Control and Prevention. Domestic Intestinal Parasite Guidelines. http:/ / www.cdc.gov/ immigrantre ugeehealth/ guidelines/ domestic/ intestinal-parasites-domestic.html. Accessed September 21, 2012. 17. Keiser J, Utzinger J. E cacy o current drugs against soil-transmitted helminth in ections: systematic review and meta-analysis. JAMA. 2008;299(16):1936-1948. 18. Knopp S, Mohammed K, Speich B, et al. Mebendazole administered alone or in combination with ivermectin against Trichuris trichiura: a randomized controlled trial. Clin In ect Dis. 2010;51(12):1420-1428. 19. World Health Organization. Obesity and Overweight Factsheet, March 2013. http:/ / www.who.int/ mediacentre/ actsheets/ s311/ en/ . Accessed November 11, 2013. 20. Popkin BM. Nutritional patterns and transitions. Pop Devel Rev. 1993;19(1):138-157. 21. Branca F, Ferrari M. Impact o micronutrient de ciencies on growth: the stunting syndrome. Ann Nutr Metab. 2002;46(suppl 1): S8-S17.

5. World Health Organization. VIPand ROEC Latrines. http:/ / www. who.int/ water_sanitation_health/ hygiene/ emergencies/ s3_5.pd . Accessed September 21, 2012.

22. Popkin BM, Richards MK, Montiero CA. Stunting is associated with overweight in children o our nations that are undergoing the nutrition transition. J Nutr. 1996;126(12):3009-3016.

6. UNICEF and WHO. Progress on DrinkingWater and Sanitation 2012 Update. http:/ / www.wssin o.org/ leadmin/ user_upload/ resources/ JMP-report-2012-en.pd . Accessed September 21, 2012.

23. Damms-Machado A, Weser G, Bischo SC. Micronutrient de ciency in obese subjects undergoing low calorie diet. Nutr J. 2012;11:34. http:/ / www.nutritionj.com/ content/ 11/ 1/ 34. Accessed November 11, 2013.

7. Epstein J, Ho man S. Typhoid ever. In: Guerrant, RL, Walker DH, Weller PF, eds. Tropical In ectious Diseases: Principles, Pathogens & Practice. 2nd ed. Philadelphia, PA: Elsevier; 2006:220-240. 8. Araujo-Jorge T, Callan M, Chappuis F, et al. Multisystem diseases and in ections. In: Eddleston M, Davidson R, Brent A, Wilkinson R,

24. World Health Organization. Global Prevalence o Vitamin A Def ciency in Populations at Risk 1995-2005. In: WHO Global Database on Vitamin A De ciency. http:/ / whqlibdoc.who.int/ publications/ 2009/ 9789241598019_eng.pd . Accessed September 21, 2012.

GLO Ba L h e a Lt h

PART 2

ISSUES IN INTERNAL MEDICINE

25. World Health Organization. Micronutrient Def ciencies:Vitamin A Def ciency. http:/ / www.who.int/ nutrition/ topics/ vad/ en/ index. html. Accessed September 21, 2012.

42. Day N. Malaria. In: Eddleston M, Davidson R, Brent A, Wilkinson R, eds. Ox ord Handbook o Tropical Medicine. 3rd ed. New York, NY: Ox ord University Press; 2008:31-65.

26. West KP. Vitamin A de ciency as a preventable cause o maternal mortality in undernourished societies: plausibility and next steps. Int J Gynaecol Obstet. 2004;85(suppl 1):S24-S27.

43. Ashley E, White N. Malaria diagnosis and treatment. In: Jong E, San ord E, eds. Travel andTropical Medicine Manual. 4th ed. Philadelphia, PA: Saunders Elsevier; 2008:303-321.

27. Hurt L, ten Asbroek A, Amenga-Etego S, et al. E ect o vitamin A supplementation on cause-speci c mortality in women o reproductive age in Ghana: a secondary analysis rom the ObaapaVitA trial. BullWorld Health Organ. 2013;91(1):19-27.

44. Ho man S, Campbell C, White N. Malaria. In: Guerrant, RL, Walker DH, Weller PF, eds. Tropical In ectious Diseases: Principles, Pathogens &Practice. 2nd ed. Philadelphia, PA: Elsevier; 2006: 1024-1062.

28. McGuire S. WHO guideline: vitamin A supplementation in pregnant women. Adv Nutr. 2012;3(2):215-216.

45. Centers or Disease Control. Treatment o Malaria (Guidelines or Clinicians). April 2011. http:/ / www.cdc.gov/ malaria/ resources/ pd / clinicalguidance.pd . Accessed September 21, 2012.

29. Ross DA. Recommendation or vitamin A supplementation. J Nutr. 2002;132(9):S2902-S2906. 30. Brown K, Wuehler S, Peerson J. The importance o zinc in human nutrition and estimation o the global prevalence o zinc de ciency. Food Nutr Bull. 2001;22:113-169. 31. Kosek M, Black R, Keusch G. Nutrition and micronutrients in tropical in ectious diseases. In: Guerrant, RL, Walker DH, Weller PF, eds. Tropical In ectious Diseases: Principles, Pathogens &Practice. 2nd ed. Philadelphia, PA: Elsevier; 2006:36-52. 32. World Health Organization. Implementing the New Recommendations o the Clinical Management o Diarrhea. Guidelines or Policy Makers and Programme Managers. Geneva, Switzerland: World Health Organization; 2006. http:/ / whqlibdoc.who.int/ publications/ 2006/ 9241594217_ eng.pd . Accessed September 21, 2012. 33. Baqui AH, Black RE, Shams EA, et al. E ect o zinc supplementation started during diarrhoea on morbidity and mortality in Bangladeshi children: community randomised trial. BMJ. 2002;325:1059.

46. World Health Organization. 10 Facts on Malaria. http:/ / www.who. int/ eatures/ act les/ malaria/ en/ index.html. Accessed September 21, 2012. 47. Centers or Disease Control and Prevention. Parasites— Leishmaniasis. http:/ / www.cdc.gov/ parasites/ leishmaniasis/ . Accessed September 15, 2012. 48. Singh S. New developments in diagnosis o leishmaniasis. Indian J Med Res. 2006;123:311-330. 49. Ryan T. Dermatology. In: Eddleston M, Davidson R, Brent A, Wilkinson R, eds. Ox ord Handbook o Tropical Medicine. 3rd ed. New York, NY: Ox ord University Press; 2008:566. 50. Schwartz E. Leishmaniasis. In: Jong E, San ord E, eds. Travel andTropical Medicine Manual. 4th ed. Philadelphia, PA: Saunders Elsevier; 2008:532-542. 51. Pub Med Health. Leishmaniasis. http:/ / www.ncbi.nlm.nih.gov/ pubmedhealth/ PMH0002362/ . Accessed September 15, 2012.

34. Brown K, Wuehler S, Peerson J. The importance o zinc in human nutrition and estimation o the global prevalence o zinc de ciency. Food Nutr Bull. 2001. http:/ / archive.unu.edu/ unupress/ ood/ nb22-2.pd . Accessed September 21, 2012.

52. Pearson R, Weller P, Guerrant R. Chemotherapy o parasitic diseases. In: Guerrant, RL, Walker DH, Weller PF, eds. Tropical In ectious Diseases: Principles, Pathogens &Practice. 2nd ed. Philadelphia, PA: Elsevier; 2006:142-168.

35. World Health Organization. Micronutrient Def ciencies. Iron Def ciency Anaemia. http:/ / www.who.int/ nutrition/ topics/ ida/ en/ index. html. Accessed September 21, 2012.

53. World Health Organization. Prevention o Blindness andVisual Impairment, Priority Eye Diseases:Trachoma. http:/ / www.who.int/ blindness/ causes/ priority/ en/ index2.html. Accessed September 21, 2012.

36. Horton S, Milo , A. Iodine status and availability o iodized salt: an across-country analysis. Food Nutr Bull. 2010;31:214-220.

54. Yorston D. Ophthalmology. In: Eddleston M, Davidson R, Brent A, Wilkinson R, eds. Ox ord Handbook o Tropical Medicine. 3rd ed. New York, NY: Ox ord University Press; 2008:523.

37. World Health Organization. Iodine StatusWorldwide. http:/ / whqlibdoc.who.int.publications/ 2004/ 9241592001.pd . Accessed September 21, 2012. 38. Prousky JE. Pellagra may be a rare secondary complication o anorexia nervosa: a systematic review o the literature. Altern Med Rev. 2003;8(2):180. 39. Lanska DJ. Historical aspects o the major neurological vitamin de ciency disorders: the water-soluble B vitamins. Handbook o Clin Neurol. 2010;95:445-476. 40. Tomkins A. Nutrition. In: Eddleston M, Davidson R, Brent A, Wilkinson R, eds. Ox ord Handbook o Tropical Medicine. 3rd ed. New York, NY: Ox ord University Press; 2008:652-653. 41. Tharp M, Shear N. Drug Eruption: Pellagra. http:/ / www.visualdx. com/ visualdx/ visualdx6/ getDiagnosisText.do?moduleId= 14&diagnosisId= 52131&view=text&topic=1. Accessed November 11, 2013.

55. Global leprosy situation. Wkly Epidemiol Rec. 2012;87(34):316-328. 56. World Health Organization. Leprosy; Fact Sheet No.101. http:/ / www. who.int/ mediacentre/ actsheets/ s101/ en/ index.html. Accessed August 26, 2012. 57. World Health Organization. Leprosy Elimination.WHO Multidrug Therapy. http:/ / www.who.int/ lep/ mdt/ en/ index.html. Accessed August 26, 2012. 58. Meyers W. Leprosy. In: Guerrant, RL, Walker DH, Weller PF, eds. Tropical In ectious Diseases: Principles, Pathogens &Practice. 2nd ed. Philadelphia, PA: Elsevier; 2006:436. 59. Gormus BJ, Meyers WM. Under-explored experimental topics related to integral mycobacterial vaccines or leprosy. Expert Rev Vaccines. 2003;2(6):791-804. 60. Sapienza A, Green S. Correction o the claw hand. Hand Clin. 2012;28(1):53-66.

47

48

PART 2

ISSUES IN INTERNAL MEDICINE 61. National Institutes o Health Clinical Guidelines Portal. Federally Approved HIV/ AIDS Medical Practice Guidelines. http:/ / www.aidsin o. nih.gov/ content les/ lvguidelines/ adult_oi_041009.pd . Accessed September 21, 2012. 62. World Health Organization. TB/ HIV FACTS 2011-2012. http:/ / www.who.int/ tb/ publications/ TBHIV_Facts_ or_2011.pd . Accessed September 21, 2012. 63. Johnson J, Ellner J. Tuberculosis and atypical mycobacterial in ections. In: Guerrant, RL, Walker DH, Weller PF, eds. Tropical

CHAPTER 6

In ectious Diseases: Principles, Pathogens &Practice. 2nd ed. Philadelphia, PA: Elsevier; 2006:411. 64. National Institutes o Health Clinical Guidelines Portal. Considerations or Antiretroviral Use in Patients with Coin ections: MycobacteriumTuberculosis Disease with HIV Coin ection. http:/ / www.aidsin o.nih.gov/ guidelines/ html/ 1/ adult-and-adolescent-treatment-guidelines/ 27/ . Accessed December 9, 2013.

PART 3

PHYSICAL AND SEXUAL ABUSE

*

St re ng t h o Re co mme nd at io n (SO R)

De f nit io n

A

Re comme nd a ion b ase d on consis e n and g ood -q uali y p a ie n -orie n e d e vid e nce .*

B

Re comme nd a ion b ase d on inconsis e n or limi e d -q uali y p a ie n -orie n e d e vid e nce .*

C

Re comme nd a ion b ase d on conse nsus, usual p rac ice , op inion, d ise ase -orie n e d e vid e nce , or case se rie s or s ud ie s o d iag nosis, re a me n , p re ve n ion, or scre e ning .*

Se e Ap p e nd ix A on p ag e s 1241-1244 or ur he r in orma ion.

50

PART 3

PHYSICAL AND SEXUAL ABUSE

Ch a pt e r 7

7 INTIMATE PARTNER VIO LENCE Mind y A. Smith, MD, MS

PATIENT STO RY A woman who ed her abusive boy riend is observed sitting at a table with other women in a residential chemical dependency treatment program. Her bruised ace could not be missed (Figure 7-1). The program physician was asked to speak with her and learned that her boy riend beat her when she told him that she was voluntarily entering this program. The boy riend was also an addict and had been physically abusive to her be ore. The violence escalated when she said that she needed help to stop the alcohol and drugs. She le t him and did not believe that he would ollow her. The program management assured her that they would not let him on the premises and would do all they could to keep her sa e while she was recovering. Figure 7-2 was taken 2 months later, when her ace was healing along with her mind and spirit. She completed the 90-day program and is currently working and actively ollowing a 12-step program.

INTRO DUCTIO N Intimate partner violence (IPV) is def ned as an intimate partner’s physical, emotional, or sexual abuse. Physical violence is the intentional use o physical orce with the potential or causing death, disability, injury, or

FIGURE 7-2 Pho og rap h o he woman in Fig ure 7-1 ake n 2 mon hs la e r. He r acial and p sycholog ical wound s are he aling . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

harm. Physical violence includes scratching; pushing; biting; punching; use o a weapon; and use o restraints or one’s body, size, or strength against another person. 1

EPIDEMIO LO GY IPV a ects up to hal o the women in the United States during their li etime. 2 • An estimated 4.9 million IPV rapes and physical assaults occur each year among US women (age 18 years and older) and 2.9 million assaults occur among US men. Most o these assaults include pushing, grabbing, shoving, slapping, and hitting and do not result in major injury. 3 In a national telephone survey o 8000 women and 8000 men, 41.5% o the women who were physically assaulted by an intimate partner were injured during their most recent assault, compared with 19.9% o men. 4 • Physical violence by an intimate partner can result in direct injury including death (1181 women and 329 men in 2005; Bureau o Justice, 2007), adverse psychological, and social consequences, and impaired endocrine and immune systems through chronic stress and other mechanisms. 4 • A national survey estimated that 503,485 women and 185,496 men are stalked by intimate partners each year. 4 • Clinicians identi y only a small number o victims (1.5-8.5%). 1 Only approximately 20% o IPV rapes or sexual assaults, 25% o physical assaults, and 50% o stalking directed toward women are reported; ewer events against men are reported. 4 • Between 4% and 8% o women are battered during pregnancy. 5 FIGURE 7-1 Bruising cause d b y in ima e p ar ne r viole nce in a woman who e d he r ab usive b o y rie nd . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• According to the National Violence Against Women Survey, more than 200,000 women age 18 years and older were raped by intimate partners in the 12 months preceding the survey. 6

INt IMa t e pa r t Ne r VIO Le NCe

PART 3

PHYSICAL AND SEXUAL ABUSE

RISK FACTO RS Risk actors or IPV include the ollowing7: • Individual actors—Individual actors include prior history o IPV, witnessing or experiencing violence as a child, being emale, young, pregnant, less educated, unemployed, heavy user o alcohol or illicit drugs, mental health problems (eg, depression, borderline or antisocial personality traits), and engaging in aggressive or delinquent behavior as a youth. • For women, having a greater education level than their partner, being American Indian/ Alaska Native or A rican American, and having a verbally abusive, jealous, or possessive partner increased the risk. In addition, a risk o IPV by either a past or a new o ender was almost double or women who had recently changed residence compared with those who had not moved.8 • For men, having a di erent ethnicity rom their partner’s increased the risk o IPV. • Relationship actors—Relationship actors include couples with income, educational, or job status disparities or in which there is dominance and control o the relationship by one partner over the other, and marital con ict or instability. • Community actors—Community actors include poverty and associated actors or weak community sanctions against IPV (eg, police unwilling to intervene).

DIAGNO SIS

FIGURE 7-3 A woman wi h a larg e cranio omy wound ha was ne e d e d o e vacua e he r in racranial b le e d ing se cond ary o b e ing b e a e n ove r he he ad wi h a b oard b y he r f ancé . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Asking patients directly about violence at routine visits or when presenting with clues (as given below) is recommended or identi ying patients su ering rom IPV (see Screening and Prevention). 1,4 It is important to use patient-centered approaches. • Questions that may be asked include general questions about how things are going at home or more specif c questions about experiences o nonviolent (eg, insulting, threatening) or violent (eg, grabbing, punching, beating, orced sex) abusive acts. • Several sel -administered instruments are available or detecting IPV including the Woman Abuse Screening Tool (WAST). 9 In a study o screening tools, women pre erred sel -completed approaches (vs aceto- ace), although no di erences in prevalence was ound or method or screening instrument. 10 In a predominantly Hispanic population, investigators ound the Spanish version o the 4-question instrument HITS (Hurt-Insult-Threaten-Scream) to be moderately reliable with good validity compared with WAST or Spanish-speaking patients;11 HITS has also been validated with male victims. 12 CLINICAL FEATURES Clues on patient history include the ollowing: • Chronic pain syndromes (eg, headache, backache, stomachache, or pelvic pain) • Depression • Drug and alcohol abuse Up to 42% o women and 20% o men who were physically assaulted as adults sustained injuries during their most recent victimization. 3 Clues on physical examination include the ollowing: • Physical injury—Most physical injuries are minor (eg, contusions, lacerations, abrasions) but include broken bones, traumatic brain injury, and kni e wounds (see Figures 7-1 to 7-3).

FIGURE 7-4 Fro n al vie w o he woman in Fig ure 7-3 a a home le ss she l e r. She was p u ing he r li e b ack og e he r ag ain wi h he he lp o he she l e r and he p rovid e rs a he clinic. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

51

52

PART 3

PHYSICAL AND SEXUAL ABUSE

Ch a pt e r 7

° Ocular injuries can include so t tissue injuries, corneal abrasions,

orbital ractures, lens dislocation, retinal detachment, visual f eld loss, double vision, and blindness (see Figure 7-1). ° Trauma to the mouth and lips may be accompanied by ractures, broken teeth, tongue lacerations, and altered taste and smell. ° Injuries suspicious or abuse are those only in areas covered by clothing, injuries in di erent stages o healing, and injuries that show a de ensive wound pattern particularly on the hands or arms. ° Upper torso injury carries a high risk o injury to cervical spine, large vessels o the neck, chest, and lungs. • Depression or symptoms o posttraumatic stress disorder (eg, emotional detachment, sleep disturbances, ashbacks, replaying assault in mind). • Evidence o orced sexual assault. • Presence o sexually transmitted in ections.

MANAGEMENT • Initial evaluation, ollowing identif cation o abuse, is to assess or immediate danger to the woman and any children (eg, Do you eel it is sa e to go home tonight? Where is your partner?). I danger is perceived, assist the woman in f nding a sa e place to go (Figures 7-4 and 7-5). • Document all f ndings and include photographs (with date), i possible (Figure 7-6). • Develop a sa ety plan. This should include the ollowing: ° A sa e physical location that is not known to the abuser ° Transportation to that location ° A list o items to take or a packed suitcase—clothes, keys, cash, valuable documents, telephone numbers, prescriptions, something meaning ul or each child • Address the needs o any children—30% to 40% o children are also injured physically. 1 • Data on e ective intervention programs are scarce. ° In a community intervention program in rural South A rica, providing loans to poor women combined with a participatory learning

FIGURE 7-6 A cop y o a p ho og rap h, which he woman had in he r p urse , showing he r b lack e ye s a e r b e ing b e a e n b y he r husb and he mon h b e ore . O u o e ar or he r li e and he we ll-b e ing o he r child , she le he r husb and . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

and action curriculum integrated into loan meetings every 2 weeks reduced IPV. 13 ° Women residents in a domestic violence shelter showed improvement in psychological distress symptoms and less health care utilization ollowing a social support intervention. 14 ° An advocacy intervention or Chinese women who were victims o IPV did not reduce depression symptoms in a clinically meaning ul way. 15 ° In a Cochrane review o cognitive behavior therapy (CBT) or abusive men, only 4 small trials could be combined and no signif cant e ect was ound or reduced risk o violence (relative risk [RR], 0.86; 95% conf dence interval [CI], 0.54, 1.38); the authors concluded that there were too ew trials to determine the e ectiveness. 16

SCREENING AND PREVENTIO N • With respect to screening, the US Preventive Services Task Force recommends screening women o childbearing age, including adolescents, or intimate partner violence and providing or re erring women who screen positive to intervention services, SO R B . 17 • In one randomized clinical trial (RCT), computer screening increased detection and opportunities to discuss IPV in a busy amily medicine practice. 18 • In an observational study o a convenience sample o 2134 patients presenting to an emergency room (25.7% screened positive), there were no harms identif ed rom screening or IPV at 1 week postvisit and at 3 months; 35% o those screening positive reported having contacted community resources. 19 FIGURE 7-5 A young , Hisp anic mom wi h he r b ab y a a clinic in a home le ss she l e r. She had e d he r ab usive husb and wi h he r child . (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

• With respect to outcomes, a Canadian RCT (N = 6743 English-speaking women ages 18-64 years) conducted in 11 emergency departments,

INt IMa t e pa r t Ne r VIO Le NCe

12 amily practices, and 3 obstetrics/ gynecology clinics, screening or IPV did not signif cantly reduce IPV recurrence (46% vs 53% in screened vs unscreened patients [odds ratio [OR], 0.82; 95% CI, 0.32, 2.12]) or quality o li e scores; loss to ollow-up, however, was high (approximately 40%). 20

PRO GNO SIS • Many women are not ready to leave an abusive relationship or a variety o reasons. In one study, duration o abuse was less than 1 year to 5 median years, and in 5% to 3% o the instances, IPV persisted or more than 20 years. 21 • Women who are abused have a higher risk o posttraumatic stress disorder, depression (1 in 6 abused women will attempt suicide1), insomnia, nightmares, and alcohol (16- old risk o alcohol use1) and drug abuse (9- old risk over nonabused patient1). • IPV or women also decreases the odds o completing substance abuse treatment. 22

PART 3

PHYSICAL AND SEXUAL ABUSE Hotline: 800-779-SAFE (7233) TTY: 800-787-3224 available or the Dea , Dea -Blind and Hard o Hearing. Administrative phone: 512-453-8117 • National Coalition Against Domestic Violence is a membership organization that includes service programs, reading lists, advocacy, educational materials, and coordinates a national collaborative e ort to assist battered women in removing the physical scars o abuse—www.ncadv.org. • Centers for Disease Control and Prevention—http:/ / www.cdc .gov/ ViolencePrevention/ pdf/ IPV_factsheet-a.pdf. PRO VIDER RESO URCES

• Centers for Disease Control and Prevention. Intimate Partner Violence—http:/ / www.cdc.gov/ ViolencePrevention/ intimatepartnerviolence/ index.html. • Futures without Violence—http:/ / www .futureswithoutviolence. org/ . • Institute on Domestic Violence in the African American Community—http:/ / www.dvinstitute.org.

FO LLO W-UP • Plan or the next visit and provide ongoing support as it o ten takes time or women to leave an abusive relationship. • Monitor or depression, insomnia, nightmares, and alcohol and drug abuse.

PATIENT EDUCATIO N • Assist patients in recognizing the cycle o abuse, that is, violence ollowed by remorse or apology, tension-building period (patient may experience ear, isolation, orced dependency, intermittent reward), ollowed by another episode o violence. • Provide victim education and in ormation on community resources (see Patient Resources below). • Acknowledge that leaving may take time. • Recovery rom abuse may include shame and guilt, but o ten leads to an improved sense o sel and sel -worth. • In a ollow-up study o women exiting a shelter, women who were employed, reported higher quality o li e, and had people in their networks who provided practical help and/ or were available to talk about personal matters were less likely to be revictimized. 23

PATIENT RESO URCES

• National Domestic Violence Hotline connects individuals to help in their area by using a nationwide database that includes detailed in ormation about domestic violence shelters, other emergency shelters, legal advocacy and assistance programs, and social service programs. Help is more than 170 languages, 24 hours a day, 7 days a week—www.ndvh.org.

REFERENCES 1. Centers or Disease Control. Intimate PartnerViolence:Def nitions. http:/ / www.cdc.gov/ ViolencePrevention/ intimatepartnerviolence/ def nitions.html. Accessed August 2013. 2. Gilchrest VJ. Abuse o women. In: Smith MA, Shimp LA, eds. 20 Common Problems inWomen’s Health Care. New York, NY: McGraw-Hill; 2000:197-224. 3. Tjaden P, Thoennes N. Extent, Nature, and Consequences o Intimate PartnerViolence: Findings rom the NationalViolence AgainstWomen Survey. Washington, DC: Department o Justice (US); 2000. Publication No. NCJ 181867. O f ce o Justice Programs. http:/ / www.ojp. usdoj.gov/ nij/ pubs-sum/ 181867.htm. Accessed August 2013. 4. Centers or Disease Control. Intimate PartnerViolence: Consequences. http:/ / www.cdc.gov/ ViolencePrevention/ intimatepartnerviolence/ consequences.html. Accessed August 2013. 5. Centers or Disease Control. Intimate PartnerViolence During Pregnancy, A Guide or Clinicians: Download Instructions. http:/ / www.cdc.gov/ reproductivehealth/ violence/ IntimatePartnerViolence/ ipvdp_ download.htm. Accessed August 2013. 6. Centers or Disease Control. CDC Injury Fact Book. www.cdc.gov/ ncipc/ act_book/ 24_Sexual_Violence.htm. Accessed August 2013. 7. Centers or Disease Control. Intimate PartnerViolence: Risk and Protective Factors. http:/ / www.cdc.gov/ ViolencePrevention/ intimatepartnerviolence/ riskprotective actors.html. Accessed August 2013. 8. Waltermaurer E, McNutt LA, Mattingly MJ. Examining the e ect o residential change on intimate partner violence risk. J Epidemiol Community Health. 2006;60(11):923-927. 9. Fogarty CT, Burge S, McCord EC. Communicating with patients about intimate partner violence: screening and interviewing approaches. Fam Med. 2002;34(5):369-375. 10. MacMillan HL, Wathen CN, Jamieson E, et al. Approaches to screening or intimate partner violence in health care settings: a randomized trial. JAMA. 2006;296(5):530-536.

53

54

PART 3

PHYSICAL AND SEXUAL ABUSE

CHAPt ER 7

11. Chen PH, Rovi S, Vega M, et al. Screening or domestic violence in a predominantly Hispanic clinical setting. Fam Pract. 2005;22(6): 617-623.

17. United States Preventive Services Task Force. Screening or Family and Intimate PartnerViolence. http:/ / www.uspreventiveservicestask orce. org/ uspst / uspsipv.htm. Accessed August 2013.

12. Shakil A, Donald S, Sinacore JM, Krepcho M. Validation o the HITS domestic violence screening tool with males. Fam Med. 2005;37(3): 193-198.

18. Ahmad F, Hogg-Johnson S, Stewart DE, et al. Computer-assisted screening or intimate partner violence and control: a randomized trial. Ann Intern Med. 2009;151(2):93-102.

13. Pronyk PM, Hargreaves JR, Kim JC, et al. E ect o a structural intervention or the prevention o intimate-partner violence and HIV in rural South A rica: a cluster randomised trial. Lancet. 2006;368(9551):1973-1983.

19. Houry D, Kaslow NJ, Kemball RS, et al. Does screening in the emergency department hurt or help victims o intimate partner violence? Ann Emerg Med. 2008;51(4):433-442.

14. Contantino R, Kim Y, Crane PA. E ects o a social support intervention on health outcomes in residents o a domestic violence shelter: a pilot study. Issues Ment Health Nurs. 2005;26(6): 575-590. 15. Tiwari A, Fong DY, Yuen KH, et al. E ect o an advocacy intervention on mental health in Chinese women survivors o intimate partner violence: a randomized controlled trial. JAMA. 2010;304(5): 536-543. 16. Smedslund G, Dalsbø TK, Steiro AK, et al. Cognitive behavioural therapy or men who physically abuse their emale partner. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD006048.

20. MacMillan HL, Wathen CN, Jamieson E, et al. Screening or intimate partner violence in health care settings: a randomized trial. JAMA. 2009;302(5):493-501. 21. Thompson RS, Bonomi AE, Anderson M, et al. Intimate partner violence: prevalence, types, and chronicity in adult women. Am J Prev Med. 2006;30(6):447-457. 22. Lipsky S, Krupski A, Roy-Bryne P, et al. E ect o co-occurring disorders and intimate partner violence on substance abuse treatment outcomes. J Subst AbuseTreat. 2010;38(3):231-244. 23. Bybee D, Sullivan CM. Predicting re-victimization o battered women 3 years a ter exiting a shelter program. Am J Community Psychol. 2005;36(1-2):85-96.

SEXUAL ASSAULT

8 SEXUAL ASSAULT Mind y A. Smith, MD, MS

PATIENT STO RIES CASE 1 A 19-year-old woman, a college student, presents to the o f ce a ter being raped 3 weeks ago. She went out on a date and was orced to have sex against her will. She states that she had been a virgin and that he made her bleed by penetrating her vagina with his penis. She tried to stop him, but was a raid to f ght too hard because he was a strong man and was drunk. She is in tears as she tells her story. She waited so long to come in or help because she did not know where to turn. She took emergency contraception (EC) immediately, and a home pregnancy test taken last night was negative. She wants to be checked or any sexually transmitted in ections (STIs). Upon examination, there is a tear o her hymen at the 5-o’clock position that has healed (Figure 8-1). There are no signs o in ection and STI screening is per ormed. She is a raid to prosecute but would like to be re erred to a rape-counseling program. CASE 2 A 47-year-old woman is seen in a ollow-up or depression. She admits to being raped in a parking lot several months ago but did not report it to the police. She is continuing to have intrusive nightmares and ashbacks o the event. She is having di f culty concentrating at work and does not eel com ortable in social situations.

PART 3

PHYSICAL AND SEXUAL ABUSE INTRO DUCTIO N Sexual violence is a sex act completed or attempted against a victim’s will or when a victim is unable to consent because o age, illness, disability, or the in uence o alcohol or other drugs. 1 It may involve actual or threatened physical orce, use o guns or other weapons, coercion, intimidation, or pressure. Sexual violence includes unwanted intercourse (completed sex act def ned as contact between the penis and the vulva or penis and anus involving penetration); an attempted sex act, abusive sexual contact (intentional touching either directly or through clothing o the genitals, anus, groin, breast, inner thigh, or buttocks against a victim’s will or when a victim is unable to consent); and noncontact sexual abuse, such as voyeurism, intentional exposure to exhibitionism, undesired exposure to pornography, verbal or behavioral sexual harassment, threats o sexual violence, or taking nude photographs o a sexual nature o another person without his or her consent or knowledge or o a person unable to consent or re use.

EPIDEMIO LO GY • Based on the National Intimate Partner and Sexual Violence Survey (NISVS, 2010) o more than 16,000 adults, nearly 1 in 5 women (18.3%) and 1 in 71 men (1.4%) in the United States has been raped. 2 More than hal o the women were raped by an intimate partner (see Chapter 7, Intimate Partner Violence) and 40.8% by an acquaintance. Among men, more than hal were raped by an acquaintance and 15.1% by a stranger. 2 • Unwanted sexual contact was reported in the NISVS by 27.2% o women and 11.7% o men. 2 • Li etime stalking victimization was reported by 1 in 6 women (16.2%) and 1 in 19 men (5.2%) in the NISVS. 2 • Most victims o sexual assault are young: ° In the NISVS, most women (79.6%) experienced their f rst completed rape be ore age 25 years and 42.2% be ore the age o 18 years.2 More than one-quarter o male victims o completed rape (27.8%) experienced their f rst rape be ore they were 11 years o age. ° Similar f ndings were reported in another national survey where 60.4% o emale and 69.2% o male victims were f rst raped be ore age 18 years.3 A quarter o emales were f rst raped be ore age 12 years. • In surveys o college students, annually 10% o women described a rape, 17% reported an attempted rape, 26% reported unwanted sexual coercion, and 63% experienced unwanted sexual contact. 4 • Women in substance abuse treatment are a particularly high-risk group or having experienced violence. In one study, 89% reported a history o interpersonal violence and 70% reported a history o sexual assault. 5 • Men are most o ten the perpetrators o sexual violence;2 even among male victims, predominantly male perpetrators committed the rape or noncontact unwanted sexual experiences reported, and almost hal o stalking victimizations o men were perpetrated by men.

FIGURE 8-1 Exte rnal g e nitalia of a 19-ye ar-old woman, a colle g e stud e nt, showing the te ar of he r hyme n at ap p roximate ly the 5-o’clock p osition. This was the re sult of d ate rap e 3 we e ks b e fore the p hotog rap h was take n. (Re p rod uce d with p e rmission from Nancy D. Ke llog g , MD.)

• According to the FBI Uni orm Crime Reports, there were an estimated 84,767 orcible rapes reported to law en orcement in 2010 or 54.2 per 100,000 women, a decrease o 5% rom 2009 and 6.7% lower than 2001.6 Most women, however, do not report being raped to the police: ° As in the cases presented in this chapter, most cases o sexual assault go unreported (only about 1 in 5 women report their rape to police). 7 Reasons or ailing to report include ear o reprisal, shame,

55

56

PART 3

PHYSICAL AND SEXUAL ABUSE

Ch a pt e r 8

ear o the justice system, and ailure to def ne the act as rape. Furthermore, according to victim accounts in the NISVS, only 37% o the rapes reported to police resulted in the rapist being criminally prosecuted, and o those prosecuted, less than hal (46.2%) were convicted o a crime. 2

ETIO LO GY AND PATHO PHYSIO LO GY Two types o actors are believed to contribute to sexual violence— Vulnerability actors that increase the likelihood that a person will su er harm and risk actors that increase the likelihood that a person will cause harm. Neither vulnerability nor risk actors are direct causes o sexual violence. 3

RISK FACTO RS Vulnerability actors or sexual assault, in addition to young age and emale gender, include the ollowing8,9:

FIGURE 8-2 The mutilate d arm of a 26-ye ar-old woman who was rap e d 5 ye ars b e fore this p hotog rap h was take n. Afte r b e ing rap e d , she b e came suicid al and b e g an cutting he r arm re p e ate d ly. The ad d itional malformation of the arm is se cond ary to oste o mye litis from p re vio us intrave nous d rug use . (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

• Prior history o sexual violence • Being disabled (physical, psychiatric illness, or cognitive impairment) • Pregnancy • Poverty, homelessness • Having many sexual partners or involved in sex work • Consuming alcohol or illicit drugs Risk actors or perpetration include the ollowing8,10: • Alcohol and drug use • Childhood history o physical or sexual abuse and/ or witnessed amily violence as a child • Coercive sexual antasies

• Women who are raped are signif cantly more likely than nonraped women to experience genital injuries and STIs, and have signif cantly greater di f culties with aspects o reproductive or sexual unctioning, including dyspareunia, endometriosis, menstrual irregularities, and chronic pelvic pain. 11 • Many women su er psychological trauma ollowing sexual assault such as posttraumatic stress disorder (PTSD) symptoms1: ° Immediate psychological consequences include con usion, anxiety, withdrawal, ear, guilt, intrusive recollections, emotional detachment, and ashbacks. ° Some victims may attempt suicide a ter being raped (Figure 8-2).

• Pre erence or impersonal sex • Hostility toward women • Association with sexually aggressive and delinquent peers • Family environment characterized by physical violence and ew resources • Poverty and lack o employment opportunities • Societal norms that support sexual violence, male superiority, and sexual entitlement • Weak laws and policies related to gender equity

DIAGNO SIS It is recommended that patients are asked directly about violence during routine visits, when seen in the emergency department, or when presenting with substance abuse, depression, and/ or physical clues (as listed below) so as to identi y those who are su ering rom the a termath o sexual or physical violence (see Chapter 7, Intimate Partner Violence). CLINICAL FEATURES • Approximately 33% o women and 16% o men have physical injuries as a result o a rape; 36.2% o injured women received medical treatment. 1

MANAGEMENT NO NPHARMACO LO GIC Following a sexual assault, many women report that they thought they were going to be killed. The survivor may be terrif ed and unable to provide a complete history o the assault. It is important to provide support, reassurance o immediate sa ety, and obtain in ormed consent or examination, procedures, and contact o others. With permission, the clinician should contact a rape crisis worker and the police, although the survivor decides whether or not to f le criminal charges; in general, notif cation o law en orcement is not required i the patient is an adult o age 18 years or older and is not disabled, mentally ill, or elderly. In these cases, reporting is done only i the patient gives his or her consent. Injury caused by any weapon or incidents involving li e-threatening assault, however, must be reported to the law en orcement agency (per statute) irrespective o reporting the sexual assault. 12 • A guideline developed or the state o Oregon is available rom the US Department o Justice or the emergency medical evaluation o a sexual assault victim. 12 Steps in the evaluation are reviewed brie y below. A medical orensic evaluation is appropriate i the assault occurred within 84 hours o presentation. A Standard Sexual Assault Forensic Evidence (SAFE) Kit should be used or gathering orensic evidence.

Se XUa L a SSa ULt

• The patient should be assessed or sa ety and immediate mental health needs. The history includes details o the assault (eg, date, time, location, descriptors o assailant[s]), type o bodily and sexual contact (orif ce[s] penetrated, objects used), and sexual activity or bathing or washing since the assault. 9,12 Laws in all 50 states strictly limit the evidentiary use o a survivor’s previous sexual history, including evidence o previously acquired STIs, as part o an e ort to undermine the credibility o the survivor’s testimony. 13 • Treat traumatic injuries—Physical examination should include observations o emotional state and descriptions o clothing and stains. Gently, and with permission, examine or lacerations, abrasions, ecchymoses, and bites. A body chart may be use ul or documenting the size, type, color, and location o any injuries. A genital examination should be conducted by an experienced clinician in a way that minimizes urther trauma to the survivor; examination is directed by history. • Test and treatment or STI—A guideline or managing STI ollowing sexual assault is available through the Centers or Disease Control and Prevention (CDC). 13 ° Trichomoniasis, bacterial vaginosis (BV), gonorrhea, and chlamydial in ection are the most requently diagnosed in ections ollowing sexual assault. As the prevalence o these in ections is high among sexually active women, their presence a ter an assault does not necessarily signi y acquisition during the assault. ° Nucleic acid amplif cation tests (NAATs) are recommended or Neisseria gonorrhoeae and Chlamydia trachomatis. These tests are preerred or the diagnostic evaluation o sexual assault victims, regardless o the sites o penetration or attempted penetration. 13 ° Wet mount or point-o -care testing o a vaginal swab specimen or Trichomonas vaginalis in ection is recommended. The wet mount also should be examined or evidence o BV and candidiasis, especially i vaginal discharge, malodor, or itching is present. ° Collect a serum sample or immediate evaluation or HIV, hepatitis B, and syphilis, and obtain serum or urine or a pregnancy test in reproductive-aged women. Obtain toxicology and/ or alcohol test i a patient has altered mental status, reports blackouts, or is concerned that he/ she may have been drugged. 12 MEDICATIO NS

PART 3

PHYSICAL AND SEXUAL ABUSE epidemiology o HIV/ AIDS, and exposure characteristics o the assault. Specif c circumstances o an assault that might increase the risk or HIV transmission are trauma, including bleeding, with vaginal, anal, or oral penetration; exposure o mucous membranes to ejaculate; viral load in ejaculate (eg, multiple assailants); and the presence o an STI or genital lesions in the assailant or survivor. • I HIV postexposure prophylaxis (PEP) is o ered, the ollowing in ormation should be discussed with the patient: (a) the unproven benef t and known toxicities o antiretrovirals; (b) the close ollow-up that will be necessary; (c) the benef t o adherence to recommended dosing; (d) the necessity o early initiation to optimize potential benef ts (as soon as possible a ter and up to 72 hours a ter the assault). Providers should emphasize that PEP appears to be well-tolerated and that severe adverse e ects are rare. • Specialist consultation on PEP regimens is recommended. I the survivor and clinician decide that PEP is warranted, provide enough medication to last until the next return visit and reevaluate the survivor 3 to 7 days a ter initial assessment and assess tolerance o medications. 13 • I PEP is started, per orm a complete blood count (CBC) and serum chemistry at baseline (initiation o PEP should not be delayed, pending results). • Collect samples or legal evidence. Most emergency departments have rape or sexual assault kits containing instructions or gathering material to support legal charges; all samples must be care ully labeled and kept under supervision. Details o these procedures may be ound elsewhere.12 • Reproductive-age emale survivors should be evaluated or pregnancy, i appropriate, and o ered EC i desired. Providers might also consider antiemetic medications, particularly i an EC containing estrogen is provided. • Consider tetanus prophylaxis i skin wounds occur and the patient is not up-to-date on tetanus immunization. O er hepatitis vaccine i the patient has not been previously ully immunized or hepatitis B, has a negative history or hepatitis B and secretion-mucosal contact occurred during the assault. 12 • Arrange or sa ety. • Provide written in ormation about the visit and any instruction given to the patient.

The ollowing prophylactic regimen is suggested as preventive therapy:

REFERRAL

• Hepatitis B vaccination, without hepatitis B immune globulin, is administered to sexual assault victims at the time o the initial examination i they have not been previously vaccinated. Follow-up doses o vaccine should be administered 1 to 2 and 4 to 6 months a ter the f rst dose.

• I the victim is amenable, re er or advocacy or counseling.

• An empiric antimicrobial regimen or Chlamydia, gonorrhea, and Trichomonas is ce triaxone 250 mg intramuscular (IM) in a single dose or cef xime 400 mg orally single dose plus metronidazole 2 g orally (single dose) plus azithromycin 1 g orally (single dose) or doxycycline 100 mg orally twice daily or 7 days. Clinicians should counsel patients about the possible benef ts and toxicities associated with these treatment regimens, such as gastrointestinal (GI) side e ects. • HIV seroconversion has occurred in persons whose only known risk actor was sexual assault or sexual abuse, but the risk is probably low (in consensual sex, the risk or HIV transmission rom vaginal intercourse is 0.1-0.2%, or receptive rectal intercourse the risk is 0.5-3%, and or oral sex the risk is substantially lower). 13 • The health care provider should assess available in ormation concerning HIV-risk behaviors o the assailant(s) (eg, a man who has sex with other men and/ or injected drug or crack cocaine use), local

• I you are not the primary health care provider, arrange or ollow-up medical care.

PREVENTIO N • Women who have been physically assaulted as adolescents are at greater risk or revictimization during their college years. 14 Although dating violence prevention–intervention programs have not been uniormly success ul, women should be counseled about strategies or avoiding uture victimization (eg, recognition o dangerous situations, limiting use o alcohol, sa ety with riends). One program, Sa e Dates, has been shown in a randomized controlled trial (RCT) to be e ective in preventing or interrupting sexual violence perpetration. 15 • Li e skills and educational programs are conducted to encourage men to take greater responsibility or their actions, relate better to others, have greater respect or women, and communicate more e ectively. Although not many programs have been ormally evaluated, there are

57

58

PART 3

PHYSICAL AND SEXUAL ABUSE

Ch a pt e r 8

reports o reduced violence against women in communities in Cambodia, the Gambia, South A rica, Uganda, and the United Republic o Tanzania attributed to these programs. 8

(d) complete hepatitis B immunization, i indicated; (e) complete counseling and treatment or other STIs; and ( ) monitor side e ects and adherence to PEP, i prescribed. 12

• Other prevention e orts include media campaigns, written materials, victim risk-reduction techniques (eg, sel -de ense, awareness), men’s activism groups (eg, Men Can Stop Rape), school-based programs, and legal and policy responses (eg, encourage reporting, broadening the def nition o rape and sexual assault). 8,16 In designing programs, in ormation provided in documents prepared or the CDC may be use ul. 16 Health providers can also become involved in prevention activities at multiple levels: ° Strengthening individual knowledge and skills through skill-building programs in high schools or training bystanders to sa ely interrupt sexist and harassing behavior ° Promoting community education by sponsoring activities such as plays that rein orce positive cultural norms and portray responsible sexual behavior or developing awards to recognize responsible media coverage ° Educating other community leaders and providers, such as little league coaches, prison guards, nursing home providers ° Fostering coalitions and networks to promote community understanding and strategies to prevent sexual violence ° Changing organizational practices such as implementation and en orcement o sexual harassment policies in schools and workplaces, implementing environmental sa ety measures such as adequate lighting and emergency call boxes ° In uencing policies and legislation such as o ering comprehensive sex education programs in middle and high schools, including violence prevention

• Initial ollow-up should be within 1 to 2 weeks ollowing the assault.

PRO GNO SIS • More than 32,000 pregnancies result yearly rom rape (approximately 5% o rapes result in pregnancy). 8 • Chronic psychological consequences—In a meta-analysis o 17 casecontrol and 20 cohort studies (N = 3,162,318 participants), there was an association between sexual abuse and a li etime diagnosis o anxiety disorder (odds ratio [OR], 3.09; 95% conf dence interval [CI], 2.43-3.94), depression (OR, 2.66; 95% CI, 2.14-3.30), eating disorders (OR, 2.72; 95% CI, 2.04-3.63), posttraumatic stress disorder (OR, 2.34; 95% CI, 1.59-3.43), sleep disorders (OR, 16.17; 95% CI, 2.06-126.76), and suicide attempts (OR, 4.14; 95% CI, 2.98-5.76). 17 • Chronic somatic consequences—Authors o a meta-analysis o 23 studies ound associations between sexual abuse and li etime diagnosis o unctional GI disorders (OR, 2.43; 95% CI, 1.36-4.31), nonspecif c chronic pain (OR, 2.20; 95% CI, 1.54-3.15), psychogenic seizures (OR, 2.96; 95% CI, 1.12-4.69), and chronic pelvic pain (OR, 2.73; 95% CI, 1.73-4.30). 18 Signif cant associations with rape included li etime diagnosis o f bromyalgia (OR, 3.35; 95% CI, 1.51-7.46), chronic pelvic pain (OR, 3.27; 95% CI, 1.02-10.53), and unctional GI disorders (OR, 4.01; 95% CI, 1.88-8.57).

FO LLO W-UP Follow-up visits provide an opportunity to (a) provide support and advocacy; (b) evaluate or resolution and healing o injury and current symptoms; (c) detect new in ections acquired during or a ter the assault;

• Provide ongoing support—Survivors o sexual abuse report strained relationships with amily, riends, and intimate partners, including less emotional support and less requent contact with riends and relatives. 8 In addition, only about hal o the victims keep this appointment, so outreach e orts may be needed. • Review results o tests and discuss the plan or redraw o Venereal Disease Research Laboratory (VDRL) 3 months a ter exposure and HIV in 6 weeks and 3 and 6 months (i initial test results were negative). • Long-term support, monitoring, and treatment include the ollowing: ° For women su ering rom PTSD, medications that may be use19 ul include selective serotonin reuptake inhibitors and Risperdal. Cognitive-Processing Therapy and Prolonged Exposure have been the most use ul therapies or treating PTSD, depression, and anxiety in emale rape victims. 20,21 However, more than one-third o women retain the diagnosis o PTSD or drop out o treatment. 21 ° Imagery rehearsal therapy appears use ul in decreasing chronic nightmares, improving sleep quality, and decreasing PTSD symptom severity. 22

PATIENT EDUCATIO N • Recovery rom sexual assault is a slow process. In one study, one-third o survivors reported recovery within 1 year but one-quarter thought that they had not recovered a ter 4 to 6 years. 23 • Counseling, and sometimes medication, is available to help control symptoms and treat depression and PTSD and patients should be encouraged to report and seek help or continuing di f culties.

PATIENT RESO URCES

• National Sexual Violence Resource Center serves as a comprehensive collection and distribution center or in ormation, statistics, and resources related to sexual violence—http:/ / www.nsvrc .org. • Centers for Disease Control and Prevention. Sexual Violence— http:/ / www.cdc.gov/ ViolencePrevention/ sexualviolence/ index.htm. • National Domestic Violence Hotline, 1-800-799-SAFE; National Sexual Assault Hotline, 1-800-656-HOPE. PRO VIDER RESO URCES

• Recommended Medical Guideline Acute Sexual Assault Emergency Medical Evaluation or the State o Oregon—http:/ / www.doj.state.or.us/ crimev/ pdf/ guidelines05_000.pdf. • United States Department of Justice—Of ce on Violence Against Women, o ers links to resources—http:/ / www.ovw.usdoj .gov/ sexassault.htm. • Assistance with PEP decisions can be obtained by calling the National Clinician’s Post-Exposure Prophylaxis Hotline (PEPLine), 1-888-448-4911.

Se XUa L a SSa ULt

• National Sexual Violence Resource Center serves as a comprehensive collection and distribution center or in ormation, statistics, and resources related to sexual violence—http:/ / www.nsvrc .org. • The American College of Obstetricians and Gynecologists provides publications about violence against women, intimate partner violence, sexual violence, adolescent dating violence, and patient education materials in both English and Spanish—http:/ / www .acog.org. • A directory of sexual assault centers in the United States can be obtained rom the ollowing URL—http:/ / www.nsvrc.org/ publications/ nsvrc-publications/ directory-sexualassault-centers-united-states. REFERENCES 1. Centers or Disease Control and Prevention. SexualViolence. Scientif c In ormation. http:/ / www.cdc.gov/ ViolencePrevention/ sexualviolence/ index.html. Accessed August 2013. 2. Black MC, Basile KC, Breiding MJ, et al. The National Intimate Partner and SexualViolence Survey (NISVS): 2010 Summary Report. Atlanta, GA: National Center or Injury Prevention and Control, Centers or Disease Control and Prevention; 2011. http:/ / www.cdc.gov/ ViolencePrevention/ pd / NISVS_Executive_Summary-a.pd . Accessed August 2013. 3. Basile KC, Chen J, Lynberg MC, Saltzman LE. Prevalence and characteristics o sexual violence victimization. ViolenceVict. 2007;22(4):437-448. 4. Koss MP. Detecting the scope o rape: a review o prevalence research methods. J InterpersViolence. 1993;8:198-222. 5. Lincoln AK, Liebschutz JM, Cherno M, et al. Brie screening or co-occurring disorders among women entering substance abuse treatment. Subst AbuseTreat Prev Policy. 2006;1:26. 6. Federal Bureau o Investigation. Uni orm Crime Reports or the United States. Washington, DC: U.S. Department o Justice; 2010. http:/ / www. bi.gov/ about-us/ cjis/ ucr/ crime-in-the-u.s/ 2010/ crime-inthe-u.s.-2010/ violent-crime/ rapemain. Accessed August 2013. 7. National Institute o Justice. Extent Nature and Consequences o Rape Victimization: Findings rom the NationalViolence AgainstWomen Survey (2006). https:/ / www.ncjrs.gov/ pd f les1/ nij/ 210346.pd . Accessed August 2013. 8. World Health Organization. World Report onViolence and Health, Sexual Violence. Chapter 6. http:/ / www.who.int/ violence_injury_ prevention/ violence/ global_campaign/ en/ chap6.pd . Accessed August 2013. 9. Williams A. Managing adult sexual assault. Aust Fam Physician. 2004;33(10):825-828.

PART 3

PHYSICAL AND SEXUAL ABUSE 10. Centers or Disease Control and Prevention. SexualViolence. Risk and Protective Factors. http:/ / www.cdc.gov/ ViolencePrevention/ sexualviolence/ riskprotective actors.html. Accessed August 2013. 11. Weaver TL. Impact o rape on emale sexuality: review o selected literature. Clin Obstet Gynecol. 2009;52(4):702-711. 12. Recommended Medical Guideline Acute Sexual Assault Emergency Medical Evaluation or the State o Oregon. http:/ / www.doj.state.or.us/ crimev/ pd / guidelines05_000.pd . Accessed August 2013. 13. Workowski KA, Berman S; Centers or Disease Control and Prevention. Sexual assault and STDs in sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010;59(RR-12):90-95. http:/ / www.guideline.gov/ content.aspx?id=25597&search= sexual+ assault. Accessed August 2013. 14. Smith PH, White JW, Holland LJ. A longitudinal perspective on dating violence among adolescent and college-age women. Am J Public Health. 2003;93(7):1104-1109. 15. Foshee V, Bauman KE, Ennett ST, et al. Assessing the long-term e ects o the Sa e Dates program and a booster in preventing and reducing adolescent dating violence victimization and perpetration. Am J Public Health. 2004;94:619-624. 16. Centers or Disease Control and Prevention. SexualViolence: Prevention Strategies. http:/ / www.cdc.gov/ ViolencePrevention/ sexualviolence/ prevention.html. Accessed August 2013. 17. Chen LP, Murad MH, Paras ML, et al. Sexual abuse and li etime diagnosis o psychiatric disorders: systematic review and metaanalysis. Mayo Clin Proc. 2010;85(7):618-629. 18. Paras ML, Murad MH, Chen LP, et al. Sexual abuse and li etime diagnosis o somatic disorders: a systematic review and metaanalysis. JAMA. 2009;302(5):550-561. 19. Padala PR, Madison J, Monnahan M, et al. Risperidone monotherapy or post-traumatic stress disorder related to sexual assault and domestic abuse in women. Int Clin Psychopharmacol. 2006;21(5): 275-280. 20. Nishith P, Nixon RD, Resick PA. Resolution o trauma-related guilt ollowing treatment o PTSD in emale rape victims: a result o cognitive processing therapy targeting comorbid depression? JA ect Disord. 2005;86(2-3):259-265. 21. Vickerman KA, Margolin G. Rape treatment outcome research: empirical f ndings and state o the literature. Clin Psychol Rev. 2009;29:431-448. 22. Krakow C, Hollif eld M, Johnston L, et al. Imagery rehearsal therapy or chronic nightmares in sexual assault survivors with posttraumatic stress disorder: a randomized controlled trial. JAMA. 2001;286(5): 537-545. 23. Burgess AW, Holmstrom LL. Adaptive strategies and recovery rom rape. Am J Psychiatry. 1979;136:1278-1282.

59

This page intentionally left blank

PART 4

O PHTHALMO LO GY

*

S

St re ng t h o Re co mme nd at io n (SO R)

De f nit io n

A

R comm nd ation b as d on consist nt and g ood -q uality p ati nt-ori nt d vid nc .*

B

R comm nd ation b as d on inconsist nt or limit d -q uality p ati nt-ori nt d vid nc .*

C

R comm nd ation b as d on cons nsus, usual p ractic , op inion, d is as -ori nt d vid nc , or cas s ri s or stud i s o d iag nosis, tr atm nt, p r v ntion, or scr ning .*

Ap p nd ix A on p ag s 1241-1244 or urth r in ormation.

62

PART 4

O PHTHALMO LO GY

9 PTERYGIUM He id i Chumle y, MD

PATIENT STO RY A 50-year-old man had spent most o his adult li e working outdoors in southern Texas near the Mexico border. He denies any problems with his vision, but wonders what is growing on his eye and i it should be removed (Figure 9-1). His eyes are o ten dry and irritated. He is diagnosed with a pterygium and instructed that it does not need to be removed unless it inter eres with his vision in the uture. Liquid tears are suggested or his dry and irritated eyes. He is also instructed to wear wraparound sunglasses to avoid ultraviolet (UV) exposure and irritation rom wind and dust.

INTRO DUCTIO N A pterygium is a generally benign growth o broblastic tissue on the eye o an adult with chronic UV exposure. Pterygia can be unilateral or bilateral, are usually located on the nasal side, and extend to the cornea. Pterygia o ten require no treatment, but can be removed surgically i they inter ere with vision. Patients with dry eyes are prone to the development and progression o pterygia.

EPIDEMIO LO GY • Pterygium most o ten develops between the ages 20 and 50 years. • The requency o pterygium increases with sun exposure and age. In a population-based study (Indonesia), it was ound that the prevalence ranged rom 3% (in 21- to 29-year-olds) to 18% (older than 50 years o age).1 In rural China, the prevalence was 3.76% and also increased with age.2

Ch a pt e r 9

ETIO LO GY AND PATHO PHYSIO LO GY • A pterygium is a proli eration o brovascular tissue on the sur ace o the eye, which extends onto the cornea. • The etiology o pterygium is incompletely understood; however, chronic UV exposure is accepted as a causative agent. Chronic inf ammation and oxidative stress may also play a role in pathogenesis. • Pterygia have eatures seen in malignant tissues, such as normal tissue invasion and high recurrence rate. 4 Pterygia can be associated with premalignant lesions. 4

RISK FACTO RS Risk actors are related to chronic UV exposure: • Living in low latitude, low precipitation area2 • Male gender2

DIAGNO SIS CLINICAL FEATURES • Redness, itching, and/ or irritation o the involved eyes (some are symptom ree). • Visual blurring i the pterygium grows over the visual axis. Even i not obscuring the visual axis, the pterygium can cause poor vision by leading to irregular and high astigmatism. • Pterygia are diagnosed clinically by their distinctive appearance (Figures 9-1 to 9-4). TYPICAL DISTRIBUTIO N • Unilateral or bilateral.

• In one study carried out in Australia, it was ound that sun exposure is consistently the greatest risk actor, contributing 43% o the risk. 3

FIGURE 9-1 A nasal p t ryg ium. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 9-2 Pt ryg ium that has g rown onto th corn a b ut not cov r d th visual axis. This f b rovascular tissu has th shap o a b ird ’s wing (lit ral d f nition o p t ryg ium). Th small v ss ls ar p romin nt in this vi w. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 4

pt e r YGIUM

FIGURE 9-3 A p t ryg ium that has g rown ov r th visual axis and is int r ring with this p rson’s vision. Th p ati nt p lans to und rg o surg ry. (Re p rod uce d with p e rmission from Paul D. Come au.)

O PHTHALMO LO GY

FIGURE 9-5 Ping u cula nod ul on conjunctiva that d o s not xt nd to th corn a. Not th y llow color. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

• Nasal or nasal and temporal. • Consider another diagnosis with a unilateral temporal distribution. BIO PSY Biopsy is not indicated; however, excised pterygia are sent or histologic examination because o their association with premalignant lesions. 4

DIFFERENTIAL DIAGNO SIS • Pinguecula is a yellowish patch or nodule on the conjunctiva, and it does not extend onto the cornea (Figure 9-5). • Conjunctivitis is conjunctival in ection with discom ort and eye discharge (see Chapter 13, Conjunctivitis). • Squamous cell carcinoma o the conjunctiva is rare. Consider carcinoma when a unilateral growth is noted on the temporal side. Also consider malignancy i there are grossly aberrant-appearing blood vessels on the sur ace o the eye. Patients with abnormal immune systems (eg, cancer, HIV) are at a particular risk or ocular sur ace malignancy.

MANAGEMENT NO NPHARMACO LO GIC Avoid sun exposure and use UV ltering sunglasses when sun exposure is unavoidable. MEDICATIO NS Nonprescription arti cial tears and/ or topical lubricating drops are recommended to soothe the inf ammation. Ophthalmologists will occasionally prescribe a short course o topical corticosteroid anti-inf ammatory drops when symptoms o the pterygia are more intense. SURGICAL • Pterygia are usually treated when they inter ere with vision or when they cause signi cant irritation or pain (see Figure 9-3). The standard therapy is surgical removal. • Pterygia have a high rate o recurrence. Conjunctival autogra ting and an anti brotic treatment (eg, mitomycin-C) can be used intraoperatively to lower the recurrence. 5 ASSO CIATED RISKS • Pterygia a ect astigmatism6,7 and are associated with increased rates o macular degeneration; however, it is unclear whether treatment reduces this risk. • Eyes with a pterygium or previous pterygium surgery (but not pinguecula) have a higher risk o incident late age-related maculopathy (ARM) (odds ratio [OR] 3.3, 95% con dence interval [CI], 1.1-10.3) and early ARM (OR 1.8, 95% CI, 1.1-2.9). 8

PREVENTIO N

FIGURE 9-4 Bilat ral p t ryg ia g rowing ov r th corn a. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Sunglasses with 100% UV protection should be used by everyone to protect the eyes rom UV damage (Figure 9-6). Sunglasses should t close to the eye to block scattered or ref ected light in addition to direct light. 9

63

PART 4

64

O PHTHALMO LO GY

CHAPTe R 9

PATIENT RESO URCES

• PubMed Health. Pterygium—http:/ / www.ncbi.nlm.nih.gov/ pubmedhealth/ PMH0002006/ . PRO VIDER RESO URCES

• Fisher JP. Pterygium—http:/ / emedicine.medscape.com/ article/ 1192527.

REFERENCES 1. Gazzard G, Saw SM, Farook M, et al. Pterygium in Indonesia: prevalence, severity and risk actors. Br J Ophthalmol. 2002;86(12): 1341-1346.

FIGURE 9-6 Nasal p t ryg ium g rowing ov r th visual axis in a man living clos to th q uator. Th p ati nt d id not us sung lass s. Th m lanosis within th p t ryg ium is b nig n. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

PRO GNO SIS Most pterygia do not require surgical treatment. Pterygia that inter ere with vision and are removed have a high chance o recurrence.

FO LLO W-UP No speci c ollow-up is needed; however, consider monitoring vision during annual examinations because o the increased risk o age-related macular degeneration.

PATIENT EDUCATIO N Wraparound sunglasses are help ul to avoid UV exposure and irritation rom wind and dust. Liquid tears are suggested or dry and irritated eyes.

2. Liang QF, Xu L, Jin XY, et al. Epidemiology o pterygium in aged rural population o Beijing, China. Chin Med J (Engl). 2010;123(13):1699-1701. 3. McCarty CA, Fu CL, Taylor HR. Epidemiology o pterygium in Victoria, Australia. Br J Ophthalmol. 2000;84(3):289-292. 4. Chui J, Coroneo MT, Tat LT, et al. Ophthalmic pterygium: a stem cell disorder with premalignant eatures. Am J Pathol. 2011;178(2):817-827. 5. Detorakis ET, Spandidos DA. Pathogenetic mechanisms and treatment options or ophthalmic pterygium: trends and perspectives. Int J Mol Med. 2009;23(4):439-447. 6. Ashaye AO. Re ractive astigmatism and size o pterygium. Afr J Med Med Sci. 2002;31(2):163-165. 7. Kampitak K. The e ect o pterygium on corneal astigmatism. J Med AssocThai. 2003;86(1):16-23. 8. Pham TQ, Wang JJ, Rochtchina E, Mitchell P. Pterygium/ pinguecula and the ve-year incidence o age-related maculopathy. Am J Ophthalmol. 2005;139(3):536-537. 9. Wang SQ, Balaqula Y, Osterwalder U. Photoprotection: a review o the current and uture technologies. Dermatol Ther. 2010;23(1):31-47.

HO RDEO LUM AND CHALAZIO N

PART 4

O PHTHALMO LO GY

10 HO RDEO LUM AND CHALAZIO N He id i Chumle y, MD

PATIENT STO RY A 35-year-old woman presented with a tender nodule on the upper eyelid along with crusting and erythema to both eyelids (Figure 10-1). The upper eyelid had a large external hordeolum. When the lower eyelid was inverted, an internal hordeolum was also present. The physician recommended that she apply warm moist compresses to her eyelids 4 times a day. Her hordeola resolved within 7 days. FIGURE 10-1 Exte rnal hord e olum (b lack arrow) and an inte rnal hord e olum (white arrow). (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

INTRO DUCTIO N A hordeolum is an acute pain ul in ection o the glands o the eyelid, usually caused by bacteria. Hordeola can be located on the internal or external eyelid. Internal hordeola that do not completely resolve become cysts called chalazia. External hordeola are commonly known as styes.

SYNO NYMS External hordeolum is also known as stye.

EPIDEMIO LO GY Unclear incidence or prevalence in the United States, but o ten stated to be more common in school-age children (0.2% chalazion and 0.3% hordeolum)1 and in 30- to 50-year old adults.

FIGURE 10-2 Exte rnal hord e olum on up p e r lid with surround ing e rythe ma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

ETIO LO GY AND PATHO PHYSIO LO GY HO RDEO LUM (ACUTELY TENDER NO DULE IN THE EYE) • In ection in the meibomian gland (internal hordeolum), o ten resolves into a chalazion (Figure 10-1). • In ection in the Zeiss or Moll gland (external hordeolum) (Figures 10-2 and 10-3). • Staphylococcus aureus is the causative agent in most cases. CHALAZIO N • Meibomian gland becomes blocked, o ten in a patient with blepharitis. • Blocked meibomian gland’s duct releases gland contents into the so t tissue o eyelid. • Gland contents cause a lipogranulomatous reaction (Figure 10-4). • Reaction can cause acute tenderness and erythema, which then resolves into a chronic nodule (Figure 10-5).

FIGURE 10-3 Exte rnal hord e o lum with visib le p urule nce and the normal contour o the e ye lid is d isrup te d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

65

PART 4

66

O PHTHALMO LO GY

Ch a pt e r 10

FIGURE 10-6 Hid rocystoma showing te lang ie ctasias. The cyst was e asily re se cte d and the f uid was cle ar. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.) FIGURE 10-4 Chalazion vie we d rom inte rnal e ye lid showing the ye llow lip og ranulo matous mate rial. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIFFERENTIAL DIAGNO SIS RISK FACTO RS • Hordeolum: S. aureus blepharitis, previous hordeolum • Chalazion: Seborrheic blepharitis and rosacea

DIAGNO SIS • Chalazion and hordeolum are clinical diagnoses. • Chalazion is a nontender nodule on the eyelid. • Hordeolum. ° Tenderness and erythema are localized to a point on the eyelid (see Figures 10-1 to 10-3). ° Conjunctival injection may be present. ° Fever, preauricular nodes, and vision changes should be absent. ° Laboratory tests are generally not indicated.

• Hidrocystoma—Benign cystic lesion that grows on the edge o the eyelids and is lled with clear f uid (Figure 10-6). • Xanthelasma—Yellowish plaques, generally near medial canthus (see Chapter 223, Hyperlipidemia). • Molluscum contagiosum—Waxy nodules with central umbilication, generally multiple (see Chapter 129, Molluscum Contagiosum). • Sebaceous cell carcinoma—Rare cancer seen in middle-aged and elderly patients; di cult to distinguish rom recurrent chalazion or unilateral chronic blepharitis without biopsy. • Basal cell carcinoma—Pearly nodule, o ten with telangiectasias or central ulceration; more common on lower medial eyelid (see Chapter 168, Basal Cell Carcinoma).

MANAGEMENT HO RDEO LUM (INTERNAL) • No studies o nonsurgical interventions (compresses, lid scrubs, antibiotics, steroids) met criteria or inclusion in a Cochrane study. No evidence or or against nonsurgical interventions or acute internal hordeolum. 1 SO R A • Treat as described below or external hordeolum. HO RDEO LUM (Ex TERNAL) • Warm soaks, 3 to 4 times a day or 15 minutes, will elicit drainage in most cases. SO R C • Topical antibiotics (eg, bacitracin ophthalmic ointment) may be bene cial or recurrent or spontaneously draining hordeolum. SO R C • Cases that do not respond to warm soaks or that are extremely pain ul and swollen may be incised and drained with a small incision using a # 11 blade. Make the incision on either the internal or external eyelid depending on where the hordeolum is pointing. A chalazion clamp can be used to protect the globe rom damage. SO R B • Antibiotics do not provide bene t a ter incision and drainage.3 SO R B

FIGURE 10-5 Chalazion p re se nt or 4 months with minimal symp toms b ut cosme tically unap p e aling . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Systemic antibiotics are usually not needed unless patient has preseptal cellulitis. SO R C

PART 4

HO RDEO LUM AND CHALAZIO N

CHALAZIO N • Can be treated conservatively with lid hygiene and warm compresses. Warm compresses can be applied 2 to 3 times daily but may take weeks to months to work. SO R C • One study demonstrated a 58% response rate o 1% topical chloramphenicol with warm compresses. 3 SO R B

O PHTHALMO LO GY PATIENT EDUCATIO N Hordeolum commonly responds to warm soaks and topical antibiotics. It o ten recurs and can develop into a chronic chalazion, which may need to be treated with surgical removal or a steroid injection.

• Higher percentages o resolution can be achieved with either incision and curettage or injection with steroid (eg, 0.3 mL triamcinolone acetonide) (80-92%). 4-6 SO R B The chalazion is usually drained rom the internal eyelid using a chalazion clamp to protect the globe. A ter anesthetizing the area, a # 11 blade is care ully used to open the chalazion. A chalazion curette helps to scoop out the lipogranulomatous material. No suturing is needed.

PATIENT RESO URCES

• A study o 136 patients compared triamcinolone injection, incision and curettage, and warm compresses, and ound resolution rates o 84%, 87%, and 46%, respectively. 6 SO R B

PRO VIDER RESO URCES

• One study demonstrated a better response to incision and curettage in the ollowing situations: patients 35.1 years o age or older, with lesion duration equal to or greater than 8.5 months and size equal to or greater than 11.4 mm. 5 SO R B

• Chalazion—http:/ / emedicine.medscape.com/ article/ 1212709.

REFERRAL Re er to an ophthalmologist i the hordeolum or chalazion inter eres with vision and does not respond to therapy. I a surgical intervention is needed and you lack experience doing such a procedure, re er to ophthalmology.

PREVENTIO N Eyelid hygiene, keeping the area around the eyelid clean, may prevent hordeola.

PRO GNO SIS Chalazia can persist or years i untreated. Some patients are prone to recurrence o hordeola and chalazia.

FO LLO W-UP A hordeolum with signi cant purulence and swelling should be reevaluated in 2 to 3 days or re erred to an ophthalmologist. Warm compresses are slow to work or a chalazion, so ollow-up should be no sooner than 1 month i nonsurgical treatment is prescribed.

• The American Academy of Ophthalmology—http:/ / www .geteyesmart.org/ eyesmart/ diseases/ chalazion-stye.cfm. • The American Academy of Family Physicians has a patient handout in English or Spanish on stye—http:/ / familydoctor.org/ familydoctor/ en/ diseases-conditions/ sty.html. • Hordeolum and Stye in Emergency Medicine—http:/ / emedicine .medscape.com/ article/ 798940.

• Chalazion Injection Demonstration—http:/ / www.youtube.com/ watch?v=yYCCkDZwKgg. • Chalazion Incision and Curettage—http:/ / www.youtube.com/ watch?v=tdKw_zjYCf8. REFERENCES 1. Garcia CA, Pinheiro FI, Montenegro DA, et al. Prevalence o biomicroscopic ndings in the anterior segment and ocular adnexa among schoolchildren in Natal, Brazil. Arq Bras Oftalmol. 2005;68(2):167-170. 2. Lindsley K, Nichols JJ, Dickersin K. Interventions or acute internal hordeolum. Cochrane Database Syst Rev. 2010;9:CD00742. 3. Hirunwiwatkul P, Wachirasereechai K. E ectiveness o combined antibiotic ophthalmic solution in the treatment o hordeolum a ter incision and curettage: a randomized, placebo-controlled trial: a pilot study. J Med AssocThai. 2005;88(5):647-650. 4. Chung CF, Lai JS, Li PS. Subcutaneous extralesional triamcinolone acetonide injection versus conservative management in the treatment o chalazion. Hong Kong Med J. 2006;12(4):278-281. 5. Ahmad S, Baig MA, Khan MA, et al. Intralesional corticosteroid injection vs surgical treatment o chalazia in pigmented patients. J Coll Physicians Surg Pak. 2006;16(1):42-44. 6. Goawalla A, Lee V. A prospective randomized treatment study comparing three treatment options or chalazia: triamcinolone acetonide injections, incision and curettage and treatment with hot compresses. Clin Experiment Ophthalmol. 2007;35(8):706-712. 7. Dhaliwal U, Bhatia A. A rationale or therapeutic decision-making in chalazia. Orbit. 2005;24(4):227-230.

67

68

PART 4

O PHTHALMO LO GY

Ch a pt e r 11

11 SCLERAL AND CO NJUNCTIVAL PIGMENTATIO N He id i Chumle y, MD

PATIENT STO RY A 40-year-old white man came to see his physician about a brown spot in his eye (Figure 11-1). He noticed this spot many years ago, but after recently reading information on the Internet about brown spots in the eye, became concerned about ocular melanoma. He thinks the spot has changed in size. He denies any eye discomfort or visual changes. He was referred for a biopsy, and the pathology showed a benign nevus that did not require further treatment.

INTRO DUCTIO N Scleral and conjunctival pigmentation is common and usually benign. Nevi can be observed and referred if they change in size. Primary acquired melanosis (PAM) must be biopsied because PAM with atypia has malignant potential, whereas PAM without atypia does not. Conjunctival melanoma is rare, but deadly.

EPIDEMIO LO GY Although there is little information on the prevalence of ocular pigmentation other than physiologic (racial) melanosis, in a study of pigmented lesions referred for biopsy, investigators reported that 52% were nevi, 21% were PAM, and 25% were melanoma. 1 • Scleral and conjunctival nevi (see Figures 11-1 and 11-2) are the most common causes of ocular pigmentation in light-skinned races. The pigmentation is generally noticeable by young adulthood, and is more common in whites. 2

FIGURE 11-1 Scle ral ne vus. Unilate ral localize d d istinct are a of d ark p ig me ntation on scle ra. (Re p rod uce d with p e rmission from Paul D. Come au.)

FIGURE 11-2 Conjunctival ne vus. Unilate ral localize d d istinct are a of d ark p ig me ntation on conjunctiva. (Re p rod uce d with p e rmission from Paul D. Come au.)

• Physiologic (racial) melanosis (Figure 11-3) is seen in 90% of black patients. 3 It can be congenital, and often presents early in life. • PAM (Figure 11-4) is generally noted in middle-aged to older adults, 4,5 and is also more common in whites. • Conjunctival melanoma (Figures 11-5 to 11-7) is rare, occurring in 0.000007% (7 per 1,000,000) of whites; it is even less common in other races. 5

FIGURE 11-3 Physio log ic (racial) me lanosis. Flat conjunctival p ig me ntation that p re se nts b ilate rally starting at the limb us and most p romine nt in the inte rp alp e b ral zone is like ly to b e racial me lanosis in a d arkly p ig me nte d p atie nt. (Re p rod uce d with p e rmission from Paul D. Come au.)

PART 4

SCLe r a L a ND CO NJUNCt IVa L pIGMe Nt a t IO N

O PHTHALMO LO GY

FIGURE 11-4 Primary acq uire d me lanosis (PAM). Multip le unilate ral ind istinct are as of d ark p ig me ntation. (Re p rod uce d with p e rmission from Paul D. Come au.)

FIGURE 11-7 Conjunctival me lanoma, 1 ye ar afte r the p re vious p hoto, in a p atie nt who initially d e cline d tre atme nt. (Re p rod uce d with p e rmission from Paul D. Come au.)

ETIO LO GY AND PATHO PHYSIO LO GY The etiology of scleral or conjunctival nevi is not well understood. Racial melanosis is genetically determined. Conjunctival melanoma can arise from PAM with severe atypia, nevi, or de novo. 6,7

RISK FACTO RS • In non-Hispanic whites, the incidence of conjunctival melanoma increases as latitude decreases. 8 FIGURE 11-5 Conjunctival me lanoma. Unilate ral, nod ular le sion with irre g ular contours and colors, and surround e d b y hyp e re mic ve sse ls. (Re p rod uce d with p e rmission from Paul D. Come au.)

• Fair-skinned individuals are at higher risk for conjunctival melanoma.

DIAGNO SIS De nitive diagnosis of pigmented ocular lesions is made by biopsy. CLINICAL FEATURES • Benign nevi and physiologic or racial melanosis are stable over time, whereas PAM and melanoma change. • Intrinsic cysts are common in conjunctival nevi and are rare in racial melanosis, PAM, and melanoma. They are seen with slit-lamp biomicroscopy. 9 TYPICAL DISTRIBUTIO N • Physiologic melanosis is typically bilateral and symmetrical. • Nevi, PAM, and melanoma are typically unilateral; however, one study found that 13% of PAM cases were bilateral. 7 FIGURE 11-6 Early p hoto o f conjunctival me lanoma with irre g ular b ord e rs and variations in color. (Re p ro d uce d with p e rmission fro m Paul D. Co me au.)

LABO RATO RY TESTING None indicated, other than biopsy.

69

PART 4

70

O PHTHALMO LO GY IMAGING • Often not helpful, as diagnosis is made by biopsy. • Anterior segment coherence tomography is being studied as a diagnostic aid for conjunctival nevus because cysts are detectable. In one study, there was 100% positive predictive value (PPV) but only 60% negative predictive value (NPV). 9 BIO PSY • Eighty-seven percent of biopsy-proven nevi do not change over time. 4 • Features seen more commonly in malignancy: ulceration, hemorrhage, change in color, and formation of new vessels around the lesion. • Pathologic factors of conjunctival melanoma with a higher mortality rate include increased tumor thickness, location on the palpebral, caruncular or forniceal conjunctiva, increased mitotic activity, lymphocytic invasion, and association with PAM. 10

DIFFERENTIAL DIAGNO SIS Pigmented areas on the sclera or conjunctiva include the following:

Ch a pt e r 11

It is more common in the Asian population but can be seen in any population. It can also be bilateral. Most importantly these people should be followed up by an ophthalmologist because they are at higher risk for glaucoma and possibly melanoma.

MANAGEMENT • Racial melanosis and nevi are 2 lesions that can be monitored for changes without a biopsy. • Refer any changing pigmented lesion in the eye to a specialist who can perform a biopsy. • Biopsy-proven PAM without atypia does not require excision, but must be monitored for stability. SO R C • Melanosis with atypia is generally removed with large margins because of its potential for conversion into melanoma. 4 SO R C • The primary treatment for conjunctival melanoma is surgical removal. Cryotherapy, radiotherapy, and chemotherapy may be used as adjunct therapy. SO R C

PREVENTIO N

• Benign nevi—Unilateral and stable over time (see Figures 11-1 and 11-2). • Physiologic or racial melanosis—Bilateral and symmetric, most common circumlimbally, and relatively consistent throughout patient’s life (see Figure 11-3). • PAM—Typically unilateral, often multifocal indistinct areas of dark pigmentation, and can progress to malignancy over time (see Figure 11-4). This term is used clinically when the histology is not known. • Secondary acquired melanosis—Seen with hormonal changes or after trauma to the conjunctiva with irradiation, chemical irritation, or chronic in ammation. • Conjunctival melanoma—Unilateral, nodular, with variegated color and size changes (see Figures 11-5 to 11-7).

To decrease risk of conjunctival melanoma, use sunglasses that protect the eye from ultraviolet (UV) radiation. SO R C

PRO GNO SIS In one study, PAM without atypia or with mild atypia did not progress into melanoma. Thirteen percent of PAM cases with severe atypia did progress. The risk of melanoma increases as PAM covers more of the iris circumference (see Figure 11-4). 6 In one study, conjunctival melanoma arose from PAM, nevi, and de novo. Melanoma arising de novo had a worse prognosis. Other bad factors were fornix location and nodular tumor.7

• Alkaptonuria—Rare disease accompanied by dark urine and arthritis. • Nevus of Ota (also known as oculodermal melanocytosis)—Blue-gray scleral pigment involving the periorbital skin as well (see Figure 11-8).

FO LLO W-UP Follow-up is based on the type of lesion. Nevi and physiologic melanosis that have not changed can be monitored without biopsy. PAM requires close follow-up because of its potential conversion to melanoma. Patients with nevus of Ota should be monitored for glaucoma and melanoma.

PATIENT EDUCATIO N Most pigmentation in the eye is benign and does not change over time. Discuss the importance of reporting any changing pigmented lesion, even in the eye.

FIGURE 11-8 Ne vus o f O ta (also known as oculod e rmal me lanocytosis). Unilate ral b lue -g ray ocular p ig me ntation with p e riorb ital hyp e rp ig me ntation. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

SCLe r a L a ND CO NJUNCt IVa L pIGMe Nt a t IO N

PATIENT RESO URCES

• American Academy of Ophthalmology—http:/ / www.aao.org. • Information on nevi and ocular melanoma. What Is a Nevus?—http:/ / www.geteyesmart.org/ eyesmart/ diseases/ nevus.cfm. • Ocular Melanoma Foundation. About Ocular Melanoma—http:/ / www.ocularmelanoma.org/ disease.htm. PRO VIDER RESO URCES

• Medscape. Conjunctival Melanoma—http:/ / emedicine .medscape.com/ article/ 1191840.

REFERENCES 1. Shields CL, Demirci H, Karatza E, Shields JA. Clinical survey of 1643 melanocytic and nonmelanocytic conjunctival tumors. Ophthalmology. 2004;111(9):1747-1754. 2. Shields CL, Fasiudden A, Mashayekhi A, Shields JA. Conjunctival nevi: clinical features and natural course in 410 consecutive patients. Arch Ophthalmol. 2004;122(2):167-175. 3. Singh AD, Campos OE, Rhatigan RM, et al. Conjunctival melanoma in the black population [review]. Surv Ophthalmol. 1998;43(2):127-133.

PART 4

O PHTHALMO LO GY 4. Folberg R, Mclean IW, Zimmerman LE. Conjunctival melanosis and melanoma. Ophthalmology. 1984;91(6):673-678. 5. Seregard S, af Trampe E, Månsson-Brahme E, et al. Prevalence of primary acquired melanosis and nevi of the conjunctiva and uvea in the dysplastic nevus syndrome. A case-control study. Ophthalmology. 1995;102(10):1524-1529. 6. Shields CL, Markowitz JS, Belinsky I, et al. Conjunctival melanoma: outcomes based on tumor origin in 382 consecutive cases. Ophthalmology. 2011;118(2):389-395. 7. Shields JA, Shields CL, Mashayekhi A, et al. Primary acquired melanosis of conjunctiva: risks for progression to melanoma in 311 eyes. Ophthalmology. 2008;115(3):511-519. 8. Yu GP, Hu DN, McCormick SA. Latitude and incidence of ocular melanoma. Photochem Photobiol. 2006;82(6):1621-1626. 9. Shields CL, Belinsky I, Romanelli-Gobbi M, et al. Anterior segment optical coherence tomography of conjunctival nevus. Ophthalmology. 2011;118(5):915-919. 10. Shields CL, Shields JA, Gunduz K, et al. Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients [comment]. Arch Ophthalmol. 2000;118(11):1497-1507.

71

PART 4

72

O PHTHALMO LO GY

Ch a pt e r 12

12 CO RNEAL FO REIGN BO DY AND CO RNEAL ABRASIO N He id i Chumle y, MD

PATIENT STO RY A 28-year-old man felt something y into his eye while he was using a table saw without wearing protective eye gear. He presented with pain, tearing, photophobia, and thought that something was still in his eye. On examination with a slit lamp, the physician noted that he had a wood chip that had penetrated the cornea (Figures 12-1 and 12-2). He was referred to an ophthalmologist who successfully removed the foreign body. He was treated with a short course of topical nonsteroidal antiin ammatory drugs (NSAIDs) for pain relief, and had complete healing.

INTRO DUCTIO N Corneal abrasions are often caused by eye trauma and can cause an in ammatory response. Corneal abrasions are detected using uorescein and ultraviolet (UV) light. A corneal foreign body can be seen during a careful physical examination with a good light source or slit lamp. Nonpenetrating foreign bodies can be removed by an experienced physician in the of ce using topical anesthesia. Refer all penetrating foreign bodies to an ophthalmologist.

FIGURE 12-2 Slit-lamp e xamination re ve als this wood chip has p e ne trate d the corne a. (Re p rod uce d with p e rmission fro m Paul D. Co me au.)

EPIDEMIO LO GY • Corneal abrasions with or without foreign bodies are common; however, the prevalence or incidence of corneal abrasions in the general population is unknown. • Corneal abrasions accounted for 85% of closed-eye injuries in adults presenting to an emergency department. 1

ETIO LO GY AND PATHO PHYSIO LO GY SYNO NYMS Corneal abrasion is sometimes referred to as a corneal epithelial defect.

• The cornea overlies the iris and provides barrier protection, lters UV light, and refracts light onto the retina. • Abrasions in the cornea are typically caused by direct injury from a foreign body, resulting in an in ammatory reaction. • The in ammatory reaction causes the symptoms and can persist for several days after the foreign object is out.

RISK FACTO RS • People occupied as metal workers, woodworkers, miners, and landscapers have an increased risk of corneal injuries from foreign bodies. 2 • Participating in sports such as hockey, lacrosse, or racquetball raises the risk of corneal abrasions from ocular trauma. 2 • Sedated patients (as a result of disruption of the blink re ex, and subsequent corneal exposure) are at increased risk for corneal abrasions. 2 Contact lenses, especially soft, extended wear, increase the risk of developing an infected abrasion that ulcerates. 2

DIAGNO SIS CLINICAL FEATURES History and physical FIGURE 12-1 Wood chip is visib le in the corne a on close insp e ction of the e ye . (Re p rod uce d with p e rmission from Paul D. Come au.)

• History of ocular trauma or eye rubbing (although corneal abrasions can occur with no trauma history).

CO r Ne a L FO r e IGN BO DY a ND CO r Ne a L a Br a SIO N

PART 4

O PHTHALMO LO GY

FIGURE 12-3 Me tallic fore ig n b od y with rust ring within the corne al stroma and conjunctival inje ction. (Re p rod uce d with p e rmission from Paul D. Come au.) FIGURE 12-5 Small corne al ulce r in the visual axis. (Re p rod uce d with p e rmission from Paul D. Come au.)

• Symptoms of pain, eye redness, photophobia, and a foreign-body sensation. • Foreign body seen with direct visualization or a slit lamp (Figure 12-3). • Fluorescein application demonstrates green area (which represents the disruption in the corneal epithelium) under cobalt-blue ltered light (Figure 12-4). • History of contact lens wear. • History of ocular or perioral herpes virus infection. LABO RATO RY TESTING Culture if an infection is suspected. IMAGING • If physical examination is equivocal, imaging may be useful to determine if a foreign body has perforated the cornea. An object that has fully perforated the cornea has passed through the cornea and will be

FIGURE 12-4 Fluo re sce in stains g re e n, ind icating corne al ab rasion. (Re p rod uce d with p e rmission from Paul D. Come au.)

located in the anterior or posterior segment of the eye, making it difcult to see without imaging technology. • Computed tomography (CT) or spiral CT can detect nonmetallic and metallic foreign bodies. • A metallic foreign body can be seen on an orbital radiograph. Avoid magnetic resonance imaging (MRI) if the history suggests the foreign body may be metallic. Ultrasound and ultrasound biomicroscopy can also visualize intraocular foreign bodies and may be useful in some cases.

DIFFERENTIAL DIAGNO SIS • Uveitis or iritis—Usually unilateral, 360-degree perilimbal injection, eye pain, photophobia, and vision loss (see Chapter 15, Uveitis and Iritis). • Keratitis or corneal ulcerations—Diffuse erythema with ciliary injection often with miosis; eye discharge; pain, photophobia, and vision loss depending on the location of ulceration (Figures 12-5 and 12-6).

FIGURE 12-6 Larg e r corne al ulce r p artially ob scuring the visual axis. (Re p rod uce d with p e rmission from Paul D. Come au.)

73

PART 4

74

Ch a pt e r 12

O PHTHALMO LO GY There is often a history of trauma, herpes simplex virus (HSV), or contact lens wear. Patients should see an ophthalmologist urgently. • Conjunctivitis—Conjunctival injection; eye discharge; gritty or uncomfortable feeling; no vision loss, history of respiratory infection, or contacts with others who have red eyes (see Chapter 13, Conjunctivitis). • Acute-angle closure glaucoma—Cloudy cornea and scleral injection; eye pain with ipsilateral headache; severe vision loss, acutely elevated intraocular pressure (see Chapter 16, Glaucoma).

FO LLO W-UP See all patients in 24 hours for reassessment. If there is no improvement, look for an initially overlooked foreign body or a full-thickness injury. Do not hesitate to refer to ophthalmology if patient is not improving.

PATIENT EDUCATIO N • Advise patients in speci c professions (eg, woodworking, metal working) and those who play sports, such as racquetball or hockey, to wear eye protection for primary prevention.

MANAGEMENT NO NPHARMACO LO GIC • Con rm diagnosis with uorescein and UV light (for abrasion) if no foreign body is readily visible (see Figure 12-4). • Carefully inspect for a foreign body. Invert the upper eyelid for full visualization. Slit-lamp visualization may be needed to determine if the cornea has been penetrated (see Figure 12-2). • Remove (or refer for removal) nonpenetrating foreign bodies. Apply a topical anesthetic, such as proparacaine or tetracaine. Remove with irrigation, a wet-tipped cotton applicator, or a ne-gauge needle. • Remove contact lenses until cornea is healed. 3 SO R C • Avoid patching in corneal abrasions smaller than 10 mm; it does not help. 4 SO R A

• Advise patients with corneal abrasions that healing usually occurs within 2 to 3 days, and that they should report persistent pain, redness, and photophobia. • Patients should be advised not to sleep wearing contact lenses, even if labeled “extended wear.” PATIENT RESO URCES

• FamilyDoctor.org. Patient handout on Corneal Abrasions—http:/ / amilydoctor.org/ amilydoctor/ en/ prevention-wellness/ staying-healthy/ f rst-aid/ corneal-abrasions.html. PRO VIDER RESO URCES

• Medscape. Cao C. Corneal Foreign Body Removal—http:/ / emedicine.medscape.com/ article/ 82717.

MEDICATIO NS • Prescribe ophthalmic NSAIDs for pain if needed. 5

SO R A

• Consider topical antibiotics. SO R C Chloramphenicol ointment reduced the risk of recurrent ulcer in a prospective, nonplacebo, controlled trial. 6 Although chloramphenicol is rarely used in the United States, other ophthalmic antibiotics, such as erythromycin ointment, are used for corneal abrasions. SO R C REFERRAL Refer penetrating foreign bodies to an experienced eye surgeon.

PREVENTIO N Eye protection should be worn for high-risk occupational and recreational activities.

PRO GNO SIS Prognosis is generally good. Development of infection or a rust ring worsens prognosis.

REFERENCES 1. Oum BS, Lee JS, Han YS. Clinical features of ocular trauma in emergency department. Korean J Ophthalmol. 2004;18(1):70-78. 2. Wilson SA, Last A. Management of corneal abrasions. Am Fam Physician. 2004;1(70):123-128. 3. Weissman BA. Care of the Contact Lens Patient: Reference Guide for Clinicians. St Louis, MO: American Optometric Association; 2000. 4. Turner A, Rabiu M. Patching for corneal abrasion. Cochrane Database Syst Rev. 2006;(2):CD004764. 5. Weaver CS, Terrell KM. Evidence-based emergency medicine. Update: do ophthalmic nonsteroidal anti-in ammatory drugs reduce the pain associated with simple corneal abrasion without delaying healing [review]? Ann Emerg Med. 2003;41(1):134-140. 6. Upadhyaya MP, Karmacharyaa PC, Kairalaa S, et al. The Bhaktapur eye study: ocular trauma and antibiotic prophylaxis for the prevention of corneal ulceration in Nepal. Br J Ophthalmol. 2001;85:388-392.

PART 4

CO NJUNCTIVITIS

O PHTHALMO LO GY

13 CO NJUNCTIVITIS

• In the United States, the estimated annual incidence rate or bacterial conjunctivitis is 135 per 10,000 people. 1

He id i Chumle y, MD Richard P. Usatine , MD

• Viral conjunctivitis is more common than bacterial conjunctivitis. • Allergic conjunctivitis had a point prevalence o 6.4% and a li etime prevalence o 40% in a large population study in the United States rom 1988 to 1994. 2

PATIENT STO RY ETIO LO GY AND PATHO PHYSIO LO GY A 35-year-old woman presents with 2 days o redness and tearing in her eyes (Figure 13-1). She has some thin matter in her eyes, but neither eye has been glued shut when she awakens. She does not have any trouble seeing once she blinks to clear any accumulated debris. Both eyes are uncom ortable and itchy, but she is not having any severe pain. She does not wear contact lenses and has not had this problem previously. The patient was diagnosed with viral conjunctivitis and scored –1 on the clinical scoring system (see “Diagnosis” below). She was instructed about eye hygiene and recovered in 3 days.

INTRO DUCTIO N Conjunctivitis, in ammation o the membrane lining the eyelids and globe, presents with injected pink or red eye(s), eye discharge ranging rom mild to purulent, eye discom ort or gritty sensation, and no vision loss. Conjunctivitis is most commonly in ectious (viral or bacterial) or allergic, but can be caused by irritants. Diagnosis is clinical, based on di erences in symptoms and signs.

SYNO NYMS Conjuctivitis is also known as pink eye.

EPIDEMIO LO GY • In ectious conjunctivitis is common and o ten occurs in outbreaks, making the prevalence di f cult to estimate.

FIGURE 13-1 Viral co njunctivitis d e monstrating b ilate ral conjunctival inje ctio n with little d ischarg e . The p atie nt has an incid e ntal le t e ye conjunctival ne vus. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Conjunctivitis in adults is predominately in ectious (viral) or allergic. • Adults and children o age 6 years or older are more likely to have viral or allergic causes or conjunctivitis. 3 Adenovirus is the most common viral cause. • Coxsackie viruses have caused multiple large outbreaks in several Asian countries. • Herpes simplex virus typically causes a keratitis, but may present as isolated conjunctivitis or as blepharoconjunctivitis. 4 • Children younger than 6 years are more likely to have a bacterial than viral conjunctivitis (Figure 13-2) which can be transmitted to their adult caretakers. In the United States, the most common bacterial causes are Haemophilus species and Streptococcus pneumoniae accounting or almost 90% o cases in children. 3

DIAGNO SIS • To distinguish conjunctivitis rom other causes o a red eye, ask about pain and check or vision loss. Patients with a red eye and intense pain or vision loss that does not clear with blinking are unlikely to have conjunctivitis and should undergo urther evaluation. • Always ask about contact lens use as this can be a risk actor or all types o conjunctivitis, including bacterial conjunctivitis (Figure 13-3). • Typical clinical eatures o any type o conjunctivitis may include eye discharge, gritty or uncom ortable eeling, one or both pink eyes, and

FIGURE 13-2 Bacte rial conjunctivitis with visib le p urule nt d ischarg e . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

75

76

PART 4

O PHTHALMO LO GY

Ch a pt e r 13

FIGURE 13-3 Bacte rial conjunctivitis with a small amount o d ischarg e . The p atie nt was unab le to cle an he r contacts while b e ing e vacuate d rom a hurricane -thre ate ne d Houston and the conjunctivitis was b ilate ral. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

no vision loss. The in ection usually starts in one eye, and progresses to involve the other eye days later. • Bacterial conjunctivitis (see Figures 13-2 to 13-4) has a more purulent discharge than viral or allergic conjunctivitis. • A clinical scoring system has been developed to distinguish bacterial rom other causes o conjunctivitis in healthy adults who did not wear contact lenses. A score o +5 to –3 is determined as ollows: ° Two glued eyes (+ 5); one glued eye (+ 2); history o conjunctivitis (–2); eye itching (–1). ° A score o + 5, + 4, or + 3 is use ul in ruling in bacterial conjunctivitis with specif cities o 100%, 94%, and 92%, respectively. ° Scores o –1, –2, or –3 are use ul in ruling out bacterial conjunctivitis with sensitivities o 98%, 98%, and 100%, respectively. 5 Allergic conjunctivitis is typically bilateral and accompanied by eye itching. Giant papillary conjunctivitis is a type o allergic reaction, most commonly to so t contact lenses (Figure 13-5).

FIGURE 1 3 -5 Giant p ap illary co njunctivitis in a co ntact le ns we are r. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD as contrib ute d b y Mike Johnson, MD.)

LABO RATO RY TESTING An in-o f ce rapid test or adenoviral conjunctivitis (RPS adeno detector) has a sensitivity o 88% and a specif city o 91% compared to viral cell culture with conf rmatory immuno uorescence staining. 6

DIFFERENTIAL DIAGNO SIS • Episcleritis—Segmental or di use in ammation o episclera (pink color), mild or no discom ort but can be tender to palpation, and no vision disturbance (see also Chapter 14, Episcleritis and Scleritis). • Scleritis—Segmental or di use in ammation o sclera (dark red, purple, or blue color), severe boring eye pain o ten radiating to head and neck, and photophobia and vision loss (see also Chapter 14, Episcleritis and Scleritis). • Uveitis or iritis—360-degree perilimbal injection, eye pain, photophobia, and vision loss. Frequently treated initially as conjunctivitis without resolution (see also Chapter 15, Uveitis and Iritis). • Keratitis or corneal ulcerations—Di use conjunctival injection, o ten with miosis (constriction o pupil), eye discharge, pain, photophobia, and vision loss depending on the location o ulceration. Herpes keratitis is a diagnosis that should not be missed (Figures 13-6 and 13-7). The use o uorescein and ultraviolet (UV) light can help identi y dendritic ulcers or other corneal damage and prompt an emergent re erral to an ophthalmologist (see Figure 13-7). Contact lens wearers should urgently see an ophthalmologist or keratitis.

FIGURE 13-4 Gonococcus conjunctivitis has a cop io us d ischarg e . This se ve re case re sulte d in p artial b lind ne ss. (Re p rod uce d with p e rmission from Ce nte rs for Dise ase Control and Pre ve ntion [CDC].)

• Acute-angle closure glaucoma—Cloudy cornea and scleral injection, eye pain with ipsilateral headache, elevated intraocular pressure, and severe vision loss (see also Chapter 16, Glaucoma). • A oreign body in the eye can cause conjunctival injection and lead to a bacterial superin ection. I the oreign body is not easily dislodged with

CO NJUNCt IVIt IS

PART 4

O PHTHALMO LO GY

FIGURE 13-6 He rp e tic ke ratitis in a 56-ye ar-old woman staying in a she lte r a te r hurricane Katrina. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

conservative measures, or appears to be superin ected with ulceration or leukocyte inf ltrate, prompt re erral to an ophthalmologist is required (Figure 13-8).

FIGURE 13-8 Conjunctivitis cause d b y a ore ig n b od y in the e ye o a machinist. The g round me tal sp e ck is se e n on the corne a, and the corne al inf ltrate , along with a p urule nt d ischarg e , ind icate a b acte rial sup e rin e ction. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Trachoma is an eye in ection caused by Chlamydia trachomatis that is rare in the United States but common in the rural areas o some developing countries. It is a leading cause o blindness in the developing world. Poverty and poor hygiene are major risk actors. Once the eye is in ected, ollicles can be seen on the upper tarsal conjunctiva upon eyelid eversion (Figure 13-9). Superior tarsal conjunctival scarring leads to entropion that causes corneal scarring and ultimately blindness (Figure 13-10). Vernal conjunctivitis is a severe recurrent orm o allergic conjunctivitis that is more common in summer (not in spring). The term vernal re ers to spring time, and there ore it is now re erred to as “warm weather conjunctivitis” rather than “spring catarrh.” Giant papillae that look like a cobblestone pattern may be seen in this condition. It occurs primarily in young boys, and typically ceases to recur seasonally with age. FIGURE 13-9 Trachoma showing many white ollicles on the underside o the upper eyelid. (Reproduced with permission from Richard P. Usatine, MD.)

FIGURE 13-7 Slit-lamp vie w o a d e nd ritic ulce r with uore sce in up take rom he rp e tic ke ratitis. (Re p rod uce d with p e rmission from Paul D. Come au.)

FIGURE 13-10  Ad vance d trachoma with b lind ne ss as a conse q ue nce o corne a op acitie s. Note the d e e p conjunctival inje ction and p urule nt d ischarg e rom the C. trachomatis in e ction. (Re p rod uce d with p e rmissio n fro m Richard P. Usatine , MD.)

77

PART 4

78

O PHTHALMO LO GY MANAGEMENT Hand hygiene can control the spread o in ectious conjunctivitis. Most acute conjunctival in ections are viral and resolve without treatment. Adults who score + 3 or above on the clinical scoring system or bacterial conjunctivitis are treated with topical antibiotics: • Studies show that more than 80% o patients show improvements with 0.3% cipro oxacin, tobramycin, nor oxacin, or gentamicin. 7,8 • Levo oxacin 0.5% is dosed 3 times a day. 9 • Delayed antibiotic prescription decreased antibiotic use by nearly 50% and provided similar symptom control compared to immediate antibiotics.10 Allergic conjunctivitis can be treated with antihistamines, mast-cell stabilizers, nonsteroidal anti-in ammatory agents, corticosteroids, and immunomodulatory agents. 11 REFERRAL • Re er patients who have vision loss, copious purulent discharge (this could represent gonococcal disease, which must be cultured, and which can cause vision loss), severe pain, lack o response to therapy, or a history o herpes simplex or zoster eye disease to an ophthalmologist. • Any patient who may need ocular steroid should be seen by an ophthalmologist. There is a severe risk o complications with the use o ocular steroids.

Ch a pt e r 13

PATIENT RESO URCES

• PubMed Health. Conjunctivitis—http:/ / www.ncbi.nlm.nih .gov/ pubmedhealth/ PMH0002005/ . • American Academy of Ophthalmology has patient information under For Patients and the Public—http:/ / www.aao.org. • American Academy of Ophthalmology. Conjunctivitis: What Is Pink Eye?—http:/ / www.geteyesmart.org/ eyesmart/ diseases/ conjunctivitis.cfm. • Centers for Disease Control and Prevention has patient information in English and Spanish—http:/ / www.cdc.gov. • Centers for Disease Control and Prevention. Conjunctivitis (Pink Eye)—http:/ / www.cdc.gov/ conjunctivitis/ index.html. • The Livestrong foundation has auditory patient information on YouTube. Conjunctivitis Health Byte—http:/ / www.youtube .com/ watch?v= O8LkDfbLCaY; and A Healthy Byte: Pink Eye— http:/ / www.youtube.com/ watch?v= Hp28hS7XYCo& feature=relmfu. PRO VIDER RESO URCES

• Agency for Healthcare Research and Quality. Conjunctivitis guidelines—http:/ / www.guidelines.gov/ content.aspx?id = 13501.

REFERENCES

PREVENTIO N Good hygiene practices with washing o the hands and ace with soap and water should be ollowed.

FO LLO W-UP Routine ollow-up is generally not needed i symptoms resolve in 3 to 5 days.

PATIENT EDUCATIO N • Most adults (and children older than age 6 years) have a nonbacterial cause o conjunctivitis. • Remove contact lenses until conjunctivitis has resolved. • Avoid touching the ace or rubbing the eyes and wash the hands immediately a terwards. • Do not share ace towels, eye makeup, or contact lens cases. • In orm your physician immediately i you experience eye pain or vision loss.

1. Smith AF, Waycaster C. Estimate o the direct and indirect annual cost o bacterial conjunctivitis in the United States. BMC Ophthalmol. 2009;9:13. 2. Singh K, Axelrod S, Bielory L. The epidemiology o ocular and nasal allergy in the United States, 1988-1994. JAllergy Clin Immunol. 2010;126(4):778-783. 3. Meltzer JA, Kunkov D, Crain EF. Identi ying children at low risk or bacterial conjunctivitis. Arch Pediatr Adolesc Med. 2010;164:263-267. 4. Young RC, Hodge DO, Liesegang TJ, Baratz KH. Incidence, recurrence, and outcomes o herpes simplex virus eye disease in Olmsted County, Immesota, 1976-2007: the e ect o oral antiviral prophylaxis. Arch Ophthalmol. 2010;128(9):1178-1183. 5. Rietveld RP. Predicting bacterial cause in in ectious conjunctivitis: cohort study on in ormativeness o combinations o signs and symptoms. BMJ. 2004;329:206-210. 6. Sambursky R, Tauber S, Schirra F, et al. The RPS adeno detector or diagnosing adenoviral conjunctivitis. Ophthalmology. 2006;113(10): 1758-1764. 7. Gross RD, Ho man RO, Lindsay RN. A comparison o cipro oxacin and tobramycin in bacterial conjunctivitis in children. Clin Pediatr (Phila). 1997;36(8):435-444. 8. Miller IM, Vogel R, Cook TJ, Wittreich J. Topically administered nor oxacin compared with topically administered gentamicin or the treatment o external ocular bacterial in ections. The Worldwide Nor oxacin Ophthalmic Study Group. Am J Ophthalmol. 1992;113(6):638-644.

CO NJUNCt IVIt IS

9. Sza ik J, Sza ik JP, Kaminska A. Clinical and microbiological e f cacy o levo oxacin administered three times a day or the treatment o bacterial conjunctivitis. Eur J Ophthalmol. 2009;19(1):1-9. 10. Everitt HA, Little PS, Smith PW. A randomized controlled trial o management strategies or acute in ective conjunctivitis in general practice. BMJ. 2006;333(7563):321.

PART 4

O PHTHALMO LO GY 11. Mishra GP, Tamboli V, Jwala J, Mitra AK. Recent patents and emerging therapeutics in the treatment o allergic conjunctivitis. Recent Pat Inf ammAllergy Drug Discov. 2011;5(1):26-36.

79

80

PART 4

O PHTHALMO LO GY

Ch a pt e r 14

14 SCLERITIS AND EPISCLERITIS

Scle rit is

He id i Chumle y, MD Ke lly Gre e n, MD

• Scleritis usually presents between the ages of 30 and 50 years and is twice as common in women compared to men. 1

PATIENT STO RY

EPIDEMIO LO GY

• Forty-four percent of patients presenting with scleritis to specialty health centers were found to have an associated systematic disease (37% rheumatic, 7% infection), most commonly (15%) rheumatoid arthritis. 2 Ep iscle rit is

A 45-year-old woman presents with 1 day of increasing eye pain, eye redness, and dif culty in seeing. On examination there was scleral injection and exquisite globe tenderness (Figure 14-1). Her review of systems is positive for morning stiffness and swelling in both of her hands. The patient was urgently referred to an ophthalmologist who diagnosed her with scleritis. Her visual acuity was reduced minimally. A slit-lamp examination revealed injected sclera with a bluish hue in the affected eye and a rare anterior chamber cell. The posterior segment was normal. The ophthalmologist prescribed an oral nonsteroidal anti-in ammatory drug (NSAID), speci cally indomethacin, as it effectively crosses the blood-brain barrier and gets good levels in the eye. Her rheumatoid factor was positive, so she was also referred to a rheumatologist.

INTRO DUCTIO N Episcleritis and scleritis are in ammation of the deeper layers of the eye, the vascular episclera, and the avascular sclera. Episcleritis presents with segmental eye redness, discomfort but not severe pain, and no vision loss. Scleritis can have overlying episcleritis, but also has a violaceous hue, is painful, and may cause vision loss. Scleritis typically has an associated underlying condition (autoimmune or infectious) that should be identi ed and treated. Scleritis is treated with NSAIDs, systemic glucocorticoids, or immunosuppressive medications. Patients with scleritis are often referred to an ophthalmologist as vision loss is common.

• Prevalence is unknown. • Episcleritis usually presents between the ages of 20 and 50 years and may be more common in women. • Nodular or recurrent episcleritis is more likely to be associated with an underlying systemic condition than is an isolated episode of simple episcleritis.

ETIO LO GY AND PATHO PHYSIO LO GY • Scleritis and episcleritis are in ammatory conditions causing congestion of the deeper 2 of the 3 vascular layers (conjunctival, episcleral, and scleral plexuses) overlying the avascular sclera. • Scleritis often occurs with episcleritis; episcleritis does not involve the sclera and does not progress to scleritis. • Scleritis disrupts vascular architecture and may cause vision loss; whereas episcleritis does not. Cause s o f scle rit is • Causes of scleritis include systemic autoimmune diseases such as rheumatoid arthritis, Wegener granulomatosis, seronegative spondyloarthropathies, relapsing polychondritis, systemic lupus erythematosus (SLE). Figure 14-2 shows a young woman with SLE and scleritis. • Infections (Pseudomonas, tuberculosis, syphilis, herpes zoster). • Less common causes include gout and sarcoidosis. • Idiopathic.

FIGURE 14-1 Scle ritis in a p atie nt with e ye p ain and e xq uisite g lob e te nd e rne ss. Untre ate d scle ritis can re sult in loss o vision. (Re p rod uce d with p e rmission from Paul D. Come au.)

FIGURE 14-2 Scle ritis in a young woman with syste mic lup us e rythe matosus. Note the malar rash that is also p re se nt. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

SCLe r It IS a ND e pISCLe r It IS

PART 4

O PHTHALMO LO GY

Cause s o f e p iscle rit is • Most often idiopathic. • May be associated with any of the conditions listed above, especially if the presentation is nodular or recurrent.

DIAGNO SIS CLINICAL FEATURES Scle rit is • Segmental or diffuse in ammation of sclera (dark red, purple, or blue color), with overlying episclera and conjunctival in ammation (see Figures 14-1 to 14-3). • Severe, boring eye pain often radiating to head and neck that worsens with eye movement. However, 20% of patients may not have pain, including those with the necrotizing type (scleromalacia perforans) and those taking immunosuppressive agents prior to the onset of scleritis. 1 • Photophobia and vision loss. Ep iscle rit is • Segmental or diffuse in ammation of episclera (pink color) and overlying conjunctival vessel injection (Figures 14-4 and 14-5).

FIGURE 14-4 Ep iscle ritis showing in ammation o the conjunctival and e p iscle ral tissue with associate d vascular e ng org e me nt. A se ctor o this e ye is involve d and that is typ ical. Ve sse ls we re b lanche d with 2.5% p he nyle p hrine , which he lp e d d isting uish this rom scle ritis. (Re p rod uce d with p e rmission from Paul D. Come au.)

• Mild, if any, discomfort but can be tender to palpation. • No vision disturbance.

Typ ical d ist rib ut io n

• Scleritis and episcleritis are often distinguished by history and physical examination features; however, when scleritis has extensive overlying episcleritis, the diagnosis becomes more dif cult. Scleritis must be differentiated from episcleritis because scleritis requires treatment and an evaluation for underlying medical conditions.

• Scleritis can be posterior (posterior to the medial and lateral rectus muscles) or anterior. ° Posterior scleritis can produce retinal detachments and subretinal exudates and is often associated with uveitis (in ammation of the iris, ciliary body, or choroid). with in amma° Anterior scleritis can be diffuse, nodular, necrotizing 1 tion or necrotizing without in ammation.

• Ten percent phenylephrine blanches in amed episcleral and conjunctival vessels, but not scleral vessels; in scleritis, this can reveal a focus of scleral engorgement covered by episcleral injection. • Scleritis and episcleritis, as opposed to iritis with overlying episcleral injection, often have areas of focal tenderness to palpation. These can be elicited with a sterile cotton swab after applying a topical anesthetic.

• Scleritis is bilateral in 50% of patients. 1 • Episcleritis is often segmental, but can be diffuse, and is typically benign. LABO RATO RY TESTING In scleritis, if an associated systemic disease has not been previously diagnosed, consider ordering these tests: complete blood count, metabolic

FIGURE 14-3 Scle ritis in a p atie nt with We g e ne r g ranulomatosis. De e p ve sse ls are a e cte d , g iving the e ye a p urp lish or b lue hue . (Re p rod uce d with p e rmission from Eve re tt Alle n, MD.)

FIGURE 14-5 Ep iscle ritis showing in ammation o only the conjunctival and e p iscle ral tissue . Note the ab se nce o violace ous color that is se e n in scle ritis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

81

PART 4

82

O PHTHALMO LO GY

Ch a pt e r 14

panel, urinalysis, antineutrophil cytoplasmic antibody, antinuclear antibody, rheumatoid factor, anticyclic citrullinated peptide antibodies, rapid plasma reagin, and Lyme antibody in Lyme infested regions. Also consider tuberculin skin test, viral hepatitis panel, and cultures for bacteria, virus, and fungi. IMAGING In scleritis, if an associated systemic disease has not been previously diagnosed, consider the following: chest radiographs, sinus computed tomography (CT), or sacroiliac joint radiographs. To diagnose posterior scleritis, ultrasound or orbital CT can demonstrate sclera thickening. BIO PSY An ophthalmologist may perform a biopsy when it is important to distinguish among scleritis caused by rheumatic diseases, infections, or sarcoidosis. • Rheumatic—Zonal necrotizing granulomatous scleral in ammation with loss of anterior scleral tissue. • Infectious—Necrotizing scleritis with microabscesses. • Sarcoid—Sarcoidal granulomatous in ammation can be identi ed in cases of sarcoidosis.

DIFFERENTIAL DIAGNO SIS Following are the causes of red eye, other than scleritis and episcleritis: • Uveitis or iritis—360 degrees perilimbal injection, which is most intense at the limbus; eye pain, photophobia, and vision loss (see also Chapter 15, Uveitis and Iritis) • Keratitis or corneal ulcerations—Diffuse erythema with ciliary injection often with pupillary constriction; eye discharge; pain, photophobia, and vision loss depending on location of ulceration • Conjunctivitis—Conjunctival injection, eye discharge, gritty or uncomfortable feeling, no vision loss (see Chapter 13, Conjunctivitis) • Acute-angle closure glaucoma—Cloudy cornea and scleral injection; eye pain with ipsilateral headache; severe vision loss (see Chapter 16, Glaucoma)

MANAGEMENT For patients presenting with scleritis who do not have a previously diagnosed associated systemic condition, a search for an underlying cause is indicated. • Evaluate for signs and symptoms of rheumatoid arthritis, Wegener granulomatosis (respiratory or renal symptoms), relapsing polychondritis (vasculitis around ear or nose cartilage or trachea; Figure 14-6), and seronegative spondyloarthropathies (in ammatory back pain, arthritis, and in ammatory bowel symptoms). • Evaluate for signs, symptoms, and risk factors for infection including eye trauma, recent ocular surgery, recurrent herpes simplex or varicella zoster, or risk factors for tuberculosis. • Evaluate for signs and symptoms of gout and sarcoidosis.

FIGURE 14-6 Scle ritis associate d with re lap sing p olychond ritis. Note the op p y e ar which is a classic f nd ing in re lap sing p olychond ritis (Re p rod uce d with p e rmission from Eve re tt Alle n, MD.)

MEDICATIO NS • Scleritis is initially treated with systemic NSAIDs and/ or topical steroids; however, in one study only 47% of patients responded to 2 drops of 1% prednisolone every 2 hours for up to 2 weeks. 3 SO R B • Scleritis that does not respond to NSAIDs and/ or topical steroids may need systemic steroids, subconjunctival steroids, or immune modulators. SO R C • Episcleritis often resolves spontaneously. Eye redness and irritation improve by 50% in less than a week. Treatment with topical NSAIDs was no better than arti cial tears on measures of redness and comfort. 4 SO R B

REFERRAL • If you suspect scleritis, refer the patient to an ophthalmologist immediately. This is especially important if there is any visual loss or eye pain. • If episcleritis is not resolved, refer to an ophthalmologist.

PRO GNO SIS Simple episcleritis improves in 7 to 10 days. Episcleritis that is nodular or associated with an underlying disease may take 2 to 3 weeks to resolve. Patients who smoke may take longer to recover from episcleritis or scleritis. One retrospective trial demonstrated that patients who smoked and had episcleritis or scleritis were 5.4 times more likely to have a delayed response of more than 4 weeks to any medication (95% con dence interval [CI] = 1.9-15.5). 5 Vision loss with scleritis is common and the risk is dependent on the type of scleritis: diffuse anterior, 9%; nodular, 26%; necrotizing, 74%; posterior, 84%. 6

FO LLO W-UP • Advise patients with episcleritis to follow up for any increases in eye pain, changes in vision, or no improvement in 1 week. • Advise patients with scleritis to follow up testing for underlying systemic illnesses. If none is found, consider retesting as patients with idiopathic scleritis develop a systemic illness at a 4% annual rate. 2

PART 4

SCLe r It IS a ND e pISCLe r It IS

PATIENT EDUCATIO N • Reassure patients with episcleritis of its generally benign nature and that oral NSAIDs may be used for discomfort. • Advise patients with scleritis of its association with systemic illnesses and the need for further workup. PATIENT RESO URCES

• PubMed Health. Scleritis—http:/ / www.ncbi.nlm.nih.gov/ pubmedhealth/ PMH0001998/ . • PubMed Health. Episcleritis—http:/ / www.ncbi.nlm.nih.gov/ pubmedhealth/ PMH0002014/ .

O PHTHALMO LO GY REFERENCES 1. Galor A, Thorne JE. Scleritis and peripheral ulcerative keratitis. Rheum Dis Clin North Am. 2007;33(4):835-854. 2. Akpek EK, Thorne JE, Qazi FA, et al. Evaluation of patients with scleritis for systemic disease. Ophthalmology. 2004;111(3):501-506. 3. McMullen M, Kovarik G, Hodge WG. Use of topical steroid therapy in the management of nonnecrotizing anterior scleritis. Can J Ophthalmol. 1999;34(4):214-221. 4. Williams CP, Browning AC, Sleep TJ, et al. A randomised, doubleblind trial of topical ketorolac vs arti cial tears for the treatment of episcleritis. Eye (Lond). 2005;19(7):739-742.

PRO VIDER RESO URCES

5. Boonman ZF, de Keizer RJ, Watson PG. Smoking delays the response to treatment in episcleritis and scleritis. Eye (Lond). 2005;19(9): 945-955.

• Patient.co.uk. Scleritis and Episcleritis—http:/ / www.patient .co.uk/ doctor/ Scleritis-and-Episcleritis.htm.

6. Tuft SJ, Watson PG. Progression of sclera disease. Ophthalmology. 1991;98(4):467-471.

83

PART 4

84

O PHTHALMO LO GY

15 UVEITIS AND IRITIS He id i Chumle y, MD

PATIENT STO RY A 28-year-old man presented with sudden onset of a right red eye, severe eye pain, tearing, photophobia, and decreased vision. He denied eye trauma. His review of systems was positive for lower back pain and stiffness over the past year. On examination, he had a ciliary ush (Figure 15-1) and decreased vision. He was referred to an ophthalmologist who conrmed the diagnosis of acute anterior uveitis. He was found to be HLAB27 positive with characteristics of ankylosing spondylitis. His uveitis was treated with topical steroids.

INTRO DUCTIO N Uveitis is in ammation of any component of the uveal tract: iris (anterior), ciliary body (intermediate), or choroid (posterior). Most uveitis is anterior and is also called iritis. Uveitis is caused by trauma, in ammation, or infection and the most common etiologies vary by location in the uveal tract. Patients present with vision changes and, if uveitis is anterior, eye pain, redness, tearing, and photophobia. All patients with uveitis should be referred to an ophthalmologist.

Ch a pt e r 15

EPIDEMIO LO GY • Annual incidence of uveitis is 17 to 52 per 100,000 population and prevalence is 38 to 714 per 100,000 population. 1 • Occurs at any age, but most commonly between 20 and 59 years. 1 • Anterior uveitis (iritis) accounts for approximately 90% of uveitis as seen in primary care settings. 1 • In the United States, noninfectious uveitis accounts for 10% of legal blindness. 2

ETIO LO GY AND PATHO PHYSIO LO GY • Uveitis can be caused by trauma, infections, in ammation, or, rarely, neoplasms. Most likely causes differ by location. 3 • Iritis—Trauma is common (Figure 15-2). In nontraumatic cases, causes include idiopathic (50%); seronegative spondyloarthropathies, that is, ankylosing spondylitis, reactive arthritis, psoriatic arthritis, in ammatory bowel disease (20%); and juvenile idiopathic arthritis (10%). Infections are less common and include herpes, syphilis, and tuberculosis. 3 Untreated HIV-positive patients may also develop iritis. • Intermediate—Most are idiopathic3 (Figure 15-3). • Posterior—Toxoplasmosis is the most common, followed by idiopathic. 3 • Panuveitis (affecting all layers)—Idiopathic (22-45%) and sarcoidosis (14-28%). 3 Unilateral panuveitis is often endophthalmitis (endogenous or related to trauma or surgery). Bilateral panuveitis can be caused by sarcoidosis or syphilis.

SYNO NYMS Anterior uveitis includes iritis and iridocyclitis. Iritis is when the in ammation is limited to the iris. If the ciliary body is involved too, then it is called iridocyclitis. Posterior uveitis includes choroiditis and chorioretinitis.

FIGURE 15-1 Acute ante rior uve itis with corne al e nd othe lial white ce ll ag g re g ate s (b lack arrow) and p oste rior syne chiae ormation (iris ad he sions to the le ns, white arrows). (Re p rod uce d with p e rmission from Paul D. Come au.)

RISK FACTO RS Patients with Behçet disease and ankylosing spondylitis have uveitis more commonly than the general population (relative risk of 4-20) because of human leukocyte antigen (HLA) associations. 4

FIGURE 15-2 A young man with traumatic iritis (ante rior uve itis) a te r b e ing hit in the e ye with a b ase b all. He has p hotop ho b ia and e ye p ain. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

UVe It IS a ND Ir It IS

PART 4

O PHTHALMO LO GY Behçet syndrome and HLA-B27 disease are the only 2 common noninfectious causes of hypopyon. Intermediate and posterior uveitis includes the following symptoms: • Presents with altered vision or oaters. • Often there is no pain, redness, tearing, or photophobia. Sarcoid uveitis presents with the following symptoms: • Panuveitis (anterior, intermediate, and posterior) • Gradual and usually a bilateral onset • Few vision complaints unless cataracts or glaucoma develops • Characteristic ndings on slit-lamp examination (ie, mutton-fat keratic precipitates, posterior iris synechiae)5 Typ ical d ist rib ut io n Anterior uveitis is typically unilateral and sarcoid uveitis is typically bilateral.

FIGURE 15-3 Id iop athic inte rme d iate uve itis. The ciliary ush is p e rilimb al inje ction rom d ilation o b lood ve sse ls ad jace nt to the corne a, e xte nd ing 3 mm into the scle ra. Pe rilimb al inje ction may ap p e ar as a viole t hue around the limb us with b lurring o ind ivid ual ve sse ls. (Re p rod uce d with p e rmission from Paul D. Come au.)

DIAGNO SIS CLINICAL FEATURES Anterior acute uveitis presents with the following symptoms: • Usually unilateral eye pain, redness, tearing, photophobia, and decreased vision. • 360-degree perilimbal injection, which is most intense at the limbus (see Figures 15-1, 15-2, and 15-4). • History of eye trauma, an associated systemic disease, or risk factors for infection. • Severe anterior uveitis may cause a hypopyon from layering of leukocytes and brous debris in the anterior chamber (see Figure 15-4).

DIFFERENTIAL DIAGNO SIS Causes of red eye, other than uveitis • Scleritis—Segmental or diffuse in ammation of sclera (dark red, purple, or blue color); severe, boring eye pain often radiating to head and neck; photophobia and vision loss (see Chapter 14, Scleritis and Episcleritis). • Episcleritis—Segmental or diffuse in ammation of episclera (pink color), mild or no discomfort, but can be tender to palpation, and no vision disturbance (see Chapter 14, Scleritis and Episcleritis). • Keratitis or corneal ulcerations—Diffuse erythema with ciliary injection often with constricted pupil; eye discharge; pain, photophobia, and vision loss depending on the location of ulceration. This is frequently associated with trauma, a history of herpes simplex virus (HSV) infection, or contact lens wear. Needs urgent evaluation by an ophthalmologist. There will be staining of the cornea with uorescein. • Conjunctivitis—Conjunctival injection, eye discharge, gritty or uncomfortable feeling, and no vision loss (see Chapter 13, Conjunctivitis). Recent history of red eye contacts or upper respiratory infection (URI) symptoms. • Acute-angle closure glaucoma—Cloudy cornea and scleral injection, eye pain with ipsilateral headache, and severe vision loss (see Chapter 16, Glaucoma). May be a family history of the same.

MANAGEMENT Refer patients for any red eye along with loss of vision to an ophthalmologist. Patients with uveitis warrant additional examinations by the ophthalmologist. • Traumatic uveitis—Dilated funduscopy for other ocular trauma, measurement of intraocular pressure, gonioscopy to evaluate for angle recession and risk for future glaucoma, and treatment may include steroid and/ or cycloplegics for comfort. FIGURE 15-4 Hyp op yon with se ve re ante rior uve itis, showing laye ring o le uko cyte s and f b rinous d e b ris in the ante rior chamb e r, may b e ste rile or in e ctious. An inte nse ciliary ush is se e n. Most commonly se e n in HLAB27-p ositive p atie nts with uve itis. Hyp op yon may also b e a p re se nting sig n o malig nancy (re tinob lastoma and lymp homa). (Re p rod uce d with p e rmission from Paul D. Come au.)

• Nontraumatic uveitis—Slit-lamp examination and laboratory tests to assist with diagnosis of underlying cause; treatment is based on underlying cause but is usually topical steroid drops with or without cycloplegia. • Therapeutic dilation is used to break the posterior synechiae that can occur (Figure 15-5).

85

PART 4

86

O PHTHALMO LO GY

Ch a pt e r 15

PATIENT EDUCATIO N • See a physician immediately for a red eye with loss of vision. • A series of tests may be performed to determine the cause of the uveitis; however, the underlying cause is often elusive.

PATIENT RESO URCES

• PubMed Health. Uveitis—http:/ / www.ncbi.nlm.nih.gov/ pubmedhealth/ PMH0002000/ . PRO VIDER RESO URCES

• Medscape. Iritis and Uveitis—http:/ / emedicine.medscape .com/ article/ 798323. FIGURE 15-5 This p atie nt with uve itis had p oste rior syne chiae that are attachme nts o the iris to the ante rior cap sule o the le ns. The rap e utic d ilation b ro ke the syne chiae , b ut le t re sid ual p ig me nt on the ante rior cap sule . (Re p rod uce d with p e rmission from Paul D. Come au.)

PRO GNO SIS Uveitis causes vision loss, cataract, and often glaucoma if treatment is delayed or not provided. HLA-B27 disease is the most common etiology for anterior uveitis, and is associated with recurrent, bilateral, anterior uveitis.

FO LLO W-UP Appropriate follow-up is based on the underlying cause.

REFERENCES 1. Wake eld D, Chang JH. Epidemiology of uveitis. Int Ophthalmol Clin. 2005;45(2):1-13. 2. Gritz DC, Wong IG. Incidence and prevalence of uveitis in northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology. 2004;111(3):491-500. 3. Brazis PW, Stewart M, Lee AG. The uveo-meningeal syndromes. Neurologist. 2004;10(4):171-184. 4. Capsi RR. A look at autoimmunity and in ammation in the eye. J Clin Invest. 2010;120(9):3073-3083. 5. Uyama M. Uveitis in sarcoidosis. Int Ophthalmol Clin. 2002;42(1): 143-150.

GLAUCO MA

PART 4

O PHTHALMO LO GY

16 GLAUCO MA

• Women comprise approximately 60% o all glaucoma cases, but 70% o patients with acute angle-closure glaucoma. 2

He id i Chumle y, MD

• Asians comprise approximately 47% o all glaucoma cases, but 87% o acute angle-closure glaucoma. 2

PATIENT STO RY A 50-year-old black man was noted to have a large cup-to-disc ratio during a unduscopic examination by his primary care provider (Figure 16-1). The patient reported no visual complaints. Further evaluation revealed elevated intraocular pressure (IOP) and early visual eld de ects. He was started on medication to lower his IOP. He remained asymptomatic, and his visual eld de ects did not progress or the next several years.

INTRO DUCTIO N Glaucoma is a leading cause o blindness in the United States and globally. Open-angle glaucoma is an acquired loss o retinal ganglion cells characterized by either normal or increased intraocular pressure, a large cup-to-disc ratio, and visual eld de ects. Open-angle glaucoma is treated by reducing intraocular pressure, most commonly with eye drops. Angle-closure glaucoma, which is much less common, is an acute increase in IOP rom a mechanical obstruction that must be treated emergently to preserve vision.

EPIDEMIO LO GY • Approximately 2.5 million people in the United States have glaucoma. • Glaucoma is the second leading cause o blindness in the United States and the leading cause o blindness among A rican Americans. 1

• The incidence o primary open-angle glaucoma was 8.3 per 100,000 population in people older than 40 years in a Minnesota population study.3 • According to a population-based study, a amily history o glaucoma increased the risk o having glaucoma (odds ratio [OR] = 3.08). 4

ETIO LO GY AND PATHO PHYSIO LO GY • Glaucoma pathophysiology is incompletely understood, but the end point is the acquired loss o retinal ganglion cells and axons with resulting irreversible vision loss. • Increased IOP is a well-known risk actor; however, recent attention has turned to ocular per usion pressure (OPP), the di erence between blood pressure (BP) and IOP. OPP is essentially BP minus IOP. As such, OPP is decreased by either high IOP or low BP. 5 I a patient with apparently well-controlled IOP continues to have progressive visual eld loss, it may be because o lack o per usion o the optic nerve rom aggressively lowered diastolic BPs. There ore, the management o glaucoma requires attention to diastolic BP. • Glaucoma is categorized as either open-angle glaucoma or angle-closure glaucoma. ° Open-angle—Dys unction o the aqueous humor drainage system with no visible pathology to the anterior chamber angle ° Angle-closure—Occlusion o the anterior chamber angle • Impaired outf ow o aqueous humor elevates IOP in some patients, but many patients with open-angle glaucoma have normal IOPs.

• Population studies predict there will be 60.5 million people worldwide with glaucoma by 2010, and o these, 74% will have open-angle glaucoma.2

• Optic nerve atrophy is seen as optic disc cupping and irreversible visual eld loss. Compare Figures 16-1 and 16-2 to see the di erence between abnormal (see Figure 16-1) and normal (see Figure 16-2) optic disc cupping.

Fig u r e 16-1 A 50-ye ar-old man with g laucoma has an incre ase d op tic cup -to-d isc ratio of 0.8. Me d ian cup -to-d isc ratio is 0.2 to 0.3, b ut varie s consid e rab ly among ind ivid uals. (Re p rod uce d with p e rmission fro m Paul D. Come au.)

Fig u r e 16-2 Normal e ye with a no rmal cup -to-d isc ratio of 0.4. A cup -tod isc ratio of more than 0.5 re q uire s furthe r e valuation. (Re p rod uce d with p e rmission from Paul D. Come au.)

87

PART 4

88

O PHTHALMO LO GY RISK FACTO RS Open-angle risk actors include the ollowing: • Nonmodi able: age older than 50 years, rst-degree amily history, and A rican ancestry6 • Modi able: high IOP, high or low BP, and maybe diabetes mellitus6 Acute closed-angle glaucoma is more common in people o Asian descent.

DIAGNO SIS CLINICAL FEATURES • Open-angle glaucoma ° History—Usually asymptomatic, occasionally “tunnel vision” ° Physical examination—Optic cupping and/ or elevated IOP (glaucomatous changes can occur with IOPs in the normal range), loss o peripheral vision by automated perimetry (typically bilateral, but maybe asymmetric) • Acute closed-angle glaucoma ° History—Pain ul red eye (unilateral), vision loss, headache, nausea, halos around lights, and vomiting (Figure 16-3) ° Physical examination—Shallow anterior chamber, optic cupping and elevated IOP, injection o the conjunctiva, and cloudy cornea (see Figure 16-3)

Ch a pt e r 16

DIFFERENTIAL DIAGNO SIS Glaucoma is the most common cause o optic disc cupping and is sometimes accompanied by elevated IOP. • Optic disc cupping without elevated IOP can be caused by the ollowing7: ° Physiologic cupping (see Figure 16-2) ° Congenital optic disc anomalies (ie, coloboma or tilted discs) ° Ischemic (ie, compression by tumors), traumatic (closed-head injury), or hereditary optic neuropathies • Glaucomatous optic disc cupping compared to other causes has the ollowing7: ° Larger cup-to-disc ratios (compare Figure 16-1 to Figure 16-2) ° Vertical (as opposed to horizontal) elongation o the cup ° Disc hemorrhages

MANAGEMENT Treat with topical agents to decrease IOP by 20% to 40%, which has been demonstrated to decrease glaucoma progression. 8 SO R A Many medications are available including the ollowing: • Nonspeci c β-blockers (eg, timolol 0.5%, once or twice a day) • Prostaglandin analogs (eg, latanoprost 0.005%, once a day) • Carbonic anhydrase inhibitors (eg, dorzolamide 2%, 2-3 times a day)

Typ ical d ist rib ut io n

• α -Agonists (eg, brimonidine 1.0%, 2-3 times a day)

• Open-angle glaucoma is typically bilateral. • Closed-angle glaucoma is typically unilateral. However, there is a risk or the other eye to undergo the same process, as the abnormal anatomically narrow angle is usually present in the other eye too.

REFERRAL • Emergently re er patients with suspected angle-closure glaucoma to an ophthalmologist (see Figure 16-3). • Evaluate (or re er or evaluation) patients with abnormal optic nerve cupping (cup-to-disc ratio >0.5; di erence in cup-to-disc ratio o 0.2 or greater between eyes; asymmetric cup), or increased IOP measured by tonometry, or visual eld de cits. • Document the location and extent o visual eld de cits with automated perimetry. • Re er patients with shallow anterior chambers, severe arsightedness (hyperopia), or previous history o acute angle-closure glaucoma to an ophthalmologist. • Re er or surgical evaluation i you are unable to medically reduce the IOP.

PREVENTIO N

Fig u r e 16-3 Acute close d -ang le g laucoma with a p ainful re d e ye , vision lo ss, he ad ache , nause a, and vomiting . This is a p hacomorp hic (ie , le ns ind uce d ) se cond ary acute ang le closure . The mature cataract incre ase d in ante rop oste rior (AP) d iame te r, thus moving the le ns-iris d iap hrag m forward and closing off the ang le as we ll as the p up il thus re sulting in hig h intraocular p re ssure (IO P), inje cte d conjunctiva, and a cloud y corne a. (Re p rod uce d with p e rmission from Gilb e rto Ag uirre , MD.)

Screening—According to the US Preventive Services Task Force update in 2005 (http:/ / www.ahrq.gov/ clinic/ uspstf/ uspsglau.htm) there is insu cient evidence to recommend or or against population screening or open-angle glaucoma. However, A rican Americans have been underrepresented in trials. Previously screening has been recommended or A rican Americans older than age 40 years, Caucasians older than age 65 years, and patients with a amily history o glaucoma. 1 SO R C

PART 4

GLa UCO Ma

PRO GNO SIS Most patients with open-angle glaucoma, provided they are treated, will not lose vision. Angle-closure glaucoma must be treated emergently to prevent vision loss.

FO LLO W-UP Patients with glaucoma should have regular measurements o their IOP and visual elds to ollow treatment e cacy.

PATIENT EDUCATIO N Advise patients that glaucoma is a progressive disease requiring continued therapy to prevent vision loss. PATIENT RESO URCES

• Glaucoma research foundation Web site has information on treatment, research progress, personal stories, and practical tips— http:/ / www.glaucoma.org. • PubMed Health. Glaucoma—http:/ / www.ncbi.nlm.nih.gov/ pubmedhealth/ PMH0002587/ . PRO VIDER RESO URCES

• Medscape. Acute angle-closure glaucoma—http:/ / emedicine .medscape.com/ article/ 798811. • Medscape. Primary open-angle glaucoma—http:/ / emedicine .medscape.com/ article/ 1206147.

O PHTHALMO LO GY REFERENCES 1. Distelhorst JS, Hughes GM. Open-angle glaucoma. Am Fam Physician. 2003;67(9):1937-1944. 2. Quigley HA, Broman AT. The number o people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262-267. 3. Erie JC, Hodge DO, Gray DT. The incidence o primary angle-closure glaucoma in Olmsted County, Minnesota. Arch Ophthalmol. 1997;115(2):177-181. 4. Leske MC, Warheit-Roberts L, Wu SY. Open-angle glaucoma and ocular hypertension: the Long Island Glaucoma Case-control Study. Ophthalmic Epidemiol. 1996;3(2):85-96. 5. He Z, Vingrys AJ, Armitage JA, Bui BV. The role o blood pressure in glaucoma. Clin Exp Optom. 2011;94(2):133-149. 6. Leske MC, Wu SY, Hennis A, et al. Risk actors or incident openangle glaucoma: the Barbados Eye Studies. Ophthalmology. 2008;115:85-93. 7. Piette SD, Sergott RC. Pathological optic-disc cupping. Curr Opin Ophthalmol. 2006;17(1):1-6. 8. Heijl A, Leske MC, Bengtsson B, et al. Reduction o intraocular pressure and glaucoma progression: results rom the Early Mani est Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-1279.

89

90

PART 4

O PHTHALMO LO GY

17 DIABETIC RETINO PATHY He id i Chumle y, MD Ke lly Gre e n, MD

PATIENT STO RY A 38-year-old man saw a physician for the rst time in 10 years after noticing visual loss in his left eye. His history revealed many risk factors for and symptoms of diabetes mellitus (DM). On an undilated funduscopic examination, his physician was able to see some hemorrhages and hard exudates. A ngerstick in the of ce showed a blood glucose level of 420 mg/ dL. He was treated for DM and referred to an ophthalmologist to be evaluated for diabetic retinopathy (Figure 17-1).

INTRO DUCTIO N Diabetic retinopathy (DR) is a leading cause of blindness in the United States. Nonproliferative DR is characterized by microaneurysms, macular edema, cotton-wool spots, super cial ( ame) or deep (dot-blot) hemorrhages, and exudates. Proliferative DR also has neovascularization of the retina, optic nerve head, or iris. Because patients may be asymptomatic until vision loss occurs, screening is indicated in all diabetic patients. Excellent glycemic control lowers a patient’s risk of developing DR.

EPIDEMIO LO GY • In developed nations, DR is the leading cause of blindness among people younger than age 40 years. 1

FIGURE 17-1 Dilat d und uscop ic p otog ap d monst ating mic oan uysms (small d sw lling s attac d to v ss ls), w ic a o t n t st c ang in d iab tic tinop at y. Also p s nt a f am mo ag s (b lack oval) and a d xud at s (white arrowhe ad s). T a d xud at s a y llow in colo . T is cas is an xamp l o d iab tic nonp oli ativ tinop at y. (Re p rod uce d with p e rmission fro m Paul D. Come au.)

Ch a pt e r 17

• In a community-based study, 29% of adults older than age 40 years with DM had DR. Prevalence in black patients was higher than in Caucasians patients (38.8% vs 26.4%). 2 • Twenty-one percent of patients have retinopathy at the time type 2 diabetes is diagnosed. 3 • More than 60% of patients with type 2 DM have retinopathy within 20 years of diagnosis. 3 • After 40 years of type 1 DM, 84% of patients have retinopathy. 4

ETIO LO GY AND PATHO PHYSIO LO GY • Hyperglycemia results in microvascular complications including retinopathy. • Several biochemical pathways linking hyperglycemia and retinopathy have been proposed. 3 • In nonproliferative retinopathy, microaneurysms weaken vessel walls. Vessels then leak uid, lipids, and blood resulting in macular edema, exudates, and hemorrhages (Figures 17-1 and 17-2). • Cotton-wool spots result when small vessel occlusion causes focal ischemia to the super cial nerve ber layer of the retina. • In proliferative retinopathy, new blood vessels form in response to ischemia (Figure 17-3).

RISK FACTO RS • In type 1 DM, identi ed risk factors include longer diabetes duration, high hemoglobin (Hgb) A1c, hypertension, smoking, and male gender.4,5 • In type 2 DM, identi ed risk factors include longer diabetes duration, high HgbA1c, elevated systolic blood pressure, male gender, presence of albuminuria, and pharmacologic therapy. 6

FIGURE 17-2 V y s v nonp oli ativ d iab tic tinop at y wit multip l d p d ot-b lot mo ag s, v nous b ad ing , and loop ing . T is p ati nt may b n t om p an tinal p otocoag ulation. (Re p rod uce d with p e rmission from Paul D. Come au.)

PART 4

DIa Be t IC r e t INO pa t h Y

O PHTHALMO LO GY MANAGEMENT Diabetes and vascular risk factors should be controlled. • Glycemic control lowers the risk of retinopathy (35% risk reduction per 1 point HgbA1C reduction). 3 SO R A • Blood pressure control improves visual outcomes (34% risk reduction in retinopathy progression; 47% risk reduction for declines in visual acuity). 3 SO R A • Treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in type 1 DM or an ARB in type 2 DM have been shown to reduce retinopathy progression independent of blood pressure control. 8,9 SO R B • Patients with high lipids have more hard exudates and a higher risk of vision loss, but it is unclear if lipid control changes outcomes. SO R C REFERRAL

FIGURE 17-3 P oli ativ d iab tic tinop at y s owing n wly d v lop d , p o ous, iab l b lood v ss ls. N w v ss ls can b s n on t op tic d isc and p ip al tina. Pan tinal p otocoag ulation may lp p v nt vit ous mo ag , tinal d tac m nt, and n ovascula g laucoma. (Re p rod uce d with p e rmission from Paul D. Come au.)

DIAGNO SIS De nitive diagnosis is made by an eye specialist. • Gold standard is grading of stereoscopic color fundus photographs in seven standard elds. 3 • In comparison with the gold standard, a single monochromatic digital photo through a nondilated eye is suf cient to determine the presence or absence of DR with a sensitivity and speci city of 71% and 96%, respectively. 7 SO R B

Work with an ophthalmologist to prevent vision loss. • Complications of DR are vitreous hemorrhage (Figure 17-4), retinal detachment, and neovascular glaucoma. Each of these complications can result in devastating vision loss. • Ophthalmologists will determine when peripheral retinal photocoagulation is indicated (Figure 17-5). Photocoagulation reduces the risk of severe visual loss by more than 50% with side effects of peripheral and night vision loss. 10 SO R A Other surgical treatments, including vitrectomy, have been less successful. 3

PREVENTIO N Prevent DR by preventing development of type 2 DM or tightly controlling type 1 or type 2 DM.

CLINICAL FEATURES • Central vision loss as a result of macular edema or macular ischemia. • Nonproliferative retinopathy—Microaneurysms are seen initially (mild), followed by macular edema, cotton-wool spots, super cial ( ame) or deep (dot-blot) hemorrhages, and exudates (Figure 17-1 shows moderate, and Figure 17-2 shows severe). • Proliferative retinopathy—Neovascularization, that is, growth of new blood vessels on the optic disc (see Figure 17-3), the retina, or iris.

DIFFERENTIAL DIAGNO SIS Retinopathy is also seen with other systemic illnesses and infections including the following: • Hypertensive retinopathy—Arterial narrowing or atrioventricular nicking in addition to cotton-wool spots (see Chapter 18, Hypertensive Retinopathy) • HIV retinopathy—Cotton-wool spots and infections such as cytomegalovirus

FIGURE 17-4 T is vit ous mo ag occu d w n iab l n ovascula m mb an s b ok sp ontan ously. T p ati nt d sc ib d a “s ow o d d ots” ob scu ing t vision and t n loss o vision in t at y . (Re p rod uce d with p e rmission from Paul D. Come au.)

91

PART 4

92

O PHTHALMO LO GY

Ch APTe r 17

REFERENCES 1. Congdon NG, Friedman DS, Lietman T. Important causes of visual impairment in the world today. JAMA. 2003;290(15):2057-2060. 2. Zhang X, Saaddine JB, Chou CF, et al. Prevalence of diabetic retinopathy in the United States, 2005–2008. JAMA. 2010;304(6): 649-656. 3. Fong DS, Aiello LP, Ferris FL III, Klein R. Diabetic retinopathy. Diabetes Care. 2004;27(10):2540-2553. 4. Hammes HP, Kerner W, Hofer S, et al. Diabetic retinopathy in type 1 diabetes—a contemporary analysis of 8,784 patients. Diabetologia. 2011;54(8):1977-1984. 5. Romero-Aroca P, Baget-Bernaldiz M, Fernandez-Ballart J, et al. Ten-year incidence of diabetic retinopathy and macular edema. Risk factors in a sample of type 1 diabetes patients. Diabetes Res Clin Pract. 2011;94(1):126-132.

FIGURE 17-5 Pan tinal p otocoag ulation is t ap p lication o las b u ns to t p ip al tina. T isc mic p ip al tina is t at d wit t ousand s o las sp ots to p sumab ly liminat vasog nic acto s sp onsib l o t d v lop m nt o n ovascula v ss ls. Las sp o ts caus sca ing o t tina and c o oid . T sca s may b yp ot op ic (white sp ots) o yp t op ic (b lack sp ots). (Re p rod uce d with p e rmission fro m Paul D. Come au.)

Screen patients with DM for DR based on national recommendations11: • Type 1 DM—Adults and children older than age 10 years—Screen for retinopathy 5 years after diagnosis and at regular intervals as recommended by an eye specialist. • Type 2 DM—Screen for retinopathy at diagnosis and then annually. Patients can be referred to an eye specialist, or screened using telemedicine or retinal photographs taken during outreach screenings or in primary care of ces. 12,13 Mathematical models are being developed to individualize screening frequency. In one study, screening intervals ranged from 6 to 60 months (mean: 29 months). This resulted in 59% fewer visits than with xed annual screening without compromising safety. 14

FO LLO W-UP Once DR is diagnosed frequency of examination is set by the ophthalmologist.

PATIENT EDUCATIO N Preventing retinopathy by controlling diabetes and hypertension leads to better vision outcomes than any available treatment. 3,10 PATIENT RESO URCES

• National Eye Institute—http:/ / www.nei.nih.gov/ health/ diabetic/ . PRO VIDER RESO URCES

• Medscape. Diabetic Retinopathy—http:/ / emedicine .medscape.com/ article/ 1225122.

6. Semeraro F, Parrinello G, Cancarini A, et al. Predicting the risk of diabetic retinopathy in type 2 diabetic patients. J Diabetes Complications. 2011;25(5):292-297. 7. Vujosevic S, Benetti E, Massignan F, et al. Screening for diabetic retinopathy: 1 and 3 nonmydriatic 45-degree digital fundus photographs vs 7 standard early treatment diabetic retinopathy study elds. Am J Ophthalmol. 2009;148(1):111-118. 8. Chaturvedi N, Sjolie AK, Stephenson JM, et al. Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. EURODIAB Controlled Trial of Lisinopril in InsulinDependent Diabetes Mellitus. Lancet. 1998;351:28-31. 9. Sjolie AK, Klein R, Porta M, et al. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial. Lancet. 2008;372:1385-1393. 10. The Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy: the second report of diabetic retinopathy study ndings. Ophthalmology. 1978;85(1): 82-106. 11. American Diabetes Association. Standards of medical care in diabetes—2009. Diabetes Care. 2009;32(suppl 1):S13-S61. 12. Sanchez CR, Silva PS, Cavallerano JD, et al. Ocular telemedicine for diabetic retinopathy and the Joslin Vision Network. Semin Ophthalmol. 2010;25(5-6):218-224. 13. Bragge P, Gruen RL, Chau M, et al. Screening for presence or absence of diabetic retinopathy: a meta-analysis. Arch Ophthalmol. 2011;129(4):435-444. 14. Aspelund T, Thornórisdóttir O, Olafsdottir E, et al. Individual risk assessment and information technology to optimise screening frequency for diabetic retinopathy. Diabetologia. 2011;54(10): 2525-2532.

PART 4

HYPERTENSIVE RETINO PATHY

18 HYPERTENSIVE RETINO PATHY He id i Chumle y, MD Ke lly Gre e n, MD

O PHTHALMO LO GY • Multiple studies show that patients with moderate HR are 2 to 3 times more likely to have a stroke than those without HR at the same level o blood pressure control independent o other risk actors. 2

ETIO LO GY AND PATHO PHYSIO LO GY High blood pressure results in the ollowing retinal f ndings3:

PATIENT STO RY A 37-year-old man comes in or a physical examination and is noted to have a blood pressure o 198/ 142 mmHg. He has no symptoms at the time. The physician per orms a dilated unduscopic examination and notes optic disc edema, cotton-wool spots, ame hemorrhages, dot-blot hemorrhages, arteriovenous nicking, and exudates (Figure 18-1). Fortunately, the remainder o the neurologic examination and the electrocardiography (ECG) are normal. The patient is sent to the emergency room to be evaluated urther and treated or a hypertensive emergency.

INTRO DUCTIO N Hypertensive retinopathy (HR) develops rom elevated blood pressure. HR is diagnosed clinically by the presence o classic retina f ndings seen on unduscopic examination or digital retinal photographs in a patient with hypertension. HR can result in vision loss. Treatment is control o blood pressure.

• Retinal vessels become narrow and straighten at diastolic blood pressure (DBP) o 90 to 110 mm Hg. • Arteriovenous “nicking” (white oval in Figure 18-1) occurs when the arteriolar wall enlarges rom arteriosclerosis, compressing the vein. Patients with hypertension are at risk or central and branch retinal vein occlusions, which can result in signif cant vision loss. • Microaneurysms and ame hemorrhages (Figures 18-1 and 18-2) result rom the increased intravascular pressure. Cotton-wool spots (dashed arrow in Figure 18-2) represent ischemia o the nerve f ber layer. Hard exudates indicate vascular leakage (see white arrowheads in Figure 17-1, Chapter 17). • DBP 110 to 115 mmHg causes leakage o plasma proteins and blood products resulting in retinal hemorrhages and hard exudates (Figures 18-1 to 18-4). • Optic nerve swelling occurs at DBP o 130 to 140 mmHg (see Figure 18-3).

DIAGNO SIS EPIDEMIO LO GY • Prevalence o 7.7% (black) versus 4.1% (Caucasians) in a population study o men and women between 49 and 73 years o age without diabetes.1

The diagnosis is made clinically rom typical retinal f ndings in a patient with hypertension. These f ndings can be seen using unduscopic examination or by viewing retinal digital images. Retinal digital images have a higher interobserver reliability than unduscopic examination. 4

FIGURE 18-1 Hyp e rte nsive re tinop athy with op tic d isc e d e ma, cotton-wool sp ots, ame he morrhag e s, d ot-b lot he morrhag e s, arte riove nous nicking , and e xud ate s. (Re p rod uce d with p e rmission from Eye Round s.o rg and The Unive rsity of Iowa.)

FIGURE 18-2 More ad vance d hyp e rte nsive re tinop athy with ame he morrhag e s (white arrow), arte riove nous nicking (white oval), and cotton-wool sp ots (d ashe d arrow). (Re p rod uce d with p e rmission from Paul D. Come au.)

93

94

PART 4

O PHTHALMO LO GY

Ch a pt e r 18

TYPICAL DISTRIBUTIO N Bilateral and symmetrical LABO RATO RY TESTING • Laboratory tests are not needed to make the diagnosis. • Recommended tests or patients with hypertension include urinalysis, blood glucose, hematocrit, serum potassium, creatinine, calcium, and a asting lipid prof le. • 12-lead ECG is also recommended. 5

DIFFERENTIAL DIAGNO SIS Retinal vessel narrowing, atrioventricular nicking, microaneurysms, retinal hemorrhages, hard exudates, and cotton-wool spots are also seen in other conditions that impair blood ow, including the ollowing: • Diabetic retinopathy (see Chapter 17, Diabetic Retinopathy) • Radiation retinopathy • Venous or carotid artery occlusive disease FIGURE 18-3 Malig nant hyp e rte nsive re tinop athy with op tic ne rve he ad e d e ma (p ap ille d e ma), ame he morrhag e s (white arrow), cotton-wool sp ots (b lack arrow), and macular e d e ma with e xud ate s (d ashe d arrows). The p atie nt was ad mitte d to the hosp ital to tre at malig nant hyp e rte nsion ag g re ssive ly. (Re p rod uce d with p e rmission fro m Paul D. Co me au.)

CLINICAL FEATURES Following are the clinical eatures in order o increasing severity: • Mild arteriolar narrowing • Severe arteriolar narrowing plus arteriovenous nicking • Retinal hemorrhages, microaneurysms, hard exudation, cotton-wool spots • Swelling o the optic nerve head and macular star, also called as accelerated or malignant HR

• Systemic illnesses such as collagen vascular disease • Hematologic diseases such as anemia and leukemia • Systemic in ectious diseases such as HIV Optic nerve swelling and a macular star (blurring o the macula in a star-like pattern) also occur in the ollowing: • Neuroretinitis • Diabetic papillopathy • Radiation optic retinopathy • Optic neuritis • Intracranial disease

MANAGEMENT Patients with unduscopic f ndings o HR should have their blood pressure measured and treated to reduce the risk o heart and cerebrovascular disease. 5 SO R A No np harmaco lo g ic • Assist patients in smoking cessation. This will result in the greatest benef t in morbidity and mortality. • Reduce weight or maintain normal body mass index (BMI). • Eat a diet rich in ruits and vegetables and low in saturated ats. • Reduce sodium to less than 6 g o sodium chloride per day. • Engage in regular physical activity or 30 minutes most days o the week. • Limit alcohol to 2 drinks per day in men and 1 drink per day in women. Me d icat io ns FIGURE 18-4 Branch re tinal ve in occlusion o a major re tinal ve in associate d with hyp e rte nsion. The p atie nt note d ne w onse t o b lurre d vision and visual f e ld constriction. Flame he morrhag e s are se e n along the course o the ob structe d ve in. (Re p rod uce d with p e rmission from Paul D. Come au.)

• Start a thiazide diuretic to achieve blood pressure o less than 140/ 90 mmHg unless contraindicated; a blood pressure goal o 130/ 80 mmHg should be used or patients with diabetes. Consider an

PART 4

h Ype r t e NSIVe r e t INO pa t h Y

angiotensin-converting enzyme inhibitor (ACEI) as an initial medication or patients with diabetes. Consider other medications only or patients with compelling indications. • Although the largest benef t in outcomes is seen with the f rst medication, additional medications should be considered to achieve blood pressure less than 140/ 90 mmHg a ter weighing the risks and benef ts with the patient. • Evaluate and manage other risk actors or cardiovascular disease, including high cholesterol and diabetes. REFERRAL Patients experiencing acute visual disturbances should be re erred or evaluation o hemorrhage or optic nerve edema (see Figures 18-3 and 18-4).

PREVENTIO N • Maintain normal blood pressure through a healthy li estyle and medications when needed. • Patients with hypertension alone do not require routine unduscopic examination, unless they also have diabetes mellitus. 6 SO R A • Prevention is obtained by preventing and controlling high blood pressure.

PRO GNO SIS • Prognosis is associated with severity o hypertension retinopathy. • Three-year survival in patients with mild arteriolar narrowing is 70% compared to 6% in patients with swelling o the optic nerve or macular star. 7

FO LLO W-UP Once diagnosed with hypertension, patients should be seen every month until blood pressure is controlled and then every 3 to 6 months. 4 SO R C

PATIENT EDUCATIO N • HR does not require treatment other than lowering blood pressure unless acute vision changes occur.

O PHTHALMO LO GY • Control o blood pressure typically reverses HR f ndings, except or optic nerve edema, which may result in permanent vision loss. • Control o blood pressure also reduces the risk o heart attack and stroke.

PATIENT RESO URCES

• PubMed Health. High blood pressure and eye disease—http:/ / www .ncbi.nlm.nih.gov/ pubmedhealth/ PMH0001994/ . PRO VIDER RESO URCES

• Medscape. Ophthalmologic Manifestations of Hypertension—http:/ / emedicine.medscape.com/ article/ 1201779. • The Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment o High Blood Pressure (JNC 8), 2012—http:/ / www.nhlbi.nih.gov/ guidelines/ hypertension/ jnc8/ index.htm.

REFERENCES 1. Wong TY, Klein R, Duncan BB, et al. Racial di erences in the prevalence o hypertensive retinopathy. Hypertension. 2003;41(5): 1086-1091. 2. Baker ML, Hand PJ, Wang JJ, Wong TY. Retinal signs and stroke: revisiting the link between the eye and brain. Stroke. 2008;39(4):1371-1379. 3. Luo BP, Brown GC. Update on the ocular mani estations o systemic arterial hypertension. Curr Opin Ophthalmol. 2004;15(3):203-210. 4. Castro AF, Silva-Turnes JC, Gonzalez F. Evaluation o retinal digital images by a general practitioner. Telemed J E Health. 2007;13(3): 287-292. 5. NIH, NHLBI, and National High Blood Pressure Education Program. The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, andTreatment of High Blood Pressure, 2004. Washington, DC: U.S. Department o Health and Human Services; 2006. 6. van den Born BJ, Hulsman CA, Hoekstra JB, et al. Value o routine unduscopy in patients with hypertension: systematic review. BMJ. 2005;331(7508):73. 7. Keith NM, Wagener HP, Barker NW. Some di erent types o essential hypertension: their course and prognosis. Am J Med Sci. 1939;197:332-343.

95

96

PART 4

O PHTHALMO LO GY

19 PAPILLEDEMA He id i Chumle y, MD

PATIENT STO RY

Ch a pt e r 19

SYNO NYMS Papilledema is also known as pseudotumor cerebri or benign intracranial hypertension.

EPIDEMIO LO GY Idiopathic intracranial hypertension (IIH) occurs in the ollowing:

A 29-year-old obese woman presented with chronic headaches that were worse in the morning or while lying down. She denied nausea or other neurologic symptoms. She had no other medical problems and took no medications. On examination, she had a visual acuity o 20/ 20 in both eyes, bilateral papilledema (Figure 19-1), no spontaneous venous pulsations (SVPs), and no other neurologic signs. She had a brain magnetic resonance imaging (MRI) showing no mass or hydrocephalus, and elevated intracranial pressure (ICP) measured by lumbar puncture. She was diagnosed with idiopathic intracranial hypertension (IIH) and was ollowed closely or any changes in her vision. She was started on acetazolamide and assisted with a weight loss program. Her symptoms resolved over the course o 18 months.

• About 1 per 100,000 people. 1 • About 20 per 100,000 obese emales o ages 15 to 44 years. 1 • Prevalence may be increasing with increasing obesity. A UK population study ound a prevalence o 85.7 per 100,000 in obese women. 2 • Mean age o diagnosis is approximately 30 years.

ETIO LO GY AND PATHO PHYSIO LO GY The optic disc swells because o elevated intracranial pressure. In IIH, the cerebral spinal uid pressure is increased. The cause o this increase in unknown, but a current hypothesis is that IIH is a syndrome o reduced cerebrospinal uid (CSF) absorption.

INTRO DUCTIO N The term papilledema re ers specif cally to optic disc swelling related to increased intracranial pressure. When no localizing neurologic signs or space-occupying lesion is present, IIH is a likely cause in patients younger than age 45 years, especially obese women. Patients with IIH usually present with daily pulsatile headache with nausea and o ten have transient visual disturbances and/ or pulsatile tinnitus. Patients o ten report a “whooshing” sound that they hear. Bilateral papilledema and visual f eld de ects on a perimetry test are ound in almost all patients. Elevated opening pressure on lumbar puncture is required or the diagnosis.

RISK FACTO RS IIH is much more common in obese women o childbearing age.

DIAGNO SIS Patients with papilledema should undergo imaging, pre erably MRI, ollowed by lumbar puncture. IIH is a diagnosis o exclusion with the ollowing criteria3: • Signs and symptoms o increased ICP (headache, transient visual disturbances, papilledema) are present. • Normal neurologic examination, except a sixth nerve palsy may be present. This will lead to a complaint o diplopia. • Elevated ICP is present, as measured by lumbar puncture opening pressure greater than 250 mm o water in the lateral decubitus position, with normal CSF on microscopic examination. • No evidence o mass, hydrocephalus, or vascular lesions is seen by MRI. • No other identif able cause o increased intracranial hypertension. CLINICAL FEATURES • More than 90% o patients with IIH are obese women o childbearing age. Look or a di erent diagnosis in children, men, and older patients.3 • Headaches and visual changes are the most common symptoms. • Di f culty in thinking or concentrating is requently reported. New studies indicate cognitive impairment, particularly in learning and memory.4

FIGURE 19-1 P p ill d m om inc s d int c ni l p ssu (ICP). T op tic d isc is l v t d nd yp mic wit ng o g d tin l v ins. T nti op tic d isc m g in is b lu d . O p tic n u o p t i s c n lso v b lu ing o t nti d isc m g in, b ut o t n, only p t o t d isc is b lu d . (Re p rod uce d with p e rmission from Paul D. Come au.)

• SVP are retinal vein pulsations at the optic disc and are typically absent in IIH patients. SVP are seen in 90% o patients with normal intracranial pressure, and are absent when the CSF pressure is above 190 mmHg. As the CSF pressure may be transiently normal in IIH, the presence o SVP does not preclude IIH, but indicates that the CSF pressure is normal at that moment. 5

PART 4

pa pILLe De Ma

O PHTHALMO LO GY Elevated ICP can also be caused by obstructing lesions, medical conditions, or medications3: • Mass lesions, hydrocephalus, venus sinus or jugular venus thrombosis, and meningeal in ections • Addison disease, hypoparathyroidism, chronic obstructive pulmonary disease (COPD), sleep apnea, renal ailure, pulmonary hypertension, and severe anemia • Antibiotics in the tetracycline amily, vitamin A, anabolic steroids, lithium, and corticosteroid withdrawal

MANAGEMENT

FIGURE 19-2 S v cut p p ill d m wit p p ill y f m mo g s nd cotton-wool sp ots t t ob scu t d isc v ss ls. T b lu d d g s o t o p tic d isc p p s st b u st. (Re p rod uce d with p e rmission from Paul D. Come au.)

TYPICAL DISTRIBUTIO N Papilledema is bilateral in the overwhelming majority o cases (see Figures 19-1 and 19-2). Unilateral optic disc swelling has been rarely noted with elevated intracranial pressure. LABO RATO RY TESTING Cerebral spinal uid is typically sent or cell count and culture. IMAGING • Traditionally, imaging was used to rule out intracranial mass or venus sinus obstruction; however, several imaging modalities show promise as tools that may mitigate the need or recurrent lumbar punctures to monitor pressures. • Transorbital sonography measurements o optic nerve sheath diameter detected raised ICP with a sensitivity o 90% and a specif city o 84%. 6 • Optical coherence tomography (OCT) is an imaging modality used in the ophthalmology o f ce that can distinguish between a normal optic disc, moderate elevation, and papilledema in patients with IIH based on di erences in retinal nerve f ber layer thickness. 7 • MRI f ndings in IIH include optic nerve tortuosity, partial empty sella, and transverse sinus narrowing. These changes reverse a ter pressure is reduced and return i pressure increases. 8

DIFFERENTIAL DIAGNO SIS • Pseudopapilledema or optic disc drusen, an optic nerve anomaly that elevates the optic disc sur ace and blurs the disc margins, which can be caused by calcif cations in the optic nerve head. • Optic neuropathies, swelling o all or parts o one or both discs, which can be caused by ischemia or demyelination (as in multiple sclerosis), and may be seen in 1% to 2% o patients with diabetes mellitus type 1 or 2. 9

In many cases, IIH is sel -limiting, presents without visual symptoms, and will resolve over several years without loss o vision. However, when patients present with persistent or worsening visual disturbances, treatment is required to lower the ICP to prevent optic nerve damage and irreversible loss o vision. Management o the headache is a key actor when choosing a therapeutic plan. Management includes the ollowing: • Nonpharmacologic ° Care ul observation (o ten by an ophthalmologist) with documentation o any visual changes. Formal visual f eld testing is indicated. ° Weight loss o 15% o body weight is benef cial but will1not decrease the ICP quickly enough i visual compromise is present. SO R C • Medications ° Acetazolamide 1000 to 2000 mg/ d; early studies indicate that topiramate may also be e ective; other diuretics such as urosemide are less e ective. 10 SO R C short time periods or rare cases o ° High-dose corticosteroids or1,10 SO R C rapidly advancing vision loss. • Re er or hospitalize ° Surgical interventions or severe, recalcitrant cases include optic nerve sheath enestration and lumbar peritoneal shunt. Surgery is also considered in special populations such as pregnant women and dialysis patients. 1,10 SO R C sinus stenting is a newer surgical technique that holds ° Transverse promise. 11

PREVENTIO N Maintenance o ideal body weight may prevent IIH.

PRO GNO SIS Although approximately two-thirds o patients with IIH present with visual impairment, the majority o patients improve. One study reported 9% o patients had permanent visual loss. 12

FO LLO W-UP Patients should be ollowed up every 3 to 6 months by a physician who can adequately view the entire optic disc and document visual acuity and visual f eld def cits. They should be seen immediately or any visual changes.

97

PART 4

98

O PHTHALMO LO GY PATIENT EDUCATIO N Advise patients with new papilledema o the need or an evaluation or dangerous causes o increased ICP, such as intracranial masses or underlying medical illnesses. Also advise patients that IIH o ten resolves spontaneously over several years, but they should report any visual changes immediately.

PATIENT RESO URCES

• The Intracranial Hypertension Research Foundation has information or patients—http:/ / www.ihrfoundation.org. PRO VIDER RESO URCES

• The Intracranial Hypertension Research Foundation has information or medical pro essionals including ongoing research studies and in ormation on patient registries—http:/ / www .ihrfoundation.org.

REFERENCES

Ch a PTe r 19

3. Friedman DI, Jacobson DM. Diagnostic criteria or idiopathic intracranial hypertension. Neurology. 2002;59(10):1492-1495. 4. Kharkar S, Hernandez R, Batra S, et al. Cognitive impairment in patients with pseudotumor cerebri syndrome. Behav Neurol. 2011;24(2):143-148. 5. Jacks AS, Miller NR. Spontaneous retinal venous pulsation: aetiology and signif cance. J Neurol Neurosurg Psychiatry. 2003;74(1):7-9. 6. Bauerle J, Nedelmann M. Sonographic assessment o the optic nerve sheath in idiopathic intracranial hypertension. J Neurol. 2011;258(11):2014-2019. 7. Waisbourd M, Leibovitch I, Goldenberg D, Kesler A. OCT assessment o morphological changes o the optic nerve head and macula in idiopathic intracranial hypertension. Clin Neurol Neurosurg. 2011;113(10):839-843. 8. George U, Bansal G, Pandian J. Magnetic resonance “ ip- op” in idiopathic intracranial hypertension. J Neurosci Rural Pract. 2011;2(1):84-86. 9. Bayraktar Z, Alacali N, Bayraktar S. Diabetic papillopathy in type II diabetic patients. Retina. 2002;22(6):752-758. 10. Friedman DI, Jacobson DM. Idiopathic intracranial hypertension. J Neuroophthalmol. 2004;24(2):138-145.

1. Mathews MK, Sergott RC, Savino PJ. Pseudotumor cerebri. Curr Opin Ophthalmol. 2003;14(6):364-370.

11. Ahmed RM, Wilkinson M, Parker GD, et al. Transverse sinus stenting or idiopathic intracranial hypertension: a review o 52 patients and o model predictions. AJNR Am J Neuroradiol. 2011;32(8):1408-1414.

2. Raoo N, Sharrack B, Pepper IM, Hickman SJ. The incidence and prevalence o idiopathic intracranial hypertension in She f eld, UK. Eur J Neurol. 2011;18(10):1266-1268.

12. Baheti NN, Nair M, Thomas SV. Long-term visual outcome in idiopathic intracranial hypertension. Ann Indian Acad Neurol. 2011;14(1):19-22.

PART 4

AGE-RELATED MACULAR DEGENERATIO N

20 AGE-RELATED MACULAR DEGENERATIO N He id i Chumle y, MD

PATIENT STO RY A 78-year-old white woman presents with loss o central vision that has gradually worsened over the last 6 months. Fully independent be ore, she can no longer drive and has di culty with activities o daily living. Her peripheral vision remains normal. Funduscopic examination reveals macular depigmentation and drusen (yellowish-colored subretinal deposits on the macula) (Figure 20-1). She is diagnosed with dry, age-related macular degeneration (AMD). A ter her physician discusses the available in ormation about antioxidants and therapeutic options, she decides to start antioxidants and see an ophthalmologist to discuss laser, surgical, or medical treatments.

INTRO DUCTIO N Age-related macular degeneration causes central vision loss in elderly patients. The pathophysiology o AMD is incompletely understood, but involves chronic changes in the retina and retinal pigment epithelium mediated by environmental and genetic actors. AMD is diagnosed by ophthalmoscopic detection o drusen. Healthy li estyle decreases the risk o development and progression o AMD. Re er patients to an ophthalmologist to evaluate or intravitreal injections, laser photocoagulation or photodynamic therapy, or surgery.

O PHTHALMO LO GY EPIDEMIO LO GY AMD is the leading cause o irreversible vision loss in the industrialized world. • Prevalence o advanced AMD is 1.4% in patients older than 40 years o age and 15% in white women older than 80 years o age. 1 • AMD that causes signi cant vision loss is more common in whites than blacks or Hispanics. 2 • Smoking increases the risk in women (relative risk [RR] 2.5 or current smokers; 2.0 or ormer smokers). 2 • AMD aggregates in amilies, but the speci c genetic and amilial risk actors are not clear. 2

ETIO LO GY AND PATHO PHYSIO LO GY AMD a ects central but not peripheral vision. Environment and genetic attributes increase the risk o these pathologic changes with aging. 3 • Oxidative stress rom the buildup o ree oxygen radicals causes retinal pigment epithelial (RPE) injury. • RPE injury evokes a chronic inf ammatory response. The complement system is involved and speci c polymorphisms o complement genes are associated with advanced disease and progression. 4 • RPE injury or inf ammation orms an abnormal extracellular matrix (ECM), which alters di usion o nutrients to the retina and RPE. • The abnormal ECM and di usion leads to retinal atrophy and new vessel growth.

RISK FACTO RS • For advanced AMD, strong risk actors are age, current cigarette smoking, previous cataract surgery (replaced lens provides less eye protection rom sunlight), and amily history o AMD. • Moderate risk actors include higher body mass index, history o cardiovascular disease, hypertension, and high plasma brinogen. • Weak or inconsistent risk actors include gender, ethnicity, diabetes, iris color, history o cerebrovascular disease, total cholesterol, highdensity lipoprotein, and triglyceride levels. 5

DIAGNO SIS Diagnosis is made by ophthalmoscopy. AMD can be dry (early, intermediate, or advanced) or wet (always considered advanced). • Early dry—May have no vision change; drusen present (Figure 20-2). • Intermediate dry—Distortion in the center o vision; multiple medium-sized drusen (see Figure 20-1). • Advanced dry—(Nonexudative) Signi cant central vision loss rom breakdown o support tissues around the macula.

FIGURE 20-1 Inte rme d iate , d ry, ag e -re late d macular d e g e ne ration wit macular d e p ig me ntation and d ruse n (ye llowis -colore d sub re tinal d e p osits on t e macula). T is p atie nt as ce ntral vision d istortion. (Re p rod uce d with p e rmission from Paul D. Come au.)

• Advanced wet—(Exudative) Gradual or sudden signi cant loss o vision; new onset o distortion in vision (straight lines appear wavy); abnormal blood vessels grow under the macula and can cause hemorrhage (Figure 20-3). Late changes include subretinal scarring and retinal atrophy (Figure 20-4).

99

100

PART 4

O PHTHALMO LO GY

FIGURE 20-2 Early, d ry, ag e -re late d macular d e g e ne ration d e monstrating d ruse n, ye llowis -colore d sub re tinal d e p osits on t e macula. Patie nts may ave no visual comp laints at t is stag e . (Re p rod uce d with p e rmissio n from Paul D. Come au.)

CLINICAL FEATURES • Symptoms that occur be ore vision loss include metamorphopsia (distorted vision) and central scotoma (impaired vision at the point o xation). 6 • Vision loss is central. Peripheral and night vision are generally not a ected. • Drusen is the classic physical examination nding (see Figures 20-1 and 20-2): ° Hard: small, yellow punctuate nodules ° So t: large pale yellow or grayish white with less distinct borders

Ch a pt e r 20

FIGURE 20-4 Late , we t, ag e -re late d macular d e g e ne ration (e xud ative ) wit sub re tinal scarring . Patie nts usually ave sig nif cant ce ntral vision loss re sulting rom d e struction o tissue around t e macula. (Re p rod uce d with p e rmission from Paul D. Come au.)

TYPICAL DISTRIBUTIO N Bilateral, although usually one eye is a ected be ore the other ANCILLARY TESTING Macular unction is impaired be ore visual loss and can be detected by tests including macular recovery unction and central visual eld sensitivity. 7 Optical coherence tomography (OCT) and f uorescein angiography are most commonly used to assess or leakage rom abnormal blood vessels. I leakage is present, this indicates that antivascular endothelial growth actor (anti-VEGF) treatment may help.

DIFFERENTIAL DIAGNO SIS Vision loss in the elderly can also be caused by any o the ollowing8: • Glaucoma (open-angle)—O ten asymptomatic until late in the disease, but then has visual eld de ects instead o central vision loss; unduscopic examination may reveal a large cup-to-disc ratio (see Chapter 16, Glaucoma). • Diabetic retinopathy—May have central vision loss with macular edema; unduscopic examination demonstrates microaneurysms, cotton-wool spots, hemorrhages, and exudates (see Chapter 17, Diabetic Retinopathy). • Cataracts—Blurred vision or glare; lens opacities seen when examining the red ref ex. Drusen can also be seen with the ollowing: • Pigmented nevi and choroidal malignant melanoma • Retinal detachment FIGURE 20-3 Late , we t, ag e -re late d macular d e g e ne ration (e xud ative ) wit sub re tinal e morr ag e s. Patie nts usually ave sig nif cant ce ntral vision loss. (Re p rod uce d with p e rmission from Paul D. Come au.)

• Glomerulonephritis, particularly membranoproli erative glomerulonephritis type II6

PART 4

a Ge -r e La t e D Ma CULa r De Ge Ne r a t IO N

MANAGEMENT

O PHTHALMO LO GY PATIENT EDUCATIO N

Re er to ophthalmologist to evaluate or treatments such as intravitreal injections, laser photocoagulation or photodynamic therapy, or surgery.

• AMD can cause a loss o vision leading to an inability to read and drive, thereby a ecting many activities o daily living.

• Nonpharmacologic ° Healthy li estyle that includes diet, exercise, and no smoking.

• A healthy li estyle may prevent development or progression o AMD.

• Medications ° Intraocular injections o pegaptanib and ranibizumab (anti-VEGFs) reduce the risk o visual acuity loss in patients with advanced neovascular AMD, number needed to treat (NNT) 3-14. 9 SO R A 10 Bevacizumab per orms similarly to ranibizumab. ° adverse ° Serious ocular or nonocular adverse events and mild ocular events occur in 1% and 5% o injections, respect ully. 11

• Most patients with AMD need to see an ophthalmologist regularly in addition to their primary care physician.

• Complementary or alternative therapy ° Consider antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and β-carotene, 15 mg) plus 80 mg zinc per day to decrease the risk o worsening vision loss in patients with intermediate to advanced AMD. 12 SO R B These antioxidants are available in single-tablet ormulations. Avoid β-carotene or smokers or people who have smoked in the last 10 years. REFERRAL • Most patients are treated by an ophthalmologist, and treatment may include intravitreal injections, laser photocoagulation or photodynamic therapy, or surgery. • Urgently re er a patient with a history o dry AMD and acute changes in vision (distortion o lines, objects) to an ophthalmologist or evaluation and treatment.

• Treatment options are available that decrease the risk o vision loss.

PATIENT RESO URCES

• The National Eye Institute has information for patients—http:/ / www.nei.nih.gov/ health/ maculardegen/ index.asp. PRO VIDER RESO URCES

• A tool for calculating the risk of advanced AMD—http:/ / caseyamdcalc.ohsu.edu/ . • Medscape. Exudative AMD—http:/ / emedicine.medscape .com/ article/ 1236030. • Medscape. Nonexudative AMD—http:/ / emedicine .medscape.com/ article/ 1233154.

REFERENCES 1. Friedman DS, O’Colmain BJ, Muñoz B, et al. Prevalence o agerelated macular degeneration in the United States. Arch Ophthalmol. 2004;123:564-572. 2. Seddon JM, Chen CA. The epidemiology o age-related macular degeneration. Int Ophthalmol Clin. 2004;44(4):17-39.

PREVENTIO N • Healthy diet—People with healthy diets, compared with nonhealthy diets, were 46% less likely to develop AMD. 13

3. Zarbin MA. Current concepts in the pathogenesis o age-related macular degeneration. Arch Ophthalmol. 2004;123(4):598-614.

• Physical activity—Active people, compared to inactive people, were 54% less likely to develop AMD. 13

4. Robman L, Baird PN, Dimitrov PN, et al. C-reactive protein levels and complement actor H polymorphism interaction in age-related macular degeneration and its progression. Ophthalmology. 2010;117(10):1982-1988.

• Healthy behaviors—People with a healthy diet who exercised and did not smoke, compared with people without these healthy behaviors, were 71% less likely to develop AMD. 13

5. Chakravarthy U, Wong TY, Fletcher A, et al. Clinical risk actors or age-related macular degeneration: a systematic review and metaanalysis. BMC Ophthalmol. 2010;10:31.

• Regular intake o age-related eye disease study (AREDS) ormula (vitamins A, C, and E, and zinc) may reduce the risk o AMD. 14

6. Kokotas H, Grigoriadou M, Petersen MB. Age-related macular degeneration: genetic and clinical ndings. Clin Chem Lab Med. 2011;49(4):601-616.

PRO GNO SIS Twenty- ve percent to 33% o patients with early age-related maculopathy (ARM), a precursor to AMD, progressed over a 7-year period. Smoking, elevated C-reactive protein, and speci c complement genotypes increase the risk o progression. 4

FO LLO W-UP Patients with ARM and AMD should have regular ollow-up with an ophthalmologist.

7. Midena E, Degli Angeli C, Blarzino MC, et al. Macular unction impairment in eyes with early age-related macular degeneration. Invest OphthalmolVis Sci. 1997;38(2):469-477. 8. Kroll P, Meyer CH. Which treatment is best or which AMD patient? Br J Ophthalmol. 2006;90(2):128-130. 9. Vedula SS, Krystolik MG. Antiangiogenic therapy with anti-vascular endothelial growth actor modalities or neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2008;16(2):CD005139. 10. Fadda V, Maratea D, Trippoli S, Messori A. Treatments or macular degeneration: summarizing evidence using network meta-analysis. Br J Ophthalmol. 2011;95(10):1476-1477.

101

102

PART 4

O PHTHALMO LO GY

Ch APTER 20

11. Van der Reis MI, La Heij EC, De Jong-Hesse Y, et al. A systematic review o the adverse events o intravitreal anti-vascular endothelial growth actor injections. Retina. 2011;31(8):1449-1469.

13. Mares JA, Voland RP, Sondel SA, et al. Healthy li estyles related to subsequent prevalence o age-related macular degeneration. Arch Ophthalmol. 2011;129(4):470-480.

12. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial o high-dose supplementation with vitamins C and E, beta carotene, and zinc or age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119(10):1417-1436.

14. Wong IY, Koo SC, Chan CW. Prevention o age-related macular degeneration. Int Ophthalmol. 2011;31(1):73-82.

PART 4

EYE TRAUMA—HYPHEMA

21 EYE TRAUMA—HYPHEMA He id i Chumle y, MD

PATIENT STO RY A 22-year-old man was hit in the eye with a baseball and presented to the emergency department with eye pain and redness and decreased visual acuity. There was a collection o blood in his anterior chamber (Figure 21-1) and he was diagnosed with a hyphema. He was given an eye shield or protection, advised to take acetaminophen or pain, and counseled not to engage in sporting activities until his hyphema resolved. He was re erred to ophthalmology urgently, but his eye was otherwise healthy. His hyphema resolved in 5 days.

O PHTHALMO LO GY ETIO LO GY AND PATHO PHYSIO LO GY • A hyphema is a collection o blood, mostly erythrocytes, that layer within the anterior chamber. • Trauma is the most common cause, o ten resulting rom a direct blow rom a projectile object such as a ball, air pellet or BB, rock, or st. • Direct orce to the eye (blunt trauma) orces the globe inward, distorting the normal architecture. • Intraocular pressure rises instantaneously causing the lens/ iris/ ciliary body to move posteriorly, thus disrupting the vascularization with resultant bleeding. • Intraocular pressure continues to rise and bleeding stops when this pressure is high enough to compress the bleeding vessels. • A brin-platelet clot orms and stabilizes in 4 to 7 days; this is eventually broken down by the brinolytic system and cleared through the trabecular meshwork.

INTRO DUCTIO N Hyphema, blood in the anterior chamber, can be seen ollowing eye trauma or as a result o clotting disturbances, vascular abnormalities, or mass e ects rom neoplasms. Traumatic hyphema occurs more o ten in boys and men, o ten related to work or sports. Hyphema typically resolves in 5 to 7 days, but some cases are complicated by rebleeding.

DIAGNO SIS The diagnosis o hyphema is clinical, depending on the classic appearance o blood layering in the anterior chamber. CLINICAL FEATURES

EPIDEMIO LO GY

History and physical • Layered blood in the anterior chamber.

• Hyphema occurs in 17 to 20 per 100,000 persons per year in the United States. 1

• History o eye trauma or risk actor or nontraumatic hyphema.

• Sixty percent o hyphemas result rom sports injuries. 2 Sports with higher risk or eye injuries include paintball, baseball or so tball, basketball, soccer, shing, ice hockey, racquet sports, encing, lacrosse, and boxing.

• Decreased vision.

• Increased intraocular pressure (32%). • Hyphemas are classi ed according to the amount o blood in the anterior chamber1: ° Grade 1: Less than one-third o the anterior chamber (see Figure 21-1); 58% o all hyphemas ° Grade 2: One-third to one-hal o the anterior chamber; 20% o all hyphemas ° Grade 3: One-hal to almost completely lled anterior chamber; 14% o all hyphemas ° Grade 4: Completely lled anterior chamber; 8% o all hyphemas • Eye trauma without hyphema (Figures 21-2 and 21-3) can lead to subconjunctival hemorrhage, anterior uveitis, and/ or distortion o the normal architecture, including globe rupture. LABO RATO RY TESTING (INCLUDE ANCILLARY TESTING, TO O ) Consider laboratory tests to evaluate or bleeding disorders: bleeding time, electrophoresis or sickle cell trait, platelet count, prothrombin and partial thromboplastin time, and liver tests. IMAGING

FIGURE 21-1 Laye ring o re d b lood ce lls in the ante rior chamb e r ollowing b lunt trauma. This g rad e 1 hyp he ma has b lood f lling in le ss than one -third o the ante rior chamb e r. (Re p rod uce d with p e rmission from Paul D. Come au.)

Consider computed tomography (CT) imaging i a mechanism o injury suggests an associated orbital racture or concern or orbital or intraocular oreign body.

103

104

PART 4

O PHTHALMO LO GY

Ch a pt e r 21

• Melanoma or retinoblastoma—Variety o presentations depending on the size and location; hyphema occurs when mass e ect shears the lens/ iris/ ciliary body causing bleeding. • Abnormal vasculature, that is, juvenile xanthogranuloma—Red to yellow papules and nodules in the eyes, skin, and viscera, most o ten present by 1 year o age.

MANAGEMENT • Most hyphemas resolve in 5 to 7 days; management strategies protect the eye and decrease complications, including rebleeding. • Evaluate or re er or evaluation or elevated intraocular pressure and other associated injuries. Urgent re erral i concern or globe rupture. FIGURE 21-2 This p atie nt was hit in the e ye with the corne r o a laminate d name card . The sharp e d g e p e r orate d the corne a and p ulle d a p ortion o the iris out o the wound . Note the ab normal conf g uration o the p up il (d yscoria). No hyp he ma note d . This p atie nt re q uire d e me rg e nt surg ical re p air. (Re p rod uce d with p e rmission from Paul D. Come au.)

DIFFERENTIAL DIAGNO SIS Hyphema is an unmistakable physical examination nding that can be caused by any o the ollowing: • Trauma—History o trauma, including nonaccidental trauma (ie, child abuse). • Blood clotting disturbances—Personal or amily history o bleeding disorder, little or no trauma, and black race (increased incidence o sickle trait and disease).

A recent Cochrane review evaluated these interventions: anti brinolytic agents, corticosteroids, cycloplegics, miotics, aspirin, conjugated estrogens, eye patching, head elevation, and bed rest. • No interventions had a signi cant e ect on visual acuity. • Aminocaproic acid (anti brinolytic) use resulted in a slower resolution o the primary hyphema. • Anti brinolytics: aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid reduced the rate o secondary hemorrhage. 3 NO NPHARMACO LO GIC Eye patching, head elevation, and bed rest do not independently a ect visual acuity. However, experts recommend to patch and shield the injured eye and allow the patient to remain ambulatory as part o a comprehensive treatment plan. 1 SO R C MEDICATIO NS

• Medication-induced anticoagulation—Chronic use o aspirin or war arin and little or no trauma.

Although controversy remains about the best treatment, each o the ollowing has been demonstrated to lower the risk o rebleeding in randomized-controlled trials:

• Neovascularization—Diabetes with diabetic retinopathy, history o other ocular disease (central retinal vein occlusion), or history o prior eye surgery (cataract); without trauma, o ten painless, sudden, blurry vision.

• Oral anti brinolytic agents (aminocaproic acid 50 mg/ kg every 4 hours or 5 days, not to exceed 30 g/ d, or tranexamic acid 75 mg/ kg per day divided into 3 doses). 4 SO R C • Topical aminocaproic acid (30% in a gel vehicle 4 times a day) is as e ective as oral. 4 SO R C • Avoid aspirin and nonsteroidal anti-inf ammatory drugs (NSAIDs) which have been associated with higher rates o rebleeding. • Use acetaminophen, i needed, or pain. REFERRAL O R HO SPITALIZATIO N • Signs o a violated globe, such as a per oration o the cornea, conjunctiva or sclera, distorted ocular architecture, or exposed and/ or distorted uveal tissue such as the iris (causing a peaked pupil), require immediate surgical evaluation and repair (see Figure 21-2). • Surgical intervention has been recommended or patients with persistent total hyphema or prolonged elevated intraocular pressure. • Outpatient management is acceptable or adults i patient is likely to be able to ollow treatment plan. 4,5 SO R B

PREVENTIO N FIGURE 21-3 Sub conjunctival he mo rrhag e and e ye lid e cchymosis ollowing accid e ntal trauma. The re was no hyp he ma p re se nt. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Ninety percent o sports-related eye injuries can be prevented with appropriate eyewear. 6

PART 4

EYE TRAUMA—HYPHEMA

PRO GNO SIS The percentage o patients who regain 20/ 40 vision varies by severity o the hyphema: grade I, 80%; grade III, 60%; grade IV, 35%. 1

O PHTHALMO LO GY PATIENT RESO URCES

• Play Hard Play Safe Web site has recommended eye protection by sport—http:/ / www.lexeye.com. • The National Eye Institute has information for parents, teachers, and coaches—http:/ / www.nei.nih.gov/ sports. PRO VIDER RESO URCES

FO LLO W-UP Patients should be monitored daily or the rst 5 or more days by a provider amiliar with caring or hyphemas. Patient with a hyphema should be ollowed subsequently or signs o angle recession and high intraocular pressure, which predisposes the patient to traumatic glaucoma, an insidious cause o blindness in patients with a history o trauma.

PATIENT EDUCATIO N • Complications include rebleeding, decreased visual acuity, posterior or peripheral anterior synechiae, corneal bloodstaining, glaucoma, and optic atrophy. Patients may need surgical or medical management or glaucoma. • Patients who are more likely to rebleed include black patients (irrespective o sickle cell/ trait status), 7,8 patients with a grade 3 or 4 hyphema, and patients with high initial intraocular pressure. • Warn patients that they may have angle recession rom traumatic causes o the hyphema. This will predispose the patient to a li etime risk o traumatic glaucoma, which can cause blindness without any symptoms. These patients need to be monitored regularly by an ophthalmologist or increased pressure and glaucomatous nerve changes.

• Coalition to prevent eye injuries has a variety of handouts suitable or displaying or giving to patients—http:/ / www .sportseyeinjuries.com.

REFERENCES 1. Sheppard J, Hyphema. Medscape Reference. http:/ / emedicine. medscape.com/ article/ 119016. Accessed June 15, 2012. 2. Schein OD, Hibberd PL, Shingleton BJ, et al. The spectrum and burden o ocular injury. Ophthalmology. 1988;95(3):300-305. 3. Gharaibeh A, Savage HI, Scherer RW, et al. Medical interventions or traumatic hyphema. Cochrane Database Syst Rev. 2011;19(1):CD005431. 4. Walton W, Von HS, Grigorian R, Zarbin M. Management o traumatic hyphema. Surv Ophthalmol. 2002;47(4):297-334. 5. Rocha KM, Martins EN, Melo LA Jr, Moraes NS. Outpatient management o traumatic hyphema in children: prospective evaluation. JAAPOS. 2004;8(4):357-361. 6. Harrison A, Telander DG. Eye injuries in the youth athlete: a casebased approach. Sports Med. 2002;l31(1):33-40. 7. Lai JC, Fekrat S, Barron Y, Goldberg MF. Traumatic hyphema in children: risk actors or complications. Arch Ophthalmol. 2001;119(1): 64-70. 8. Spoor TC, Kwitko GM, O’Grady JM, Ramocki JM. Traumatic hyphema in an urban population. Am J Ophthalmol. 1990;109(1):23-27.

105

106

PART 4

O PHTHALMO LO GY

Ch a pt e r 22

22 DIFFERENTIAL DIAGNO SIS O F THE RED EYE He id i Chumle y, MD Richard P. Usatine , MD

PATIENT STO RY A 41-year-old man wakes up with eyes that are reddened bilaterally (Figure 22-1). He has some burning and itching in the eyes, but no pain. He describes minimal crusting on his eyelashes. Examination shows no loss o vision, no oreign bodies, and pupils that are equal, round, and reactive to light. He is diagnosed with viral conjunctivitis, which does not require antibiotic treatment. He is advised about methods to prevent spreading conjunctivitis to others and is asked to noti y the physician immediately i he experiences eye pain or loss o vision. He recovers spontaneously without complications a ter a ew days.

FIGURE 22-2 Bacte rial conjunctivitis in a contact le ns use r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

ETIO LO GY AND PATHO PHYSIO LO GY INTRO DUCTIO N A red eye signif es ocular in ammation. The di erential diagnosis includes both benign and sight-threatening conditions. The pattern o redness; presence or absence o eye pain or photophobia, vision loss, or eye discharge; involvement o cornea; and visual acuity are help ul in di erentiating among causes (Table 22-1). Although most red eyes seen in the primary care setting are a result o viral conjunctivitis, several causes o red eye require urgent re erral.

EPIDEMIO LO GY • An acute red eye or eyes is a common presentation in ambulatory and emergency departments. • Conjunctivitis is the most common cause o a nontraumatic red eye in primary care.

FIGURE 22-1 Bilate ral viral conjunctivitis in a 41-ye ar-old man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Red eye is caused by any o the ollowing: • In ectious or nonin ectious in ammation o any layer o the eye (conjunctivitis, episcleritis, scleritis, uveitis, keratitis) • Eyelid pathology (blepharitis, entropion, ie, inward turning o the eyelid, or other eyelid malposition) • Acute glaucoma (usually angle-closure) • Trauma • Subconjunctival hemorrhage

DIFFERENTIAL DIAGNO SIS An acute red eye can be caused by any o the ollowing: • Conjunctivitis2—Conjunctival injection, eye discharge, gritty or uncom ortable eeling, and no vision loss (Figures 22-1 to 22-4) (see Chapter 13, Conjunctivitis).

FIGURE 22-3 Giant p ap illary conjunctivitis se cond ary to contact le ns use . (Re p rod uce d with p e rmission from Paul D. Come au.)

TABLE 22-1 Clinical Fe ature s in the Diag nosis o Re d Eye

Clo se d -Ang le Glauco ma

Sub co njunct ival O cular He mo rrhag e Ro sace a

Scle rit is

Uve it is

Ke rat it is

Re d ne ss

Di use

Se g me ntal; p ink

Se g me ntal or d i use ; d ark re d , p urp le , or b lue

360-De g re e p e rilimb al (worse at limb us)

Di use , ciliary inje ction

Di use , scle ral

Blotchy, outsid e ve sse ls

Di use

Eye p ain

No

Mild , may b e te nd e r to touch

Se ve re , b oring

Some time s

Usually

Ye s

No, unle ss cause d b y trauma

No

Vision loss

No

No

Some time s

Some time s

Mayb e , d e p e nd ing on location

Ye s

No

In se ve re case s

Discharg e

Usually

No

No

No

Mayb e

No

No

No

Photop hob ia * No

No

Ye s

Ye s, i ante rior

Ye s

Ye s

No

Some time s

Pup il

Normal

Normal

Normal

Constricte d

Normal to constricte d

Mild d ilation, le ss re sp onsive

Normal; unle ss a e cte d b y trauma

Normal

Corne a

Cle ar

Cle ar

Cle ar

Cle ar to hazy

Hazy

Usually hazy

Cle ar

Cle ar or ne ovascularization, cloud y

Associate d d ise ase s

URI, alle rg y, e xp osure

O ccasional syste mic d ise ase

Syste mic d ise ase

Syste mic d ise ase , id iop athic

Contact le nse s, Cause s he ad HSV or variache s, nauce lla, rosace a se a, vomiting , GI symp toms

HTN, trauma, Valsalva, coug h, b lood thinne rs

Acne rosace a (can e xist without also), b le p haritis

Y E O P H T

P

H

A

A

R

L

4

T

M O L O G

7

0

1

Y

HSV, he rp e s simp le x virus; HTN, hyp e rte nsion; URI, up p e r re sp iratory in e ction. * For id e nti ying se rious cause s o re d e ye , the p re se nce o p hotop hob ia e licite d with a p e nlig ht in a g e ne ral p ractice had a p ositive p re d ictive value o 60% and a ne g ative p re d ictive value o 90%.1

E

D

E

R

E

H

T

F

O

S

I

S

O

N

G

A

I

D

L

A

I

T

N

E

R

E

F

F

I

D

Conjunctivitis Ep iscle rit is

108

PART 4

O PHTHALMO LO GY

FIGURE 22-4 Conjunctival irritation cause d b y a e ck o me tal (at 9-o’clock p osition) that was e mb e d d e d in the e ye o a man who was g rind ing ste e l. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Ch a pt e r 22

FIGURE 22-6 Scle ritis with d e e p e r, d arke r ve sse ls than the e p iscle ritis. (Re p rod uce d with p e rmissio n from Paul D. Come au.)

• Episcleritis—Segmental or di use in ammation o episclera (pink color), mild or no discom ort, but can be tender to palpation, and no vision disturbance (Figure 22-5) (see Chapter 14, Episcleritis and Scleritis). • Scleritis—Segmental or di use in ammation o sclera (dark red, purple, or blue color), severe boring eye pain o ten radiating to head and neck, and photophobia and vision loss (Figure 22-6) (see Chapter 14, Episcleritis and Scleritis). • Keratitis or corneal ulcerations—Di use erythema with ciliary injection o ten with pupillary constriction; eye discharge; and pain, photophobia, vision loss depending on the location o ulceration (Figure 22-7). It is o ten associated with the use o contact lenses. • Subconjunctival hemorrhage (Figure 22-8)—Bright red subconjunctival blood; usually not pain ul; can present a ter signif cant coughing or sneezing, a ter trauma, or in the setting o dry eyes with minor trauma rom rubbing with a f nger. Not vision-threatening.

FIGURE 22-7 Di use ciliary inje ction and cloud y corne a d e monstrating ke ratitis with corne al ulce r ormation and a le ucocyte inf ltrate . (Re p rod uce d with p e rmission from Paul D. Come au.)

FIGURE 22-5 Ep iscle ritis showing a se ctor o e rythe ma. (Re p rod uce d with pe rmission from Richard P. Usatine , MD.)

FIGURE 22-8 Sub conjunctival he morrhag e se cond ary to trauma. (Re p rod uce d with p e rmission from Paul D. Come au.)

DIFFERENTIAL DIAGNO SIS O F THE RED EYE

FIGURE 22-9 O cular rosace a with ne w ve sse ls g rowing o nto the corne a. Many p atie nts with rosace a have some ocular f nd ing s includ ing b le p haritis (in ammation o the e ye lid ), conjunctivitis (most common), e p iscle ritis (rare ), ke ratitis, or corne al ulce ration/ne ovascularization. (Re p rod uce d with p e rmission from Paul D. Come au.)

PART 4

O PHTHALMO LO GY

FIGURE 22-11 Iritis (ante rior uve itis) with a limb al ush, re d to p urp le p e rilimb al ring . For contrast, note the p e rilimb al are a is not involve d in conjunctivitis, as b e st se e n in Fig ure 22-2. This p atie nt has e ye p ain and vision loss, which are also ab se nt in conjunctivitis. (Re p rod uce d with p e rmission from Paul D. Come au.)

• Ocular rosacea—Eye f ndings present in more than 50% o people with acial rosacea. Can present as blepharitis, conjunctivitis, or episcleritis or cause corneal ulcerations and neovascularization (Figures 22-9 and 22-10). • Uveitis or iritis—A 360-degree injection, which is most intense at the limbus, eye pain, photophobia, and vision loss (Figure 22-11) (see Chapter 15, Uveitis and Iritis). • Trauma causing globe injury, or hemorrhage into the anterior chamber called hyphema (Figures 22-12 and 22-13) (see Chapter 21, Eye Trauma—Hyphema). • Pterygium—Fibrovascular tissue on the sur ace o the eye extending onto the cornea (Figure 22-14) (see Chapter 9, Pterygium). • Hypopyon is a term or visible white cells (pus) layered out in the anterior chamber. It may be caused by in ammation o the iris or an eye in ection. The in ammation and/ or in ection also causes the conjunctiva and sclera to become red (Figure 22-15). • Acute angle-closure glaucoma—Cloudy cornea and scleral injection, shallow anterior chamber (check other eye i di f cult to assess chamber

FIGURE 22-12 Trauma to the e ye re sulting in an op e n g lob e injury with e xtrusion o some o the iris throug h the corne a and an ab normal p up il. The re is conjunctival inje ction and he morrhag e causing this re d e ye . (Re p rod uce d with p e rmission from Paul D. Come au.)

FIGURE 22-10 Se ve re ocular rosace a with b lood ve sse ls g rowing ove r the corne a le ad ing to b lind ne ss. (Re p rod uce d with p e rmission from Paul D. Come au.)

FIGURE 22-13 Hyp he ma with re d ce lls in the ante rior chamb e r and an in e rior b lood clot. (Re p rod uce d with p e rmission from Paul D. Come au.)

109

PART 4

110

O PHTHALMO LO GY

FIGURE 22-14 Pte ryg ium that o te n b e co me s irritate d and inje cte d . (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

depth in the red eye), eye pain with ipsilateral headache, and severe vision loss (see Chapter 16, Glaucoma). • Eyelid pathology—Blepharitis (in ammation o the eyelid) (Figure 22-16). Entropion is turning inward o the eyelid and can cause irritation to the conjunctiva and cornea.

MANAGEMENT

CHAPTER 22

FIGURE 22-16 Ble p haritis showing e rythe ma o the e ye lid s and aking in the e ye lashe s. Note the scale that has accumulate d in the e ye lashe s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• History o herpes simplex virus (HSV) eye disease • History o contact lens wear

PRO GNO SIS Prognosis depends on underlying cause (see corresponding chapters).

Treatment or specif c causes is discussed in the corresponding chapters. Re er patients with any o the ollowing to an ophthalmologist3: SOR C • Visual loss • Moderate or severe pain • Severe, purulent discharge • Corneal involvement • Conjunctival scarring • Lack o response to therapy • Topical steroid therapy

FO LLO W-UP Timing o ollow-up and need or urther testing is determined by the underlying cause (see corresponding chapters).

PATIENT EDUCATIO N Advise patients to noti y their physician immediately or eye pain (other than gritty discom ort) and/ or loss o vision.

• Recurrent episodes • Open globe or per oration

PATIENT RESO URCES

• Mayo Clinic. Red Eye—http:/ / www.mayoclinic.com/ health/ red-eye/ MY00280. PHYSICIAN RESO URCES

• Medscape. Red Eye—http:/ / emedicine.medscape.com/ article/ 1192122. REFERENCES 1. Yaphe J, Pandher K. The predictive value o the penlight test or photophobia or serious eye pathology in general practice. Fam Pract. 2003;20(4):425-427. 2. American Academy o Ophthalmology Cornea/ External Disease Panel, Pre erred Practice Patterns Committee. Conjunctivitis. San Francisco, CA: American Academy o Ophthalmology; 2003:25. FIGURE 22-15 Hyp op yon with white ce lls laye re d in the ante rior chamb e r. (Re p rod uce d with p e rmission from Paul D. Come au.)

3. Cronau H, Kankanala RR, Mauger T. Diagnosis and management o red eye in primary care. Am Fam Physician. 2010;81(2):137-144.

PART 5

EAR, NO SE, AND THRO AT

*

St re ng t h o Re co mme nd at io n (SO R)

De f nit io n

A

Re comme nd ation b ase d on consiste nt and g ood -q uality p atie nt-orie nte d e vid e nce .*

B

Re comme nd ation b ase d on inconsiste nt or limite d -q uality p atie nt-orie nte d e vid e nce .*

C

Re comme nd ation b ase d on conse nsus, usual p ractice , op inion, d ise ase -orie nte d e vid e nce , or case se rie s or stud ie s o d iag nosis, tre atme nt, p re ve ntion, or scre e ning .*

Se e Ap p e nd ix A on p ag e s 1241-1244 or urthe r in ormation.

112

PART 5

EAR, NO SE, AND THRO AT

SECTIO N 1

Ch a pt e r 23

EAR

23 O TITIS MEDIA: ACUTE O TITIS AND O TITIS MEDIA WITH EFFUSIO N Brian Z. Rayala, MD

PATIENT STO RY A 35-year-old business man comes to see his physician with le t ear pain. He had been traveling or work and was ghting a cold all week. He experienced plugging o both ears on the airplane f ight home 3 days ago. His right ear cleared quickly but his le t ear remained plugged and rom the last day he had been experiencing pain. On otoscopy, his le t tympanic membrane (TM) appears retracted and slightly erythematous (Figure 23-1). His le t TM ails to move on pneumatic otoscopy. The physician diagnoses acute otitis media and prescribes a 10-day course o amoxicillin.

INTRO DUCTIO N Acute otitis media (AOM) is characterized by middle-ear e usion in a patient with signs and symptoms o acute illness (eg, ever, otalgia). Otitis media with e usion (OME) is a disorder characterized by f uid in the middle ear in a patient without signs and symptoms o acute ear in ection; it is very common in children.

EPIDEMIO LO GY • AOM accounted or $5 billion o the total national health expenditure in 2000. 1 • While the vast majority o children has had an episode o AOM by 2 to 3 years o age, 2 ew adults experience purulent otitis media. In one retrospective study and literature review, the incidence was 0.25%. 3 • Based on a study rom the International Primary Care Network, adults make up ewer than 20% o patients presenting with AOM. 4 • AOM is the most common reason or outpatient antibiotic treatment in the United States. 5 • The combined direct and indirect health care costs o OME, diagnosed in over 2 million children, amount to $4 billion annually. 6

ETIO LO GY AND PATHO PHYSIO LO GY AOM is o ten preceded by upper respiratory symptoms such as cough and rhinorrhea. • Pathogenesis o AOM includes the ollowing7: ° Eustachian tube dys unction (usually a result o an upper respiratory in ection) and subsequent tube obstruction ° Increased negative pressure in the middle ear ° Accumulation o middle-ear f uid ° Microbial growth ° Suppuration (that leads to clinical signs o AOM). • Most common pathogens in the United States and United Kingdom are as below8,9: ° Strains o Streptococcus pneumoniae not in the heptavalent pneumococcal vaccine (PCV7) (a ter introduction o PCV7 vaccine in 2000) ° Nonencapsulated (nontypeable) Haemophilus inf uenzae (NTHi) ° Moraxella catarrhalis ° Staphylococcus aureus. • In an older study o 34 adults with otitis media, H. inf uenzae and S. pneumoniae were cultured rom 9 and 7 patients (26% and 21%), respectively. 10 • Viruses account or 16% o cases. Respiratory syncytial viruses, rhinoviruses, inf uenza viruses, and adenoviruses have been the most common isolated viruses. 11 OME most commonly ollows AOM; it may also occur spontaneously. • Fluid limits sound conduction through the ossicles and results in decreased hearing. • Reasons or the persistence o f uid in otitis media remain unclear, although potential etiologies include allergies, bio lm, and physiologic eatures. • “Glue ear” re ers to extremely viscous mucoid material within the middle ear and is a distinct subtype o OME.

FIGURE 23-1 Early acute otitis me d ia (AO M) at the stag e o e ustachian tub e ob struction. Note the slig ht re traction o the TM, the more horizontal p osition o the malle us, and the p romine nce o the late ral p roce ss. (Re p rod uce d with p e rmission from William Clark, MD.)

RISK FACTO RS The most important risk actor in adults is smoking.

O t It IS Me DIa : a CUt e O t It IS a ND O t It IS Me DIa WIt h e FFUSIO N

PART 5

EAR, NO SE, AND THRO AT

DIAGNO SIS CLINICAL FEATURES O F AO M • To diagnose AOM, the clinician should con rm a history o acute onset, identi y signs o middle-ear e usion (MEE), and evaluate or the presence o signs and symptoms o middle-ear inf ammation. 6 SO R C • Elements o the de nition o AOM are all o the ollowing6: 1. Recent, usually abrupt, onset o signs and symptoms o middleear inf ammation and MEE. 2. The presence o MEE (Figure 23-2). Although MEE is o ten presumed by erythema o the TM (see Figure 23-1), bulging o the TM (Figure 23-3) or air–f uid level behind the TM (see Figure 23-2), the guideline stresses use o objective measures o con rming MEE such as the ollowing6: a. Limited or absent mobility o the TM established by pneumatic otoscopy—The TM does not move during air insu f ation; o ten initially seen as retraction o the TM (Figures 23-1 and 23-4). b. Objective measures such as tympanometry. c. Otorrhea. 3. Signs or symptoms o middle-ear inf ammation as indicated by either o the ollowing: a. Distinct erythema o the TM (see Figures 23-1 and 23-3) in contrast to the normal TM (Figure 23-5), or b. Distinct otalgia (discom ort clearly re erable to the ear[s] that results in inter erence with or precludes normal activity or sleep). CLINICAL FEATURES O F O ME • The most common symptom, present in more than hal o patients, is mild hearing loss.

FIGURE 23-3 Acute otitis me d ia, stag e o sup p uration. Note p re se nce o p urule nt e xud ate b e hind the TM, the outward b ulg ing o the TM, p romine nce o the p oste rosup e rior p ortion o the d rum, and g e ne ralize d TM e d e ma. The white are a is tymp anoscle rosis rom a p re vious in e ction. (Re p rod uce d with p e rmission from William Clark, MD.)

• Common otoscopic ndings include the ollowing: ° Air–f uid level or bubble (see Figure 23-2). ° Cloudy TM (see Figure 23-1) in contrast to the normal TM (see Figure 26-5). ° Redness o the TM may be present in approximately 5% o ears with OME.

• Absence o signs and symptoms o acute illness assists in di erentiating OME rom AOM.

FIGURE 23-2 O titis me d ia with e usion (O ME) in the rig ht e ar. Note multip le air– uid le ve ls in this slig htly re tracte d , transluce nt, none rythe matous tymp anic me mb rane . (Re p rod uce d with p e rmission from Frank Mille r, MD.)

FIGURE 23-4 O titis me d ia with e usion in the le t e ar showing re traction o the TM and straig hte ning o the hand le o the malle us as the re traction p ulls the b one up ward . (Re p rod uce d with p e rmission fro m Gle n Me d e llin, MD.)

113

114

PART 5

EAR, NO SE, AND THRO AT

Ch a pt e r 23

LABO RATO RY TESTS AND IMAGING • Because AOM and OME are clinical diagnoses, diagnostic testing has a limited role. When clinical presentation and physical examination (including otoscopy) do not establish the diagnosis, the ollowing can be used as adjunctive techniques: ° Tympanometry—This procedure records compliance o the TM by measuring ref ected sound. AOM and OME will plot as a reduced or f at wave orm. ° Acoustic ref ectometry—This procedure, very similar to tympanometry, measures sound ref ectivity rom the middle ear. With this test, the clinician is able to distinguish air- or f uid- lled space without requiring an airtight seal o the ear canal. ° Middle ear aspiration—For patients with AOM, aspiration may be warranted i patient is toxic, immunocompromised, or has ailed prior courses o antibiotics.

DIFFERENTIAL DIAGNO SIS The key di erentiating eature between AOM and OME is the absence o signs and symptoms o acute illness in OME (eg, ever, irritability, otalgia). Otoscopic ndings may be similar. Other clinical entities that may be con used with AOM and OME include the ollowing: • Otitis externa—Otitis externa presents with otalgia, otorrhea, and mild hearing loss, all o which can be present in AOM. Tragal pain on physical examination and signs o external canal inf ammation on otoscopic examination di erentiate it rom AOM. Care ul ear irrigation i tolerated may be help ul to visualize the TM to di erentiate otitis externa rom AOM (see Chapter 24, Otitis Externa). • Otitic barotrauma—This o ten presents with severe otalgia. Key historical eatures include recent air travel, scuba diving, or ear trauma, preceded by an upper respiratory in ection. • Cholesteatoma—Unlike AOM, this is a clinically silent disease in its initial stages. Presence o white keratin debris in the middle ear cavity (on otoscopy) is diagnostic (Figures 23-6 and 26-7).

FIGURE 23-5 A. Normal rig ht tymp anic me mb rane with comp arison using normal b ony land marks o the inne r e ar. B. The ossicle s we re re move d in this d isse ction. (Re p rod uce d with p e rmission from William Clark, MD.)

• Clinicians should use pneumatic otoscopy as the primary diagnostic method or OME. 12 SO R A ° Impaired mobility o the TM is the hallmark o MEE. ° According to a meta-analysis, impaired mobility on pneumatic otoscopy has a pooled sensitivity o 94% and speci city o 80%, and positive likelihood ratio o 4.7 and negative likelihood ratio o 0.075. 12

FIGURE 23-6 Chole ste atoma. (Re p rod uce d with p e rmission from Vlad imir Zlinsky, MD, in Roy F. Sullivan, PhD. Aud io log y Forum: Vid e o O to scop y, www.rcsullivan.com.)

O t It IS Me DIa : a CUt e O t It IS a ND O t It IS Me DIa WIt h e FFUSIO N

PART 5

EAR, NO SE, AND THRO AT

A

FIGURE 23-7 Primary acq uire d chole ste atoma with d e b ris re move d rom the attic re traction p ocke t. (Re p rod uce d with p e rmission from William Clark, MD.)

• Foreign body—A oreign body may present with otalgia. Otoscopy reveals presence o oreign body (see Chapter 25, Ear: Foreign Body). • Bullous myringitis—Bullous myringitis is o ten associated with viral or mycoplasma in ection as well as usual AOM pathogens; in approximately one-third o patients, there is a component o sensorineural hearing loss. Otoscopy shows serous- lled bulla on the sur ace o the TM (Figure 23-8). Patients present with severe otalgia.

B FIGURE 23-9 A. Mastoid itis in a man with 4 we e k history o an e ar in e ction. The use o an inap p rop riate antib iotic without ap p rop riate ollow up re sulte d in “maske d mastoid itis”. CT scan showe d b o ne e rosion intracranially and late rally as a sub p e rioste al ab sce ss. B. Ne e d le asp iration o the ab sce ss re sulte d in ove r 20 mL o p us b e ing d raine d b e ore a mastoid e ctomy was p e r orme d . The p atie nt und e rwe nt mastoid e ctomy in the op e rating room to cle an out the re maining in e ction. Fortunate ly he d id not d e ve lop a b rain ab sce ss and he re cove re d ully a te r surg e ry. (Re p rod uce d with p e rmission from Rand al A. O tto, MD.)

• Chronic suppurative otitis media (CSOM)—Otoscopy shows TM peroration and otorrhea; history reveals a chronically draining ear and recurrent middle-ear in ections with or without hearing loss. • Re erred otalgia—This is rare in cases o bilateral otalgia, but should be considered in cases o otalgia that do not t clinical eatures o AOM. Re erred pain is usually rom other head and neck structures (eg, teeth, jaw, cervical spine, lymph and salivary glands, nose and sinuses, tonsils, tongue, pharynx, meninges).

FIGURE 23-8 Bullous myring itis can b e d i e re ntiate d rom otitis me d ia with e usion b y id e nti ying se rous-f lle d b ulla on the sur ace o the TM. (Re p rod uce d with p e rmission from Vlad imir Zlinsky, MD, in Roy F. Sullivan, PhD. Aud iolog y Forum: Vid e o O toscop y, www.rcsullivan.com.)

• Mastoiditis—Mastoiditis can be di erentiated rom simple AOM by presence o increasing pain and tenderness over mastoid bone in a patient with AOM who has not been treated with antibiotics, or recurrence o mastoid pain and tenderness in patients treated with antibiotics. Recurrence or persistence o ever, as well as progressive otorrhea, are other historical clues. The mastoid swelling may cause the pinna to protrude urther than normal (Figure 23-9). • Traumatic per oration o the TM (Figure 23-10)—A hole in the TM is seen without purulent drainage.

115

116

PART 5

EAR, NO SE, AND THRO AT

Ch a pt e r 23

° Antibiotics ound to be e ective in AOM include amoxicillin,

amoxicillin/ clavulanic acid, ampicillin, penicillin, erythromycin, azithromycin, trimethoprim-sul amethoxazole, and cephalosporins. ° Longer (8- to 10-day) courses o antibiotics reduce short-term treatment ailure but have no long-term bene ts compared with shorter regimens (5-day courses). 13,15 • Immediate antibiotic treatment (ie, given at initial consultation) may reduce the duration o symptoms o AOM, but increases the risk o vomiting, diarrhea, and rash compared with delayed treatment (ie, given a ter 72 hours). 13 SO R B • Treatment o AOM with decongestants and antihistamines is not recommended. 16 SO R B • Antihistamines and decongestants are not e ective or OME. 6

SO R

A

• Antimicrobials and corticosteroids are not recommended or OME. 6 SO R A

FIGURE 23-10 Traumatic p e r oration o the le t tymp anic me mb rane . (Re p rod uce d with p e rmission from William Clark, MD.)

REFERRAL • Re er to specialist (otolaryngologist, audiologist, or speech-language pathologist) or the ollowing reasons6: SO R C ° Persistent f uid or 4 or more months with persistent hearing loss ° Structural damage to TM or middle-ear

MANAGEMENT Most studies on management o AOM and OME have been per ormed with children. In the absence o data, the ollowing is o ered as likely to be use ul in adults. NO NPHARMACO LO GIC Antibiotics are not necessary to treat uncomplicated AOM. 13 SO R A Management o OME primarily consists o watch ul waiting. Most cases resolve spontaneously within 3 months; only 5% to 10% last 1 year or longer. Treatment depends on duration and associated conditions. The ollowing options should be considered:

PREVENTIO N • Xylitol chewing gum or syrup given 5 times daily has a small preventive e ect on recurrence o AOM. 13 SO R B • Tympanostomy tubes lead to short-term reduction in the number o episodes o AOM in children but increase the risk o complications (ie, tympanosclerosis; Figure 23-11). 13 SO R B

• Document the laterality, duration o e usion, and presence and severity o associated symptoms. 6 SO R C • Hearing testing is recommended when OME persists in children or 3 months or longer6 (SO R B ), but its role in adults is unclear. • Autoinf ation with a nasal balloon has been shown to provide shortterm bene ts in children, and adults can be taught to insu f ate the ears by holding their nose, closing their mouth, and trying to blow their nose. MEDICATIO NS • Oral acetaminophen (paracetamol) and ibupro en may reduce earache. ° There is insu cient14data to evaluate the e ectiveness o topical analgesics in AOM. SO R B • Antibiotics may lead to more rapid reduction in symptoms o AOM, but increase the risk o adverse e ects, including diarrhea, vomiting, and rash. 13 SO R B ° Antibiotics seem to reduce pain at 2 to 7 days, and may prevent development o contralateral AOM, but increase the risks o adverse e ects compared with placebo. o data regarding which antibiotic ° There is insu cient e ectiveness regimen is better than another. 13

FIGURE 23-11 Tymp anoscle rosis as the re sult o p re vious re curre nt e p isod e s o otitis me d ia and p olye thyle ne (PE) tub e p lace me nt. (Re p rod uce d with p e rmission from Gle n Me d e llin, MD.)

O t It IS Me DIa : a CUt e O t It IS a ND O t It IS Me DIa WIt h e FFUSIO N

PRO GNO SIS

PART 5

EAR, NO SE, AND THRO AT PATIENT RESO URCES

Acute Otitis Media

• Without antibiotics, AOM resolves within 24 hours in approximately 60% o children and within 3 days in approximately 80% o children. Rate o suppurative complications i antibiotics are withheld is 0.13%. 17

• Medline Plus. Ear in ection-acute—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000638.htm.

• Most cases o OME resolve spontaneously within 3 months; only 5% to 10% last 1 year or longer. However, e usion will recur in 30% to 40% o patients. 6

• FamilyDoctor.org. Middle Ear In ections—http:/ / www .kidshealth.org/ PageManager.jsp?dn=familydoctor&lic= 44&article_set=22743.

FO LLO W-UP • I a patient with AOM ails to respond to the initial management option within 48 to 72 hours, the clinician should reassess the patient to con rm AOM and exclude other causes o illness. I AOM is conrmed in a patient initially managed with observation, the clinician should begin antibiotics. I the patient was initially managed with antibiotics, the clinician should change antibiotics. 6 SO R B • Potentially serious complications o AOM, such as mastoiditis or acial nerve involvement, require urgent re erral. • There is no consensus in the medical community regarding timing o posttreatment ollow-up o AOM or who should be receiving ollowup. There is some evidence that parents can be reliable predictors in the resolution or persistence o AOM ollowing antibiotic treatment. 18

PATIENT EDUCATIO N • Smoking cessation should be recommended and assistance o ered to smokers (see Chapter 237, Tobacco Addiction). • Parents should be made aware o the high rates o spontaneous resolution o AOM and potential adverse e ects o antibiotics. Providing a prescription or an antibiotic at the initial visit but advising delay o initiation o medication (ie, observational approach or up to 48 hours) is an alternative to immediate treatment and is associated with lower antibiotic use. 19 • Patients should be in ormed that the natural history o OME is spontaneous resolution. ° Periodic ollow-up to monitor resolution o MEE is important and i MEE with hearing loss persists, additional treatment or re erral may be considered.

• NIDCD. Ear In ections in Children—http:/ / www.nidcd.nih.gov/ health/ hearing/ earinfections.

• NHS. Middle ear in ection (otitis media)—http:/ / www.nhs.uk/ conditions/ Otitis-media/ Pages/ Introduction.aspx. Otitis Media with Effusion • Medline Plus. Otitis Media with E usion—http:/ / www.nlm.nih .gov/ medlineplus/ ency/ article/ 007010.htm. PRO VIDER RESO URCES

Acute Otitis Media • Guideline: diagnosis and management of acute otitis media. Clinical Practice Guideline by the American Academy o Family Physicians, American Academy o Otolaryngology-Head and Neck Surgery, and American Academy o Pediatrics Subcommittee on Management o Acute Otitis Media. Pediatrics. 2004;113:1451-1465. • NHS. Acute otitis media—http:/ / www.npc.nhs.uk/ merec/ infect/ commonintro/ resources/ merec_bulletin_vol17_ no3_acute_otitis_media.pdf. • British Columbia Medical Association. Acute Otitis Media (AOM)—http:/ / www.bcguidelines.ca/ pdf/ otitaom.pdf. • General Practice Notebook. Acute Otitis Media (AOM)—http:/ / www.gpnotebook.co.uk/ simplepage.cfm?ID=1926234161. Otitis Media with Effusion • British Columbia Medical Association. Otitis Media with E usion (OME)—http:/ / www.bcguidelines.ca/ pdf/ otitome.pdf.

REFERENCES 1. Bondy J, Berman S, Glazner J, Lezotte D. Direct expenditures related to otitis media diagnoses: extrapolations rom a pediatric medicaid cohort. Pediatrics. 2000;105(6):E72. 2. Paradise JL, Rockette HE, Colborn DK, et al. Otitis media in 2253 Pittsburgh-area in ants: prevalence and risk actors during the rst two years o li e. Pediatrics. 1997;99(3):318-333. 3. Schwartz LE, Brown RB. Purulent otitis media in adults. Arch Intern Med. 1992;152(11):2301-2304. 4. Culpepper L, Froom J, Bartelds AI, et al. Acute otitis media in adults: a report rom the International Primary Care Network. JAm Board Fam Pract. 1993;6:333-339. 5. Del Mar C, Glasziou P, Hayem M. Are antibiotics indicated as initial treatment or children with acute otitis media? A meta-analysis. BMJ. 1997;314:1526-1529. 6. Guideline: otitis media with e usion. Clinical practice guideline by the American Academy o Family Physicians, American Academy o Otolaryngology-Head and Neck Surgery, and American Academy o Pediatrics Subcommittee on Otitis Media With E usion. Pediatrics. 2004;113:1412-1429.

117

118

PART 5

EAR, NO SE, AND THRO AT 7. Rovers MM, Schilder AG, Zielhuis GA, Rosen eld RM. Otitis media. Lancet. 2004;363:465. 8. Casey JR, Adlowitz DG, Pichichero ME. New patterns in the otopathogens causing acute otitis media six to eight years a ter introduction o pneumococcal conjugate vaccine. Pediatr In ect Dis J. 2010;29(4):304-309. 9. McEllistrem MC. Acute otitis media due to penicillin-nonsusceptible Streptococcus pneumoniae be ore and a ter the introduction o the pneumococcal conjugate vaccine. Clin In ect Dis. 2005;40(12):1738-1744.

CHAPTER 23

14. Foxlee R, Johansson A, Wej alk J, Dawkins J, Dooley L, Del Mar C. Topical analgesia or acute otitis media. Cochrane Database Syst Rev. 2006;3:CD005657. 15. Kozyrskyj AL, Hildes-Ripstein GE, Longsta e SE, et al. Shortcourse antibiotics or acute otitis media. Cochrane Database Syst Rev. 2000;(2):CD001095. 16. Flynn CA, Gri n GH, Schultz JK. Decongestants and antihistamines or acute otitis media in children. Cochrane Database Syst Rev. 2004;3:CD001727.

10. Celin SE, Bluestone CD, Stephenson J, et al. Bacteriology o acute otitis media in adults. JAMA. 1991;266(16):2249-2252.

17. Rosen eld RM. Natural history o untreated otitis media. Laryngoscope. 2003;113:1645-1657.

11. Ruuskanen O, Arola M, Heikkinen T, Ziegler T. Viruses in acute otitis media: increasing evidence or clinical signi cance. Pediatr In ect Dis J. 1991;10:425.9.

18. Raimer PL. Parents Can Be Reliable Predictors in the Resolution or Persistence o Acute Otitis Media Following AntibioticTreatment. University o Michigan Department o Pediatrics Evidence-based Pediatrics Web site. 2005. http:/ / www.med.umich.edu/ pediatrics/ ebm/ cats/ omparent.htm. Accessed February 2012.

12. Takata GS, Chan LS, Morphew T, et al. Evidence assessment o the accuracy o methods o diagnosing middle ear e usion in children with otitis media with e usion. Pediatrics. 2003;112:1379-1387. 13. Williamson I. Otitis media with e usion in children. Clin Evid. 2011;01:502-531.

19. Spiro DM, Tay KY, Arnold DH, et al. Wait-and-see prescription or the treatment o acute otitis media: a randomized controlled trial. JAMA. 2006;296:1235-1241.

O TITIS EXTERNA

PART 5

EAR, NO SE, AND THRO AT

24 O TITIS EXTERNA Brian Z. Rayala, MD

PATIENT STO RY A 40-year-old woman with type 2 diabetes presents to her amily physician with a 2-day history o bilateral otalgia, otorrhea, and hearing loss. Symptoms started in the right ear and then rapidly spread to the le t ear. She had a low-grade ever and was systemically ill. The external ear was swollen with honey-crusts (Figures 24-1 and 24-2). The external auditory canal (EAC) was narrowed and contained purulent discharge (Figure 24-3). Ear, nose, and throat (ENT) was consulted and she was admitted to the hospital or the presumptive diagnosis o malignant otitis externa. The magnetic resonance imaging (MRI) showed some destruction o the temporal bone. She was started on IV cipro oxacin and the ear culture grew out Pseudomonas aeruginosa sensitive to cipro oxacin. The patient responded well to treatment and was able to go home on oral cipro oxacin 5 days later.

FIGURE 24-2 Anot e vie w of t e malig nant o ne c otizing otitis e xte na. (Re p rod uce d with p e rmission from E.J. Maye aux, MD.)

FIGURE 24-1 Malig nant o ne c otizing otitis e xte na in a 40-ye a -old woman wit d iab e te s. Note t e swe lling and one y-c usts of t e inna. T e EAC and te m o al b one we e involve d . (Re p rod uce d with p e rmission from E.J. Maye aux, MD.)

FIGURE 24-3 C onic su u ative otitis me d ia wit u ule nt d isc a g e c onically d aining f om t e e a of t is 25-ye a -old man. T is imag e could b e se e n in acute otitis me d ia wit e fo ation of t e tym anic me mb ane o in a u ule nt otitis e xte na. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

119

120

PART 5

EAR, NO SE, AND THRO AT

Ch a pt e r 24

INTRO DUCTIO N Otitis externa (OE) is common in all parts o the world. OE is def ned as in ammation, o ten with in ection, o the EAC. 1

EPIDEMIO LO GY • Incidence o OE is not known precisely; its li etime incidence was estimated at 10% in one study. 2 • Occurs more o ten in adults than in children.

ETIO LO GY AND PATHO PHYSIO LO GY • Common pathogens, which are part o normal EAC ora, include aerobic organisms predominantly (P. aeruginosa and Staphylococcus aureus) and, to a lesser extent, anaerobes (Bacteroides and Peptostreptococcus). Up to a third o in ections are polymicrobial. A small proportion (2-10%) o OE is caused by ungal overgrowth (eg, Aspergillus niger usually occurs with prolonged antibiotic use). 1 • Pathogenesis o OE includes the ollowing: ° Trauma, the usual inciting event, leads to breech in the integrity o EAC skin. ° Skin in ammation and edema ensue, which, in turn, lead to pruritus and obstruction o adnexal structures (eg, cerumen glands, sebaceous glands, and hair ollicles). ° Pruritus leads to scratching, which results in urther skin injury. ° Consequently, the milieu o the EAC is altered (ie, change in quality and quantity o cerumen, increase in pH o EAC, and dys unctional epithelial migration). ° Finally, the EAC becomes a warm, alkaline, and moist environment—ideal or growth o di erent pathogens.

RISK FACTO RS • Environmental actors3 ° Moisture—Macerates skin o EAC, elevates pH, and removes protective cerumen layer ( rom swimming, perspiration, high humidity). ° Trauma—Leads to injury o EAC skin ( rom cotton buds, f ngernails, hearing aids, ear plugs, paper clips, match sticks, mechanical removal o cerumen). ° High environmental temperatures. • Host actors ° Anatomic—Wax and debris accumulate and lead to moisture retention (eg, a narrow ear canal, hairy ear canal). ° Cerumen—Absence or overproduction o cerumen (leads to loss o the protective layer and moisture retention, respectively). ° Chronic dermatologic disease (eg, atopic dermatitis, psoriasis, seborrheic dermatitis). ° Immunocompromise (eg, chemotherapy, HIV, AIDS).

DIAGNO SIS CLINICAL FEATURES • OE can either be localized, like a uruncle, or generalized (Figure 24-4). The latter is known as “di use OE,” or simply OE. Seborrheic

FIGURE 24-4 Se b o e ic d e matitis causing e yt e ma and g e asy scale of t e e xte nal e a and e a canal. T e se b o e ic d e matitis itse lf cause s b e aks in t e skin and t e coe xisting u itus may le ad t e atie nt to d amag e t e i own e a canal. T is can b e come se cond a ily infe cte d . (Re p rod uce d with p e rmission from Eric Kraus, MD.)

dermatitis o the external ear and EAC can be di use or generalized (see Figure 24-4). • Forms o (di use) OE1 ° Acute (< 6 weeks; Figures 24-5 and 24-6). ° Chronic (> 3 months)—May cause hearing loss and stenosis o the EAC (Figure 24-7). ° Necrotizing or malignant orm—Def ned by destruction o the temporal bone, usually in diabetic or immunocompromised people; o ten li e threatening (see Figure 24-1). • Key historical eatures ° Otalgia, including pruritus ° Otorrhea (see Figure 24-3) ° Mild hearing loss • Key physical f ndings ° Pain with tragal pressure or pain when the auricle is pulled superiorly, this may be absent in very mild cases. ° Signs o EAC in ammation (edema, erythema, aural discharge) (see Figures 24-5 to 24-7). ° Fever, periauricular erythema, and lymphadenopathy point to severe disease. ° Complete obstruction o EAC occurs in advanced OE. • Establishing the integrity o the tympanic membrane (TM) (through direct visualization) and the absence o middle-ear e usion (through pneumatic otoscopy) is crucial in di erentiating OE rom other diagnoses (eg, suppurative otitis media, cholesteatoma).

O TITIS EXTERNA

PART 5

EAR, NO SE, AND THRO AT

FIGURE 24-5 Acute otitis e xte na s owing u ule nt d isc a g e and na owing of t e e a canal. (Re p ro d uce d with p e rmission from Roy F. Sullivan, PhD. Aud iolog y Forum: Vid e o O toscop y, www.rcsullivan.com.) FIGURE 24-7 C onic otitis e xte na in an old woman w o we a s a e a ing aid . T e e a canal is not na owe d b ut is coate d wit a u ule nt d isc a g e . (Re p ro d uce d with p e rmission fro m Roy F. Sullivan, PhD. Aud iolog y Forum: Vid e o O toscop y, www.rcsullivan.com.)

LABO RATO RY AND IMAGING • Because OE is mostly a clinical diagnosis, diagnostic testing has a limited role. When a patient ails to respond to empiric treatment, obtaining a culture o aural discharge may help guide proper choice o treatment (antibacterial vs anti ungal agents). • I necrotizing or malignant OE is suspected, computed tomography (CT) or MRI o the ear or skull base is warranted.

DIFFERENTIAL DIAGNO SIS • Chronic suppurative otitis media—Otoscopy shows TM per oration; history reveals a chronically draining ear and recurrent middle-ear in ections with or without hearing loss (see Figure 24-3). • Seborrheic dermatitis involving the external ear and EAC can lead to in ammation and breaks in the skin (see Figure 24-4). The coexisting pruritus may lead the patient to damage their own ear canal. This can all become secondarily in ected and become an in ected OE. • Acute otitis media with per orated TM—Presents with purulent drainage rom the canal in the setting o ear pain and clinical signs or symptoms o acute illness such as ever. I the TM is visible, it will be red with a per oration (see Chapter 23, Otitis Media: Acute Otitis and Otitis Media with E usion). • Foreign body in the EAC—Otoscopy, with or without aural toilet, conf rms presence o oreign body (that incites an in ammatory response, leading to otalgia and otorrhea); see Chapter 25, Ear: Foreign Body. • Otomycosis—Pruritus is generally more prominent and EAC in ammation (otalgia and otorrhea) is less pronounced; ungal organisms have a characteristic appearance in the EAC. • Contact dermatitis—Usually caused by ototopical agents (eg, neomycin, benzocaine, propylene glycol); seen in patients with poor response to empiric OE treatment; prominent clinical eatures include pruritus, erythema o conchal bowl, crusting, and excoriations.

MANAGEMENT FIGURE 24-6 Acute otitis e xte na in an old man w o we a s a e a ing aid . Note t e viscous u ule nt d isc a g e and na owing of t e e a canal. (Re p rod uce d with p e rmission from Roy F. Sullivan, PhD. Aud iolog y Forum: Vid e o O toscop y, www.rcsullivan.com.)

NO NPHARMACO LO GIC • The e ectiveness o ear cleaning is unknown. 3 SO R B

121

122

PART 5

EAR, NO SE, AND THRO AT • The e ectiveness o specialist aural toilet (use o operating microscope to mechanically remove material rom external canal) or treating OE is unknown. 1 SO R B MEDICATIO NS • The management o acute OE should include an assessment o pain. The clinician should recommend analgesic treatment based on the severity o pain. 4 SO R B • Topical treatments alone are e ective or uncomplicated acute OE. Additional oral antibiotics are not required. 3 SO R B • The evidence or steroid-only drops is very limited. 3 SO R B • Given that most topical treatments are equally e ective, it would appear that in most cases the pre erred choice o topical treatment may be determined by other actors, such as risk o ototoxicity, risk o contact sensitivity, risk o developing resistance, availability, cost, and dosing schedule. 3 SO R B ° Evidence rom one trial o low quality ound no di erence in clinical e f cacy between quinolone and nonquinolone drops. Quinolones are more expensive than nonquinolones. 3 SO R B ° There is some evidence indicating that patients treated with topical preparations containing antibiotics and steroids benef t rom reduced swelling, severe redness, secretion, and analgesic consumption compared to preparations without steroids. There is a suggestion that high-potency steroids may be more e ective than low-potency steroids (in terms o severe pain, in ammation, and swelling). 3 SO R B ° Acetic acid was e ective and comparable to antibiotic or steroid at week 1. However, when treatment needed to be extended beyond this point it was less e ective. In addition, patient symptoms lasted 2 days longer in the acetic acid group compared to antibiotic or steroid group. 3 SO R B ° Topical aluminum acetate may be as e ective as a topical antibiotic or steroid at improving cure rates in people with acute OE. 1 SO R B • Patients prescribed with antibiotic or steroid drops can expect their symptoms to last or approximately 6 days a ter treatment has begun. Although patients are usually treated with topical medication or 7 to 10 days, it is apparent that this will undertreat some patients and overtreat others. It may be more use ul when prescribing ear drops to instruct patients to use them or at least a week. I they have symptoms beyond the f rst week they should continue the drops until their symptoms resolve (and possibly or a ew days a ter), or a maximum o an additional 7 days. 3 SO R B • Evidence rom one low-quality trial suggests a glycerine-ichthammol medicated wick may provide better pain relie in early severe acute OE than a triamcinolone/ gramicidin/ neomycin/ nystatin medicated wick.3 SOR B • There is no evidence on the use o topical anti ungal agents (with or without steroids) in OE. 1 SO R B

PREVENTIO N Prophylactic treatments to prevent OE (topical acetic acid, topical corticosteroids, or water exclusion) have not been evaluated in clinical trials. 1 SO R B

PRO GNO SIS Acute OE o ten resolves within 6 weeks but can recur.

Ch ApTEr 24

FO LLO W-UP • I the patient ails to respond to empiric therapy within 48 to 72 hours, the clinician should reassess the patient to conf rm the diagnosis o OE and to exclude other causes o illness. 4 SO R B • Patients with persisting symptoms beyond 2 weeks should be considered treatment ailures and alternative management should be initiated. 3 SO R B

PATIENT EDUCATIO N • To avoid recurrent in ections the ollowing recommendations or suggestions should be ollowed5: ° Recommend that patients not use cotton swabs inserted into the ear canal. ° Avoid requent washing o the ears with soap as this leaves an alkali residue that neutralizes the normal acidic pH o the ear canal. ° Avoid swimming in polluted waters. ° Ensure that the canals are emptied o water a ter swimming or bathing—This can be done by turning the head or holding a acial tissue on the outside o the ear to act as a wick. • Consider ear drops or swimmers who get requent OE. A combination o a 2:1 ratio o 70% isopropyl alcohol and acetic acid may be used a ter each episode o swimming to assist in drying and acidi ying the ear canal. 5 SO R C • Do not use earplugs while swimming because they may cause trauma to the ear canal leading to OE. 5

PATIENT RESO URCES

• Patient.co.uk. Otitis Externa—http:/ / www.patient.co.uk/ health/ otitis-externa. PRO VIDER RESO URCES

• Medscape. Otitis Externa—http:/ / emedicine.medscape.com/ article/ 994550.

REFERENCES 1. Hajio D, MacKeith S. Otitis externa. Clin Evid (Online). 2010 Aug 03;2010. pii:0510. 2. Raza SA, Denholm SW, Wong JC. An audit o the management o otitis externa in an ENT casualty clinic. J Laryngol Otol. 1995;109: 130-133. 3. Kaushik V, Malik T, Saeed SR. Interventions or acute otitis externa. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD004740. 4. Rosen eld RM, Brown L, Cannon CR, et al; American Academy o Otolaryngology—Head and Neck Surgery Foundation. Clinical practice guideline: acute otitis externa. Otolaryngol Head Neck Surg. 2006;134(suppl 4):S4-S23. 5. Waitzman AA. Otitis Externa. Updated January 22, 2013. http:/ / emedicine.medscape.com/ article/ 994550-overview. Accessed on July 28, 2013.

EAR: FO REIGN BO DY

PART 5

EAR, NO SE, AND THRO AT

25 EAR: FO REIGN BO DY Brian Z. Rayala, MD Mind y A. Smith, MD, MS

PATIENT STO RY A 28-year-old woman comes to urgent care with le t ear pain stating that, while hiking today, an insect ew into her ear. She tried rinsing her ear with water but nothing came out and she could hear the insect moving around in her ear. She is in obvious distress and on otoscopy you visualize a small live beetle near the tympanic membrane (TM). There is erythema in the external canal but the TM appears intact. The physician instills mineral oil into her ear which stops the movement. She then irrigates the ear and with suction removes the insect.

INTRO DUCTIO N Ear oreign bodies (FBs) can present with otalgia, otorrhea, or decreased hearing. At other times, patients may be asymptomatic.

EPIDEMIO LO GY Ear FBs are commonly seen in children, 1 but can be seen in adults, both healthy and cognitively impaired.

ETIO LO GY AND PATHO PHYSIO LO GY • In a retrospective case series rom 2 Australian emergency departments, most patients presenting with ear FBs were adults (217/ 330). 2 Types o oreign bodies seen in adults included the ollowing: ° Inanimate objects such as cotton tips, cotton wool, and silicone ear plugs ° Insects (Figure 25-1) • Adults in this study were more likely to have associated otitis externa than children (see Chapter 24, Otitis Externa). 2 Following are some key elements o otitis externa in patients with ear oreign bodies: ° Initial breakdown o the skin-cerumen barrier (caused by presence o FB). ° Skin in ammation and edema leading to subsequent obstruction o adnexal structures (eg, cerumen glands, sebaceous glands, and hair ollicles). ° FB reaction leading to urther skin injury. ° In the case o alkaline battery electrochemical reaction, severe alkaline burns may occur.

RISK FACTO RS Silicone and wax ear plugs can become impacted in the ear canal when body temperature so tens them to a dough-like consistency becoming e ectively glued to the surrounding ear canal. 3

FIGURE 25-1 Ant in the e ar canal. (Re p rod uce d with p e rmissio n from Vlad imir Zlinsky, MD in Roy F. Sullivan, PhD. Aud iolog y Forum: Vid e o O toscop y, www.rcsullivan.com.)

DIAGNO SIS CLINICAL FEATURES • Key historical eatures include the ollowing: ° Otalgia ° Otorrhea or otorrhagia ° Mild hearing loss ° Ear itching or oreign body sensation ° Tinnitus ° History suspicious or FB insertion or witnessed FB insertion • Patients may be asymptomatic. • Hallmark o diagnosis includes visualization o FB on otoscopy (see Figures 25-1 to 25-3). • Otoscopy may reveal signs o external auditory canal (EAC) in ammation (eg, edema, erythema, aural discharge) (see Figure 25-2). LABO RATO RY AND IMAGING Aural FB is a clinical diagnosis. Laboratory and imaging studies have very limited use.

DIFFERENTIAL DIAGNO SIS • Otitis externa—Presents with otalgia, otorrhea, and mild hearing loss, all o which can be present in ear FB. Absence o FB (on otoscopic examination) is the key di erentiating actor (see Chapter 24, Otitis Externa). • Acute otitis media (with or without per orated TM)—Otoscopy shows absence o FB and presence o middle-ear in ammation and e usion (ie, bulging, erythematous, cloudy, immobile TM). Patients present with clinical signs or symptoms o acute illness like ever (see Chapter 23, Otitis Media: Acute Otitis and Otitis Media With E usion).

123

124

PART 5

EAR, NO SE, AND THRO AT

Ch a pt e r 25

PRO CEDURES • Proper instrumentation allows the uncomplicated removal o many ear FBs. SO R C ° The use o general anesthesia may be needed in some ear FBs whose contour, composition, or location predispose to traumatic removal in the ambulatory setting. 3 SO R C

FIGURE 25-2 Fore ig n b o d y (b e ad ) in the e ar canal of a 3-ye ar-o ld g irl with re active tissue around it. (Re p rod uce d with p e rmission from William Clark, MD.)

• Chronic suppurative otitis media—Otoscopy shows absence o FB and presence o TM per oration; history reveals a chronically draining ear and recurrent middle-ear in ections with or without hearing loss.

• Ear FBs can be removed by irrigation, suction, or instrumentation. The type o procedure depends on the type o FB being removed. ° Small inorganic objects can be removed rom the EAC by irrigation. Contraindications to irrigation include the ollowing: ■ Per orated TM. ■ Vegetable matter—Irrigation causes swelling o the vegetable matter which leads to urther obstruction. ■ Alkaline (button) battery—Irrigation enhances leakage and potential or lique action necrosis and severe alkaline burns. ° Objects with protruding sur aces or irregular edges can be removed with alligator orceps under direct visualization. ° Objects that are round or breakable can be removed using a wire loop, a curette, or a right-angle hook that is slowly advanced beyond the object and care ully withdrawn. ° Cyanoacrylate adhesive (eg, “superglue”) has been used to remove tightly wedged, smooth, round FBs. ° Live insects should be killed be ore removing them (by irrigation or orceps). Instilling alcohol or mineral oil into the auditory canal can kill them. REFERRAL

MANAGEMENT MEDICATIO NS Topical treatment may be needed i there is accompanying otitis externa (see Chapter 24, Otitis Externa).

Re erral to otolaryngology should be considered in case o the ollowing: • More than one attempt has been carried out without success. 4 • More than one instrument is needed or removal. 5 • Patients who have f rm, rounded FBs. 6 • Patients who have FBs with smooth, nongraspable sur aces (see Figure 25-1). 7

PREVENTIO N • E orts should ocus on preventing small children or cognitively impaired adults rom having access to tiny objects (eg, beads, small toys, etc). • Adults should be instructed to avoid use o cotton swabs inserted into the ear canal and to use caution with silicone or wax ear plugs, avoiding prolonged placement.

PRO GNO SIS Several retrospective studies rom urban emergency departments showed that emergency physicians success ully removed most FBs (53-80%) with minimal complications and no need or operative removal. 4-7 However, timely re erral or di f cult removal or ollowing unsuccess ul patient attempts at removal is prudent.

FO LLO W-UP FIGURE 25-3 Be ach sand g ranule s with e xostosis in the e ar of a cold wate r surfe r. The e xostose s are common in cold wate r swimme rs and surfe rs. (Re p rod uce d with p e rmission from Roy F. Sullivan, PhD. Aud iolog y Forum: Vid e o O toscop y, www.rcsullivan.com.)

Follow-up is important in cases where EAC in ammation or in ection is likely (eg, numerous attempts, use o numerous instruments, protracted exposure to the FB).

EAR: FO REIGN BO DY

PATIENT EDUCATIO N Parents should be in ormed that success ul removal depends a great deal on the length o time the FB has remained in the EAC. PATIENT RESO URCES

• eMedicine Health. Foreign Body, Ear—http:/ / www .emedicinehealth.com/ foreign_body_ear/ article_ em.htm. • WebMD Pain Management Center. Objects in the Ear—http:/ / www.webmd.com/ pain-management/ tc/ objects-in-theear-topic-overview.

PRO VIDER RESO URCES

• ENT USA. External Ear Canal—http:/ / www.entusa.com/ external_ear_canal.htm. • Medline Plus. Ear emergencies—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000052.htm. • Medscape. Ear foreign body removal—http:/ / emedicine .medscape.com/ article/ 763712.

PART 5

EAR, NO SE, AND THRO AT REFERENCES 1. Baker MD. Foreign bodies o the ears and nose in childhood. Pediatr Emerg Care. 1987;3:67-70. 2. Ryan C, Ghosh A, Wilson-Boyd B, et al. Presentation and management o aural oreign bodies in two Australian emergency departments. Emerg Med Australas. 2006;18:372-378. 3. Shakeel M, Carlile A, Venkatraman J, et al. Earplugs presenting as an impacted oreign body in the ear canal. Clin Otolaryngol. 2013;38(3):280-281. 4. Marin JR, Trainor JL. Foreign body removal rom the external auditory canal in a pediatric emergency department. Pediatr Emerg Care. 2006;22:630-634. 5. Ansley JF, Cunningham MJ. Response to O’Donovan. Glue ear and oreign body. Pediatrics. 1999;103(4):857. 6. Thompson SK, Wein RO, Dutcher PO. External auditory canal oreign body removal: management practices and outcomes. Laryngoscope. 2003;113:1912-1915. 7. DiMuzio J Jr, Deschler DG. Emergency department management o oreign bodies o the external ear canal in children. Otol Neurotol. 2002;23:473-475.

125

126

PART 5

EAR, NO SE, AND THRO AT

26 CHO NDRO DERMATITIS NO DULARIS HELICIS AND PREAURICULAR TAGS

Ch a pt e r 26

SYNO NYMS It is also known as chondrodermatitis nodularis chronica helicis.

Lind a Sp e e r, MD

EPIDEMIO LO GY CHO NDRO DERMATITIS NO DULARIS

PATIENT STO RY A 44-year-old white man presents with a pain ul nodule on his right ear or 1 year (Figure 26-1). He has a long history o occupational sun exposure but no skin cancers. He states that it is too pain ul to sleep on his right side because o the ear nodule. He tried to remove it once with nail clippers but it bled too much. The patient is told that this is likely a benign condition called chondrodermatitis nodularis helicis. A shave biopsy is per ormed or diagnostic purposes. It is explained to the patient that this could be a skin cancer as a result o his sun exposure history. The biopsy con rms chondrodermatitis nodularis helicis, and the options or de nitive treatment are described to the patient.

INTRO DUCTIO N Chondrodermatitis nodularis helicis is a benign neoplasm o the ear cartilage commonly believed to be related to excessive pressure, or example, during sleep, and sun exposure. The result is a localized overgrowth o cartilage, and subsequent skin changes. Preauricular tags are mal ormations o the external ear.

• The incidence o chondrodermatitis nodularis has not been determined. • Occurs most commonly in men older than 40 years o age, but older women can also be a ected. PREAURICULAR TAGS Occur in approximately 1 o 10,000 to 12,500 births without predilection or gender or race. Several chromosomal abnormalities include preauricular tags1 as one o the phenotypic expressions.

ETIO LO GY AND PATHO PHYSIO LO GY CHO NDRO DERMATITIS NO DULARIS HELICIS In rare cases, especially when occurring at younger ages, the lesion may be related to an underlying disease associated with microvascular injury, such as vasculitis or other necrobiotic collagen disease. 2 PREAURICULAR TAGS • Arise rom remnants o supernumerary branchial hillocks. 3 • Early-stage embryology involves the ormation o several slit-like structures on the side o the head, the branchial cle ts. The 3 hillocks between the rst 4 cle ts eventually orm the structure o the outer ear. Preauricular tags are generally minor mal ormations arising rom remnants o supernumerary branchial hillocks. 4

DIAGNO SIS CLINICAL FEATURES O F CHO NDRO DERMATITIS • Firm, pain ul nodule 3 to 20 mm in size (Figures 26-1 to 26-4). • The helix is most o ten a ected especially in men (see Figures 26-1 and 26-2). The antihelix is a ected more o ten in women (see Figures 26-3 and 26-4). • Overlying skin is normal in color or erythematous; a central ulcer may be present. CLINICAL FEATURES O F PREAURICULAR TAGS • Fleshy knob in ront o the ear (Figures 26-5 and 26-6) • Present rom the time o birth • Generally asymptomatic TYPICAL DISTRIBUTIO N • Chondrodermatitis is located at the helix or antihelix o the ear. The right ear is more o ten a ected than the le t. FIGURE 26-1 Chond rod e rmatitis nod ularis he licis on the rig ht e ar of a 44-ye ar-old man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Preauricular tags may be unilateral or bilateral, more o ten present on the le t.

CHO NDRO DERMATITIS NO DULARIS HELICIS AND PREAURICULAR TAGS

PART 5

EAR, NO SE, AND THRO AT

FIGURE 26-2 Chond rod e rmatitis nod ularis on the he lix of the rig ht e ar in a 62-ye ar-old man. Note the p e arly ap p e arance , which may b e se e n with a b asal ce ll carcinoma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

BIO PSY • O ten required or chondrodermatitis nodularis to rule out malignancy, especially when occurring in individuals with actinic damage and/ or history o other skin cancers. • Not indicated or preauricular tag.

FIGURE 26-3 Chond rod e rmatitis nod ularis on the antihe lix of the rig ht e ar of an 86-ye ar-old woman. Note the e rythe ma and scale . A shave b iop sy was p e rforme d to make sure this was not a sq uamous ce ll carcinoma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 26-4 Chond rod e rmatitis nod ularis on the antihe lix of the rig ht e ar of a 52-ye ar-old wo man. Note the p e arly nod ule with ce ntral scale . A shave b iop sy was p e rforme d to rule out b asal ce ll carcinoma and sq uamous ce ll carcinoma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 26-5 Pre auricular tag in an ad ult man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

127

128

PART 5

EAR, NO SE, AND THRO AT

FIGURE 26-6 Pre auricular tag p re se nt since b irth in a 59-ye ar-old man. The p atie nt has ne ve r had any re nal ab normalitie s or re late d me d ical p rob le ms. He wants it re move d for cosme tic p urp ose s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIFFERENTIAL DIAGNO SIS • Chondrodermatitis nodularis helicis may be con used with skin cancer, especially squamous cell carcinoma (SCC; see Chapter 169, Squamous Cell Carcinoma). In SCC, the overlying skin is o ten ulcerated and the tumor has poorly de ned margins. • Preauricular tags can be an isolated anomaly or part o a syndrome involving vital organs, especially the kidneys. Skin lesions that could appear similar include basal cell carcinoma (Figure 26-7) and cysts (Figure 26-8).

Ch a pt e r 26

FIGURE 26-7 Basal ce ll carcinoma in a p re auricular location. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Photodynamic therapy (combines a photosensitizer with a speci c type o light to kill nearby cells) has been reported to decrease pain in case reports. 6 SO R C • A small elliptical excision o the nodule with removal o inf amed cartilage provides excellent results (Figure 26-9). 7,8 SO R C • Preauricular tags can be le t alone or surgically excised or cosmetic reasons. SO R C

FO LLO W-UP Recurrences are common and may require urther treatment.

MANAGEMENT Chondrodermatitis nodularis is treated with the ollowing: NO NPHARMACO LO GIC A pressure-relieving prosthesis or donut-shaped pillow can be used. 4,5 SO R C This can also be created by cutting a hole rom the center o a bath sponge. The sponge can then be held in place with a headband i needed. A special pre abricated pillow is available rom http:/ / www .cnhpillow.com/ . PRO CEDURES • Shave biopsy can be used to make the diagnosis and may relieve symptoms temporarily. SO R C • Cryotherapy, intralesional steroids, or curettage and electrodesiccation can be per ormed a ter the result rom the shave biopsy is known and there is no malignancy. SO R C

FIGURE 26-8 Pre auricular cyst marke d for e xcision. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

CHO NDRO DERMATITIS NO DULARIS HELICIS AND PREAURICULAR TAGS

PART 5

EAR, NO SE, AND THRO AT REFERENCES 1. Roth DA, Hildesheimer M, Bardenstein S, et al. Preauricular skin tags and ear pits are associated with permanent hearing impairment in newborns. Pediatrics. 2008;122(4):e844-e890. 2. Magro CM, Frambach GE, Crowson AN. Chondrodermatitis nodularis helices as a marker o internal disease associated with microvascular injury. J Cutan Pathol. 2005;32:329-333. 3. Ostrower ST. Preauricular Cysts, Pits, and Fissures. http:/ / emedicine. medscape.com/ article/ 845288-overview# a05. Accessed July 20, 2011. 4. Sanu A, Koppana R, Snow DG. Management o chondrodermatitis nodularis chronica helicis using a “donut pillow”. J Laryngol Otol. 2007;121(11):1096-1098. 5. Moncrie M, Sassoon EM. E ective treatment o chondrodermatitis nodularis chronica helices using a conservative approach. Br J Dermatol. 2004;150:892-894. 6. Pellegrino M, Taddeucci P, Mei S, et al. Chondrodermatitis nodularis chronics helicis and photodynamic therapy: a new therapeutic option? Dermatol Ther. 2011;24(1):144-147. 7. Rex J, Ribera M, Bielsa I, et al. Narrow elliptical skin excision and cartilage shaving or treatment o chondrodermatitis nodularis. Dermatol Surg. 2006;32:400-404.

FIGURE 26-9 Ellip tical e xcision of chond rod e rmatitis nod ularis he licis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PATIENT EDUCATIO N Chondrodermatitis nodularis is a benign lesion that tends to recur; therapeutic options can be discussed. PATIENT RESO URCES

• A special prefabricated pillow is available that helps relieve pressure on the ear. For more in ormation, contact: CNH Pillow, PO Box 1247, Abilene, TX 79604; phone (800) 255-7487; http:/ / www .cnhpillow.com/ . • Medline Plus. Ear tag—http:/ / nlm.nih.gov/ medlineplus/ ency/ article/ 003304.htm. PRO VIDER RESO URCES

• To learn how to perform an easy elliptical excision of chondrodermatitis nodularis helicis re er to the text and DVD: Usatine R, P enninger J, Stulberg D, Small R. Dermatologic and Cosmetic Procedures in O f ce Practice. Text and DVD. Philadelphia, PA: Elsevier; 2012. • Medscape. Chondrodermatitis Nodularis Helicis—http:/ / emedicine.medscape.com/ article/ 1119141-overview. • Medscape. Preauricular Cysts, Pits, and Fissures—http:/ / emedicine.medscape.com/ article/ 845288-overview.

8. Hudson-Peacock MJ, Cox NH, Lawrence CM. The long-term results o cartilage removal alone or the treatment o chondrodermatitis nodularis. Br J Dermatol. 1999;141:703-705.

129

130

PART 5

EAR, NO SE, AND THRO AT

SECTIO N 2

Ch a pt e r 27

NO SE AND SINUS

27 NASAL PO LYPS Lind a Sp e e r, MD

ETIO LO GY AND PATHO PHYSIO LO GY • The precise cause o nasal polyp ormation is unknown. • In ectious agents causing desquamation o the mucous membrane may play a triggering role.

PATIENT STO RY A 35-year-old man complains o unilateral nasal obstruction or the past several months o gradual onset. On examination o the nose, a nasal polyp is ound (Figure 27-1).

• Activated epithelial cells appear to be the major source o mediators that induce an inf ux o inf ammatory cells, including eosinophils prominently; these in turn lead to proli eration and activation o broblasts. 2 Cytokines and growth actors play a role in maintaining the mucosal inf ammation associated with polyps. • Food allergies are strongly associated with nasal polyps.

INTRO DUCTIO N Nasal polyps are benign lesions arising rom the mucosa o the nasal passages including the paranasal sinuses. They are most commonly semitransparent.

DIAGNO SIS CLINICAL FEATURES • The appearance is usually smooth and rounded (see Figure 27-1). • Moist and translucent (Figure 27-2).

EPIDEMIO LO GY • Prevalence o 1% to 4% o adults. 1 • The male-to- emale ratio in adults is approximately 2:1. • Peak age o onset is between 20 and 40 years; rare in children younger than 10 years. • Associated with the ollowing conditions: ° Nonallergic and allergic rhinitis and rhinosinusitis ° Asthma—in 20% to 50% o patients with polyps ° Cystic brosis ° Aspirin intolerance—in 8% to 26% o patients with polyps ° Alcohol intolerance—in 50% o patients with polyps

FIGURE 27-1 N s l oly in l t mid d l m tus wit no m l su ound ing mucos . (Re p rod uce d with p e rmission from William Clark, MD.)

• Variable size. • Color ranging rom nearly none to deep erythema. TYPICAL DISTRIBUTIO N The middle meatus is the most common location. LABO RATO RY AND IMAGING • Consider allergy testing. • Computed tomography (CT) o the nose and paranasal sinuses may be indicated to evaluate extent o lesion(s) (Figure 27-3). BIO PSY Not usually indicated. Histology typically shows pseudostrati ed ciliary epithelium, edematous stroma, epithelial basement membrane, and proinf ammatory cells with eosinophils present in 80% to 90% o cases.

FIGURE 27-2 N s l oly in ig t n s l c vity in ti nt wit in m d mucos om ll g ic initis. (Re p ro d uce d with p e rmission fro m William Clark, MD.)

NASAL PO LYPS

PART 5

EAR, NO SE, AND THRO AT • Oral doxycycline 100 mg daily or 20 days was shown to decrease polyp size, providing bene t or 12 weeks in one randomized controlled trial. 10 SO R B • Topical nasal decongestants may provide some symptom relie , but do not reduce polyp size. 11 SO R B • Montelukast reduces symptoms when used as an adjunct to oral and inhaled steroid therapy in patients with bilateral nasal polyposis.12 SOR B PRO CEDURES • Surgical excision is o ten required to relieve symptoms. • Consider immunotherapy or patients with allergies.

PRO GNO SIS Lesions are benign and tend to recur.

FO LLO W-UP FIGURE 27-3 CT sc n s owing oly s (aste risk) nd b il t l o cif d m xill y sinus s (MS). Not t n s l oly s to b coming om t l t m xill y sinus nd is b ov t in io tu b in t . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Periodic reevaluation is recommended because recurrence rates are high. 13

PATIENT EDUCATIO N DIFFERENTIAL DIAGNO SIS Many relatively rare conditions can cause an intranasal mass including the ollowing:

Patients should be in ormed about the benign nature o nasal polyps and their tendency to recur. PATIENT RESO URCES

• Papilloma—About 1% o nasal tumors, a ecting 1 in 100,000 adults per year. Locally invasive, these tend to recur especially i excision is not complete. Papillomas are o unknown etiology but are associated with chronic sinusitis, air pollution, and viral in ections. They are irregular and riable in appearance and bleed easily. 3

• Mayo Clinic. Nasal Polyps—http:/ / www.mayoclinic.com/ health/ nasal-polyps/ DS00498.

• Meningoencephalocele—Grayish gelatinous appearance. 4

PRO VIDER RESO URCES

• Nasopharyngeal carcinoma—Firm, o ten ulcerated.

• Medscape. Nasal Polyps—http:/ / emedicine.medscape.com/ article/ 994274.

• Pyogenic granuloma—Relatively common benign vascular neoplasm o skin and mucous membranes (see Chapter 159, Pyogenic Granuloma). 5 • Chordoma—Locally invasive neoplasms with gelatinous appearance that arise rom notochordal (embryonic) remnants. Occurs in all age groups (mean age: 48 years). 6 • Glioblastoma—Rare mani estation o the most common kind o brain tumor in adults.

MANAGEMENT MEDICATIO NS • Medical treatment consists o intranasal corticosteroids. 7 SO R A • An initial short course (2-4 weeks) o oral steroids can be considered in severe cases. 8,9 SO R A • Steroid treatment reduces polyp size, but does not generally resolve them. Corticosteroid treatment is also use ul preoperatively to reduce polyp size.

• Medline Plus. Nasal Polyps—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 001641.htm.

• Medscape. Nonsurgical Treatment of Nasal Polyps—http:/ / emedicine.medscape.com/ article/ 861353.

REFERENCES 1. McClay JE. Nasal Polyps. http:/ / emedicine.medscape.com/ article/ 994274. Accessed July 26, 2013. 2. Pawliczak R, Lewandowska-Polak A, Kowalski ML. Pathogenesis o nasal polyps: an update. Curr Allergy Asthma Rep. 2005;5:463-471. 3. Sadeghi N. Sinonasal Papillomas. http:/ / emedicine.medscape.com/ article/ 862677. Accessed July 26, 2013. 4. Kumar KK, Ganapathy K, Sumathi V, et al. Adult meningoencephalocele presenting as a nasal polyp. J Clin Neurosci. 2005;12:594-596. 5. Hoving EW. Nasal encephaloceles. Childs Nerv Syst. 2000;16: 702-706. 6. Palmer CA. Chordoma. http:/ / emedicine.medscape.com/ article/ 250902. Accessed July 20, 2011.

131

132

PART 5

EAR, NO SE, AND THRO AT

Ch a pTe r 27

7. Joe SA, Thambi R, Huang J. A systematic review o the use o intranasal steroids in the treatment o chronic rhinosinusitis. Otolaryngol Head Neck Surg. 2008;139(3):340-347.

10. Van Zele T, Gevaert P, Holtappels G, et al. Oral steroids and doxycycline: two di erent approaches to treat nasal polyps. JAllergy Clin Immunol. 2010;125(5):1069-1076.e4.

8. Martinez-Devesa P, Patiar S. Oral steroids or nasal polyps. Cochrane Database Syst Rev. 2011;6(7):CD005232.

11. Johansson L, Oberg D, Melem I, Bende M. Do topical nasal decongestants a ect polyps? Acta Otolaryngol. 2006:126:288-290.

9. Vaidyanathan S, Barnes M, Williamson P, et al. Treatment o chronic rhinosinusitis with nasal polyposis with oral steroids ollowed by topical steroids: a randomized trial. Ann Intern Med. 2011;154(5):293-302.

12. Stewart RA, Ram B, Hamilton G, et al. Montelukast as an adjunct to oral and inhaled steroid therapy in chronic nasal polyposis. Otolaryngol Head Neck Surg. 2008;139(5):682-687. 13. Vento SI, Ertama LO, Hytonen ML, et al. Nasal polyposis: clinical course during 20 years. Ann Allergy Asthma Immunol. 2000;85:209-214.

SINUSITIS

PART 5

EAR, NO SE, AND THRO AT

28 SINUSITIS Mind y A. Smith, MD, MS

PATIENT STO RY A 55-year-old woman complains o sinus pressure or the past 2 weeks along with headache, rhinorrhea, postnasal drip, and cough. This all started with a cold 3 weeks ago. She has chronic allergic rhinitis, but now the pressure on the right side o her ace has become intense and her right upper molars are pain ul. The nasal discharge has become discolored and she eels everish. She is diagnosed clinically with right maxillary sinusitis and is prescribed an antibiotic. Two weeks later when her symptoms have persisted, a computed tomography (CT) is ordered and she is ound to have air- uid levels in both maxillary sinuses and loculated uid on the right side. (Figures 28-1 and 28-2.) The antibiotic is changed to amoxicillin/ clavulanate and she is given in ormation about nasal saline irrigation or symptom relie . I the symptoms do not improve the clinician plans to send her to ear, nose, and throat (ENT) or urther evaluation.

INTRO DUCTIO N Rhinosinusitis is symptomatic in ammation o the sinuses, nasal cavity, and their epithelial lining. 1 Mucosal edema blocks mucous drainage, creating a culture medium or viruses and bacteria. Rhinosinusitis is classif ed by duration as acute ( 12 weeks).

FIGURE 28-2 Maxillary sinusitis on coronal CT o same p atie nt. (Re p rod uce d with p e rmission from Chris McMains, MD.)

EPIDEMIO LO GY • Rhinosinusitis is common in the United States, with an estimated prevalence o 14% to 16% o the adult population annually. 1,2 The prevalence is increased in women and in individuals living in the southern United States. • Only one-third to one-hal o primary care patients with symptoms o sinusitis actually have bacterial in ection. 3 • Sinusitis is the f th leading diagnosis or which antibiotics are prescribed in the United States. 1 • This problem is responsible or millions o o f ce visits to primary care physicians each year. 1

ETIO LO GY AND PATHO PHYSIO LO GY • Sinus cavities are lined with mucous-secreting respiratory epithelium. The mucus is transported by ciliary action through the sinus ostia (openings) to the nasal cavity. Under normal conditions, the paranasal sinuses are sterile cavities and there is no mucous retention. • Bacterial sinusitis occurs when ostia become obstructed or ciliary action is impaired, causing mucus accumulation and secondary bacterial overgrowth.

FIGURE 28-1 Bilate ral maxillary sinusitis on axial CT. Note that f uid le ve ls are g re ate r o n the rig ht. (Re p rod uce d with p e rmission from Chris McMains, MD.)

• The causes o sinusitis include the ollowing4: ° In ection—Most commonly viral (eg, rhinovirus, parain uenza, and in uenza) ollowed by bacterial in ection (eg, community-acquired acute cases—about hal rom Streptococcus pneumoniae and Haemophilus inf uenzae ollowed by Moraxella catarrhalis). In immunocompromised patients, ulminant ungal sinusitis may occur (eg, rhinocerebral mucormycosis—Figure 28-3).

133

134

PART 5

EAR, NO SE, AND THRO AT

Ch a pt e r 28

is seen more o ten with bacterial sinusitis. Halitosis is also attributed to bacterial causes. • In a study o patients with chronic rhinosinusitis, diagnosis based on symptoms was problematic and only dysosmia (impairment in the sense o smell) and the presence o polyps could distinguish between normal and abnormal radiographs. 6 TYPICAL DISTRIBUTIO N Most sinus in ections involve the maxillary sinus ollowed in requency by the ethmoid (anterior), rontal, and sphenoid sinuses; however, most cases involve more than one sinus. LABO RATO RY AND IMAGING • Culture o nasal or nasopharyngeal secretions is not recommended as these have not been shown to di erentiate between bacterial and viral rhinosinusitis. 1

FIGURE 28-3 Mucormycosis sinusitis in a p atie nt with d iab e te s showing the classic b lack nasal d ischarg e . (Re p rod uce d with p e rmission from Rand al A. O tto, MD.)

° Nonin ectious obstruction—Allergies, polyposis, barotrauma (eg,

deep-sea diving, airplane travel), chemical irritations, tumors (eg, squamous cell carcinoma, granulomatous disease, inverting papilloma), and conditions that alter mucous composition (eg, cystic f brosis).

DIAGNO SIS The diagnosis is based on the clinical picture with typical symptoms listed below. Symptoms arising rom viral in ection generally peak by day 5 or be ore. Acute bacterial rhinosinusitis is diagnosed when symptoms are present or 10 days or longer or when symptoms worsen a ter initial stability or improvement (“double worsening” or “double sickening”); it can also be presumed in patients with unusually severe presentations or extrasinus mani estations o in ection. 1 Superimposed bacterial in ection is estimated to occur in 0.5% to 2% o cases o viral rhinosinusitis. 1

• I culture is needed because o suspected bacterial resistance or persistence o in ection, a recent meta-analysis ound endoscopically directed middle meatal cultures to be reasonably sensitive (80.9%), specif c (90.5%), and accurate (87%; 95% conf dence interval, 81.3-92.8%) compared with maxillary sinus taps. 7 • Radiography should not be obtained or patients meeting diagnostic criteria or acute rhinosinusitis, unless a complication or alternate diagnosis is suspected. 1 I per ormed in cases o clinical uncertainty or or complications (eg, orbital, intracranial, or so t tissue involvement), plain sinus radiography is considered positive or acute sinusitis with the presence o air- uid level, complete opacif cation, or at least 6 mm o mucosal thickening; it has a reported sensitivity o 76% and specif city 79%. 8 There are considerable limitations to the sensitivity o plain f lms, especially in diagnosing ethmoid and sphenoid disease. • Nasal endoscopy, identi ying purulent material within the drainage area o the sinuses, may be comparable to plain sinus radiography in diagnosing acute sinusitis. 7 In one case series o patients with suspected chronic rhinosinusitis, the addition o endoscopy to symptom criteria had similar sensitivity (88.7% vs 84.1%) but signif cantly improved specif city (66% vs 12.3%) using CT as the gold standard. 9

CLINICAL FEATURES

• In acute disease, CT scanning is generally reserved or persistent or recurrent symptoms to conf rm sinusitis, or to investigate in ectious complications (Figures 28-4 and 28-5). Radiation dose (about 10 times that o plain radiography) can be lowered with care ul choice o technical actors. 1

• Most cases are seen in conjunction with viral upper respiratory in ections and represent sinus in ammation rather than in ection. 3

REFER O R HO SPITALIZE

• Nonspecif c symptoms include cough, sneezing, ever, nasal discharge (may be purulent or discolored), congestion, and headache.

• Potentially li e-threatening complications include subperiosteal orbital abscess, meningitis, epidural or cerebral abscess, and cavernous sinus thrombosis (Figures 28-6 and 28-7).

• The American Academy o Otolaryngology guideline and the European Position Paper on Rhinosinusitis and Nasal Polyps recommend a diagnosis o rhinosinusitis with a combination (2 or more) o purulent nasal drainage associated with nasal obstruction, acial pain-pressure- ullness, or both; the latter also recognizes reduction or loss o smell as a cardinal eature. 1,5 There are no prospective trials that validate this approach. • Other localizing symptoms include acial pain or pressure over the involved sinus when bending over or supine (ie, orehead in rontal sinusitis, cheek with maxillary sinusitis, between the eyes with ethmoid sinusitis, and neck and top o the head with sphenoid sinusitis) and maxillary tooth pain, most commonly the upper molars; the latter

• The risks o rontal sinusitis includes eroding through the rontal bone orward and causing a Pott’s pu y tumor, inward and spreading into the brain and cavernous sinuses (see Figure 28-5). • Orbital abscess is highly dangerous and can be the result o spread rom the rontal or ethmoid sinuses (see Figure 28-6). • In immunocompromised patients, ulminant ungal sinusitis may cause orbital swelling, cellulitis, proptosis, ptosis, impairment o extraocular motion, nasopharyngeal ulceration, and epistaxis. Bony erosion may be evident. 5 Nasal mucosa may appear black (see Figure 28-3), blanched white, or erythematous.

SINUSITIS

PART 5

EAR, NO SE, AND THRO AT

FIGURE 28-6 Rig ht orb ital ab sce ss with p rop tosis as a comp licatio n o rontal sinusitis e rod ing throug h the sup e rior orb ital b one s. (Re p rod uce d with p e rmission from Rand al A. O tto, MD.)

FIGURE 28-4 Mucop yoce le in the sp he noid sinus (arrow) as a comp lication o b acte rial sinusitis. (Re prod uce d with pe rmission from Randal A. O tto, MD.)

• In hospitalized patients, patients may be critically ill and without localizing symptoms. In ections in these patients are o ten polymicrobial including Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Klebsiella pneumoniae, and Enterobacter. 5

DIFFERENTIAL DIAGNO SIS • Upper respiratory tract in ections (URIs)—These are common in ections, primarily viral (most commonly rhinovirus), that cause 2 to 4 in ections per year in adults and 6 to 8 in ections per year in children.

FIGURE 28-5 Frontal sinusitis e rod e d throug h the rontal b one inward toward the b rain thre ate ning such comp lications as a b rain ab sce ss and cave rnous sinus thromb osis. Se e n on CT scan. (Re p rod uce d with p e rmission from Rand al A. O tto , MD.)

In ections are sel -limited (lasting approximately 7-10 days) and typical symptoms include rhinorrhea, nasal congestion, sore throat, and cough. URI o ten precedes acute sinusitis. • Allergic rhinitis—Sneezing, itching, watery rhinorrhea. • Tumor (usually squamous cell carcinoma)—Rare; unilateral epistaxis or discharge and obstruction, recurrent sinusitis, sinus pain. Other causes o acial pain include the ollowing: • Migraine headache or cluster headache—Moderate-to-severe head pain that is usually deep seated, persistent, and pulsatile. There is a history o multiple occurrences and head pain may be associated with nausea, vomiting, photophobia, and scotomata. Attacks last or 4 to 72 hours.

FIGURE 28-7 Mucop yoce le (re d arrow) in the rig ht rontal sinus se e n on mag ne tic re sonance imag ing (MRI) scan as a comp lication o rontal sinusitis. (Re p rod uce d with p e rmission from Rand al A. O tto, MD.)

135

136

PART 5

EAR, NO SE, AND THRO AT

Ch a pt e r 28

• Trigeminal neuralgia—Pain ul condition characterized by excruciating, paroxysmal, shock-like pain lasting seconds to minutes along the distribution o the trigeminal nerve (ophthalmic, maxillary and/ or mandibular branches). Pain may be triggered by ace washing, air dra t, and chewing.

• In a Cochrane review o 59 trials evaluating antibiotic treatment or acute maxillary sinusitis, antibiotics decreased clinical ailure by approximately 10%. 15 Comparisons between classes o antibiotics showed no signif cant di erences; there ore, narrow-spectrum antibiotics should be the f rst-line therapy. 15

• Dental pain—Tooth pain may be secondary to caries or gingivitis. When caries extend into the tooth pulp, the tooth becomes sensitive to percussion and hot and cold ood and beverages. I pulp necrosis occurs, pain becomes severe, sharp, throbbing, and o ten worse when supine. Abscess ormation results in pain, swelling and erythema o the gum and surrounding tissue, and possibly purulent drainage.

• Based on the Otolaryngology Head and Neck Surgery clinical guideline, the modest benef t o antibiotics or improving rates o clinical cure or improvement at 7 to 12 days (number needed to treat = 7) must be weighed against the risks o harm (primarily gastrointestinal, but also skin rash, vaginal discharge, headache, dizziness, and atigue [number needed to harm = 9]). 1

• Temporal arteritis—Unilateral pounding headache that may be associated with visual changes and systemic symptoms (eg, ever, weight loss, muscle aches). Onset is usually in older adults (older than age 50 years) and laboratory testing reveals an elevated erythrocyte sedimentation rate (>50).

PRO CEDURES • Surgery and intravenous antibiotics are used or complications, including abscess and cases with orbital involvement. 4 • Patients with ungal sinusitis are treated with aggressive debridement and adjunctive anti ungals (eg, amphotericin). 4

Duration o illness assists in decision making as most patients improve without specif c treatment; a period o watch ul waiting or up to 7 days is consistent with guidelines. 1 Treatment o symptoms, including pain, is important.

• Based on 3 RCTs, endoscopic sinus surgery is not superior to medical treatment; in one study there was a lower relapse rate (2.4% vs 5.6% without surgery). 16 SO R B Patients should be selected based on the severity o disease ( requency o antibiotics or oral steroid use), comorbidities (asthma, aspirin sensitivity, etc), and overall clinical picture (presence o polyps or ungal disease).

NO NPHARMACO LO GIC

CO MPLEMENTARY AND ALTERNATIVE MEDICINE

Nasal saline irrigation or acute upper respiratory tract in ection in adults is generally not help ul, although data are limited;10 2 trials suggested modest benef t rom bu ered hypertonic (3-5%) saline irrigation or acute rhinosinusitis. 1 SO R B In adults with chronic sinusitis, nasal saline irrigation provides symptom relie , both alone and as an adjunct to nasal steroids, and is well tolerated. 11 SO R B

With respect to alternative therapy, there is limited evidence that Sinupret and bromelain may be e ective adjunctive treatments in acute rhinosinusitis. 17 SO R B

MANAGEMENT

MEDICATIO NS • Analgesics (acetaminophen or nonsteroidal anti-in ammatory drugs alone or in combination with an opioid) should be used or pain. 1 • Oral and topical (nasal) decongestants may be o ered or symptomatic relie ; however, there are no randomized controlled trials (RCTs) demonstrating e ectiveness or sinusitis and the e ect is limited to the nasal cavity. 12 Topical agents are more potent but rebound nasal congestion may develop a ter discontinuation; use or 3 days only is suggested. 1 • Topical corticosteroids appear to be o benef t in improvement and resolution o symptoms or acute sinusitis. 13 SO R B • There have been no clinical trials o mucolytics reported in adults with acute bacterial sinusitis. However, they may be use ul in preventing crust ormation and lique ying secretions. SO R C • Patients who ail to improve or have severe symptoms can be o ered oral antibiotics. SO R A Although 10 days is usually recommended or adults, a shorter course (3-5 days) may be equally e ective. 1 (500 mg 3 times daily or 875 mg ° Adults (a ter 7 days)—Amoxicillin twice daily) or 10 days;1 alternatives include trimethoprim-sul amethoxazole (TMS-SMX) (1 DS twice daily) or a macrolide or 10 days. 1 ° The In ectious Disease Society o America recommends use o amoxicillin-clavulanate rather than amoxicillin alone as empiric antimicrobial therapy or acute bacterial sinusitis in adults (low-quality evidence). 14

PREVENTIO N Smoking increases the risk or sinusitis; patients should be counseled about cessation. 1

PRO GNO SIS • Based on a Cochrane review, cure or improvement rate or acute sinusitis within 2 weeks was high in both the placebo group (80%) and the antibiotic group (90%). 15 • For patients with chronic sinusitis, a retrospective study o medical treatment reported treatment success in about hal o patients (N = 74); 26 patients had partial resolution and 45 patients underwent surgery. Facial pressure or pain, mucosal in ammation, and higher endoscopic severity grade predicted treatment ailure. 18

FO LLO W-UP For those adults who ail treatment a ter 7 days o antibiotic therapy, 1 a nonbacterial cause or resistant organism should be considered; amoxicillin-clavulanate (4 g per day amoxicillin equivalent) twice daily or 10 days, or a respiratory uoroquinolone (eg, levo oxacin, 500 mg daily) or 7 days are alternatives. 1,4 SO R C

SINUSITIS

PATIENT EDUCATIO N • Nasal congestion, purulent rhinitis, and acial pain ollowing a cold may indicate a sinus in ection. Symptoms due to a cold usually abate within 1 week. • Methods to improve sinus drainage include oral and nasal decongestants and nasal saline irrigation. Patients should be cautioned against using nasal decongestants or more than 3 days to avoid rebound symptoms. For longer-term management, topical nasal steroids may prove use ul. • Patients should be encouraged to see their primary care provider i symptoms persist or worsen a ter 10 days, suggesting bacterial in ection that may benef t rom antibiotic treatment. PATIENT RESO URCES

• National Institute of Allergy and Infectious Diseases. Sinusitis— http:/ / www.niaid.nih.gov/ topics/ sinusitis/ Pages/ Index.aspx. • MedlinePlus. Sinusitis—http:/ / www.nlm.nih.gov/ medlineplus/ sinusitis.html. PRO VIDER RESO URCES

• Rosenfeld RM, Andes D, Neil B, et al. Clinical practice guideline: adult sinusitis. Otolaryngol Head Neck Surg. 2007;137:365-377. • IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults—http:/ / cid.oxfordjournals.org/ content/ 54/ 8/ 1041.long. REFERENCES 1. Rosen eld RM, Andes D, Neil B, et al. Clinical practice guideline: adult sinusitis. Otolaryngol Head Neck Surg. 2007;137:365-377. 2. Anand VK. Epidemiology and economic impact o rhinosinusitis. Ann Otol Rhinol Laryngol. 2004;193(suppl):3-5. 3. Holleman DR Jr, Williams JW Jr, Simel DL. Usual care and outcomes in patients with sinus complaints and normal results o sinus roentgenography. Arch Fam Med. 1995;4:246-251. 4. Rubin MA, Gonzales R, Sande MA. In ections o the upper respiratory tract. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson, JL, eds. Harrison’s Principles o Internal Medicine. New York, NY: McGraw-Hill; 2005:185-188.

PART 5

EAR, NO SE, AND THRO AT 5. Daudia A, Jones NS. Sinus headaches. Rhinology. 2007;45:1-2. 6. Bhattacharyya N. Clinical and symptom criteria or the accurate diagnosis o chronic rhinosinusitis. Laryngoscope. 2006;116(7 pt 2 suppl 110):1-22. 7. Benninger MS, Payne SC, Ferguson BJ, et al. Endoscopically directed middle meatal cultures versus maxillary sinus taps in acute bacterial maxillary rhinosinusitis: a meta-analysis. Otolaryngol Head Neck Surg. 2006;134(1):3-9. 8. Berger G, Steinberg DM, Popoytzer A, Ophir D. Endoscopy versus radiography or the diagnosis o acute bacterial rhinosinusitis. Eur Arch Otorhinolaryngol. 2005;262(5):416-422. 9. Bhattacharyya N, Lee LN. Evaluating the diagnosis o chronic rhinosinusitis based on clinical guidelines and endoscopy. Otolaryngol Head Neck Surg. 2010;143(1):147-151. 10. Kassel JC, King D, Spurling GKP. Saline nasal irrigation or acute upper respiratory tract in ections. Cochrane Database Syst Rev. 2010;(3):CD006821. 11. Harvey R, Hannan SA, Badia L, Scadding G. Nasal saline irrigations or the symptoms o chronic rhinosinusitis. Cochrane Database Syst Rev. 2007;(3):CD006394. 12. Shaikh N, Wald ER, Pi M. Decongestants, antihistamines and nasal irrigation or acute sinusitis in children. Cochrane Database Syst Rev. 2010;(12):CD007909. 13. Zalmanovici Trestioreanu A, Yaphe J. Intranasal steroids or acute sinusitis. Cochrane Database Syst Rev. 2009;(4):CD005149. 14. Chow AW, Benninger MS, Brook I, et al. IDSA clinical practice guideline or acute bacterial rhinosinusitis in children and adults. Clin In ect Dis. 2012;54(8):e72-e112. 15. Ahovuo-Saloranta A, Rautakorpi U-M, Borisenko OV, et al. Antibiotics or acute maxillary sinusitis. Cochrane Database Syst Rev. 2008;(2):CD000243. 16. Khalil HS, Nunez DA. Functional endoscopic sinus surgery or chronic rhinosinusitis. Cochrane Database Syst Rev. 2006;3:CD004458. 17. Guo R, Canter PH, Ernst E. Herbal medicines or the treatment o rhinosinusitis: a systematic review. Otolaryngol Head Neck Surg. 2006;135(4):496-506. 18. Lal D, Scianna JM, Stankiewicz JA. E f cacy o targeted medical therapy in chronic rhinosinusitis, and predictors o ailure. Am J Rhinol Allergy. 2009;23:396-400.

137

138

PART 5

EAR, NO SE, AND THRO AT

SECTIO N 3

Ch a pt e r 29

MO UTH AND THRO AT

29 ANGULAR CHEILITIS Lind a Sp e e r, MD Richard P. Usatine , MD

PATIENT STO RY A middle-aged woman presents to your o ce with soreness at the right corner o her mouth or 4 months (Figure 29-1). On examination, she has cracking and ssures at the right corner o her mouth. She is diagnosed with angular cheilitis and treated with nonprescription clotrimazole cream and 1% hydrocortisone ointment twice daily. Within 2 weeks she was ully healed.

INTRO DUCTIO N

FIGURE 29-2 Cand id a alb icans s n und th mic oscop a t g ntly sc ap ing a cas o ang ula ch ilitis and using KO H and b lu ink on th slid . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Angular cheilitis is an inf ammatory lesion o the commissure or corner o the lip characterized by scaling and ssuring.

ETIO LO GY AND PATHO PHYSIO LO GY SYNO NYMS Angular cheilitis is also known as perlèche, angular cheilosis, commissural cheilitis, and angular stomatitis.

EPIDEMIO LO GY

• Maceration is the usual predisposing actor. Microorganisms, most o ten Candida albicans, can then invade the macerated area (Figure 29-2). 2 Can also occur a ter use o antibiotics, especially in patients with risk actors described below (Figure 29-3). • Lip licking can cause a contact dermatitis to the saliva along with perlèche (Figure 29-4). Perlèche is derived rom the French word, “lecher,” meaning to lick.

It is most common in the elderly. In one study o institutionalized elderly patients in Scotland, angular cheilitis was present in 25% o patients. 1

• Historically associated with vitamin B de ciency, which is rare in developed countries.

FIGURE 29-1 Angula ch ilitis (p lèch ). Not d y, yth matous, and f ssu d app a anc . (Reproduced with permission from Richard P. Usatine, MD.)

FIGURE 29-3 Ang ula ch ilitis in a woman with p oo d ntition and th ush at c iving antib iotics o a u ina y t act in ction. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 5

ANGULAR CHEILITIS

FIGURE 29-4 P lè ch in a woman with co ntact d matitis lat d to lip licking . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

RISK FACTO RS • Maceration can be related to poor dentition, deep acial wrinkles, orthodontic treatment, or poorly tting dentures in the elderly (Figure 29-5). • Other risk actors include incorrect use o dental f oss causing trauma or diseases that enlarge the lips such as oro acial granulomatosis.

EAR, NO SE, AND THRO AT

FIGURE 29-6 Ang ula ch ilitis in a woman with atop ic d matitis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

TYPICAL DISTRIBUTIO N Corners o the mouth (oral commissures or angles o the mouth), hence the names commissural cheilitis and angular cheilitis. LABO RATO RY DIAGNO SIS

• Atopic dermatitis (Figure 29-6).

A light scraping o the corner o the mouth can be placed on a slide with potassium hydroxide (KOH) to look or Candida (see Figures 29-2 and 29-3).

• HIV or other types o immunode ciency may lead to more severe case o angular cheilitis with overgrowth o Candida (Figure 29-7).

BIO PSY

• Use o isotretinoin dries the lips and predisposes to angular cheilitis.

Not usually indicated.

DIAGNO SIS CLINICAL FEATURES Erythema and ssuring at the corners o the mouth, without exudates or ulceration (see Figures 29-3 to 29-7)

FIGURE 29-5 Ang ula ch ilitis in an ld ly woman. Not th w inkl lin xt nd ing d ownwa d om th co n o h mouth ind icating som chang in h acial anatomy that can p d isp os to this cond ition. Th p lè ch sta t d whil sh was waiting o h d ntu s to b p ai d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIFFERENTIAL DIAGNO SIS • Impetigo—Yellowish crusts or exudates are characteristic o impetigo but not angular cheilitis (see Chapter 118, Impetigo). • Herpes simplex (cold sores)—Initial blisters, ollowed by shallow ulcers, are characteristic o herpes simplex, but not angular cheilitis (see Chapter 128, Herpes Simplex).

FIGURE 29-7 S v ang ula ch ilitis in an HIV-p ositiv man with th ush. Not th whit Cand id a g owth on b oth co n s o his mouth. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

139

PART 5

140

EAR, NO SE, AND THRO AT MANAGEMENT NO NPHARMACO LO GIC

CHAPTe r 29

Protective lip balm may be help ul to prevent recurrences as long as the patient is not allergic to chemicals within the product. Plain petrolatum is o ten the sa est product or dry lips.

• Attempt to relieve precipitating causes such as poorly tting dentures. • Counsel patients to stop licking their lips i this is part o the cause (see Figure 29-4). • Recommend protective petrolatum or lip balm as needed. • Counsel patients to stop using tobacco, either chewing or smoking. MEDICATIO NS • Recommend topical anti ungal creams or ointments, such as clotrimazole, to be applied twice daily. 3 SO R B • Low-potency topical corticosteroid, such as 1% hydrocortisone cream twice daily, may be added to treat the inf ammatory component. SO R B

• Nystatin lozenges work well but their use is limited because o their unpleasant taste. 3 SO R C I thrush is also present, prescribe clotrimazole troches or treatment o both conditions. • One randomized controlled study showed that medicated chewing gum can decrease the risk o angular cheilitis in older occupants o nursing homes. Consider recommending xylitol-containing gum to elderly patients with angular cheilitis. 4 SO R B

PREVENTIO N Attempt to identi y predisposing actors and correct i possible, such as the ollowing: • Being edentulous • Poorly tting dentures • Drooling • Lip licking (see Figure 29-4) • Atopic dermatitis (see Figure 29-6)

PATIENT EDUCATIO N Encourage patients to identi y and correct predisposing actors (listed earlier). Protective lip balm may be help ul.

PATIENT AND PRO VIDER RESO URCES

• Dr. Steven R. Pohlhaus’ website. Angular Chelitis—http:/ / www .stevedds.com/ toppage2.htm# Angular Cheilitis. • National Center for Emergency Medicine Informatics. Perleche— http:/ / www.ncemi.org/ cse/ cse0409.htm. REFERENCES 1. Samaranayake LP, Wilkieson CA, Lamey PJ, MacFarlane TW. Oral disease in the elderly in long-term hospital care. Oral Dis. 1995;1(3): 147-151. 2. Sharon V, Fazel N. Oral candidiasis and angular cheilitis. Dermatol Ther. 2010;23(3):230-242. 3. Skinner N, Junker JA, Flake D, Ho man R. Clinical inquiries. What is angular cheilitis and how is it treated? J Fam Pract. 2005 May;54(5): 470-471. 4. Simons D, Brails ord SR, Kidd EA, Beighton D. The e ect o medicated chewing gums on oral health in rail older people: a 1-year clinical trial. JAm Geriatr Soc. 2002 Aug;50(8):1348-1353.

TO RUS PALATINUS

PART 5

EAR, NO SE, AND THRO AT

30 TO RUS PALATINUS Lind a Sp e e r, MD Mind y A. Smith, MD, MS

PATIENT STO RY An elderly woman is in the o ce or a physical examination. While looking in her mouth, a torus is seen at the midline on the hard palate (Figure 30-1). She states that she has had this or her whole adult li e and it does not bother her. You explain to her that it is a torus palatinus and that nothing needs to be done. She is pleased to know the name o this lump and even happier to know that it is not harm ul.

INTRO DUCTIO N Torus palatinus is a benign bony exostosis (bony growth) occurring in the midline o the hard palate. Torus mandibularis o ten presents as multiple benign bony exostoses on the f oor o the mouth.

EPIDEMIO LO GY

FIGURE 30-2 To us l tinus in 42-y -old wom n. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIAGNO SIS CLINICAL FEATURES • Hard lump protruding rom the hard palate into the mouth covered with normal mucous membrane (Figures 30-1 and 30-2). • Small size (< 2 mm) appear most requent (70% to 91%). 1

• Most common bony maxillo acial exostosis, unclear origin. • Usually in adults older than 30 years o age.

• Shapes include f at, nodular, lobular, or spindle-shaped; nodular appears most common. 1 They may even by bi d (Figure 30-3).

• Prevalence ranges rom 9.5% to 26.9%; among ethnic groups, the range is wider (0.9% in Vietnamese to 30.8% among A rican Americans). 1

TYPICAL DISTRIBUTIO N

• More common in women than men.

Midline hard palate.

• Some populations seem to be more predisposed (eg, Middle Eastern). 2

DIFFERENTIAL DIAGNO SIS • Torus mandibularis is also a bony exostosis but is ound under the tongue. These appear similar to a torus palatinus but are usually bilateral rather than midline (see Figure 30-4).

FIGURE 30-1 To us l tinus in 66-y -old wom n. T ti nt w s sym tom tic nd t is w s n incid nt l f nd ing . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 30-3 Bif d to us Richard P. Usatine , MD.)

l tinus. (Re p rod uce d with p e rmission from

141

142

PART 5

EAR, NO SE, AND THRO AT

FIGURE 30-4 To us m nd ib ul is s n und t tong u c us d b y b ony xostos s. Not t s b il t l nd simil to to us l tinus. T to i w sym tom tic nd t is w s n incid nt l f nd ing . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Squamous cell carcinoma is not as hard and the mucous membranes are usually ulcerated. Mucous membranes are normal in appearance with torus palatinus unless traumatized. • Adenoid cystic carcinoma is a rare tumor that can start in a minor salivary gland over the hard palate. Note that this tumor will not be midline as ound in the torus palatinus. I a suspected torus is not midline a biopsy is needed to rule out this potentially atal carcinoma (Figure 30-5).

MANAGEMENT • Excision can be considered i the lesion inter eres with unction, such as the t o dentures. This is per ormed as an outpatient procedure. 3,4 • Sometimes it needs to be removed because o disturbances o phonation, traumatic inf ammation or ulcer, aesthetic reasons, or as source o autogenous cortical bone or gra ts in periodontal surgery. 1

PRO GNO SIS • Very slow growing; can stop growth spontaneously. 1 • Surgical complications include per oration o nasal cavities, palatine nerve damage, bone necrosis, hemorrhage, and racture o palatine bone. 1

Ch a pTe r 30

FIGURE 30-5 a d noid cystic c cinom in 22-y -old wom n. T ow oints to t is unil t l tumo t t s ould not b con us d wit to us l tinus. (Re p rod uce d with p e rmission from Rand al A. O tto, MD.)

PATIENT EDUCATIO N Patients should be in ormed about the benign nature o the lesion and that removal can be considered, i bothersome. PATIENT RESO URCES

• Brea Dentistry. Torus Palatinus—http:/ / www.breadentistry .com/ f les/ pd / OPG_tor_pal.pd . PRO VIDER RESO URCES

• Otolaryngology Dr. T. Balasubramanian has posted information on his Web site including a video o surgical excision—http:/ / www.drtbalu.co.in/ torus.html.

REFERENCES 1. García-García AS, Martínez-González JM, Gómez-Font R, et al. Current status o the torus palatinus and torus madibularis. Med Oral Patol Oral Cir Bucal. 2010;15(2):e353-e360. 2. Yildiz E, Deniz M, Ceyhan O. Prevalence of torus palatinus in Turkish school children. Surg Radiol Anat. 2005;27:368-371. 3. Al-Quran FA, Al-Dwairi ZN. Torus palatinus and torus mandibularis in edentulous patients. J Contemp Dent Pract. 2006;7:112-119. 4. Cagirankaya LB, Dansu O, Hatipoglu MG. Is torus palatinus a feature o a well-developed maxilla? Clin Anat. 2004;17:623-625.

PHARYNGITIS

PART 5

EAR, NO SE, AND THRO AT

31 PHARYNGITIS

• Highest prevalence in winter.

Brian Williams, MD Richard P. Usatine , MD Mind y A. Smith, MD

• Up to 14% of deep neck infections result from pharyngitis. 3

• Acute rheumatic fever is currently rare in the United States.

ETIO LO GY AND PATHO PHYSIO LO GY PATIENT STO RY A 27-year-old woman complains of 2 days of sore throat, fever, and chills. She is unable to swallow anything other than liquids because of severe odynophagia. She denies any congestion or cough. On examination, she has bilateral tonsillar erythema and exudate (Figure 31-1). Her anterior cervical lymph nodes are tender. Based on the presence of fever, absence of cough, tender lymphadenopathy, and tonsillar exudate, she is diagnosed with a high probability of group A β-hemolytic Streptococcus (GABHS) pharyngitis and prescribed antibiotics.

INTRO DUCTIO N Pharyngitis is in ammation of the pharyngeal tissues, and is usually associated with pain. The complaint of “sore throat” is a common one in the primary care of ce, and can be accompanied by other symptoms and signs including throat scratchiness, fever, headache, malaise, rash, joint and muscle pains, and swollen lymph nodes.

• Some viruses, such as adenovirus, cause in ammation of the pharyngeal mucosa by direct invasion of the mucosa or secondary to suprapharyngeal secretions. 4 Other viruses, such as rhinovirus, cause pain through stimulation of pain nerve endings by mediators, such as bradykinin. • The GABHS releases exotoxins and proteases. Erythrogenic exotoxins are responsible for the development of the scarlatiniform exanthem (Figure 31-2). 5 Secondary antibody formation because of cross-reactivity may result in rheumatic fever and valvular heart disease. 6 Antigen–antibody complexes may lead to acute poststreptococcal glomerulonephritis. • Untreated GABHS pharyngitis can result in suppurative complications including bacteremia, otitis media, meningitis, mastoiditis, cervical lymphadenitis, endocarditis, pneumonia, or peritonsillar abscess formation (Figure 31-3). Nonsuppurative complications include rheumatic fever and poststreptococcal glomerulonephritis.

RISK FACTO RS • Immune de ciency

EPIDEMIO LO GY

• Chronic irritation (eg, allergies, cigarette smoking)

• Pharyngitis accounts for 1% of primary care visits. 1 • Viral infections account for an estimated 60% to 90% of cases of pharyngitis. • Bacterial infections are responsible for between 5% and 30% of pharyngitis cases, depending on the age of the population and the season. • The GABHS accounts for 5% to 10% of pharyngitis in adults and 15% to 30% in children.2 Up to 38% of cases of tonsillitis are because of GABHS.

FIGURE 31-1 Str p p haryng itis showing to nsillar xud at and ryth ma. (Re p rod uce d with p e rmission from Michae l Ng uye n, MD.)

FIGURE 31-2 Scarlatiniform rash in scarl t f v r. This 7-y ar-old b oy has a typ ical sand p ap r rash with his str p throat and f v r. Th ryth ma is p articularly conc ntrat d in th axillary ar a. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

143

PART 5

144

EAR, NO SE, AND THRO AT

A

Ch a pt e r 31

FIGURE 31-4 Mononucl osis in a young ad ult with consid rab l tonsillar xud at . (Re p rod uce d with p e rmissio n from Trace y Cawthorn, MD.)

anterior cervical lymphadenopathy with severe tenderness to palpation are additional ndings. • Palatal petechiae can be seen in all types of pharyngitis (Figure 31-6). • A sandpaper rash is suggestive of scarlet fever (see Figure 31-2). • Lymphoid hyperplasia can cause a cobblestone pattern on the posterior pharynx or palate from viral infections, gastroesophageal re ux disease (GERD), or allergies (Figure 31-7). Although it usually is more suggestive of a viral infection or allergic rhinitis, lymphoid hyperplasia can be seen in strep pharyngitis (Figure 31-8).

B FIGURE 31-3 A. P ritonsillar ab sc ss on th l ft showing uvular d viation away from th sid with th ab sc ss. B. P ritonsillar ab sc ss with sw lling and anato mic d istortion of th rig ht tonsillar r g ion. (Re p rod uce d with p e rmission from Charlie Gold b e rg , MD. Cop yrig ht © 2005 The Re g e nts of the Unive rsity of California.)

DIAGNO SIS CLINICAL FEATURES • Rhinorrhea and cough are more consistent with viral etiology. • Rapid-onset odynophagia, tonsillar exudates, anterior cervical lymphadenopathy, and fever are consistent with streptococcal pharyngitis. • Not all tonsillar exudates are caused by streptococcal pharyngitis. Mononucleosis and other viral pharyngitis can cause tonsillar exudates (Figures 31-4 and 31-5). The positive predictive value for tonsillar exudate in strep throat is only 31%; that is, 69% of patients with tonsillar exudate will have a nonstreptococcal cause. • Para- and supra-tonsillar edema with medial and/ or anterior displacement of the involved tonsil and uvular displacement to the contralateral side suggest peritonsillar abscess (see Figure 31-3). Trismus and

FIGURE 31-5 Viral p haryng itis in a young ad ult showing nlarg d cryp tic tonsils with som ryth ma and xud at . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

ph a r YNGIt IS

FIGURE 31-6 Viral p haryng itis with visib l p alatal p t chia . Palatal p t chia can b s n in all typ s of p haryng itis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 5

EAR, NO SE, AND THRO AT

FIGURE 31-7 Viral p haryng itis with p romin nt vascular inj ction of th so ft p alat and lymp hoid hyp rp lasia. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

• The following criteria are helpful in the diagnosis of GABHS pharyngitis7-10: ° History of fever or temperature of 38°C (100.4°F) (1 point) ° Absence of cough (1 point) ° Tender anterior cervical lymph nodes (1 point) ° Tonsillar swelling or exudates (1 point) ° Age ■ Less than 15 years (1 point) ■ 15 to 45 years (0 points) ■ Greater than 45 years (–1 point) The probability of GABHS is approximately 1% with –1 to 0 points and approximately 51% with 4 to 5 points. 11 LABO RATO RY TESTS AND IMAGING • Rapid antigen detection is often used to diagnose GABHS. Test options include enzyme immunoassays, latex agglutination, liposomal method, and immunochromatograph assays; the latter has the highest reported sensitivity (0.97), speci city (0.97), and positive (32.3) and negative (0.03) likelihood ratios.12 • The gold standard for the diagnosis of streptococcal infection is a positive throat culture. However, GABHS is part of the normal oropharyngeal ora in many patients and the diagnosis of acute streptococcal pharyngitis must include both the clinical signs of acute infection and a positive throat culture. • False-positive tests for streptococcal infection can occur when the patient is colonized with GABHS but it is not the cause of the acute disease.

FIGURE 31-8 Str p p haryng itis with d ark n crotic ar a on rig ht tonsil and p romin nt lymp hoid hyp rp lasia in a cob b l ston p att rn on th p ost rior p harynx. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

145

146

PART 5

EAR, NO SE, AND THRO AT • False-negative tests for streptococcal infection can occur when poor sampling technique with the throat swab fails to recover the streptococcal organism when it is the cause of the acute infection. • A positive mono spot (likelihood ratio in the rst week of illness 5.7) and/ or greater than 40% atypical lymphocytes on the peripheral smear (likelihood ratio 39) indicate mononucleosis. 12 • Viral cultures obtained from vesicles can be obtained in Coxsackievirus and herpes infections, but the diagnosis is usually based on clinical suspicion and ndings. • Head-neck computed tomography (CT) scan can assist in the diagnosis and localization of peritonsillar abscess and should be obtained if further extension into the deeper neck is suspected. 13

DIFFERENTIAL DIAGNO SIS • Infectious mononucleosis—Nausea, anorexia without vomiting, uvular edema, generalized symmetric lymphadenopathy, and lethargy particularly in teenagers and young adults, are more suggestive of acute mononucleosis (Epstein-Barr virus [EBV]) although the pharyngeal examination has a similar appearance to GABHS (see Figure 31-4). Hepatosplenomegaly is indicative of EBV in this group. • Herpangina or Coxsackievirus infection—Oropharyngeal vesicles and ulcers on the palate indicate herpangina, which is caused by Coxsackievirus A16 in the majority of cases (Figure 31-9). • Oral Candida—Whitish plaques of the oropharyngeal mucosa indicate oral Candida or thrush, which can be found in adults with immunosuppression (see Chapter 135, Candidiasis). • Sexually transmitted infections—Primary human immunode ciency virus, gonococcal and syphilitic pharyngitis can all present with the symptom of sore throat. Although uncommon, these diagnoses should be considered in high-risk populations.

Ch a pt e r 31

• Primary herpes gingivostomatitis causes oral ulcers and pain in the mouth. The wide distribution of ulcers with the rst case of herpes simplex virus (HSV)-1 distinguishes this infection from other types of pharyngitis (see Chapter 128, Herpes Simplex). • Cytomegalovirus (CMV)—Primary CMV infection in the immunocompetent host is usually asymptomatic. In the immunocompromised host, CMV may present with a mononucleosis-like syndrome clinically indistinguishable from EBV infection. • Deep neck infections—Asymmetry of the neck, neck masses, and any displacement of the peripharyngeal wall should raise suspicion. Associated shortness of breath may be a warning sign of impending airway obstruction. Other complications include aspiration, thrombosis, mediastinitis, and septic shock. 13 • Epiglottitis—Rapid-onset fever, malaise, sore throat, and drooling in the absence of coughing characterize acute epiglottitis; uncommon in adults. Progression of the disease can lead to life-threatening airway obstruction. Fortunately, this is a rare condition because of the preventive effect of the Haemophilus inf uenzae type b (HIB) vaccine. • Supraglottitis—Symptoms are similar to epiglottitis. Sore throat and painful swallowing are the most common presenting symptoms, seen in more than 90% of cases. Muf ed voice and drooling, dyspnea, stridor, and cough reported in less than 50% of cases. No de nite organism is identi ed in the majority of cases. Unlike epiglottitis in children, HIB is responsible for less than 20% of adult cases but still accounts for the majority of positive cultures. Mortality rates have been reported up to 20%. Currently it is more common than epiglottitis, because of HIB vaccine. • Diphtheria—A rare condition in the United States today, as most patients have been immunized. However, it needs to be considered, especially in unvaccinated and immigrant populations. Pharyngeal diphtheria presents with sore throat, low-grade fever, and malaise. The pharynx is erythematous with a grayish pseudomembrane that cannot be scraped off. Complications include myocarditis resulting in acute and severe congestive heart failure (CHF), endocarditis, and neuropathies. • Other bacterial causes—Non–group A Streptococcus, Fusobacterium necrophorum, Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Arcanobacterium haemolyticum have all been isolated as bacterial causes of pharyngitis; not as clinically signi cant, but all generally respond to treatments prescribed for strep pharyngitis.

MANAGEMENT NO NPHARMACO LO GIC • Hydration with plenty of liquids • Salt-water gargles • Lozenges for comfort MEDICATIO NS • Acetaminophen and ibuprofen can be used for symptomatic relief of fever and pain. Doses can be alternated as needed.

FIGURE 31-9 H rp ang ina caus d b y Coxsacki virus A16.

• Steroids (eg, dexamethasone single 10-mg injection) are indicated in severe tonsillitis in patients without immunocompromise. 12 SO R However, there is no good evidence to recommend steroids in infectious mononucleosis. 14

ph a r YNGIt IS

• In extreme cases of pharyngitis, 1 teaspoon of viscous lidocaine 2% in a half glass of water gargled 20 to 30 minutes before meals helps the odynophagia. This is typically only recommended in rare cases because of risk of aspiration, potential toxicity of lidocaine, and the risk for oral mucosal burns—consider hospitalization if symptoms are severe. • Antibiotic use—Use the clinical prediction rule (given earlier [see “Clinical Features”]) for estimating the probability of GABHS7-11: ° Low probability (no test, no treatment for GABHS): Patients scoring 0 points should be treated symptomatically and should not be given antibiotics. ° Intermediate probability (test and treatment based on result): Patients with 1 to 3 points (probability of GABHS is approximately 18%) should undergo a rapid antigen test and be treated with antibiotics if positive. ° High probability (no test, treatment for GABHS): Patients with 4 to 5 points should be considered for empiric antibiotic treatment. • For suspected or proven GABHS, penicillin V 500 mg orally 2 to 3 times daily for 10 days continues to be the treatment of choice for adults. 15 Erythromycin 500 mg orally 4 times daily may be used in penicillin allergic patients. Penicillin G 1.2 million units intramuscular (IM) single dose may be used if unable to tolerate oral medication. • Penicillin G (600 mg IV every 6 h for 24-48 h) in combination with metronidazole (15 mg/ kg IV more than 1 h followed by 7.5 mg/ kg IV more than 1 h every 6-8 h) is recommended for peritonsillar abscess. REFERRAL • If signs of airway impairment are present, the patient should be immediately transported to an emergency department. Intubation can be extremely dif cult and risky. • Refer patients with peritonsillar abscess to ear, nose, and throat (ENT). Incision and drainage is the treatment of choice in addition to using systemic antibiotics. • Consider ENT referral for tonsillectomy in proven recurrent GABHS cases, or under certain other conditions (eg, antibiotic allergies or intolerances) with recurrence. 16 However, there is no evidence to support tonsillectomy for isolated cases. 17

PRO GNO SIS • Sore throat, regardless of the cause, is typically self-limiting. Typical symptoms last for 3 to 4 days. • Longer-term complications are rare but antibiotic treatment to prevent these sequelae remains justi ed for treatment. Antibiotics shorten the duration of illness by approximately 1 day and can reduce the risk of rheumatic fever by approximately two-thirds in communities where this complication is common. 15 However, gastrointestinal (GI) symptoms like mild diarrhea are common side effects of antibiotic therapy. The number needed to treat to prevent 1 sore throat at day 3 is less than 6; at week 1 it is 21. 15

FO LLO W-UP Follow up if clinically deteriorating, especially if swallowing or breathing becomes more dif cult or severe headache develops.

PART 5

EAR, NO SE, AND THRO AT PATIENT EDUCATIO N • The treatment for most cases of non-GABHS pharyngitis is education. Explain to patients the difference between a viral and a bacterial infection to help them understand why antibiotics were prescribed or not prescribed. Antibiotic treatment for a patient with an obvious viral infection is inappropriate, despite patient requests. Studies demonstrate that spending time with the patient to explain the disease process is associated with greater patient satisfaction than prescribing an antibiotic. 18,19 • Rest, liquids, and analgesics should be encouraged. • Patients receiving antibiotics should be reminded to complete the entire course, even if symptoms improve. Common antibiotic side effects, like rash, nausea, and diarrhea should be reviewed. • Patients with mononucleosis and splenomegaly should be warned to avoid contact sports because of the risk of splenic rupture.

PATIENT RESO URCES

• Healthline. Pharyngitis—http:/ / www.healthline.com/ health/ pharyngitis# Overview1. • MedlinePlus. Strep throat—www.nlm.nih.gov/ medlineplus/ ency/ article/ 000639.htm. • FamilyDoctor.org. Mononucleosis—http:/ / amilydoctor.org/ amilydoctor/ en/ diseases-conditions/ mononucleosis .html. PRO VIDER RESO URCES

• Free clinical calculator online: Modi ed Centor Score for Strep Pharyngitis—http:/ / www.mdcalc.com/ modif ed-centorscore- or-strep-pharyngitis.

REFERENCES 1. Vital Health and Statistics. US Department of Health and Human Services, Series 13, Number 169 April 2011; Ambulatory Medical Care Utilization Estimates or 2007. 2. Bisno AL, Gerber MA, Gwaltney JM, et al. Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. Clin In ect Dis. 2002;35:(2):113-125. 3. Bottin R, Marioni G, Rinaldi R, et al. Deep neck infection: a presentday complication. A retrospective review of 83 cases (1998-2001). Eur Arch Otorhinolaryngol. 2003;260(10):576-579. 4. Aung K, Ojha A, Lo C. Viral Pharyngitis. http:/ / emedicine.medscape.com/ article/ 225362-overview. Accessed July 2013. 5. Halsey E. Bacterial Pharyngitis. http:/ / emedicine.medscape.com/ article/ 225243-overview. Accessed July 2013. 6. Guilherme L, Kalil J, Cunningham M. Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease. Autoimmunity. 2006;39(1):31-39. 7. Singh S, Dolan JG, Centor RM. Optimal management of adults with pharyngitis: a multi-criteria decision analysis. BMC Med In orm Decis Mak. 2006;6:14. 8. Choby BA. Diagnosis and treatment of streptococcal pharyngitis. Am Fam Physician. 2009;79(5):383-390.

147

148

PART 5

EAR, NO SE, AND THRO AT 9. Aalbers J, O’Brien KK, Chan WS, et al. Predicting streptococcal pharyngitis in adults in primary care: a systematic review of the diagnostic accuracy of symptoms and signs and validation of the Centor score. BMC Med. 2011 Jun 1;9:67. 10. Merrill B, Kelsberg G, Jankowski TA, Danis P. Clinical inquiries. What is the most effective diagnostic evaluation of streptococcal pharyngitis? J Fam Pract. 2004;53(9):734, 737-738, 740. 11. McIsaac WJ, Goel V, To T, Low DE. The validity of a sore throat score in family practice. CMAJ. 2000;163:811-815. 12. Ebell MH. Sore throat. In: Sloane PD, Slatt LM, Ebell MH, Jacques LB, eds. Essentials o Family Medicine. Baltimore, MD: Lippincott Williams & Wilkins; 2002:727-738. 13. Wang LF, Kuo WR, Tsai SM, Huang KJ. Characterizations of lifethreatening deep cervical space infections: a review of one hundred ninety-six cases. Am J Otolaryngol. 2003;24(2):111-117. 14. Candy B, Hotopf M. Steroids for symptom control in infectious mononucleosis. Cochrane Database Syst Rev. 2006;3:CD004402.

CHAPTe R 31

15. Spinks A, Glasziou PP, Del Mar CB. Antibiotics for sore throat. Cochrane Database Syst Rev. 2006;(4):CD000023. 16. Baugh RF, Archer SM, Mitchell RB, et al. Clinical practice guideline: tonsillectomy in children. Otolaryngol Head Neck Surg. 2011;144(suppl 1):S1-S30. 17. Neill RA, Scoville C. Clinical inquiries. What are the indications for tonsillectomy in children? J Fam Pract. 2002;51(4):314. 18. Hamm RM, Hicks RJ, Bemben DA. Antibiotics and respiratory infections: are patients more satis ed when expectations are met. J Fam Pract. 1996;43(1):56-62. 19. Ong S, Nakase J, Moran GJ, et al. Antibiotic use for emergency department patients with upper respiratory infections: prescribing practices, patient expectations, and patient satisfaction. Ann Emerg Med. 2007;50(3):213-220.

PART 5

THE LARYNX (HO ARSENESS)

149

EAR, NO SE, AND THRO AT

32 THE LARYNX (HO ARSENESS) Laura Matrka, MD C. Blake Simp son, MD J. Michae l King , MD

PATIENT STO RY

Esophagus

F VF

Trachea TVF

A 47-year-old man with a 40 pack-year history of smoking presents with worsening hoarseness that began approximately 6 weeks ago. He complains of globus sensation and dif culty swallowing solid foods. He denies odynophagia, otalgia, hemoptysis, and hematemesis. There is no associated cough, and he has not had any constitutional symptoms such as fevers, chills, or recent weight loss. Hoarseness in a middle-aged man with the above symptoms is very common, and the differential diagnosis is long (all the diseases discussed later are possibilities in this case scenario). The patient’s smoking history and duration of symptoms should raise concern for a possible laryngeal malignancy. However, there is a higher incidence of laryngopharyngeal re ux (LPR) followed by benign vocal fold (cord) lesions.

INTRO DUCTIO N The evaluation of hoarseness typically involves rst ruling out the most serious pathologies, such as laryngeal squamous cell carcinoma (SCC), in adults or recurrent respiratory papillomatosis in children, and then proceeding with a more focused and subtle evaluation to uncover any of the many benign pathologies that affect the larynx. Treatment of these benign pathologies must take into account the patient’s lifestyle and voice needs. It also often incorporates education on vocal hygiene, which involves increasing hydration, decreasing mucus and vocal abuse, and reducing acid re ux if a factor.

Epiglottis

FIGURE 32-1 Normal larynx (true and alse vocal old s). FVF, alse vocal old ; TVF, true vocal old (cord ). (Re p rod uce d with p e rmission from C. Blake Simp son, MD.)

• Squamous cell carcinoma accounts for 95% of laryngeal cancer. Approximately 11,000 new cases are diagnosed in the United States each year. Peak incidence is in the sixth and seventh decades of life with a strong male predominance. 1 • Recurrent respiratory papillomatosis (RRP) represents the most common benign neoplasm of the larynx among children and should be considered in children with chronic hoarseness. A known risk factor for juvenile onset is the triad of a rstborn child (75%), teenage mother, and vaginal delivery. The incidence is 4.3 per 100,000 children and 1.8 per 100,000 adults. 2 There is a known association between cervical human papillomavirus (HPV) infection in the mother and juvenileonset RRP, but the precise mode of transmission is unclear. The risk of a child contracting RRP after delivery from an actively infected mother with genital HPV ranges from 0.25% to 3%. 3 Because cesarean section does not prevent RRP in all cases, routine prophylactic cesarean section in mothers with active condyloma acuminata is currently not recommended.

SYNO NYMS AND DEFINITIO NS • Hoarseness, dysphonia, vocal strain, breathiness, raspiness

Vocal Process

• Vocal cords, true vocal cords, true vocal folds, glottis (Figure 32-1) • False vocal folds, false vocal cords (mucosal folds in the supraglottis, just superior to the true vocal folds and separated from the true folds by the ventricle) • Flexible beroptic laryngoscopy, direct laryngoscopy, nasopharyngeal scope (NP scope), transnasal beroptic laryngoscopy • Stroboscopy, videolaryngostroboscopy (VLS), strobe examination Right

Left

EPIDEMIO LO GY • The most common cause of hoarseness in adults and children overall is viral infection causing laryngitis (Figure 32-2). • LPR disease may be present in up to 50% of patients presenting with voice and laryngeal disorders. 1 It is less commonly the sole cause of hoarseness.

FIGURE 32-2 Laryng itis—d i use e rythe ma and in ammation, irre g ular vocal old e d g e s. (Re p ro d uce d with p e rmission fro m C. Blake Simp son, MD.)

150

PART 5

EAR, NO SE, AND THRO AT ETIO LO GY AND PATHO PHYSIO LO GY • Laryngitis is a nonspeci c term to describe in ammation of the larynx from any cause. Most commonly this is due to a viral upper respiratory infection. Compare the anatomy of the normal larynx (see Figure 32-1) with that of acute laryngitis (see Figure 32-2), with the primary differences being in the diffuse erythema and edema of the vocal folds and the often transient irregularities of the vocal fold medial edge as compared to the straight medial edge of the normal vocal fold. Laryngeal symptoms result from dry throat, mucous stasis, and recurrent trauma from coughing and throat clearing. • LPR must be differentiated from gastroesophageal re ux disease (GERD), in which acid re ux is more likely to cause heartburn, indigestion, and regurgitation and does not necessarily reach the larynx or upper aerodigestive tract. LPR is more likely to present with frequent throat clearing, dry cough, hoarseness, and globus sensation and does not include heartburn in more than 60% of patients. The larynx is highly sensitive to even small amounts of acid or pepsin. Thus, patients who do not have severe enough re ux to cause esophagitis, with its associated symptoms of GERD, may still develop symptomatic laryngeal mucosal injury, with its associated symptoms of LPR. 1,4-6 • SCC has a multifactorial etiology, but 90% of patients have a history of heavy tobacco and/ or alcohol use. These risk factors have a synergistic effect. Other independent risk factors include employment as a painter or metalworker, exposure to diesel or gasoline fumes, and exposure to therapeutic doses of radiation. • RRP is caused by HPV-6 and HPV-11. Onset is predominantly in young children, although an adult-onset variant exists. Its course is unpredictable and highly variable. Tracheal and bronchopulmonary spread can occur, as can malignant transformation to SCC; the latter is rare. Bronchopulmonary spread is uniformly fatal as a consequence of the lack of surgical options. • Vocal cord nodules are benign lesions arising from mechanical trauma (vocal abuse or misuse) and are often described as a “callous” of the vocal folds. Vocal cord polyps or cysts can arise from vocal abuse, a blocked mucous gland, vocal fold hemorrhage, a background of polypoid corditis (see below), or idiopathic etiologies. They are a common cause of dysphonia in singers, teachers, and other professional voice users. Vocal cord granulomas are associated with LPR and/ or intubation trauma and rarely require surgery. • Causes of vocal cord paresis or paralysis are myriad:1,7 ° Iatrogenic surgical injury (anterior spine fusion, carotid endarterectomy, thyroidectomy) is most common (25%). ° Nonlaryngeal malignancy (mediastinal, bronchopulmonary, and skull base) (24%). ° No identi able cause (idiopathic), often assumed to be viral (20%). ° Nonsurgical trauma (penetrating or blunt injury and intubation injury) (10%). ° Neurologic causes (stroke, central nervous system [CNS] tumors, multiple sclerosis [MS], and amyotrophic lateral sclerosis [ALS]) (8%). ° In ammatory or infectious disease (2-5%). • Presbyphonia is a diagnosis of exclusion denoting vocal changes from aging of the larynx (gradually weakening voice, poor vocal projection, and vocal “roughness”). Hoarseness in patients older than 60 years of age is most commonly a result of benign vocal fold lesions followed by malignancy and vocal fold paralysis. Once a thorough evaluation has

Ch a pt e r 32

been done to rule out organic causes, presbyphonia is the cause of hoarseness in approximately 10% of elderly patients; it is characterized by atrophied vocal folds. 8

DIAGNO SIS CLINICAL FEATURES • Key historical and physical examination ndings can help differentiate benign pathology from potentially more serious problems: ° Otalgia (ear pain)—Often a source of referred pain from primary laryngeal and pharyngeal carcinomas; it is not typically seen with benign pathologies. ° Dysphagia and odynophagia (pain when swallowing)—Nonspeci c complaints, but potentially worrisome for obstructing lesions or reactive pharyngeal edema. ° Stridor or dyspnea—“Noisy breathing” with respiratory distress should be evaluated urgently to rule out impending airway obstruction. Less-severe dyspnea may be noted by patients with vocal cord paralysis caused by air escape during speech; a detailed history should reveal that it occurs only during speech or from the inability to perform adequate Valsalva maneuver as a result of loss of tight glottic closure. ° Globus pharyngeus—The persistent or intermittent nonpainful sensation of a lump or foreign body in the throat. This is commonly associated with LPR. ° Neck mass—Associated unilateral or bilateral lymphadenopathy is suspicious for a laryngeal neoplasm until proven otherwise. ° Timing—Onset, duration, and frequency of symptoms are important. • Red ags for laryngeal carcinoma include a history of smoking and/ or alcohol abuse, associated neck mass, weight loss or severe dysphagia, presence of stridor (often initially noted with sleep or when lying at), and otalgia. • LPR symptoms include hoarseness, throat clearing, “postnasal drip,” chronic cough, dysphagia, globus pharyngeus, and sore throat. “Heartburn” is not a requisite symptom! • Hallmark of diagnosis is direct visualization of the larynx, often performed by an otolaryngologist with a exible laryngoscopic examination. Stroboscopy is added to the evaluation when visualization of the mucosal wave of the vocal folds is necessary. Assessment of the mucosal wave aids in determining the depth of a lesion within the vocal fold and the severity of its effect on the voice. LABO RATO RY AND IMAGING • Laboratory studies are not usually helpful, except in the rare case that a previously undiagnosed rheumatologic disease presents with vocal complaints as the initial symptom. • Plain lms of the chest are useful to rule out bronchopulmonary or mediastinal masses as a cause of vocal cord paralysis, but are generally not helpful for primary laryngeal lesions. • A computed tomography (CT) of the neck and chest with contrast is useful in ruling out pathology along the length of the recurrent laryngeal nerve in cases of unexplained vocal cord paralysis and in cases suspicious for carcinoma, especially if there is associated cervical lymphadenopathy. A chest X-ray is sometimes used to replace the chest CT. • A magnetic resonance imaging (MRI) with and without gadolinium offers the best imaging for suspected primary CNS or skull base

t h e La r YNX (h O a r Se Ne SS)

PART 5

EAR, NO SE, AND THRO AT

Edema

R ight

Left G lottic SCC

Left

FIGURE 32-3 Laryng op haryng e al re ux. Postcricoid re g ion e d e ma (normal is le ss ull and ne arly concave ) and e d e ma just in e rior to the true vocal old e d g e (in rag lottic e d e ma) ind icative o chronic in ammation rom re ux, o te n calle d “p se ud osulcus.” O the r f nd ing s o LPR not se e n in this imag e includ e thick mucus and mucosal e rythe ma. (Re p rod uce d with p e rmission from C. Blake Simp son, MD.)

lesions; this is typically added to the workup for vocal cord paralysis when evidence of high vagal injury such as weakness in palate elevation is present. • Referral to a gastroenterologist for dual-channel 24-hour pH probe monitoring (while on antiref ux medications) is a useful diagnostic tool for patients with suspected LPR.

DIFFERENTIAL DIAGNO SIS • Laryngitis (see Figure 32-2)

FIGURE 32-5 Sq uamous ce ll carcino ma, ad vance d stag e with le t true vocal cord p aralysis. (Re p rod uce d with p e rmission from C. Blake Simp son, MD.)

• Laryngeal papillomatosis (Figures 32-6 and 32-7) • Vocal cord nodule (Figure 32-8) • Vocal cord polyp (Figure 32-9) • Vocal cord cyst • Vocal cord paresis or paralysis • Presbyphonia • Neurologic disorders (MS, Parkinson disease, ALS, and essential tremor) • Systemic diseases (Wegener granulomatosis, sarcoidosis, rheumatoid arthritis)

MANAGEMENT

• Laryngopharyngeal re ux (Figures 32-3 and 32-4) • Laryngitis—Empiric treatment is aimed at alleviating symptoms such as cough and thinning nasal or pharyngeal secretions. Hydration is critical for healing (increased water intake, steam showers, humidi ers,

• SCC (Figure 32-5)

Esophagus A-E Fold

Arytenoid Process

Edema

Mucous Papilloma FIGURE 32-4 Laryng op haryng e al re ux d uring p honation with d i use e rythe ma, in ammation, and thick mucus. (Re p rod uce d with p e rmission from C. Blake Simp son, MD.)

FIGURE 32-6 Ad ult re curre nt re sp iratory p ap illomatosis. Arye p ig lottic old (A-E old ). (Re p rod uce d with p e rmissio n from C. Blake Simp son, MD.)

151

152

PART 5

EAR, NO SE, AND THRO AT

Ch a pt e r 32

Esophagus Polyp Mucous

Papilloma

FIGURE 32-7 Re curre nt re sp iratory p ap illomatosis in a 3-ye ar-old child . The p ap illomas are ne arly ob structing the airway and have re q uire d d e b rid e me nt. (Re p rod uce d with p e rmission from C. Blake Simp son, MD.)

and saunas may help). Throat clearing should be discouraged and voice rest encouraged. Talking should be conserved, not prohibited. Inform patients that whispering causes even more vocal strain than normal speech. • Vocal cord nodules, polyps, and cysts—Initial management involves speech therapy accompanied by medical treatment of dehydration, allergies, sinonasal secretions (postnasal drip), and LPR. Refractory disease may require surgical excision. • Laryngeal papillomatosis—Most children have a recalcitrant course that requires periodic surgical debridement by an otolaryngologist to prevent airway obstruction. Spontaneous remission may occur. Adjuvant therapy, such as intraepithelial injection of cidofovir at the time of surgery, is commonly utilized in more aggressive disease. It is hoped that the administration of the Gardasil vaccine will decrease the incidence of RRP over time. Some practitioners administer the Gardasil vaccine in a nonprophylactic manner to patients with existing RRP,

FIGURE 32-9 Larg e , ob structing laryng e al p olyp with thick mucus colle cting around it. (Re p rod uce d with p e rmission fro m C. Blake Simp son, MD.)

although there is no strong evidence currently to support a treatment effect of the vaccine. 2,3 • LPR—Mainstay treatment involves patient education to modify diet and behavior (avoidance of acidic or greasy foods, tobacco cessation, limiting alcohol and caffeine, weight loss, and avoiding meals shortly before lying down). Medical therapy consists of twice-daily proton pump inhibitors (PPIs) 30 to 60 minutes before meals, which can often be weaned after several months of therapy. Some patients bene t from adding an H2-blocker, such as ranitidine 300 mg, at bedtime. • SCC—Multidisciplinary management is best. Depending on the staging and extent of disease, patients often receive one or more modalities of treatment including surgery, radiation, and chemotherapy. • Vocal cord paresis or paralysis—Treatment is targeted at the underlying disorder. Some patients may be candidates for surgical intervention to reposition the paralyzed cord medially with an implant. With a mobile vocal fold on the contralateral side, airway is rarely compromised by medialization of the paralyzed vocal fold. These procedures restore voice quality and often alleviate chronic aspiration problems. • Neurologic diseases—Laryngeal complaints can be associated with MS, myasthenia gravis, Parkinson disease, ALS, and essential tremor. In addition to managing the underlying disorder, a trial of voice therapy is sometimes useful.

N odules

• Systemic diseases—Diseases such as Wegener granulomatosis, sarcoidosis, relapsing polychondritis, and rheumatoid arthritis rarely may involve the larynx. Voice and swallowing problems in these patients should be evaluated by an otolaryngologist for possible therapies to improve the voice and to rule out associated airway stenosis. • Presbyphonia—This is a diagnosis of exclusion. Once organic etiologies have been ruled out, a trial of voice therapy is recommended before considering surgical options, such as vocal fold injection augmentation to plump the atrophied vocal fold.

FO LLO W-UP

FIGURE 32-8 Vocal cord nod ule s. (Re p rod uce d with p e rmission from C. Blake Simp son, MD.)

• Urgent referral to an otolaryngologist for exible laryngoscopic examination of the larynx is advisable when the history and physical are suspicious for carcinoma.

t h e La r YNX (h O a r Se Ne SS)

PART 5

EAR, NO SE, AND THRO AT

• When symptoms worsen or fail to resolve, referral to an otolaryngologist (or laryngologist) is indicated (see “Provider Resources” below to nd a laryngologist in your area).

REFERENCES

• Patients suspected of having LPR should be seen approximately 6 to 8 weeks after initiating empiric therapy with a PPI and lifestyle measures. An otolaryngology and/ or gastroenterology consultation is indicated when symptoms do not improve after optimized behavioral and medical management or for patients who require long-term PPI therapy (longer than 12 months). Some of these patients, particularly those with chronic cough or long-standing requirement for PPIs, may require transnasal esophagoscopy (performed in the otolaryngologist’s of ce) or esophagogastroduodenoscopy (performed by a gastroenterologist in the endoscopy suite). Recent evidence has pointed to chronic cough as an independent indicator of esophageal adenocarcinoma, and Barrett esophagus should be ruled out in any patient requiring longterm PPI use. 9

2. Derkay CS. Recurrent respiratory papillomatosis. Laryngoscope. 2001;111:57-69.

PATIENT EDUCATIO N • In cases of nonmalignant pathology, vocal hygiene and other lifestyle measures often play an important role in treatment. Efforts should focus on increasing hydration, decreasing caffeine intake, tobacco cessation, and prevention of excessive alcohol use. • Vocal cord nodules, polyps, and cysts typically occur in professional voice users (ministers, auctioneers, teachers, singers, etc). Speech therapists can be integral in preventing and healing lesions by teaching patients how to avoid vocal misuse. • Benign laryngeal pathology may be improved, but not necessarily resolved, by controlling both gastroesophageal and LPR disease. Patients should be educated about GERD or LPR risk factors: ° Spicy, acidic, or greasy foods ° Tobacco and alcohol abuse ° Caffeinated beverages (especially carbonated sodas) ° Citric juices, tomato sauces, chocolate, mints ° Obesity ° Eating meals within 2 to 3 hours of lying down

PATIENT RESO URCES

• American Academy of Otolaryngology-Head and Neck Surgery— http:/ / www.entnet.org/ healthinfo/ index.cfm. • ENT USA—http:/ / www.entusa.com. • VoiceProblem.org—http:/ / www.voiceproblem.org. PRO VIDER RESO URCES

• VoiceProblem.org—http:/ / www.voiceproblem.org. • Information about laryngeal pathology as well as an extensive list of laryngologists worldwide—http:/ / www.voicedoctor.net/ links/ physicians.html.

1. Ossoff R, Shapshay S, Woodson G, Netterville J. The Larynx. Philadelphia, PA: Lippincott Williams & Wilkins; 2003.

3. Gallagher TQ, Derkay CS. Recurrent respiratory papillomatosis: update 2008. Curr Opin Otolaryngol Head Neck Surg. 2008;16:532-542. 4. Simpson CB. Patient of the month program: breathy dysphonia. American Academy o Otolaryngol Head Neck Surg. 2002;31(7):19-28. 5. Koufmann JA, Amin MA, Panetti M. Prevalence of re ux in 113 consecutive patients with laryngeal and voice disorders. Otolaryngol Head Neck Surg. 2000;123:385-388. 6. Koufman JA, Aviv JE, Casiano RR, Shaw GY. Laryngopharyngeal re ux: position statement of the committee on speech, voice, and swallowing disorders of the American Academy of OtolaryngologyHead and Neck Surgery. Otolaryngol Head Neck Surg. 2002;127:32-35. 7. Benninger MS, Gillen JB, Altman JS. Changing etiology of vocal fold immobility. Laryngoscope. 1998;108:1346-1349. 8. Kendall K. Presbyphonia: a review. Curr Opin Otolaryngol Head Neck Surg. 2007;15:137-140. 9. Reavis KM, Morris CD, Gopal DV, et al. Laryngopharyngeal re ux symptoms better predict the presence of esophageal adenocarcinoma than typical gastroesophageal re ux symptoms. Ann Surg. 2004;239(6): 849-858.

153

This page intentionally left blank

Pa r t 6

O RAL HEALTH

*

St re ng t h o Re co mme nd at io n (SO R)

De f nit io n

A

Re comme nd ation b ase d on consiste nt and g ood -q uality atie nt-orie nte d e vid e nce .*

B

Re comme nd ation b ase d on inconsiste nt or limite d -q uality atie nt-orie nte d e vid e nce .*

C

Re comme nd ation b ase d on conse nsus, usual ractice , o inion, d ise ase -orie nte d e vid e nce , or case se rie s or stud ie s o d iag nosis, tre atme nt, re ve ntion, or scre e ning .*

Se e A

e nd ix A on ag e s 1241-1244 or urthe r in ormation.

156

PART 6

O RAL HEALTH

33 BLACK HAIRY TO NGUE Richard P. Usatine , MD Wand a C. Gonsalve s, MD

Ch a pt e r 33

SYNO NYMS BHT is also known as hyperkeratosis o the tongue, lingua villosa nigra.

EPIDEMIO LO GY PATIENT STO RY A 60-year-old man who smokes presents to the physician’s o ce smelling o alcohol. He complains o a black discoloration o his tongue and a gagging sensation on occasion. He admits to smoking 1 to 2 packs per day along with drinking at least 6 to 8 beers per day. The patient brushes his teeth in requently and has not seen a dentist or a long time. On physical examination, his teeth are stained and his tongue shows elongated papillae with brown discoloration (Figure 33-1). Diagnoses include black hairy tongue (BHT), poor oral hygiene, and tobacco and alcohol addiction.

INTRO DUCTIO N BHT is a benign disorder o the tongue characterized by abnormally hypertrophied and elongated li orm papillae on the sur ace o the tongue. 1 In addition, there is de ective desquamation o the papillae on the dorsal tongue resulting in a hair-like appearance. 2

The prevalence o BHT varies depending on the risk actors in the population being studied. • It can be as high as 57% in persons incarcerated or addicted to drugs. 3 • The prevalence in Minnesota schoolchildren was 0.06%. 4 • Turkish dental patients showed higher rates o BHT in men, smokers, and black tea drinkers. The highest prevalence was 54% in heavy smokers. 5

ETIO LO GY AND PATHO PHYSIO LO GY • BHT (see Figure 33-1) is a disorder characterized by elongation and hypertrophy o li orm papillae and de ective desquamation o the papillae. 2,6 • These papillae, which are normally about 1 mm in length, may become as long as 12 mm. ° The elongated li orm papillae 1can then collect debris, bacteria, ungus, or other oreign materials. • In an extensive literature review o reported cases o drug-induced BHT, 82% o the cases were caused by antibiotics (Figure 33-2). 1 • Dry mouth (xerostomia) rom medications, tobacco, and radiation therapy can lead to BHT. 1

FIGURE 33-1 Black hairy tong ue (BHT) showing e long ate d f li orm a illae with b rown d iscoloration in a man who is a he avy smoke r and d rinke r. Note the tob acco-staine d te e th. (Re p rod uce d with p e rmission from Brad Ne ville , DDS.)

FIGURE 33-2 Drug -ind uce d b lack hairy tong ue (BHT) with ye llowish-b rown e long ate d f li orm a illae in a atie nt taking a b road -s e ctrum antib iotic. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 6

BLa CK h a Ir Y t O NGUe

RISK FACTO RS • Tobacco (smoking and chewing)1 • Alcoholism and drug abuse (especially drugs that are smoked) • Poor oral hygiene • Medications (especially antibiotics and those causing xerostomia) • Oxidizing mouthwashes (containing peroxide) • Cancer, especially with radiation therapy • Drinking black tea or co ee

DIAGNO SIS CLINICAL FEATURES • Patients may be asymptomatic. However, the accumulation o debris in the elongated papillae may cause taste alterations, nausea, gagging, halitosis, and pain or burning o the tongue. 1 The diagnosis is made by visual inspection: • BHT may exhibit a thick coating o black, brown, or yellow discoloration, depending on oods ingested, tobacco use, and amount o co ee or tea consumed (Figure 33-3). TYPICAL DISTRIBUTIO N The lesion is restricted to the dorsum o the tongue, anterior to the circumvallate papillae, rarely involving the tip or sides o the tongue. LABO RATO RY TESTS Consider per orming a potassium hydroxide (KOH) preparation to rule out associated candidiasis.

FIGURE 33-3 Black hairy tong ue (BHT) that is also urrowe d in a he avy smoke r. Note this man also has ang ular che ilitis, oor d e ntition, and halitosis. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

O RAL HEALTH DIFFERENTIAL DIAGNO SIS • Black tongue can occur with the ingestion o bismuth subsalicylate or minocycline. Although the tongue has a black coating, the papillae are not elongated. Without the hypertrophy o papillae this is not a BHT (Figure 33-4). • Hairy leukoplakia—Appears as aint white vertical keratotic streaks typically on the lateral side o the tongue (Figure 33-5). Do not conuse BHT with oral hairy leukoplakia, an Epstein-Barr virus–related condition typically a ecting the lateral tongue bilaterally in immunocompromised patients, especially those with HIV in ection. • Oral candidiasis—White plaques typically ound on the buccal mucosa, tongue, and palate when removed has an erythematous base. The white color should make this easy to distinguish rom BHT (see Chapter 135, Candidiasis).

MANAGEMENT NO NPHARMACO LO GIC • Avoidance o predisposing risk actors (eg, tobacco, alcohol, and antibiotics). SO R • Stop the o ending medication in drug-induced BHT whenever possible.1 SO R

• Regular tongue brushing using a so t toothbrush or tongue scraper. SO R

MEDICATIO NS I candidiasis is present, an oral anti ungal is indicated. I there is no liver disease, the pre erred regimen or oral candidiasis is f uconazole 100 mg daily or 14 days. An alternative is clotrimazole troches 5 times a day or 14 days. Nystatin is less e ective. Fluconazole-treated HIV patients with oropharyngeal candidiasis were more likely to remain disease- ree than those treated with other anti ungal agents. 7 SO R

FIGURE 33-4 Black tong ue without e long ate d a illae in a woman with untre ate d e m hig us vulg aris. Note the alatal e rosions along with the b lack co lor o the tong ue . The b lack color was g one in 2 d ays a te r re d nisone was initiate d and the atie nt was ab le to e at ag ain. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

157

PART 6

158

O RAL HEALTH

CHApTER 33

PATIENT EDUCATIO N Tell the patients to brush their teeth and tongue twice a day or to use a tongue scraper. Address addictions and o er help to quit. Suggest that patients should eat rm oods, like resh apples, that will help to clean the tongue.

PATIENT RESO URCES

• Mayo Clinic. Black, Hairy Tongue—http:/ / www.mayoclinic .com/ health/ black-hairy-tongue/ DS01134. PRO VIDER RESO URCES FIGURE 33-5 O ral hairy le uko lakia cause d b y E ste in-Barr virus on the tong ue o a man with AIDS. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

REFERRAL Patients with poor oral hygiene should be re erred to a dentist. All patients should be encouraged to see a dentist at least twice yearly.

PREVENTIO N Good oral hygiene and avoidance o risk actors are essential.

PRO GNO SIS BHT is generally a sel -limited disorder, so the prognosis should be excellent with good oral hygiene and treatment.

• Medscape. Hairy Tongue—http:/ / emedicine.medscape.com/ article/ 1075886.

REFERENCES 1. Thompson DF, Kessler TL. Drug-induced black hairy tongue. Pharmacotherapy. 2010;30(6):585-593. 2. Harada Y, Gaa ar H. Black hairy tongue. A scanning electron microscopic study. J Laryngol Otol. 1977;91:91-96. 3. Bouquot JE. Common oral lesions ound during a mass screening examination. JAm Dent Assoc. 1986;112(1):50-57. 4. Redman RS. Prevalence o geographic tongue, ssured tongue, median rhomboid glossitis, and hairy tongue among 3,611 Minnesota schoolchildren. Oral Surg Oral Med Oral Pathol. 1970;30:390-395. 6. Sarti GM, Haddy RI, Scha er D, Kihm J. Black hairy tongue. Am Fam Physician. 1990;41:1751-1755. 7. Albougy HA, Naidoo S. A systematic review o the management o oral candidiasis associated with HIV/ AIDS. SADJ. 2002;57(11):457-466.

PART 6

GEO GRAPHIC TO NGUE

34 GEO GRAPHIC TO NGUE Erne st Vald e z, DDS Richard P. Usatine , MD Wand a C. Gonsalve s, MD

O RAL HEALTH SYNO NYMS Geographic tongue is also known as benign migratory glossitis, geographic stomatitis.

EPIDEMIO LO GY PATIENT STO RY A 23-year-old man presents to the physician’s o ce complaining o his tongue’s “strange appearance.” He denies pain or discom ort and is unsure how long the lesions have been present. The lesions seem to change areas o distribution on the tongue. The examination reveals large, well-delineated, shiny and smooth, erythematous spots on the surace o the tongue (Figure 34-1). The diagnosis is geographic tongue (benign migratory glossitis). The physician explains that it is benign and that no treatment is needed unless symptoms develop.

INTRO DUCTIO N Geographic tongue is a recurrent, benign, usually asymptomatic, inf ammatory disorder o the mucosa o the dorsum and lateral borders o the tongue. Geographic tongue is characterized by circinate, irregularly shaped erythematous patches bordered by a white keratotic band. The central erythematous patch represents loss o li orm papillae o tongue epithelium. Geographic tongue can, although rarely, present as symptomatic.

• Geographic tongue has an estimated prevalence o 1% to 3% o the population. 1 • It may occur in either children or adults, and exhibits a emale predilection. • Geographic tongue in the United States has a greater prevalence among white and black persons than among Mexican Americans. 2

ETIO LO GY AND PATHO PHYSIO LO GY • Geographic tongue is a common oral inf ammatory condition o unknown etiology. • Some studies have shown an increased requency in patients with allergies, pustular psoriasis, stress, type 1 diabetes, ssured tongue, and hormonal disturbances. 3 • Histopathologic appearance resembles psoriasis. 4 • Oddly, geographic tongue has an inverse association with cigarette smoking. 2,5

DIAGNO SIS CLINICAL FEATURES • The diagnosis is made by visual inspection and history o the lesion. The lesions are suggestive o a geographic map (hence geographic tongue) with pink continents surrounded by whiter oceans (see Figure 34-1). • Geographic tongue consists o large, well-delineated, shiny, and smooth, erythematous patches surrounded by a white halo (Figure 34-2). • Tongue lesions exhibit central erythema because o atrophy o the liorm papillae and are usually surrounded by slightly elevated, curving, white-to-yellow elevated borders (see Figures 34-1 and 34-2). • The condition typically waxes and wanes over time so the lesions appear to be migrating (hence migratory glossitis). • Lesions may last days, months, or years. The lesions do not scar. • Most patients are asymptomatic, but some patients may complain o pain or burning, especially when eating spicy oods. • Suspect systemic intraoral mani estations o psoriasis or reactive arthritis i the patient has psoriatic skin lesions or has conjunctivitis, urethritis, arthritis, and skin involvement suggestive o reactive arthritis (see Chapter 153, Reactive Arthritis). TYPICAL DISTRIBUTIO N FIGURE 34-1 Ge og rap hic to ng ue (b e nig n mig ratory g lossitis). Note the p ink contine nts among the white oce ans. (Re p rod uce d with p e rmission from Gonsalve s WC, Chi AC, Ne ville BW. Common oral le sions: p art II. Am Fam Phys. 2007;75(4):501-508. Cop yrig ht © 2007 Ame rican Acad e my of Family Physicians. All rig hts re se rve d .)

• The lesions are typically ound on the anterior two-thirds o the dorsal tongue mucosa. • Geographic tongue usually a ects the tongue, although other oral sites may be involved such as the buccal mucosa, the labial mucosa and less requently, the so t palate. 3

159

160

PART 6

O RAL HEALTH

FIGURE 34-2 Ge og rap hic to ng ue le sions in a 71-ye ar-old woman. Note the white halos around the p ink are as o atrop hy o f li orm p ap illae . (Re p rod uce d with p e rmission from Michae ll Hub e r, DMD.)

DIFFERENTIAL DIAGNO SIS • Erythroplakia or leukoplakia—May be suspected when lesions a ect the so t palate (see Chapter 38, Leukoplakia). • Lichen planus—Reticular orms are characterized by interlacing white lines commonly ound on the buccal mucosa, or erosive orms, characterized by atrophic erythematous areas with central ulceration and surrounding radiating striae (see Chapter 152, Lichen Planus) (Figure 34-3). • Psoriasis—Intraoral lesions have been described as red or white plaques associated with the activity o cutaneous lesions (see Chapter 150, Psoriasis) (Figure 34-4).

Ch a pt e r 34

FIGURE 34-4 White p laq ue s on the tong ue o a b lack woman with se ve re cutane ous p laq ue p soriasis. A histolog ic sp e cime n would ap p e ar similar to g e og rap hic tong ue . (Re p ro d uce d with p e rmission fro m E.J. Maye aux, Jr., MD.)

described as painless ulcerative papules on the buccal mucosa and palate (see Chapter 153, Reactive Arthritis). • Fissured tongue—An inherited condition in which the tongue has ssures that are asymptomatic. Although it has been called a scrotal tongue in the past, the term f ssured tongue is pre erred by patients (Figure 34-5).

MANAGEMENT Most individuals are asymptomatic and do not require treatment (Figure 34-6).

• Reactive arthritis—A condition characterized by the triad o “urethritis, arthritis, and conjunctivitis,” may have rare intraoral lesions

FIGURE 34-3 Liche n p lanus o the tong ue . The re are white striae ; the surace is smooth in the a e cte d are a b e cause o the lo ss o p ap illae . (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 34-5 Fissure d to ng ue p re se nt since b irth. Althoug h this has also b e e n calle d a scrotal tong ue , the p re e rre d te rminolog y is now f ssure d tong ue , or ob vious re asons. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

PART 6

Ge O Gr a ph IC t O NGUe

O RAL HEALTH • The tongue swells signi cantly. • The patient has trouble breathing. • The patient has trouble talking or chewing/ swallowing.

PATIENT EDUCATIO N Patients should be reassured o the conditions that are benign in nature. Tell patients with geographic tongue to avoid irritating spicy oods and liquids. PATIENT RESO URCES

• Medline Plus. Geographic Tongue—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 001049.htm. PRO VIDER RESO URCES FIGURE 34-6 A mild asymp tomatic case o g e og rap hic tong ue . Note the atrop hic f li orm p ap illae and the sub tle white halo. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• For symptomatic cases, several treatments have been proposed but not proven e ective with good clinical trials6,7: ° Topical steroids such as triamcinolone dental paste (Oralone or Kenalog in Orabase) SO R ° Supplements such as zinc, vitamin B12, niacin, and ribof avin SO R ° Antihistamine mouth rinses (eg, diphenhydramine elixir 12.5 mg per 5 mL diluted in a 1:4 ratio with water) SO R 6,7 ° Topical anesthetic rinses SO R Geographic tongue can rarely present as persistent and pain ul (Figure 34-7). In one case report, 0.1% tacrolimus ointment was applied twice daily or 2 weeks with signi cant improvement o symptoms. 8 SO R No treatment has been proven to be uni ormly e ective. 9

FO LLO W-UP Tell the patient to contact you i the symptoms continue rom the past 10 days and to go to the emergency department immediately i the ollowing conditions occur:

• Medscape. Geographic Tongue—http:/ / emedicine.medscape .com/ article/ 1078465. • Mayo Clinic. Geographic Tongue—http:/ / www.mayoclinic .com/ health/ geographic-tongue/ DS00819.

REFERENCES 1. Redman RS. Prevalence o geographic tongue, ssured tongue, median rhomboid glossitis, and hairy tongue among 3,611 Minnesota schoolchildren. Oral Surg Oral Med Oral Pathol. 1970;30:390-395. 2. Shulman JD, Carpenter WM. Prevalence and risk actors associated with geographic tongue among US adults. Oral Dis. 2006;12:341-346. 3. Assimakopoulos D, Patrikakos G, Fotika C, Elisa M. Benign migratory glossitis or geographic tongue: an enigmatic oral lesion. Am J Med. 2002;113:751-755. 4. Espelid M, Bang G, Johannessen AC, et al. Geographic stomatitis: report o 6 cases. J Oral Pathol Med. 1991;20:425-428. 5. Darwazeh AM, Almelaih AA. Tongue lesions in a Jordanian population. Prevalence, symptoms, subject’s knowledge and treatment provided. Med Oral Patol Oral Cir Bucal. 2011;16:e745-e749. 6. Abe M, Sogabe Y, Syuto T, et al. Success ul treatment with cyclosporin administration or persistent benign migratory glossitis. J Dermatol. 2007;34:340-343. 7. Reamy BV, Derby R, Bunt CW. Common tongue conditions in primary care. Am Fam Physician. 2010; 81:627-634. 8. Ishibashi M, Tojo G, Watanabe M, et al. Geographic tongue treated with topical tacrolimus. J Dermatol Case Rep. 2010;4:57-59. 9. Gonsalves W, Chi A, Neville B. Common oral lesions: part 1. Supercial mucosal lesions. Am Fam Physician. 2007;75:501-507.

FIGURE 34-7 Ge og rap hic to ng ue with more se ve re symp tomatolog y, includ ing p ain and a b urning se nsation whe n e ating sp icy ood s. The contrast b e twe e n the normal tong ue tissue and the p ink atrop hic p ap illae is striking . (Re p rod uce d with p e rmission from Elle n Eise nb e rg , DMD.)

161

162

PART 6

O RAL HEALTH

Ch a pt e r 35

35 GINGIVITIS AND PERIO DO NTAL DISEASE Richard P. Usatine , MD Wand a C. Gonsalve s, MD

PATIENT STO RY A 35-year-old woman presents to clinic for a routine physical examination. She says that for the last 6 months her gums bleed when she brushes her teeth. She reports smoking 1 pack of cigarettes per day. The oral examination nds generalized plaque and red swollen intradental papilla (Figure 35-1). The physician explains to her that she has gingivitis and that she should brush twice daily and use oss daily. The physician tells her that smoking is terrible for her health in all ways, including her oral health. The physician offers her help to quit smoking and refers her to a dentist for a cleaning and full dental examination.

INTRO DUCTIO N Gingivitis is the in ammation of the gingiva (gums). Gingivitis alone does not affect the underlying supporting structures of the teeth and is reversible (see Figure 35-1). Periodontitis (periodontal disease) is a chronic in ammatory disease, which includes gingivitis along with loss of connective tissue and bone support for the teeth. It damages alveolar bone (the bone of the jaw in which the roots of the teeth are connected) and the periodontal ligaments that hold the roots in place. It is a major cause of tooth loss in adults (Figures 35-2 to 35-4).

EPIDEMIO LO GY

FIGURE 35-2 He althy p e riod ontal anatomy ve rsus p e riod ontal d ise ase . (Re p rod uce d with p e rmission from the Ame rican Acad e my of Pe riod o ntolog y; http ://www.p e rio.org /consume r/2a.html. Cop yrig ht 2014, Ame rican Acad e my of Pe riod ontolog y.)

• It is estimated that 35% of adults of age 30 years or older in the United States have periodontal disease: 22% have a severe form and 13% have a moderate-to-severe form. 1 • Homeless people are a very high-risk group for gingivitis, periodontitis, and all dental disease (see Figure 35-4). • Periodontal disease has been shown in some studies to be an associated factor in coronary heart disease and chronic kidney disease. 2 • Periodontal disease in pregnancy is associated with an increase in preterm birth. 3,4

• Gingivitis and periodontal diseases are the most common oral diseases in adults.

FIGURE 35-1 Chronic g ing ivitis in which the intrad e ntal p ap illae are e d e matous and b lunte d . The re is some loss of g ing ival tissue . The g ums b le e d with b rushing . (Re p rod uce d with p e rmission from Ge rald Fe rre tti, DMD.)

FIGURE 35-3 Se ve re p e riod ontal d ise ase in a woman who smoke s and is ad d icte d to cocaine . Note the b lunting of the intrad e ntal p ap illae and the d ramatic loss of g ing ival tissue . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 6

GINGIVIt IS a ND pe r IO DO Nt a L DISe a Se

O RAL HEALTH associated with α -hemolytic streptococci, anaerobic fusiform bacteria, and nontreponemal oral spirochetes. The term trench mouth was coined in World War I when ANUG was common among soldiers in the trenches. Predisposing factors now include diabetes, HIV, and chemotherapy. 2 • The most common form of gingivitis is chronic gingivitis induced by plaque (see Figure 35-1). This type of gingivitis occurs in half of the population 4 years of age or older. The in ammation worsens as mineralized plaque forms calculus (tartar) at and below the gum surface (sulcus). The plaque that covers calculus causes destruction of bone (an irreversible condition) and loose teeth, which result in tooth mobility and tooth loss. • Gingivitis may persist for months or years without progressing to periodontitis. This suggests that host susceptibility plays an important role in the development of periodontal disease. 5

FIGURE 35-4 Se ve re p e riod ontal d ise ase in an alcoholic smoke r with ve ry e d e matous and b lunte d intrad e ntal p ap illa. This home le ss man has alre ad y lost 2 te e th se cond ary to his se ve re p e riod ontal d ise ase . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

ETIO LO GY AND PATHO PHYSIO LO GY • Periodontal diseases are caused by bacteria in dental plaque that create an in ammatory response in gingival tissues (gingivitis) or in the soft tissue and bone supporting the teeth (periodontitis).

RISK FACTO RS Risk factors that contribute to the development of periodontal disease include poor oral hygiene, smoking, alcohol dependence, environmental factors (eg, crowded teeth and mouth breathing), and comorbid conditions, such as a weakened immune status (eg, HIV, steroids, or diabetes), low educational attainment, and low income. 6-8

DIAGNO SIS

• The normal healthy gingival attachments form the gingival cuff around the tooth to help protect the underlying bone and teeth from the bacteria of the mouth.

CLINICAL FEATURES

• Gingivitis is caused by a reversible in ammatory process that occurs as the result of prolonged exposure of the gingival tissues to plaque and tartar (see Figure 35-2).

• Simple or marginal gingivitis rst causes swelling of the intradental papillae and later affect the gingiva and dental interface (see Figures 35-1 to 35-4).

• Gingivitis may be classi ed by appearance (eg, ulcerative, hemorrhagic), etiology (eg, drugs, hormones), duration (eg, acute, chronic), or by quality (eg, mild, moderate, or severe).

• Mild gingivitis is painless and may bleed when brushing or eating hard foods.

• A severe form, acute necrotizing ulcerative gingivitis (ANUG) (Figure 35-5), also known as Vincent disease or trench mouth, is

• ANUG (see Figure 35-5) is painful, ulcerative, and edematous, and produces halitosis and bleeding gingival tissue. Patients with ANUG may have systemic symptoms such as myalgias and fever. TYPICAL DISTRIBUTIO N Gingivitis begins at the gingival and dental margins and may extend onto the alveolar ridges. LABO RATO RY STUDIES AND IMAGING Radiographs of the mouth are used to evaluate for bone loss in periodontal disease.

DIFFERENTIAL DIAGNO SIS • Gingivitis can be from poor dental hygiene only or secondary to conditions that affect the immune system such as diabetes, Addison disease, HIV, and pregnancy. FIGURE 35-5 Acute ne crotizing ulce rative g ing ivitis (ANUG) with inte nse e rythe ma and ulce rations around the te e th. This is an acute infe ctious p roce ss. Note the d e struction of the p ap illae b e twe e n the te e th. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Gingival hyperplasia is an overgrowth of the gingiva with various etiologies, including medications such as calcium channel blockers, phenytoin, and cyclosporine. This can occur with or without coexisting gingivitis (see Chapter 36, Gingival Overgrowth).

163

PART 6

164

O RAL HEALTH MANAGEMENT • Recommend smoking cessation for all patients who smoke. 7 SO R Offer help to support the patients’ smoking cessation efforts with behavioral counseling and pharmacologic methods (see Chapter 237, Tobacco Addiction). SO R • Recommend alcohol cessation for patients with alcoholism and refer to Alcoholics Anonymous (AA) or another resource. For patients in whom alcohol use is heavy but addiction has not been diagnosed, at least recommend a decrease in alcohol use (see Chapter 238, Alcoholism). 8 SO R • Dental experts recommend tooth brushing twice a day and ossing daily. SO R However, a Cochrane systematic review failed to show a bene t for daily ossing on plaque and clinical parameters of gingivitis. 9 SO R • Some experts suggest that electric toothbrushes may have additional bene t over manual brushing, but this remains unproven. SO R In fact, one study of dental students showed that one electric toothbrush was no better than 2 different manual toothbrushes with respect to plaque control. 10 SO R • Systematic reviews indicate that there is strong evidence supporting the ef cacy of chlorhexidine as an antiplaque, antigingivitis mouthrinse. 11 SO R Mouthwashes should not be used as a replacement for tooth brushing. Chlorhexidine oropharyngeal 0.12% is available as a generic mouthrinse. Recommended dosing is 15 mL to swish (for 30 seconds) and spit twice daily. • The treatments with chlorhexidine (gel and spray) achieved a signi cant reduction in plaque and gingival bleeding in children with special needs. The parents or caregivers preferred the administration of chlorhexidine in spray form. 12 SO R

Ch a pt e r 35

• Consider use of chlorhexidine-containing mouthrinse. • Consult a dentist for regular checkups, especially when the condition does not improve after using good oral hygiene. • Pregnancy is not a contraindication for dental visits and cleaning.

FO LLO W-UP Follow up patients with ANUG closely. All patients need regular dental care and follow-up with their dentist.

PATIENT RESO URCES

• PubMed Health. Gingivitis—http:/ / www.ncbi.nlm.nih.gov/ pubmedhealth/ PMH0002051/ . • The American Academy of Periodontology. Types of Gum Disease— http:/ / www.perio.org/ consumer/ 2a.html. PRO VIDER RESO URCES

• Stephen JM. Gingivitis—http:/ / emedicine.medscape.com/ article/ 763801.

REFERENCES 1. Albandar JM, Brunelle JA, Kingman A. Destructive periodontal disease in adults 30 years of age and older in the United States, 1988-1994. J Periodontol. 1999;70:13-29. 2. Fisher MA, Borgnakke WS, Taylor GW. Periodontal disease as a risk marker in coronary heart disease and chronic kidney disease. Curr Opin Nephrol Hypertens. 2010;19:519-526.

• In patients with ANUG, treatment involves antibiotics, nonsteroidal anti-in ammatory drugs (NSAIDs), and topical 2% viscous lidocaine for pain relief. Oral rinses with saline, hydrogen peroxide 3% solution, or chlorhexidine 0.12% may be of bene t. SO R

3. Corbella S, Taschieri S, Francetti L, et al. Periodontal disease as a risk factor for adverse pregnancy outcomes: a systematic review and meta-analysis of case-control studies. Odontology. 2012;100(2): 232-240.

• Antibiotics recommended for ANUG include penicillin VK, erythromycin, doxycycline, and clindamycin. SO R

4. Chambrone L, Pannuti CM, Guglielmetti MR, Chambrone LA. Evidence grade associating periodontitis with preterm birth and/ or low birth weight: II: a systematic review of randomized trials evaluating the effects of periodontal treatment. J Clin Periodontol. 2011;38: 902-914.

• Everyone should receive ongoing care from a dental professional for prevention and treatment of periodontal disease.

PREVENTIO N • No smoking or tobacco use at all • Avoid alcohol and drug abuse • Good oral hygiene with tooth brushing and ossing • Dental visits at least twice yearly even during pregnancy

PATIENT EDUCATIO N • There is no safe level of smoking. Quitting is crucial to good health. • Drink alcohol in moderation or do not drink at all. • Practice good oral hygiene to remove plaque (ie, brush twice a day and use oss daily).

5. Kornman KS, Crane A, Wang HY, et al. The interleukin-1 genotype as a severity factor in adult periodontal disease. J Clin Periodontol. 1997;24:72-77. 6. Boillot A, El Halabi B, Batty GD, et al. Education as a predictor of chronic periodontitis: a systematic review with meta-analysis population-based studies. PLoS One. 2011;6(7):e21508. 7. Hanioka T, Ojima M, Tanaka K, et al. Causal assessment of smoking and tooth loss: a systematic review of observational studies. BMC Public Health. 2011;11:221. 8. Amaral CS, Vettore MV, Leao A. The relationship of alcohol dependence and alcohol consumption with periodontitis: a systematic review. J Dent. 2009;37:643-651. 9. Berchier CE, Slot DE, Haps S, Van der Weijden GA. The ef cacy of dental oss in addition to a toothbrush on plaque and parameters of gingival in ammation: a systematic review. Int J Dent Hyg. 2008;6:265-279.

GINGIVIt IS a ND pe r IO DO Nt a L DISe a Se

10. Parizi MT, Mohammadi TM, Afshar SK, et al. Ef cacy of an electric toothbrush on plaque control compared to two manual toothbrushes. Int Dent J. 2011;61:131-135. 11. Gunsolley JC. Clinical ef cacy of antimicrobial mouthrinses. J Dent. 2010;38(suppl 1):S6-S10.

PART 6

O RAL HEALTH 12. Chibinski AC, Pochapski MT, Farago PV, et al. Clinical evaluation of chlorhexidine for the control of dental bio lm in children with special needs. Community Dent Health. 2011;28:222-226.

165

PART 6

166

O RAL HEALTH

Ch a pt e r 36

36 GINGIVAL O VERGRO WTH Richard P. Usatine , MD Wand a C. Gonsalve s, MD

PATIENT STO RY A 31-year-old woman with a history o seizure disorder notices increasing gum enlargement (Figure 36-1). She is unemployed and does not have dental insurance. She has not been to a dentist in at least 10 years. She brushes her teeth only once a day and does not oss at all. She has been on phenytoin (Dilantin) since early childhood, and this does prevent her seizures. You talk to her about dental hygiene and re er her to a lowcost dental clinic that cares or people with limited resources.

INTRO DUCTIO N Gingival overgrowth (GO) (hyperplasia) can be hereditary or induced as a side e ect o systemic drugs, such as phenytoin, cyclosporine, or calcium channel blockers. Besides the cosmetic e ect it can make good oral hygiene more di f cult to maintain.

SYNO NYMS It is also known as gingival hyperplasia, drug-induced gingival overgrowth (DIGO), hereditary gingival f bromatosis.

EPIDEMIO LO GY • The prevalence o phenytoin-induced gingival hyperplasia is estimated at 15% to 50% in patients taking the medication1,2 (Figures 36-1 and 36-2).

FIGURE 36-1 Ging ival ov g ow s cond a y o p ny oin (Dilan in) in a woman wi p il p sy. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 36-2 Mul ip l iny ama omas on g ums f om Cowd n d is as wi g ing ival ov g ow s cond a y o p ny oin. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• In patients receiving cyclosporine or more than 3 months, the incidence o GO can approach 70%3 (Figure 36-3). • The incidence o gingival hyperplasia has been reported as 10% to 20% in patients treated with calcium channel blockers in the general population. 2

ETIO LO GY AND PATHO PHYSIO LO GY • Although the etiology o GO is not entirely known, risk actors known to contribute to GO include the ollowing: nonspecif c chronic in ammation associated with poor hygiene, hormonal changes (pregnancy), medications (calcium channel blockers, phenytoin, and cyclosporine), and systemic diseases (leukemia, sarcoidosis, and Crohn disease). ° Studies suggest that phenytoin, cyclosporine, and ni edipine interact with epithelial keratinocytes, f broblasts, and collagen to lead to an overgrowth o gingival tissue in susceptible individuals. 2

FIGURE 36-3 Ging ival ov g ow s cond a y o cyclo sp o in us fo 1 y a o a s v p laq u p so iasis. No b lun d and ick n d in d nal p ap illa . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 6

GINGIVa L O Ve r Gr O Wt h

O RAL HEALTH

° More than 15 drugs have been shown to cause GO. ° The most common nonreversible DIGO is caused by phenytoin (see Figures 36-1 and 36-2).

• Histopathologically, tissue enlargement is the result o proli eration o f broblasts, collagen, and chronic in ammatory cells.

RISK FACTO RS • Prolonged use o phenytoin, cyclosporine, or calcium channel blockers (especially ni edipine) • Pregnancy • Systemic diseases (leukemia, sarcoidosis, and Crohn disease) • Poor oral hygiene and the presence o periodontal disease

DIAGNO SIS

FIGURE 36-4 Pyog nic g anuloma g owing ap id ly on g ums af mino auma. (Re p rod uce d with p e rmission fro m Gonsalve s WC, Chi AC, Ne ville BW. Common oral le sions: p art II. Masse s and ne op lasia. Am Fam P ysician. 2007;75(4):509-512. Cop yrig ht © 2007 Ame rican Acad e my of Family Physicians. All Rig hts Re se rve d .)

SIGNS AND SYMPTO MS • The diagnosis is made by visual inspection and by obtaining a thorough history (see Figures 36-1 to 36-3). • The gingiva appears edematous and bulky with loss o its stippling. It may be so t or f rm. • Nonspecif c chronic in ammation, hormonal and systemic causes such as leukemia appear red and in amed and may bleed. TYPICAL DISTRIBUTIO N Lobular gingiva enlargement occurs f rst at the interdental papillae and anterior acial gingiva approximately 2 to 3 months a ter starting the drug, and increases in maximum severity in 12 to 18 months (see Figure 36-3). LABO RATO RY TESTS Consider checking a complete blood count (CBC) with di erential count to investigate or leukemia i there is not an obvious etiology. IMAGING The periodontist or oral medicine specialist may order bitewing radiographs and periapical f lms to evaluate or the presence o periodontal disease.

DIFFERENTIAL DIAGNO SIS • Generalized gingivitis—Gums around the teeth become in amed. This condition o ten occurs with poor oral hygiene (see Chapter 35, Gingivitis and Periodontal Disease). • Pregnancy gingivitis—In amed gums. More than hal o pregnant women will develop gingivitis during pregnancy because o hormonal changes. • Pyogenic granuloma—A small red bump that may bleed and grow to approximately hal an inch. These are most o ten ound on the skin but can occur in the mouth secondary to trauma or pregnancy. When they occur in pregnancy, they are sometimes called pregnancy tumor. In reality, these are neither pyogenic nor granulomatous but are a type o

lobular capillary hemangioma (see Chapter 159, Pyogenic Granuloma) (Figure 36-4). • Leukemia—Leukemic cells may inf ltrate the oral so t tissues producing a di use, boggy, nontender swelling o the gingiva that may ulcerate or bleed.

MANAGEMENT NO NPHARMACO LO GIC • Teach and emphasize good oral hygiene including cleanings at least every 3 months to control plaque. SO R C • The use o a powered toothbrush, together with oral hygiene instruction, reduces GO or pediatric transplantation patients on cyclosporine. In one study, the sonic toothbrushing and oral hygiene instruction group had less severe GO a ter 12 months than did the control group. 4 SO R B • I possible, stop drugs that induce gingival hyperplasia as discontinuing the medications may reverse the condition in most cases (except phenytoin). • I drugs cannot be stopped, try reducing the dose, i possible, as gingival hyperplasia can be dose dependent. MEDICATIO NS • Tacrolimus is an alternative to cyclosporine to prevent transplant rejection; it causes less GO. In one study on the prevalence o gingival growth a ter renal transplantation, GO occurred in 29% o patients treated with tacrolimus and in 60% o patients treated with cyclosporine. 5 SO R B In another study, switching patients rom cyclosporine to tacrolimus reduced GO in the f rst month a ter the change was made. 6 SO R B • Case reports have reported regression o overgrowth with both oral metronidazole and azithromycin. In one randomized controlled trial (RCT), patients with GO were randomized to receive either 1 course o 5 days o azithromycin or 7 days o metronidazole. The extent o GO was measured at 0, 2, 4, 6, 12, and 24 weeks, and azithromycin was ound to be more e ective than metronidazole.3 SO R B

167

PART 6

168

O RAL HEALTH • Azithromycin with an oral hygiene program resulted in a reduction in cyclosporine-induced GO, whereas oral hygiene alone improved oral symptoms (pain, halitosis, and gum bleeding) but did not decrease cyclosporine-induced GO. 7 Patients were randomized into 2 groups, both receiving oral hygiene instructions, with the treatment group receiving 3 days o azithromycin 500 mg daily. They were evaluated a ter 15 and 30 days and only the azithromycin group had a reduction in GO. 7 SO R B • Chlorhexidine 12% (Peridex) once be ore going to bed or Biotene mouthwash a ter meals is recommended or patients who are known to be at risk or gingivitis. 2 SO R C Warn patients that chlorhexidine 12% will taste bad and can stain the teeth. This staining can be removed with dental cleaning. This in ormation should help improve adherence to the use o this mouthwash. REFERRAL For patients who do not respond to the above measures, re er to a dental health pro essional or possible gingivectomy. This can be done with a scalpel or a laser.

PREVENTIO N Ensure healthy periodontal tissue prior to starting calcium channel blockers or phenytoin, or be ore any organ transplantation in which cyclosporine will be prescribed. Folic acid supplementation, 0.5 mg per day, is associated with prevention o GO in children taking phenytoin monotherapy. O patients in the olic acid arm, 21% developed GO, as compared with 88% receiving placebo. 1 SO R B

PATIENT EDUCATIO N Advise patients to practice good oral hygiene (ie, brush at least twice a day and oss at least once a day) and have regular ollow-up with their dental health pro essional to monitor or worsening periodontal disease.

FO LLO W-UP Patients should be monitored by a periodontist or an oral medicine specialist as long as the patients are taking medicines that induce gingival hyperplasia.

Ch APt e r 36

PATIENT RESO URCES

• The Merck Manual of Health and Aging. Periodontal Disease— http:/ / www.merck.com/ pubs/ mmanual_ha/ sec3/ ch36/ ch36c.html. PRO VIDER RESO URCES

• Mejia L. Drug-induced Gingival Hyperplasia—http:/ / emedicine .medscape.com/ article/ 1076264.

REFERENCES 1. Arya R, Gulati S, Kabra M, et al. Folic acid supplementation prevents phenytoin-induced gingival overgrowth in children. Neurology. 2011;76:1338-1343. 2. Mejia L. Drug-Induced Gingival Hyperplasia. http:/ / emedicine.medscape.com/ article/ 1076264. Accessed January 23, 2012. 3. Chand DH, Quattrocchi J, Poe SA, et al. Trial o metronidazole vs. azithromycin or treatment o cyclosporine-induced gingival overgrowth. PediatrTransplant. 2004;8:60-64. 4. Smith JM, Wong CS, Salamonik EB, et al. Sonic tooth brushing reduces gingival overgrowth in renal transplant recipients. Pediatr Nephrol. 2006;21:1753-1759. 5. Cota LO, Aquino DR, Franco GC, et al. Gingival overgrowth in subjects under immunosuppressive regimens based on cyclosporine, tacrolimus, or sirolimus. J Clin Periodontol. 2010;37:894-902. 6. Parraga-Linares L, Almendros-Marques N, Berini-Aytes L, GayEscoda C. E ectiveness o substituting cyclosporin A with tacrolimus in reducing gingival overgrowth in renal transplant patients. Med Oral Patol Oral Cir Bucal. 2009;14:e429-e433. 7. Ramalho VL, Ramalho HJ, Cipullo JP, et al. Comparison o azithromycin and oral hygiene program in the treatment o cyclosporineinduced gingival hyperplasia. Ren Fail. 2007;29:265-270.

APHTHO US ULCER

PART 6

O RAL HEALTH

37 APHTHO US ULCER Richard P. Usatine , MD

PATIENT STO RY A 58-year-old man presents with a 1-year history o pain ul sores in his mouth. (Figures 37-1 to 37-3). He has lost 20 lb over the past year because it hurts to eat. The ulcers come and go, but are ound on his tongue, gums, buccal mucosa, and inner lips. Prior to the onset o these lesions the patient had been in good health and was not on any medications. The physician recognized his condition as recurrent aphthous ulcers with giant ulcers. No underlying systemic diseases were ound on workup. The patient was started on oral prednisone and given dexamethasone oral elixir to swish and swallow. Within 1 week the patient was able to eat and drink liquids com ortably and began regaining his lost weight. Long-term management o his problem required the use o other medications so as to success ully taper him o prednisone without recurrences.

FIGURE 37-2 Two t ous ulc s on t tong u o 58-y -old m n wit cu nt t ous stom titis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

EPIDEMIO LO GY INTRO DUCTIO N Aphthous ulcers are pain ul ulcerations in the mouth which can be single, multiple, occasional, or recurrent. These ulcers can be small or large but are uni ormly pain ul and may inter ere with eating, speaking, and swallowing. Oral trauma, stress, and systemic diseases can contribute to the occurrence o these ulcers but no precise etiology is apparent. Recurrent aphthous stomatitis (RAS) is a rustrating condition that merits aggressive treatment aimed at pain relie and prevention.

SYNO NYMS Aphthous ulcers are also known as canker sores, aphthous stomatitis, aphthae, recurrent aphthous ulcer (RAU), RAS.

FIGURE 37-1 M jo t ous ulc on t b ucc l mucos o 58-y m n w o s b n su ing wit cu nt t ous stom titis o t y . (Re p ro d uce d with p e rmission fro m Richard P. Usatine , MD.)

-old st

• Twenty percent o general population are estimated to have aphthous ulcers. 1 • Incidence rates o RAUs o 0.85% among adults and 1.5% among adolescents have been reported. 1 • RAS is more common in women, in people younger than age 40 years, in whites, in nonsmokers, and in people o high socioeconomic status. 1

ETIO LO GY AND PATHO PHYSIO LO GY • The precise etiology and pathogenesis o this condition remains unknown, although a variety o host and environmental actors have been implicated.

FIGURE 37-3 Mino t ous ulc occu ing simult n ously wit m jo t ous ulc s on t b ucc l mucos nd to ng u o 58-y -old m n wit cu nt t ous ulc s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

169

PART 6

170

O RAL HEALTH

Ch a pTe r 37

• A positive amily history is seen in about one-third o RAS patients. A genetic predisposition is suggested by an increased requency o human leukocyte antigen (HLA) types A2, A11, B12, and DR2. 1 • In one study, Th1 (T-helper subtype 1) activation was more intense in the patients with RAUs. Many conditions that increase the incidence o RAUs, such as psychological stress, nonsteroidal anti-in ammatory drugs (NSAIDs), Crohn disease, and celiac disease, also shi t the immune response toward the Th1 subtype. Conditions and medications that inhibit the Th1 immune response pathway, such as pregnancy, thalidomide, glucocorticoids, and tetracycline, decrease the incidence o RAUs. 2 • Another study ound signif cantly higher-than-normal serum level o tumor necrosis actor (TNF)-α in 20% to 39% o patients in the ulcerative stage o RAUs. 3 Medications that have anti–TNF-α e ects, such as pentoxi ylline, levamisole, and thalidomide, have also been ound to be use ul in the treatment o RAUs. 1-4 • Although studies show that there are active immune mechanisms associated with RAUs, there is still much to learn regarding their etiology and pathogenesis.

FIGURE 37-4 Two t ous ulc s on t insid o t low li in 27-y -old m n wit isto y o cu nt t ous ulc s. Not t g y n c otic c nt s nd su o und ing yt m on t l b i l mucos . T t ous ulc s t nd to cu d u ing tim s o st ss. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

RISK FACTO RS TYPICAL DISTRIBUTIO N • Oral trauma • Stress and anxiety • Systemic diseases (celiac disease, Crohn disease, Behçet syndrome, HIV, reactive arthritis) • Medications (NSAIDs, β-blockers, angiotensin-converting enzyme inhibitors [ACEIs]) • Vitamin def ciencies (zinc, iron, B12, olate) • Food and chemical sensitivities

DIAGNO SIS CLINICAL FEATURES History • Symptoms may begin with a burning sensation and the pain is exacerbated by moving the area a ected by the ulcer. • Eating o ten hurts, especially oods and drinks with a high acid content. • Ask about recurrences and onset in relation to the use o medications. • Ask about gastrointestinal (GI) symptoms, genital ulcers, HIV risk actors, and joint pain. Physical • Three clinical variations are described based on the size o the ulcers: 1. Minor (4-9 mm) (see Figure 37-3)—most common 2. Major (>10 mm) (see Figure 37-1) 3. Herpeti orm ( 3 d ays or major surg e ry within 12 we e ks re q uiring g e ne ral/re g ional ane sthe sia

1

Localize d te nd e rne ss along the d istrib ution o the d e e p ve nous syste m

1

Entire le g swolle n

1

Cal swe lling 3-cm larg e r than asymp tomatic sid e (me asure d 10 cm b e low the tib ial tub e rosity)

1

Pitting e d e ma con ne d to the symp tomatic le g

1

• Risk actors including recent immobilization, cancer history, hormone therapy

Collate ral sup e r cial ve ins (nonvaricose )

1

Pre viously d ocume nte d DVT

1

PHYSICAL EXAMINATIO N

Alte rnative d iag nosis at le ast as like ly as DVT

-2

FIGURE 46-2 Rig ht lowe r-e xtre mity DVT with ob vious swe lling and e rythe ma note d in the cal and oot. Dup le x ultrasound re ve ale d thromb osis in the p e rone al and p oste rior tib ial ve ins. (Re p rod uce d with p e rmission from De an S, Satiana B. Color Atlas and Synop sis o Vascular Dise ase . Ne w York, NY: McGraw-Hill; 2014.)

DIAGNO SIS HISTO RY • Leg pain and/ or swelling • Previous history o DVT

• There is unilateral swelling, erythema, and tenderness to palpation o the a ected extremity (Figure 46-2). • Increased cal diameter (> 3 cm) in the symptomatic leg is consistent with DVT but not specif c. LABO RATO RY STUDIES • Dimerized plasmin ragment D(D-dimer) assays are sensitive but not specif c or VTE (a positive test does not “rule in” VTE; however, a negative test lowers the likelihood o VTE). • A normal D-dimer in outpatients with low or intermediate probability o DVT is associated with a 0.4% to 0.5% 3-month incidence o DVT.

CLINICAL PREDICTIO N RULES • The most widely accepted method or making the diagnosis o DVT is use o the modif ed Wells clinical score. • The modif ed Wells clinical score (Table 46-1) assigns a specif ed point value or each patient characteristic present. 4 ° History items—active cancer, immobilization o leg, recently bedridden, previous conf rmed DVT. ° Physical examination items—tenderness along the deep venous system, swelling o entire leg, cal swelling greater than 3 cm, pitting edema o involved leg, collateral superf cial veins.

DIAGNO STIC STEPS The ollowing diagnostic steps are used3: 1. I Wells score indicates low probability, measure the D-dimer. a. I D-dimer measurement is negative, DVT is e ectively ruled out. b. I D-dimer measurement is positive, per orm a compression ultrasound o the a ected extremity.

Total score ≤0 ind icate s low p rob ab ility or DVT. Total score 1-2 ind icate s inte rme d iate p rob ab ility or DVT. Total score ≥3 ind icate s hig h p rob ab ility or DVT.

i. I ultrasound is positive, begin treatment or DVT. ii. I ultrasound is negative, repeat the ultrasound in 1 week. (1) I repeat ultrasound is negative, DVT is e ectively ruled out. (2) I repeat ultrasound is positive, begin treatment or DVT. 2. I Wells score indicates intermediate or high probability, per orm a compression ultrasound o the a ected extremity. a. I ultrasound is positive, begin treatment or DVT. b. I ultrasound is negative, measure the D-dimer. i. I D-dimer measurement is negative, DVT is e ectively ruled out. ii. I D-dimer measurement is positive, repeat the ultrasound in 1 week. (1) I repeat ultrasound is negative, DVT is e ectively ruled out. (2) I repeat ultrasound is positive, begin treatment or DVT.

DIFFERENTIAL DIAGNO SIS The ollowing entities may mimic the presentation o DVT3: • Venous insu f ciency rom incompetent venous valves can be age related or caused by obesity. • Superf cial thrombophlebitis typically presents as a tender and f rm varicose vein (Figure 46-3). • Muscle strain/ tear can be di erentiated by pain that occurs with a particular range o motion o a muscle group, usually with an antecedent leg injury or trauma. • A Baker cyst can lead to pain located in the popliteal portion o the posterior leg, typically diagnosed by ultrasound. Once a Baker cyst ruptures, the pain and in ammation can mimic a DVT.

De e p Ve NO US t h r O MBO SIS

PART 7

CARDIO VASCULAR

FIGURE 46-4 Ce llulitis with lymp hang itic sp re ad up the le g . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.) FIGURE 46-3 Sup e r cial thromb o p hle b itis p re se nting with a line ar inf ammatory ind uration ove r the p o ste rior asp e ct o this p atie nt’s le g . (Re p rod uce d with p e rmission from Wolff K, Johnson RA. Fitzp atrick’s Color Atlas and Syno p sis o Clinical De rmato lo g y. 6th e d . Ne w Yo rk, NY: McGraw-Hill; 2013.)

• Cellulitis presents with erythema, warmth, and edema o the skin (Figure 46-4). There may also be an ascending lymphangitis, which would not be seen in a DVT. I a DVT is being considered, then an ultrasound will be negative or thrombosis. • Lymphedema o the leg o ten causes more swelling in the oot than DVT. Lymphedema is most o ten chronic, causing long-standing changes in the tissues, which become brawny with a red-brown coloration. There may also be papules o lymphatic swelling and weeping o uid (Figure 46-5).

MANAGEMENT • The mainstay o treatment is anticoagulation. A DVT in the upper extremity is treated in the same manner as a DVT in the lower extremity. An upper extremity DVT caused by a catheter does not require that the catheter be removed i it is unctioning properly and there is an ongoing need or the catheter. 2 • Hospitalization is recommended in the ollowing situations3,5: ° Renal insu f ciency (CrCl < 30 mL/ min) ° Presence o pulmonary embolus ° Presence o bilateral DVTs or recurrent DVTs ° Severe pain requiring opioids ° Increased risk o bleeding ° Recent immobility ° Chronic heart ailure ° Cancer

° A known hypercoagulable state ° Pregnancy ° Those not likely to be adherent to outpatient therapy • Outpatient treatment or the treatment o DVT is sa e and e ective compared to inpatient treatment in selected patients. 5 (SO R ) • Anticoagulation with one o the ollowing should be started immediately once a DVT is strongly suspected (barring any contraindications)3,5: ° Guidelines suggest the use o low molecular weight heparin (LMWH), not un ractionated heparin (UFH), as f rst-line therapy in patients with DVT (SO R ). 5 ■ The dose or LMWH is • Dalteparin—200 IU/ kg SC once daily • Enoxaparin—1 mg/ kg SC twice daily • Tinzaparin—175 IU/ kg SC once daily ■ For patients not able to take heparin (eg, a history o heparininduced thrombocytopenia), consider ondaparinux at 7.5 mg SC once daily. ■ I using UFH because o unavailability o LMWH, the dose is 80 U/ kg bolus, ollowed by 18 U/ kg/ h titrated to a partial thromboplastin time (PTT) 1.5 to 2.5 times the upper limit o normal. ° Long-term oral anticoagulation with war arin should also be started on day 1, overlapping with one o the previously mentioned or at least 4 to 5 days and until the INR is in the therapeutic range o 2.0 to 3.0 or 2 consecutive days. ■ At this point, heparin/ LMWH/ ondaparinux can be discontinued and oral anticoagulation continued with war arin. ■ The duration o war arin therapy depends on the circumstances surrounding the diagnosis o DVT (Table 46-2). 3,5 ■ Extended-duration therapy with war arin decreases the risk o recurrent DVT or as long as it is used; although the overall risk o recurrent DVT declines with time, the risk o bleeding remains. 5,6

217

PART 7

218

CARDIO VASCULAR

Ch a pt e r 46

TABLE 46-2 Re comme nd e d Duratio n o Tre atme nt or DVT

A

Charact e rist ic

Durat io n o f The rap y

Transie nt risk actor (now re solve d )

3 months

Transie nt risk actor (p e rsiste nt)

Continue until 6 we e ks a te r actor re solve d

Id iop athic (1st e ve nt)—low susp icion or hyp e rcoag ulab le state

6 months

Id iop athic (1st e ve nt)—hig h susp icion or hyp e rcoag ulab le state

Ind e nite

Re curre nt id iop athic e ve nt

Ind e nite

Re curre nt thromb osis while on anticoag ulants (whe the r cause d b y id e nti e d risk or id iop athic)

Ind e nite

Thromb osis with malig nancy

Ind e nite

• Adjunctive measures3,5: ° Early ambulation—highly recommended or an uncomplicated DVT while on anticoagulants. ° Compression stockings—decrease the rate o postthrombotic syndrome by 50%. These should be worn at a pressure o 20 to 40 mm Hg or 6 to 12 months (SO R ). 5,9

PRO GNO SIS/ CLINICAL CO URSE • Recurrence rate o VTE is approximately 7% in the f rst 6 months. 1 • Within 3 years a ter an initial, unprovoked DVT, 19.7% o men will develop a recurrence, as will 9.1% o women. 10 • War arin decreases the risk o recurrent DVT or as long as it is used, and although the overall risk o recurrent DVT declines with time, the risk o bleeding remains. • In one study, the incidence o postthrombotic syndrome was 24.5%, 29.6%, and 29.8%, a ter 2, 5, and 8 years, respectively. 11 B FIGURE 46-5 Lymp he d e ma with le g swe lling and re d -b rown coloration. Note the p ap ule s that re p re se nt d ilatio n o the lymp hatic tissue . A. The b rown color is rom he mosid e rin d e p osition. B. Note the we e p ing o f uid and the d ilate d lymp hatic tissue . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FO LLO W-UP • Patients on war arin will need to have their INR monitored regularly to ensure that it is in the therapeutic range. • I a hypercoagulable state is suspected, workup or this should be perormed 2 weeks a ter the cessation o anticoagulation therapy.

° Newer anticoagulants, including direct thrombin inhibitors (eg, dabigatran) and actor Xa inhibitors (eg, rivaroxaban) have shown promise in treating DVT (SO R ). 7,8 2 ° Other options : ■ In erior vena cava f lter—should be placed i anticoagulation is contraindicated, i recurrent thrombosis occurs while on anticoagulants, or i patient is at high risk or a pulmonary embolus ■ Catheter-directed thrombolysis— used or a massive, limbthreatening ileo emoral DVT ■ IV tissue plasminogen activator (tPA)—used or a hemodynamically signif cant pulmonary embolus

• Monitor and treat patients or postthrombotic syndrome (presence o recurrent pain, swelling, and dermatologic signs o stasis).

PATIENT EDUCATIO N • Anticoagulation can increase the risk o serious bleeding, and patients should avoid activities that predispose to potential bodily injury. • Large amounts o dietary vitamin B12 will a ect the quality o anticoagulation. The dose o war arin needs to be adjusted in such cases to prevent suboptimal therapy.

De e p Ve NO US t h r O MBO SIS

PATIENT RESO URCES

• Agency for Healthcare Research and Quality (AHRQ): Blood Thinner Pills—http:/ / www.ahrq.gov/ consumer/ btpills.htm. • National Heart, Lung, and Blood Institute: What Is Deep Venous Thrombosis? http:/ / www.nhlbi.nih.gov/ health/ healthtopics/ topics/ dvt/ . • American Academy of Orthopaedic Surgeons. Deep Vein Thrombosis— http:/ / orthoinfo.aaos.org/ topic.cfm?topic=A00219&return_ link=0. PRO VIDER RESO URCES

• Antithrombotic and Thrombolytic Therapy, 8th Ed.: ACCPGuidelines— http:/ / chestjournal.chestpubs.org/ content/ 133/ 6_suppl.

REFERENCES 1. White RH. The epidemiology o venous thromboembolism. Circulation. 2003;107(23)(suppl 1):I4-I8. 2. Blann AD, Lip GYH. Venous thromboembolism. BMJ. 2006;332(7535): 215-219. 3. Goodacre S. In the clinic. Deep venous thrombosis. Ann Intern Med. 2008;149(5):ITC3-1. 4. Wells PS, Owen C, Doucette S, et al. The Rational Clinical Examination. Does this patient have deep venous thrombosis? JAMA. 2006;295(2):199-207.

PART 7

CARDIO VASCULAR 5. Snow V, Qaseem A, Barry P, et al. Management o venous thromboembolism: a clinical practice guideline rom the American College o Physicians and the American Academy o Family Physicians. Ann Intern Med. 2007;146:204. 6. Hutten BA, Prins MH. Duration o treatment with vitamin K antagonists in symptomatic venous thromboembolism [Cochrane Review]. Cochrane Libr. 2011 Issue 3. Chichester, UK: John Wiley and Sons, Ltd. 7. The EINSTEIN Investigators, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban or symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499-2510. 8. Schulman S, Kearon C, Kakkar AK, et al, or the RE-COVER Study Group. Dabigatran versus war arin in the treatment o acute venous thromboembolism. N Engl J Med. 2009;361(24):2342-2352. 9. Brandjes DP, Büller HR, Heijboer H, et al. Randomised trial o e ect o compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet. 1997;349(9054):759-762. 10. Douketis J, Tosetto A, Marucci M, et al. Risk o recurrence a ter venous thromboembolism in men and women: patient level metaanalysis. BMJ. 2011;342:d813. 11. Prandoni P, Villalta S, Bagatella P, et al. The clinical course o deepvein thrombosis. Prospective long-term ollow-up o 528 symptomatic patients. Haematologica. 1997;82(4):423-428.

219

220

PART 7

CARDIO VASCULAR

Ch a pt e r 47

47 BACTERIAL ENDO CARDITIS He id i Chumle y, MD

PATIENT STO RY A 25-year-old man presented to the o ce because he had been eeling tired and everish or several weeks. He admitted to injecting heroin regularly in the last 2 months. On examination, he was ebrile and had a heart murmur o which he was previously unaware. His ngernails showed splinter hemorrhages (Figure 47-1). His unduscopic examination revealed Roth spots (Figures 47-2 and 47-3). An echocardiogram demonstrated vegetation on the tricuspid valve. He was hospitalized and treated empirically or bacterial endocarditis. A ter his blood cultures returned Staphylococcus aureus, his regimen was adjusted based on sensitivities and continued or 6 weeks.

INTRO DUCTIO N Bacterial endocarditis is a serious in ection seen most commonly in patients with prosthetic valves; injection drug users; patients with HIV, especially those who use intravenous (IV) drugs; and patients who are immunosuppressed. Diagnosis is made based on Duke criteria. Treatment is IV antibiotics. Mortality, despite treatment, is 26% to 37%.

EPIDEMIO LO GY

FIGURE 47-1 Sp lint r morr ag s ap p aring as r d lin ar str aks und r t nail p lat and wit in t nail b d . Alt oug nd ocard itis can caus t is, sp lint r morr ag s ar mor commonly s n in p soriasis and trauma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Common organisms include S. aureus (IV drug users, nosocomial in ections, prosthetic valve patients), Streptococcus bovis (elderly patients), enterococci (nosocomial in ections), and Staphylococcus epidermis (early in ection in prosthetic valve patients). • Blood contacts subendothelial actors, which promote coagulation.

1

• About 5 to 7.9 cases per 100,000 patient-years. ° Historically it is more common in men; however, the incidence in women is increasing. Incidence in men and women 8.6 to 12.7 and 1.4 to 6.7 cases per 100,000 person-years, respectively. 1 increased rom 46.5 years (1980-1984) to 70 years ° Average age has (2001-2006). 1 ° Incidence2 in IV drug users is 3 per 1000 person-years or 1% to 5% per year. 2 Incidence in HIV-positive IV drug users is 13.8 per 1000 person-years. °

• Pathogens bind and activate monocyte, cytokine, and tissue actor production, enlarging the vegetations on the heart valves.

• Seen in immunosuppressed patients with central venous catheters or hemodialysis patients. care associated, 43% community acquired, and ° Fi ty percent health 7.5% nosocomial. 1 3 Mortality ranges rom 16% to 37%. ° • Prosthetic valve endocarditis makes up 10% to 15% o endocarditis cases. 4 4 Incidence o 0.1% to 2.3% person-year. ° ° Can occur early (2 months a ter surgery) or late.

ETIO LO GY AND PATHO PHYSIO LO GY • Endothelium is injured by mechanical or inf ammatory processes. • Microbes adhere to compromised endothelium during transient bacteremia.

FIGURE 47-2 Rot sp ots t at ar r tinal morr ag s wit w it c nt rs s n in b act rial nd ocard itis. T s can also b s n in l uk mia and d iab t s. (Re p rod uce d with p e rmission from Paul D. Come au.)

Ba Ct e r Ia L e NDO Ca r DIt IS

PART 7

CARDIO VASCULAR • Diagnosis is considered possible with 1 major and 1 minor or 3 minor criteria. 5

FIGURE 47-3 Clos -up o a Rot sp ot, w ic is actually a cotton-wool sp ot surround d b y morr ag . T cotton-wool com s rom isc mic b ursting o axons and t morr ag com s rom isc mic b ursting o an art riol . (Re p rod uce d with p e rmission from Paul D. Come au.)

• The vegetations enlarge and damage the heart valves (Figure 47-4). This process can lead to death i not treated adequately in time. • Septic emboli can occur, most commonly in the brain, spleen, or kidney. 4

RISK FACTO RS • Prosthetic valve • Injection drug use • HIV in ection

• Major criteria include the ollowing5: ° Two separate blood cultures positive with the ollowing actors: ■ Streptococcus viridans, S. bovis, Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella ■ Community-acquired S. aureus or Enterococcus without a primary ocus ■ Microorganisms consistent with prior positive blood cultures in in ective endocarditis ° Endocardial involvement as evidenced by the ollowing actors: ■ Echocardiogram evidence o vegetation, abscess, or new partial dehiscence o a prosthetic valve ■ New valvular regurgitation 5: Minor criteria include the ollowing ° ■ Predisposition (eg, heart condition such as a congenital or acquired valvular de ect, injection drug use, prior history o endocarditis) ■ Temperature greater than 38°C (100.4°F) ■ Clinical signs that include arterial emboli, septic pulmonary in arcts, mycotic aneurysms, intracranial hemorrhages, Janeway lesions (Figures 47-5 and 47-6) ■ Glomerulonephritis, Osler nodes, Roth spots, or positive rheumatoid actor (see Figures 47-2, 47-3, and 47-6) ■ Positive blood culture not meeting major criteria ■ Echocardiographic ndings consistent with in ective endocarditis that do not meet major criteria CLINICAL FEATURES • Fever—Seen in 85% to 99% o patients, typically low grade, approximately 39°C (102.2°F) • New or changing heart murmur—Seen in 20% to 80% o patients

• Immunode ciency

DIAGNO SIS • Duke criteria use a combination o history, physical examination, laboratory, and echocardiogram ndings, and have a sensitivity o approximately 80% across several studies. 5 • Diagnosis is considered de nite when patients have 2 major, 1 major and 3 minor, or 5 minor criteria. 5

FIGURE 47-4 Pat olog y sp cim n o a p ati nt w o d i d o b act rial nd ocard itis. Bact rial g rowt can b s n on t 3 cusp s o t is art valv . (Re p rod uce d with p e rmission from Larry Fowle r, MD.)

FIGURE 47-5 Jan way l sions on t p alm o a woman osp italiz d wit acut b act rial nd ocard itis. T s w r not p ain ul. (Re p rod uce d with p e rmission from David A. Kasp e r, DO , MBA.)

221

222

PART 7

CARDIO VASCULAR

Ch a pt e r 47

• Prosthetic valve endocarditis—Site o any prosthetic valve • In IV drug users—Tricuspid valve, ollowed by aortic valve LABO RATO RY AND ANCILLARY TESTING In addition to blood cultures, consider a complete blood count or anemia and leukocytosis, erythrocyte sedimentation rate (ESR) (elevated in approximately 90%), and urinalysis or proteinuria or microscopic hematuria (seen in approximately 50%). • Positive blood culture—First 2 sets o cultures are positive in 90%. 4 IMAGING • Abnormal echocardiogram in 85%. 5 • I transthoracic echocardiogram is normal and endocarditis is still suspected, order a transesophageal echo. 6 SO R

DIFFERENTIAL DIAGNO SIS Fever without a clear cause may be seen with the ollowing: • Connective tissue disorders—Typically with other signs depending on the disorder, negative blood cultures, normal echocardiogram • Fever o unknown origin—Negative blood cultures or positive cultures with atypical organisms, normal echocardiogram in noncardiac causes FIGURE 47-6 O sl r nod causing p ain wit in p ulp o t b ig to in t sam woman osp italiz d wit acut b act rial nd ocard itis. (O sl r nod s ar p ain ul—r m mb r “O ” or O uc and O sl r.) Not t multip l p ainl ss f at Jan way l sions ov r t sol o t o ot. (Re p rod uce d with p e rmission from David A. Kasp e r, DO , MBA.)

• Intra-abdominal in ections—Fever and positive blood cultures, normal echocardiogram Echocardiogram ndings similar to bacterial endocarditis may be seen with the ollowing: • Nonin ective vegetations—No ever and negative blood cultures

• Septic emboli—Seen in up to 60%, largely dependent on the size (> 10 mm) and mobility o the vegetation

• Cardiac tumors—Embolic complications, right or le t heart ailure, o ten located o valves in cardiac chambers, negative blood cultures

• Intracranial hemorrhages—Seen in 30% to 40% o patients, bleeding rom septic emboli or cerebral mycotic aneurysms

• Cusp prolapse—No ever and negative blood cultures

• Mycotic aneurysms—Aneurysms resulting rom in ectious process in the arterial wall, most commonly in the thoracic aorta, also ound in the cerebral arteries

• Lamb excrescences—Stranding rom wear and tear on the valve, most commonly aortic, no ever, and negative blood cultures

• Janeway lesions—Very rare, f at, painless, red to bluish-red spots on the palms and soles (see Figures 47-5 and 47-6) • Splinter hemorrhages—Red, linear streaks in the nail beds o the ngers or toes (see Figure 47-1) • Glomerulonephritis—Immune mediated that can result in hematuria and renal insu ciency, occurs in approximately 15% o patients with endocarditis • Osler nodes—Tender, subcutaneous nodules in the pulp o the digits (see Figure 47-6) • Roth spots—Retinal hemorrhages rom microemboli, seen in approximately 5% o endocarditis (see Figures 47-2 and 47-3) • Positive rheumatoid actor—Seen in up to 50% o patients TYPICAL DISTRIBUTIO N • Native endocarditis—Mitral valve (prior rheumatic ever or mitral valve prolapse), ollowed by aortic (prior rheumatic ever, calci c aortic stenosis o bicuspid valve)

• Myxomatous changes—Extra connective tissue in the valve leaf ets

MANAGEMENT • Draw blood cultures (2 to 3 sets) and admit suspected cases to the hospital or IV antibiotics. • Start antibiotics empirically (SO R

or speci c regiments).

MEDICATIO NS • Cover Streptococcus in native valve endocarditis: penicillin G 12 to 18 million units divided every 4 hours and gentamicin 1.5 mg/ kg loading dose, then 1 mg/ kg every 8 hours. • Cover Staphylococcus in IV drug abusers: na cillin 2 g every 4 hours and gentamicin; use vancomycin instead o na cillin when concerned about methicillin-resistant S. aureus (MRSA) (prior history o MRSA in ection). • Cover MRSA in prosthetic valve endocarditis: Vancomycin 30 mg/ kg per day divided every 8 hours and gentamicin.

PART 7

Ba Ct e r Ia L e NDO Ca r DIt IS

• Alter antibiotics based on culture results. SO R • Treat gram-positive with a β-lactam; current evidence does not support adding an aminoglycoside. 7 SO R SURGICAL CO NSULTATIO N • Surgical excision o in ected tissue has a 10% to 16% mortality rate in the immediate post-op period. 8,9 Consider surgical consultation when the ollowing occur: ° Congestive heart ailure is severe with mitral or aortic regurgitation. ° Fever and/ or bacteremia persist or 7 to 10 days despite adequate antibiotic therapy, abscesses or perivalvular involvement occurs, or ungal organisms are identi ed. ° Embolic events recur on adequate antibiotic therapy or the risk o embolic events is high because o vegetations larger than 10 mm. SO R

• Early surgery in patients with large vegetations reduced the risk o embolic events, but did not a ect all-cause mortality. 10 • Anticoagulation and aspirin are not indicated or in ective endocarditis and are contraindicated with cerebral complications or aneurysms.

CARDIO VASCULAR PRO GNO SIS Bacterial endocarditis requires early detection and aggressive antibiotic therapy to decrease mortality. • Thirty-day mortality is 16% to 25%. 3 • Ninety-day mortality is 14.5%. 3 • Greater than 6-month mortality is 20% to 37%. 3

FO LLO W-UP • Most patients with bacterial endocarditis will require 4 to 6 weeks o IV antibiotics. • Depending on the antibiotics, some patients will need to have medication levels monitored. • Repeat blood cultures to ensure response to therapy. • An echocardiogram at the end o treatment provides baseline imaging, as patients with endocarditis are at risk or another episode. 6 SO R

PREVENTIO N • Bacterial endocarditis is a serious li e-threatening disease requiring long-term antibiotics and close ollow-up. • Educate patients with high risk or endocarditis o the importance o prophylactic antibiotics be ore certain procedures. Following are the 2007 American Heart Association recommendations11: ° Prescribe prophylactic antibiotics only to patients at the highest risk: SO R

Patients with prosthetic cardiac valves ■ Patients with previous bacterial endocarditis ■ Cardiac transplant recipients with cardiac valvuloplasty ■ Patients with these congenital heart de ects (CHDs): unrepaired cyanotic CHD, CHD repaired with prosthetic material within the last 6 months, repaired CHD with a residual de ect at or adjacent to the site o a prosthetic device ° Prophylactic antibiotics are no longer recommended or patients with mitral valve prolapse. ° Prescribe prophylactic antibiotics only to patients undergoing one o the ollowing: ■ Any dental procedure that involves manipulation o gingival tissue or the periapical region o teeth or per oration o the oral mucosa ■

SO R

Respiratory procedures involving incision or biopsy o the respiratory mucosa such as a tonsillectomy or adenoidectomy SO R ■ Procedures on in ected skin or musculoskeletal tissue ° Endocarditis prophylaxis is no longer recommended or patients undergoing gastrointestinal or genitourinary procedures. SO R regimen to be taken 30 minutes to 1 hour ° Prescribe a one-dose 11 be ore the procedure : ■ Amoxicillin 2 g orally. ■ Unable to take oral medications: ampicillin 2 g intramuscular (IM) or IV or ce azolin or ce triaxone 1 g IM or IV. ■ Penicillin allergic: clindamycin 600 mg PO, IM, or IV; or azithromycin or clarithromycin 500 mg PO. I allergy to penicillin is not anaphylaxis, angioedema, or urticaria, may also use cephalexin 2 g PO; or ce azolin or ce triaxone 1 g IM or IV. ■

PATIENT EDUCATIO N • Bacterial endocarditis is a serious disease with a signi cant mortality rate. • Finish all antibiotics and keep ollow-up appointments to ensure adequate treatment. • Mortality remains elevated even 6 months a ter an episode. • Recurrence is common, especially i risk actors remain (ie, continued immunosuppression or IV drug use). PATIENT RESO URCES

• The American Heart Association has information about who is at risk or bacterial endocarditis and a printable wallet card or at-risk patient, available in English or Spanish—http:/ / www.heart .org/ HEARTORG/ Conditions/ CongenitalHeartDefects/ TheImpactofCongenitalHeartDefects/ InfectiveEndocarditis_UCM_307108_Article.jsp. PRO VIDER RESO URCES

• The American Heart Association guidelines on endocarditis prophylaxis—http:/ / circ.ahajournals.org/ content/ 116/ 15/ 1736 .full.pdf. • Guidelines on Infective Endocarditis: Diagnosis, Antimicrobial Therapy, and Management o Complications—http:/ / circ .ahajournals.org/ content/ 111/ 23/ e394.full. • MedCalc has an interactive Web site with Duke criteria for infective endocarditis—www.medcalc.com/ endocarditis.html.

REFERENCES 1. de Sa DD, Tleyjeh IM, Anavekar NS, et al. Epidemiological trends o in ective endocarditis: a population-based study in Olmsted County, Minnesota. Mayo Clin Proc. 2010;85(5):422-426.

223

224

PART 7

CARDIO VASCULAR 2. Wilson LE, Thomas DL, Astemborski J, et al. Prospective study of in ective endocarditis among injection drug users. J Infect Dis. 2002;185(12):1761-1766. 3. Nomura A, Omata F, Furukawa K. Risk actors o mid-term mortality o patients with in ective endocarditis. Eur J Clin Microbiol Infect Dis. 2010;29(11):1355-1360. 4. Prendergast BD. The changing ace o in ective endocarditis. Heart. 2006;92(7):879-885. 5. Habib G. Management o in ective endocarditis. Heart. 2006;92(1): 124-130. 6. Baddour LM, Wilson WR, Bayer AS, et al. American Heart Association Scienti c Statement on In ective Endocarditis. Circulation. 2005;111:e394-e434. 7. Falagas ME, Matthaiou DK, Bliziotis IA. The role o aminoglycosides in combination with a beta-lactam or the treatment o bacterial

Ch APTe R 47

endocarditis: a meta-analysis o comparative trials. JAntimicrob Chemother. 2006;57(4):639-647. 8. Fayad G, Leroy G, Devos P, et al. Characteristics and prognosis o patients requiring valve surgery during active in ective endocarditis. J HeartValve Dis. 2011;20(2):223-228. 9. Mokhles MM, Ciampichetti I, Head SJ, et al. Survival o surgically treated in ective endocarditis: a comparison with the general Dutch population. AnnThorac Surg. 2011;91(5):1407-1412. 10. Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment or in ective endocarditis. N Engl J Med. 2012;366: 2466-2473. 11. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: a guideline rom the American Heart Association. Circulation. 2007;116:1736-1754.

PART 7

HYPERTENSIO N

48 HYPERTENSIO N He id i Chumle y

CARDIO VASCULAR • Blood pressure control is lowest among those without health insurance (29%), Mexican Americans (37%), and adults ages 18 to 39 years (31%). 1,2 • Ninety percent o patients with uncontrolled HTN have a usual source o care and health insurance. 2

PATIENT STO RY A 40 year-old man presents a ter his blood pressure was measured as 180/ 100 mm Hg at a health screening. He has no complaints. His blood pressure today is 178/ 98 mm Hg. Based on these 2 readings, he is diagnosed with stage 2 hypertension (HTN). His amily history is very positive or essential HTN. His examination is normal other than an enlarged and laterally displaced point o maximal impulse. His body mass index is normal. The provider sends him or a urinalysis, complete blood count (CBC), asting lipid pro le, and a chemistry panel that includes blood glucose, potassium, serum creatinine, and calcium. An electrocardiogram (ECG) shows le t ventricular hypertrophy (Figure 48-1). He is counseled regarding li estyle change, started on 2 medications, and asked to ollow-up within a couple o weeks.

• In the United States, HTN contributes to 1 o every 7 deaths and to hal o the cardiovascular disease-related deaths. 2 • Cost o HTN to the US health care system is estimated to be $131 billion per year. 2

ETIO LO GY AND PATHO PHYSIO LO GY • Primary HTN (> 90% o patients)—The speci c cause is unknown, but environmental actors (ie, salt intake, excess alcohol intake, obesity) and genetics both play a role. • Secondary HTN (5%-10% o patients)—Causes include medications, kidney disease, renal artery stenosis (Figure 48-2), thyroid disease, hyperaldosteronism, and sleep apnea. Rare causes include coarctation o the aorta, Cushing syndrome, and pheochromocytoma.

INTRO DUCTIO N Hypertension is a major risk actor or both myocardial in arction and stroke. Primary HTN constitutes 90% o HTN cases. Initial treatment includes li estyle modi cations and medications. Most patients require at least 2 medications to achieve control. Patients who are not controlled on 3 medications should undergo a workup or secondary causes.

RISK FACTO RS • Family history or genetic predisposition • Obesity • High sodium chloride intake

EPIDEMIO LO GY • O US adults older than age 18 years, 30.4% have HTN. 1,2 • Blood pressure is controlled in approximately 50% o adults with HTN. 1,2

• Medications, including oral contraceptives, nonsteroidal antiinf ammatory drugs (NSAIDs), decongestants, and some antidepressants • Substances, including ca eine, licorice, amphetamines, cocaine, and tobacco

FIGURE 48-1 ECG showing le t ve ntricular hyp e rtrop hy in this 58-ye ar-old man with curre nt b lood p re ssure o 178/98. Note how S V1 + R V5 > 35 mm. Also his ECG shows le t axis d e viation and nonsp e ci c ST chang e s in the hig h late ral le ad s (I and aVL). (Re p rod uce d with p e rmission from Gary Fe re nchick, MD.)

225

PART 7

226

CARDIO VASCULAR

Ch a pt e r 48

FIGURE 48-3 Hypertensive and diabetic retinopathy with dot-blot hemorrhage s, a f ame hemorrhag e, and hard exudates. The arte rioles are attenuate d rom the hypertension. (Re produced with p ermission from Carrie Cooke.)

• Consider testing or thyroid disorders with a thyroid-stimulating hormone (TSH) i other signs or symptoms are present. FIGURE 48-2 Ang iog ram re ve aling b ilate ral re nal arte ry ste nosis (arrows), one o the mo re common cause s o se cond ary hyp e rte nsion, most o te n a re sult o athe roscle rotic d ise ase in old e r p atie nts. (Re p rod uce d with p e rmission from Fig ure 111-15A in Hurst’s the He art, 13th e d .)

DIAGNO SIS Average o 2 or more seated blood pressure readings on each o 2 or more o ce visits based on systolic (SBP) and diastolic (DBP) blood pressures. • Prehypertension—SBP 120 to 139 mm Hg or DBP 80 to 89 mm Hg • Stage 1 HTN—SBP 140 to 159 mm Hg or DBP 90 to 99 mm Hg • Stage 2 HTN—SBP equal to or greater than 160 mm Hg or DBP equal to or greater than 100 mm Hg

• For patients with abnormal screening tests, signs indicating a secondary cause, or inadequate control on 3 medications include the ollowing: ° Serum aldosterone and plasma renin activity are use ul in patients with hypokalemia. ° A 24-hour urine protein and creatinine or suspected renal disease. ° A 24-hour urine- ree cortisol or a dexamethasone suppression test or suspected Cushing syndrome. ° Plasma and urine catecholamines or metanephrines or suspected pheochromocytoma. ° Parathyroid hormone level or suspected hyperparathyroidism. IMAGING AND ANCILLARY TESTS • ECG on all patients with HTN.

CLINICAL FEATURES

• Chest radiograph is usually not ordered or primary HTN; however, i obtained, cardiomegaly may be present. I coarctation o the aorta is expected, rib notching may be present.

• No symptoms may be present.

• Echocardiogram may also demonstrate le t ventricular hypertrophy.

• When blood pressure is high, patients may have headaches, vision changes, con usion, chest pain or myocardial in arction, pulmonary edema, stroke, or hematuria.

• Renal artery stenosis can be seen on magnetic resonance angiography or by angiography (see Figure 48-2).

• Hypertensive retinopathy may be present (Figure 48-3 and Chapter 18, Hypertensive retinopathy). • An S4 can be an early physical examination nding. • Le t ventricular hypertrophy may be mani est as an enlarged laterally displaced point o maximal impulse, abnormal ECG (see Figure 48-1), or abnormal chest radiograph. • Abdominal bruits may be present with renal artery stenosis.

• Renal ultrasound may demonstrate small or absent kidney.

DIFFERENTIAL DIAGNO SIS • Falsely elevated blood pressure readings can be a result o improper cu size (too small with a large-arm diameter) or method (patient not seated, arm in incorrect position, etc).

LABO RATO RY TESTING

• Acute elevations in blood pressure may be caused by substances (eg, tobacco).

• Be ore initiating therapy or presumed primary HTN per orm the ollowing tests: urinalysis, CBC, asting lipid pro le, and chemistry panel, including asting blood glucose, potassium, creatinine, and calcium.

• White-coat HTN is de ned as blood pressure that is consistently over 140/ 90 mm Hg in the presence o a health care provider with an ambulatory monitoring average o less than 135/ 85 mm Hg.

PART 7

h Ype r t e NSIO N

MANAGEMENT

CARDIO VASCULAR FO LLO W-UP

NO NPHARMACO LO GIC

• Schedule visits monthly until blood pressure goal is obtained.

• Weight reduction i overweight or obese.

• Consider more requent visits or patients with stage 2 HTN or signi cant comorbid conditions.

• Dietary approaches to stop hypertension (DASH) diet, rich in ruits and vegetables, aimed at reducing sodium intake and eating a variety o oods rich in nutrients that help lower blood pressure, such as potassium, calcium, and magnesium. • Low- at diet. • Low dietary sodium chloride. • Regular aerobic exercise. • Moderate alcohol intake: no more than 2 drinks per day or men and 1 drink per day or women.

• See patients with controlled HTN every 3 to 6 months.

PATIENT EDUCATIO N • HTN is a chronic disease requiring li elong li estyle modi cations and one or more daily medications or most patients. • Adequate control o HTN reduces the risk or heart attack and stroke.

• Smoking cessation or cardiovascular risk reduction (see Chapter 237, Tobacco Addiction).

PATIENT RESO URCE

MEDICATIO NS

• The National Heart Lung and Blood Institute. What Is High Blood Pressure?—http:/ / www.nhlbi.nih.gov/ health/ healthtopics/ topics/ hbp/ .

• Start a thiazide-type diuretic in most patients. An angiotensin-converting enzyme inhibitor (ACEI) may be the initial choice in white males. • Consider starting 2 medications when blood pressure is 20/ 10 mm Hg higher than goal. Goal is 140/ 90 mm Hg or 130/ 80 mm Hg in patients with diabetes or chronic kidney disease. • Add an ACEI, angiotensin receptor blocker (ARB), β-blocker (BB), or calcium channel blocker (CCB) i control is not achieved with initial agent. • Speci c medications have compelling indications in these situations: ° Heart ailure—Diuretic, BB, ACEI, ARB, aldosterone antagonist (AA) ° Postmyocardial in arction—BB, ACEI, AA ° Diabetes—Diuretic, BB, ACEI, ARB, CCB ° Chronic kidney disease—ACEI, ARB ° Recurrent stroke prevention—Diuretic, ACEI REFERRAL O R HO SPITALIZATIO N • Re er patients in whom adequate blood pressure control is not obtained. • Women with HTN who are planning a pregnancy or who become pregnant should be re erred to a provider with experience managing chronic HTN in pregnancy.

PREVENTIO N Healthy li estyle or all persons, including weight reduction (i overweight or obese), use o DASH, initiation and maintenance o adequate physical activity, and moderate alcohol intake.

PRO GNO SIS • Risk o cardiovascular disease increases as blood pressure increases. • Between 115/ 75 and 185/ 115 mm Hg, every 20 mm Hg SBP or 10 mm Hg DBP doubles the risk o cardiovascular disease or adults ages 40 to 70 years. 3

PRO VIDER RESO URCES

• The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment o High Blood Pressure (JNC 7)—http:/ / www.nhlbi.nih.gov/ guidelines/ hypertension/ express.pdf. • The Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment o High Blood Pressure (JNC 8)—http:/ / www.nhlbi.nih.gov/ guidelines/ hypertension/ jnc8/ index.htm.

REFERENCES 1. Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment and control o hypertension, 1988-2008. JAMA. 2010;303(2):2043-2050. 2. Centers or Disease Control and Prevention. Vital signs: awareness and treatment o uncontrolled hypertension among adults—United States, 2003-2010. MMWR Morb MortalWkly Rep. 2012;61(35): 703-709. 3. Lewington S, Clarke R, Qizilbash N, et al. Age-speci c relevance o usual blood pressure to vascular mortality: a metaanalysis o individual data or one million adults in 61 prospective studies. Lancet. 2002;360:1903-1913.

227

PART 7

228

CARDIO VASCULAR

49 PERICARDITIS AND PERICARDIAL EFFUSIO N He id i Chumle y, MD

Ch a pt e r 49

• Six-and-a-hal percent o adults (< 1% with age 20-30 years; 15% older than 80 years o age) had echocardiogram ndings consistent with pericardial e usion in a population-based study o 5652 adults and adult amily members o participants in the Framingham Heart Study. 2 • Seventy-seven percent o patients a ter cardiac surgery or valves or bypass have pericardial e usions, which rarely ( 90%. ■ Fetal hemoglobin (HbF) = approximately 6%. ■ HbA = approximately 3.5%. 2 ■ HbA = 0% (unless the patient has received a blood trans usion in the past ew months).

• Simple trans usion is given when urgently needed; the goal is to restore hemoglobin and reduce HbS levels. SO R ° Urgent indications include aplastic crisis, acute chest syndrome or acute neurologic event, sepsis (including meningitis), multiple organ ailure, acute hemorrhage, and sequestration in the liver or spleen. ° Repeated trans usions are associated with iron overload and are not indicated as a primary treatment or acute pain ul crises. ° Do not trans use to a hemoglobin level o greater than 10 g/ dL as blood viscosity increases. • Consider a simple trans usion to a hemoglobin o 10 g/ dL preoperatively. 2 • Consider an urgent exchange trans usion in patients with SSA with acute CVA because this more rapidly decreases the HbS concentration. SO R

• Sickle cell trait ° Approximately 10% o blacks have sickle cell trait; that is, they are heterozygous or the sickle cell gene, and their genotype is bS/ bA. ° Sickle cell trait is benign, and patients are essentially normal and protected against alciparum malaria, but they may have di f culty concentrating their urine (hyposthenuria). ° Hemoglobin electrophoresis shows both HbA and HbS: ■ HbA is always greater than 50%, and ■ HbS percentage depends on the a genotype; thus HbS occurs in • 35% to 45% in patients with 4a genes • 30% to 35% with 3a genes • 25% to 30% with 2a genes • 17% to 25% with 1a gene

• Analgesics (opioid and nonopioid) are given or pain. Patients may require large doses o narcotics or pain relie .

• Hemoglobin SC disease (one b chain has hemoglobin S and the other has hemoglobin C) ° HbS approximately 50% ° Hemoglobin C (HbC) approximately 50%

• Hydroxyurea increases HbF and reduces long-term mortality in patients with SSA and decreases daily pain intensity. The decrease in pain intensity correlates with the amount o HbF increase in response to treatment. 11,12 SO R

• Sickle-b + -thalassemia ° Thalassemia genes produce normal hemoglobin but in reduced amounts. + ° Di erentiation among SSA and sickle-b-thalassemia (both b , in which there are some b chains, and b°, in which there are no b chains) may be di f cult.

• Treatment o acute chest syndrome includes oxygen, adequate hydration, broad-spectrum antibiotics, bronchodilators/ incentive spirometry, and trans usions to decrease the raction o HbS to less than 30%. 2 • Inhaled nitric oxide was not associated with resolution o the sickle cell crisis among 150 patients presenting with a sickle cell vaso-occlusive pain crisis. 10 CHRO NIC MANAGEMENT • For newborns who screen positive, give a pneumococcal vaccine and provide prophylactic oral penicillin or 5 years to prevent serious in ections. SO R

• Long-term use o hydroxyurea reduced mortality as measured over 17.5 years and was not associated with an increased risk o malignancy. 11 20% may be a threshold or the prevention o vaso-occlusive ° HbF o6,12,13 crisis.

PART 8

SICKLe Ce LL DISe ASe

° Hydroxyurea was associated with a 44% reduction in pain crises and a 40% lower mortality rate. ° Exchange trans usions decrease the percentage o HbS. ° Omega-3 atty acid supplements in 16 patients with SSA decreased the number o pain ul crises in a 6-month pilot study. 14 SO R ° Bone marrow transplantation can cure patients, with a 95% diseaseree survival. 15 SO R ° Iron overload rom multiple trans usions is a risk or patients with SSA. Guidelines suggest initiating iron chelation therapy in patients with a serum erritin over 1000 ng/ mL or patients with a cumulative trans usion o more than 120 packed RBCs. Patients with SSA treated with a once-daily oral iron chelator (de erasirox) decreased serum erritin by 50%; this has a clinically acceptable sa ety prof le in patients with SSA at risk or iron overload because o requent trans usions. 16,17

PRO GNO SIS/ CLINICAL CO URSE • Major complications o SCD include the ollowing: ° Cerebrovascular complications occur in 8.5% to 17% o patients with SSA in the United States. ° Neurocognitive def cits are common in patients with SSA, including those relating to IQ, memory, processing speed, and measures o executive unction. 18 ° Proli erative retinopathy is more common in HbSCD than other sickle cell syndromes. ° Cardiopulmonary complications, including acute chest syndrome, are the most requent cause o death o patients with SSA, congestive heart ailure, and pulmonary hypertension, which is associated with a 25% to 50% chance o death within 2 years. 19 ° Cholelithiasis occurs in patients with SCD with symptomatic bilirubin stones. ° Splenic sequestration can occur. ° Renal complications ■ A “normal” creatinine in SCD is di erent rom that or other patients; serum creatinine is very low (0.2 to 0.5 mg/ dL) in patients with SCD. ■ A normal creatinine level o 1.2 mg/ dL is associated with up to 40% loss o renal unction in SCD. ■ Conf rm with glomerular f ltration rate and consider early therapy with angiotensin-converting enzyme (ACE) inhibitors. ° Priapism—A ter major attacks o priapism, about one-third o the patients are completely impotent, one-third are partially impotent, and one-third recover normal unction. ° Leg ulcers—Approximately 5% to 10% o adult patients with SCD with SSA develop a leg ulcer at some time, especially near the malleoli. These are more common in male versus emale patients with SCD20 (Figure 54-1). ° Avascular necrosis is a problem. ° In ection—Patients with SSA have a compromised immune system that predisposes them to in ection. ° Blood pressure is generally lower than normal in patients with SSA. Patients with high values relative to this population are at an increased risk or increased morbidity and mortality. ° Dactylitis (hand- oot syndrome) (Figure 54-3), splenomegaly, and splenic sequestration are common in children, especially be ore age 5 years. ° Aplastic crises are commonly caused by coin ection with parvovirus B19.

HEMATO LO GY FO LLO W-UP • Stable patients should be ollowed every 4-6 months. • Consider periodic retinal screening by an ophthalmologist and periodic echocardiography to assess or pulmonary hypertension.

PATIENT EDUCATIO N Avoid extreme heat or cold and maintain adequate hydration. PATIENT RESO URCES

• Sickle Cell Disease Association of America—http:/ / www .sicklecelldisease.org. • American Academy of Pediatrics. Health Supervision for Children with Sickle Cell Disease—http:/ / pediatrics.aappublications.org/ content/ 109/ 3/ 526.full. • National Heart, Lung, and Blood Institute. Sickle Cell Disease— http:/ / ghr.nlm.nih.gov/ condition/ sickle-cell-disease. PRO VIDER RESO URCES

• Geneva Foundation for Medical Education and Research. Clearinghouse or many articles and guidelines or SSA—http:/ / www.gfmer.ch/ Guidelines/ Anemia_and_ hemoglobinopathies/ Sickle_cell_anemia.htm. • Note that the SCDAA does not support the screening of athletes for sickle cell trait as a means to decrease heat- and exertion-related deaths among athletes—http:/ / www.sicklecelldisease.org/ index.cfm?page=sickle-cell-trait-athletics. • Bender MA, Hobbs W. Sickle cell disease. Gene Rev. 2012, May. http:/ / www.ncbi.nlm.nih.gov/ books/ NBK1377/ .

REFERENCES 1. Taylor LE, Stotts NA, Humphreys J, et al. A review o the literature on the multiple dimensions o chronic pain in adults with sickle cell disease. J Pain Symptom Manage. 2010;40(3):416-435. 2. Steinberg MH. Sickle cell disease. Ann Int Med. 2011;155:ITC31. 3. Platt OS, Thorington BD, Brambilla DJ, et al. Pain in sickle cell disease. Rates and risk actors. N Engl J Med. 1991;325(1):11-16. 4. Laurie GA. Acute chest syndrome in sickle cell disease. Intern Med J. 2010;40(5):372-376. 5. Gladwin MT, Vichinsky E. Pulmonary complications o sickle cell disease. N Engl J Med. 2008;359(21):2254-2265. 6. Smith WR, Penberthy LT, Bovbjerg VE, et al. Daily assessment of pain in adults with sickle cell disease. Ann Intern Med. 2008;148:94-101. 7. Strouse JJ, Jordan LC, Lanzkron S, et al. The excess burden o stroke in hospitalized adults with sickle cell disease. Am J Hematol. 2009;84:548-552. 8. Adams RJ, McKie VC, Hsu L, et al. Prevention o a f rst stroke by trans usions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. 1998;339:5-11. 9. Parent F, Bachir D, Inamo J, et al. A hemodynamic study o pulmonary hypertension in sickle cell disease. N Engl J Med. 2011;365:44-53.

257

258

PART 8

HEMATO LO GY

CHAPTe R 54

10. Gladwin MT, Kato GJ, Weiner D, et al. Nitric oxide for inhalation in the acute treatment o sickle cell pain crisis: a randomized controlled trial. JAMA. 2011;305(9):893-902.

16. Voskaridou E, Plata E, Douskou M, et al. De erasirox e ectively decreases iron burden in patients with double heterozygous HbS/ b-thalassemia. Ann Hematol. 2011;90(1):11-15.

11. Steinberg MH, McCarthy WF, Castro O, et al. The risks and benef ts o long-term use o hydroxyurea in sickle cell anemia: a 17.5 year ollow-up. Am J Hematol. 2010;85:403-408.

17. Vichinsky E, Bernaudin F, Forni GL, et al. Long-term sa ety and e f cacy o de erasirox (Exjade) or up to 5 years in trans usional iron-overloaded patients with sickle cell disease. Br J Haematol. 2011;154(3):387-397.

12. Ware RE, Aygun B. Advances in the use of hydroxyurea. Hematology Am Soc Hematol Educ Program. 2009:62-69. 13. Smith WR, Ballas SK, McCarthy WF, et al. The association between hydroxyurea treatment and pain intensity, analgesic use, and utilization in ambulatory sickle cell anemia patients. Pain Med. 2011;12(5): 697-705. 14. Okpala I, Ibegbulam O, Duru A, et al. Pilot study o omega-3 atty acid supplements in sickle cell disease. APMIS. 2011;119(7):442-448. 15. Hsieh MM, Kang EM, Fitzhugh CD, et al. Allogeneic hematopoietic stem-cell transplantation or sickle cell disease. N Engl J Med. 2009;361:2309-2317.

18. Vichinsky EP, Neumayr LD, Gold JI, et al. Neuropsychological dysunction and neuroimaging abnormalities in neurologically intact adults with sickle cell anemia. JAMA. 2010;303:1823-1831. 19. Gladwin MT, Sachdev V, Jison ML, et al. Pulmonary hypertension as a risk actor or death in patients with sickle cell disease. N Engl J Med. 2004;350:886-895. 20. Koshy M, Entsuah R, Koranda A, et al. Leg ulcers in patients with sickle cell disease. Blood. 1989;74(4):1403-1408.

Pa r t 9

PULMO NARY

*

St re ng t h o Re co mme nd at io n (SO R)

De f nit io n

A

Re comme nd ation b ase d on consiste nt and g ood -q uality p atie nt-orie nte d e vid e nce .*

B

Re comme nd ation b ase d on inconsiste nt or limite d -q uality p atie nt-orie nte d e vid e nce .*

C

Re comme nd ation b ase d on conse nsus, usual p ractice , op inion, d ise ase -orie nte d e vid e nce , or case se rie s or stud ie s o d iag nosis, tre atme nt, p re ve ntion, or scre e ning .*

Se e Ap p e nd ix A on p ag e s 1241-1244 or urthe r in ormation.

260

PART 9

PULMO NARY

55 ASTHMA AND PULMONARY FUNCTIO N TESTING Mind y A. Smith, MD, MS

PATIENT STO RY A 32-year-old Hispanic woman presents to your o ce with a chronic cough or 3 months. She states the cough is dry and started with a cold 3 months ago. She denies ever, chills, and night sweats. She has never been diagnosed with asthma or lung disease in the past. She does admit to having had persistent dry coughs that linger on a ter getting colds in the past. She is not sure what wheezing is but she has noticed a tight eeling in her chest at night with some whistling sound. On physical examination, her lungs are clear and she is moving air well. Her height is 5 t and her weight is 220 lb giving her a body mass index (BMI) o 43. Her peak expiratory f ow (PEF) in the o ce is at 80% o predicted. Even though she is not wheezing, her history and physical examination are highly suspicious or asthma. You prescribe a short-acting β 2-agonist (SABA) rescue inhaler with spacer and order pulmonary unction tests (PFTs). You have your nurse provide asthma education (including proper use o an inhaler) and suggestions or weight loss. The patient returns 1 week later and the cough is much improved. You review her PFTs (Figure 55-1) and note that she has reversible bronchospasm especially in the small airways ( orced expiratory f ow [FEF]25%-75% shows a 70% improvement with inhaled albuterol). See Table 55-1 or the meaning o the typical abbreviations using with PFTs. Her lung volumes (Figure 55-1B) show hyperinf ation with a high residual volume and her di using capacity is normal. The whole picture is consistent with asthma. An asthma action plan is created and a re erral to a nutritionist is o ered to help the patient with her obesity.

INTRO DUCTIO N Asthma is a chronic inf ammatory airway disorder with variable airf ow obstruction and bronchial hyperresponsiveness that is at least partially reversible, spontaneously or with treatment (eg, β 2-agonist treatment). Patients with asthma have recurrent episodes o wheezing, breathlessness, chest tightness, and cough (particularly at night or in the early morning).

EPIDEMIO LO GY • Estimated prevalence o asthma in noninstitutionalized adults over age 18 years in the United States (2010) is approximately 8.2% (18.7 million cases). 1 • The number o deaths rom asthma in 2009 was 3388 (1.1/ 100,000 population). 1

Ch a pt e r 55

ETIO LO GY AND PATHO PHYSIO LO GY • Although the precise cause is unknown, early exposure to airborne allergens (eg, house–dust mite, cockroach antigens) and childhood respiratory in ections (eg, respiratory syncytial virus, parainf uenza) are associated with asthma development. • In addition to environmental actors, asthma has an inherited component, although the genetics involved remain complex. 3 The gene ADAM 33 (a disintegrin and metalloproteinase) may increase the risk o asthma as metalloproteinases appear to e ect airway remodeling. 4 • The pulmonary obstruction characterizing asthma results rom combinations o mucosal swelling, mucous production, constriction o bronchiolar smooth muscles, and neutrophils (the latter, particularly important in smokers or those with occupational asthma). 4 Over time, airway smooth muscle hypertrophy and hyperplasia, remodeling (thickening o the subbasement membrane, subepithelial brosis, and vascular proli eration and dilation), along with mucous plugging complicate the disease. 4 • Allergen-induced acute bronchospasm involves immunoglobulin E (IgE)-dependent release o mast cell mediators. 4

RISK FACTO RS • Family history o asthma. 5 • Recurrent childhood chest in ections or atopy. 5 • Parental smoking. 5 • Male gender. 5 • Recent use o acetaminophen has also been associated with asthma symptoms in adolescents (odds ratio [OR], 1.43; 95% con dence interval [CI], 1.33-1.53 and OR, 2.51; 95% CI, 2.33-2.70 or at least once a year and at least once a month use vs no use, respectively). 6 One possible mechanism is through acetaminophen reducing the immune response and prolonging rhinovirus in ection. 7 • Modi able risk actors include obesity (OR 3.3 or adult-onset asthma) and tobacco smoking; the latter also increases the risk o occupational asthma. 4

DIAGNO SIS The diagnosis o asthma is made on clinical suspicion (presence o symptoms o recurrent and partially reversible airf ow obstruction and airway hyperresponsiveness) and con rmed with spirometry. 3 Alternative diagnoses should be excluded. CLINICAL FEATURES

• Asthma was the rst-listed diagnosis or 479,000 hospital discharges in 2009 with an average length o stay o 4.3 days. 1

Asthma’s most common symptoms are recurrent wheezing, di culty breathing, chest tightness, and cough. An absence o wheezing or normal physical examination does not exclude asthma. 3 In act, up to 25% o patients with asthma have normal physical examinations even though abnormalities are seen on pulmonary unction testing. 4 As part o the diagnosis o asthma, ask about the ollowing3:

• Estimated direct costs associated with asthma in the United States grew rom about $53 billion in 2002 to about $56 billion in 2007 (6% increase). 2

• Pattern o symptoms and precipitating actors. Symptoms o ten occur or worsen at night and during exercise, viral in ection, exposure to inhalant allergens or irritants (eg, tobacco smoke, wood smoke,

• Asthma accounts or 17 million visits per year (physician o ces, emergency departments, and hospital outpatient sites). 1

a St h Ma a ND pULMONa r Y FUNCt IO N t e St ING

PART 9

PULMO NARY

A

B FIGURE 55-1 Pulmonary unction te sts (PFTs) in a woman with susp e cte d asthma. A. Sp irome try b e ore and a te r b ronchod ilation with ow volume loop s and g rap h o orce d vital cap acity (FVC). The FEV1 is normal, b ut the FEV1/FVC ratio and FEF25%-75% are re d uce d . Following ad ministration o b ronchod ilators, the re is a g oo d re sp o nse e sp e cially in the small airways as re p re se nte d b y FEF25%-75%. B. Lung volume s are all incre ase d (e sp e cially the re sid ual volume ) ind icating ove rin ation and air trap p ing . The d i using cap acity is normal. Conclusions: minimal airway ob struction, ove rin ation, and a re sp onse to b ronchod ilators are consiste nt with a d iag nosis o asthma. The p atie nt has minimal ob structive airways d ise ase o the asthmatic typ e . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

261

PART 9

262

PULMO NARY

Ch a pt e r 55

TABLE 55-1 Pulmonary Function Te sts, Ke y to Ab b re viations

FVC (L)

Force d vital cap acity

FEV1(L)

Force d vital cap acity at one se cond

FEV1/FVC %

FEV1 d ivid e d b y FVC

FEF25%-75% (L/s)

Force d e xp iratory ow b e twe e n 25% and 75% o cap acity—same as maximal mid e xp iratory ow rate (MMFR)

FEFmax (L/s)

Force d e xp iratory ow maximum

FEF25% (L/s)

Force d e xp iratory ow rate whe n 25% o the FVC has b e e n e xhale d (slop e o FVC curve at 25% e xhale d )

FEF50% (L/s)

Force d e xp iratory ow rate whe n 50% o the FVC has b e e n e xhale d

FEF75% (L/s)

Force d e xp iratory ow rate whe n 75% o the FVC has b e e n e xhale d

FITC (L)

Force d insp iratory vital cap acity

FIF50% (L/s)

Force d insp iratory ow at 50% cap acity

SVC (L)

Slow vital cap acity

TLC (L)

Total lung cap acity

RV (L)

Re sid ual volume

RV/TLC

Re sid ual volume d ivid e d b y total lung cap acity

TGV (L)

Thoracic g as volume

Raw

Airway re sistance

ERV (L)

Exp iratory re se rve volume

IC (L)

Insp iratory cap acity

DLCO

Di using cap acity o lung (using carb on monoxid e me asuring )

VA (L)

Alve olar volume

DL/VA

Di using cap acity d ivid e d b y alve olar volume

airborne chemicals), changes in weather, strong emotional expression (laughing hard or crying), menstrual cycle, and stress. 3 • Family history o asthma, allergy or atopy in close relatives. • Social history (eg, day care, workplace, social support). • History o exacerbations (eg, requency, duration, treatment) and impact on patient and amily. Findings on physical examination may include the ollowing3: • Upper respiratory tract—Increased nasal secretion, mucosal swelling, and/ or nasal polyp. • Lungs—Decreased intensity o breath sounds is the most common (33%-65% o patients). 4 Additional ndings can include wheezing, prolonged phase o orced exhalation, use o accessory respiratory muscles, appearance o hunched shoulders, and chest de ormity. During a severe exacerbation o asthma, minimal airf ow can result in no audible wheezing. • Skin—Atopic dermatitis and/ or eczema (see Chapters 143, 145, and 146). There is a strong association between asthma, allergic rhinoconjunctivitis, and eczema (Figure 55-2), although the “atopic or allergic triad” with the coexistence o all 3 conditions at one time (Figure 55-3)

is not very common. Data support a sequence o atopic mani estations beginning typically with atopic dermatitis in in ancy ollowed by allergic rhinitis and/ or asthma in later stages. 8 Findings in patients with status asthmaticus (prolonged or severe asthma attack that is not responsive to standard treatment) may include the ollowing4: • Tachycardia (heart rate >120 beats/ min) and tachypnea (respiratory rate > 30 breaths/ min) • Use o accessory respiratory muscles • Pulsus paradoxus (inspiratory decrease in systolic blood pressure > 10 mm Hg) • Mental status changes (due to hypoxia and hypercapnia) • Paradoxical abdominal and diaphragmatic movement on inspiration LABO RATO RY TESTING • Spirometry is recommended by National Asthma Education Program (NAEP) or all adolescent and adult patients to determine airway obstruction that is at least partially reversible (Figures 55-1, 55-4 and 55-5). 3 SO R

PART 9

a St h Ma a ND pULMONa r Y FUNCt IO N t e St ING

263

PULMO NARY

FIGURE 55-2 Patie nt with se ve re asthma, atop ic d e rmatitis, and alle rg ic rhinitis—atop ic triad . (Re p ro d uce d with p e rmission fro m Richard P. Usatine , MD.)

FIGURE 55-3 Patie nt with the “atop ic triad ” and a visib le cre ase ove r he r nose rom the “alle rg ic salute ” se cond ary to alle rg ic rhinitis. (Re p ro d uce d with p e rmission from Richard Usatine , MD.)

• Assess severity—Severity is de ned as the intrinsic intensity o the disease process.3 The NAEP divides severity into 4 groups: intermittent, persistent-mild, persistent-moderate, and persistent-severe (Table 55-2).

• Additional tests that may be use ul include the ollowing3:

• Initially, severity can be assessed in the o ce, urgent or emergency care setting with predicted orced expiratory volume in 1 second (FEV1) or PEF; a value o less than 40% indicates a severe exacerbation. A value o equal to or greater than 70% predicted FEV1 or PEF is a goal or discharge rom the emergency care setting. • Once asthma control is achieved, severity can be assessed by the step o care required or control (ie, amount o medication) (see Medications).

IRV

• Pulmonary unction testing i a diagnosis o chronic obstructive pulmonary disease (COPD), restrictive lung disease, or vocal cord dys unction is considered. • Bronchoprovocation (using methacholine, histamine, cold air or exercise challenge) i spirometry is normal or near-normal and asthma is still suspected; a negative test is help ul in ruling out asthma. • Pulse oximetry or arterial blood gas i hypoxia is suspected (eg, cyanosis, rapid respiratory rate). • In the emergency room setting, B-type natriuretic peptide can help distinguish between heart ailure and pulmonary disease. 4

Ins pira tory Ca pa city (IC)

VC TV

Ins pira tory Re s e rve Volume (IRV) Vita l Ca pa city (VC)

Expira tory Re s e rve Volume (ERV)

ERV FRC RV

Re s idua l Volume (RV)

Re s idua l Volume (RV)

Tida l Volume (TV)

Functiona l Re s idua l Ca pa city (FRC)

FIGURE 55-4 Grap h o lung volume s showing the re lationship o tid al volume to vital cap acity and othe r imp ortant lung volume s.

Tota l Lung Ca pa city (TLC)

PART 9

264

Ch a pt e r 55

PULMO NARY

DIFFERENTIAL DIAGNO SIS The di erential diagnosis o an adult with episodic wheezing, chest tightness, cough, and di culty breathing includes the ollowing: • Chronic obstructive pulmonary disease—Usually begins a ter age 40 years with dyspnea (persistent or progressive or worse with exercise), chronic cough (even i intermittent or nonproductive) and/ or sputum production, and/ or a history o COPD risk actors including a amily history o COPD (Chapter 56, Chronic Obstructive Pulmonary Disease). • Chronic bronchitis—A clinical diagnosis de ned as the presence o cough and sputum production o at least 3 months in 2 consecutive years9; although o ten seen in patients with COPD, chronic bronchitis can occur in patients with normal spirometry. FIGURE 55-5 Patie nt having p ulmonary unction te sts (PFTs). (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Pneumonia—Symptoms include ever, chills, and pleuritic chest pain; physical ndings include dullness to percussion, bronchial breathing, egophony (E-A change), and crackles with area o in ltrate or pneumonia usually con rmed on CXR (Chapter 59, Pneumonia). • Tuberculosis—Any age, symptoms o chronic cough. CXR shows in ltrate, positive culture con rms (Chapter 64, Tuberculosis).

IMAGING A chest X-ray (CXR) is not use ul or diagnosis but is help ul or excluding other diseases (eg, pneumonia) or identi ying comorbidity (eg, heart ailure). The main nding on CXR is hyperinf ation (occurring in about 45% o patients with asthma). 4 Hyperinf ation is maniested by the ollowing: • Increased anteroposterior (AP) diameter

• Congestive heart ailure—Nonspeci c basilar crackles, CXR shows cardiomegaly, echocardiogram con rms (Chapter 44, Congestive Heart Failure). • Cough secondary to drugs (eg, angiotensin-converting enzyme inhibitor), vocal cord dys unction—identi ed on medication history or PFT. • Asthma may occur in conjunction with these conditions.

• Increased retrosternal air space (Figure 55-6)

MANAGEMENT

• In racardiac air • Low-set f attened diaphragms (best assessed in lateral chest) • Vertical heart Atelectasis is another nding seen during acute severe episodes (Figure 55-7).

NAEP outlines 4 components o care: assessment and monitoring, provision o education, control o environmental actors and comorbid conditions, and use o medications. 3 The goals o asthma therapy are 2- old3:

TABLE 55-2 Classif cation o Asthma Se ve rity

Int e rmit t e nt

Mild Pe rsist e nt

Mo d e rat e Pe rsist e nt

Se ve re Pe rsist e nt

Symp t o ms

2 or le ss d ays p e r we e k

More than 2 d ays p e r we e k

Daily

Throug hout the d ay

Nig ht t ime Awake ning s

2 ×’s p e r month or le ss

3-4 × ’s p e r month

More than once p e r we e k Nig htly b ut not nig htly

Re scue Inhale r Use

2 or le ss d ays p e r we e k

More than 2 d ays p e r we e k, b ut not d aily

Daily

Se ve ral time s p e r d ay

Int e r e re nce Wit h No rmal Act ivit y

None

Minor limitation

Some limitation

Extre me ly limite d

Lung Funct io n

FEV1 >80% p re d icte d and normal b e twe e n e xace rb ations

FEV1 > 80% p re d icte d

FEV1 60%-80% p re d icte d

FEV1 le ss than 60% p re d icte d

Data rom National He art, Lung and Blood Institute . Exp e rt Pane l Re p ort 3: g uid e line s or the d iag nosis and manag e me nt o asthma.

PART 9

a St h Ma a ND pULMONa r Y FUNCt IO N t e St ING

PULMO NARY

FIGURE 55-6 Acute asthma e xace rb ation with incre ase d lung volume s on CXR. The late ral p roje ction re ve als e nlarg e me nt o the re troste rnal cle ar sp ace (arrow). (Re p rod uce d with p e rmissio n from Carlos Santiag o Re stre p o, MD.)

• Reduce impairment—Prevent chronic symptoms, require in requent (twice weekly or less) use o rescue inhaler, maintain near-normal pulmonary unction, maintain normal activity levels, meet patient and amily expectations and satis action with care. • Reduce risk—Prevent recurrent exacerbations and minimize need or emergency or hospital care, prevent loss o lung unction, and provide optimal pharmacotherapy while minimizing side e ects and adverse e ects.

NO NPHARMACO LO GIC • Exercise should be encouraged. In a randomized clinical trial (RCT) o aerobic exercise in patients with persistent asthma, the group randomized to exercise showed signi cant improvements in physical limitations, requency o symptoms, health-related quality o li e, number o asthma-symptom- ree days, and anxiety and depression levels over the control group (education and breathing exercises only). 10 • For patients exposed to secondhand smoke in the home, use o highe ciency, particulate-arresting (HEPA) air cleaners was shown in one RCT to decrease unscheduled asthma visits or children ages 6 to 12 years. 11 • Dietary changes may also be use ul. In a cross-sectional study, greater adherence to a Mediterranean-type diet was associated with a lower prevalence o asthma symptoms. 12 • Provide patient education. SO R Reduction in hospital and emergency department (ED) visits and missed work or school has also been shown or sel -management education with written asthma action plans and physician review. 4 • Consider interventions to control home environmental triggers; comprehensive individual programs may reduce symptom days. 4 SO R ° Many people who have asthma are allergic to dust mites (Figure 55-8). Two relatively easy interventions to decrease dust mite exposure are encase pillows and mattresses in special dust mite–proo covers and wash the sheets and blankets on the bed each week in hot water. 3 environmental triggers can be ound ° Other suggestions or reducing in the NAEP re erence3 at http:/ / www.nhlbi.nih.gov/ guidelines/ asthma/ asthsumm.pd .

FIGURE 55-7 Acute asthma e xace rb ation in a 28-ye ar-old man. Frontal che st rad iog rap h d e monstrate s incre ase d lung volume s and ill-d e f ne d op acity in the rig ht in rahilar re g ion consiste nt with mid d le lob e se g me ntal ate le ctasis (arrow). (Re p rod uce d with p e rmission from Carlos Santiag o Re stre p o, MD.)

MEDICATIO NS To determine appropriate medication management, assess severity based on symptoms, medication usage, and lung unction. In addition, assess risk based on number o exacerbations requiring systemic steroids.

265

PART 9

266

PULMO NARY

CHAPTER 55

(severe asthma). 3 In a RCT with inner-city children, adolescents, and young adults (N = 419) with persistent asthma, omalizumab reduced symptom days, and the proportion o subjects who had one or more exacerbations (30.3% vs 48.8% on placebo). 15 • To assist with smoking cessation, consider nicotine replacement therapy (bupropion [150 mg, twice daily], varenicline [1 mg twice daily], nortriptyline [75-100 mg daily], or nicotine replacement [gum, inhaler, spray, patch]) and supportive counseling and ollow-up; using these interventions improves rates o smoking cessation by up to 2- old. 16-18 SO R (Chapter 237, Tobacco Addiction) • In patients with persistent asthma attributed to allergies, consider allergy immunotherapy. 3 SO R One meta-analysis concluded that speci c immunotherapy or patients with positive skin tests resulted in a reduction in need or increased medications (number needed to treat = 5) and another study in patients with high IgE ound immunotherapyreduced exacerbations. 4 FIGURE 55-8 Dust mite s und e r the microscop e . Dust mite s are a common alle rg e n or p atie nts who su e r ro m asthma and alle rg ic rhinitis. Environme ntal control to minimize d ust mite e xp osure can he lp control asthma or some ind ivid uals. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

For youths (age 12 years and up) and adults, persistent asthma is divided into mild, moderate, or severe; these categories are matched to steps o medications described below. The NAEP 6 steps o care with respect to asthma medications are as below3: • Step 1: For all aged patients with intermittent asthma, an inhaled SABA is recommended. SO R Metered-dose inhalers with spacers are at least as e ective (with ewer side e ects) as nebulized treatment or most patients. • Step 2: Low-dose inhaled corticosteroids (ICS) are the pre erred longterm control therapy or all ages with persistent asthma. SO R Alternatives include cromolyn inhaler, leukotriene receptor antagonist (LTRA), nedocromil, or theophylline. LTRAs are less e ective than ICS but better than placebo. 3 SO R • Step 3: Combination low-dose ICS and long-acting β 2-agonist (LABA) or medium-dose ICS are equally pre erred options. 3 SO R Alternatives include low-dose ICS plus LTRA (less e ective than ICS and LABA), theophylline, or zileuton. Theophylline requires monitoring serum concentration levels. Zileuton is less desirable due to limited supporting data and need to monitor liver unction. Authors o a Cochrane review ound the combination ICS-LABA modestly more e ective in reducing the risk o exacerbations requiring oral corticosteroids than higher-dose ICS or adolescents and adults. 13 • Step 4: Combination medium-dose ICS and LABA. Alternatives are combination medium-dose ICS plus LTRA, theophylline, or zileuton (see above). • Step 5: Combination high-dose ICS and LABA. • Step 6: Combination high-dose ICS and LABA plus oral corticosteroid. Other drug options • In a RCT, the addition o tiotropium bromide (a long-acting anticholinergic agent approved or the treatment o COPD but not asthma) to inhaled ICS was superior to doubling the ICS dose in improving lung unction and symptoms and nonin erior to the addition o a LABA to ICS (step 3). 14 • Omalizumab should be considered or patients over 11 years o age who have allergies or or adults who require step 5 or 6 care

• The use o proton pump inhibitor therapy in adults with asthma is not likely to add signi cant bene t. 19 For patients with an exacerbation o asthma (dyspnea with activity, PEF ≥70% predicted or personal best), SABAs and sometimes oral corticosteroids are used or home management o patients with a mild exacerbation, ollowing their action plan. NAEP does not recommend doubling the dose o ICS or home management versus oral steroids or exacerbations. 3 A Cochrane review concluded that a short course o oral steroids was e ective in reducing the number o relapses to additional care, hospitalizations, and use o SABA without an apparent increase in side e ects. 20 • Moderate exacerbation (dyspnea inter eres with usual activity, PEF 40% to 69% predicted or personal best) usually requires an o ce or ED visit; SABA and oral corticosteroids (typically 40-60 mg prednisone or adults) are recommended or 3 to 10 days. SO R SABA can be administered every 20 minutes as needed and the addition o inhaled ipratropium bromide may reduce the need or hospitalization (0.68-0.75). 4 SO R Symptoms usually abate in 1 to 2 days. • Severe exacerbation (dyspnea at rest, PEF < 40% predicted or personal best) usually requires an ED visit and/ or hospitalization; consider combination SABA and anticholinergic nebulized treatment hourly or continuously as needed, oral corticosteroids, and adjunctive treatment as needed (see below). Symptoms last or longer than 3 days a ter treatment begins. • Li e-threatening exacerbation (too dyspneic to speak, diaphoresis, PEF 3 cm b ut < 5 cm (2a) and has any o the ollowing : involve s the main b ronchus (> 2 cm d istal to the carina), invad e s visce ral p le ura, or associate d with ate le ctasis or ob structive p ne umonitis e xte nd ing to the hilar re g ion (T2a N0 M0) • Stag e IIA—Tumor size > 5 cm b ut < 7 cm (2b ) (T2b N0 M0, T1a,b N1 M0, T2a N1 M0) • Stag e IIB—Tumor size >5 cm b ut 7 cm or d ire ctly invad e s the che st wall, d iap hrag m, p hre nic ne rve , me d iastinal p le ura, p arie tal p e ricard ium; or tumor in the main b ronchus < 2 cm d istal to the carina b ut without carina involve me nt; or associate d ate le ctasis or ob structive p ne umonitis o the e ntire lung or se p arate tumor nod ule (s) in the same lob e as the p rimary (T3) (T2b N1 M0, T3 N0 M0) • Stag e IIIA—Any size tumor includ ing a tumor that invad e s the me d iastinum, he art, g re at ve sse ls, trache a, re curre nt laryng e al ne rve , e sop hag us, ve rte b ral b od y, carina, or se p arate tumor in a d i e re nt ip silate ral lob e to that o the p rimary (T4) (T1a,b or T2a,b N2 M0, T3 N1or 2 M0, T4 N0 or 1 M0) T, Tumor (size and e xte nt); N, re g ional lymp h nod e s (N0 no re g ional lymp h nod e me tastasis, N1 me tastasis in ip silate ral p e rib ronchial and / o r ip silate ral hilar lymp h no d e s and intrap ulmo nary no d e s, includ ing involve me nt b y d ire ct e xte nsion, N2 me tastasis in ip silate ral me d iastinal and /or sub carinal lymp h nod e [s], N3 me tastasis in contralate ral me d iastinal, contralate ral hilar, ip silate ral or contralate ral scale ne , or sup raclavicular lymp h nod e [s]); M, me tastase s (M0 no d istant me tastasis, M1 d istant me tastasis).

• Pain medication should be provided as needed (Chapter 4, End o Li e). Opioids, such as codeine or morphine, may reduce cough.

• Preoperative chemotherapy in patients with NSCLC increases survival by about 6% (absolute bene t) at 5 years. 20 Advantages o preoperative chemotherapy include early start on potential micrometastases and higher adherence to therapy. 8 • Maintenance therapy with either cytotoxic agents or tyrosine kinase inhibitor agents (or switch therapy) can be considered as it appears to increase overall survival or patients with nonprogressive NSCLC. 21 • Management o patients with SCLC includes combination, platinumbased chemotherapy (see later). 5,22 SO R Targeted therapies have not proven bene cial or patients with SCLC. 22 CO MPLEMENTARY O R ALTERNATIVE THERAPY In a small RCT o patients with NSCLC on chemotherapy, nutritional intervention with 2.2 g o sh oil per day provided a bene t on maintenance o weight and muscle mass over standard care. 23 Fish oil also increased the response to chemotherapy in those with advanced NSCLC and may provide a survival bene t (trend). 24 SURGERY AND RADIATIO N Management o patients with NSCLC includes the ollowing: • Localized stage I and II—Pulmonary resection. 5,25,26 SO R Evidence is conf icting about whether video-assisted thoracoscopic surgery o ers advantages over standard lobectomy; either technique can be used. 8,25,26 • In patients undergoing resection, intraoperative systematic mediastinal lymph node sampling or dissection is recommended or accurate staging. 25 Although data are limited, a Cochrane review concluded that resection combined with complete mediastinal lymph node dissection is associated with a modest survival improvement compared with resection combined with systematic sampling o mediastinal nodes in patients with stage I to IIIA NSCLC. 27 • For patients with stage I disease who are not surgical candidates, external beam radiotherapy is recommended;28 stereotactic body radiation therapy or percutaneous ablation can be considered as a treatment option. 25,26 SO R • Adjuvant chemotherapy is recommended or patients with stage II disease. 25,29 • Stage IIIA and avorable age, cardiovascular unction, and anatomy— Possible surgery and/ or concurrent chemo- or radiation therapy. • Stage IIIB—Concurrent chemo- or radiation therapy. 25 • Stage IV—Options include radiation therapy to symptomatic local sites, chemotherapy or molecular targeted agents, chest tube or

PART 9

LUNG Ca NCe r

malignant e usion, and consideration o resection o primary or isolated brain or adrenal metastases. 5,25 A Cochrane review concluded that chemotherapy improves overall survival in patients with advanced NSCLC (absolute improvement in survival o 9% at 12 months [20%-29%] or absolute increase in median survival o 1.5 months [ rom 4.5 months to 6 months]). 30 • Curative radiotherapy should be considered or patients with good perormance status and inoperable stage I to III disease. 25 Management o patients with very limited (stage I) SCLC is surgical resection and adjuvant combined cisplatin-based chemotherapy, possibly with prophylactic cranial irradiation. 22 • Other patients with limited-stage SCLC (stages II-III) should be o ered thoracic irradiation concurrently with the rst or second cycle o chemotherapy or ollowing completion o chemotherapy i there has been at least a good partial response within the thorax. 5,22 Prophylactic cranial irradiation should be considered i nonprogressive a ter induction treatment. 22 • For patients with extensive disease (stage IV), limited data support prolonged survival (added 63-84 days) using chemotherapy. 31 Supportive care plus palliative thoracic irradiation should be considered ollowing chemotherapy (combination etoposide and cisplatin or non-Asian patients and irinotecan and cisplatin or Asian patients). 22 • For patients who are not candidates or chemotherapy, palliative radiotherapy should be considered. 22 Palliative radiotherapy is associated with a modest increase in survival (5% at 1 year) in patients with better per ormance status who are given higher-dose radiotherapy. 32 Other targeted therapies, based on molecular testing o tumor mutational pro iles (eg, erlotinib or mutant EGFR) should be considered. • External beam radiotherapy could also be considered or the relie o breathlessness, cough, hemoptysis, or chest pain. 5

PREVENTIO N • Avoid smoking or smoking exposure or quit, i already smoking. • Avoid workplace and home exposures (listed in risk actors). • Daily aspirin appears to protect against lung adenocarcinoma. 33 • Routine screening or lung cancer is not currently recommended; the US Preventive Services Task Force concluded insu cient evidence to support screening with any modality. 34 Results o the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (N = 154,901) demonstrated no bene t o annual CXR screening on reducing lung cancer mortality compared with usual care. 35 • However, the National Lung Screening Trial (N = 53,454 patients at high risk or lung cancer) reported lower mortality rom lung cancer a ter 3 annual screenings or patients randomized to low-dose CT versus single-view posteroanterior chest radiography (247 deaths rom lung cancer per 100,000 person-years and 309 deaths per 100,000 person-years, respectively). 36 There was also reduced all-cause mortality in this group by 6.7%. As the risk o alse positives with low-dose CT is high (33% a ter 2 screenings)37 and there is potential or radiation-induced cancer, it is not clear that routine screening or high-risk patients should be conducted.

PULMO NARY PRO GNO SIS • Perioperative mortality rom a large database o over 18,000 lung cancer resections per ormed at 111 participating centers was 2.2% and composite morbidity and mortality occurred in 8.6%. 38 Predictive actors o mortality included pneumonectomy, bilobectomy, per ormance status, induction chemoradiation, steroids, age, and renal dys unction among other actors. • Adverse prognostic actors or NSCLC include presence o pulmonary symptoms, large tumor size (> 3 cm), nonsquamous histology, metastases to multiple lymph nodes within a TNM-de ned nodal station, and vascular invasion. 4 • The overall 5-year relative survival rom lung cancer (SEER data 2001-2007) was 15.6%. Five-year relative survival by race and sex was 18.3% or white women, 14.5% or black women, 13.7% or white men, and 11.6% or black men. 2 • Five-year survival decreases by stage at diagnosis ranging rom 52.2% or localized disease to 3.6% or those with distant metastases. 2 Estimates or 5-year survival by stage are stage IA 73%, stage IB 65%, stage IIA 46%, stage IIB 36%, stage IIIA 24%, stage IIIB 9%, and stage IV 13%. 16 • For SCLC, median survival or patients with limited-stage disease is about 15 to 20 months (20%-40% survive to 2 years). For those with extensive-stage SCLC disease, median survival is about 8 to 13 months with 2-year survival o 5%. 8 • Following lung cancer resection, there is a 1% to 2% risk per patient per year that a second lung cancer will occur. 5 One author reported higher risks o second tumors in long-term survivors, including rates o 10% or second lung cancers and 20% or all second cancers. 39 For patients with SCLC, second primary tumors are reported in 2% to 10% o patients per year. 22

FO LLO W-UP Surveillance or the recognition o a recurrence o the original lung cancer and/ or the development o a metachronous tumor should be coordinated through a multidisciplinary team approach. • This team should develop a li elong surveillance plan appropriate or the individual circumstances o each patient immediately ollowing initial curative-intent therapy. 5 SO R • In patients ollowing curative-intent therapy or lung cancer, the use o blood tests, FDG-PET scanning, sputum cytology, tumor markers, and f uorescence bronchoscopy is not currently recommended or surveillance. 2

PATIENT EDUCATIO N • Smoking cessation, never initiating smoking, and avoidance o occupational and environmental exposure to carcinogenic substances are recommended to reduce the risk o recurrence or a second primary in curatively treated patients. In patients with metastatic disease, although smoking cessation has little e ect on overall prognosis, it may improve respiratory symptoms.

283

PART 9

284

PULMO NARY • In ormation about local hospice services and support groups should be provided. The Lung Cancer Alliance Web site, listed in “Patient Resources” below, can be used to nd support groups.

PATIENT RESO URCES

• Information for patients can be accessed at the Web site of National Cancer Institute—http:/ / www.cancer.gov/ cancertopics/ types/ lung. • More information for patients can be accessed from—http:/ / www.mayoclinic.com/ health/ lung-cancer/ DS00038. • American Lung Association—http:/ / www.lungusa.org. • Support groups for patients and families can be found at the following Web site—http:/ / www.lungcanceralliance.org/ get-help-and-support/ coping-with-lung-cancer/ support-groups.html. PRO VIDER RESO URCES

• Providers may nd information on lung cancer and ongoing clinical trials at the ollowing Web sites—http:/ / www.nlm.nih.gov/ medlineplus/ lungcancer.html and http:/ / www.cancer .gov/ cancertopics/ types/ lung.

REFERENCES 1. Centers or Disease Control and Prevention. Lung Cancer Statistics. http:/ / www.cdc.gov/ cancer/ lung/ statistics/ index.htm. Accessed January 2012. 2. National Cancer Institute. SEER Stat Fact Sheets: Lung and Bronchus. http:/ / seer.cancer.gov/ stat acts/ html/ lungb.html. Accessed January 2012. 3. Centers or Disease Control and Prevention. Basic Information About Lung Cancer. http:/ / www.cdc.gov/ cancer/ lung/ basic_in o/ index. htm. Accessed January 2012. 4. National Cancer Institute. Non-Small Cell Lung CancerTreatment (PDQ). http:/ / cancer.gov/ cancertopics/ pdq/ treatment/ non-small-celllung/ healthpro essional. Accessed January 2012. 5. Minna JD. Neoplasms o the lung. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson, JL eds. Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2005:506-516. 6. Olsson AC, Gustavsson P, Kromhout H, et al. Exposure to diesel motor exhaust and lung cancer risk in a pooled analysis rom casecontrol studies in Europe and Canada. Am J Respir Crit Care Med. 2011;183(7):941-948. 7. Chlebowski RT, Schwartz AG, Wakelee H, et al. Oestrogen plus progestin and lung cancer in postmenopausal women (Women’s Health Initiative trial): a post-hoc analysis o a randomised controlled trial. Lancet. 2009;374(9697):1243-1251. 8. Goldstraw P, Ball D, Jett JR, et al. Non-small-cell lung cancer. Lancet. 2011;378(9804):1727-1740. 9. Dacic S. Molecular diagnostics o lung carcinomas. Arch Pathol Lab Med. 2011;135(5):622-629. 10. Rosell R, Moran T, Queralt C, et al. Screening or epidermal growth actor receptor mutations in lung cancer. N Engl J Med. 2009;361(10):958-967.

Ch a pt e r 57

11. Ray CE Jr, English B, Funaki BS, et al. Expert Panel on Interventional Radiology. ACR Appropriateness Criteria biopsies o thoracic nodules and masses. Reston, VA: American College o Radiology (ACR); 2011:7. http:/ / www.guideline.gov/ content.aspx?id= 3261 6&search= lung+neoplasm. Accessed February 2012. 12. Yasu uku K, PierreA, Darling G, et al. A prospective controlled trial o endobronchial ultrasound-guided transbronchial needle aspiration compared with mediastinoscopy or mediastinal lymph node staging o lung cancer. JThorac Cardiovasc Surg. 2011;142(6):1393-1400.e1. 13. Ravenel JG, Mohammed TH, Movsas B, et al., Expert Panel on Thoracic Imaging and Radiation-Oncology-Lung. ACR Appropriateness Criteria non-invasive clinical staging o bronchogenic carcinoma. Reston, VA: American College o Radiology (ACR); 2010:11. http:/ / www.guideline.gov/ content.aspx?id=32627&search= lung+ neoplasm. Accessed February 2012. 14. Maziak DE, Darling GE, Inculet RI, et al. Positron emission tomography in staging early lung cancer: a randomized trial. Ann Intern Med. 2009;151(4):221-228, W-48. 15. Fischer B, Lassen U, Mortensen J, et al. Preoperative staging o lung cancer with combined PET-CT. N Engl J Med. 2009;361(1):32-39. 16. Goldstraw P, Crowley J, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals or revision o the TNM stage grouping in the orthcoming (seventh) edition o the TNM Classi cation o malignant tumours. JThorac Oncol. 2007;2(8):706-714. 17. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care or patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733-742. 18. Parsons A, Daley A, Begh R, Aveyard P. Inf uence o smoking cessation a ter diagnosis o early stage lung cancer on prognosis: systematic review o observational studies with meta-analysis. BMJ. 2010 Jan 21;340:b5569. 19. NSCLC Meta-analysis Collaborative Group, Arriagada R, Auperin A, Burdett S, et al. Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses o individual patient data. Lancet. 2010;375(9722): 1267-1277. 20. Burdett S, Stewart L, Rydzewska L. Chemotherapy and surgery versus surgery alone in non-small cell lung cancer. Cochrane Database of Syst Rev. 2007;(3):CD006157. 21. Zhang X, Zhang J, Xu J, et al. Maintenance therapy with continuous or switch strategy in advanced non-small cell lung cancer: a systematic review and meta-analysis. Chest. 2011;140(1):117-126. 22. vanMeerbeeck JP, Fennell DA, DeRuysscher DKM. Small-cell lung cancer. Lancet. 2011;378(9804):1741-1755. 23. Murphy RA, Mourtzakis M, Chu QS, et al. Nutritional intervention with sh oil provides a bene t over standard o care or weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy. Cancer. 2011;117(8):1775-1782. 24. Murthy RA, Mourizakis M, Chu QS, et al. Supplementation with sh oil increases rst-line chemotherapy e cacy in patients with advanced nonsmall cell lung cancer. Cancer. 2011;117(16):3774-3780. 25. Carr LL, Finigan JH, Kern JA. Evaluation and treatment o patients with non-small cell lung cancer. Med Clin North Am. 2011;95(6): 1041-1054. 26. Scott WJ, Howington J, Feigenberg S, et al. American College o Chest Physicians. Treatment o non-small cell lung cancer stage I and

LUNG Ca NCe r

stage II: ACCP evidence-based clinical practice guidelines (2nd ed). Chest. 2007 Sep;132(suppl 3): S234-S242. http:/ / www.guideline. gov/ content.aspx?id=11415&search=lung+cancer. Accessed February 2012. 27. Manser R, Wright G, Hart D, Byrnes G, Campbell D. Surgery or local and locally advanced non-small cell lung cancer. Cochrane Database Syst Rev. 2005;25(1):CD004699. 28. Gewanter RM, Movsas B, Rosenzweig KE, et al. Expert Panel on Radiation Oncology-Lung. ACR Appropriateness Criteria nonsurgical treatment or non-small-cell lung cancer: good per ormance status/ de nitive intent. Reston, VA: American College o Radiology (ACR); 2010:11. http:/ / www.guideline.gov/ content.aspx?id= 238 40&search= lung+cancer+acr. Accessed February 2012. 29. Decker RH, Langer CJ, Movsas B, et al., Expert Panel on Radiation Oncology-Lung. ACR Appropriateness Criteria postoperative adjuvant therapy in non-small-cell lung cancer. Reston, VA: American College o Radiology (ACR); 2010:10. http:/ / www.guideline.gov/ content.aspx?id= 32607&search= lung+ cancer+ acr. Accessed February 2012. 30. Non-Small Cell Lung Cancer Collaborative Group. Chemotherapy and supportive care versus supportive care alone or advanced nonsmall cell lung cancer. Cochrane Database Syst Rev. 2010;(5):CD007309. 31. Pelayo Alvarez M, Gallego Rubio Ó, Bon ll Cosp X, Agra Varela Y. Chemotherapy versus best supportive care or extensive small cell lung cancer. Cochrane Database Syst Rev. 2009;(4):CD001990.

PART 9

PULMO NARY 32. Lester JF, MacBeth F, Toy E, Coles B. Palliative radiotherapy regimens or non-small cell lung cancer. Cochrane Database Syst Rev. 2006;(4):CD002143. 33. Rothwell PM, Fowkes FG, Belch JF, et al. E ect o daily aspirin on long-term risk o death due to cancer: analysis o individual patient data rom randomised trials. Lancet. 2011;377(9759):31-41. 34. United States Preventive Services Task Force. Lung Cancer Screening. http:/ / www.uspreventiveservicestask orce.org/ uspst / uspslung. htm. Accessed January 2012. 35. Oken NM, Hocking WG, Kvale PA, et al.; PLCO Project Team. Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial. JAMA. 2011;306(17):1865-1873. 36. National Lung Screening Trial Research Team, Aberle DR, Adams AM, Bery CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5): 395-409. 37. Croswell JM, Baker SG, Marcus PM, et al. Cumulative incidence o alse-positive test results in lung cancer screening: a randomized trial. Ann Intern Med. 2010;152(8):505-512. 38. Kozower BD, Sheng S, O’Brien SM, et al. STS database risk models: predictors o mortality and major morbidity or lung cancer resection. AnnThorac Surg. 2010;90(3):875-881. 39. Fry WA, Menck HR, Winchester DP. The National Cancer Data Base report on lung cancer. Cancer. 1996;77(9):1947-1955.

285

286

PART 9

PULMO NARY

58 PLEURAL EFFUSIO N Satish Chand olu, MD

Ch a pt e r 58

SYNO NYMS • Hydrothorax • Parapneumonic e usion

PATIENT STO RY A 63-year-old woman with a 48 pack-year smoking history and lung cancer that was diagnosed 1 year ago with metastasis involving mediastinal lymph nodes presents with shortness o breath or the past 3 days. She also admits to experiencing cough with no sputum production and orthopnea. She was admitted 3 months previous or a similar problem, at which time she was diagnosed with a malignant pleural e usion and was treated with therapeutic thoracentesis. On examination, she is noted to have dullness to percussion on the right side o her chest, with the dullness extending rom the right base to the apex, and decreased breath sounds and vocal remitus on the same side. Chest radiography shows a pleural e usion extending to the apex o the lung on the right side o her chest (Figure 58-1). She is admitted to the hospital and is put on a PleurX catheter drain; within several hours, her dyspnea resolves.

INTRO DUCTIO N The pleural space exists between the visceral and parietal pleura, which normally has about 10 mL o uid. A pleural e usion is the presence o an excess amount o uid in the pleural space. Pleural uid is ormed by capillaries and drained by lymphatics in the same parietal pleura. 1 The lymphatics in parietal pleura have the capacity to drain 20 times more uid than the capillaries in the periphery.

• Chylothorax—lymphatic uid (chyle) accumulating in the pleural cavity • Empyema—pus in the pleural cavity

ETIO LO GY/ PATHO PHYSIO LO GY • Conditions that can decrease the oncotic pressure, leading to a transudate, include the ollowing: ° Cirrhosis ° Nephrotic syndrome ° Peritoneal dialysis ° Myxedema • Conditions that can increase hydrostatic pressure, leading to a transudate, include the ollowing: ° Congestive heart ailure (CHF) ° Pulmonary embolism ° Superior vena cava obstruction • Conditions that can disrupt the vessel wall, leading to exudates, include the ollowing: ° Trauma (including esophageal rupture) ° Any in ection ° Collagen vascular disorders ° Malignancy ° Iatrogenic ° Lymphatic abnormalities ° Treatments (certain drugs and chemotherapy) ° Intra-abdominal conditions (exudate) ° Pancreatic disease ° Intra-abdominal abscesses ° Diaphragmatic hernia ° A ter abdominal surgery ° Endoscopic variceal sclerotherapy ° A ter liver transplant • Fluid may also accumulate rom visceral pleura or rom the abdomen (through diaphragmatic openings).

DIAGNO SIS HISTO RY/ SYMPTO MS Based on the etiology, the patient may present with the ollowing: • shortness o breath, • orthopnea, • paroxysmal nocturnal dyspnea, • chest pain, • cough, • ever, • chills, FIGURE 58-1 A p oste roante rior che st rad iog rap h d e monstrating a larg e p le ural e usion in the rig ht he mithorax rom a p ulmonary malig nancy. (Re p rod uce d with p e rmission from Gary Fe re nchick, MD.)

• weight loss, or • abdominal distention

PART 9

pLe Ur a L e FFUSIO N

287

PULMO NARY

PHYSICAL EXAMINATIO N • Inspection may show tracheal deviation to the opposite side o pleural e usion depending on the onset and severity o the e usion. • Palpation, depending on the etiology, may show tenderness o the chest or abdomen. • Percussion will show a stony dullness at the site o involvement. I the abdomen is involved, uid thrill or shi ting dullness may be present. • Auscultation will reveal decreased breath sounds at the site o pleural involvement, and egophony may be heard at the air- uid level. IMAGING • Chest radiography (both posteroanterior [PA] and lateral) is the most use ul test or diagnosing a pleural e usion. ° Based on the etiology, it can show bilateral or unilateral e usion. ° Typically, about 300 mL o uid are necessary to appreciate a pleural e usion in the PA f lm, but a lateral decubitus f lm can detect as little as 50 mL uid. 2 ° The other advantage o a decubitus radiograph is to di erentiate loculated e usion rom ree uid. ° The typical radiographic signs o pleural e usion include blunting o the costophrenic (ie, the angle between pleura and diaphragm) and cardiophrenic (ie, the angle between heart borders and diaphragm) angles, opacity caused by uid (Figure 58-2). Depending on the etiology, radiography also may show le t atrial enlargement and prominent pulmonary vasculature (i the cause is cardiac), inf ltrate or cavity changes (eg, parapneumonic e usions), or lymph node enlargement. • Thoracic computed tomographic (CT) scanning is most sensitive in diagnosing uid in the thorax and can detect as little as 10 mL o uid (Figure 58-3). CT can also detect underlying lung inf ltrate, suggesting parapneumonic e usion, thickened pleura, splitting o pleura,

FIGURE 58-3 A che st comp ute d tomog rap hic scan d e monstrating an e usion me asuring more than 10 mm rom the lung to the che st wall. (Re p rod uce d with p e rmission from Gary Fe re nchick, MD.)

pleural calcif cations, lung abscess, empyema, hemothorax, or liver cirrhosis and helps in guiding thoracentesis. 3 • Thoracic ultrasound can help in identif cation o ree uid rom loculated uid and helps di erentiating the latter with solid masses. 4 LABO RATO RY TESTING • Thoracentesis is a procedure to remove uid rom the pleural space. It can be diagnostic or therapeutic. • Diagnostic thoracentesis is indicated i the cause o e usion is not clear. • Pleural uid analysis may di erentiate a transudate rom an exudate. This di erentiation and uid analysis are crucial in planning a specif c treatment. • Light’s criteria to di erentiate transudate rom exudative e usions include the ollowing5: Parame t e r

Transud at e Exud at e

Ple ural f uid p rote in/se rum p rote in

< 0.5

>0.5

Ple ural f uid LDH/se rum LDH

< 0.6

>0.6

Ple ural f uid LDH more than twothird s o se rum LDH

No

Ye s

LDH, lactate d e hyd rog e nase .

° A transudate should meet all three criteria. ° These criteria, however, may classi y nearly 25% o transudates as exudates, and i the clinical suspicion o a transudate is high, measuring the protein gradient (a di erence o protein level between serum and pleural uid) may help. ° Although the uid is exudate per the criteria, a gradient o more than 31 g/ L is almost always a transudate. FIGURE 58-2 A che st rad iog rap h d e monstrating b ilate ral p le ural e usion in a p atie nt with cirrhosis. Note the me niscal sig n at the costop hre nic ang le (ye llow arrows). Also note the p romine nt horizontal ssure on the rig ht rom f uid in the ssure (re d arrow). (Re p rod uce d with p e rmissio n from Gary Fe re nchick, MD.)

• In an exudate, urther uid analysis, including Gram stain, acid- ast bacillus (AFB) stain, glucose, amylase, pH, cytology, di erential cell count, triglycerides, cholesterol, and culture, may help identi y the underlying diagnosis.

PART 9

288

PULMO NARY

Ch a pt e r 58

• New criteria have been proposed whose diagnostic accuracy is similar to Light’s criteria. Presence o at least one criterion rom this list qualif es the uid as an exudate: 6 ° Two-test rule ■ Pleural uid cholesterol greater than 45 mg/ dL ■ Pleural uid LDH greater than 0.45 times the upper limit o the laboratory’s normal serum LDH 6 ° Three-test rule ■ Pleural uid protein greater than 2.9 g/ dL (29 g/ L) ■ Pleural uid cholesterol greater than 45 mg/ dL (1.165 mmol/ L) ■ Pleural uid LDH greater than 0.45 times the upper limit o the laboratory’s normal serum LDH

MANAGEMENT • Transudates and exudates rom nonmalignant pleural e usions (NMPF) o ten respond to treatment o underlying disease. • But, i the symptoms are rom the pleural uid or i the uid persists even a ter the treatment o an underlying condition, a therapeutic thoracentesis may be necessary. • Reaccumulation o uid—Repeat thoracentesis may be needed i the uid accumulates slowly (nearly once in a month, but no specif c guidelines) and i the procedure is not burdensome to the patient. • Pleurodesis ° This treatment involves obliterating the pleural space by injecting talc, bleomycin, or tetracyclines to create in ammation and then f brosis. It is necessary or f brosis to develop between the visceral and parietal pleural space without creating a gap where uid can reaccumulate. Chemical pleurodesis may not be success ul i the pleural uid initially accumulated rapidly (eg, hepatic hydrothorax) or i any anatomical inter erence (eg, trapped lung) is present. 7 ° The e f cacy o pleurodesis is high in chronic ambulatory peritoneal dialysis, yellow nail syndrome, chylothorax, nephrotic syndrome, lupus pleuritis, heart ailure, and malignant pleural e usions.

FIGURE 58-4 A che st rad iog rap h d e monstrating a massive le t p le ural e usion with a “white out” and a p ig tail ind welling cathe te r at the b ottom o the le t lung (arrow). (Re produce d with pe rmission from Gary Fe re nchick, MD.)

• Pleurodesis rom talc may cause an acute in ammatory reaction, including a systemic in ammatory response. • Pleurodesis may ail i lungs are not well expanded during the process o sclerosis.

• Other treatment options ° Chest tube placement to acilitate uid drainage and to let the underlying lung expand during the acute episode is an option when the patient has signif cant dyspnea rom pleural e usion. ° Indwelling catheter drainage (commonly called a “pigtail” catheter or PleurX) in the dependent part o the uid can be used to drain uid out intermittently8 (Figure 58-4). 9 ° Pleuroperitoneal shunts (internal drainage) are an option. ° Pleurovenous shunts (internal drainage) can be used. 10 ° Surgical pleurectomy can be a treatment option.

CO MPLICATIO NS • Untreated uid may become in ected. • Fluid may prevent the underlying lung rom expanding, causing atelectasis or pneumonia. • Thoracentesis may rupture blood vessels and may cause bleeding and hemothorax. • Thoracentesis may injure underlying lung parenchyma and cause pneumothorax (Figure 58-5).

FIGURE 58-5 A che st rad iog rap h d e monstrating a comb ination o p ne umothorax (ye llow arrows) and a hyd rothorax (re d arrows) in a 62-ye ar-old woman with an iatrog e nic p ne umothorax. (Re p rod uce d with p e rmissio n from Gary Fe re nchick, MD.)

PART 9

pLe Ur a L e FFUSIO N

PULMO NARY

SPECIAL SITUATIO NS

PATIENT RESO URCES

• Congestive heart ailure ° CHF commonly produces bilateral e usions. ° I a unilateral e usion is present in a patient with CHF, per orm thoracentesis and assess pleural uid N-terminal pro-brain natriuretic peptide (NT-proBNP); i it is greater than 1500 pg/ mL, this is virtually diagnostic o an e usion secondary to CHF.

• PubMed Health. Pleural Effusion—http:/ / www.ncbi.nlm.nih .gov/ pubmedhealth/ PMH0001150/ .

• Parapneumonic e usions ° The possibility o a parapneumonic e usion should be considered whenever a patient with bacterial pneumonia is initially evaluated. ° I the ree uid separates the lung rom the chest wall by more than 10 mm, a therapeutic thoracentesis should be per ormed. Consider the ollowing actors or determining therapeutic thoracentesis in parapneumonic e usions11: ■ Loculated pleural uid ■ Pleural uid pH less than 7.20 ■ Pleural uid glucose less than 3.3 mmol/ L (0) or has hypoxia, worsening symptoms, preexisting conditions that compromise sa ety o home care or or patients who ail to improve in more than 72 hours. 3,14

PREVENTIO N • Vaccination—Pneumococcal polysaccharide vaccine is recommended or persons greater than or equal to 65 years o age and or those with selected high-risk concurrent diseases. 14 SO R All adolescents, persons greater than or equal to 50 years o age, others at risk or in uenza complications, and health care workers should be immunized annually with vaccines or in uenza virus to prevent CAP. 14 SO R Vaccination status should be assessed at the time o hospital admission or all patients and appropriate vaccines should be o ered at discharge. 14 SO R • Smoking cessation assistance should be o ered to patients who smoke. • To prevent spread o respiratory pathogens, respiratory hygiene measures should be practiced. 14 These include the coughing into the elbow and use o hand hygiene and masks or tissues or patients with cough, particularly in outpatient settings and emergency departments.

SO R

coverage (quinolone monotherapy to β-lactams or cephalosporins) in hospitalized patients with CAP. 23 • Hospitalized patient in ICU—β-Lactam (ce otaxime, ce triaxone, or ampicillin-sulbactam) plus either azithromycin SO R or a uoroquinolone. SO R For penicillin-allergic patients, a respiratory uoroquinolone and aztreonam are recommended. For Pseudomonas in ection, an antipneumococcal, antipseudomonal β-lactam (piperacillin-tazobactam, ce epime, imipenem, or meropenem) plus either cipro oxacin or levo oxacin (750-mg dose) or above β-lactam plus an aminoglycoside and azithromycin or above β-lactam plus an aminoglycoside and an antipneumococcal uoroquinolone. • I the etiology o CAP is identif ed on the basis o reliable microbiological methods, antimicrobial therapy should be directed at that pathogen. • Early treatment (within 48 hours o the onset o symptoms) with oseltamivir or zanamivir is recommended or in uenza A. 14

PRO GNO SIS • Patients on adequate therapy or CAP should demonstrate clinical (and laboratory) signs o improvement within 48 to 72 hours. • Outpatient mortality rate is 1%. The mortality rate or those who require admission to the hospital averages 12%, and the mortality rate or patients with severe CAP in the ICU setting approaches 40%. 3 In a multihospital study in Canada, 9% (N = 89) o patients died in hospital, 10% had died at 30 days, and 247 (26%) had died by 1 year. In-hospital mortality was higher among patients with admission hypoglycemia. 25 • Using a large database, guideline concordant therapy or CAP (65% o cases) was associated with decreased in-hospital mortality (OR, 0.70; 95% CI, 0.63-0.77), sepsis (OR, 0.83; 95% CI, 0.72-0.96), and renal ailure (OR, 0.79; 95% CI, 0.67-0.94), and reduced hospital LOS and duration o parenteral therapy (0.6 days or both). 26

FO LLO W-UP

• Duration—A minimum o 5 days. SOR The patient should be a ebrile or 48 to 72 hours and have no more than one CAP-associated sign o instability (eg, temperature >37.8°C, tachycardia, respiratory rate >24 breaths/ min, hypotension, oxygen saturation 2 cm rom the edge o the lung to the thorax as measured at the level o the hilum) should be hospitalized and have a chest tube inserted to reexpand the lung. SO R • Patients who are clinically stable with a smaller pneumothorax (1-2 cm rom the edge o the lung to the thorax as measured at the level o the hilum) should be hospitalized and treated with aspiration with a 16- to 18-gauge needle cannula in an attempt to reexpand the lung, with the goal o achieving a pneumothorax o less than 1 cm. I this is not success ul, then a chest tube should be inserted. SO R • Unstable patients with pneumothoraces o any size should be hospitalized and have a chest tube inserted to reexpand the lung. SO R • Because a secondary pneumothorax can be lethal, a procedure to prevent urther pneumothorax recurrence is recommended. SO R Surgical thoracoscopy is the pre erred method o recurrence prevention. • Patients with persistent air leaks who re use a surgical procedure can continue to be observed with prolonged chest tube drainage or 5 days. SO R

• Tension pneumothorax should always be treated by per orming a large tube thoracostomy.

PRO GNO SIS/ CLINICAL CO URSE • The prognosis o patients with pneumothorax depends on the patient’s underlying condition, severity o prior lung dys unction, and physiological impairment rom the pneumothorax itsel . 4 ° PSP is seldom atal. ° SSP is more dangerous than PSP and can be li e threatening. • Patients who are critically ill and those with a tension pneumothorax have the worst prognoses. Early studies showed mortality rom tension pneumothorax to be 7%; delayed diagnosis increased mortality to 31%.

Ch APTe r 60

• The incidence o recurrent PSP is estimated to be 25% to more than 50%; most recurrences occur within 1 year o the initial event. tall stature, low ° Risk actors or recurrence include male gender, body weight, and ailure to stop smoking. 4 ° Estimates o recurrence rates ollowing SSP range rom 39% to 47%. • Complications associated with pneumothorax include bronchopleural stula and pulmonary edema related to reexpansion. ° Bronchopleural stula is more commonly associated with SSP, traumatic pneumothorax, and pneumothorax in mechanically ventilated patients. ° Pulmonary edema related to reexpansion is a rare complication characterized by unilateral pulmonary edema that occurs within 48 hours a ter lung reexpansion. Treatments include supportive management and mechanical ventilation or acute respiratory ailure.

PATIENT EDUCATIO N • Smokers have a higher risk o recurrence. Patients who smoke should be advised to stop smoking (see Chapter 237, Tobacco Addiction). 5 The patients who continued smoking had a higher recurrence rate (70%) than those patients who stopped smoking a ter the rst pneumothorax (40%). 5 • Patients are advised to avoid diving permanently unless the patient has a de nite bilateral surgical pleurectomy. 4,6 • A 1- to 2-month delay is recommended or air travelers who recovered rom PSP. 7 PATIENT RESO URCES

• Pneumothorax.org—http:/ / www.pneumothorax.org/ . PRO VIDER RESO URCES

• MacDuff A, Arnold A, Harvey J; BTS Pleural Disease Guideline Group. Management of spontaneous pneumothorax: British Thoracic Society pleural disease guideline 2010. Thorax. 2010;65(suppl 2): ii18-ii31. http:/ / thorax.bmj.com/ content/ 65/ Suppl_2/ ii18.long. REFERENCES 1. Melton LJ III, Hepper NG, Offord KP. Incidence of spontaneous pneumothorax in Olmsted County, Minnesota: 1950 to 1974. Am Rev Respir Dis. 1979;120:1379-1382. 2. Abolnik IZ, Lossos IS, Gillis D, Breuer R. Primary spontaneous pneumothorax in men. Am J Med Sci. 1993;305:297-303. 3. Bense L, Eklund G, Wiman LG. Smoking and the increased risk of contracting spontaneous pneumothorax. Chest. 1987;92:1009-1012. 4. MacDuff A, Arnold A, Harvey J; BTS Pleural Disease Guideline Group. Management of spontaneous pneumothorax: British Thoracic Society pleural disease guideline 2010. Thorax. 2010;65(suppl 2):ii18-ii31. 5. Sadikot RT, Greene T, Meadows K, Arnold AG. Recurrence of primary spontaneous pneumothorax. Thorax. 1997;52:805-809. 6. Ziser A, Vaananen A, Melamed Y. Diving and chronic spontaneous pneumothorax. Chest. 1985;87:264-265. 7. Curtin SM, Tucker AM, Gens DR. Pneumothorax in sports: issues in recognition and ollow-up care. Phys Sportsmed. 2000;28:23-32.

PART 9

PULMO NARY EMBO LISM

61 PULMO NARY EMBO LISM Mind y A. Smith, MD, MS

PATIENT STO RY A 52-year-old woman developed acute shortness o breath 3 weeks a ter a hysterectomy. She denied leg pain or swelling. She has no chronic medical problems and takes no medications. Her pulse is 105 beats/ min, respiratory rate is 20 breaths/ min, and the rest o her examination is unremarkable. She had an elevated hemidiaphragm on chest X-ray (CXR). These ndings placed her at moderate risk or pulmonary embolism (PE) based on the Geneva score. Chest computed tomography (CT) demonstrated a moderate-sized PE similar to the one shown in Figure 61-1. She was treated with anticoagulation without complications.

INTRO DUCTIO N PE is a thromboembolic occlusion (total or partial) o one or more pulmonary arteries usually arising rom a deep venous thrombosis (DVT).

EPIDEMIO LO GY • Population estimate o the age- and sex-adjusted annual incidence o DVT is 48 per 100,000 and 69 per 100,000 or PE; the incidence increases with age. 1

PULMO NARY • PEs are noted as incidental ndings in 1% to 4% o chest CT studies. 2 • One meta-analysis concluded that nearly 1 in every 4 to 5 patients presenting with an exacerbation o chronic obstructive pulmonary disease has a PE; presenting signs and symptoms did not distinguish patients with and without PE. 3 • In a meta-analysis o randomized controlled trials (RCTs) o patients on venous thromboembolism (VTE) prophylaxis, the pooled rates o symptomatic DVT were 0.63% (95% con dence interval [CI], 0.47%-0.78%) ollowing knee arthroplasty and 0.26% (95% CI, 0.14%-0.37%) ollowing hip arthroplasty. The pooled rates or PE were 0.27% (95% CI, 0.16%-0.38%) ollowing knee arthroplasty and 0.14% (95% CI, 0.07%-0.21%) ollowing hip arthroplasty. 4

ETIO LO GY AND PATHO PHYSIO LO GY • PE is most commonly caused by embolization o a thrombus rom a proximal leg or pelvic vein that enters the pulmonary artery circulation and obstructs a vessel. PE may also be caused by the ollowing actors1: ° An upper extremity thrombus ( rom indwelling catheters or pacemakers) (see Figure 61-1) ° Fat embolus ( ollowing surgery or trauma) ° Hair/ talc/ cotton embolus ( rom intravenous drug use) ° Amniotic f uid embolus ( rom a tear at the placental margin in a pregnant woman) • PE results rom vascular endothelial injury which promotes platelet adhesion, blood f ow stasis, and/ or hypercoagulation causing more coagulants to accumulate than usual and resulting obstruction. Although most PEs are asymptomatic and do not alter physiology, PE can cause the ollowing: ° Increased pulmonary, vascular, and airway resistance ( rom obstruction o vessels or distal airways). ° Impaired gas exchange ( rom increased dead space and right-to-le t shunting). ° Alveolar hyperventilation ( rom stimulation o irritant receptors). ° Decreased pulmonary compliance ( rom lung edema, hemorrhage, or loss o sur actant). ° Right ventricular (RV) dys unction ( rom increased pulmonary vascular resistance, increased RV wall tension, and reduced right coronary artery f ow). in arction; most PEs are ° Only about 10% o emboli cause pulmonary multiple and involve the lower lobes. 5

RISK FACTO RS In a population study, independent risk actors or DVT included the ollowing6: • Surgery (odds ratio [OR], 21.7; 95% CI, 9.4-49.9). • Trauma (OR, 12.7; 95% CI, 4.1-39.7). • Hospital or nursing home con nement (OR, 8.0; 95% CI, 4.5-14.2). • Malignant neoplasm with (OR, 6.5; 95% CI, 2.1-20.2) or without (OR, 4.1; 95% CI, 1.9-8.5) chemotherapy. • Central venous catheter or pacemaker (OR, 5.6; 95% CI, 1.6-19.6). FIGURE 61-1 C e st X-ray s owing a we d g e -s ap e d p ulmonary in arction wit t e b ase on t e p le ural sur ace and t e ap e x at t e tip o a p ulmonary arte ry cat e te r; t e cat e te r cause d t e occlusion o a p e rip e ral arte ry. (Re prod uce d with p e rmission from Mille r WT, Jr. Diag nostic T oracic Imag ing . Ne w York, NY: McGraw-Hill; 2006:272, Fig ure 5-61, Cop yrig ht 2006.)

• Super cial vein thrombosis (OR, 4.3; 95% CI, 1.8-10.6). A recent study ound a slightly higher OR, 6.3 (95% CI, 5-8) or DVT and 3.9 (95% CI, 3-5.1) or PE. 7 • Neurologic disease with extremity paresis (OR, 3.0; 95% CI, 1.3-7.4).

299

PART 9

300

Ch APTER 61

PULMO NARY • Other risk actors or PE include hormonal treatment (ie, combined estrogen/ progestogen oral contraceptives [OCs] or menopausal hormone therapy), pregnancy, obesity, smoking, chronic obstructive pulmonary disease, immobility, bed rest or more than 3 days, and clotting disorders. In a Danish population study, the risk o venous thrombosis in current users o combined OCs decreased with duration o use (OR 4 years 2.76 [95% CI, 2.53-3.02]) and decreasing oestrogen dose.8 OCs with desogestrel, gestodene, or drospirenone were associated with a signi cantly higher risk o venous thrombosis than those with levonorgestrel while progestogen-only pills and hormone-releasing intrauterine devices were not associated with an increased risk.

Diagnostic strategy begins with the determination o a patient’s (pretest) probability o PE using a clinical decision rule (see Figure 61-2). The 2 most requently used rules are the Geneva and the Wells score. 11,12 Online calculators are available or the Wells score (http:/ / www.mdcalc.com/ wells-criteria- or-pulmonary-embolism-pe/ . Accessed June 2013). The Geneva score appears to be the most consistent across experience o examiner;13 and the revised Geneva scoring system per orms as well as the Wells and also does not require laboratory testing or imaging. 14 A score o 0 to 3 indicates a low probability o PE (8%); 4 to 10 indicates intermediate probability o PE (28%); and greater than 10 indicates a high probability o PE (74%). The revised Geneva score is derived by summing the ollowing points:

• Genetic predisposition includes actor V Leiden and prothrombin gene mutations.

• Age older than 65 years (+1)

• Use o an antipsychotic agent (particularly atypical antipsychotics) increased risk o DVT in a population nested case-control study (OR 1.32, 95% CI, 1.23-1.42). 9

• Previous DVT or PE (+3) • Surgery or racture within 1 month (+ 2) • Active malignant condition (+ 2) • Unilateral lower limb pain (+3) • Hemoptysis (+ 2)

DIAGNO SIS A history and physical examination should be completed to assess risk actors and determine whether the patient is clinically stable. I unstable (eg, hemodynamic instability [including systolic blood pressure < 90 mm Hg, or a drop in 40 mm Hg], syncope, severe hypoxemia, or respiratory distress), thrombolytic therapy should be considered (Figure 61-2). 2,10

• Heart rate 75 to 94 beats/ min (+ 3) or greater than or equal to 95 beats/ min (+ 5) • Pain on lower limb deep venous palpation and unilateral edema (+4) The Wells score is derived by summing the actors below; a score less than 2 indicates a low probability o PE (15%); 2 to 6 indicates intermediate

Pa tie nt with s us pe cte d P E Ye s

Uns ta ble or initia l te s ting s ugge s ts ma s s ive P E

Be gin a nticoa gula tion e me rge nt CT or be ds ide e choca rdiogra phy Cons ide r thrombolytics

No S OR B

De te rmine clinica l proba bility of P E

If clinica l s igns of DVT, pe rform compre s s ion ve nous ultra s ound Ne ga tive

Low proba bility

Inte rme dia te

Pos itive

High proba bility

S OR C

High s e ns itivity D-dime r Pos itive

Ne ga tive

CTPA or V/Q s ca n if pre fe rre d or CTPA contra indica te d Ne ga tive ; s till s us pe ct P E*

No

Nondia gnos tic

Pos itive

Be gin a nticoa gula tion

Ye s

P E exclude d; look for a lte rna tive dia gnos is Ne ga tive

If inte rme dia te proba bility, cons ider a nd if high proba bility or nondia gnos tic te s t, pe rform a dditiona l te s ting: CTPA if not done D-dime r V/Q s ca n if not done Lowe r limb ima ging Pulmona ry a rte riogra phy

*Ba s e d on clinica l impre s s ion, high proba bility with pos itive D-dime r a nd ne ga tive CTPA, or confus ing pre s e nta tion.

FIGURE 61-2 Ap p roac to t e p atie nt wit susp e cte d p ulmonary e mb o lus.

PULMO NARY EMBO LISM

PART 9

PULMO NARY

probability o PE (29%); and greater than 6 indicates a high probability o PE (59%). Alternatively, the Wells score can be dichotomized as PE less likely or likely (the latter with score greater than 4)2: • Clinically suspected DVT (+ 3) • Alternative diagnosis is less likely than PE (+ 3) • Tachycardia (+ 1.5) • Immobilization or surgery in previous 4 weeks (+1.5) • History o DVT or PE (+ 1.5) • Hemoptysis (+ 1) • Malignancy (treatment or within 6 months, palliative) (+1) Patients with a high pretest probability o PE or high risk due to comorbidities (eg, pulmonary hypertension) should be started on anticoagulation during the workup. 2,10 CLINICAL FEATURES • Dyspnea—It is the most common symptom and tachycardia is the most common sign. Sudden onset o dyspnea is the best single predictor (positive likelihood ratio [LR+ ] 2.7). • Chest pain—May be caused by a small, peripheral PE with pulmonary in arction. • Other signs—Include ever, neck vein distention, and accentuated pulmonic component o the second heart sound. • Massive PE—May present with shock, syncope, and cyanosis. LABO RATO RY STUDIES AND ECG • The combination o a clinical decision rule and sensitive plasma 15,16 SO R d -dimer is used to rule out PE (sensitive but not speci c). The test is suggested or patients with low or moderate probability o a PE; i low probability and negative (< 500 ng/ mL), there is only approximately a 0.4% chance that the patient has a PE. 14 I low or intermediate probability, a negative d -dimer concentration is associated with a posttest probability o PE below 5% (negative likelihood ratio [LR− ] 0.08 [0.04-0.18]). 17 O patients with a PE, 90% will have a value greater than 500 ng/ mL. Use o an age-adjusted d -dimer (patient’s age × 10 µg/ L) was shown in one study to increase the percentage o patients in whom PE could be sa ely excluded ( rom 13% to 14% to 19% to 22%). 18 I the d -dimer is positive, urther testing is needed (see Figure 61-2). 2

FIGURE 61-3 C e st X-ray s owing b ilate ral p ulmonary inf ltrate s t oug t to re p re se nt p ne umonia. (Re p ro d uce d with p e rmission fro m Mille r WT, Jr. Diag nostic T oracic Imag ing . Ne w York, NY: McGraw-Hill; 2006:273, Fig ure 5-63 A, Cop yrig ht 2006.)

° A peripheral wedge-shaped density (see Figure 61-1). ° Decreased vascular markings (Figure 61-5). • When a patient has an intermediate or high PE probability score, PE is con rmed by a positive CT pulmonary angiography (CTPA) or highprobability lung scan and ruled out by a negative CTPA or normal lung scan (see Figure 61-2). The American College o Radiology (ACR) and Institute or Clinical Systems Improvement recommend CTPA over V/ Q scan or patients with suspected PE, unless the ormer is contraindicated or nondiagnostic (see Figure 61-2). 2,19 CT (see Figure 61-4) can also provide evidence o alternate diagnoses.

• An electrocardiography (ECG) may be indicated to search or alternate diagnoses. The most requent, sensitive, and speci c ECG nding or PE is T-wave inversion in leads V1-4 indicative o RV strain. Other ndings include tachycardia, new-onset atrial brillation or f utter, S in lead I, Q and inverted T in lead III, and a QRS axis greater than 90 degrees. • An arterial blood gas is obtained i clinically indicated. A platelet count should be obtained prior to initiation o ondaparinux. 10 IMAGING • CXR is o ten nonspeci c; dyspnea with a near-normal CXR should suggest PE. Findings that may be seen on CXR include the ollowing: ° Triad o basal in ltrate, blunted costophrenic angle, and elevated hemi-diaphragm. ° In ltrates similar to pneumonia (Figure 61-3) that may be diagnosed using CT (Figure 61-4).

FIGURE 61-4 CT scan rom t e p atie nt in Fig ure 61-3 d e monstrate s se ve ral larg e we d g e -s ap e d p ulmonary op acitie s wit air b ronc og rams c aracte ristic o p ulmonary in arcts (re d arrows). Incid e ntally note d is t e p re se nce o b ilate ral p le ural e usions (g re e n arrows). (Re p ro d uce d with p e rmission from Mille r WT, Jr. Diag nostic T oracic Imag ing . Ne w York, NY: McGraw-Hill; 2006:273, Fig ure 5-63 B, Cop yrig ht 2006.)

301

302

PART 9

PULMO NARY

FIGURE 61-5 Pulmonary e mb o lism: We ste rmark sig n, an avascular zone b e cause o ob structe d ve sse l rom a b lood clot. In t is p atie nt, b ot lung ap ice s and t e mid -to -lowe r t orax ave d e cre ase d vascular marking s. Note t e usi orm e nlarg e me nt o b ot ila and t e p romine nt p ulmonary arte ry me d iastinal s ad ow c aracte ristic o p ulmonary yp e rte nsion. (Re p rod uce d with p e rmission from Mille r WT, Jr. Diag nostic T oracic Imag ing . Ne w York, NY: McGraw-Hill; 2006:748, Fig ure 14-19 A, Cop yrig ht 2006.)

Ch a pt e r 61

FIGURE 61-6 Pulmonary ang iog ram in t e p atie nt in Fig ure 61-5 s owing ab rup tly truncate d p ulmonary arte rie s associate d wit re g ions o d iminis e d p e r usion typ ical o c ronic p ulmonary e mb oli. (Re p rod uce d with p e rmission from Mille r WT, Jr. Diag nostic T oracic Imag ing . Ne w York, NY: McGraw-Hill; 2006:748, Fig ure 14-19 B, Cop yrig ht 2006.)

DIFFERENTIAL DIAGNO SIS • A V/ Q scan is considered the initial test or patients with high probability o PE who have renal insu ciency or dye allergy. A highprobability scan or PE (positive predictive value o 90%) has 2 or more segmental per usion de ects with normal ventilation. • For pregnant women with suspected PE, the American Thoracic Society or Society o Thoracic Radiology recommend CXR as the initial study ollowed by lung scintigraphy (V/ Q scan) i the CXR is normal and CTPA i the V/ Q scan is nondiagnostic. 20 • I the CTPA or lung scan is nondiagnostic, a leg ultrasound with compression is usually per ormed. I positive or a DVT, proceed with treatment as below. I normal or nondiagnostic, other testing such as a pulmonary angiogram is suggested (see Figure 61-2). • Pulmonary angiography is generally reserved or patients with nondiagnostic CTPA, lung scans, or leg ultrasound and or patients who will undergo embolectomy or catheter-directed thrombolysis. ACR also recommends pulmonary angiography in circumstances where a speci c diagnosis (ie, PE) is considered necessary or the proper patient management and be ore placement o an in erior vena cava (IVC) lter. 10 An intraluminal lling de ect may be seen along with truncated arteries associated with regions o diminished per usion (Figure 61-6). • Although magnetic resonance imaging (MRI) is not indicated in the routine evaluation o suspected PE, magnetic resonance angiography (MRA) is used in certain centers with particular interest and expertise, and in patients in whom contrast administration or CTPA or pulmonary angiography is thought to be contraindicated because o renal ailure, prior reaction to iodinated contrast, pulmonary hypertension or or other reasons. 19

The di erential diagnosis o a symptomatic PE includes the ollowing: • Pneumonia—Symptoms include chills, ever, and pleuritic chest pain (the latter 2 can occur with PE); physical ndings include dullness to percussion, bronchial breathing, egophony (E-A change), and crackles with area o in ltrate or pneumonia usually con rmed on CXR (see Chapter 59, Pneumonia). • Congestive heart ailure—History o previous heart ailure or myocardial in arction; symptoms o paroxysmal nocturnal dyspnea, orthopnea or the presence o bilateral lower extremity edema, third heart sound, hepatojugular ref ex, and jugular venous distention. CXR may show pulmonary venous congestion, interstitial or alveolar edema, and cardiomegaly (see Chapter 44, Congestive Heart Failure). • Pneumothorax—History o previous pneumothorax or chronic obstructive pulmonary disease, or current rib racture; physical ndings include absence o breath sounds and CXR may show ree air, an elevated hemidiaphragm or a shi t o the mediastinum to the contralateral side with a tension pneumothorax.

MANAGEMENT NO NPHARMACO LO GIC • Knee-high compression stockings (30-40 mm Hg) are recommended to reduce recurrence and prevent postthrombotic syndrome. 10 SO R • Psychological support may be needed.

PART 9

pULMO Na r Y e MBO LISM

MEDICATIO N • Primary treatment o PE is considered or patients with hemodynamic instability, RV dys unction, or in arct. In selected patients with massive PE, systemic administration o thrombolytic therapy (via a peripheral vein with a 2-hour in usion) is suggested. 2,10 SO R Brain natriuretic peptide and troponin testing, combined with echocardiography, can help identi y patients at high risk o deterioration who would be candidates or thrombolytic therapy. 2

PULMO NARY most or massive or submassive PEs in the main pulmonary trunk or bilateral main pulmonary arteries, operative mortality was 5.3%. 27 No patients exhibited newly developed neurologic damage. • IVC lter placement is reserved or patients with contraindications to anticoagulation or or ailure o anticoagulation (ie, recurrence or progression o thromboembolism despite anticoagulation). 2,10 SO R While decreasing recurrent PE, they do not appear to improve longterm survival.

• Moderate-to-large PE can be treated similarly or with anticoagulation only. In a recent Cochrane review, authors ound no trials comparing thrombolytic therapy to surgical intervention and were unable to determine whether thrombolytic therapy was better than heparin or PE. 21

• Adjunctive therapy, i needed, includes pain relie and supplemental oxygen. RV ailure or shock may be treated with dobutamine.

• Acute PEs or proximal DVT are treated with oral anticoagulation to prevent uture PE. In addition to beginning oral anticoagulation (eg, war arin 5 mg daily, adjusted based on international normalized ratio [INR]), treatment options include intravenous un ractionated heparin (IV UFH) using a weight-based nomogram, subcutaneous (SC) lowmolecular-weight heparin (LMWH; 1 mg/ kg twice daily) or SC ondaparinux (a selective actor Xa inhibitor) or a minimum o 5 days. 2,10 SO R The American College o Chest Physicians (ACCP) recommends LMWH as rst choice unless there is a massive PE, concern about SC absorption, severe renal insu ciency, or thrombolytic therapy is under consideration or planned; IV UFH is then the pre erred agent. 10 I UFH is used, therapeutic levels (activated partial thromboplastin time [aPTT] 1.5-2.5 times normal) should be achieved within 24 hours. 22

• Consider consultation with a coagulation specialist or patients with recurrent VTE, i alternative anticoagulants are being considered, i there is an increased risk o bleeding, and or pregnant women.

• Once the INR is therapeutic (range 2-3) ( or at least 24 hours prior to discontinuing above treatment), oral anticoagulation is continued or a minimum o 3 to 12 months or inde nitely unless there is a known reversible or time-limited risk actor (eg, recent surgery) when oral anticoagulation may be discontinued a ter 3 months. 2,10 SO R For additional recommendations on duration o therapy, see the ACCP guideline. 10 A Cochrane review reported no excess recurrence o VTE a ter stopping therapy and while absolute risk o recurrence declines over time, the risk or major bleeding remains. 23

• Mechanical methods (graduated compression stockings [GCS] and/ or intermittent pneumatic compression) are recommended or thromboprophylaxis in hospitalized patients at high risk o bleeding or possibly as an adjunct to anticoagulant-based prophylaxis. 10 SO R For more detailed in ormation on prophylaxis (eg, surgical or cancer patients), see the ACCP guidelines.

• In another Cochrane review based on 15 RCTs, xed-dose SC un ractionated heparin could not be proven nonin erior to standard treatment with respect to DVT and PE at 3 months (trend avored standard arm), but was sa e and e ective with regard to rates o major bleeding and death. 24 • Patients with a history o heparin-induced thrombocytopenia (HIT) should not be treated with either UFH or LMWH. Fondaparinux is an option although several cases o ondaparinux-associated HIT have been reported. 10 • Direct thrombin inhibitors (eg, ximelagatran) appear to be as e ective as LMWH in prevention o venous thromboembolism and treatment o PE, may have ewer side e ects, and do not require routine monitoring. They are not considered initial therapy using current guidelines. In one trial, idraparinux was not as e ective as heparin or PE treatment. 25 In another trial, oral ximelagatran was as e ective as enoxaparin ollowed by war arin in patients with PE. 26 SURGERY AND PRO CEDURES Highly compromised patients who are unable to receive thrombolytic therapy or whose critical status does not allow su cient time to in use thrombolytic therapy may be treated with pulmonary embolectomy. 10 SO R In a Japanese case series o 19 patients undergoing embolectomy,

REFER O R HO SPITALIZE

• Patients with cardiovascular or respiratory compromise should be admitted to the intensive care unit. Patients with symptomatic PE are usually hospitalized due to decreased cardiopulmonary reserve. 10 One open label trial (N = 344) ound no signi cant di erences between inpatient and outpatient treatment with only 1 patient dying in each group. 28 However, 2 outpatients had major bleeding in the rst 14 days and 3 by 90 days versus no patients in the inpatient group.

PREVENTIO N

• A Cochrane review ound GCS e ective in reducing the risk o DVT in hospitalized patients rom 26% without GCS to 13% with GCS and rom 16% with another method o prophylaxis alone to 4% with GCS with another method o prophylaxis. 29 • The American College o Physicians recommends assessment o thromboembolism and bleeding risk and pharmacologic prophylaxis with heparin or a related drug unless the assessed risk or bleeding outweighs the likely bene ts or hospitalized nonsurgical patients. They recommend against use o GCS or routine hospitalized nonsurgical patients. 30 • For long-distance travelers (eg, f ights > 8 hours) avoidance o constrictive clothing around the lower extremities or waist, maintenance o adequate hydration, and requent cal muscle contraction are recommended. 10 SO R In high-risk individuals, consider use o GCS providing 15 to 30 mm Hg o pressure at the ankle or a single prophylactic dose o LMWH, injected prior to departure. 10 SO R

PRO GNO SIS • In a large multicenter study o patients with acute PE (N = 1880), mortality rate directly attributed to PE was 1% (95% CI, 0%-1.6%). 31 Mortality rom hemorrhage was 0.2% and the all-cause 30-day mortality rate was 5.4% (95% CI, 4.4%-6.6%). Delay in initiating anticoagulation appeared to be a mortality actor as only 3 o 20 patients with atal PE had systemic anticoagulation initiated be ore diagnostic con rmation; another 3 o these 20 received a brinolytic agent.

303

PART 9

304

PULMO NARY These gures were much improved over a 3-country registry o patients (N = 2110) with acute PE rom 1999, where the 3-month mortality rate was 15.3%. 32 • In a retrospective Japanese study o patients with PE treated surgically, the 10-year survival rate was 83.5% ± 8.7%.29.

Ch a pt e r 61

REFERENCES 1. Silverstein MD, Heit JA, Mohr DN, et al. Trends in the incidence o deep vein thrombosis and pulmonary embolism. A 25-year population-based study. Arch Intern Med. 1998;158:585-593.

• In one study with a rate o adverse events o 7.4% (N = 42) at 30 days ollowing acute PE, actors associated with those events included altered mental state (OR 6.8; 95% CI, 2-23.3), shock on admission (OR 2.8; 95% CI, 1.1-7.5) and cancer (OR 2.9; 95% CI, 1.2-6.9). 33

2. Institute or Clinical Systems Improvement (ICSI). VenousThromboembolism Diagnosis andTreatment. Bloomington, MN: Institute or Clinical Systems Improvement (ICSI); 2011 Mar: 93. http:/ / www. guideline.gov/ content.aspx?id= 32482&search=pulmonary+embol ism. Accessed February 2012.

• In an Italian prospective cohort study o patients with DVT or PE ollowing discontinuation o anticoagulation therapy (N = 1626), 22.9% had a recurrence o VTE. 34

3. Rizkallah J, Man SF, Sin DD. Prevalence o pulmonary embolism in acute exacerbations o COPD: a systematic review and metaanalysis. Chest. 2009;135(3):786-793.

• Pulmonary hypertension develops in about 5% o patients ollowing PE.35

4. Januel JM, Chen G, Ru eux C, et al. Symptomatic in-hospital deep vein thrombosis and pulmonary embolism ollowing hip and knee arthroplasty among patients receiving recommended prophylaxis: a systematic review. JAMA. 2012;307(3):294-303.

FO LLO W-UP • Patients on war arin should be monitored using a standard protocol. Patients on LMWH do not require routine monitoring except or pregnant women where monitoring with anti-Xa levels is recommended. 10 SO R • For patients with serious bleeding complications, management includes holding war arin, giving vitamin K1 10-mg slow IV plus resh rozen plasma or prothrombin complex concentrate, and repeating vitamin K1 every 12 hours as needed. SO R • PE is slow to resolve; based on 4 imaging studies, the percentage o patients with residual pulmonary thrombi was 87% at 8 days a ter diagnosis, 68% a ter 6 weeks, 65% a ter 3 months, 57% a ter 6 months, and 52% a ter 11 months. 36

PATIENT EDUCATIO N • Patients taking war arin should be instructed about the importance o remaining on oral anticoagulation or at least 3 months and use o compression stockings to decrease the likelihood o recurrence. Patients should also be counseled about the signs and symptoms o bleeding, to ask about potential drug interactions be ore starting a new medication, and the importance o laboratory monitoring. • Use o an anticoagulation service or home sel -monitoring37 can be considered to improve adherence and reduce complications. • Avoidance o periods o prolonged immobilization is suggested.

PATIENT RESO URCES

• National Heart, Lung, and Blood Institute. Pulmonary Embolism— http:/ / www.nhlbi.nih.gov/ health/ health-topics/ topics/ pe/ . PRO VIDER RESO URCES

• Medline Plus. Pulmonary Embolism—www.nlm.nih.gov/ medlineplus/ pulmonaryembolism.html. • Agency for Healthcare Research and Quality. Pulmonary Embolism— http:/ / www.guideline.gov/ content.aspx?id=34040. • Agency for Healthcare Research and Quality. Thromboembolism in Pregnancy— http:/ / www.guideline.gov/ content .aspx?id=34439.

5. Moser KM. Venous thromboembolism. Am Rev Respir Dis. 1990;141:235-249. 6. Heit JA, Silverstein MD, Mohr DN, et al. Risk actors or deep vein thrombosis and pulmonary embolism: a population-based casecontrol study. Arch Intern Med. 2000;160(6):809-815. 7. vanLangevelde K, Lij ering WM, Rosendaal FR, Cannegieter SC. Increased risk o venous thrombosis in persons with clinically diagnosed super cial vein thrombosis: results rom the MEGA study. Blood. 2011;118(15):4239-4241. 8. Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk o venous thromboembolism: national ollow-up study. BMJ. 2009 Aug 13;339:b2890. 9. Parker C, Coupland C, Hippisley-Cox J. Antipsychotic drugs and risk o venous thromboembolism: nested case-control study. BMJ. 2010 Sep 21;341:c4245. 10. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management o the vitamin K antagonists: American College o Chest Physicians Evidence-Based Clinical Practice Guidelines (8th ed). Chest. 2008;133(suppl 6):S160-S198. 11. Wicki J, Perneger TV, Junod AF, et al. Assessing clinical probability o pulmonary embolism in the emergency ward: a simple score. Arch Intern Med. 2001;161:92-97. 12. Wells PS, Anderson DR, Rodger M, et al. Derivation o a simple model to categorize patients probability o pulmonary embolism: Increasing the model’s utility with the SimpliRED D-dimer. Thromb Haemost. 2000;83:416-420. 13. Iles S, Hodges AM, Darley JR, et al. Clinical experience and pretest probability scores in the diagnosis o pulmonary embolism. Q J Med. 2003;96:211-215. 14. Le Gal G, Righini M, Roy PM, et al. Prediction o pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med. 2006;144(3):165-171. 15. American College o Emergency Physicians Clinical Policies Com-

mittee; Clinical Policies Committee Subcommittee on Suspected Pulmonary Embolism. Clinical policy: critical issues in the evaluation and management o adult patients presenting with suspected pulmonary embolism. Ann Emerg Med. 2003;41(2):257-270. 16. Lucassen W, Geersing GJ, Erkens PM, et al. Clinical decision rules or excluding pulmonary embolism: a meta-analysis. Ann Intern Med. 2011;155(7):448-460.

pULMO Na r Y e MBO LISM

17. Roy PM, Colombet I, Durieux P, et al. Systematic review and meta-analysis o strategies or the diagnosis o suspected pulmonary embolism. BMJ. 2005 Jul 30;331(7511):259. 18. van Es J, Mos I, Douma R, et al. The combination o our di erent clinical decision rules and an age-adjusted d -dimer cut-o increases the number o patients in whom acute pulmonary embolism can sa ely be excluded. Thromb Haemost. 2012;107(1):167-171. 19. Bettmann MA, Lyders EM, Yucel EK, et al; Expert Panel on

Cardiac Imaging. Acute Chest Pain— Suspected Pulmonary Embolism. Reston, VA: American College o Radiology (ACR); 2006:5. http:/ / www.guideline.gov/ content.aspx?id= 35135. Accessed June 2013. 20. Leung AN, Bull TM, Jaeschke R, et al. An o cial American Thoracic Society/ Society o Thoracic Radiology clinical practice guideline: evaluation o suspected pulmonary embolism in pregnancy. Am J Respir Crit Care Med. 2011;184(10):1200-1208. 21. Dong B, Hao Q, Yue J, et al. Thrombolytic therapy or pulmonary embolism. Cochrane Database Syst Rev. 2009;(3):CD004437. 22. Hull RD, Raskob GE, Brant RF, Pineo GF, Valentine KA. Relation between the time to achieve the lower limit o the APTT therapeutic range and recurrent venous thromboembolism during heparin treatment or deep vein thrombosis. Arch Intern Med. 1997;157: 2562-2568. 23. Hutten BA, Prins MH. Duration o treatment with vitamin K

antagonists in symptomatic venous thromboembolism. Cochrane Database Syst Rev. 2006;(1):CD001367. 24. Vardi M, Zittan E, Bitterman H. Subcutaneous un ractionated heparin or the initial treatment o venous thromboembolism. Cochrane Database Syst Rev. 2009;(4):CD006771.

PART 9

PULMO NARY 28. Aujesky D, Roy PM, Verschuren F, et al. Outpatient versus inpatient treatment or patients with acute pulmonary embolism: an international, open-label, randomised, non-in eriority trial. Lancet. 2011;378(9785):41-48. 29. Sachdeva A, Dalton M, Amaragiri SV, Lees T. Elastic compres-

sion stockings or prevention o deep vein thrombosis. Cochrane Database Syst Rev. 2010;(7):CD001484. 30. Qaseem A, Chou R, Humphrey LL, et al. Venous thromboembolism prophylaxis in hospitalized patients: a clinical practice guideline rom the American College o Physicians. Ann Intern Med. 2011;155(9): 625-632. 31. Pollack CV, Schreiber D, Goldhaber SZ, et al. Clinical characteristics, management, and outcomes o patients diagnosed with acute pulmonary embolism in the emergency department: initial report o EMPEROR (Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry). JAm Coll Cardiol. 2011;57(6):700-706. 32. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;353:1386-1389. 33. Sanchez O, Trinquart L, Caille V, et al. Prognostic actors or pulmonary embolism: the prep study, a prospective multicenter cohort study. Am J Respir Crit Care Med. 2010;181(2):168-173. 34. Prandoni P, Noventa F, Ghirarduzzi A, et al. The risk o recurrent venous thromboembolism a ter discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica. 2007;92(2):199-205. 35. Kearon C. Natural history o venous thromboembolism. Circulation. 2003;107:I22-I30.

25. The van Gogh Investigators, Buller HR, Cohen AT, et al. Idraparinux versus standard therapy or venous thromboembolic disease. N Engl J Med. 2007;357:1094-1104.

36. Nijkeuter M, Hovens MM, Davidson BL, Huisman MV. Resolution o thromboemboli in patients with acute pulmonary embolism: a systematic review. Chest. 2006;129:192-197.

26. Fiessinger JN, Huisman MV, Davidson BL, et al; THRIVE, Treatment Study Investigators. Ximelagatran vs low-molecular-weight heparin and war arin or the treatment o deep vein thrombosis: a randomized trial. JAMA. 2005;293:681-689.

37. Menendez-Jandula B, Souto JC, Oliver A, et al. Comparing sel -management o oral anticoagulant therapy with clinic management. Ann Intern Med. 2005;142(1):1-10.

27. Fukuda I, Taniguchi S, Fukui K, et al. Improved outcome o surgical pulmonary embolectomy by aggressive intervention or critically ill patients. AnnThorac Surg. 2011;91(3):728-732.

305

PART 9

306

PULMO NARY

Ch a pt e r 62

62 PULMO NARY FIBRO SIS Gary Fe re nchick, MD

PATIENT STO RY A 68-year-old man presents with dyspnea on exertion and mild intermittent cough or the previous 2 months. He is a nonsmoker and denies chronic exposure to organic or nonorganic dust. On examination, he has normal vital signs and a resting oximetry o 92%, which decreased to 87% with a 6-min walk test. His cardiac examination reveals an accentuated P2 and bilateral crackles on lung auscultation. Chest radiography reveals interstitial changes, and a high-resolution chest computed tomographic (CT) scan revealed extensive pulmonary brosis (Figures 62-1 and 62-2). Subsequent testing or connective tissue disease and hypersensitivity pneumonitis is negative. A diagnosis o idiopathic pulmonary brosis (IPF) is subsequently established a ter a lung biopsy.

FIGURE 62-2 Che st comp ute d tomog rap hic scan o the same p atie nt as in Fig ure 62-1 showing g ro und -g lass co nsolid ation o inte rstitial lung d ise ase . Howe ve r, the d e ve lop me nt o b ilate ral p le ural e usions sug g e ste d a comp one nt o cong e stive card iac ailure . (Re p rod uce d with p e rmission from Carlos Tave ra, MD.)

EPIDEMIO LO GY INTRO DUCTIO N Idiopathic pulmonary brosis (IPF) is characterized by progressive dyspnea and a decline in lung unction associated with progressive brosing interstitial pneumonia o unknown etiology, occurring primarily in older adults. 1 The diagnosis o IPF requires the exclusion o other causes o interstitial lung disease, including those associated with environmental exposures, medications, or connective tissue diseases.

SYNO NYMS Usual synonyms or IPF are interstitial pneumonia, cryptogenic brosing alveolitis, and idiopathic interstitial pneumonia.

The incidence o IPF is between 4.6 and 16.3 cases per 100,000 population, and prevalence is estimated to be up to 43 per 100,000 population. 1

RISK FACTO RS • Genetic actors. • Smoking (>20 pack-years) is strongly associated with IPF. • Exposures to inorganic and organic particles, including metal, wood, vegetable, and animal dust may be associated with IPF. • No de nitive conclusions on the association between in ectious agents (such as Epstein-Barr virus in ection) and IPF can be made. • Gastroesophageal ref ux (GERD) may be a risk actor or IPF.

DIAGNO SIS HISTO RY • A history o progressive dyspnea is the most common symptom and may be accompanied by cough. • Symptoms are present or months to years and progress in varying degrees. ° Wheezing and hemoptysis are unusual eatures. • Evaluation or comorbid conditions and risk actors involves searching or occupational or environmental exposures, collagen vascular disease, human immunode ciency virus (HIV) in ection, use o drugs, or toxic exposures. • A record o environmental exposure to smoking must be obtained as well as evaluation o current or previous malignancies and amily history o lung disease. PHYSICAL EXAMINATIO N FIGURE 62-1 This che st rad iog rap h d e monstrate s d i use alve olar op acitie s throug hout b oth lung s, with more consolid ative chang e s at b oth b ase s. The re is p ulmonary f b rosis and a small p le ural e usion on the rig ht sid e . (Re p rod uce d with p e rmission from Carlos Tave ra, MD.)

• Bibasilar inspiratory “Velcro” crackles are present; they may be widespread. • Look or cor pulmonale signs with an accentuated second pulmonary sound.

PULMO pULMO Na NARY r Y FIBr FIBRO O SIS

PART 9

PULMO NARY

FIGURE 6 2-3 Club b ing showing so t-tissue swe lling o the d istal e nd s o the d ig its, asso ciate d with incre ase d curvature o the nails and lo ss o the d orsal nail- o ld ang le . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Clubbing is seen in 30% to35% o cases (Figure 62-3). • Look or extrapulmonary ndings o systemic disease (rash, joint de ormities). LABO RATO RY TESTING • Serological testing to investigate or other diagnoses includes ° Antinuclear antibody (ANA) titers, rheumatoid actor, and anticitrullinated protein antibodies (ACPA) to help identi y lupus or rheumatoid arthritis as antecedent diseases. The two ACPAs include antibodies against anti-cyclic citrullinated protein (ACCP) and antimutated citrullinated vimentin (anti-MCV). ° Elevated angiotensin-converting enzyme (ACE) levels are associated with sarcoidosis. Antibodies to organic antigens can be used to detect other explanations or brosis (eg, armer’s lung and bird ancier’s disease). • Spirometry is used to indicate restrictive lung disease (decreased vital capacity o ten with an increased ratio o orced expiratory volume in the rst second o expiration and orced vital capacity [FEV1/ FVC]) and impaired gas exchange (increased alveolar-arterial oxygen di erence with rest or exercise or decreased lung di using capacity or carbon monoxide [DLCO]). • Bronchoalveolar lavage (BAL) f uid may help to exclude in ection, tumors, pulmonary alveolar proteinosis, Langerhans cell histiocytosis, hemosiderin-laden macrophages (suggesting alveolar hemorrhage), or lipid-laden macrophages (seen in aspiration rom stomach or upper airway, lipid emboli, or amiodarone therapy). • Surgical lung biopsy may establish a rm clinicopathological diagnosis that allows patients and clinicians to make in ormed decisions about therapy and its potential risks.

IMAGING • Chest radiographs do not make the diagnosis o pulmonary brosis but are help ul in excluding other causes o breathlessness and in evaluating clinical deterioration by looking or cancer, superimposed in ection, and superimposed pulmonary edema.

FIGURE 62-4 Note the coarse ning o the inte rstitial marking at the lung base s (hone ycombing note d in the costophre nic angle s bilate rally) and uppe r lung f e lds. Also, note the large bullae at the le t ape x. This patie nt has inte rstitial f brosis rom rhe umatoid arthritis. (Re produce d with p ermission from Gary Fe renchick, MD.)

° A normal chest radiograph does not rule out pulmonary brosis in the presence o otherwise-unexplained dyspnea. ° Typical chest radiographic changes, i present, in pulmonary brosis include coarse interstitial marking at the lung bases and upper lung elds (Figure 62-4). • High-resolution CT (HRCT) scanning is an important test or patients with a suspected diagnosis o IPF and is highly accurate (90%-100% positive predictive value). 1 Findings include honeycombing (clusters o cystic air spaces between 3 mm and 2.5 cm) just below the pleural sur ace, reticular opacities, and ground-glass opacities.

DIFFERENTIAL DIAGNO SIS • Chronic hypersensitivity pneumonitis is suggested with BAL ndings o greater than 40% lymphocytosis. • Collagen vascular diseases are associated with extrapulmonary signs and symptoms, including joint pain and positive serological studies. ° Pulmonary brosis can precede other mani estations o connective tissue disease, so ordering rheumatoid actor, ACCP, and ANA studies is recommended by the American Thoracic Society (ATS). ° Note that i the patient has established criteria or connective tissue disease, the patient does not have IPF. This should be suspected (even in the absence o established diagnostic criteria) in those younger than 50 years. • Alveolar hemorrhage syndromes as seen in Goodpasture syndrome would be associated with a positive anti-GBM antibody. • Occupational lung disease is suggested by exposures to dusts, silica, umes, or radiation. • Hypersensitivity pneumonitis is suggested by exposure to thermophilic bacteria or other animal proteins. • Drug toxicity rom drugs such as amiodarone, nitro urantoin, and sulasalazine, among others.

307

PART 9

308

PULMO NARY • Cryptogenic organizing pneumonia (COP) ° The ormal term is bronchiolitis obliterans obstructive pneumonia (BOOP). ° The term organizing pneumonia is o ten used or both in ectious and nonin ectious etiologies. ° There is equal gender distribution, and it can occur in nonsmokers. ° The illness has a median presentation o less than 3 months, variable degrees o cough (may produce clear sputum), and dyspnea. Weight loss, chills, intermittent ever, and myalgias may be common. ° On chest radiography, Bilateral or unilateral patchy peripheral consolidations and consolidations can be migratory. ° CT—There are areas o air space consolidation in 90% o patients, and there are peribronchial distribution and bronchial dilation. Ground-glass attenuation occurs in 60% o cases. ° The majority o patients recover on steroidal treatment: prednisone 1 to 1.5 mg/ kg daily or 6 to 8 weeks. • Acute Interstitial Pneumonia ° Another term is Hamman-Rich syndrome, a rare ulminant orm o lung injury. ° Mean age at presentation is 50 years; there is no gender predominance, and it is not associated with smoking. ° Onset is insidious, and there is a relentless progressive course; median time rom rst symptom to presentation is less than 3 weeks, o ten preceded by viral syndrome. ° Consolidation and ground-glass opaci cation occur. ° CT scan—Bilateral patchy areas o ground-glass attenuation sometimes occur with air space consolidation. Appearance is similar to adult respiratory distress syndrome (ARDS). ° Most patients have moderate-to-severe hypoxia and develop respiratory ailure. ° Treatment is supportive. ° Mortality rate is greater than 60%, with patients dying within 6 months o presentation.

MANAGEMENT

Ch a pt e r 62

° Acetylcysteine monotherapy (as noted previously). ° Anticoagulants (low-molecular-weight heparin ollowed by wararin). Use was associated with a decrease in hospital mortality or those with acute exacerbations in one unblinded study. 3 • Therapies without speci c recommendations by the ATS include the ollowing: ° Sildena l reduces pulmonary vasculature pressures in patients with IPF and pulmonary hypertension. In patients with IPF and reduced DLCO ( 10% in FVC indicating disease progression). • A DLCO decline o 15% is also a marker o disease progression. PATIENT RESO URCES

• American Lung Association. Interstitial Lung Disease and Pulmonary Fibrosis—http:/ / www.lung.org/ lung-disease/ pulmonary-f brosis/ . • Pulmonary Fibrosis Foundation—http:/ / www .pulmonaryf brosis.org/ . • PubMed Health. Idiopathic Pulmonary Fibrosis—http:/ / www .ncbi.nlm.nih.gov/ pubmedhealth/ PMH0001134/ . PRO VIDER RESO URCES

• Raghu G, Collard HR, Egan JJ, et al. An o cial ATS/ ERS/ JRS/ ALAT statement: idiopathic pulmonary brosis: evidence-based guidelines or diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788-824. http:/ / ajrccm.atsjournals.org/ content/ 183/ 6/ 788.long# content-block. • Medscape. Idiopathic Pulmonary Fibrosis—http:/ / emedicine .medscape.com/ article/ 301226.

PULMO NARY REFERENCES 1. Raghu G, Collard HR, Egan JJ, et al. An o cial ATS/ ERS/ JRS/ ALAT statement: idiopathic pulmonary brosis: evidence-based guidelines or diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788-824. 2. Idiopathic Pulmonary Fibrosis Clinical Research Network, Raghu G, Anstrom KJ, King TE Jr, Lasky JA, Martinez FJ. Prednisone, azathioprine, and N-acetylcysteine or pulmonary brosis. N Engl J Med. 2012;366(21):1968-1977. 3. Kubo H, Nakayama K, Yanai M, et al. Anticoagulant therapy or idiopathic pulmonary brosis. Chest. 2005;128(3):1475-1482. 4. Richeldi L, Costabel U, Selman M, et al. E cacy o a tyrosine kinase inhibitor in idiopathic pulmonary brosis. N Engl J Med. 2011;365(12):1079-1087.

309

PART 9

310

PULMO NARY

63 SARCO IDO SIS Gina R. Chacon, MD

PATIENT STO RY A 39-year-old A rican-American woman presents with an acute onset o ever and new skin lesions on her shins that she noticed a week ago a ter she returned rom a spring break trip. She also complains o dry cough, mild shortness o breath, eeling tired, and pain in her ankles. Her lungs are clear, and lower extremity examination reveals a number o tender 2-cm red nodules (Figure 63-1). Her physician recognized her leg lesions as erythema nodosum and was aware that this is ound with sarcoidosis and tuberculosis. There ore, a chest radiograph is ordered; it reveals bilateral hilar lymphadenopathy without parenchymal in ltrates. As this is consistent with sarcoidosis, workup and treatment is pursued with the provisional diagnosis o sarcoidosis. It is decided not to biopsy the erythema nodosum as the ndings are nonspeci c or the etiology and the leg lesions clinically support this nding.

INTRO DUCTIO N Sarcoidosis is a multisystem granulomatous disorder o yet unknown etiology; it predominantly involves the lungs in more than 90% o cases but can also involve any organ in the body, with the lymphatics, skin, eyes, and liver the most common. 1

Ch a pt e r 63

EPIDEMIO LO GY • Sarcoidosis is a worldwide disease but with variable incidences, maniestations, and prognosis. 2 • In the United States, the age-adjusted annual incidence rate in Caucasians is 10.9 in 100,000, and in A rican Americans, it is 35.5 in 100,000. 2 • Sarcoidosis a ects all ages and races and both sexes. The prevalence is slightly higher in women than in men. 3 • Its onset is most o ten observed in adults under the age o 40 in both sexes, with a peak incidence between 20 and 29 years. 1

ETIO LO GY/ PATHO PHYSIO LO GY The cause o this disease is still uncertain. Recent ndings suggest that sarcoidosis may be caused by a chronic immune response produced by exposure o a genetically susceptible individual to an as-yet-unde ned environmental antigenic stimulus. 4,5

DIAGNO SIS For an accurate diagnosis, the multimodality approach, including clinical, radiological, and histopathological evaluation is recommended. 2 DIAGNO STIC CRITERIA • Sarcoidosis is characterized by the ormation o well- ormed, nonnecrotizing granulomas in a ected organs. There are no ormal diagnostic criteria or sarcoidosis, and the presence o noncaseating granulomas does not con rm the diagnosis o sarcoidosis on its own. 2 • Sarcoidosis is a diagnosis o exclusion, and as such, other causes o granulomas, in ectious and nonin ectious, need to be evaluated or and ruled out. 6 CLINICAL FEATURES • Sarcoidosis is a multisystem disease that can a ect any organ. 2 • The clinical presentation can vary rom asymptomatic organ involvement that is detected incidentally to a slowly progressive disease. • An acute orm o sarcoidosis, Lö gren syndrome, is de ned as an acute onset o ever, erythema nodosum, polyarthritis, and chest radiograph showing bilateral hilar lymphadenopathy (Figure 63-2) with or without parenchymal in ltrates. portends an excellent course, with ° Lo gren syndrome typically spontaneous resolution. 2,7 o sarcoidosis ° The pulmonary system is involved in more than 90%2,8 cases ollowed by skin, lymph nodes, eyes, and liver. • In the ACCESS (A Case-Control Etiologic Study o Sarcoidosis) study, hal o the sarcoidosis cohort had only 1 organ involved, 30% had 2 organs involved, 13% had 3 organs involved, and 7% had 4 or more organs involved with sarcoidosis. 8 PULMO NARY MANIFESTATIO NS

FIGURE 63-1 Erythe ma nod o sum in a 40-ye ar-old b lack woman ne wly p re se nting with sarcoid osis. Note how the e rythe ma is le ss p romine nt b e cause o the d ark p ig me ntation. The nod ule s are cle arly visib le , p alp ab le , and te nd e r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• The lungs are the most common organs involved in sarcoidosis. 9 • Patients can be asymptomatic, but more commonly they have nonspeci c symptoms, such as cough, atigue, and dyspnea on exertion.

PART 9

SARCO Sa r CO IDO SIS

A

PULMO NARY

B

FIGURE 63-2 A. Poste roante rior and B. late ral che st rad iog rap h showing b ilate ral hilar lymp had e nop athy (arrows) without p are nchymal in ltrate s rom a p atie nt with sarcoid osis. (Re p rod uce d with p e rmission from Gary Fe re nchick, MD.)

• On physical examination, ndings can include normal pulmonary examination, dry inspiratory crackles or wheezes rom airway involvement with sarcoidosis, or airway distortion rom brotic changes. 2 SKIN MANIFESTATIO NS

NEURO LO GIC MANIFESTATIO NS • Neurosarcoidosis a ects 5% to 15% o patients. • Any part o the nervous system can be a ected, but cranial nerves are those most a ected, the acial nerve being the most common, ollowed by the optic nerve.

• Skin is the second most common organ involved in sarcoidosis (see Chapter 173, Sarcoidosis). • Cutaneous mani estations occur in 20%-35% o patients with sarcoidosis. 8-10 • Sarcoidosis can present with reactive nonspeci c lesions like erythema nodosum. 3,10 • Speci c lesions typically show noncaseating granulomas when biopsied. 11 ° They include lupus pernio, papules, subcutaneous nodules, plaques, and in ltrated scars (Figures 63-3 and 63-4). ° The nasal alae are common locations or the noncaseating granulomas to orm (Figure 63-5). EYE MANIFESTATIO NS • Ocular involvement can be seen in 10% to 80% o patients with sarcoidosis. • The most common mani estation is anterior uveitis, but any part o the orbit or adnexa can be involved (Figure 63-6). 12 GASTRO INTESTINAL MANIFESTATIO NS • The liver is involved in about 30% to 80% o patients with sarcoidosis. • Patients can be asymptomatic or complain o nonspeci c abdominal pain or pruritus. Jaundice may be evident. 10,13 • Hepatomegaly is detected clinically in 21% o cases and radiographically in more than 50% o patients. 13

FIGURE 63-3 Sarcoid osis causing a lup us p e rnio p atte rn on the ace o this A rican Ame rican woman with sarcoid osis. Note how some o the p laq ue s have a malar d istrib ution, as se e n in lup us e rythe matosus. The p atie nt d oe s not have cutane ous lup us as this p atte rn is cause d b y sarcoid osis alone . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

311

312

PART 9

PULMO NARY

Ch a pt e r 63

FIGURE 63-6 O cular sarcoid osis with in ltration o the conjunctiva o the e ye lid s in this A rican Ame rican woman with e xte nsive sarcoid o sis o the skin and lung s. She has also had uve itis se cond ary to he r sarcoid osis in the p ast. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

MUSCULO SKELETAL MANIFESTATIO NS FIGURE 63-4 Cutane ous sarcoid osis on the arm with some annular p atte rns in the same p atie nt with lup us p e rnio in Fig ure 63-3. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Sometimes, the signs and symptoms are nonspeci c and include cranial neuropathies, meningeal irritation, increased intracranial pressure, peripheral neuropathies, endocrine dys unction, cognitive dys unction, and personality changes. 14 CARDIAC MANIFESTATIO NS • Cardiac sarcoidosis is detected clinically in about 5% o cases, but on autopsy in about 40% o cases. • Cardiac involvement can be asymptomatic or present with palpitations, dyspnea, syncope or presyncopal episodes, or, rarely, sudden cardiac death.15

• Sarcoidosis can involve the articular, skeletal, and muscular systems (Figure 63-7). • Early in the course o the disease, acute polyarthritis may be observed in up to 40% o patients, but this is o ten sel -limited. • Chronic or recurrent sarcoid arthritis is rare, a ecting only 1% to 4% o patients. • Asymptomatic involvement o muscles has been reported in 25% to 75% o patients in small series, but symptomatic involvement o muscles is rare (300 mg/ d) in about 30% o patients.

PART 9

Sa r CO IDO SIS

A

PULMO NARY

FIGURE 63-8 Biop sy imag e o sarcoid osis o the skin. The re is a d e nse , noncase ating g ranulomato us in ltrate locate d within the d e rmis. The g ranulomatous inf ammatio n is comp ose d o circumscrib e d colle ctions o e p ithe lioid histiocyte s with variab le numb e rs o multinucle ate d g iant ce lls. (Re p rod uce d with p e rmission from Sand ra O sswald , MD.)

• Abnormal liver unction tests o ten accompany sarcoidosis; most commonly, there is mild elevation o alkaline phosphatase levels. Alanine transaminase, aspartate transaminase, and bilirubin levels are usually normal. 17 • Increased serum angiotensin-converting enzyme levels are elevated in 60% o patients at the time o diagnosis. Sensitivity and speci city as a diagnostic tests are 60% and 70%, respectively. • Pulmonary unction test—Granulomas and brosis o lung tissue reduce total lung capacity and decrease the carbon monoxide-di using capacity.

B

• Pathology study o biopsy—Noncaseating granulomas (Figure 63-8) can be used. Cutaneous lesions can provide an easily accessible source o tissue or histopathologic examination i present. • Microscopic examination o specimens o lung tissue or other tissue o organs involved can show granulomas. 9 • Echocardiogram and ambulatory electrocardiogram (ECG) (Holter and event monitors) are help ul in urther investigating symptoms such as palpitations and dyspnea, which are suspicious or potential cardiac sarcoidosis. 15

IMAGING • Chest radiography—Bilateral hilar adenopathy can be the rst indication o sarcoidosis.

C FIGURE 63-7 63-7 Musculoske le tal sarcoid osis in a 57-ye ar-old woman who also has skin, e ye , and p ulmonary involve me nt. A. Both hand s showing joint swe lling and a swan ne ck d e ormity. B. Close -up o one hand . C. Close -up o sarcoid osis a e cting the toe s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Cardiac magnetic resonance imaging (cMRI) and cardiac positron emission tomography (PET) imaging are new modalities used in the assessment o cardiac sarcoidosis. 18 ° With cMRI and computed tomography (CT), the regions o sarcoid involvement produce a scar appearance with late gadolinium enhancement, which may be enough to establish the diagnosis in someone without other reasons or scar ormation. ° When additional con rmation is needed, PET can be used to show that these areas o the “scar” are actually hypermetabolic, consistent with sarcoid.

313

PART 9

314

PULMO NARY • Radiographs o the a ected areas may show cystic or lytic lesions. Bone scans and PET can also detect increased activity in the involved bones. 16

Ch a pt e r 63

involvement o the upper respiratory tract, advanced lung brosis, bone cysts, and eye disease. • With correct diagnosis and proper management, most patients with sarcoidosis continue to lead a normal li e.

RISK FACTO RS • A rican American • Female gender

DIFFERENTIAL DIAGNO SIS Sarcoidosis is known as the “great imitator”; there ore, the di erential diagnosis list is long (see the section on di erential diagnosis in Chapter 173, Sarcoidosis o the Skin).

MANAGEMENT • Management o patients with sarcoidosis is best accomplished in collaboration with a sarcoidosis center or expert and appropriate subspecialists as dictated by organ involvement. • Immunosuppressive therapy is indicated when major organs are involved (neurologic, ophthalmologic, or cardiac) or when there is evidence o organ dys unction or progressive disease in other organs. 2 SO R

• Corticosteroids are the basis o treatment o symptomatic sarcoidosis. Oral prednisone is o ten started to provide quick relie o symptoms. • Methotrexate is an important steroid-sparing agent and may be used to taper patients o prednisone or to treat patients when corticosteroids are contraindicated. 1 • Inf iximab may be used. • I patient has pain or ever, nonsteroidal anti-inf ammatory drugs (NSAIDs), such as ibupro en, may be taken. SO R

PRO GNO SIS/ CLINICAL CO URSE • In general, sarcoidosis appears brief y and resolves without relapse in most cases. • Lo gren syndrome is the acute mani estation o sarcoidosis, typically presenting in the springtime with arthritis, erythema nodosum, uveitis, and enlarged hilar lymph nodes. 1 • It usually has an excellent prognosis, with high rates o spontaneous remission. 2 • O these patients, 20% to 30% are le t with some permanent lung damage, and 10% to 15% develop chronic sarcoidosis that may last or many years.

MAJO R CO MPLICATIO NS O F SARCO IDO SIS • Hypercalcemia and hypercalciuria could be the initial mani estation o sarcoidosis, with patients presenting with symptoms o hypercalcemia, including lethargy, constipation, mental status changes, renal dys unction, or nephrolithiasis. 19 • High-grade conduction blocks and ventricular or atrial arrhythmias, le t ventricular dys unction, and wall motion abnormalities can occur. 15 • Portal hypertension can be present with or without cirrhosis and can also develop rom compression o the portal vein by enlarged lymph nodes in the hepatic hilum. 10,13 • Eye damage such as asymptomatic uveitis may occur.

FO LLO W-UP • I a patient ails to respond to corticosteroids, then the clinician should reassess the need or additional or di erent treatment. • Stable patients should be ollowed every 4 to 6 months. • Consider a periodic echocardiogram to assess or pulmonary hypertension i the patient presents symptoms like dyspnea and peripheral edema. • Patients need ophthalmologic examination and to be monitored or ophthalmic side e ects and toxicities rom immunosuppressive agents, such as steroids and hydroxychloroquine. 2 SO R

PATIENT EDUCATIO N • The patient should see a physician i any new symptoms appear or the medication is not working. • Smoking should be avoided. PATIENT RESO URCES

• Sarcoidosis support groups—http:/ / www.sarcoidosisonlinesites .com/ index.html. • Sarcoid Networking Association—http:/ / www .sarcoidosisnetwork.org. PRO VIDER RESO URCES

• In 5% to 10% o cases, the disease can become atal i either granulomas or brosis seriously a ects vital organs, such as the lungs, heart, nervous system, liver, or kidneys. End-stage lung disease may require lung transplantation.

• American Lung Association. Sarcoidosis—http:/ / www.lungusa .org/ lung-disease/ sarcoidosis.

• Cutaneous sarcoidosis usually has a prolonged course. Papules and nodules tend to resolve over months or years. Lupus pernio is o ten present in patients with chronic sarcoidosis and is associated with

• MedlinePlus. Sarcoidosis—http:/ / www.nlm.nih.gov/ medlineplus/ sarcoidosis.html.

• World Association for Sarcoidosis and Other Granulomatous Disorders—http:/ / www.wasog.org/ .

Sa r CO IDO SIS

REFERENCES 1. Costabel U. Sarcoidosis: clinical update. Eur Respir J. 2001;32:56s-68s. 2. Statement on sarcoidosis. Joint Statement o the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association o Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board o Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. 1999;160(2):736-755. 3. Ali MM, Atwan AA, Gonzalez ML. Cutaneous sarcoidosis: updates in the pathogenesis. J Eur Acad DermatolVenereol. 2010;24(7):747-755. 4. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007;357(21):2153-2165. 5. English JC 3rd, Patel PJ, Greer KE. Sarcoidosis. JAmAcad Dermatol. 2001;44(5):725-743; quiz 44-46. 6. Newman LS, Rose CS, Maier LA. Sarcoidosis. N Engl J Med. 1997;336(17):1224-1234. 7. Keary PJ, Palmer DG. Benign sel -limiting sarcoidosis with skin and joint involvement. N Z Med J. 1976;83(560):197-199. 8. Baughman RP, Teirstein AS, Judson MA, et al. Clinical characteristics o patients in a case control study o sarcoidosis. Am J Respir Crit Care Med. 2001;164(10 Pt 1):1885-1889. 9. Baughman RP, Lower EE. Evidence-based therapy or cutaneous sarcoidosis. Clin Dermatol. 2007;25(3):334-340. 10. Rose AS, Tielker MA, Knox KS. Hepatic, ocular, and cutaneous sarcoidosis. Clin Chest Med. 2008;29(3):509-524, ix.

PART 9

PULMO NARY 11. Abu-Hilal M, Krotva J, Chichierchio L, Obeidat N, Madanat M. Dermatologic aspects and cutaneous mani estations o sarcoidosis. G Ital DermatolVenereol. 2007;145(6):733-745. 12. Heiligenhaus A, We elmeyer D, We elmeyer E, Rosel M, Schrenk M. The eye as a common site or the early clinical mani estation o sarcoidosis. Ophthalmic Res. 2011;46(1):9-12. 13. Ebert EC, Kierson M, Hagspiel KD. Gastrointestinal and hepatic mani estations o sarcoidosis. Am J Gastroenterol. 2008;103(12): 3184-3192; quiz 93. 14. Hoitsma E, Drent M, Sharma OP. A pragmatic approach to diagnosing and treating neurosarcoidosis in the 21st century. Curr Opin Pulm Med. 2010;16(5):472-479. 15. Mehta D, Lubitz SA, Frankel Z, et al. Cardiac involvement in patients with sarcoidosis: diagnostic and prognostic value o outpatient testing. Chest. 2008;133(6):1426-1435. 16. Zisman DA, Shorr AF, Lynch JP 3rd. Sarcoidosis involving the musculoskeletal system. Semin Respir Crit Care Med. 2002;23(6):555-570. 17. Sharma OP. Vitamin D, calcium, and sarcoidosis. Chest. 1996;109(2): 535-539. 18. Ohira H, Tsujino I, Ishimaru S, et al. Myocardial imaging with 18F-f uoro-2-deoxyglucose positron emission tomography and magnetic resonance imaging in sarcoidosis. Eur J Nuclear Med Mol Imaging. 2008;35(5):933-941. 19. Burke RR, Rybicki BA, Rao DS. Calcium and vitamin D in sarcoidosis: how to assess and manage. Semin Respir Crit Care Med. 2010;31(4):474-484.

315

316

PART 9

PULMO NARY

Ch a pt e r 64

64 TUBERCULO SIS Mind y A. Smith, MD, MS

PATIENT STO RY A 25-year-old man rom Mexico presents to the emergency room in a South Texas hospital with a persistent cough or 3 weeks, low-grade ever, and night sweats. His chest X-ray (CXR) shows mediastinal and right hilar lymphadenopathy and right upper lobe consolidation concerning or primary tuberculosis (TB) (Figure 64-1). Upon review o the radiograph, the emergency room sta admits the patient to a single room with negative pressure. The patient is placed in respiratory isolation, sputum is sent or acid- ast bacillus (AFB) stain and cultures, and the results show AFB consistent with Mycobacterium spp. (Figure 64-2). While culture results are pending, the patient is started on 4 antituberculosis drugs. Fortunately the sputum culture result shows pan susceptible Mycobacterium tuberculosis, and his treatment continues with directly observed therapy (DOT) through the local city health department. A

INTRO DUCTIO N Tuberculosis is a bacterial in ection caused by M. tuberculosis, an obligate intracellular pathogen that is aerobic, acid-fast, and nonencapsulated. TB primarily involves the lungs, although other organs are involved in one-third o cases. Improvements in diagnostics, drugs, vaccines, and understanding o biomarkers o disease activity are expected to change uture management o this devastating worldwide disease.

EPIDEMIO LO GY • Over 8 million cases occur annually around the world, with nearly 2 million TB-related deaths;1 95% o TB deaths occur in low- and middle-income countries. • A total o 11,182 TB cases (3.6/ 100,000 persons) were reported in the United States in 2010. This represents the lowest incidence rate since recording began in 1953. 2 An estimated 2 billion people worldwide have latent TB. 3 • The multiple drug-resistant (MDR) TB rate in the United States was 1.2% (88 cases) in 2010; a rate which remains relatively stable in the United States. 1 MDR TB rates are highest in India, China, the Russian ederation, South A rica, and Bangladesh. 3 • Based on the 2010 data, 60% o reported US cases o M. tuberculosis occurred in oreign-born individuals (case rate 11 times higher than US-born individuals). 1

B FIGURE 64-1 Typ ical p re se ntation o a p rimary p ulmonary TB in e ction in a 20-ye ar-old man. A. Frontal che st rad iog rap h shows me d iastinal and rig ht hilar lymp had e nop athy (b lack arrows) and rig ht up p e r lob e consolid ation (white arrow). B. Contrast-e nhance d CT d e monstrate s low-d e nsity e nlarg e d me d iastinal lymp h nod e s with p e rip he ral rim e nhance me nt consiste nt with ne crotizing lymp had e nop athy (arrows). (Re p rod uce d with p e rmissio n from Carlos Santiag o Re stre p o, MD.)

ETIO LO GY AND PATHO PHYSIO LO GY • In ection is transmitted by aerosolized respiratory droplet nuclei. 4

• There were 547 reported deaths rom TB in the United States in 2009 (a 7% decrease rom 2008). 1

• About 10% o those in ected develop active TB, usually within 1 to 2 years o exposure; risk actors or the development o active TB are listed later.

• Prophylactic treatment o those with latent TB (in ection without active disease—diagnosed by tuberculin skin test conversion rom negative to positive or by an inter eron-γ release assay per ormed on blood) can reduce the risk o active TB by 90% or more. 4 SO R

• There are 3 host responses to in ection: immediate nonspeci c macrophage and likely neutrophil ingestion o those bacilli reaching the alveoli, later tissue-damaging response (delayed-type hypersensitivity reaction), and speci c macrophage activating and potentially

PART 9

TUBERCULO t UBe r CULO SIS

PULMO NARY

FIGURE 64-2 The acid - ast b acilli o Mycob acte rium tub e rculosis se e n with acid - ast staining at 100 p owe r with oil imme rsion micro scop y. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

neutrophil-related response—the latter, i e ective, walling o in ection into granulomas. Recent evidence suggests that mycobacteria themselves may promote granuloma ormation and these granulomas are dynamic, blurring distinctions between latent and active TB. 3 • In areas o high prevalence, TB is o ten seen in children. The disease process usually localizes to the middle and upper lung zones accompanied by hilar and paratracheal lymphadenopathy (as the tubercle bacilli spread rom lung to lymphatic vessels). The primary ocus usually heals spontaneously and may disappear entirely or, i encapsulated by broblasts and collagen bers, be visible as a calci ed lung nodule (Ghon complex) (Figure 64-3).

RISK FACTO RS Risk actors or in ection or progression to active TB include the ollowing2,3,4:

FIGURE 64-3 Primary TB may coale sce into a small g ranulo ma in the up p e r lob e re e rre d to as a Ghon comp le x. (Re p rod uce d with p e rmission from Mille r WT, Jr. Diag nostic Thoracic Imag ing . Ne w York, NY: McGraw-Hill; 2006:289, Fig ure 6-5 E..)

• Adult women (ratio 2:1 adult man). • Older age (both in ection and progression). • Children under 4 years o age who are exposed to high-risk individuals.

• Minority and oreign-born populations (subject to overcrowding and malnutrition).

• Recent in ection (< 1 year) (RR [progression to active TB] 12.9 vs old in ection).

• HIV (relative risk [RR] or progression to active TB 100) and other immunocompromised states (eg, cancer, treatment with tumor necrosis actor antagonists) (RR [progression to active TB] 10). As a result o the high susceptibility o HIV-in ected patients, 12% o worldwide TB cases are HIV-associated with sub-Saharan A rica accounting or 4 out o every 5 o these cases. 3

• Fibrotic lung lesions (spontaneously healed) (RR [progression to active TB] 2-20).

• Chronic diseases such as diabetes mellitus (RR 3) or chronic renal ailure/ hemodialysis (RR [in ection and progression to active TB] 10-25 or renal ailure). • Malignancy.

• Silicosis (RR [in ection] 3 and RR [progression to active TB] 30). • Malnutrition (RR [progression to active TB] 2). • In a study o hospital personnel, only the percentage o low-income persons within the employee’s residential postal zone was independently associated with conversion (odds ratio [OR] 1.39, 95% con dence interval [CI], 1.09-1.78). 5

DIAGNO SIS

• Genetic susceptibility. • Bariatric surgery or jejunoileal bypass (RR [progression to active TB] 30-60) recipients. • Injection drug users (RR [progression to active TB] 10-30). • Smoking (RR 2 or progression and in ection). • Personnel who work or live in high-risk settings (eg, prisons, longterm care acilities, and hospitals).

The diagnosis o active TB requires a high index o suspicion. In addition, targeted testing or latent TB in vulnerable populations who would bene t rom treatment (recent [ 15,000). ■ Vancomycin 125 mg every 6 h orally or 10 to 14 days. SO R ■ Colonic levels i vancomycin are extremely high a ter an oral dose. It is not e ective with intravenous dosing. ■ Use vancomycin per rectum as a retention enema i ileus is present. ° Intravenous immunoglobulin (IVIG) may be tried as more than 50% o the population has detectable antibodies to C. di f cile toxins A and B; thus, IVIG has toxin-neutralizing capability (400 mg/ kg). 2 However, no controlled trials have been per ormed. ° ° Per orm a subtotal colectomy or severely ill patients or i there are signs o toxic megacolon. 2 SO R Monitor serum lactate levels; i greater than 5, there is an increase in perioperative mortality.

CHApTER 65

■

Pulse dose course o vancomycin 125, 250, or 500 mg every 3 days or 4 to 6 weeks

PATIENT EDUCATIO N • Colonization with C. di f cile is with ecal-oral transmission; there ore, hand hygiene is important. • The use o antibiotics disrupts the balance o the intestinal ora, predisposing to CDI in patients colonized with C. di f cile; there ore, limiting the unnecessary use and duration o antibiotic therapy is important.

PATIENT RESO URCES

• Kelly CP, LaMont JT. Patient information: antibiotic-associated diarrhea caused by Clostridium di f cile (Beyond the Basics). UpToDate. http:/ / www.uptodate.com/ contents/ patientin ormation-antibiotic-associated-diarrhea-caused-byclostridium-di f cile-beyond-the-basics?source=search_ result&search=clostridium+di f cile&selectedTitle=1~ 2. • JAMA Patient Page: Clostridium dif cile Colitis—http:/ / jama .ama-assn.org/ content/ 301/ 9/ 988. ull.pd +html?sid= a210a6c7-b4e5-4dda-9891-b4209905e 90. PRO VIDER RESO URCES

PRO GNO SIS • Complications o CDI include dehydration, electrolyte disturbance, toxic megacolon, bowel per oration, renal ailure, systemic in ammatory response syndrome, sepsis, and death. 2

• Clinical Practice Guidelines or Clostridium di f cile In ection in Adults: 2010 Update by the Society or Healthcare Epidemiology o America (SHEA) and the In ectious Diseases Society o America (IDSA). http:/ / www.jstor.org/ stable/ 10.1086/ 651706.

• Recurrent episodes o CDI occur in 6% to 25% o patients with a frst episode.2 REFERENCES

FO LLO W-UP • Patients should be ollowed or signs o clinical improvement, including resolution o ever, reduction in stool requency, improvement in stool consistency, and rehydration. • Repeated stool testing is not necessary in patients with resolved symptoms as treatment o asymptomatic carriers is not indicated. ° I C. di f cile diarrhea recurs, treat the second episode with the same regimen as the f rst episode. ° Third and subsequent episodes should be treated with only vancomycin to avoid neurotoxicity associated with repeated administrations o metronidazole. ■ These recurrences should be treated with 10 to 14 days o oral vancomycin, ollowed by one o the ollowing: ■ Tapering dose o vancomycin 125 mg orally twice a day or 7 days, then 125 mg orally every day or 7 days, then 125 mg orally every 2 to 3 days or 2-8 weeks

1. Hessen MT. In the clinic. Clostridium di f cile in ection. Ann Intern Med. 2010;153(7):ITC41-15; quiz ITC416. 2. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines or Clostridium di f cile in ection in adults: 2010 update by the Society or Healthcare Epidemiology o America (SHEA) and the In ectious Diseases Society o America (IDSA). In ect Control Hosp Epidemiol. 2010;31(5):431-455. 3. Oughton MT, Loo VG, Dendukuri N, et al. Hand hygiene with soap and water is superior to alcohol rub and antiseptic wipes or removal o Clostridium di f cile. In ect Control Hosp Epidemiol. 2009;30:939-44. 4. Owens RC Jr, Donskey CJ, Gaynes RP, et al. Antimicrobialassociated risk actors or Clostridium di f cile in ection. Clin In ect Dis. 2008;46 Suppl 1:S19-31. 5. Bartlett JG and Gerding DN. Clinical recognition and diagnosis of Clostridium di f cile in ection. Clin In ect Dis. 2008;46 Suppl 1:S12-8.

CO LO N CANCER

66 CO LO N CANCER Mind y A. Smith, MD, MS Bonnie Wong , MD

PART 10

GASTRO INTESTINAL • The incidence and mortality have been slowly but steadily declining in the United States or the past decade. 2 The American Cancer Society estimated 142,570 new cases o colorectal cancer (102,900 colon cancer cases) and 51,370 deaths in 2010. 3 • Onset is a ter age 50 years and peaks at around age 65 years. • Proximal colon carcinoma rates in blacks are higher than in whites. 4

PATIENT STO RY A 72-year-old man reports rectal bleeding with bowel movements over the past several months and the stool seems narrower with occasional diarrhea. He has a history o hemorrhoids but at this time is not experiencing rectal irritation or itching, as with previous episodes. His medical history is signi cant or controlled hypertension and a remote history o smoking. On digital rectal examination, his stool sample tests positive or blood but anoscopy ails to identi y the source o bleeding. On colonoscopy, a mass is seen at 30 cm (Figure 66-1). A biopsy was obtained and pathology con rmed adenocarcinoma.

INTRO DUCTIO N Colon cancer is a malignant neoplasm o the colon, most commonly adenocarcinoma. With the establishment o screening programs and treatment improvements, there has been a slow decline in both the incidence and mortality rom colon cancer, although it is still a leading cause o cancer death. 1

• Colon cancer appears to be a multipathway disease with tumors usually arising rom adenomatous polyps or serrated adenomas; mutational events occur within the polyp including activation o oncogenes and loss o tumor-suppressor genes. 1,5 • The probability o a polyp undergoing malignant trans ormation increases or the ollowing cases1: ° The polyp is sessile, especially i villous histology or f at. ° Larger size—Malignant trans ormation is rare i smaller than 1.5 cm, 2% to 10% i 1.5 to 2.5 cm, and 10% i larger than 2.5 cm. • Important genes involved in colon carcinogenesis include adenomatous polyposis gene mutations, KRAS oncogene, chromosome 18 loss o heterozygosity leading to inactivation o SMAD4, and DCCtumor suppression genes (deleted in colon cancer). Other mutations in genes such as MSH2, MLH1, and PMS2 result in what is known as high- requency microsatellite instability (H-MSI), which is ound in cases o hereditary nonpolyposis colon cancer and in about 20% o sporadic colon cancers.4

RISK FACTO RS

EPIDEMIO LO GY • Colon cancer is the third most common cancer in both men and women in the United States, second only to lung cancer as a cause o death. 1

FIGURE 66-1 A s ssil colon mass s Michae l Harp e r, MD.)

ETIO LO GY AND PATHO PHYSIO LO GY

• Ingestion o red and processed meat1,6 • Hereditary syndromes—Polyposis coli and nonpolyposis syndromes (40% li etime risk)4

n at 35 cm. At su g y, this was ound to b a Duk stag A ad noca cinoma. (Re p rod uce d with p e rmission from

329

PART 10

330

GASTRO INTESTINAL • Inf ammatory bowel disease • Bacteremia with Streptococcus bovis— Increased incidence o occult tumors

Ch a pt e r 66

Physical signs o ten appear later in the course o the disease and can include the ollowing4: • Weight loss and cachexia

• Following ureterosigmoidostomy procedures (5%-10% incidence over 30 years)

• Abdominal distention, discom ort, or tenderness

• Smoking

• Ascites

• Alcohol consumption

• Rectal bleeding or occult blood on rectal examination

• Family history o colon cancer in a rst-degree relative • Obesity

DIAGNO SIS The diagnosis o colon cancer is sometimes made ollowing a positive screening test (ie, digital rectal examination, ecal occult blood testing [FOBT], sigmoidoscopy, colonoscopy, or barium enema). For patients who have symptoms and signs suggestive o colon cancer, the con rmative diagnostic test most commonly per ormed is colonoscopy with biopsy. Colonoscopy allows direct visualization o the lesion, examination o the entire large bowel or synchronous and metachronous lesions, and an ability to obtain tissue or histologic diagnosis. CLINICAL FEATURES Symptoms vary, primarily based on anatomic location, as ollows1: • Right-sided colon tumors more commonly ulcerate, occasionally causing anemia without change in stool or bowel habits. • Tumors in the transverse and descending colon (Figure 66-2) o ten impede stool passage causing abdominal cramping, occasional obstruction, and rarely per oration. • Tumors in the rectosigmoid region are associated more o ten with hematochezia, tenesmus (ie, urgency with a eeling o incomplete evacuation), narrow caliber stool, and uncommonly, anemia.

• Abdominal or rectal mass

TYPICAL DISTRIBUTIO N Colon cancers are approximately equally distributed between the right and le t colon. 7 IMAGING, ENDO SCO PY, AND WO RKUP • Colonoscopy o the entire colon is recommended to identi y additional neoplasms or polyps (see Figures 66-1 and 66-2). • Evaluation or metastatic disease includes the ollowing8: ° Local metastasis: Abdominal or pelvic computed tomography(CT) scans. ° Lung metastasis: Chest X-ray (CXR) or chest CT. ° Liver metastasis: magnetic resonance imaging (MRI) (pelvis), CT (abdomen and pelvis), or positron emission tomography (PET) CT scan (whole body). ° The American College o Radiology also recommends transrectal rectum ultrasound or pretreatment staging or patients with rectal cancer and the addition o MRI o the abdomen or patients with large rectal tumors. 9 ° Preoperative carcinoembryonic antigen (CEA)—An elevated pretreatment CEA (C-stage) has been shown to be an independent predictor o overall mortality (60% increased risk) in patients with colon cancer. 10 CEA may be elevated or reasons other than colon cancer, such as pancreatic or hepatobiliary disease; elevation does not always ref ect cancer or disease recurrence. Post-treatment CEA levels can be used to monitor or recurrence.

FIGURE 66-2 Plat 2 in this s i s shows no mal c cum. Th maining am s show a la g iabl mass. Biopsy conf m d ad noca cinoma. Th tumo was s ct d and d t min d to b Duk stag B ad noca cinoma. Colonoscopy 3 y a s lat was n g ativ . (Re produce d with pe rmission from Michae l Harpe r, MD.)

PART 10

CO LO N CANCER

° At surgery, surgeons per orm an examination o the liver, pelvis, hemidiaphragm, and ull length o the colon or evidence o tumor spread. 1 BIO PSY Colonic adenocarcinomas can be microscopically well-di erentiated or poorly di erentiated glandular structures. 4 The addition o cytology brushings to orceps biopsies may increase the diagnostic yield, especially in the setting o obstructing tumors that cannot be traversed. 11

DIFFERENTIAL DIAGNO SIS Other causes o abdominal pain in patients in this age group are as ollow: • Inf ammatory bowel disease, which includes ulcerative colitis and Crohn disease (see Chapter 77, Inf ammatory Bowel Disease); symptoms include bloody diarrhea, tenesmus, passage o mucus, and cramping abdominal pain. Extraintestinal mani estations, more common in Crohn disease, include skin involvement (eg, erythema nodosum), rheumatologic symptoms (eg, peripheral arthritis, symmetric sacroiliitis), and ocular problems (eg, uveitis, iritis). Diagnosis can be made on the basis o endoscopy and biopsy.

GASTRO INTESTINAL MANAGEMENT MEDICATIO NS • Chemotherapy with f uorouracil (5-FU), irinotecan, with or without leucovorin (LV) is o marginal bene t with overall response in approximately 15% to 20% o patients. 1 For patients with stage II (Duke B) tumors (invasion into or through muscularis propria), authors o a systematic review ound similar mortality rates with and without adjuvant chemotherapy. 12 • Six months o postoperative treatment with 5-FU and LV decreased recurrence or stage III (Duke C) tumors (lymph node involvement) by 40% and increased survival;1 the absolute survival bene t in one trial over LV alone was approximately 12% (49% vs 37%, respectively). 13 A reduction in relapse rate and a modest increase in 3-year disease- ree survival were also seen in patients with Duke B and C colon cancer by adding oxaliplatin to 5-FU–leucovorin; however, overall survival is only improved or a subgroup o patients. 14 • For patients with metastatic disease (stage IV/ Duke D), rst-line multiagent chemotherapy can be considered. Three randomized controlled trials (RCTs) have demonstrated improved response rates, progression- ree survival, and overall survival when a biological agent (irinotecan or oxaliplatin) was combined with 5-FU–leucovorin. 15

• Diverticulitis—Patients present with ever, anorexia, lower le t-sided abdominal pain, and diarrhea. Abdominal distention and peritonitis may be ound on physical examination. Diagnosis is clinical or made on the basis o abdominal CT scan.

SURGERY O R O THER TREATMENTS

• Appendicitis—Initial symptoms include periumbilical or epigastric abdominal pain with time becoming more severe and localized to the right lower quadrant. Additional symptoms include ever, nausea, vomiting, and anorexia.

• For super cial lesions, local excision or polypectomy with clear margins is per ormed; or other localized disease, wide surgical resection and reanastomosis is used.

Following are other causes o rectal bleeding: • In ectious agents—Salmonella, Shigella, certain Campylobacter species, enteroinvasive Escherichia coli, Clostridium di f cile, and Entamoeba histolytica can cause bloody, watery diarrhea, and are identi ed by culture test. Bacterial toxins may be identi ed with C. di f cile. Additional symptoms include ever and abdominal pain and the disease is o ten sel -limited. • Hemorrhoids (see Chapter 72, Hemorrhoids) and ssures—Bleeding is usually bright red and seen in the toilet or with wiping a ter bowel movements. Hemorrhoids can sometimes be visible as a protruding mass o ten associated with pruritus and ssures are identi ed as a cut or tear occurring in the anus. Hemorrhoidal pain is described as a dull ache but may be severe i thrombosed. • Diverticula—Bleeding is usually abrupt in onset, painless, and can be massive, but o ten stops spontaneously. These may be seen on endoscopy or in radiographic study. • Vascular colonic ectasias—Bleeding tends to be chronic resulting in anemia. Bleeding source may be identi ed during colonoscopy, but a radionuclide scan or angiography may be needed. • Colon polyp (see Chapter 67, Colon Polyps)—Usually asymptomatic, although abdominal pain, diarrhea, or constipation can occur o ten with decreased stool caliber. Imaging studies o ten can distinguish and biopsy con rms absence o malignancy. Other causes o intestinal obstruction include adhesions, peritonitis, inf ammatory bowel disease, ecal impaction, strangulated bowels, and ileus. 2

• Total resection o the tumor is completed or attempted cure or or symptoms; open surgery or laparoscopic techniques can be used. 16

• For patients with metastatic disease (stage IV/ Duke D), treatment options include surgical resection, resection o liver metastases, palliative radiation or chemotherapy, rst-line multiagent chemotherapy (see above) or participation in clinical trials. • Total colonic resection is per ormed or patients with amilial polyposis and multiple colonic polyps. • For rectal carcinoma, sharp dissection is recommended (vs blunt) or rectal tumors to reduce recurrence to approximately 10%. 1 In addition, radiation therapy o the pelvis also decreases regional recurrence. 1 Postoperative treatment with 5-FU and radiation decreases recurrence or stage B2 and C tumors. 1 • Preoperative radiation therapy can be used to shrink large tumors prior to resection.

PREVENTIO N AND SCREENING • Primary prevention—Increased dietary ber (conf icting evidence) and possibly increased ingestion o ruits, vegetables, sh, and milk. 6,17 High levels o physical activity also appear protective. 6,17 Low-dose aspirin is also associated with a lower risk o colon cancer and death rom colon cancer. 18 Other medications possibly associated with a lower colon cancer risk include hormone therapy and oral contraceptives. • Individuals who undergo at least one round o screening or colon cancer have a reduced risk o death rom bowel cancer. In addition,

331

PART 10

332

GASTRO INTESTINAL

Ch a pt e r 66

early polyp removal by colonoscopy with polypectomy is associated with a reduced risk or colorectal cancer in the population setting. 19 O the screening tests, high-sensitivity ecal occult blood testing (FOBT), f exible sigmoidoscopy (FSG) with FOBT, and colonoscopy are recommended options. 20 The US Preventive Services Task Force (USPSTF) recommends screening or colorectal cancer in adults, beginning at age 50 years and continuing until age 75 years. 20 SO R

• FOBT—This test will be positive in 2% to 4% o asymptomatic patients; less than 10% will have colon cancer. 1 There is a good evidence that periodic FOBT reduces mortality rom colorectal cancer; annual screening is recommended. 20 • FSG—There is good evidence that sigmoidoscopy in combination with FOBT reduces mortality rom colon cancer. 11 The ideal interval or surveillance is unknown but the USPSTF recommended a 5-year interval o surveillance by FSG combined with high-sensitivity FOBT every 3 years. 20 • Colonoscopy—There is emerging evidence that screening colonoscopy is e ective in reducing colorectal cancer mortality. Population-based observational study has shown a declining incidence o colon cancer and gains in li e-years where colonoscopy screening programs are in place. Colonoscopy also allows inspection o the proximal colon and early removal o polyps. 11,21 Examples o colonoscopy pictures are shown in Figures 66-1 to 66-3. • Double-contrast barium enema—This test o ers an alternative means o whole-bowel examination, but is less sensitive than colonoscopy and there is no direct evidence that it is e ective in reducing mortality rates. Figures 66-4 and Figure 66-5 display classic “apple-core de ormities” o the colon rom colon cancer. • Other Tests—CT colonography and stool DNA test have been available or colorectal cancer screening. However, more research is needed to study their potential bene ts and harms be ore widespread clinical use o these tests can be recommended as screening tools. 22

FIGURE 66-4 An “ap p l -co ” l sion on b a ium n ma consist nt with colon canc . Th p ati nt is a 72-y a -old A ican Am ican man who p s nt d with w ig ht loss. A comp l t b lood count d monst at d mod at an mia and his H moccult ca d s w p ositiv . (Re p ro d uce d with p e rmission from E.J. Maye aux, Jr., MD.)

• Secondary prevention—Low-dose aspirin (81 mg) has been shown to prevent adenomas in patients with previous colon cancer. 23

FIGURE 66-3 Ad noca cinoma in th c cum ound on colonoscop y. (Re p rod uce d with p e rmission from Marvin De re zin, MD.)

FIGURE 66-5 A b a ium n ma v als a la g “ap p l -co ” l sion consist nt with colon canc . Th p ati nt in a 64-y a -old man who had a b a ium n ma p o m d as p a t o th wo kup o w ig ht loss and vag u ab d ominal p ain. (Re p rod uce d with p e rmission from E.J. Maye aux, Jr., MD.)

PART 10

CO LO N CANCER

PRO GNO SIS • Duke A (T1N0M0)—Cancer limited to mucosa and submucosa; 5-year survival: 90.1%. 1, 24

GASTRO INTESTINAL PATIENT RESO URCES

• Medline Plus. Colon cancer—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000262.htm. • National Cancer Institute—http:/ / www.cancer.gov/ cancertopics/ pdq/ treatment/ colon/ patient.

• Duke B1 (T2N0M0)—Cancer extends into muscularis; 5-year survival: 85%.

PRO VIDER RESO URCES

• Duke B2 (T3N0M0)—Cancer extends into or through serosa; 5-year survival: 70% to 80%.

• National Cancer Institute—http:/ / www.cancer.gov/ cancertopics/ pdq/ treatment/ colon/ HealthProfessional.

• Duke C (TxN1M0)—Cancer involves regional lymph nodes; 5-year survival: 35% to 69.2%.

• Medscape. Colon Adenocarcinoma—http:/ / emedicine.medscape .com/ article/ 277496-overview.

• Duke D (TxNxM1)—Distant metastases (ie, lung, liver); 5-year survival: 5% to 11.7%. • In addition to node involvement and metastases, poor outcome is associated with the ollowing1: ° ° ° ° ° ° ° °

Number o regional lymph nodes involved Tumor penetration or per oration through the bowel wall Histology o poor di erentiation Tumor adherence to adjacent organs Venous invasion Elevated preoperative CEA (ie, > 5 ng/ mL) Aneuploidy Speci c chromosomal deletion (eg, allelic loss on chromosome 18q)

FO LLO W-UP • Staging is based on tumor depth and spread and predicts survival as above1: • Surveillance recommendations are as ollows25: ° O ce visits and CEA evaluations should be per ormed at a minimum o 3 times per year or the rst 2 years o ollow-up. SO R ° There is insu cient data to recommend or or against CXR as a part o routine colorectal cancer ollow-up. SO R ° Posttreatment colonoscopy should be per ormed at 3-year intervals. SO R

° Periodic anastomotic evaluation is recommended or patients who have undergone resection/ anastomosis or local excision o rectal cancer. SO R ° Serum hemoglobin, Hemoccult II (FOBT), and liver unction tests (hepatic enzymes tests) should not be routine components o a ollow-up program. SO R • For patients with progressive disease, options or urther therapy must be discussed including discontinuing therapy, intrahepatic chemotherapy (i appropriate), and experimental (ie, phase I) therapy.

PATIENT EDUCATIO N • Most recurrences occur within the rst 3 to 4 years, so survival at 5 years is a good indication o cure. 1 • Surveillance or recurrence should be conducted over the irst 5 years ollowing treatment as noted above. In addition to identi ying recurrence, a second tumor is ound in 3% to 5% and adenomatous polyps will be ound in more than 15% o patients over that period. 1

REFERENCES 1. Mayer R. Gastrointestinal tract cancer. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds. Harrison’s Principles o Internal Medicine. 16th ed. New York, NY: McGraw-Hill, 2005:523-533. 2. Edwards B, Ward E, Kohler B, et al. Annual report to the nation on the status o cancer, 1975-2006, eaturing colorectal cancer trends and impact o interventions (risk actors, screening, and treatment) to reduce uture rates. Cancer. 2010;116(3):544-573. 3. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277-300. 4. Dragovich T. Colon Adenocarcinoma. http:/ / emedicine.medscape. com/ article/ 277496-overview. Accessed June 2013. 5. Jass JR. Classi cation o colorectal cancer based on correlation o clinical, morphological, and molecular eatures. Histopathology. 2007;50:113-130. 6. Cancer Research UK. Bowel Cancer. http:/ / in o.cancerresearchuk. org/ cancerstats/ types/ bowel/ risk actors/ . Accessed June 2013. 7. Topazian M. Gastrointestinal endoscopy. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds. Harrison’s Principles o Internal Medicine. 16th ed. New York, NY: McGraw-Hill, 2005: 1730-1739. 8. Niekel MC, Bipat S, Stoker J. Diagnostic imaging o colorectal liver metastases with CT, MR imaging, FDG PET, and/ or FDG PET/ CT: a meta-analysis o prospective studies including patients who have not previously undergone treatment. Radiology. 2010;257(3):674-684. 9. Rosen MP, Bree RL, Foley WD, et al; Expert Panel on Gastrointestinal Imaging. ACR Appropriateness Criteria® Pretreatment Staging o Colorectal Cancer. http:/ / www.guideline.gov/ content.aspx?id=35139. Accessed June 2013. 10. Thirunavukarasu P, Sukumar S, Sathaiah M, et al. C-stage in colon cancer: implications o carcinoembryonic antigen biomarker in staging, prognosis, and management. J Natl Cancer Inst. 2011;103(8): 689-697. 11. Davila RE, Rajan E, Adler D, et al. ASGE guideline: The role o endoscopy in the diagnosis, staging, and management o colorectal cancer. Gastrointest Endosc. 2005;61(1):1-7. 12. Figueredo A, Charette ML, Maroun J, et al. Adjuvant therapy or stage II colon cancer: a systematic review rom the Cancer Care Ontario Program in evidence-based care’s gastrointestinal cancer disease site group. J Clin Oncol. 2004;22(16):3395-3407.

333

334

PART 10

GASTRO INTESTINAL 13. Laurie JA, Moertel CG, Fleming TR, et al. Surgical adjuvant therapy o large-bowel carcinoma: an evaluation o levamisole and the combination o levamisole and f uorouracil. The North Central Cancer Treatment Group and the Mayo Clinic. J Clin Oncol. 1989;7(10): 1447-1456. 14. André T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, f uorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27 (19):3109-3116. 15. National Cancer Institute. http:/ / www.cancer.gov/ cancertopics/ pdq/ treatment/ colon/ HealthPro essional/ page9. Accessed June 2013. 16. National Cancer Institute. http:/ / www.cancer.gov/ cancertopics/ pdq/ treatment/ colon/ HealthPro essional/ page4. Accessed June 2013. 17. National Cancer Institute. Colorectal Cancer Prevention. http:/ / cancer .gov/ cancertopics/ pdq/ prevention/ colorectal/ HealthPro essional. Accessed November 2011. 18. Rothwell PM, Wilson M, Elwin CE, et al. Long-term e ect o

aspirin on colorectal cancer incidence and mortality: 20-year ollow-up o ve randomised trials. Lancet. 2010;376(9754): 1741-1750. 19. Brenner H, Chang-Claude J, Seiler CM, et al. Protection rom colorectal cancer a ter colonoscopy: a population-based, case-control study. Ann Intern Med. 2011;154(1):22-30.

CHAPTe r 66

20. U.S. Preventive Services Task Force. Screeening or Colorectal Cancer. http:/ / www.uspreventiveservicestask orce.org/ uspst 08/ colocancer/ colosum.htm. Accessed June 2013. 21. Meza R, Jeon J, Renehan AG, Luebeck EG. Colorectal cancer incidence trends in the United States and United kingdom: evidence o right- to le t-sided biological gradients with implications or screening. Cancer Res. 2010;70(13):5419-5429. 22. Zauber AG, Lansdorp-Vogelaar I, Knudsen AB, et al. Evaluating test strategies or colorectal cancer screening: a decision analysis or the U.S. Preventive Services Task Force. Ann Intern Med. 2008;149(9): 659-669. 23. Sandler RS, Halabi S, Baron JA, et al. A randomized trial o aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med. 2003;348(10):883-890. 24. National Cancer Institute. Surveillance Epidemiology and End Results. http:/ / seer.cancer.gov/ stat acts/ html/ colorect.html. Accessed June 2013. 25. Anthony T, Simmang C, Hyman N, et al. Practice parameters or the surveillance and ollow-up o patients with colon and rectal cancer. Dis Colon Rectum. 2004;47(6):807-817.

CO LO N PO LYPS

67 CO LO N PO LYPS Cathy Ab b ott, MD Mind y A. Smith, MD, MS

PART 10

GASTRO INTESTINAL • Familial adenomatous polyposis o the colon is a rare autosomal dominant disorder. Thousands o adenomatous polyps appear in the large colon, generally by age 25 years, and colorectal cancer develops in almost all o these patients by age 40 years. 1 Other hereditary polyposis syndromes include Gardner syndrome, Turcot syndrome, PeutzJeghers syndrome, Cowden disease, amilial juvenile polyposis, and hyperplastic polyposis. 3

PATIENT STO RY A 62-year-old woman presents to her physician or routine annual examination. She has no known amily history o colon disease and is asymptomatic. Stool cards and exible sigmoidoscopy were recommended and on exible sigmoidoscopy a 2.4-cm polyp was noted at 35 cm. A colonoscopy was per ormed and additional polyps were identif ed in the descending colon and cecum (Figure 67-1).

INTRO DUCTIO N Colon polyps are growths that arise rom the epithelial cells lining the colon.

EPIDEMIO LO GY • More than 30% o middle-aged and elderly patients are ound to have adenomatous polyps on screening and based on autopsy surveys; ewer than 1% will become malignant. 1 The li etime risk o colon cancer is 5.12%. 2 • Patients with an adenomatous polyp have a 30% to 50% risk or developing another adenoma and are at higher risk or colon cancer. This risk is greatest in the f rst 4 years a ter diagnosis o the f rst polyp, and greater i a villous adenoma or more than 3 polyps were ound.

ETIO LO GY AND PATHO PHYSIO LO GY • Following are the several types o colon polyps: ° Hyperplastic polyps—These contain increased numbers o glandular cells with decreased cytoplasmic mucus and an absence o nuclear hyperchromatism, stratif cation, or atypia. Traditionally thought to be benign, recent evidence suggests malignant potential particularly or right-sided polyps, especially proximal hyperplastic serrated polyps1 and those associated with hyperplastic polyposis syndrome (a amilial disorder with multiple [>30] hyperplastic polyps proximal to the sigmoid colon with 2 or more > 10 mm). 3 The percentage o polyps reported to be in this category ranges rom 12% to 90%. 3,4 ° Adenomatous polyps—These may be tubular, villous (papillary), or tubulovillous. In a case series o 582 patients who had a polyp removed, 81% were adenomatous, including 65% that were tubular, 25.8% tubulovillous, 7.2% villous adenomas, and 0.5% mixed adenomatous hyperplastic polyps; 12 (1.4%) were invasive carcinomas. 4 ■ Adenomatous polyps may be pedunculated or sessile; cancers more requently develop in sessile polyps. 1 ° Villous polyps can cause hypersecretory syndromes characterized by hypokalemia and pro use mucous discharge; these more requently harbor carcinoma in situ or invasive carcinoma than other adenomas. 3 ° Nonneoplastic hamartoma (juvenile polyp)—These are benign cystic polyps with mucous- illed glands, most commonly ound

FIGURE 67-1 Colon p olyp s se e n on colonoscop y. (Re p rod uce d with p e rmission from Michae l Harp e r, MD.)

335

PART 10

336

GASTRO INTESTINAL in male children, ages 2 to 5 years, and are o ten ound as singular lesions, but additional polyps are ound on panendoscopy in 40% to 50% o children. Juvenile polyps in adolescence may be associated with hereditary syndromes that carry malignant potential. 5 • A series o genetic or molecular changes have been ound that are thought to represent a multistep process rom normal colon mucosa to malignant tumor. 3 These include the ollowing: ° Point mutations in the K-ras protooncogene lead to gene activation and deletion o DNA at the site o tumor-suppressor gene. ° This results in an altered proli erative pattern and polyp ormation. ° Mutational activation o an oncogene, coupled with loss o tumorsuppressor genes, leads to malignant trans ormation. ° Serrated polyps, which have in the past been characterized as hyperplastic polyps, are now known to have epigenetic alterations that may develop into colon cancers by another pathway—the CpG-island-methylation-phenotype pathway. 6 ° Patients with amilial polyposis inherit a germline alteration that leads into the above pathway. • Insulin resistance, with increased concentrations o insulin-like growth actor type I, may also stimulate proli eration o the intestinal mucosa.

Ch a pt e r 67

• For patients with a amily history o amilial adenomatous polyposis, DNA testing may be per ormed to detect the adenomatous polyposis coli (APC) gene mutation; this can lead to a def nitive diagnosis be ore the development o polyps. 1 SO R A positive test f nding only indicates susceptibility, not the actual presence o a polyp. 3 • Genetic testing can also be considered or patients with a amily history o hereditary nonpolyposis colorectal cancer (HNPCC), which is caused by germline mutation o the DNA mismatch repair genes (hMLH1, hMSH2, hPMS1, hPMS2, hMSH6). 10 SO R IMAGING AND ENDO SCO PIC FEATURES • Polyps may be identif ed on barium enema (Figures 67-2 and 67-3), exible sigmoidoscopy, or colonoscopy (including virtual computer tomography colonoscopy) (Figures 67-1 and 67-4). • A polyp is def ned as a grossly visible protrusion rom the mucosal surace, although adenomas can also be at or even depressed. 11 • Colonoscopy must be subsequently per ormed to identi y additional lesions and remove all lesions. • Synchronous lesions occur in one-third o cases (see Figure 67-1). BIO PSY • Polyps upon removal are sent or histology to determine type and whether dysplasia or carcinoma in situ is present (Figure 67-5).

RISK FACTO RS • Older age—99% o cases occur in people older than age 40 years and 85% in those older than age 60 years. 7 • Family history—Present in 10% to 20% o cases. 7 • Diet appears to be associated with colon polyps and colon cancer. Animal ats may alter anaerobes in the gut micro ora, increasing conversion o normal bile acids to carcinogens. Also, increased cholesterol is associated with an enhanced risk o development o adenomas. • There may be an association between Helicobacter exposure and colonic polyps. 8,9

DIAGNO SIS CLINICAL FEATURES • Usually asymptomatic. • Patients may experience overt or occult rectal bleeding. • Change in bowel habits—Diarrhea or constipation can occur, o ten with decreased stool caliber. • Secretory villous adenomas can occasionally mani est as a syndrome o severe diarrhea with massive uid and electrolyte loss. 3 TYPICAL DISTRIBUTIO N • Cancer distribution is approximately equal between the right and le t colon. Juvenile polyps are usually ound in the rectosigmoid region. LABO RATO RY TESTING • Occult blood in the stool is ound in less than 5% o patients with polyps. 1 O the 2% to 4% o asymptomatic patients who have heme positive stool on screening, 20% to 30% will have polyps. 1

FIGURE 67-2 A 69-ye ar-old woman with a family history of colon cance r p re se nte d for scre e ning . He r He moccult te st was p ositive . He r d oub le -contrast b arium e ne ma (air contrast) d e monstrate d a larg e colonic p olyp , which was found on surg e ry to b e hig hly d ysp lastic. (Re p rod uce d with p e rmission from E.J. Maye aux, Jr., MD.)

CO LO N PO LYPS

FIGURE 67-3 While g e tting a b arium e ne ma for othe r re asons, this p atie nt was found to have a larg e colonic p olyp . Biop sy of the p olyp d e monstrate d e arly-stag e colon cance r, which was tre ate d b y surg ical re se ction. (Re p rod uce d with p e rmission from E.J. Maye aux, Jr., MD.)

DIFFERENTIAL DIAGNO SIS Other causes o rectal bleeding include the ollowing: • In ectious agents—Salmonella, Shigella, certain Campylobacter species, enteroinvasive Escherichia coli, Clostridium di f cile, and Entamoeba histolytica can cause bloody, watery diarrhea and are identif ed by culture. Bacterial toxins may be identif ed with C. di f cile (see Chapter 65, Clostridium di f cile Colitis). Additional symptoms include ever and abdominal pain, and the disease is o ten sel -limited. • Hemorrhoids and f ssures—Bleeding is usually bright red blood and seen in the toilet or with wiping a ter bowel movements. Hemorrhoids can sometimes be visible as a protruding mass o ten associated with pruritus, and f ssures are identif ed as a cut or tear occurring in the anus (see Chapter 72, Hemorrhoids). Hemorrhoidal pain is described as a dull ache, but may be severe i thrombosed.

PART 10

GASTRO INTESTINAL

FIGURE 67-5 Polyp e cto my b e ing p e rforme d throug h the colonoscop e . (Re p rod uce d with p e rmission from Marvin De re zin, MD.)

• Diverticula—Bleeding is usually abrupt in onset, painless, and may be massive but o ten stops spontaneously. These may be seen on endoscopy or on radiographic study. • Vascular colonic ectasias—Bleeding tends to be chronic, resulting in anemia. Bleeding source may be identif ed during colonoscopy but a radionuclide scan or angiography may be needed. • Colon cancer—Other symptoms include abdominal cramping, tenesmus (ie, urgency with a eeling o incomplete evacuation), narrow caliber stool, occasional obstruction, and, rarely, per oration. Imaging studies o ten can distinguish and biopsy conf rms malignancy (see Chapter 66, Colon Cancer). • In ammatory bowel disease—This includes ulcerative colitis and Crohn disease; symptoms include diarrhea, tenesmus, passage o mucus, and cramping abdominal pain (see Chapter 77, In ammatory Bowel Disease). Extraintestinal mani estations are more common in Crohn disease and include skin involvement (eg, erythema nodosum), rheumatologic symptoms (eg, peripheral arthritis, symmetric sacroiliitis), and ocular problems (eg, uveitis, iritis). Diagnosis may be made on endoscopy.

MANAGEMENT Removal o a solitary polyp can be completed during sigmoidoscopy or colonoscopy (see Figure 67-5).

PREVENTIO N

FIGURE 67-4 Polyp in the ce cum se e n on colonosco p y. (Re p rod uce d with p e rmission from Marvin De re zin, MD.)

• Primary prevention o colon cancer should be encouraged. ° Dietary alterations may be use ul. ■ Decreasing animal ats as diets high in animal ats are thought to be a major risk actor based on epidemiologic studies. However, in the Women’s Health Initiative study, a low- at dietary intervention did not reduce the risk o colorectal cancer in postmenopausal women during 8.1 years o ollow-up. 12

337

PART 10

338

GASTRO INTESTINAL Additional dietary f ber has not shown to be help ul in controlled studies. 13 ■ Increasing water consumption to 8 glasses per day may be help ul. ■ Diets high in avonols ( ruits, vegetables, and tea) are associated with decreased risk o colon polyps, possibly by reducing serum interleukin (IL)-6, which is associated with in ammation and carcinogenesis. 14 ° Calcium supplements (1200 mg/ d) have been shown to reduce the development o adenomatous polyps. 15 SO R 16 Hormone therapy in women reduces colon cancer incidence. ° ■

SO R

° A meta-analysis ailed to show that olic acid supplementation reduced the risk o recurrent colon adenomas. 17 ° Low-dose aspirin (81 mg/ d) was ound to decrease recurrent adenomas, including those containing advanced neoplasms. 18 SO R In patients with amilial adenomatous polyposis, once-daily treatment with 25-mg ro ecoxib signif cantly decreased the number and size o rectal polyps in one randomized trial. 19 20 ° Smoking cessation. polyps and ° Increasing physical activity reduces the risk o advanced neoplasia, possibly by decreasing insulin resistance. 21

Ch a pt e r 67

PATIENT EDUCATIO N • Attention to li estyle actors can contribute to decreasing the risk o colon polyps. • Patients should be encouraged to undergo screening or colon cancer, including use o high-sensitivity Hemoccult cards, exible sigmoidoscopy, or colonoscopy. 25 SO R • Patients diagnosed with polyps should be encouraged to engage in continued surveillance or polyps and colon cancer. Those at increased risk or a subsequent advanced neoplasia (see earlier) should have a ollowup colonoscopy at 3 or ewer years. 23 SO R For other patients, ollow-up is recommended at 5 to 10 years. 10 SO R PATIENT RESO URCES

• National Digestive Diseases Information Clearinghouse. Colon Polyps—http:/ / digestive.niddk.nih.gov/ ddiseases/ pubs/ colonpolyps_ez/ index.htm. • Mayo Clinic. Colon Polyps—http:/ / www.mayoclinic.com/ health/ colon-polyps/ DS00511/ DSECTION=4. PRO VIDER RESO URCES

PRO GNO SIS Patients with a polyp with tubulovillous eatures or with more than 3 polyps larger than 10 mm are at increased risk or urther aggressive lesions on ollow-up colonoscopy, and untreated patients with polyps larger than 10 mm are at increased risk or colon cancer both at the site o polyp and at other sites. 22

FO LLO W-UP • Secondary prevention o colon cancer should be maximized through screening and removal o additional or recurrent polyps or colon cancer in these patients (see Chapter 66, Colon Cancer). Although there is debate regarding the requency o screening, the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College o Radiology updated guideline recommends repeat colonoscopy at the ollowing intervals: ° Every 5 to 10 years or those with 1 to 2 small tubular adenomas with low-grade dysplasia a ter initial polypectomy. ° Every 3 years or patients with 3 to 10 adenomas or 1 adenoma larger than 1 cm or any adenoma with villous eatures or high-grade dysplasia. ° Less than every 3 years or patients with more than 10 adenomas. in patients with sessile ° At 2 to 6 months to veri y complete removal adenomas that are removed piecemeal. 23 • Although screening options that enable detection o both adenomatous polyps and colon cancer include exible sigmoidoscopy, colonoscopy, double-contrast barium enema, and computed tomography (CT) colonography (use o dyes or other visual enhancements during colonoscopy), authors o a Cochrane review ound that chromoscopic colonoscopy enhances the detection o polyps in the colon and rectum. 24 This orm o colonoscopy can be used to identi y at polyps, increasing the sensitivity o colonoscopy, and may allow or detection o high-risk polyps without the need or biopsy.

• Medscape. Colonic Polyps—http:/ / emedicine.medscape .com/ article/ 172674. REFERENCES 1. Mayer R. Gastrointestinal tract cancer. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson, JL, eds. Harrison’s Principles o Internal Medicine, 16th ed. New York, NY: McGraw-Hill; 2005:523-533. 2. National Cancer Institute. http:/ / seer.cancer.gov/ stat acts/ html/ colorect.html. Accessed July 2013. 3. Enders GH. Colon Polyps. http:/ / emedicine.medscape.com/ article/ 172674-overview. Accessed July 2013. 4. Khan A, Shrier I, Gordon PH. The changed histologic paradigm o colorectal polyps. Surg Endosc. 2002;16(3):436-440. 5. Barnard J. Gastrointestinal polyps and polyp syndromes in adolescents. Adolesc Med Clin. 2004;15(1):119-129. 6. No singer AE. Serrated polyps and colorectal cancer: new pathway to malignancy. Annu Rev Pathol. 2009;4:343-364. 7. Ballinger AB, Anggiansah C. Colorectal cancer. BMJ. 2007;335: 715-718. 8. Mizuno S, Morita Y, Inui T, et al. Helicobacter pylori in ection is associated with colon adenomatous polyps detected by high-resolution colonoscopy. Int J Cancer. 2005;117(6):1058-1059. 9. Abbass K, Gul W, Beck G, et al. Association o Helicobacter pylori in ection with the development o colorectal polyps and colorectal cancer. South Med J. 2011;104(7):473-476. 10. American Gastroenterological Association medical position statement: hereditary colorectal cancer and genetic testing. Gastroenterology. 2001;121(1):195-197. 11. Anderson JC. Risk actors and diagnosis o at adenomas o the colon. Expert Rev Gastroenterol Hepatol. 2011;5(1):25-32. 12. Beres ord SA, Johnson KC, Ritenbaugh C, et al. Low- at dietary pattern and risk o colorectal cancer: the Women’s Health Initiative

CO LO N PO LYPS

Randomized Controlled Dietary Modif cation Trial. JAMA. 2006;295(6):643-654. 13. Asano TK., McLeod RS. Dietary f bre or the prevention o colorectal adenomas and carcinomas. Cochrane Database Syst Rev. 2002;(2): CD003430. 14. Bobe G, Albert PS, Sansbury LB, et al. Interleukin-6 as a potential indicator or prevention o high risk adenoma recurrence by dietary avonols in the polyp prevention trial. Cancer Prev Res (Phila). 2010;3(6):764-775. 15. Weingarten MAMA, Zalmanovici Trestioreanu A, Yaphe J. Dietary calcium supplementation or preventing colorectal cancer and adenomatous polyps. Cochrane Database Syst Rev. 2008;(1):CD003548. 16. Nelson HS, Humphrey LL, Nygren P, et al. Postmenopausal hormone replacement therapy. JAMA. 2002;288(7):872-881. 17. Ibrahim EM, Zekri JM. Folic acid supplementation or the prevention o colorectal adenomas: metaanalysis o interventional trials. Med Oncol. 2010;27(3):915-918. 18. Baron JA, Cole BF, Sandler RS, et al. A randomized trial o aspirin to prevent colorectal adenomas. N Engl J Med. 2003;348(10):891-899. 19. Higuchi T, Iwama T, Yoshinaga K, et al. A randomized, doubleblind, placebo-controlled trial o the e ects o ro ecoxib, a selective

PART 10

GASTRO INTESTINAL cyclooxygenase-2 inhibitor, on rectal polyps in amilial adenomatous polyposis patients. Clin Cancer Res. 2003;9(13):4756-4760. 20. Botteri E, Iodice S, Raimondi S. Cigarette smoking and adenomatous polyps: a meta-analysis. Gastroenterology. 2008;134:388-395. 21. Wolin KY, Yan Y, Colditz GA. Physical activity and risk o colon adenoma: a meta-analysis. Br J Cancer. 2011;104(5):882-885. 22. Hassan C, Pickhardt PJ, Kim DH, et al. Systematic review: distribution o advanced neoplasia according to polyp size at screening colonoscopy. Aliment Pharmacol Ther. 2010;31(2):210-217. 23. Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance or the early detection o colorectal cancer and adenomatous polyps, 2008: a joint guideline rom the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College o Radiology. Gastroenterology. 2008;134: 1570-1595. 24. Brown SR, Baraza W. Chromoscopy versus conventional endoscopy or the detection o polyps in the colon and rectum. Cochrane Database Syst Rev. 2010;(10):CD006439. 25. United States Preventive Services Task Force. Colorectal Cancer Screening. Summary. http:/ / www.ahrq.gov/ clinic/ colorsum.htm. Accessed July 2013.

339

340

PART 10

GASTRO INTESTINAL

Ch a pt e r 68

68 DIVERTICULITIS O live r Ab e la, MD

PATIENT STO RY A 68-year-old man presents with a 3-day history o constant pain in the le t lower quadrant (LLQ) associated with nausea, ever, and chills. The pain is not relieved by bowel movement. He has never had abdominal pain in the past, and he has never had a colonoscopy. His past medical history is signif cant or hypertension and headaches, or which he takes hydrochlorothiazide and acetaminophen as needed. On physical examination, his temperature is 102.1°F, his blood pressure is 135/ 75 mm Hg, his pulse rate is 93/ min, and his respiration rate is 16/ min. There is tenderness to palpation o the LLQ without rebound or guarding, and his bowel sounds are decreased. His rectal examination is normal, and examination o his stool or occult blood is negative. His leukocyte count is 16,000/ µL (16 × 109/ L), and his contrast-enhanced computed tomographic (CT) scan o the abdomen and pelvis shows diverticula o the sigmoid colon with pericolic atty inf ltration and thickening o the bowel wall consistent with diverticulitis (Figure 68-1). The CT also shows a 1-cm abscess in association with the diverticulitis and a small amount o air in the abscess. There are no masses, strictures, obstructions, or f stula present. Patient is started on cipro oxacin and metronidazole, clear liquids, intravenous uids, and pain medications. He improves a ter 3 days o medical management; his diet is advanced, and he is sent home to f nish a 14-day course o antibiotics.

INTRO DUCTIO N Diverticulitis is a disease in a spectrum that includes subclinical in ammation through a li e-threatening in ammatory in ectious condition. Diverticulitis is associated with acquired diverticulum. It rarely a ects people in developing countries owing to the highly cultural risk actors o low-f ber diet and

FIGURE 68-2 Multip le d ive rticuli are se e n p roje cting o the sig moid colon in this b arium e ne ma imag e . (Re p rod uce d with p e rmissio n from Gary Fe re nchick, MD.)

minimal physical activity ound in industrialized cultures. In cultures in which diverticular disease is prevalent, it is highly correlated with increasing age.

TERMINO LO GY • Diverticulosis is the presence o diverticula (outpouchings) that are asymptomatic (Figure 68-2). • Diverticular disease is the presence o diverticula associated with symptoms (ie, hematochezia). • Diverticulitis re ers to evidence o diverticular in ammation commonly associated with symptoms o ever or tachycardia, with or without localized symptoms. • Complicated diverticulitis includes per oration into the peritoneum, abscess, phlegmon, f stula ormation, stricture, and obstruction.

EPIDEMIO LO GY • O the US population, 30% have diverticulosis by 60 years and 60% by 80 years. 1 • O the population with diverticulosis, 10% to 25% will develop diverticulitis, and 25% o these cases will be complicated. 1,2 • Overall annual age-adjusted admissions or acute diverticulitis increased rom 120,500 in 1998 to 151,900 in 2005, a 26% increase. 3

ETIO LO GY/ PATHO PHYSIO LO GY FIGURE 68-1 Ab d ominal comp ute d tomog rap hic scan d e monstrating sig moid d ive rticulitis. Note the in ammatory d e nsity outsid e the sig moid colon, with a small amount o air sug g e sting p e r oration in this 45-ye ar-old man, who p re se nte d with acute le t lowe r q uad rant ab d ominal p ain. (Re p rod uce d with p e rmission from Gary Fe re nchick, MD.)

• A low-f ber diet leads to less-bulky stools that retain less water and increase transit time, and these actors increase intracolonic pressure. • Increased intracolonic pressure causes the mucosa and submucosa to protrude as pouches through the musculature.

PART 10

DIVe r t ICULIt IS

° Such protrusions occur at locations o weakness, o 4ten where the vasculature travels through the layers o the colon. • Stasis or obstruction in the narrow-necked diverticulum by ecal material leads to increased mucus secretion, bacterial overgrowth, tissue in ammation, and ischemia, subsequently leading to translocation o bacteria into the peritoneum and per oration. 2,4 • In ammation and ocal necrosis lead to micro- or macroscopic per orations. 5

GASTRO INTESTINAL • Inquire about the presence or absence o a known history o diverticular disease, symptoms o prior hematochezia, constipation, and lowf ber diet. • Because o the broad di erential based on the symptoms described by the patient, many times the diagnosis is not conf rmed until CT imaging is completed. IMAGING

• An acute episode o diverticulitis ranges rom subclinical in ammation to generalized peritonitis with abscess and f stula ormation. 5

• CT scanning is 97% sensitive and 99% specif c or diverticulitis. 4

• The sigmoid colon is less compliant than the ascending colon. This may predispose to the classic type o diverticulosis seen in Western countries characterized by increased intraluminal pressures, in ectious complications, and per oration. 2

• CT can also assess or the presence o complications and their severity, such as abscess ormation, and likelihood o responding to medical management. 5

RISK FACTO RS ° Age—The risk o diverticulosis is 10%2 or those younger than 40 and up to 67% or those older than 80. ° Low-f ber, high- at diets. 4 Chronic constipation. °

DIAGNO SIS CLINICAL FEATURES

SO R

• Specif c CT f ndings include the ollowing: ° Pericolonic at stranding is present in 98% (Figure 68-3). ° Diverticula are present in 84% (Figure 68-3). ° Bowel wall thickening greater than 4 mm is present in 70% (Figure 68-3B). ° Phlegmon/ pericolic uid is present in 35% (Figure 68-3). • Contrast barium enema radiography (Figure 68-2), cystography, ultrasound, and endoscopy are sometimes help ul in the initial workup o suspected diverticulitis but are used less o ten because o the superiority o CT scanning. 5 DIFFERENTIAL DIAGNO SIS

• Classic symptoms include LLQ abdominal pain and tenderness, nausea, constipation, and ever.

• Nephrolithiasis/ ureteral calculi are di erentiated by the presence o colicky pain associated with gross or microscopic hematuria and a positive CT scan or the presence o a stone.

• Variable symptoms include right or central abdominal pain, vomiting, or diarrhea.

• Cystitis/ pyelonephritis can be di erentiated by the presence o pyuria/ bacteriuria and costovertebral angle tenderness.

A

B

FIGURE 68-3 A. The re is a hazy ap p e arance to the p e ricolonic at cause d b y e d e ma (op e n arrow p oints to p e ricolonic ascia thicke ning ). B. Contrast-f lle d d ive rticulum p roje cts o thicke ne d p roximal sig moid colon (arrow).

341

PART 10

342

GASTRO INTESTINAL • Small-bowel obstruction (SBO) is associated with more prominent emesis plus obstipation and abdominal radiographs demonstrating dilated loops o bowel and air uid levels. • Colonic cancer presents with symptoms most likely rom a secondary obstructive process, chronic anemia rom stool occult bleeding, and no previous screening colonoscopy. • In ectious colitis should be considered i the patient had recent antibiotic use, is presenting with rank hematochezia, and the microscopic examination o the stool reveals positive stool white blood cells. • In ammatory bowel disease (IBD) is associated with markedly elevated C-reactive protein/ erythrocyte sedimentation rate (CRP/ ESR), Hemoccult-positive stool, CT consistent with IBD, and a conf rmatory biopsy on colonoscopy. • Ovarian cyst or ectopic pregnancy should be considered in premenopausal women; the pregnancy test will be positive in an ectopic pregnancy, and a transvaginal ultrasound can conf rm diagnosis o both. • Appendicitis is commonly associated with early-onset epigastric pain migrating to the right lower quadrant (RLQ).

Ch a pt e r 68

options should be considered. Some studies showed stages I and II

were reasonably managed with drainage and antibiotics and stages III and IV usually required surgery. 7 Other studies showed more o ten those with stages I and II having a sigmoid colectomy with a primary anastomosis and in stage III or IV having a colostomy and Hartmann pouch as the most commonly used procedure to avoid the risk o anastomosis leakage associated with primary anastomosis in overly in amed colon. 8,9

PRO GNO SIS/ CLINICAL CO URSE • O patients with uncomplicated diverticulitis, 85% will resolve with medical management. 1 • Abscesses are present in 16% o those with acute diverticulitis without peritonitis. 10 • Purulent peritonitis mortality is 6%. • Fecal peritonitis mortality is 35%. • O those a ected, 33% will have a recurrent attack. 1

MANAGEMENT • Factors to consider or admission include severity o pain, oral intake tolerance, older age, and comorbidities. 5 • Provide bed rest, clear liquids i tolerated, and analgesics. 5 ° Hospitalization is recommended i the patient cannot tolerate oral intake, needs better pain control, has complicated diverticulitis, ailed outpatient treatment, or is immunocompromised. 4 • Antibiotics are given to cover gram-negative rods and anaerobes (ie, typical dose in a patient without renal compromise includes metronidazole 500 mg orally or intravenously every 6 hours or 7-14 days plus cipro oxacin 400 mg orally or intravenously every 8-12 hours or 7-14 days). 5 • Indications or emergent surgery1 SO R ° Purulent or ecal peritonitis ° Uncontrolled sepsis ° Fistula ° Obstruction ° Inability to exclude carcinoma ° Failure o medical management

• The likelihood o recurrence does not increase with requency o attacks but with the severity o an attack and its complications. 1 • O all patients with a diagnosis o acute diverticulitis, 20% will require surgery at some point in their li etime. 10 • Approximately 2% to 11% o surgical patients may need repeat surgery or recurrent episode in the more proximal colon. 5

FO LLO W-UP • The standard o care is to recommend colonoscopy approximately 6 weeks a ter an episode (so that per oration risk is closer to baseline) to assess or other possible etiologies, including malignancy, IBD, and ischemia. 1 SO R Colonoscopy will commonly demonstrate a diverticulum (Figure 68-4).

• Abscess size greater than 2 cm is less likely to resolve; CT-guided drainage ollowed by one-stage primary anastomosis is an option. 1 SO R

• Operative treatment options include colectomy, descending ° Hartmann procedure, which is a sigmoid colostomy, and rectal stump closure1 1 ° Primary anastomosis with or without intraoperative colonic lavage ° Resection with temporary diverting ileostomy 1 ■ Laparoscopic approach is optimal in selected patients SO R • Hinchey classif cation6 ° Stage 1—Pericolic or mesenteric abscess (mortality < 5%) ° Stage 2—Walled-o or pelvic abscess (mortality < 5%) ° Stage 3—Generalized purulent peritonitis (mortality < 13%) ° Stage 4—Generalized ecal peritonitis (mortality < 43%) • The Hinchey classif cation provides mortality likelihoods and aids in the individualized decision making about which operative management

FIGURE 68-4 Asymp tomatic d ive rticulosis. This is a common f nd ing in scre e ning colonoscop ie s and ind icate s p re cursor le sions or the d e ve lop me nt o d ive rticulitis. (Re p rod uce d with p e rmission from John Rod ne y, MD.)

DIVe r t ICULIt IS

• Elective surgery to prevent urther attacks should be individualized. SO R

° Factors that should be considered include the patient’s age; comorbidities (diabetes mellitus, collagenous disease, compromised immune system); severity o attacks (with complications); and persistent symptoms a ter acute attack. 5 ° Young age is more likely a actor in elective resection preventing urther attacks because o an inherent increased cumulative risk over time (not because o increased severity in younger individuals). 1 ° Recurrence o diverticulitis is 36% at 5 years; complicated recurrence, which is def ned by the presence o a f stula, per oration, or abscess ormation, recurs in about 4% o patients. ■ Recurrent disease is more common in patients with a amily history o diverticulitis, diverticulitis involving more than 5 cm o the sigmoid colon, or the presence o a retroperitoneal abscess. Patients with right-side diverticulitis (5% o total cases) are at low risk o recurrence. 11

PATIENT EDUCATIO N • Sel -reported vegetarians are at a 31% lower risk o diverticular disease than meat eaters. 12 • High dietary f ber is associated with a 41% lower risk o diverticular disease. 12

PART 10

GASTRO INTESTINAL 2. Janes SE, Meagher A, Frizelle FA. Management o diverticulitis. BMJ. 2006;332:271-275. 3. Etzioni DA, Mack TM, Beart RW Jr, Kaiser AM. Diverticulitis in the United States: 1998-2005: changing patterns o disease and treatment. Ann Surg. 2009;249:210-217. 4. Jacobs DO. Clinical practice. Diverticulitis. N Engl J Med. 2007;357: 2057-2066. 5. Szojda MM, Cuesta MA, Mulder CM, Felt-Bersma RJ. Review article: management o diverticulitis. Aliment Pharmacol Ther. 2007;26(suppl 2):67-76. 6. Schwesinger WH, Page CP, Gaskill HV 3rd, et al. Operative management o diverticular emergencies: strategies and outcomes. Arch Surg. 2000;135:558-562; discussion 62-63. 7. Hinchey EJ, Schaal PG, Richards GK. Treatment o per orated diverticular disease o the colon. Adv Surg. 1978;12:85-109. 8. Wong WD, Wexner SD, Lowry A, et al. Practice parameters or the treatment o sigmoid diverticulitis—supporting documentation. The Standards Task Force. The American Society o Colon and Rectal Surgeons. Dis Colon Rectum. 2000;43:290-297. 9. Schilling MK, Maurer CA, Kollmar O, Buchler MW. Primary vs. secondary anastomosis a ter sigmoid colon resection or per orated diverticulitis (Hinchey Stage III and IV): a prospective outcome and cost analysis. Dis Colon Rectum. 2001;44:699-703; discussion 705.

PATIENT RESO URCES

10. Chautems RC, Ambrosetti P, Ludwig A, Mermillod B, Morel P, Soravia C. Long-term ollow-up a ter f rst acute episode o sigmoid diverticulitis: is surgery mandatory? A prospective study o 118 patients. Dis Colon Rectum. 2002;45:962-966.

• National Digestive Diseases Information Clearinghouse (NDDIC). Diverticulosis and Diverticulitis— http:/ / digestive.niddk.nih .gov/ ddiseases/ pubs/ diverticulosis/

11. Hall JF, Roberts PL, Ricciardi R, et al. Long-term ollow-up a ter an initial episode o diverticulitis: what are the predictors o recurrence? Dis Colon Rectum. 2011; 54(3):283-288.

PRO VIDER RESO URCES

12. Crowe FL, Appleby PN, Allen NE, Key TJ. Diet and risk o diverticular disease in Ox ord cohort o European Prospective Investigation into Cancer and Nutrition (EPIC): prospective study o British vegetarians and non-vegetarians. BMJ. 2011;343:d4131. doi:10.1136/ bmj.d4131.

• Nuts, corn, or popcorn consumption is not a risk actor in diverticulosis ormation, diverticulitis, or complications. 13

• Medscape. Diverticulitis—http:/ / emedicine.medscape.com/ article/ 173388. REFERENCES 1. Ra erty J, Shellito P, Hyman NH, Buie WD. Practice parameters or sigmoid diverticulitis. Dis Colon Rectum. 2006;49:939-944.

13. Strate LL, Liu YL, Syngal S, Aldoori WH, Giovannucci EL. Nut, corn, and popcorn consumption and the incidence o diverticular disease. JAMA. 2008;300:907-914.

343

344

PART 10

GASTRO INTESTINAL

69 GALLSTO NES Mind y A. Smith, MD, MS

PATIENT STO RY A 44-year-old woman reports frequent episodes of severe pain in the mid and upper right side of her abdomen that usually occurs shortly after her evening meal and sometimes at night. She is obese, but otherwise healthy. The pain lasts for several hours and is steady and often causes vomiting. On physical examination she complains of slight tenderness in the right upper quadrant (RUQ). An ultrasound con rms the presence of gallstones (Figure 69-1).

INTRO DUCTIO N Gallstones are inorganic masses usually composed of cholesterol that form in the gallbladder or bile duct. They are formed by concretion (joining together of adjacent parts and hardening) or accretion (growth by addition or adherence of parts normally separated) of normal and/ or abnormal bile constituents.

EPIDEMIO LO GY • Based on autopsy data, 20% of women and 8% of men have gallstones. 1 • Approximately 20 million people in the United States are affected, with 1 million new cases each year. 1 • In a Swedish incidence study of 621 randomly selected individuals ages 35 to 85 years, 42 (8.3%) of the 503 subjects available at 5 years developed gallstones; this yielded an incidence for newly developed gallstones of 1.39 per 100 person-years. 2

Ch a pt e r 69

• Among pregnant women, 5% to 12% have gallstones and 20% to 30% have gallbladder sludge (thick mucus material containing cholesterol crystals and mucin thread or mucous gels). Gallbladder sludge is a possible precursor form of gallstone disease. 1 • Patients with asymptomatic gallstones have a 1% to 2% risk per year of developing symptoms or complications of gallstones. Based on data primarily for men, this will occur in 10% by 5 years, 15% by 10 years, and 18% by 15 years following diagnosis. 1 • Gallstone disease is responsible for approximately 10,000 deaths per year in the United States. Most (7000) of these deaths are attributable to acute gallstone complications (eg, cholecystitis, pancreatitis, cholangitis). 3 • Although gallbladder cancers most often occur in the setting of stones (91% of 34 patients with gallbladder cancer in one study), 4 gallbladder cancer is rare. An incidence rate of 0.28% for incidental gallbladder carcinoma was reported in a Swiss database study of a population of more than 30,000 patients undergoing laparoscopic cholecystectomy. 5

ETIO LO GY AND PATHO PHYSIO LO GY • There are 2 types of gallstones: cholesterol stones (80%) and pigmented stones (primarily calcium bilirubinate, 20%). • The solute components of bile include bile acids (80%), lecithin and other phospholipids (16%), and unesteri ed cholesterol (4%). 1 Cholesterol gallstones form when there is excess cholesterol or an abnormal ratio of cholesterol, bile acids, and lecithin. • Excess biliary cholesterol can occur from a secondary increase in secretion of cholesterol caused by obesity, high cholesterol diet, clo brate therapy, or a genetic predisposition to increased hydroxymethylglutarylcoenzyme A reductase. • The excess cholesterol becomes supersaturated and can precipitate out of solution in a process called nucleation, forming solid cholesterol monohydrate crystals that can become trapped in gallbladder mucus, producing sludge, and/ or grow and aggregate to form cholesterol gallstones. • Gallbladder hypomotility is a predisposing and possibly necessary factor in stone formation because of the failure to completely empty supersaturated or crystal-containing bile. 1 Situations associated with hypomotility include pregnancy, prolonged parenteral nutrition, surgery, burns, and use of oral contraceptives or estrogen therapy. • Pigmented stones occur when increasing amounts of unconjugated bilirubin in bile precipitate to form stones. Bilirubin, a yellow pigment derived from the breakdown of heme, is actively secreted into bile by liver cells. In situations of high heme turnover such as chronic hemolytic states (eg, sickle cell anemia), calcium bilirubinate can crystallize from solution and form stones. • Chronic gallstones may cause progressive brosis of the gallbladder wall and loss of function.

RISK FACTO RS FIGURE 69-1 Ultr sound s owing 2 e c og e nic g llstone s in t e g llb l d d e r. Note t e b se nce o e c oe s p oste rior to t e g llstone c lle d “s d owing ” (arrowhe ad s). (Re p rod uce d with p e rmission from Schwartz’s Princip le s of Surg e ry. 9th e d . Ne w York, NY: McGraw-Hill; 2010:1141, Fig ure . 32-6. Cop yrig ht 2010, McGraw-Hill.)

• Genetic mutations can result in reduction of bile acids and lecithin that predispose some patients to stone formation. A high prevalence of gallstones is found in rst-degree relatives of patients with gallstones and among Native Americans, Chilean Indians, and Chilean Hispanics. 1

Ga LLSt O Ne S

PART 10

GASTRO INTESTINAL

• In a case-control study, the prevalence of gallstones was 28.6% in rstdegree relatives of subjects with gallstones versus 12.4% in rst-degree relatives of subjects without gallstones (relative risk [RR] 1.80, 95% con dence interval [CI] 1.29-2.63). 3 • Other risk factors for gallstones include rapid weight loss (10%-20% of these patients form stones), 1 increasing age, liver or ileal disease, and cystic brosis.

DIAGNO SIS CLINICAL FEATURES • Symptoms of gallstones are caused from in ammation or obstruction as stones migrate into the cystic or common bile duct (CBD). ° Biliary colic is a steady, severe pain or ache, usually of sudden onset, located in the epigastrium or RUQ. Pain episodes last between 30 minutes and 5 hours and may radiate to the interscapular area, right scapula, or right shoulder. ° Gallstone-related pain may be precipitated by a fatty meal, a regular meal, or a large meal followed by a prolonged fast. ° Pain is recurrent and often nocturnal. • RUQ tenderness may be elicited on physical examination. • Nausea and vomiting are common. • Accompanying fever and chills suggests a complication of gallstones. Complications are more common in patients with a calci ed gallbladder or in those who have had a previous episode of acute cholecystitis. 1 LABO RATO RY STUDIES • No laboratory testing is usually indicated as the results are usually normal. However, an elevated γ-glutamyl transpeptidase suggests a CBD stone. In a study of patients with acute calculous gallbladder disease, investigators found a 1-in-3 chance of CBD stones when the γ-glutamyl transpeptidase level was above 90 U/ L and a 1-in-30 chance when the level was less than 90 U/ L. 6 IMAGING

FIGURE 69-2 G llstone s visib le in t e g llb l d d e r o 43-ye r-old wom n wit rig t up p e r q u d r nt (RUQ ) p in nd p ositive Murp y sig n. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Radioisotope scans (eg, technetium [Tc]-99m hepatoiminodiacetic acid [HIDA]) can be used to con rm acute cholecystitis (nonvisualizing gallbladder) and can be useful in evaluating functional abnormalities. • Endoscopic retrograde cholangiopancreatography is used for imaging bile ducts. Stones in bile appear as lling defects in the opaci ed ducts. Endoscopic retrograde cholangiopancreatography is usually performed in conjunction with endoscopic retrograde sphincterotomy and gallstone extraction.

DIFFERENTIAL DIAGNO SIS Severe epigastric and RUQ pain can be seen in the following conditions: • Acute cholecystitis—Pain may radiate to the back, and fever is usually present. Physical examination can reveal RUQ rigidity and guarding with a positive Murphy sign (RUQ pain worsening with deep

• Ultrasound is the diagnostic test of choice and is 95% accurate for stones as small as 2 mm in diameter (see Figure 69-1). 1 Shadowing, a discrete acoustic shadow caused by the absorption and re ection of sound by the stone that changes with patient positioning, is an important diagnostic feature that is shown in Figures 69-1 and 69-2. • In one study, high-resolution ultrasound was more accurate than endoscopic ultrasonography or CT in differentiating benign disease from malignancy in cases with gallbladder polypoid lesions. 7 • Gallstones may be seen on plain lm, but only calci ed stones are seen (Figures 69-3 and 69-4). This includes only 10% to 15% of cholesterol stones and 50% of pigmented stones. 1 Stones may be single or multiple and the gallbladder wall may be calci ed (referred to as a porcelain gallbladder), indicating severe chronic cholecystitis or adenocarcinoma. • CT is less sensitive and more expensive than ultrasound for the detection of gallstones (Figures 69-5 and 69-6). However, CT can detect both radiopaque stones and radiolucent stones. • An oral cholecystogram can be used to assess cystic duct patency and emptying function. This test has largely been replaced by gallbladder ultrasound.

FIGURE 69-3 Pl in f lm s owing multip le g llstone s (white arrow). (Re p rod uce d with p e rmission from Schwartz DT, Re isd orff EJ. Eme rg e ncy R d iolog y. Ne w York, NY: McGraw-Hill; 2000:536, Fig ure . 19-37. Cop yrig ht 2000, McGraw-Hill.)

345

346

PART 10

GASTRO INTESTINAL

Ch a pt e r 69

FIGURE 69-6 R d iog r p ic Me rce d e s-Be nz sig n se e n o n CT cut t roug t e g llb l d d e r (t e g llstone s p rod uce b l ck p tte rn t t re se mb le s Me rce d e s-Be nz log o in t e ce nte r). (Re p rod uce d with p e rmissio n from Mike Fre ckle ton, MD.)

amylase are found and pancreatic pseudocysts or abscess may be present on ultrasound (see Chapter 75, Pancreatitis).

FIGURE 69-4 G llstone ile us in n e lde rly p tient wit di be te s; note dil te d loops o sm ll bowe l nd n e ctopic g llstone (arrow). (Re prod uce d with pe rmission from Schwartz DT, Re isdorff EJ. Eme rge ncy R diology. Ne w York, NY: McGraw-Hill; 2000:527, Fig ure . 19-21. Cop yrig ht 2000, McGraw-Hill.)

inspiration while the examiner maintains steady pressure below the right costal margin). White blood count, serum amylase, aspartate transaminase, and alanine transaminase may all be elevated. • Pancreatitis—Pain is located in the midepigastrium and left upper quadrant, but may radiate to the RUQ. Abdominal distention and diminished bowel sounds may be present. Elevations in lipase and

• Peptic ulcer disease—Pain may be described as burning and is usually epigastric and often relieved by antacids. Onset is 1 to 3 hours after meals or following nonsteroidal anti-in ammatory drug usage. Stool Hemoccult testing may be positive. An ulcer may be visualized on upper gastrointestinal (GI) barium swallow or endoscopy (see Chapter 76, Peptic Ulcer Disease). • Hepatitis—Other symptoms and signs include malaise, anorexia, pruritus, tender liver, and low-grade fever. Jaundice may be present and urine may be dark (ie, bilirubinuria). Aspartate transaminase and alanine transaminase are elevated (see Chapter 74, Liver Disease).

MANAGEMENT • Silent gallstones may be managed expectantly; prophylactic cholecystectomy is unwarranted based on the few who develop symptoms over time and the very low rate of complications (3%-4%). 8 There are no randomized controlled trials comparing cholecystectomy to watchful waiting for silent gallstones. 9 SO R • Cholecystectomy should be considered for patients with the following symptoms:1 ° Frequent symptoms that interfere with daily life ° A prior complication of gallstone disease ° The presence of an underlying condition (eg, calci ed gallbladder) that predisposes the patient to increased risk of complications • Laparoscopic cholecystectomy is the surgical treatment of choice because of the low rate of complications (4%) and mortality ( 1000 mg/ dL). ° Hypercalcemia caused by hyperparathyroidism. ° Post-ERCP (~ 5% o patients have pancreatitis within 30 days o ERCP). ° Congenital anomalies o pancreatic biliary system ■ Pancreatic divisum (absence o usion between dorsal and ventral ductal systems, leading to stenosis, which prevents normal drainage o pancreatic secretions, leading to increased pressure within pancreatic ducts, eg, ductal hypertension). ■ Pancreatic divisum, however, occurs in about 5% o the healthy population, and only a small minority develop pancreatitis. ° Consider genetic causes in unexplained recurrent pancreatitis.

HISTO RY/ SYMPTO MS Speci cally ask about the ollowing: • Location o pain—Pancreatitis causes epigastric or RUQ pain. • Onset and duration o pain ° Pain rom gallstone pancreatitis is sudden in onset. ° Pain rom alcoholic pancreatitis is more gradual in onset. ° Pancreatitis pain is usually acute in onset and constant in duration. • Radiation o pain—pain radiates to the back. • Nausea/ vomiting—These are common with pancreatitis. PHYSICAL EXAMINATIO N speci cally look or or establish the ollowing: • Tenderness in the epigastric area and RUQ. • Ecchymoses in the f ank (Turner sign or Grey-Turner sign as seen in Figure 75-2) or periumbilical area (Cullen sign as seen in Figure 75-3) are seen in less than 3% o patients, but their presence is associated with high mortality (~ 40%).

373

374

PART 10

GASTRO INTESTINAL

Ch a pt e r 75

other inf ammatory diseases in the abdomen, such as penetrating peptic ulcers and cholecystitis. ° Macroamylasemia is the presence o high serum but low urine amylase. • Serum lipase concentrations remain higher or longer than serum amylase concentrations. IMAGING • Acute abdominal series might show a localized ileus.

FIGURE 75-2 Turne r sig n se e n in he morrhag ic p ancre atitis. This 40-ye ar-old woman had worse ning e p ig astric p ain o 5 d ays’ d uration. O n e xamination, she had hyp ote nsion, a b oard -like ab d ome n, and e xte nsive e cchymose s ove r he r rig ht loin. Eme rg e ncy ce liotomy d isclose d a b og g y p ancre as, at ne crosis o the ome ntum, and re d d ish-b rown pe ritone al f uid . The e cchymotic d iscoloration o he r loin (Turne r’s sig n) is not sp e ci c or p ancre atitis. In the ab se nce o trauma or blood disord e rs, it is a mani e station o re trop e ritone al or intra-ab d ominal he morrhag e . The imag e shown d isp lays anothe r ind ication o re trop e ritone al he morrhag e : e cchymotic p atche s on the ante rolate ral sur ace o one or b oth thig hs just b e low the ing uinal lig ame nt (Fox sig n). The d iscoloration (arrows) p re sumab ly re sults rom b lood y f uid tracking e xtrap e ritone ally along the ascia o the p soas and iliacus muscle s, be coming sub cutane ous in the up p e r thig h. (Re p rod uce d with p e rmission from Fre d HL, van Dijk HA. Imag e s o Me morab le Case s: 50 Ye ars at the Be d sid e . Houston, TX: Long Tail Pre ss/Rice Unive rsity Pre ss; 2007.)

LABO RATO RY TESTING • Serum amylase that is more than 3 times normal supports the diagnosis. ° Amylase values rise within several hours o symptom onset and returns to normal within 5 days. ° Normal amylase values may be seen in about 20% o patients with acute pancreatitis on admission, possibly because o rapid urinary clearance. ° False-positive increases in serum amylase are seen in macroamylasemia, renal insu ciency (because o decreased clearance o amylase), salivary gland diseases (ie, mumps and parotitis), and

FIGURE 75-3 Culle n sig n in acute p ancre atitis. This 36-ye ar-old man p re se nte d with a 4-d ay history o se ve re e p ig astric p ain ollowing an alcoholic b ing e . His se rum amylase le ve l was 821 U/L, and an ab d ominal comp ute d tomog rap hic scan showe d marke d inf ammatory chang e s in his p ancre as, ome ntum, and surround ing me se nte ry. In p atie nts with acute p ancre atitis, e cchymose s o the ab d ominal wall may ap p e ar ne ar the mid line anywhe re rom the umb ilicus to the symp hysis p ub is (Culle n sig n). The se e cchymose s, howe ve r, are not sp e ci c o r p ancre atitis and , in the ab se nce o trauma and b lood d isord e rs, me re ly sig nal re trop e ritone al or intra-ab d ominal he morrhag e . (Re p rod uce d with p e rmission from Fre d HL, van Dijk HA. Imag e s o Me morab le Case s: 50 Ye ars at the Be d sid e . Houston, TX: Long Tail Pre ss/ Rice Unive rsity Pre ss; 2007.)

• Abdominal computed tomographic (CT) scan is 90% sensitive and speci c or the diagnosis o pancreatitis. ° CT can also be help ul in identi ying gallstones and ruling out other causes o pain. • Ultrasound is more sensitive or identi ying gallstones, gall bladder sludge, and bile duct dilation.

DIFFERENTIAL DIAGNO SIS • Cholang itis

RUQ p ain, e ve r, jaund ice ; b ilirub in > 4; asp artate aminotrans e rase (AST) > 1000

• Acute chole cystitis Pain in the e p ig astrium and RUQ and b iliary colic rad iate s to rig ht should e r or should e r b lad e ; live r unction te sts (LFTs) incre ase d • Inte stinal ob struction

Pain is colicky; ob structive p atte rn se e n on imag ing

• Disse cting aortic ane urysm

Sud d e n onse t; p ain may rad iate to lowe r e xtre mitie s

• Pe r orate d p e p tic ulce r d ise ase (PUD)

RUQ or mid e p ig astric p ain; sud d e n onse t; re e intrap e ritone al air; p e r oratio n o PUD mimics chole cystitis

• Pulmonary/p le ural d ise ase

Consid e r i p le uritic p ain is a d ominant symp tom

• He p atitis

Malaise ; alanine aminotrans e rase (ALT) > 1000

• In e rior wall myocard ial in arction (MI)

Mid e p ig astric p ain; shortne ss o b re ath; ab normal e le ctrocard iog ram; MI should b e in the d i e re ntial d iag nosis in all p atie nts with up p e r ab d ominal p ain

• Me se nte ric ische mia

Ab d ominal p ain se ve re , out o p rop ortion to te nd e rne ss, with a airly b e nig n e xamination; look or p ostp rand ial ab d ominal p ain, we ig ht loss, and ab d ominal b ruit

• Fitz-Hug h-Curtis synd rome

Gonococcal p e rihe p atitis with RUQ p ain, ad ne xal te nd e rne ss

• Pne umonia

Fe ve r and re sp iratory symp toms (d ysp ne a, coug h, sp utum, che st p ain) p re se nt

• Ap p e nd icitis

Pain may start in e p ig astrium b ut e ve ntually move s to rig ht lowe r q uad rant (RLQ )

ACUTE PANCREATITIS

PART 10

GASTRO INTESTINAL

MANAGEMENT ACUTE MANAGEMENT • Determine the cause o pancreatitis. • Studies have shown that ERCP or persistent biliary obstruction lowers the risk o pancreatitis-associated complications. 2 SO R • Supportive ° Intravenous f uids are given to maintain adequate intravascular volume to prevent hemoconcentration (250-500 cc/ h i no renal or heart disease)2; a hematocrit value above 44 is a risk actor or pancreatic necrosis. ° Pain medications. ° Supplemental oxygen. ° Antiemetics as needed. ° Nothing by mouth—to avoid stimulation o the pancreas; begin eeding when pain is diminished and there is no small bowel ileus (usually 2-3 days). ° Venous thromboembolism prophylaxis. • Consider in ection o pancreatic necrosis (usually occurs 1-2 weeks a ter onset o the symptoms) i there is ever, leukocytosis, ailure to improve, or sudden deterioration (Figure 75-4). ° This occurs during second week in about 50% o patients. ° I suspected, give intravenous imipenem or meropenem or 14 days. ° Consider prophylactic antibiotics in severe acute pancreatitis (> 30% necrosis seen on CT) to prevent translocation o bacteria rom gut to pancreatic bed. 2 SO R ° Surgical consult is needed i there is biliary pancreatitis or in ected necrosis, abscess, or pseudocyst. LO NG-TERM MANAGEMENT • Pseudocysts develop over the course o weeks and are caused by pancreatic duct disruptions that lead to localized collection o f uid with high concentrations o pancreatic enzymes (Figure 75-5).

FIGURE 75-5 Two p se ud ocysts (ye llow arrows) in the p ancre as se e n on this comp ute d tomog rap hic scan 4 we e ks a te r an e p isod e o acute g allstone p ancre atitis. Disrup tion o the p ancre atic d uct rom inf ammation allows e nzyme s and f uid to colle ct in an are a walle d o b y b rous tissue and g ranulation tissue . Consid e r the d iag nosis o p se ud ocyst whe n p ain p e rsists a te r an e p isod e o acute p ancre atitis. Most re solve with sup p ortive care , b ut ab out 10% b e come in e cte d . (Re p rod uce d with p e rmission from Gary Fe re nchick, MD.)

• I there are no symptoms, treat conservatively. • Obtain a surgical consult i the patient has pain unresponsive to medical treatment; especially i the disease is limited to the head or tail o the pancreas, the pancreatic duct is dilated.

PRO GNO SIS/ CLINICAL CO URSE • Severity is determined by the presence or absence or organ ailure or the development o local complications. • O the cases, 80% are mild and sel -limited. • Severe disease associated with complications, such as multiple organ dys unction, is seen in 20% o cases. O the patients with severe pancreatitis, up to 30% will die; severe pancreatitis is commonly associated with the ollowing: ° Hypovolemia ° Renal impairment ° Pulmonary complications (mild → acute respiratory distress syndrome [ARDS]) • Pancreatic necrosis is the most severe local complication and is commonly associated with pancreatic in ections (Figure 75-4).

FIGURE 75-4 Acute p ancre atitis with ne crosis o p ancre atic tissue (re d arrow) on this comp ute d tomog rap hic scan. Note the e d e matous p ancre as with e vid e nce o air (b lack) within the ne crotic mass. (Re p rod uce d with p e rmission from Gary Fe re nchick, MD.)

• Markers o the risk o severe pancreatitis include ° C-reactive protein (CRP) or predicting severity o pancreatitis— Use ul marker o necrosis (> 150 mg/ L) when measured 48 hours a ter admission 3 ° CT severity index (Table 75-1) ° Clinically with Ranson criteria, Acute Physiology and Chronic Health Evaluation II (APACHE II), or Sequential Organ Failure Assessment (SOFA) scores

375

PART 10

376

CHAPTER 75

GASTRO INTESTINAL TABLE 75-1 CT Se ve rity Ind e x (CSI)

■

Pro g no st ic Ind icat o r

Po int s

CT Grad e

■ ■

SIRS Age above 60 Presence o pleural e usion

• Obesity (body mass index [BMI] > 30) is associated with 3 times increased risk o severe clinical course.

Normal p ancre as

0

Enlarg e d p ancre as

1

PATIENT RESO URCES

Fat strand ing

2

Sing le colle ction o f uid

3

• PubMed Health. Acute pancreatitis—http:/ / www.ncbi.nlm.nih .gov/ pubmedhealth/ PMH0001332/ .

Multip le colle ctions o f uid or g as

4

• National Digestive Diseases Information Clearinghouse. Pancreatitis—http:/ / digestive.niddk.nih.gov/ ddiseases/ pubs/ pancreatitis/ index.aspx.

None

0

Ne crosis 30%

2

• American Gastroenterological Association. Understanding Pancreatitis—http:/ / www.gastro.org/ patient-center/ digestive-conditions/ pancreatitis.

Ne crosis 50%

4

Ne crosis > 50%

6

Ne crosis Score

CSI Sco re O ut co me

PRO VIDER RESO URCES

• UK Working Party on Acute Pancreatitis. UK guidelines or the management o acute pancreatitis. Gut. 2005;54(suppl 3):iii1-iii9. doi:10.1136/ gut.2004.057026. http:/ / www.ncbi.nlm.nih .gov/ pmc/ articles/ PMC1867800/ pdf/ v054p0iii1.pdf.

0-3

4-6

7-10

Comp lications (%)

8

35

92

REFERENCES

De ath (%)

3

6

17

1. Frossard JL, Steer ML, Pastor CM. Acute pancreatitis. Lancet. 2008;371(9607):143-152.

° These measure injuries in extrapancreatic organs; the greater number o organs involved, the higher the score will be. ° The Bedside Index o Severity has recently been shown to be as accurate as the APACHE II score in predicting mortality in acute pancreatitis. Mortality is less than 1% or a score less than 2 and 20% or a score o 5. 4 One point is given or each o the ollowing: ■ Serum urea nitrogen (BUN) greater than 25 mg/ dL ■ Impaired mental status

2. Tonsi AF, Bacchion M, Crippa S, Maleo G, Bassi C. Acute pancreatitis at the beginning o the 21st century. The state o the art. World J Gastroenterol. 2009;15:2945-2959. 3. Whitcomb DC. Clinical practice. Acute pancreatitis. N Engl J Med. 2006;354(20):2142-2150. 4. Wu BU, Johannes RS, Sun S, Tabak Y, Conwell DL, Banks PA. The early prediction o mortality in acute pancreatitis: a large populationbased study. Gut. 2008;57(12):1698-1703.

PEPTIC ULCER DISEASE

PART 10

GASTRO INTESTINAL

76 PEPTIC ULCER DISEASE He nd Azhary, MD Mind y A. Smith, MD, MS

PATIENT STO RY A 41-year-old man presents with a 4-month history o epigastric pain. The pain is dull, achy, and intermittent; there is no radiation o the pain; and it has not changed in character since it began. Co ee intake seems to exacerbate the symptoms, whereas eating or drinking milk helps. In requently, he is awakened at night rom the pain. He reports no weight loss, vomiting, melena, or hematochezia. On examination, there is mild epigastric tenderness with no rebound or guarding. The reminder o the examination is unremarkable. A stool antigen test is positive or Helicobacter pylori, and the patient is treated or peptic ulcer disease with eradication therapy.

INTRO DUCTIO N Peptic ulcer disease (PUD) is a disease o the gastrointestinal (GI) tract characterized by a break in the mucosal lining o the stomach or duodenum secondary to pepsin and gastric acid secretion; this damage is greater than 5 mm in size and with a depth reaching the submucosal layer. 1

EPIDEMIO LO GY • PUD is a common disorder a ecting approximately 4.5 million people annually in the United States. It encompasses both gastric and duodenal ulcers (Figures 76-1 and 76-2). 2 • One-year point prevalence is 1.8%, and the li etime prevalence is 10% in the United States. 2 • Prevalence is similar in both sexes, with increased incidence with age. 1 Duodenal ulcers most commonly occur in patients between the ages o

FIGURE 76-2 End oscop ic vie w of p ylo ic ulce nd n e o sio n of t e mucos . T e ulce nd e osion e b e nig n p e p tic ulce d ise se nd not m lig n nt. (Re p rod uce d with p e rmission from Marvin De re zin, MD.)

30 and 55 years, whereas gastric ulcers are more common in patients between the ages o 55 and 70 years. 2 • PUD incidence in H. pylori-in ected individuals is approximately 1% per year (6- to 10- old higher than unin ected subjects). 1 • Physician o ce visit and hospitalization or PUD have decreased in the last ew decades. 1 • The current U.S. annual direct and indirect health care costs o PUD are estimated at approximately $10 billion. However, the incidence o peptic ulcers keeps declining, possibly as a result o the increasing use o proton pump inhibitors and eradication o H. pylori in ection. 3

ETIO LO GY AND PATHO PHYSIO LO GY • Causes o PUD include the ollowing: ° NSAIDs, chronic H. pylori in ection,2and acid hypersecretory states such as Zollinger-Ellison syndrome. ° Uncommon causes include Cytomegalovirus (especially in transplantation recipients), systemic mastocytosis, Crohn disease, lymphoma, and medications (eg, alendronate). 2 2 Up to 10% o ulcers are idiopathic. ° • In ection with H. pylori, a short, spiral-shaped, microaerophilic gramnegative bacillus, is the leading cause o PUD. It is associated with up to 70% to 80% o duodenal ulcers. 2 • H. pylori colonize the deep layers o the gel that coats the mucosa and disrupt its protective properties causing release o certain enzymes and toxins. These make the underlying tissues more vulnerable to damage by digestive juices and thus cause injury to the stomach (Figures 76-1 to 76-3) and duodenum cells. 1 • NSAIDs are the second most common cause o PUD and account or many H. pylori-negative cases.

FIGURE 76-1 End oscop ic p ictu e s of g st ic ulce . Pl te s 1 nd 2 s ow e osions. Note t t t e b le e d ing is f om b iop sy. Pl te s 3 nd 4 s ow l g e c te wit e vid e nce of e ce nt b le e d ing . Bot e consiste nt wit se ve e ulce d ise se . (Re p rod uce d with p e rmission from Michae l Harp e r, MD.)

• NSAIDs and aspirin inhibit mucosal cyclooxygenase activity reducing the level o mucosal prostaglandin causing de ects in the protective mucous layer. • There is a 10% to 20% prevalence o gastric ulcers and a 2% to 5% prevalence o duodenal ulcers in long-term NSAID users. 2 The annual

377

PART 10

378

GASTRO INTESTINAL

Ch a pt e r 76

• Around 20% o patients with ulcer complications such as bleeding and nearly 61% o patients with NSAID-related ulcer complications have no antecedent symptoms. • Rare and nonspeci c physical ndings include the ollowing: ° Epigastric tenderness ° Heme-positive stool ° Hematemesis or melena in cases o GI bleeding TYPICAL DISTRIBUTIO N • Duodenal ulcers occur most o ten in the rst portion o the duodenum (> 95%), with approximately 90% o ulcers located within 3 cm o the pylorus. 1

FIGURE 76-3 Stom c ulce in p tie nt wit with p e rmission from Michae l Harp e r, MD.)

i t l e ni . (Re p rod uce d

risk o a li e-threatening ulcer-related complication is 1% to 4% in long-term NSAID users, with older patients having the highest risk. 4

RISK FACTO RS • Severe physiologic stress—Burns, central nervous system trauma, surgery, and severe medical illness increase the risk or secondary (stress) ulceration. 5 • Smoking—Evidence that tobacco use is a risk actor or duodenal ulcers in not conclusive, with several studies producing contradictory ndings. However, smoking in the setting o H. pylori in ection may increase the risk o relapse o PUD. 6 • Alcohol use—Ethanol is known to cause gastric mucosal irritation and nonspeci c gastritis. Evidence that consumption o alcohol is a risk actor or duodenal ulcer is inconclusive. 6 • Medications—Corticosteroids alone do not increase the risk or PUD; however, they can potentiate ulcer risk in patients who use NSAIDs concurrently. 5

DIAGNO SIS CLINICAL FEATURES • Epigastric pain (dyspepsia), the hallmark o PUD, is present in 80% to 90% o patients; however, this symptom is not sensitive or speci c enough to serve as a reliable diagnostic criterion or PUD. Pain is typically described as gnawing or burning, occurring 1 to 3 hours a ter meals and relieved by ood or antacids. It can occur at night, and sometimes radiates to the back. 2 Less than 25% o patients with dyspepsia have ulcer disease at endoscopy. 5 • Other dyspeptic symptoms including belching, bloating, and distention are common but also not speci c eatures o PUD as they are commonly encountered in many other conditions. • Additional symptoms include atty ood intolerance, heartburn, and chest discom ort.

• Benign gastric ulcers are located most commonly in the antrum (60%) and at the junction o the antrum and body on the lesser curvature (25%) (Figure 76-3). 1 LABO RATO RY STUDIES • In most patients with uncomplicated PUD, routine laboratory tests are not help ul. 5 • Noninvasive tests include serum H. pylori antibody detection, ecal antigen tests, and urea breath tests; the latter 2, i positive, indicate active disease. 7 • Serum enzyme-linked immunosorbent assay (ELISA) is the least accurate test and is use ul only or diagnosing the initial in ection. • The stool antigen test is less convenient but is highly accurate and also can be used to con rm H. pylori eradication, as can the urea breath test. 7 • Obtaining a serum gastrin may be use ul in patients with recurrent, re ractory, or complicated PUD and in patients with a amily history o PUD to screen or Zollinger-Ellison syndrome. 1 IMAGING • Upper endoscopy is the procedure o choice or the diagnosis o duodenal and gastric ulcers (Figures 76-1 to 76-3). 2 • Endoscopy provides better diagnostic accuracy than barium radiography and a ords the ability to biopsy or the presence o malignancy and H. pylori in ection. Endoscopy is usually reserved or the ollowing situations: ° Patients with red f ag signs (eg, bleeding, dysphagia, severe pain, abdominal mass, recurrent vomiting, weight loss) or age older than 55 years ° Patients who ail initial therapy ° Patients whose symptoms recur a ter appropriate therapy • Duodenal ulcers are virtually never malignant and do not require biopsy. 2 • Gastric ulcers should be biopsied because 3% to 5% o benign-appearing gastric ulcers prove to be malignant. 2 • Barium upper gastrointestinal (UGI) series is an acceptable alternative to endoscopy but is not as sensitive or the diagnosis o small ulcers (< 0.5 cm) and does not allow or biopsy with gastric ulcer. 7

• Nausea and anorexia may occur with gastric ulcers.

• Patient’s testing positive or PUD should undergo noninvasive testing or H. pylori.

• Signi cant vomiting and weight loss are unusual with uncomplicated ulcer disease and suggest gastric outlet obstruction or gastric malignancy. 2

• UGI series has limited accuracy in distinguishing benign rom malignant gastric ulcers; there ore, all patients diagnosed this way should be reevaluated with endoscopy a ter 8 to 12 weeks o therapy.

PEPTIC ULCER DISEASE

DIFFERENTIAL DIAGNO SIS Disease processes that may present with “ulcer-like” symptoms include the ollowing: • Nonulcer or unctional dyspepsia (FD)—The most common diagnosis among patients seen or upper abdominal discom ort; it is a diagnosis o exclusion. Dyspepsia has been reported to occur in up to 30% o the U.S. population. • Gastroesophageal ref ux—Classic symptoms are heartburn (ie, substernal pain that may be associated with acid regurgitation or a sour taste) aggravated by bending orward or lying down, especially a ter a large meal. Endoscopy is considered i symptoms ail to respond to treatment (eg, histamine-2-receptor agonist, proton pump inhibitor [PPI]) or red f ag signs and symptoms occur. • Gastric cancer—Most patients do not become symptomatic until late in the disease; symptoms include upper abdominal pain, postprandial ullness, anorexia and mild nausea, vomiting (especially with pyloric tumors), weight loss, and a palpable mass. Endoscopic biopsy is used to make this diagnosis (see Chapter 60, Gastric Cancer). • Biliary colic is characterized by discrete, intermittent episodes o pain that should not be con used with other causes o dyspepsia. • Gastroduodenal Crohn disease—Symptoms include epigastric pain, nausea, and vomiting. On endoscopy, patients o ten have H. pylori-negative gastritis and may develop gastric outlet obstruction. Extraintestinal maniestations include erythema nodosum, peripheral arthritis, conjunctivitis, uveitis, and episcleritis. Endoscopy shows an inf ammatory process with skip lesions, stulas, aphthous ulcerations, and rectal sparing. Small bowel involvement is seen on imaging with longitudinal and transverse ulceration (cobblestoning) in addition to segmental colitis and requent stricture (see Chapter 77, Inf ammatory Bowel Disease).

MANAGEMENT • The approach to patients with dyspepsia includes per orming endoscopy or patients with red f ag symptoms or who are older than age 55 years. For patients who have an ulcer identi ed on endoscopy, eradication o H. pylori is attempted (as below) and a PPI is continued or 4 to 8 weeks. For those without an ulcer on endoscopy, treatment with a PPI or H2 blocker is provided. 4 • For patients without red f ag ndings, testing and treating or H. pylori; counseling to avoid smoking, alcohol, and NSAIDs; and appropriate use o antisecretory therapy or 4 weeks will be success ul in the majority o patients. 4 • The goals o treatment o active H. pylori-associated ulcers are to relieve dyspeptic symptoms, to promote ulcer healing, and to eradicate H. pylori in ection. Eradication o H. pylori is better than ulcerhealing drug therapy or duodenal ulcer healing8 and greatly reduces the incidence o ulcer recurrence rom 67% to 6% in patients with duodenal ulcers and rom 59% to 4% in patients with gastric ulcers. 4 • The worldwide empiric use o traditional triple therapy with PPI, clarithromycin, and amoxicillin no longer provides an acceptable cure rate (cure rate below 80%) because o the increasing prevalence o clarithromycin resistance. 9 • Four drug combinations currently provide the best results and consist o 2 general combinations: (1) a PPI, amoxicillin, clarithromycin, metronidazole/ tinidazole given either sequentially or concomitantly,

PART 10

GASTRO INTESTINAL or (2) a PPI, a bismuth, tetracycline HCL, and metronidazole/ tinidazole. 9 SO R • A PPI, levof oxacin, and amoxicillin or 10 days appears to be more e ective and better tolerated than a PPI, bismuth, tetracycline, and metronidazole in patients with persistent H. pylori in ection but requires validation in North America. 7 • The European Helicobacter Study Group consensus guideline states that triple therapy (PPI-clarithromycin-amoxicillin/ metronidazole) or Bismuth quadruple therapy remain rst-line treatment in areas with low clarithromycin resistance. For areas with high clarithromycin resistance (> 20%), Bismuth or non-Bismuth quadruple therapy are pre erred. 10 • Treat NSAID-induced ulcers with cessation o NSAIDs, i possible, and an appropriate course o standard ulcer therapy with an H2-receptor antagonist or a PPI. I NSAIDs are continued, prescribe a PPI. SO R • H. pylori-negative ulcers that are not caused by NSAIDs can be treated with appropriate antisecretory therapy, either H2-receptor antagonist or PPI. SO R • For patients with bleeding peptic ulcers, high-dose PPIs do not reduce rates o rebleeding, surgical intervention, or mortality a ter endoscopic treatment compared with non–high-dose PPIs. 11

PREVENTIO N • In a large randomized controlled trial (RCT) (N = 2426) o PUD prevention in patients taking low-dose acetylsalicylic acid who were at risk or ulcer development (eg, prior ulcer, GI symptoms and erosions, age older than 65 years), esomeprazole 40 mg or 20 mg reduced the rate o endoscopically con rmed peptic ulcer development (1.5% and 1.1%, respectively) versus placebo (7.4%). 12 • Authors o a metaanalysis ound the use o prophylactic H2 blockers to prevent stress ulcers was not necessary in patients receiving enteral nutrition and that such therapy was associated with pneumonia and higher risk o hospital mortality. 13 In another metaanalysis, PPIs were similar to H2-receptor antagonists in terms o stress-related UGI bleeding prophylaxis, pneumonia, and mortality among patients admitted to intensive care units. 14

PRO GNO SIS • Hospitalization rate is approximately 30 per 100,000 cases. 5 • Mortality rate is approximately 1 per 100,000 cases. 5 • When the underlying cause is addressed, the prognosis is excellent. • With the eradication o H. pylori in ection, there has been a decrease in the ulcer recurrence rate rom 60% to 90% to approximately 10% to 20% with the regard to NSAID-related ulcers. 5 • The incidence o per oration is approximately 0.3% per patient year, and the incidence o obstruction is approximately 0.1% per patient year. 5

FO LLO W-UP • Endoscopy is required to document healing o gastric ulcers and to rule out gastric cancer; this is per ormed 6 to 8 weeks a ter the initial diagnosis.

379

PART 10

380

GASTRO INTESTINAL

Ch a PTEr 76

• Con rmation o H. pylori eradication in patients with uncomplicated ulcers is not necessary.

4. Ramakrishnan K, Salinas RC. Peptic ulcer disease. Am Fam Physician. 2007;76(7):1005-1012.

• Con rmation o healing with endoscopy is required in all patients with ulcer complicated by bleeding, per oration, or obstruction.

5 Anand BS, Bank S, Qureshi WA, et al. Peptic Ulcer D isease. http:/ / emedicine.medscape.com/ article/ 181753-overview. Accessed October 2011.

• For patients without initial endoscopy who have persistent symptoms ollowing initial treatment, the PPI or H2 blocker can be continued or another 4 to 8 weeks. 4 I there is inadequate response to therapy, endoscopy and evaluation or hypersecretory states should be considered.

PATIENT EDUCATIO N Patients with PUD should be encouraged to eat balanced meals at regular intervals, avoid heavy alcohol use, and avoid smoking (which has been shown to retard the rate o ulcer healing and increase the requency o recurrences); stress-reduction counseling might be help ul in individual cases. PATIENT RESO URCES

• National Digestive Diseases Information Clearing House—http:/ / digestive.niddk.nih.gov/ ddiseases/ pubs/ pepticulcers_ez/ index.htm. • Centers for Disease Control and Prevention—http:/ / www.cdc .gov/ ulcer/ . PRO VIDER RESO URCES

• Medscape. Peptic Ulcer Disease—http:/ / emedicine.medscape .com/ article/ 181753. REFERENCES 1. Del Valle J. Peptic ulcer disease and related disorders. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds. Harrison’s Principles of Internal Medicine, 16th ed. New York, NY: McGraw-Hill; 2005:1746-1762. 2. McPhee SJ, Papadakis MA, Tierney LW Jr. Current Medical Diagnosis andTreatment. New York, NY: McGraw-Hill; 2007. 3. University o Michigan Health System. Peptic Ulcer Disease. http:/ / www.cme.med.umich.edu/ pd / guideline/ PUD05.pd . Accessed October 2011.

6. Aldoori WH, Giovannucci EL, Stamp er MJ, et al. A prospective study o alcohol, smoking, ca eine, and the risk o duodenal ulcer in men. Epidemiology. 1997;8(4):420-424. 7. Chey WD, Wong BCY; Practice Parameters Committee o the American College o Gastroenterology. American College o Gastroenterology guideline on the management o Helicobacter pylori in ection. Am J Gastroenterol. 2007;102:1808-1825. 8. Ford AC, Delaney B, Forman D, Moayyedi P. Eradication therapy or peptic ulcer disease in Helicobacter pylori positive patients. Cochrane Database Syst Rev. 2006;(2):CD003840. 9. Graham DY, Rugge M. Diagnosis and evaluation o dyspepsia: clinical practice. J Clin Gastroenterol. 2010;44(3):167-172. 10. Mal ertheiner P, Megraud F, O’Morain CA, et al; The European Helicobacter Study Group (EHSG). Management o Helicobacter pylori in ection—The Maastricht IV/ Florence Consensus Report. Gut. 2012;61:646-664. 11. Wang CH, Ma MH, Chou HC, et al. High-dose vs non-high-dose proton pump inhibitors a ter endoscopic treatment in patients with bleeding peptic ulcer: a systematic review and meta-analysis o randomized controlled trials. Arch Intern Med. 2010;170(9): 751-758. 12. Scheiman JM, Devereaux PJ, Herlitz J, et al. Prevention o peptic ulcers with esomeprazole in patients at risk o ulcer development treated with low-dose acetylsalicylic acid: a randomised, controlled trial (OBERON). Heart. 2011;97(10):797-802. 13. Marik PE, Vasu T, Hirani A, Pachinburavan M. Stress ulcer prophylaxis in the new millennium: a systematic review and meta-analysis. Crit Care Med. 2010;38(11):2222-2228. 14. Lin PC, Chang CH, Hsu PI, et al. The e cacy and sa ety o proton pump inhibitors vs histamine-2 receptor antagonists or stress ulcer bleeding prophylaxis among critical care patients: a meta-analysis. Crit Care Med. 2010;38(4):1197-1205.

INFLAMMATO RY BO WEL DISEASE

77 INFLAMMATO RY BO WEL DISEASE Mind y A. Smith, MD, MS

PATIENT STO RY A 30-year-old man presents with several days o diarrhea with a small amount o rectal bleeding with each bowel movement. This is his second episode o bloody diarrhea; the rst seemed to resolve a ter several days and occurred several weeks ago. He has cramps that occur with each bowel movement, but eels ne between bouts o diarrhea. He has no travel history outside o the United States. He is o Jewish descent and has a cousin with Crohn disease. Colonoscopy shows mucosal riability with super cial ulceration and exudates con ned to the rectosigmoid colon, and he is diagnosed with ulcerative colitis (Figure 77-1).

INTRO DUCTIO N Inf ammatory bowel disease (IBD) comprises ulcerative colitis (UC) and Crohn disease. The intestinal inf ammation in UC is usually con ned to the mucosa and a ects the rectum with or without parts or the entire colon (pancolitis) in an uninterrupted pattern. In Crohn disease, inf ammation is o ten transmural and a ects primarily the ileum and colon, o ten discontinuously. Crohn disease, however, can a ect the entire GI tract rom mouth to anus.

EPIDEMIO LO GY • Incidence o UC in the West is 8 to 14 per 100,000 people and 6 to 15 per 100,000 people or Crohn disease. 1 Prevalence or UC and Crohn disease in North America (one o the highest rates in the world) is 37.5 to 238 per 100,000 people and 44 to 201 per 100,000 people, respectively; IBD, there ore, a ects an estimated 1.3 million people in

PART 10

GASTRO INTESTINAL the United States. 1 Rates o IBD are increasing in both the West and in developing countries. 1 • Age o onset is typically 30 to 40 years or UC and 20 to 30 years or Crohn disease. A bimodal distribution with a second peak at ages 60 to 70 years has been reported but not con rmed. 1 • Predilection or those o Jewish ancestry (especially Ashkenazi Jews) ollowed in order by non-Jewish whites and A rican Americans, Hispanics, and Asians. 1 • Inheritance (polygenic) plays a role with a concordance o 20% in monozygous twins and a risk o 10% in rst-degree relatives o an incidence case. 2

ETIO LO GY AND PATHO PHYSIO LO GY • Unknown etiology—Current theory is that colitis is an inappropriate response to microbial gut f ora or a lack o regulation o intestinal immune cells in a genetically susceptible host with ailure o the normal suppression o the immune response and tissue repair. 2,3 • Genetic regions containing nucleotide oligomerization domain 2 (NOD2; encodes an intracellular sensor o peptidoglycan), autophagy genes (regulate clearing o intracellular components like organelles), and components o the interleukin-23–type 17 helper T-cell (Th17) pathway are associated with IBD; the autophagy gene, ATG16L1, is associated with Crohn disease. 3 • Multiple bowel pathogens (eg, Salmonella, Shigella species, and Campylobacter) may trigger UC. This is supported by a large cohort study where the hazard ratio o developing IBD was 2.4 (95% con dence interval [CI], 1.7 to 3.3) in the group who experienced a bout o in ectious gastroenteritis compared with the control group; the excess risk was greatest during the rst year a ter the in ective episode. 4 People with IBD also have depletion and reduced diversity o some members o the mucosa-associated bacterial phyla, but it is not known whether this is causal or secondary to inf ammation. 3 • Other abnormalities ound in patients with IBD include increased permeability between mucosal epithelial cells, de ective regulation o intercellular junctions, in ltration into the lamina propria o innate (eg, neutrophils) and adaptive (B and T cells) immune cells with increased production o tumor necrosis actor α and increased numbers o CD4+ T cells, dysregulation o intestinal CD4+ T-cell subgroups, and the presence o circulating antimicrobial antibodies (eg, antif agellin antibodies). 3 Many o the therapeutic approaches target these areas. • Psychological actors (eg, major li e change, daily stressors) are associated with worsening symptoms. • Patients with long-standing UC are at higher risk o developing colon dysplasia and cancer; this is believed to be a developmental sequence (see “Prognosis” below).

RISK FACTO RS • Smokers are at increased risk or Crohn disease and tend to have more severe disease, whereas ormer smokers and nonsmokers are at greater risk or UC. 1,2

FIGURE 77-1 Ulce tive colitis in t e e ctosig moid colon s vie we d t oug t e colonoscope . (Re p rod uce d with p e rmission from Marvin De re zin, MD.)

• Environmental actors appear to be important triggers, especially o Crohn disease in children. 1 • Appendectomy reduces the risk o UC. 1

381

PART 10

382

GASTRO INTESTINAL

Ch a pt e r 77

DIAGNO SIS The diagnosis depends on the clinical evaluation, sigmoid appearance, histology, and a negative stool or bacteria, Clostridium di cile toxin, and ova and parasites. 2 CLINICAL FEATURES • Major symptoms o UC—Diarrhea, rectal bleeding, tenesmus (ie, urgency with a eeling o incomplete evacuation), passage o mucus, and cramping abdominal pain. • Symptoms in patients with Crohn disease depend on the location o disease; patients become symptomatic when lesions are extensive or distal (eg, colitis), systemic inf ammatory reaction is present, or when disease is complicated by stricture, abscess, or stula. Gross blood and mucus in the stool are less requent and systemic symptoms, extracolonic eatures, pain, perineal disease, and obstruction are more common. 2 There is no relationship between symptoms and anatomic damage. 1 • UC is classi ed by severity based on the clinical picture and results o endoscopy5; treatment is based on disease classi cation. ° Mild: Less than 4 stools per day, with or without blood, no signs o systemic toxicity, and a normal erythrocyte sedimentation rate (ESR). ° Moderate: More than 4 stools per day but with minimal signs o toxicity. ° Severe: More than 6 bloody stools per day, and evidence o toxicity demonstrated by ever, tachycardia, anemia, and elevated ESR. ° Fulminant: May have more than 10 bowel movements daily, continuous bleeding, toxicity, abdominal tenderness and distention, a blood trans usion requirement, and colonic dilation on abdominal plain lms. • Extraintestinal mani estations are present in 25% to 40% o patients with IBD but are more common in Crohn disease than UC:2,6 ° Dermatologic (2%-34%)—Erythema nodosum (10%) that correlates with disease activity (see Chapter 176, Erythema Nodosum) and pyogenic gangrenosum (pustule that spreads concentrically and ulcerates surrounded by violaceous borders) in 1% to 12% o patients. 2 ° Rheumatologic—Peripheral arthritis (5%-20%), spondylitis (1%-26%, but nearly all who are positive or human leukocyte antigen B27), and symmetric sacroiliitis (< 10%). 6 ° Ocular—Conjunctivitis, uveitis, iritis, and episcleritis (0.3%-5%). ° Hepatobiliary—The most serious complication in this category is primary sclerosing cholangitis; although 75% o patients with this disease have UC, only 5% o those with UC and 2% o patients with Crohn disease develop it. 6 Hepatic steatosis ( atty liver) and cholelithiasis can also occur. ° Cardiovascular—Increased risk o deep venous thrombosis, pulmonary embolus, and stroke (because o a hypercoagulable state rom thrombocytosis and gut losses o antithrombin III among other actors); endocarditis; myocarditis; and pleuropericarditis. 2 ° Bone—Osteoporosis and osteomalacia rom multiple causes including medications, reduced physical activity, inf ammatory-mediated bone resorption, vitamin D de ciency, and calcium and magnesium malabsorption. Fracture risk in patients with IBD is 1 per 100 patient-years (40% higher than the general population). 6 and stulization o ° Renal—Nephrolithiasis, obstructive uropathy, the urinary tract occur in 6% to 23%. 6

FIGURE 77-2 C o n colitis wit d e e p long itud in l ulce s nd no m lp p e ing tissue b e twe e n. T e b iop sie s t t s owe d no m l tissue b e twe e n t e ulce s clinc e d t e d i g nosis o C o n d ise se . Ulce tive colitis is d i use w e e s C o n d ise se o te n skip s e s s se e n in t is p tie nt’s colon. (Re p rod uce d with p e rmission from Marvin De re zin, MD.)

• Extraintestinal mani estations may occur prior to the diagnosis o IBD. For example, 10% to 30% o patients with IBD-related arthritis develop arthritis prior to IBD diagnosis. 6 • Severe complications include toxic colitis (15% initially present with catastrophic illness), massive hemorrhage (1% o those with severe attacks), toxic megacolon (ie, transverse colon diameter >5-6 cm) (5% o attacks may be triggered by electrolyte abnormalities and narcotics), and bowel obstruction (caused by strictures and occurring in 10% o patients). 1 • On endoscopy in patients with Crohn disease, rectal sparing is requent and cobblestoning o the mucosa is o ten seen. Small bowel involvement is seen on imaging in addition to segmental colitis and requent strictures (Figure 77-2). • Diagnosis is changed rom UC to Crohn disease over time in 5% to 10% o patients. 7 TYPICAL DISTRIBUTIO N • At presentation, about a third o patients with UC have disease localized to the rectum, another third have disease present in the colorectum distal to the splenic f exure, and the remainder with disease proximal to the splenic f exure; pancolitis is present in 1 quarter. 1 Adults appear to always have rectal involvement, which is not the case or children. Over time (20 years), hal will have pancolitis (Figure 77-1). 8 • In patients with Crohn disease, lesions occur in equal proportions in the ileum, colon, or both; 10% to 15% have upper GI lesions, 20% to 30% present with perianal lesions; and about hal eventually develop perianal disease. Around 15% to 20% o patients have or have had a stula. 1 LABO RATO RY TESTS • Acute disease can result in a rise o acute phase reactants (eg, C-reactive protein) and elevated ESR (rare in patients with just proctitis). C-reactive protein is elevated in nearly all patients with Crohn disease and in approximately hal o the patients with UC. 9

INFLAMMATO RY BO WEL DISEASE

PART 10

GASTRO INTESTINAL

• Obtain hemoglobin (to assess or anemia) and platelets (to assess or reactive thrombocytosis). • O the biomarkers available to detect IBD, ecal calprotectin and lacto errin are most commonly used. 9 The ormer is an indirect measure o neutrophil in ltrate in the bowel mucosa, and the later is an iron-binding protein secreted by mucosal membranes and ound in neutrophil granules and serum. Although the optimal threshold value or calprotectin in detecting IBD is unknown, a study o adult patients suspected o having IBD based on clinical evaluation reported a sensitivity and speci city o the test o 93% and 96%, respectively. 10 Test characteristics or lacto errin are lower at 80% and 82%. • Stool should be examined to rule out in ectious causes including C. di cile; the incidence o C. di cile is increasing in patients with UC and is associated with a more severe course in those with IBD. 11 ENDO SCO PY AND IMAGING Imaging has become more important or patients with IBD, not only or diagnosis in symptomatic patients but or early detection and treatment o inf ammation in asymptomatic patients with Crohn disease and or monitoring inf ammation and disease complications. 12 • Colonoscopy with ileoscopy and mucosal biopsy should be per ormed in the evaluation o IBD and or di erentiating UC rom Crohn disease (Figures 77-1 to 77-5). 13 SO R It is the best test or detection o colonic inf ammation. 5,10 • Colonoscopy can show pseudopolyps in both active UC (Figure 77-4) and inactive UC (Figure 77-5). Risks o ileocolonoscopy include peroration, limited small bowel evaluation, and inability to stage penetrating disease. 12 • Capsule endoscopy (CE) is a less-invasive technique or evaluating the small intestine in patients with Crohn disease and is more sensitive than radiologic and endoscopic procedures or detecting small bowel lesions and mucosal inf ammation. 12,13 SO R CE should not be

FIGURE 77-4 Pseudopolyps in “ ctive” ulce tive colitis viewed t oug colonoscope. (Reproduced with permission from Marvin Derezin, MD.)

per ormed in patients with Crohn disease known or suspected to have a high-grade stricture. In that case, consider CT enterography. 13 The major risk is retention. 12 • In patients with initial presentation o symptomatic Crohn disease, the American College o Radiology (ACR) recommends CT enterography.14 Magnetic resonance (MR) enterography may be substituted based on institutional pre erence as this test appears to have similar test characteristics and avoids radiation exposure; it is the pre erred test or investigating perianal disease. 13 In addition to radiation, risks o CT enterography are related to the iodine dye and or MR enterography, image quality can be suboptimal in some patients; both tests have limited ability to detect colonic cancer. 12

FIGURE 77-3 Ulce tive colitis. End oscop ic im g e s owing i b ility nd e xud te s ove sup e f ci l ulce tion in t e sig moid co lon. T e e is e d e m in t e ce cum t t, ll tog e t e , ind ic te s p n colitis. (Re p rod uce d with p e rmission from Michae l Harp e r, MD.)

383

PART 10

384

GASTRO INTESTINAL

FIGURE 77-5 Pse ud op olyp s in “in ctive ” ulce tive colitis vie we d t oug colonoscop e . (Re p rod uce d with p e rmission from Marvin De re zin, MD.)

• In patients with severe disease, a plain supine lm may show edematous, irregular colon margins, mucosal thickening, and toxic dilation. 2

DIFFERENTIAL DIAGNO SIS • In ections o the colon—Salmonella, Shigella species, and Campylobacter have a similar appearance with bloody diarrhea and abdominal pain but disease is usually sel -limited and stool culture can con rm the presence o these bacteria. C. di cile and Escherichia coli can also mimic IBD. • Numerous in ectious agents including Mycobacterium, Cytomegalovirus, and protozoan parasites can mimic UC in immunocompromised patients. • Ischemic colitis—May present with sudden onset o le t lower quadrant pain, urgency to de ecate, and bright red blood via rectum (See Chapter 73, Ischemic Colitis). It can be chronic and di use and should be considered in elderly patients ollowing abdominal aorta repair or when a patient has a hypercoagulable state. Endoscopic examination o ten demonstrates normal rectal mucosa with a sharp transition to an area o inf ammation in the descending colon or splenic f exure (Figure 77-6). • Colitis associated with NSAIDs—Clinical eatures o diarrhea and pain, but may be complicated by bleeding, stricture, obstruction, and per oration. History is help ul and symptoms improve with withdrawal o the agent.

MANAGEMENT MEDICATIO N Treatment o acute disease in patients with UC (treatment algorithms can be ound in the re erence provided) is based on disease activity as ollows15: • Mild to moderate distal disease—Oral aminosalicylates (ASAs), topical mesalamine, or topical steroids. 5 SOR An oral 5-ASA agent can be a

Ch a PTEr 77

FIGURE 77-6 Isc e mic colitis in n e ld e ly p tie nt. (Re p ro d uce d with p e rmission Marvin De re zin, MD.)

prodrug (eg, sul asalazine, 4-6 g/ day), a drug with a pH-dependent coating (eg, Asacol, 2.4-4.8 g/ day), or a slow-release agent (Pentasa, 2-4 g/ day). Mesalamine suppositories (1 g/ day) are the best way to induce remission in patients with proctitis. 15 Rectal suppositories or enemas should also be used to improve medication delivery when treating active distal colitis, and a combination o oral and rectal mesalamine is better than monotherapy or stopping rectal bleeding (89% vs. 46% [oral only] or 69% [rectal only]). 5,15 SOR Fi ty percent to 75% o patients will show clinical improvement with 2 g/ day o 5-ASA and a similar percentage will maintain remission with doses o 1.5 to 4 g/ day. 2 • For patients with mild to moderate active proctitis who do not respond to topical mesalamine, adding a topical corticosteroid should be considered. In patients re ractory to oral ASAs or topical corticosteroids, mesalamine enemas or suppositories may still be e ective. 5 SO R An oral steroid (eg, prednisone, 40-60 mg/ day) or inf iximab (induction regimen o 5 mg/ kg at weeks 1, 2, and 6) can be added or patients with mild-moderate local disease who have an inadequate response to initial therapy; the latter is o ten reserved or patients who do not respond to or tolerate steroids. 5,13 SO R • Mild to moderate extensive colitis—Oral sul asalazine (titrated to 4-6 g/ day) or 5-ASA (up to 4.8 g/ day) with or without topical therapy. SO R Oral steroids are generally reserved or patients re ractory to combined oral and topical ASA therapy or or those with severe symptoms requiring more prompt improvement. 5 SO R Immunomodulators (6-mercaptopurine and azathioprine) are e ective or patients who do not respond to oral steroids and continue to have moderate disease. 5 SO R Patients who are steroid re ractory, intolerant, or steroid-dependent despite adequate doses o a thiopurine can be considered or inf iximab induction as above. 5 SO R Inf iximab is contraindicated in patients with active in ection, untreated latent tuberculosis, preexisting demyelinating disorder or optic neuritis, moderate to severe congestive heart ailure, or current or recent malignancies. • Severe colitis—Patients presenting with toxicity should be admitted to the hospital or IV steroids (methylprednisolone, 40 to 60 mg/ day, or hydrocortisone, 200 to 300 mg/ day) ollowing hospitalization. 5,15 SO R Otherwise, treat with oral prednisone, oral ASA drugs, and

INFLAMMATO RY BO WEL DISEASE

PART 10

385

GASTRO INTESTINAL

topical medications with the addition o inf iximab (5 mg/ kg) i re ractory to treatment and urgent hospitalization is not necessary. 5 SO R I the patient ails to improve within 3 to 5 days, colectomy SO R or IV cyclosporine SO R should be considered. Antibiotics have no proven e cacy without proven in ection and parenteral nutrition has not been shown to be o bene t as primary therapy or UC. 5 • Fulminant disease—Patients should be treated as above with IV glucocorticoid and maintained without oral intake and with use o a decompression tube i small bowel ileus is present.5 IV cyclosporine (2-4 mg/ kg per day) or inf iximab may be considered or patients who are not improving on maximal medical therapy as above. • Patients with Crohn disease are treated similarly except that there is limited response to mesalamine or cyclosporin and better response to nutritional therapy. A research tool called the Crohn Disease Activity Index can be used to monitor disease activity (online calculator available at http:/ / www.ibdjohn.com/ cdai/ . Accessed July 2013). • Mild to moderate active ileocolic Crohn disease—Budesonide (9 mg) or prednisone i distal colonic disease is present. 15 Nutrition therapy is the rst-line treatment or children. For patients who do not tolerate steroids or in cases where steroids are ine ective, biologic therapy with inf iximab, adalimumab, or certolizumab pegol is appropriate. Methotrexate (up to 25 mg/ week) is also e ective. 15 Patients with weight loss or strictures may bene t rom early introduction o biologic or immunomodulator therapy. 15 • Severe Crohn disease in any location-Initial treatment with oral or intravenous steroids; antitumor necrosis actor therapy is reserved or patients who do not respond to initial therapy. In a single-center cohort study o 614 patients treated with inf iximab, only 10.9% were not primary responders by 12 weeks, and sustained bene t was seen in 63% who received long-term treatment (mean ollow-up: 55 months). 16 Management also includes nutritional support and treatment o iron de ciency. • Side e ects o biologic therapy include serious in ections, induction o autoimmune phenomena, and neurotoxicity.17 However, in a report o a cohort o 734 patients with IBD treated with inf iximab, the most commonly observed systemic side e ects were skin eruptions including psoriasi orm eruptions in 20%; 2 patients developed tuberculosis but none o the 16 patients with positive skin tests who received prophylaxis.18 SURGERY Surgery—Total proctocolectomy with ileostomy or continence-preserving operation (ie, ileal pouch-anal anastomosis [IPAA]) is per ormed in approximately hal o patients with UC within 10 years o disease onset. Indications or surgery include the ollowing2,5: SO R • Intractable or ulminant disease • Toxic megacolon • Massive hemorrhage • Colonic obstruction or per oration • Colon cancer or dysplasia in f at mucosa, 8 SO R prophylaxis.

or or cancer

PRO GNO SIS • In UC (Figure 77-7), disease f ares and remissions with mucosal healing occur; remission is seen in about hal o the patients within a year o onset. 1 Those who have complete clinical and endoscopic remission

FIGURE 77-7 Ulce tive colitis in 27-ye -old m n p e se nting wit b le e d ing . (Re p rod uce d with p e rmission from Mark Koch, MD.)

e ct l

have a signi cantly decreased risk o colectomy. 1 Disease activity lessens over time with longer periods o remission. In a population study o 1575 patients with UC in Denmark, 13% had no relapse, 74% had 2 or more relapses, and 13% had active disease every year or 5 years a ter diagnosis. 19 • The probability o colectomy over 25 years or those with UC is 20% to 30%. 1 Colectomy is not necessarily curative as pouchitis episodes occur in hal o these patients by 5 years postoperatively, and in up to 10% o cases, pouchitis is chronic and o ten re ractory to antibiotic treatment. 1 • Overall mortality is not increased or patients with UC, unless there is severe disease. 1 Although UC-related mortality rom liver disease or colorectal cancer is increased, there is a decreased rate o death rom pulmonary cancer and other tobacco-related diseases. 1 • Recurrence postoperatively is the norm or patients with Crohn disease; only 5% have normal endoscopy at 10 years ollow-up and symptoms occur about 2 to 3 years a ter anatomic lesions are ound. 20 Natural progression o the disease with or without surgery is variable with spontaneous and treatment-related remissions, especially o more super cial lesions. Only approximately 10% to 15% o patients have chronic continuous disease. 1 • Most patients with Crohn disease (60%-80%) require surgery by the time they have had the disease or 20 to 30 years (estimated at 3%-5% per year) and greater than 10% eventually require ecal diversion, especially in patients with colorectal disease or anal stenosis. 1 • Factors associated with poor prognosis in IBD are younger age and more extensive disease. Other actors associated with poor prognosis are pouchitis and extraintestinal mani estations at surgery (IPAA) or UC and need or steroids at presentation or Crohn disease. 1 • Mortality rate or Crohn disease is slightly increased (standardized mortality ratio = 1.52); most deaths are connected to malnutrition, postoperative complications, and intestinal cancer.

386

PART 10

GASTRO INTESTINAL • Both patients with UC and Crohn disease are at increased risk or colorectal cancer. The risk increases with duration and extent o disease and decreases ollowing success ul treatment. 21 Colorectal cancer is rare within the rst 7 years o colitis onset and increases at a rate o approximately 0.5% to 1% per year therea ter, which is likely associated with histologic disease activity. 9 It is not clear i anti-inf ammatory medications reduce this risk. 9 • Patients with cholestasis should be evaluated or primary sclerosing cholangitis and subsequent cholangiocarcinoma. 5

Ch a pt e r 77

PATIENT RESO URCES

• National Digestive Diseases Information Clearinghouse, Ulcerative Colitis—http:/ / digestive.niddk.nih.gov/ ddiseases/ pubs/ colitis/ . • National Digestive Diseases Information Clearinghouse, Crohn Disease—http:/ / digestive.niddk.nih.gov/ ddiseases/ pubs/ crohns/ . • Crohn’s and Colitis Foundation of America—www.ccfa.org. PRO VIDER RESO URCES

FO LLO W-UP • Support and patient education should be provided to address medication side e ects, the uncertain nature o the disease, and potential complications. Discuss medication adherence in patients with apparent inadequate response to treatment. • For maintenance o remission o mild to moderate distal disease—Mesalamine suppositories (proctitis) or enemas (distal colitis) can be dosed as in requently as every third night.5 SOR Patients, however, pre er oral therapy. 15 Sul asalazine, mesalamine compounds, and balsalazide are also e ective in maintaining remission; the combination o oral and topical mesalamine is more e ective than either one alone.5 SOR I these ail, thiopurines and inf iximab may be e ective.5 SO R • For maintenance o remission o mild to moderate extensive colitis— Sul asalazine, olsalazine, mesalamine (2.4 g/ day), and balsalazide are e ective in reducing relapses; chronic steroid use should be avoided. 5 SO R Inf iximab can be used or maintenance o remission in patients who respond to inf iximab induction. 5 SO R For patients who relapse despite therapy, azathioprine or 6-mercaptopurine can be used (number needed to treat to prevent 1 recurrence is 5). 15 • For patients with severe colitis, long-term remission is signi cantly enhanced with the addition o maintenance 6-mercaptopurine. 5 SO R • Periodic bone mineral density assessment is recommended or patients on long-term corticosteroid therapy (> 3 months). 22 SO R • Annual ophthalmologic examinations are recommended or patients on long-term corticosteroid therapy. 22 SO R • Patients with long-standing IBD are at higher risk o developing colon dysplasia and cancer. For patients with pancolitis, the risk is 0.5% to 1% per year a ter 8 to 10 years o disease. 1,2 Surveillance colonoscopy with multiple biopsies should be per ormed every 1 to 2 years beginning a ter 8 to 10 years o disease. 5 SO R There is evidence that cancers are detected at an earlier stage in patients who are undergoing surveillance. 23 • In the near uture, it may be possible to monitor patients or intestinal ulcerations or thickening using noninvasive techniques (assays or C-reactive protein, ecal calprotectin, and lacto errin; videocapsule and magnetic resonance imaging) and treat them as early as possible to prevent disease progression.1,12 In addition, biomarkers may be use ul or assessing mucosal healing, predicting relapse, and making therapeutic adjustments.9

PATIENT EDUCATIO N

• Kornbluth A, Sachar D; Practice Committee o the American College o Gastroenterology. Ulcerative colitis practice guidelines in adults: American College o Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105:501-523. • Burger D, Travis S. Conventional medical management o IBD. Gastroenterology. 2011;140(6):1827-1837. REFERENCES 1. Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and natural history o inf ammatory bowel diseases. Gastroenterology. 2011;140(6):1785-1794. 2. Friedman S, Blumberg RS. Inf ammatory bowel disease. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds. Harrison’s Principles o Internal Medicine, 16th ed. New York, NY: McGraw-Hill; 2005:1776-1789. 3. Abraham C, Cho J. Inf ammatory bowel disease. N Engl J Med. 2009;361:2066-2078. 4. Garcia Rodriguez LA, Ruigomez A, Panes J. Acute gastroenteritis is ollowed by an increased risk o inf ammatory bowel disease. Gastroenterology. 2006;130(6):1588-1594. 5. Kornbluth A, Sachar D; Practice Committee o the American College o Gastroenterology. Ulcerative colitis practice guidelines in adults: American College o Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105:501-523. 6. Levine JS, Burako R. Extraintestinal mani estations o inf ammatory bowel disease. Gastroenterol Hepatol (NY). 2011;7(4):235-241. 7. Langholz E, Munkholm P, Davidsen M, et al. Course o ulcerative colitis: analysis o changes in disease activity over years. Gastroenterology. 1994;107:3-11. 8. Langholz E, Munkholm P, Davidsen M, et al. Changes in extent o ulcerative colitis: a study on the course and prognostic actors. Scand J Gastroenterol. 1996;31:260-266. 9. Lewis JD. The utility o biomarkers in the diagnosis and therapy o inf ammatory bowel disease. Gastroenterology. 2011;140(6):1817-1826. 10. van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin or screening o patients with suspected inf ammatory bowel disease: diagnostic meta-analysis. BMJ. 2010;341:c3369. 11. Ananthakrishnan AN, McGinley EL, Binion DG. Excess hospitalization burden associated with Clostridium di cile in patients with inf ammatory bowel disease. Gut. 2008;57:205-210.

• Patients should be in ormed about the unpredictable course o IBD and the need or requent contact with an experienced provider or medical management, support, and surveillance.

12. Fletcher JG, Fider JL, Bruining DH, Huprich JE. New concepts in intestinal imaging or inf ammatory bowel disease. Gastroenterology. 2011;140(6):1795-1806.

• Smoking cessation should be stressed, particularly or patients with Crohn disease. 2

13. Leighton JA, Shen B, Baron TH, et al; Standards o Practice Committee, American Society or Gastrointestinal Endoscopy.

INFLAMMATO RY BO WEL DISEASE

ASGE guideline: endoscopy in the diagnosis and treatment o inf ammatory bowel disease. Gastrointest Endosc. 2006;63(4):558-565. 14. ACR Appropriateness Criteria Crohn’s Disease. http:/ / www.guideline .gov/ content.aspx?id= 35137. Accessed July 2013. 15. Burger D, Travis S. Conventional medical management o inf ammatory bowel disease. Gastroenterology. 2011;140(6):1827-1837. 16. Schnitzler F, Fidder H, Ferrante M, et al. Long-term outcome o treatment with in iximab in 614 patients with Crohn’s disease: results rom a single-centre cohort. Gut. 2009;58:492-500. 17. Van Assche G, Vermeire S, Rutgeerts P. Sa ety issues with biological therapies or inf ammatory bowel disease. Curr Opin Gastroenterol. 2006;22(4):370-376. 18. Fidder H, Schnitzler F, Ferrante M, et al. Long-term sa ety o inf iximab or the treatment o inf ammatory bowel disease: a single-centre cohort study. Gut. 2009;58(4):501-508. 19. Jess T, Riis L, Vind I, et al. Changes in clinical characteristics, course, and prognosis o inf ammatory bowel disease during the last

PART 10

GASTRO INTESTINAL 5 decades: a population-based study rom Copenhagen, Denmark. Inf amm Bowel Dis. 2007;13:481-489. 20. Olaison G, Smedh K, Sjodahl R. Natural course of Crohn’s disease a ter ileocolic resection: endoscopically visualized ileal ulcers preceding symptoms. Gut. 1992;33:331-335. 21. Ullman TA, Itzkowitz SH. Intestinal inf ammation and cancer. Gastroenterology. 2011;140(6):1807-1816. 22. Lichtenstein GR, Abreu MT, Cohen R, Tremaine W. American gastroenterological association institute medical position statement on corticosteroids, immunomodulators, and inf iximab in inf ammatory bowel disease. Gastroenterology. 2006;130(3): 935-939. 23. Collins PD, Mpo u C, Watson AJ, Rhodes JM. Strategies or detecting colon cancer and/ or dysplasia in patients with inf ammatory bowel disease. Cochrane Database Syst Rev. 2006;(2): CD000279.

387

This page intentionally left blank

PART 11

GENITO URINARY/ RENAL

*

St re ng t h o Re co mme nd at io n (SO R)

De f nit io n

A

Re comme nd ation b ase d on consiste nt and g ood -q uality atie nt-orie nte d e vid e nce .*

B

Re comme nd ation b ase d on inconsiste nt or limite d -q uality atie nt-orie nte d e vid e nce .*

C

Re comme nd ation b ase d on conse nsus, usual ractice , o inion, d ise ase -orie nte d e vid e nce , or case se rie s for stud ie s of d iag nosis, tre atme nt, re ve ntion, or scre e ning .*

Se e A

e nd ix A on ag e s 1241-1244 for furt e r information.

390

PART 11

GENITO URINARY/ RENAL

Ch a pt e r 78

78 BLADDER CANCER Mind y A. Smith, MD, MS

PATIENT STO RY A 68-year-old man, who is a retired painter and in good health, comes to the o ce at the insistence o his wi e. He reports that his urinary stream is smaller and he has occasional dysuria. He has no major medical problems, although he continues to smoke one pack o cigarettes per day. His urinalysis in the o ce shows microscopic hematuria, and an irregular mass is seen in the bladder on CT scan (Figure 78-1). Cystoscopy shows a bladder tumor (Figure 78-2). Complete endoscopic resection is perormed and con rms transitional cell carcinoma.

INTRO DUCTIO N Bladder cancer is a malignant neoplasm o the bladder, almost exclusively urothelial (transitional cell) carcinoma.

EPIDEMIO LO GY • In 2008, there were approximately 398,329 men and 139,099 women alive in the United States who had a history o cancer o the urinary bladder. 1 • Almost 70,000 new cases (52,020 men and 17,230 women) were diagnosed and approximately 14,990 deaths occurred rom bladder cancer in 2011. 1 Mean age at diagnosis is 73 years. • The age-adjusted incidence rate (based on 2004-2008 data) was 21.1 per 100,000 men and women per year with a male-to- emale ratio o approximately 4:1. Among men, bladder cancer is more prevalent in whites than in blacks or Hispanics (ratio o 2:1) and more prevalent in whites than in Asian/ Paci c Islander or American Indian/ Alaska Natives (ratio 2.4:1); or white women, incidence rates are also higher but the di erences are not as great. 1

FIGURE 78-1 CT wit contrast re ve als a b lad d e r cance r in a 68-ye ar-old man wit e maturia. (Re p rod uce d with pe rmission from Michae l Freckle ton, MD.)

FIGURE 78-2 Cystosco ic vie w of t e transitional ce ll carcinoma in t e man in Fig ure 72-1. (Re p rod uce d with p e rmission from Carlos Enriq ue Be rme jo, MD.)

ETIO LO GY AND PATHO PHYSIO LO GY • Around 90% to 95% are transitional cell cancers and the remainder are nonurothelial neoplasms, including primarily squamous cell, adenocarcinoma, and small cell carcinoma2,3 (Figures 78-1 to 78-4). Rare orms include nonepithelial neoplasms (approximately 1%), including benign tumors, such as hemangiomas or lipomas, and malignant tumors, such as angiosarcomas. 3 • Transitional cells line the urinary tract rom the renal pelvis to the proximal two-thirds o the urethra. Ninety percent o transitional cell tumors develop in the bladder, and the others develop in the renal pelvis, ureters, or urethra. 2

FIGURE 78-3 CT wit contrast of a small transitional ce ll carcinoma of t e b lad d e r t at was b are ly visib le until t e atie nt was scanne d on sid e . A small b lad d e r d ive rticulum is visib le as we ll. (Re p rod uce d with p e rmission from Michae l Fre ckle ton, MD.)

PART 11

BLa DDe r Ca NCe r

GENITO URINARY/ RENAL • Irritative symptoms (ie, dysuria, requency) are the most common presentation. • Obstructive symptoms may occur i the tumor is located near the urethra or bladder neck. LABO RATO RY • Urine microscopy and culture to rule out bladder in ection.3 • Urine cytology (high speci city [90%-95%] but low sensitivity [23%-60%]), CT scan o the pelvis (Figures 78-1, 78-3, and 78-4) or intravenous urography (IVU), and cystoscopy with biopsy (Figure 78-2) comprise the basic work-up. 2 Fluorescence cystoscopy (use o photosensitizer instilled into the bladder), can enhance detection o f at neoplastic lesions like carcinoma in situ (CIS).4 When CIS is ound in a cystectomy specimen, 9% to 13% o patients have upper urinary tract disease.4

FIGURE 78-4 CT of locally invasive transitional cell carcinoma (arrow) of t e blad der exte nding outsid e of t e bladd er in a 71-year-old man. T e carcinoma on t e atie nt’s rig t is dis lacing t e contrast toward t e left sid e of t e atient’s b lad der. (Reproduced with permission from Michael Freckleton, MD.)

• Most tumors are super cial (75%-85%). 4 At diagnosis, approximately 51% are in situ and 35% are localized (con ned to primary site) with an additional 7% o cases having regional spread and 4% having distant metastases at diagnosis (3% unknown). 2 • Multiple tumors are seen in 30% o cases. 4 • Bladder tumor cells are also graded based on their appearance and behavior into well di erentiated or low grade (grade 1), moderately well di erentiated or moderate grade (grade 2), and poorly di erentiated or high grade (grade 3). • The most common sites o hematogenous spread are lung, bone, liver, and brain. Super cial lesions do not metastasize until they invade deeply and may remain indolent or years. 2

RISK FACTO RS • Risk actors include smoking (odds ratio increased by 3-4 old; 50% attributable risk) and exposure to pelvic radiation, 5 the drugs phenacetin and chlornaphazine, external-beam radiation, and chronic in ection, including Schistosoma haematobium and genitourinary tuberculosis. 2,3 • There is an increased risk in certain occupations, particularly those involving exposure to metals (eg, aluminum), paint and solvents, polycyclic aromatic hydrocarbons, diesel engine emissions, aniline dyes (eg, workers in chemical plants exposed to benzidine or o-toluidine), 2 and textiles. 6 • An increased risk was also seen with drinking tap water (odds ratio [OR] or > 2 L/ day vs. ≤0.5 L/ day was 1.46 [1.20-1.78]), with a higher risk among men (OR = 1.50, 1.21-1.88). 7 • Familial cases indicate a genetic predisposition. 8

• Bladder wash cytology during cystoscopy detects most CIS. 3 • A complete blood count, blood chemistry tests (including alkaline phosphatase tests), liver unction tests, CT or MRI o the chest or abdomen, and a bone scan may be needed or suspected metastatic disease. 2,3 Bone scanning may be limited to patients with bone pain and/ or elevated levels o serum alkaline phosphatase. 4 • Tumor markers such as f uorescence in situ hybridization (FISH) analysis and nuclear matrix protein (NMP) 22 identi y changes in cells in the urine and are more sensitive than urine cytology or low-grade tumors with equivalent sensitivity or high-grade tumors and CIS. 9 As speci city is low, tumor markers should not be used or diagnosis. IMAGING • For pretreatment staging o invasive bladder cancer, the American College o Radiology (ACR) recommends a chest X-ray (with chest CT i equivocal), CT o the abdomen and pelvis (without and with contrast) or MRI o the pelvis (especially in cases where patients are unable to undergo contrast injection), and possibly IVU; contrastenhanced MRI is pre erred over CT or local staging. 4 SO R • The European Association o Urology (EAU) recommends multidetector-row CT (MDCT) o the chest, abdomen, and pelvis as the optimal orm o staging or patients with con rmed muscle-invasive bladder cancer, including MDCT urography or examination o the upper urinary tracts. 9 I MDCT is not available, alternatives are excretory urography and a chest X-ray. SO R • EAU recommends renal and bladder ultrasonography, and IVU or CT prior to transurethral resection or presumed invasive bladder cancer. 10 SO R ACR agrees that ultrasound is use ul or local tumor staging. 4 For patients with veri ed invasive bladder cancer, EAU recommends either MRI with ast dynamic contrast-enhancement or MDCT with contrast enhancement or patients considered suitable or radical treatment. SO R BIO PSY Diagnosis is made by cystoscopy, biopsy, and histology.

DIAGNO SIS CLINICAL FEATURES • Hematuria in 80% to 90%; with microscopic hematuria approximately 2% have bladder cancer and with gross hematuria approximately 20% have bladder cancer. 3

DIFFERENTIAL DIAGNO SIS • Among adult patients with microscopic hematuria, most patients have benign pathology, such as urinary tract in ection, with 25% having prostate cancer and only 2% having bladder cancer. 2

391

PART 11

392

Ch a pt e r 78

GENITO URINARY/ RENAL • Among adult patients with gross hematuria, 22% have benign cystitis and 15% to 20% have bladder cancer. 2

• Cisplatin-containing combination chemotherapy is rst-line therapy or patients with metastatic disease, and treated patients can achieve a median survival o up to 14 months. 9,13 SO R SURGICAL

MANAGEMENT MEDICATIO NS Neoadjuvant cisplatin-containing combination chemotherapy (administered prior to main treatment) improves overall 5-year survival by 5% to 7% and should be considered in muscle-invasive bladder cancer irrespective o de initive treatment. 9,11 SO R It is not recommended or patients with per ormance status o 2 or more and impaired renal unction or or primary therapy or localized bladder cancer. 9 • The role o adjuvant chemotherapy (usually administered a ter surgery) or invasive bladder cancer is under debate. A Cochrane review based on 6 small trials (N = 491) ound a 25% relative reduction in the risk o death or chemotherapy compared to control patients (hazard ratio or survival 0.75; 95% CI 0.60, 0.96), suggesting a bene t or these patients. 12

It depends on the extent (depth and grade) or spread o the disease (Table 78-1). Recommendations have been provided by the American Urological Association (AUA, 2007)13 and the EAU (2009)9 as given below: • Non–muscle-invasive disease (70%-75% o cases)—Complete endoscopic resection with or without intravesical treatment (bacille Calmette-Guérin [BCG] weekly or 6 weeks or inter eron or mitomycin C). SO R Low-grade tumors (Ta tumors) can be treated with resection alone or with a single postoperative dose o intravesical chemotherapy. SO R In a metaanalysis o 3 trials, tumor recurrence was signi cantly lower with intravesical BCG, but there was no di erence in disease progression or survival. 14 SO R BCG treatment causes urinary requency (71%), cystitis (67%), hematuria (23%), ever (25%), 15 and, rarely, systemic granulomatous in ection requiring antituberculosis treatment.

TABLE 78-1 Blad d e r Cance r Cate g orie s, Stag e , and 5-Ye ar Survival Rate

Tumo r Cat e g o ry

St ag e o Tumo r *

De scrip t io n

5-Ye ar Survival

Non–muscle -invasive d ise ase Ta

Stag e 0 (N0,M0)

Nonmuscle -invasive a illary carcinoma

90%

Tis

Stag e 0 (N0,M0)

Carcinoma in situ

96.6%

T1

Stag e I (N0,M0)

Tumor invad ing t e lamina ro ria

T2a

Stag e II (N0,M0)

Tumor g rown into inne r alf of muscle laye r

T2b

Stag e II (N0,M0)

Tumor g rown into oute r alf of muscle laye r

T3†

Stag e III (N0,M0)

Tumor t roug muscle laye r into fatty tissue

T4a

Stag e III (N0,M0)

Tumor b e yond fatty tissue into ne arb y org ans ‡

T4b

Stag e IV (N0,M0)

Tumor b e yond into e lvic or ab d ominal wall‡

N0

Stag e IV

No lym

N1

Stag e IV

S re ad to sing le lym

N2

Stag e IV

S re ad to 2 or more lym

Muscle -invasive d ise ase 70.7%

Lymp h nod e

N3

nod e involve me nt

34.6%

nod e in true e lvis nod e s in true e lvis

S re ad to nod e s along t e common iliac arte ry

Me tastatic d ise ase M0 M1 *

Stag e IV

No d istant s re ad

5.4%

Cance r as s re ad to d istant site s *

De te rmine d b y comb ining t e tumor cate g ory wit re se nce or ab se nce and numb e r of lym nod e s involve d (N), and re se nce or ab se nce or d istant s re ad (e g , d istant lym nod e s, b one s, lung s, and live r). † Also d ivid e d into a (microsco ic s re ad into fatty tissue ) and b (visib le s re ad on imag ing or to t e e ye ). ‡ Also d ivid e d into a (s re ad to rostate or ute rus/vag ina) and b (s re ad to e lvic or ab d ominal wall). Information b ase d on SEER d ata. tt ://se e r.cance r.g ov/statfacts/ tml/urinb . tml. Acce sse d June 2014.

BLa DDe r Ca NCe r

PART 11

GENITO URINARY/ RENAL

• For Ta, Tis, or T1 tumors that are initially histologically con irmed as high grade, the AUA recommends repeat resection and additional intravesical therapy (induction course o BCG ollowed by maintenance therapy). 13 SO R A Cochrane review based on 5 small trials ound that immunotherapy with intravesical BCG ollowing surgery bene its patients with medium/ high risk Ta or T1 bladder cancer on delaying tumor recurrence. 15 Additional Cochrane reviews ound intravesical BCG more e ective than intravesical epirubicin or mitomycin C in reducing tumour recurrence (the latter only or patients at high risk o recurrence) 16,17; mitomycin C, however, was equivalent to BCG or disease progression and survival. SO R

• The EAU working group suggests use o a weighted scoring system to estimate recurrence and progression risk. 19 Factors include number, size, category, and grade o tumors; recurrence; and concomitant CIS. Scores range rom 0 to 17 or recurrence and 0 to 23 or progression. These scores are translated into probabilities or 1-year and 5-year recurrence (15% and 31%, respectively, or a score o 0, and 61%78%, respectively, or a score o 10-17) and 1-year and 5-year progression (0.2% and 0.8%, respectively, or a score o 0, and 17%-45%, respectively, or a score o 14-23).

• Persistent or recurrent super icial disease—Repeat resection with an induction course o BCG; maintenance BCG or mitomycin C is recommended or consideration o intravesical chemotherapy (valrubicin or gemcitabine). SO R For treatment ailure o patients with non–muscle-invasive bladder tumors, EAU recommends radical cystectomy or those with high-grade tumors and cystectomy or other patients with T1 tumors. 9 SO R Delay in cystectomy or these patients increases the risk o progression and cancer-speci ic death. 9

• Five-year survival rates or super cial disease are 90%; in ltrating (stage II or III), 35% to 70%; metastatic disease (stage IV), 5.4% to 20% (see Table 78-1). 1 Long-term disease- ree survival is reported in approximately 15% o patients with nodal disease and good per ormance status.

• Recurrent high-grade T1 tumors or invasive-muscle disease (extends to muscle or lymph nodes)—Radical cystectomy and pelvic lymphadenectomy with or without systemic chemotherapy. 2,9 SO R In men, radical cystectomy includes removal o the prostate, seminal vesicles, and proximal urethra resulting in impotence. In women, the uterus, ovaries, and anterior vaginal wall are removed. Most patients receive cutaneous reservoirs (bowel or orthotopic neobladder) drained by intermittent sel -catheterization.

• Recurrence rates overall are 50% with a median recurrence at 1 year (0.4 to 11 years), and 5% to 20% progress to a more advanced stage. Patients should be seen every 3 months or the rst year. SO R The ACR and EAU recommend stopping oncologic surveillance a ter 5-years o normal ollow-up to be replaced by unctional surveillance (eg, renal unction). 4,9

• Chemotherapy is not used or nonurothelial cancers, such as squamous cell carcinoma or adenocarcinoma, which are primarily treated with cystectomy. 2

• Risk o disease progression by tumor grade: 10% to 15% progress with grade 1 tumors, 14% to 37% with grade 2, and 33% to 64% with grade 3 tumors. 20

FO LLO W-UP

• For patients with high-grade Ta and T1 disease, cystoscopy, urinalysis, and urine cytology are recommended every 3 months or 2 years, then every 6 months or 2 years, then annually. Imaging o the upper tract collecting system is per ormed every 1 to 2 years. 2,4

O THER THERAPY

• For patients with muscle-invasive disease, laboratory tests (liver unction test, creatinine clearance, electrolyte panel) in addition to a chest X-ray are recommended every 6 to 12 months with imaging o upper urinary tract, abdomen, and pelvis or recurrence every 3 to 6 months or 2 years, and then as clinically indicated. 3

• In a Cochrane review o 3 trials comparing radical radiotherapy ollowed by surgery (salvage cystectomy) versus radical cystectomy, overall survival was better with radical cystectomy. 18 SO R

• For patients undergoing bladder-sparing surgery, urine cytology with or without biopsy is conducted every 3 months or 1 year, then at increasing intervals. 3

• External-beam radiotherapy alone is considered an option or patients un t or cystectomy or to stop the bleeding rom a tumor when local control can’t be achieved by transurethral manipulation because o extensive local tumor growth. 9 SO R

• For patients undergoing cystectomy, urine cytology is conducted every 6 to 12 months, and or those undergoing cystectomy and cutaneous diversion, urethral wash cytology is recommended every 6 to 12 months. 3

• Upper urinary tract recurrence—Radical nephroureterectomy. SO R

PREVENTIO N Eliminate active and passive smoking. 9 SO R

PRO GNO SIS

• For patients with cystectomy and continent orthotopic diversion, vitamin B12 level should be checked annually. 3,21 • Bladder tumor markers rom voided urine will likely improve detection o recurrence in the uture, but data are still insu cient to warrant substitution o cystoscopic ollow-up. 4,22

PATIENT EDUCATIO N

• Most recurrences are also super cial tumors with only approximately 10% to 15% o tumors progressing to invasive disease. 4

• The most important primary prevention or muscle-invasive bladder cancer is to eliminate active and passive smoking.

• Per ormance status, ranging rom 0 ( ully active) to 4 (completely disabled), and the presence or absence o visceral metastases are independent prognostic actors or survival.

• Tumor recurrence and progression risk can be estimated rom clinical and pathologic actors;4 this in ormation may help in joint decisionmaking or primary treatment and ollow-up intervals.

393

394

PART 11

GENITO URINARY/ RENAL PATIENT RESO URCES

• Medline plus. Bladder Cancer—www.nlm.nih.gov/ medlineplus/ bladdercancer.html. • Cancer Research, UK. Bladder Cancer—http:/ / cancerhelp .cancerresearchuk.org/ type/ bladder-cancer/ about/ . • Macmillan Cancer Support. Bladder Cancer—http:/ / www .macmillan.org.uk/ Cancerinformation/ Cancertypes/ Bladder/ Bladdercancer.aspx. PRO VIDER RESO URCES

• SEER Cancer Statistics Review—http:/ / seer.cancer.gov/ statfacts/ html/ urinb.html. REFERENCES 1. SEER Cancer Statistics Review. http:/ / seer.cancer.gov/ stat acts/ html/ urinb.html. Accessed November 2011. 2. Scher HI, Motzer RJ. Bladder and renal cell carcinomas. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds. Harrison’s Principles of Internal Medicine, 16th ed. New York, NY: McGraw-Hill; 2005:539-540. 3. Sharma S, Ksheersagar P, Sharma P. Diagnosis and treatment of bladder cancer. Am Fam Physician. 2009;80(7):717-723. 4. American College o Radiology (ACR), Expert Panel on Urologic Imaging. ACR Appropriateness Criteria® Pretreatment Staging of Invasive Bladder Cancer (2009). http:/ / www.guideline.gov/ content.aspx?id= 43878&search= bladder+ cancer. Accessed July 2013. 5. Quilty PM, Kerr GR. Bladder cancer following low or high dose pelvic irradiation. Clin Radiol. 1987;38(6):583-585. 6. Band PR, Le ND, MacArthur AC, et al. Identi cation o occupational cancer risks in British Columbia: a population-based casecontrol study o 1129 cases o bladder cancer. J Occup Environ Med. 2005;47(8):854-858. 7. Villanueva CM, Cantor KP, King WD, et al. Total and speci c uid consumption as determinants o bladder cancer risk. Int J Cancer. 2006;118(8):2040-2047. 8. Aben KK, Witjes JA, Schoenberg MP, et al. Familial aggregation of urothelial cell carcinoma. Int J Cancer. 2002;98(2):274-278. 9. Gutiérrez Baños JL, Rebollo Rodrigo MH, Antolín Juárez FM, Martín García B. NMP 22, BTA stat test and cytology in the diagnosis o bladder cancer: a comparative study. Urol Int. 2001;66(4):185-190.

Ch ApTER 78

10. European Association o Urology. Guidelines on Bladder Cancer: MuscleInvasive and Metastatic. http:/ / www.guidelines.gov/ content.aspx?id =12524&search= bladder+ cancer. Accessed July 2013. 11. Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy or invasive bladder cancer. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD005246. 12. Vale CL, Advanced Bladder Cancer Meta-analysis Collaboration. Adjuvant chemotherapy or invasive bladder cancer (individual patient data). Cochrane Database Syst Rev. 2006 Apr 19;(2): CD006018. 13. American Urological Association guideline. http:/ / www.guidelines. gov/ content.aspx?id=11795&search= bladder+ cancer. Accessed July 2013. 14. Shelley MD, Wilt TJ, Court J, et al. Intravesical bacillus CalmetteGuerin is superior to mitomycin C in reducing tumour recurrence in high-risk super cial bladder cancer: a meta-analysis o randomized trials. BJU Int. 2004;93(4):485-490. 15. Shelley M, Court JB, Kynaston H, et al. Intravesical bacillus Calmette-Guérin in Ta and T1 bladder cancer. Cochrane Database Syst Rev. 2000;(4):CD001986. 16. Shang PF, Kwong J, Wang ZP, et al. Intravesical Bacillus CalmetteGuérin versus epirubicin or Ta and T1 bladder cancer. Cochrane Database Syst Rev. 2011 May 11;(5):CD006885. 17. Shelley M, Court JB, Kynaston H, et al. Intravesical bacillus Calmette-Guérin versus mitomycin C or Ta and T1 bladder cancer. Cochrane Database Syst Rev. 2003;(3):CD003231. 18. Shelley M, Barber J, Wilt T, Mason M. Surgery versus radiotherapy or muscle invasive bladder cancer. Cochrane Database Syst Rev. 2002;(1):CD002079. 19. European Association o Urology. Guidelines onTaT1 (Non-Muscle Invasive) Bladder Cancer. http:/ / www.guideline.gov/ content.aspx?id= 34059. Accessed July 2013. 20. Canadian Cancer Society. http:/ / www.cancer.ca/ ?Val= E. Accessed July 2013. 21. Ganesan T, Khadra MH, Wallis J, Neal DE. Vitamin B12 malabsorption ollowing bladder reconstruction or diversion with bowel segments. ANZ J Surg. 2002;72(7):479-482. 22. Lokeshwar VB, Habuchi T, Grossman HB, et al. Bladder tumor markers beyond cytology: International consensus panel on bladder tumor markers. Urology. 2005;66:35-63.

HYDRO NEPHRO SIS

79 HYDRO NEPHRO SIS

PART 11

GENITO URINARY/ RENAL • Hydronephrosis is common in pregnancy because o the compression rom the enlarging uterus and unctional e ects o progesterone.

Mind y A. Smith, MD, MS

ETIO LO GY AND PATHO PHYSIO LO GY PATIENT STO RY A 74-year-old man presented with a 2-day history o severe, steady pain radiating down to the lower abdomen and le t testicle. He has had urinary requency, nocturia, hesitancy, and urinary dribbling or several years with slight worsening with time. CT scan revealed le t-sided hydronephrosis (Figure 79-1). In this patient, an irregular mass was seen at the le t ureterovesical junction compressing the bladder. Prostate cancer was ound on biopsy.

INTRO DUCTIO N Hydronephrosis re ers to distention o the renal calyces and pelvis o 1 or both kidneys by urine. Hydronephrosis is not a disease but a physical result o urinary blockage that may occur at the level o the kidney, ureters, bladder, or urethra. The condition may be physiologic (eg, occurring in up to 80% o pregnant women) or pathologic.

EPIDEMIO LO GY • O acquired causes in adults, pelvic tumors, renal calculi, and urethral stricture predominate. 1 I renal colic is present, renal stone is likely present (90% in 1 study). 2

• Bilateral hydronephrosis is caused by a blockage to urine ow occurring at or below the level o the bladder or urethra. • Unilateral hydronephrosis is caused by a blockage to urine ow occurring above the level o the bladder. • Multiple causes result in this condition including congenital (eg, vesicoureteral re ux [VUR]), acquired intrinsic (eg, calculi, in ammation, and trauma), and acquired extrinsic (eg, pregnancy or uterine leiomyoma, retroperitoneal f brosis). Within these groupings, obstruction may be a result o mechanical (eg, benign prostatic hypertrophy) or unctional (eg, neurogenic bladder) de ects. • Urinary obstruction causes a rise in ureteral pressure leading to declines in glomerular f ltration, tubular unction (eg, ability to transport sodium and potassium or adjust urine concentration), and renal blood ow. • I obstruction persists, tubular atrophy and permanent nephron loss can occur.

DIAGNO SIS A work-up or hydronephrosis in adults is o ten triggered by the discovery o azotemia (caused by impaired excretory unction o sodium, urea, and water). Sudden or new onset o hypertension (because o the increased renin release with unilateral obstruction) may also trigger an investigation. A f rst step in the evaluation is to per orm bladder catheterization. I diuresis occurs, the obstruction is below the bladder neck. CLINICAL FEATURES • Pain is the symptom that most commonly leads an adult patient to seek medical attention. This is caused by distention o the collecting system or renal capsule. The pain is o ten described as severe, steady, and radiating down to the lower abdomen, testicles, or labia. Flank pain with urination is pathognomonic or VUR. • Disturbed excretory unction or di f culty in voiding: Oliguria and anuria are symptoms o complete obstruction whereas polyuria and nocturia occur with partial obstruction (impaired concentrating ability causes osmotic diuresis). • Fever or dysuria can occur with associated urinary tract in ection (UTI). • The physical examination may reveal distention o the kidney or bladder. Rectal examination may show an enlarged prostate, or rectal/ pelvic mass and pelvic examination may reveal an enlarged uterus or pelvic mass. LABO RATO RY TESTING • Urinalysis may show hematuria, pyuria, proteinuria, or bacteruria but the sediment is o ten normal. 3

FIGURE 79-1 Intrave nous urog ram showing le t hyd rone p hrosis and hyd roure te r. (Re p ro d uce d with p e rmission fro m Schwartz DT, Re isd orff EJ. Eme rg e ncy Rad iolog y. Ne w York: McGraw-Hill; 2000:540, Fig ure . 19-45. Cop yrig ht 2000.)

• Assess renal unction (blood urea nitrogen [BUN], creatinine). • Urodynamic testing may be indicated or patients with neurogenic bladder or other suspected bladder causes o hydronephrosis.

395

PART 11

396

GENITO URINARY/ RENAL

Ch a pt e r 79

• One study o magnetic resonance (MR) pyelography (vs. ultrasound and urography) reported a sensitivity in detecting stones, strictures, and congenital ureteropelvic junction obstructions o 68.9%, 98.5%, and 100%, respectively, with a specif city o 98%. 3 Accuracy regarding the level o obstruction was high (100%). • Antegrade urography (percutaneous placement o ureteral catheter) or retrograde urography (cystoscopic placement o ureteral catheter) may be needed in patients with azotemia and poor excretory unction or in those at high risk o acute renal ailure rom IV contrast (ie, diabetes, multiple myeloma). • A voiding cystourethrogram is use ul in the diagnosis o VUR and bladder neck and urethral obstructions.

DIFFERENTIAL DIAGNO SIS Hydronephrosis is usually ound during an investigation or symptoms such as ank pain or renal ailure. Following are other causes o ank pain: FIGURE 79-2 Large irre g ular calcif cation (arrow) re pre se nting ure te rolithiasis in the le t sid e o the p e lvis in the p atie nt in Fig ure 69-1. (Re p rod uce d with p e rmission from Schwartz DT, Re isd orff EJ. Eme rg e ncy Rad iolog y. Ne w York: McGraw-Hill; 2000:539, Fig ure . 19-43. Cop yrig ht 2000.)

IMAGING • Ultrasound imaging has a sensitivity and specif city o 90% or identi ying the presence o hydronephrosis i no diuresis occurs ollowing bladder catheterization. 4 • I a source remains unidentif ed, an IV urogram (Figures 79-1 and 79-2) and/ or CT scan (Figure 79-3) should be obtained to diagnose intraabdominal or retroperitoneal causes.

• Pyelonephritis—Fever, chills, nausea, vomiting, and diarrhea o ten occurring with or without symptoms o cystitis. • Cholelithiasis—Pain is more typical in the epigastrium and right upper quadrant (biliary colic) and o ten nausea and vomiting occurs (see Chapter 69, Gallbladder Disease). • Other urologic disorders include ureteropelvic junction obstruction, renal subcapsular hematoma, and renal cell carcinoma (see Chapter 85, Renal Cell Carcinoma). Causes o unexplained renal ailure in adults: • Hypoper usion (prerenal ailure) (see Chapter 86, Renal Failure). • Acute tubular necrosis (ATN), interstitial, glomerular, or small vessel disease (intrarenal ailure). • Hypoper usion and ATN account or the majority o cases o acute renal ailure.

MANAGEMENT NO NPHARMACO LO GIC Functional causes can be treated by requent voiding or catheterization (intermittent pre erred). SO R MEDICATIO NS • Adult patients with hydronephrosis, complicated by in ection, should be treated with appropriate antibiotics or 3 to 4 weeks. Chronic or recurrent unilateral in ections may require nephrectomy. SO R • Anticholinergic drugs (eg, oxybutynin, tolterodine) are recommended or patients with neurogenic bladder. SO R PRO CEDURES AND SURGERY • Hydronephrosis with in ection is a urologic emergency that can be treated by prompt drainage using retrograde stent insertion or percutaneous nephrostomy. 4 FIGURE 79-3 Rig ht-sid e d hyd rone p hrosis (arrow) se e n on CT. (Re p rod uce d with p e rmission from Karl T. Re w, MD.)

• Pyeloplasty is a surgical technique or repairing an obstruction between the ureter and kidney that involves excising the obstructing segment with reanastomosis o the ureter. In 1 review o largely retrospective

HYDRO NEPHRO SIS

data, both open and laparoscopic pyeloplasty had higher success rates than endopyelotomy (94.1% and 95.9%-97.2% vs. 62%-83%, respectively). 5 • Treatment or VUR includes surgical repair (ureteral reimplantation or ureteroneocystostomy) or endoscopic injection o a bulking agent. Surgical repair reduces rates o pyelonephritis compared to medical treatment, but not UTI or renal scarring. 6 • Stenting (conventional and metallic) is also used or bypassing ureteral obstruction to alleviate hydronephrosis. 7 The American College o Radiology (ACR) recommends percutaneous antegrade ureteral stenting or percutaneous nephrostomy or a ebrile nonanuric patients with acute hydronephrosis. 8 In a septic patient with acute obstruction, ACR recommends urgent percutaneous nephrostomy (pre erred) or urgent retrograde ureteral stenting. 8

PART 11

GENITO URINARY/ RENAL PATIENT RESO URCES

• National Kidney Foundation (800-622-9010) or www. kidney.org. • National Institutes of Health, MedlinePlus. Bilateral Hydronephrosis— http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000474.htm. PRO VIDER RESO URCES

• Lusaya DG, Lerma EV. Hydronephrosis and Hydroureter— http:/ / emedicine.medscape.com/ article/ 436259. • Vatakencherry G, Funaki BS, Ray CE Jr, et al; Expert Panel on Interventional Radiology. ACR Appropriateness Criteria® Treatment o Urinary Tract Obstruction. [online publication]. Reston, VA: ACR; 2010. 7 p. http:/ / www.guideline.gov/ content.aspx?id=23819.

• Patients with renal ailure can be treated with dialysis (see Chapter 86, Renal Failure). SO R • Elective surgery or drainage is per ormed or persistent pain or progressive loss o renal unction. SO R

PREVENTIO N AND SCREENING The prevalence o VUR in siblings o an index case is 27.4% and in o spring 35.7%; severe re ux is identif ed in approximately 10% o screened patients. 9 Because o the lack o randomized controlled trials o treated versus untreated screened siblings with VUR regarding health outcomes, the best screening strategy is not known.

PRO GNO SIS Prognosis depends on the underlying etiology.

FO LLO W-UP • Prognosis or an adult patient depends on the duration and completeness o the obstruction and associated complications like in ection; complete obstruction or 1 to 2 weeks may be ollowed by partial return o renal unction, but a ter 8 weeks, recovery is unlikely. 1 • Postobstructive diuresis can cause loss o sodium, potassium, and magnesium that may require replacement in the setting o hypovolemia, hypotension, or electrolyte imbalance.

PATIENT EDUCATIO N Education regarding VUR should include a discussion o the treatment rationale, treatment approaches, and likely adherence with the care plan.

REFERENCES 1. Sei ter JL, Brenner BM. Urinary tract obstruction. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds. Harrison’s Principles o Internal Medicine, 16th ed. New York, NY: McGraw-Hill; 2005:1722-1724. 2. Pepe P, Motta L, Pennisi M, Aragona F. Functional evaluation o the urinary tract by color-Doppler ultrasonography (CDU) in 100 patients with renal colic. Eur J Radiol. 2005;53(1):131-135. 3. Blandino A, Gaeta M, Minutoli F, et al. MR pyelography in 115 patients with a dilated renal collecting system. Acta Radiol. 2001;42(5): 532-536. 4. Ramsey S, Robertson A, Ablett MJ, et al. Evidence-based drainage o in ected hydronephrosis secondary to ureteric calculi. J Endourol. 2010;24(2):185-189. 5. Gallo F, Schenone M, Giberti C. Ureteropelvic junction obstruction: which is the best treatment today? J Laparoendosc Adv SurgTech A. 2009; 19(5):657-652. 6. Estrada CR, Cendron M. Vesicoureteral Ref uxTreatment and Management. http:/ / emedicine.medscape.com/ article/ 439403-treatment# a1128. Accessed January 2012. 7. Modi AP, Ritch CR, Arend D, et al. Multicenter experience with metallic ureteral stents or malignant and chronic benign ureteral obstruction. J Endourol. 2010;24(7):1189-1193. 8. Vatakencherry G, Funaki BS, Ray CE Jr; Expert Panel on Interventional Radiology. ACR Appropriateness Criteria®;Treatment o Urinary Tract Obstruction [online publication]. Reston, VA: American College o Radiology; 2010. 7 p. http:/ / www.guideline.gov/ content.aspx?id= 23819&search= hydronephrosis. Accessed January 2012. 9. Skoog SJ, Peters CA, Arant BS Jr, et al. Pediatric Vesicoureteral Re ux Guidelines Panel summary report: clinical practice guidelines or screening siblings o children with vesicoureteral re ux and neonates/ in ants with prenatal hydronephrosis. J Urol. 2010;184(3): 1145-1151.

397

398

PART 11

GENITO URINARY/ RENAL

Ch a pt e r 80

80 KIDNEY STO NES Karl T. Re w, MD Mind y A. Smith, MD, MS

PATIENT STO RY A 55-year-old woman presents with severe pain in the right ank. The pain began suddenly a ter supper and increased dramatically over the next hour. Urinalysis shows blood but no signs o in ection. Abdominal X-ray reveals bilateral renal stones (Figure 80-1). A noncontrast CT scan conf rms multiple bilateral renal stones, with an obstructing right distal ureteral stone and enlargement o the right kidney (Figure 80-2). She is subsequently ound to have hyperparathyroidism, which is the cause o her multiple stones.

INTRO DUCTIO N A kidney stone is a solid mass that orms when minerals crystallize and collect in the urinary tract. Kidney stones can cause pain and hematuria and may lead to complications such as urinary tract obstruction and in ection.

SYNO NYMS

FIGURE 80-2 Noncont ast CT of t ab d om n and p lvis of t sam woman s owing s v al of t ston s s n in Fig ure 80-1, includ ing a nonobst ucting ston in t int p ola gion of t ig t kid n y. B caus t ig t u t is ob st uct d b y a distal ston (not visib l on t is imag ), t ig t kid n y is nla g d , wit coll cting syst m d ilation and p in p ic st and ing . T la g l ft p oximal u t al ston s n in t is imag is only pa tially ob st ucting , causing mild d ilation in t l ft kid n y coll cting syst m. S v al small ston s a visib l in t l ft kid n y, and t l ft kid n y is som w at at op i d f om c onic ob st uction. (Re p rod uce d with p e rmission from Karl T. Re w, MD.)

Kidney stone, nephrolithiasis, renal calculus, renal stone, urinary tract stone, ureterolithiasis, and urolithiasis.

EPIDEMIO LO GY • The prevalence o kidney stones is increasing in the United States. 1 More than 5% o adults have kidney stone disease, with a li etime risk o 13% or men and 7% or women. • Men between the ages o 40 and 60 years have the highest risk o stones; or women, the risk peaks in their 50s. 2 • A rican Americans have a lower rate o kidney stones than white Americans. 1 • Calcium oxalate and calcium phosphate stones are the most common, occurring in 75% to 85% o patients. Struvite (magnesium ammonium phosphate) stones occur in 5% o cases. Uric acid stones occur in 5% to 10% o patients and cystine stones occur in 1% o cases. Other types o stones are less common. 3 • Calcium stones are more common in men than in women (ratio 2:1), whereas struvite stones are more common in women than in men (ratio 3:1). 3

ETIO LO GY AND PATHO PHYSIO LO GY

FIGURE 80-1 Plain X- ay of t ab d om n in a 55-y a -o ld woman s owing s v al ston s in t ig t kid n y (re d arrow) and a la g l ft u t al ston (white arrow) ad jac nt to t L2-L3 d isc sp ac . (Re p ro d uce d with p e rmission from Karl T. Re w, MD.)

• Kidney stones orm when there is supersaturation o otherwise soluble materials, usually rom increased excretion o these compounds or dehydration. Urine pH is a actor in stone ormation because urinary phosphate increases in alkaline urine, whereas uric acid predominates in acidic urine (pH 65 years old) ° Focal segmental glomerulosclerosis (35% overall, but up to 57% o NS cases among patients o A rican descent) ° Minimal-change disease and immunoglobulin (Ig) A nephropathy (25%) • Secondary NS ° Diabetes (the most common cause o NS in the United States) ° Amyloid (consider in older patients with otherwise-unexplained NS) ° Systemic lupus erythematosus (SLE) ° Myeloma ° Medications (eg, nonsteroidal anti-inf ammatory drugs [NSAIDs], lithium, inter eron-al a)

B FIGURE 81-1 Palp ation o this p atie nt’s ab d ominal wall (A) d uring the course o an ab d ominal e xamination re sulte d in ab d ominal wall p itting e d e ma as e xe mp lif e d b y the e xamine r’s hand imp rint (B). This p atie nt p re se nte d with a se ve ral-month history o incre asing lowe r-e xtre mity e d e ma and a se ve ral-ye ar history o untre ate d and p oorly controlle d typ e II d iab e te s me llitus. In the course o his workup , a re nal b iop sy conf rme d a d iag nosis o d iab e tic re nal d ise ase . Also, note the p e au d ’orang e chang e o the skin o the ab d ominal wall cause d b y the massive sub cutane ous e d e ma rom this p atie nt’s ne p hrotic synd rome . (Re p rod uce d with p e rmission from Gary Fe re nchick, MD.)

° In ections (eg, human immunode ciency virus [HIV], hepatitis B and C, syphilis) ° Congenital etiologies (eg, Alport syndrome)

DIAGNO SIS/ SCREENING HISTO RY/ SYMPTO MS Speci cally ask about the ollowing: • New onset o edema (the key clinical eature o NS) ° Periorbital edema ° Lower-extremity edema ° Abdominal wall edema (Figures 81-1 and 81-2)

Ne ph r O t IC SYNDr O Me

PART 11

GENITO URINARY/ RENAL ° Symptoms or signs o chronic in ectious hepatitis, including a recognized history o jaundice or elevated liver tests. ° Symptoms and signs o malignancy (especially bowel and lung as these have an association with membranous nephropathy). PHYSICAL EXAMINATIO N Speci cally look or or establish the ollowing: • The presence o periorbital or lower-extremity edema (Figures 81-3 and 81-4); in severe cases, anasarca may be present with edema o the scrotum and abdominal wall and the presence o ascites.

A

• The presence o xanthomas or xanthelasma (Figures 81-3 and 81-4, respectively). Xanthelasma consists o yellow lipid-laden deposits on the eyelids in some patients with hyperlipidemia. However, 50% o people with xanthelasma have normal lipids. ° Xanthomas are yellow, pink, or brown papules and plaques that can erupt on the skin o people with very high lipid levels. ° Although the NS causes hyperlipidemia, it does not necessarily lead to xanthomas and xanthelasma. ° NS should be considered in the di erential diagnosis o any patient with the skin ndings and hyperlipidemia (see Chapter 223, Hyperlipidemia). ° Cardiomyopathy, peripheral neuropathy, and hepatomegaly suggesting amyloidosis. ° Pulmonary ndings o a pleural e usion. ° Cutaneous ndings o chronic liver disease. LABO RATO RY TESTING • Proteinuria above 3 g in a 24-hour period or spot urine protein:creatinine (mg/ mg) ratio o 3 represents nephrotic-range proteinuria. Note that recent iodinated contrast studies inter ere with urinary protein determination. • Urinalysis is used to assess or hematuria, which i present would suggest glomerulonephritis, and to assess or the presence o a urinary tract in ection.

B FIGURE 81-2 The se p hoto s show the se ve re p e rip he ral e d e ma in the le t p re tib ial are a o the same p atie nt as in Fig ure 81-1 p re se nting with ne p hro tic synd ro me ro m d iab e tic ne p hro p athy. Comp re ssion with the thumb (A) le ave s an imp re ssive thumb p rint in the e d e mato us tissue (B). (Re p rod uce d with p e rmission fro m Gary Fe re nchick, MD.)

° Ascites ° Scrotal edema • Weight gain and atigue • Medications (including NSAIDs) • Symptoms o , or risk actors or, acute or chronic infections (eg, HIV, hepatitis B and C, syphilis), including being rejected as a blood donor, known history o a sexually transmitted disease, high-risk sexual behavior, injection drug use, mild right upper quadrant pain, atigue • Symptoms suggestive o systemic disease ° Neuropathy or visual changes o DM—Diabetic retinopathy is present in the majority o type 1 diabetic patients with nephropathy; there ore, i a diabetic patient presents with NS and has no retinopathy, a nondiabetic cause o NS should be sought. 1 ° Photosensitivity rash and arthralgias which might suggest SLE.

FIGURE 81-3 Erup tive xanthomas in a man with ve ry hig h trig lyce rid e s and chole ste rol. Althoug h ne p hrotic synd rome can cause this, the re are othe r cause s o se ve re hyp e rlip id e mia than can le ad to e rup tive xanthomas. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

403

PART 11

404

GENITO URINARY/ RENAL

Ch a pt e r 81

history o known cardiovascular disease and other ndings o cardiac compromise, such as pulmonary congestive symptoms and signs o reduced ventricular compliance, such as and S3 or S4 and abnormal echocardiogram. • Hypoalbuminemia can be a mani estation o severe chronic liver disease and can be di erentiated rom NS by other stigmata o chronic liver disease, the presence o portal hypertension, abnormal tests o liver unction, and abnormal hepatic imaging.

MANAGEMENT LO NG-TERM MANAGEMENT

FIGURE 81-4 Xanthe lasma in a p atie nt with marke d hyp e rchole ste ro le mia. Hyp e rcho le ste role mia is no t sp e cif c o r ne p hro tic synd ro me ; howe ve r, most p atie nts with ne p hrotic synd rome have hyp e rchole ste role mia, and most should b e strong ly consid e re d or statin the rap y. (Re p ro d uce d with p e rmission from Gary Fe re nchick, MD.)

• Serum albumin less than 2.5 gm/ dL is common is patients with NS. • Serum lipids should be evaluated as total cholesterol levels above 300 mg/ dL are present in 53% o patients. 2 • Serum urea nitrogen (BUN), creatinine level, and glomerular ltration rate (GFR) assess or renal ailure. • Tests can assess or potential systemic etiologies o NS, including ° Urine microscopy or red blood cells (which, i present, suggest glomerulonephritis) and to assess or the presence o in ection ° Liver unction tests to help identi y the presence o hepatitis ° Speci c tests or hepatitis B and C and HIV ° Glucose and hemoglobin A1c (HbA1c) to assess or the presence, or degree, o glucose intolerance ° C-reactive protein and sedimentation rate, although nonspeci c, to screen or the presence o systemic inf ammatory conditions ° Antinuclear antibodies (ANA) (and ollow-up anti-Smith antibody and anti-double-stranded DNA (anti-dsDNA) i the ANA value is positive) ° Serum and urine electrophoresis to identi y multiple myeloma or amyloid • Renal biopsy alters management 85% o the time. 3

• Edema management (goal weight loss o 0.5 kg per day). ° Sodium restriction (< 3 g a day). ° Restricted f uid intake (< 1.5 L a day). ° Loop diuretics initiated in a stepwise slow ashion to limit the potential or hypovolemia. ° Sequential nephron blockade may be appropriate or patients resistant to the use o a loop diuretic (combination o a loop diuretic and aldosterone antagonist with or without addition o thiazide). 4 ° Diuretics may need to be given intravenously initially as gut wall edema may limit absorption o oral diuretics. • The majority o patients with NS, regardless o etiology, ace the prospect o continued heavy protein loss, which can be associated with metabolic and immunologic disorders. 4 • Treat proteinuria with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists. 4-6 SO R ° Aggressive antihypertensive treatment in patients with type 2 diabetes with nephrotic-range albuminuria with ACE inhibitors or angiotensin II receptor blockers is associated with a 66% improved survival rate and 66% decreased risk o progression to end-stage renal disease in patients achieving a decrease in albuminuria rom 2.5 g per day to less than 600 mg per day in response to therapy. 7 SO R

C

• Treat hyperlipidemia with a statin. 8 SO R C • Advise normal protein intake. 4 SO R C • Assess bone mineral density and treat i osteoporosis is present (T < -2.5) or i the patient is osteopenic with a 10-year risk o hip racture greater than 3% or a 10-year risk o any osteoporotic racture o greater than 10%. • Consider corticosteroids. 9 SO R B

PRO GNO SIS/ CLINICAL CO URSE

IMAGING • Chest radiography to assess or the presence o a pleural e usion

Major complications o NS

• Echocardiogram to assess or the presence o a pericardial e usion

• Venous thrombosis is a result o antithrombotic actors being ltered through the glomeruli, producing an imbalance between procoagulant and anticoagulant actors. ° Greatest risk or venous thrombosis is within the rst 6 months o NS diagnosis. ° NS is associated with elevated procoagulant brinogen and actors V and VII and is associated with a decrease in brinolysis and anticoagulant actor antithrombin III. 4 ° Greatest risk is in patients with a serum albumin o < 2.5 mg/ dl ■ Lower-extremity deep vein thrombosis (DVT) occurs in 1.5% o patients with NS.

• Renal ultrasound or renal size and shape • Doppler o renal veins i f ank pain and hematuria are present to assess or renal vein thrombosis

DIFFERENTIAL DIAGNO SIS • Congestive heart ailure (CHF) is a primary di erential diagnosis in patients presenting with edema. Commonly, such patients have a

Ne ph r O t IC SYNDr O Me

■ ■

■

Renal vein thrombosis occurs in 0.5% o patients with NS. However, rates o thromboembolism as high as 35% have been reported, with the highest risk in patients with membranous nephropathy. 10 Patients with NS at high risk or thromboembolism (albumin < 2.5 mg/ dL, bed rest, membranous nephropathy, and clinical hypovolemia) should be considered or prophylactic anticoagulation with heparin during periods o en orced bed rest or systemic anticoagulation11 i serum albumin is persistently less than 2 g/ dL.

• In ection (cellulitis, bacterial pneumonia) occurs partly as a result o loss o protective IgG and complement levels and reduced T-cell unction. • Patients with NS should be given the pneumococcal vaccine. • Loss o vitamin D produces bone disease.

FO LLO W-UP • Assess the patient’s GFR and the amount o proteinuria using the protein-creatinine ratio every 3 months initially, then every 4 to 6 months therea ter in stable patients. • Monitor patients or worsening GFR, in ections, venous thromboembolism, cytopenias in patients on immunosuppressive therapy, and bone mineral density in patients on glucocorticoids.

PATIENT EDUCATIO N Educate patients on the potential adverse e ects o their medications, the potential complications o NS, and their expected clinical course. PATIENT RESO URCES

PART 11

GENITO URINARY/ RENAL REFERENCES 1. Parving HH, Hommel E, Mathiesen E, et al. Prevalence o microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin dependent diabetes. Br Med J (Clin Res Ed). 1988;296(6616):156-160. 2. Radhakrishnan J, Appel AS, Valeri A, Appel GB. The nephrotic syndrome, lipids, and risk actors or cardiovascular disease. Am J Kidney Dis. 1993;22(1):135-142. 3. Richards NT, Darby S, Howie AJ, Adu D, Michael J. Knowledge of renal histology alters patient management in over 40% o cases. Nephrol Dial Transplant. 1994;9(9):1255-1259. 4. Charlesworth JA, Gracey DM, Pussell BA. Adult nephrotic syndrome: non-speci c strategies or treatment. Nephrology (Carlton). 2008;13(1):45-50. 5. Korbet SM. Angiotensin antagonists and steroids in the treatment o ocal segmental glomerulosclerosis. Semin Nephrol. 2003;23(2): 219-228. 6. Ruggenenti P, Mosconi L, Vendramin G, et al. ACE inhibition improves glomerular size selectivity in patients with idiopathic membranous nephropathy and persistent nephrotic syndrome. Am J Kidney Dis. 2000;35(3):381-391. 7. Rossing K, Christensen PK, Hovind P, et al. Remission of nephroticrange albuminuria reduces risk o end-stage renal disease and improves survival in type 2 diabetic patients. Diabetologia. 2005;48(11):2241-2247. 8. Thomas ME, Harris KP, Ramaswamy C, et al. Simvastatin therapy or hypercholesterolemic patients with nephrotic syndrome or signi cant proteinuria. Kidney Int. 1993;44(5):1124-1129. 9. Crook ED, Habeeb D, Gowdy O, et al. E ects o steroids in ocal segmental glomerulosclerosis in a predominantly A rican-American population. Am J Med Sci. 2005;330(1):19-24.

• National Institute of Diabetes and Digestive and Kidney Diseases. Nephrotic Syndrome in Adults.—http:/ / kidney.niddk.nih.gov/ kudiseases/ pubs/ nephrotic/ .

10. Ponticelli C, Passerini P. Treatment o the nephrotic syndrome associated with primary glomerulonephritis. Kidney Int. 1994;46(3): 595-604.

• National Kidney Foundation. Nephrotic Syndrome—http:/ / www .kidney.org/ atoz/ content/ nephrotic.cfm.

11. Kayali F, Najjar R, Aswad F, Matta F, Stein PD. Venous thromboembolism in patients hospitalized with nephrotic syndrome. Am J Med. 2008;121(3):226-230.

PRO VIDER RESO URCES

• Medscape. Nephrotic Syndrome—http:/ / emedicine.medscape .com/ article/ 244631.

405

406

PART 11

GENITO URINARY/ RENAL

Ch a pt e r 82

82 PO LYCYSTIC KIDNEYS Mind y A. Smith, MD, MS

PATIENT STO RY A 43-year-old woman with newly diagnosed hypertension reports persistent bilateral ank pain. She has a family history of “kidney problems.” On urinalysis, she is noted to have microscopic hematuria. An ultrasound and abdominal CT scan show bilateral polycystic kidneys (Figure 82-1).

INTRO DUCTIO N Polycystic kidney disease (PKD) is a manifestation of a group of inherited disorders resulting in renal cyst development. In the most common form, autosomal-dominant polycystic kidney disease (ADPKD), extensive epithelial-lined cysts develop in the kidney; in some cases, abnormalities also occur in the liver, pancreas, brain, arterial blood vessels, or a combination of these sites.

EPIDEMIO LO GY • Most common tubular disorder of the kidney, affecting 1 in 300 individuals. • Autosomal dominant in 90% of cases, rarely as an autosomal recessive trait. 1 • Sporadic mutation in approximately 1:1000 individuals. • ADPKD accounts for approximately 5% to 10% of cases of end-stage renal disease (ESRD) in the United States. • Most frequently seen in the third and fourth decades of life, but can be diagnosed at any age.

FIGURE 82-2 CT scan showing multip le live r cysts and multip le cysts in b oth kid ne ys in a p atie nt with p olycystic kid ne y d ise ase . (Re p rod uce d with p e rmission of Ve s Dimov, M.D., Se ction of Alle rg y, Asthma and Immunolog y, De p artme nt of Pe d iatrics, De p artme nt of Me d icine , Unive rsity of Chicag o, ClinicalCase s.org )

ETIO LO GY AND PATHO PHYSIO LO GY • ADPKD results from mutations in either of 2 genes that encode plasma membrane–spanning polycystin 1 (PKD1) and polycystin 2 (PKD2). 2 Polycystins regulate tubular and vascular development in the kidneys and other organs (liver, brain, heart, and pancreas). PKD1 and PKD2 are colocalized in primary cilia and appear to mediate Ca2+ signaling as a mechanosensor, essential for maintaining the differentiated state of epithelia lining tubules in the kidney and biliary tract. 3 These mutations result in many abnormalities including increased proliferation and apoptosis and loss of differentiation and polarity.4 • Few (1%-5%) nephrons actually develop cysts. • Remaining renal parenchyma shows varying degrees of tubular atrophy, interstitial brosis, and nephrosclerosis. • Cysts are also found in other organs such as liver (Figure 82-2), spleen, pancreas, and ovaries. Liver cysts are found in up to 80% of patients with ADPKD. 2 There is also an increased incidence of intracranial aneurysms (5%-12%). • Autosomal-recessive PKD (ARPKD) is the neonatal form of PKD that is associated with enlarged kidneys and biliary dysgenesis. 3 • Rare syndromic forms of PKD include defects of the eye, central nervous system, digits, and/ or neural tube.3 • A variant of PKD is glomerulocystic kidney (GCK), which refers to a kidney with greater than 5% cystic glomeruli. 5 This condition is usually diagnosed in young patients. Although PKD-associated gene mutations have been excluded in many cases, there is a familial form of GCK presenting with cystic kidneys, hyperuricemia, and isosthenuria (concentration similar to plasma). 5

DIAGNO SIS Family history is a useful tool for diagnosing early ADPKD. CLINICAL FEATURES FIGURE 82-1 Bilate ral p olycystic kid ne ys se e n on CT scan in a 43-ye ar-old woman with hyp e rte nsion, he maturia and f ank p ain. (Re p rod uce d with p e rmission of Michae l Fre ckle ton, MD.)

• Chronic ank pain as a result of the mass effect of enlarged kidneys. • Acute pain with infection, obstruction, or hemorrhage into a cyst.

PART 11

pO LYCYSt IC KIDNe YS

• Enlarged liver. • Hypertension is common in adults (75%) and may be present in 10% to 30% of children.

GENITO URINARY/ RENAL 2 to 3 L/ day; hematuria generally declines to microscopic levels in a few days. 2 SO R C

• Kidney stones (calcium oxalate and uric acid) develop in 15% to 20% of affected individuals because of urinary stasis from distortion of the collecting system, low urine pH, and low urinary citrate.

MEDICATIO NS

• Nocturia may also be present from impaired renal concentrating ability.

• In 1 randomized controlled trial (RCT) of 46 patients with ADPKD and hypertension, no differences in renal function, urinary albumin excretion, or left ventricular mass index were detected between those treated with ramipril versus metoprolol, during 3 years of follow-up. 12 Renal function declined signi cantly in both groups. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are the traditionally used agents for patients with chronic kidney disease and hypertension. SO R

LABO RATO RY TESTING Gross or microscopic hematuria (60%). 2 Obtain a urinalysis to document hematuria and a complete blood count or hemoglobin to identify anemia. IMAGING • Diagnosis often made with ultrasound. More than 80% of patients have cysts present by age 20 years and 100% by age 30 years. In one study, the sensitivity of ultrasound in at-risk individuals younger than age 30 years was 70% to 95%, depending on the type of PKD present. 6 For younger patients or those with small cysts, CT scan (Figures 82-1 and 82-2) or MRI may be preferred. • Cysts are commonly found in the liver (50%-80%) (Figure 82-2), spleen, pancreas, and ovaries. • The diagnosis of PKD can usually be made from ultrasound characteristics, the presence or absence of extrarenal abnormalities, and screening of parents older than 40 years of age. 7 Age-dependent ultrasound criteria have been established for both diagnosis and disease exclusion in subjects at risk of PKD1 (the more severe disorder). 8 • If the diagnosis is uncertain, genetic testing is available for both ADPKD and ARPKD.

DIFFERENTIAL DIAGNO SIS2 • Simple cyst—Diagnosed at any age; few cysts seen; benign features. • Acquired cystic disease—Diagnosed in adulthood; few to many cysts; cyst development preceded by renal failure. • Tuberous sclerosis—Diagnosed at any age; few to many renal angiomyolipomas; inherited nonmalignant tumors grow in the skin, brain/ nervous system, kidneys, and heart.

MANAGEMENT The current role of therapy in PKD is to slow the rate of progression of renal disease and minimize symptoms. However, speci c treatments are on the horizon.

• Control blood pressure to reduce the risk of associated cardiovascular disease. SO R

• Treat infection as early as possible. If pyocyst is suspected, agents that penetrate cysts such as trimethoprim-sulfamethoxazole, chloramphenicol, and cipro oxacin are used. SO R C • Future therapies focus on exploiting signaling mechanisms underlying disease pathogenesis. Experimental and observational studies suggest that the mammalian target of rapamycin (mTOR) pathway plays a critical role in cyst growth. • A 2-year RCT of the mTOR inhibitor everolimus for 46 patients with ADPKD demonstrated a slowing of the increase in total kidney volume over placebo but not the progression of renal impairment. 13 An openlabel trial (N = 100 patients with ADPKD and early chronic kidney disease) of the mTOR inhibitor sirolimus did not show slowing of kidney growth or improved function over standard care. 14 • In an RCT of octreotide (a long-acting somatostatin analog) versus placebo for patients with polycystic liver disease (some of whom had ADPKD), patients with ADPKD randomized to octreotide had a stabilization of kidney volume (versus an increase in the control group) and all patients randomized to treatment showed a reduced liver volume; there was no difference between groups in GFR. 15 SURGERY AND O THER PRO CEDURES • Cyst puncture and a sclerosing agent (ie, ethanol) can be used in painful cysts. SO R C • For painful liver enlargement, partial hepatectomy can be performed, with good outcomes reported at experienced centers. 2 SO R C • For patients with ESRD as a result of PKD, transplantation and dialysis are options. • In a nationwide study of 15-year outcomes following renal transplantation (N = 534 patients with ADPKD and 4779 patients without ADPKD), patients with ADPKD had better graft survival and no difference in infections, but more thromboembolic complications, more metabolic complications, and increased incidence of hypertension. 16

NO NPHARMACO LO GIC • Neither protein restriction nor tight blood pressure control decreased the decline in glomerular ltration rate (GFR) in clinical trials.9,10 However, in a UK population study, increasing coverage (from 7% to 46% of the population prescribed an antihypertensive agent) showed a trend toward decreasing mortality and increased intensity of antihypertensive therapy was associated with decreasing mortality in people with ADPKD.11

REFERRAL

• For episodes of gross hematuria, one author recommends bed rest, analgesics, and hydration suf cient to increase the urinary ow rate to

• Consider hospitalization for patients with PKD who develop acute pyelonephritis and symptomatic cyst infection. 2

• Patients with PKD with progressive renal failure and/ or ESRD should be managed by a team of providers as they often require dialysis or kidney transplantation and can develop multiple complications; other considerations include anemia management, aneurysm screening pretransplantation, and nephrectomy of the native ADPKD kidneys. 17 SO R C

407

408

PART 11

GENITO URINARY/ RENAL PRO GNO SIS • Approximately 50% of patients with ADPKD progress slowly to ESRD; kidney failure requiring renal-replacement therapy typically develops in the fourth to sixth decade of life. 2 Patients with ADPKD and ESRD may have more favorable outcomes compared to those with other causes of kidney failure. 16 • The following are the characteristics that predict a faster rate of decline in GFR in persons with ADPKD18: ° Greater serum creatinine (independent of GFR). ° Greater urinary protein excretion. ° Higher mean arterial pressure (MAP). ° Young age. 2 ° Increased kidney volume (> 1500 mL). 19 ° Disease caused by PKD1 mutation. 20 The presence of tubulointerstitial brosis. ° • Patients with ADPKD are also more prone to kidney stones (Chapter 80, Kidney Stones). 21

FO LLO W-UP • Monitor patients renal function and watch for hypertension and posttransplantation diabetes mellitus; imaging to assess the rate of increased kidney and total cyst volume may be useful in prognosis. 22 • Avoid exogenous estrogen use for women with ADPKD and liver cystic enlargement; consider limiting use in women with liver cysts. 2 • For all patients with PKD with renal dysfunction, review medications to adjust for level of kidney function and avoid nephrotoxic drugs if possible. SO R C • The prognosis for patients following renal transplant is fairly good. In a follow-up study of patients with ADPKD, adult cadaveric renal transplant survival at 5 years was found to be 79%. 23 • In the absence of a family history of aneurysm, screening is not routinely recommended for asymptomatic patients; diagnostic testing should be considered in patients with ADPKD and new-onset or severe headache or other central nervous system symptoms or signs. 2 • Posttransplantation, patients with ADPKD may be more prone to the development of diabetes mellitus (odds ratio 2.3, 95% con dence interval, 1.008 to 5.14). 24

PATIENT EDUCATIO N • Explain the genetics (among patients with ADPKD disease will develop in half of their offspring) and prognosis to patients. Referral to a genetic counselor may be useful for patients considering childbearing. • Hypertension is common and should be treated. • Kidney dysfunction is also common and should be monitored. • Avoid high-impact sports in which abdominal trauma may occur (eg, boxing). 2 • In otherwise healthy women with ADPKD, pregnancy is usually uncomplicated but the risks of severe hypertension and preeclampsia are higher than those in the general population when elevated blood pressure or renal insuf ciency is present before conception. 25

Ch a pt e r 82

PATIENT RESO URCES

• National Kidney Foundation (800-622-9010)—http:/ / www .kidney.org. • National Kidney Disease Education Program—http:/ / www .nkdep.nih.gov. • PubMed Health. Polycystic Kidney Disease—http:/ / www.ncbi .nlm.nih.gov/ pubmedhealth/ PMH0001531/ . PRO VIDER RESO URCES

• Roser T. Polycystic Kidney Disease—http:/ / emedicine.medscape .com/ article/ 244907.

REFERENCES 1. Asplin JR, Coe FL. Tubular disorders. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds. Harrison’s Principles of Internal Medicine, 16th ed. New York, NY: McGraw-Hill; 2005:1694-1696. 2. Grantham JJ. Autosomal dominant polycystic kidney disease. Ann Transplant. 2009;14(4):86-90. 3. Harris PC, Torres VE. Polycystic kidney disease. Annu Rev Med. 2009;60:321-337. 4. Park EY, Woo YM, Park JH. Polycystic kidney disease and therapeutic approaches. BMB Rep. 2011;44(6):359-368. 5. Lennerz JK, Spence DC, Iskandar SS, et al. Glomerulocystic kidney: one hundred-year perspective. Arch Pathol Lab Med. 2010;134(4):583-605. 6. Nicolau C, Torra R, Bandenas C, et al. Autosomal dominant polycystic kidney disease types 1 and 2: assessment of US sensitivity for diagnosis. Radiology. 1999;213(1):273-276. 7. Sweeney WE Jr, Avner ED. Diagnosis and management of childhood polycystic kidney disease. Pediatr Nephrol. 2011;26(5):675-692. 8. Barua M, Pei Y. Diagnosis of autosomal-dominant polycystic kidney disease: an integrated approach. Semin Nephrol. 2010;30(4):356-365. 9. Klahr S, Breyer JA, Beck GJ, et al. Dietary protein restriction, blood pressure control, and the progression of polycystic kidney disease. Modi cation of Diet in Renal Disease Study Group. JAm Soc Nephrol. 1995;6(4):1318. 10. Schrier R, McFann K, Johnson A, et al. Cardiac and renal effects of standard versus rigorous blood pressure control in autosomal-dominant polycystic kidney disease: results of a seven-year prospective randomized study. JAm Soc Nephrol. 2002;13(7):1733-1739. 11. Patch C, Charlton J, Roderick PJ, Gulliford MC. Use of antihypertensive medications and mortality of patients with autosomal dominant polycystic kidney disease: a population-based study. Am J Kidney Dis. 2011;57(6):856-862. 12. Zeltner R, Poliak R, Stiasny B, et al. Renal and cardiac effects of antihypertensive treatment with ramipril vs metoprolol in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2008;23(2): 573-579. 13. Walz G, Budde K, Mannaa M, et al. Everolimus in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2010;363(9):830-840. 14. Serra AL, Poster D, Kistler AD, et al. Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med. 2010;363(9):820-829.

pO LYCYSt IC KIDNe YS

PART 11

GENITO URINARY/ RENAL

15. Hogan MC, Masyuk TV, Page LJ, et al. Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney and liver disease. JAm Soc Nephrol. 2010;21(6):1052-1061.

21. Nishiura JL, Neves RF, Eloi DR, et al. Evaluation of nephrolithiasis in autosomal dominant polycystic kidney disease patients. Clin JAm Soc Nephrol. 2009;4(4):838-844.

16. Jacquet A, Pallet N, Kessler M, et al. Outcomes of renal transplantation in patients with autosomal dominant polycystic kidney disease: a nationwide longitudinal study. Transpl Int. 2011;24(6):582-587.

22. Bae KT, Grantham JJ. Imaging for the prognosis of autosomal dominant polycystic kidney disease. Nat Rev Nephrol. 2010;6(2):96-106.

17. Alam A, Perrone RD. Management of ESRD in patients with autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 2010;17(2):164-172. 18. Klahr S, Breyer JA, Beck GJ, et al. Dietary protein restriction, blood pressure control, and the progression of polycystic kidney disease. Modi cation of Diet in Renal Disease Study Group. JAm Soc Nephrol. 1995;6(4):1318. 19. Pei Y. Practical genetics for autosomal dominant polycystic kidney disease. Nephron Clin Pract. 2011;118(1):c19-c30. 20. Norman J. Fibrosis and progression of autosomal dominant polycystic kidney disease (ADPKD). Biochim Biophys Acta. 2011;1812(10): 1327-1336.

23. Johnston O, O’Kelly P, Donohue J, et al. Favorable graft survival in renal transplant recipients with polycystic kidney disease. Ren Fail. 2005;27(3):309-314. 24. Gonclaves S, Guerra J, Santana A, et al. Autosomal-dominant polycystic kidney disease and kidney transplantation: experience of a single center. Transplant Proc. 2009;41(3):887-890. 25. Vora N, Perrone R, Bianchi DW. Reproductive issues for adults with autosomal dominant polycystic kidney disease. Am J Kidney Dis. 2008;51(2):307-318.

409

410

PART 11

GENITO URINARY/ RENAL

Ch a pt e r 83

83 PRO STATE CANCER Rowe na De Souza, MD Me lanie Ke tchand ji, MD

PATIENT STO RY A 65-year-old man in good health comes to the of ce having had a prostate speci c antigen (PSA) test performed at a local health fair. He reports a normal voiding pattern and normal erectile function with no evidence of weight loss or bone pain. He has no major medical problems but does have a strong family history of prostate cancer. His PSA is 9.3 ng/ mL, and he chooses to have a prostate biopsy. Pathology demonstrates prostate cancer with a Gleason score of 6 (Figure 83-1).

INTRO DUCTIO N Prostate cancer is a very common cancer in men. Secondary to widespread testing, we have seen a stage migration in prostate cancer. Most patients are diagnosed with asymptomatic, clinically localized disease. Multiple factors—such as Gleason score, PSA level, stage at diagnosis, and life expectancy—are all applied to risk stratify patients associated with varying possibilities of achieving a cure. It is especially important to consider life expectancy prior to offering PSA screening.

EPIDEMIO LO GY • In United States, prostate cancer (Figure 83-2) is the leading cancer in men and the second leading cause of cancer deaths in men. 1 • It is the second most common cancer in men worldwide, with an estimated 900,000 cases and 258,000 deaths in 2008. 2 • Incidence is increased with age.

FIGURE 83-2 Photog ap h showing ad e noca cinoma on the le ft lowe sid e o f the sp e cime n and b ilate al b e nig n p ostatic hyp e t op hy towa d the top . (Re p rod uce d with p e rmission of E.J. Maye aux, Jr., MD.)

• The risk of developing prostate cancer increases at age 40 years in black men and in those who have a rst-degree relative with prostate cancer. • The risk of developing prostate cancer begins to increase at age 50 years in white men who have no family history of the disease. 3 • There is no peak age or modal distribution. • The highest incidence of prostate cancer in the world is found in African American men, who have approximately a 9.8% lifetime risk of developing prostate cancer. This is accompanied by a high rate of prostate cancer mortality (Figure 83-3). • The lifetime risk of prostate cancer for white men in the United States is 8%. 3 • Japanese and mainland Chinese populations have the lowest rates of prostate cancer. • Socioeconomic status appears to be unrelated to the risk of prostate cancer.

ETIO LO GY AND PATHO PHYSIO LO GY • Greater than 95% of prostate cancers are adenocarcinomas. • Histologic variants include ductal or endometrioid carcinoma, mucinous adenocarcinoma, signet cell carcinoma, small cell carcinoma, squamous and adenosquamous carcinoma, basaloid, and adenoid cystic carcinoma. • Of prostate adenocarcinomas, 70% occur in the peripheral zone, 20% in the transitional zone, and approximately 10% in the central zone (Figure 83-4).

FIGURE 83-1 Mic oscop ic imag e of b iop sy d e monst ating g land s with e nla g e d nucle i and p omine nt nucle oli (he matoxylin and e osin [H&E] staining ). The p atie nt was d iag nose d with p o state cance with a Gle ason sco e of 6. (Re p rod uce d with p e rmission of E.J. Maye aux Jr, MD.)

• Biologic behavior is affected by histologic grade as described by the Gleason grade and Score (Figure 83-5). The Gleason grade is based on the architectural pattern of prostate cancer cells. Based upon the growth pattern and differentiation, tumors are graded from 1 to 5, with grade 1 being the most differentiated and grade 5 the least differentiated. One grade is assigned to the most common tumor pattern, and a second grade to the next most common tumor pattern. The Gleason Score is obtained by adding the two grades together and ranges from 2 to 10. A higher score indicates a greater likelihood of having non–organ-con ned disease, as well as a worse outcome after treatment of localized disease.

PART 11

pr O St a t e Ca NCe r

GENITO URINARY/ RENAL

Ag e -Adjus te d U.S . Mo rtality Rate s by Rac e /Ethnic ity Po s tate , Ag e s 50+, Male 1975-20 08

350

White Bla ck 300

200

150

R

a

t

e

p

e

r

10

0

,

0

0

0

250

100

50

0 2

0 0 2

0 0 0 2

5 9 1

9

0

5

9 1

9

5 8 9 1

0 8 9 1

5 7 1

9

8

0

0

FIGURE 83-4 Diag am of p ostate zone s. Most p ostate ad e noca cinomas occu in the p e ip he al zone . (Re p rod uce d with p e rmission of E.J. Maye aux, Jr., MD.)

Ye ar o f de ath Ca nce r s ite s include inva s ive ca s e s only unle s s othe rwis e note d. Morta lity s ource : US Morta lity File s, Na tiona l Ce nte r for He a lth S ta tis tics, CDC. Ra te s a re pe r 100,000 a nd a re a ge -a djus te d to the 2000 US S td Popula tion (19 a ge groups -Ce ns us P 25–1130). Re gre s s ion line s a re ca lcula te d us ing the J oinpoint Re gre s s ion Progra m Ve rs ion 3.5, April 2011, Na tiona l Ca nce r Ins titute. FIGURE 83-3 Ag e -ad juste d US p ostate cance mo tality ate s b y ace and e thnicity in male s old e than the ag e of 50 ye a s. Note the hig he mo tality in b lacks.

• Patterns of spread include direct extension, hematogenous, and lymphatic. • Lymphatic spread occurs to the hypogastric, obturator, external iliac, presacral, common iliac, and paraaortic nodes. 4 ° Of distant metastases, 90% are osseous. ° Visceral metastases to lung, liver,4 and adrenals are less commonly seen without bone involvement.

RISK FACTO RS • Men who have a rst-degree relative with prostate cancer have approximately a 2-fold increased risk of developing prostate cancer during their lifetime. • African American ethnicity.

DIAGNO SIS CLINICAL FEATURES • Prostate cancer can be associated with urinary obstructive symptoms or hematuria, but these are usually a result of other causes. • Rarely, bone pain can be an initial symptom, but it generally represents very advanced disease. Prior to PSA screening, men commonly presented with this symptom.

• A prostatic nodule on digital rectal examination (DRE) is not always speci c for a carcinoma and can underestimate the extent of disease when it does represent a carcinoma. LABO RATO RY TESTING PSA Scre e ning • PSA is a glycoprotein produced primarily by the epithelial cells that line the acini and ducts of the prostate gland. • PSA is concentrated in prostatic tissue, and serum PSA levels are normally very low. • Disruption of the normal prostatic architecture, such as by prostatic disease, in ammation, or trauma, allows greater amounts of PSA to enter the general circulation. 5 • The sensitivity and speci city for PSA as a detection tool is 80% and 65%, respectively. 5 After treatment PSA is the primary tool used to evaluate for persistent disease or metastatic disease before imaging is employed. • The American Urological Association guidelines support screening from age 40 years old to 75 years old. 6 • The U.S. Prevention Task Force (USPSTF) has published nal recommendations against PSA-based screening for prostate cancer in asymptomatic men. 7 They gave the guidance a D recommendation, which means there is moderate or high certainty that the service has no net bene t or that the harms outweigh the bene ts, and the task force discourages use of the service. In May 2012, they concluded that many men are harmed as a result of prostate cancer screening [with PSA] and few, if any, bene t. A better test and better treatment options are needed. Until these are available, the USPSTF has recommended against screening for prostate cancer. 7 IMAGING Transre ctal Ultrasound • Transrectal ultrasound (TRUS) is a sensitive but nonspeci c method of detecting prostate cancer.

411

PART 11

412

Ch a pt e r 83

GENITO URINARY/ RENAL

Gle as o n’s Patte rn S c ale

1. S mall, unifo rm g lands .

We ll diffe re ntiate d

1 2. Mo re s pac e (s tro ma) be twe e n g lands . 2

Mo de rate ly diffe re ntiate d 3. Dis tinc tly infiltratio n o f c e lls fro m g lands at marg ins . Po o rly diffe re ntiate d Anaplas tic

3 4. Irre g ular mas s e s o f ne o plas tic c e lls with few g lands . 4

5

5. Lack o f o r o c c as io nal g lands , s he e ts o f c e lls .

FIGURE 83-5 Gle aso n sco ing o f p o state cance . (Fro m Gle ason, DF. Histo lo g ic g rad ing and clinical stag ing o f p ro static carcino ma. In Tanne nb aum M. Urolog ic Patholog y: The Prostate . Philad e lp hia, PA: Le a and Fe b ig e r; 1977:171–197.)

• A hypoechoic lesion as seen on TRUS has a 30% chance of being carcinoma. • TRUS should not be used as a screening tool. • The most important use of TRUS is in combination with 12-core prostate needle biopsy. 3 Bone Scan • Radionuclide imaging is routinely used to evaluate for disseminated disease. • Recent studies show that the likelihood of a positive bone scan in patients with a PSA value less than 10 ng/ mL and no bone symptoms is 1 per 1000. 8 CT Scan and MRI • CT scans and body-surface-coil MRI of the pelvis have poor performance characteristics for assessing metastatic disease and are not part of standard screening or staging. • MRI with an endorectal coil is sometimes used to evaluate disease beyond the capsule, in focal therapy, and for surgical planning. Prostate Biop sy • Performed with local anesthesia and ultrasound guidance using a spring-loaded biopsy needle to obtain 12 prostate biopsy specimens. The patient may experience signi cant discomfort despite the anesthetic. • There is an estimated false negative rate of 0% to 9.3% and an estimated false positive rate of 0% to 3.8% amongst pathologists. 9 • The percentage of positive cores, length, or percentage of cancer per core can provide predictive information. • Lower GI tract cleansing enemas and prophylactic antibiotics are routinely used.

DIFFERENTIAL DIAGNO SIS • Prostatitis—Infection or in ammation of the prostate. This is often associated with perineal or suprapubic pain, dysuria frequency while prostate cancer is often asymptomatic. • Benign prostatic hyperplasia—Enlarged prostate that may cause obstructive symptoms. There is no relative increase in the risk of developing prostate cancer. • Prostatic intraepithelial neoplasia (PIN)—High-grade PIN has been noted as a precursor to prostate carcinoma. 10 • Atypical glands on biopsy—The probability of detecting cancer following an atypical diagnosis is approximately 40%. Often a repeat biopsy is recommended with increased sampling of the atypical site.

MANAGEMENT • General considerations include age and general performance status, Gleason score, initial serum PSA, estimated tumor volume, tumor stage, and patient life expectancy. • Options should be explained to patients so that patients can make an informed decision about which treatment best ts their values and goals. • Active surveillance—Monitoring for disease progression over time in low-risk individuals who are likely to die with the disease rather than from the disease. Treatment is considered if signi cant disease progression is detected. This involves PSA testing and periodic rebiopsy. 11 SOR B • Radical prostatectomy—Treatment of choice for patients with organde ned disease and a life expectancy of more than 10 years. Walsh has shown that the cavernosal nerves that mediate erectile function can be identi ed and avoided, reducing postoperative erectile dysfunction. Rarely, signi cant urinary incontinence may be encountered. 3

pr O St a t e Ca NCe r

PART 11

GENITO URINARY/ RENAL PREVENTIO N • The Prostate Cancer Prevention Trial (PCPT) aimed to determine the prevalence of histologically proven prostate cancer among men randomized to receive daily nasteride or placebo. 19 • The authors described a 24.8% reduction in the prevalence of prostate cancer among men taking nasteride; however, the cancers detected in these men were signi cantly higher risk cancers. 19 • More recently, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found that although selenium does not prevent prostate cancer, vitamin E is associated with a signi cantly increased risk of prostate cancer. 20

PRO GNO SIS FIGURE 83-6 The DaVinci ob ot: th e e wo king a ms and a came a. The ob o t allows fo b e tte visualization of the p e lvic anato my. (Re p rod uce d with p e rmission of Intuitive Surg ical.`)

° Robotic-assisted laparoscopic radical prostatectomy (RALRP)— RALRP was developed to overcome of the dif culties of the standard laparoscopic prostatectomy. The robotic technique allows for magni ed high de nition 3-dimensional visualization of the operative eld and wider range of motion. The majority of men opting for radical prostatectomy in the United States are having RALRP (Figure 83-6). 12 SO R B • External beam radiation therapy (EBRT)—EBRT is also a viable treatment option for localized disease and is the choice treatment option for T3 disease. EBRT utilizes high-energy electrons to destroy cancer cells by damaging cellular DNA. Side effects can include rectal and bladder symptomatology. Short-term androgen deprivation therapy (1-3 years) may increase ef cacy. 13,14 SO R B • Brachytherapy—Outpatient, ultrasound-guided, transperineal placement of 125I or Pd radioactive seeds into the prostate. Optimal candidates have low-risk prostate cancer. Many centers utilize short-term neoadjuvant hormonal blockade given the dif culty in treated glands larger than 50 gs. 15 SO R B • Androgen ablation in combination with EBRT—There may be some synergy between the apoptotic response induced by androgen deprivation and radiotherapy. Androgen deprivation results in an average 20% decrease in prostate volume to reduce the number of target cells, and thereby improve tumor treatment. Shrinking the prostate can decrease side effects by diminishing the volume of rectum and bladder irradiated.13,16 SOR B • For recurrent or advanced disease—Docetaxel (Taxotere)-based regimens can be included among the most effective treatment options for the management of patients with advanced, androgen independent prostate cancer. Results with docetaxel as a single agent and in combination regimens with estramustine (Emcyt) have provided patient bene t through an improved palliative response and improvement in quality of life as assessed through quality of life questionnaires. In addition, treatment with Docetaxal-based regimens have produced objective responses such as reduced serum PSA levels by 50%, reduction in measurable disease on imaging, pain, and health-related quality of life. Progression-free survival was signi cantly increased in patients receiving docetaxel plus estramustine compared to those receiving mitoxantrone and prednisone (6.3 vs. 3.2 months). 17,18 SO R B

The optimal management of patients with prostate cancer varies widely and is highly dependent upon a patient’s age, overall health, and tumor risk assessment.

PATIENT EDUCATIO N • Patients should be provided balanced and objective information about the risks and bene ts of PSA screening, prostate biopsies, and the various options for prostate cancer treatment. This is challenging as there are con icting opinions and interpretations of existing data. New studies are published frequently, which can change evidence-based recommendations and expert opinions. It is the physician’s job to help patients navigate through the vast data and varied opinions to nd a course of prevention and treatment that ts their individual needs. Although some patients will want the physician to make decisions about whether or not to get a PSA test or which cancer treatment is best; many others will appreciate balanced information so they may decide for themselves. See Patient and Provider Resources below to help inform patient–doctor discussions on these matters. • Risk assessment calculations can be useful in discussions with patients to help them decide about screening, biopsy, and treatment. Links to prostate cancer online prediction tools are listed under Provider Resources below.

PATIENT RESO URCES

• National Alliance of State Prostate Cancer Coalitions—http:/ / www.naspcc.org. • Men’s Health Network—http:/ / www.menshealthnetwork .org. • Links to prostate cancer online prediction tools are listed under Provider Resources below and are useful for patients in their discussions with physicians. PRO VIDER RESO URCES

• The Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (PCPTRC) provides a person’s estimated risk of biopsy-detectable prostate cancer and high grade prostate cancer—http:/ / deb .uthscsa.edu/ URORiskCalc/ Pages/ uroriskcalc.jsp.

413

414

PART 11

GENITO URINARY/ RENAL • Prostate cancer gene 3 (PCA3) data and use of nasteride can be entered into a more advanced version of this calculator on the same site. • Prostate cancer online prediction tools are available from Memorial Sloan-Kettering Cancer Center. They can be used to in conjunction with patients to decide which treatment approaches will result in the greatest bene t at various stages of prostate cancer. The four nomograms are found at http:/ / www.mskcc.org/ mskcc/ html/ 10088.cfm. 1. Pretreatment (Diagnosed with Cancer But Not Yet Begun Treatment) 2. Postradical Prostatectomy (Recurrence After Surgery) 3. Salvage Radiation Therapy (Considering Radiation Therapy After Surgery) 4. Hormone Refractory (Progression of Metastatic Prostate Cancer That Can No Longer Be Controlled by Hormones Alone)

CHAPTEr 83

with validation in the Prostate Cancer Prevention Trial. Cancer. 2012;118(10):2651-2658. http:/ / www.ncbi.nlm.nih.gov/ pubmed/ 22006057. Accessed October 25, 2011. 7. U.S. Preventive Services Task Force. Screening for Prostate Cancer. Current Recommendation. May 2012. http:/ / www.uspreventiveservicestaskforce.org/ prostatecancerscreening.htm. Accessed September 1, 2012. 8. Oxley JD, Sen C. Error rates in reporting prostatic core biopsies. Histopathology. 2011;58(5):759-765. 9. Tanaka N, Fujimoto K, Shinkai T, et al. Bone scan can be spared in asymptomatic prostate cancer patients with PSA of < = 20 ng/ ml and Gleason Score of < = 6 at the initial stage of diagnosis. Jpn J Clin Oncol. 2011;41(10):1209-1213. http:/ / www.ncbi.nlm.nih.gov/ pubmed/ 21862505. Accessed September 12, 2011. 10. Epstein JI, Herawi M. Prostate needle biopsies containing prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma: implications for patient care. J Urol. 2006;175(3 Pt 1): 820-834.

• Additional tools for measuring PSA doubling time, male life expectancy and tumor volume are found at: http:/ / nomograms.mskcc.org/ Prostate/ index.aspx.

11. Albertsen PC, Hanley JA, Fine J. 20-year outcomes following conservative management of clinically localized prostate cancer. JAMA. 2005;293(17):2095-2101.

• National Cancer Institute (NCI). Prostate Cancer—http:/ / www .cancer.gov/ cancertopics/ types/ prostate.

12. Parsons JK, Bennett JL. Outcomes of retropubic, laparoscopic, and robotic-assisted prostatectomy. Urology. 2008;72(2):412-416.

• National Comprehensive Cancer Network (NCCN)— http:/ / www.nccn.org/ professionals/ physician_gls/ f_ guidelines.asp.

13. Payne H, Mason M. Androgen deprivation therapy as adjuvant/ neoadjuvant to radiotherapy for high-risk localised and locally advanced prostate cancer: recent developments. Br J Cancer. 2011;105(11): 1628-1634. http:/ / www.ncbi.nlm.nih.gov/ pubmed/ 22009028. Accessed October 25, 2011.

• National Prostate Cancer Coalition (NPCC)—http:/ / www.4npcc .org. • Screening for Prostate Cancer: A Review of the Evidence for the U.S. Preventive Services Task Force—http:/ / www .uspreventiveservicestaskforce.org/ uspstf12/ prostate/ prostateart.htm.

REFERENCES 1. Lim LS, Sherin K. Screening for prostate cancer in U.S. men ACPM position statement on preventive practice. Am J Prev Med. 2008;34(2): 164-170. 2. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69. 3. Morey A, Shoskes D. The American Urological Association Educational Review Manual in Urology. 1st ed. New York, NY: Castle Connolly Graduate Medical Publishing; 2007. 4. Wein A. Clinical Manual of Urology. 3rd ed. New York, NY: McGraw Hill; 2001.

14. Potosky AL, Davis WW, Hoffman RM, et al. Five-year outcomes after prostatectomy or radiotherapy for prostate cancer: the prostate cancer outcomes study. J Natl Cancer Inst. 2004;96(18):1358-1367. 15. Merrick GS, Butler WM, Wallner KE, Galbreath RW, Adamovich E. Permanent interstitial brachytherapy in younger patients with clinically organ-con ned prostate cancer. Urology. 2004;64(4):754-759. 16. Bolla M, Collette L, Blank L, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002;360(9327):103-106. 17. Logothetis CJ. Docetaxel in the integrated management of prostate cancer. Current applications and future promise. Oncology (Williston Park, N.Y.). 2002;16(6 Suppl 6):63-72. 18. Machiels J-P, Mazzeo F, Clausse M, et al. Prospective randomized study comparing docetaxel, estramustine, and prednisone with docetaxel and prednisone in metastatic hormone-refractory prostate cancer. J Clin Oncol. 2008;26(32):5261-5268.

5. Greene KL, Albertsen PC, Babaian RJ, et al. Prostate speci c antigen best practice statement: 2009 update. J Urol. 2009;182(5):2232-2241.

19. Crawford ED, Andriole GL, Marberger M, Rittmaster RS. Reduction in the risk of prostate cancer: future directions after the Prostate Cancer Prevention Trial. Urology. 2010;75(3):502-509.

6. Williams SB, Salami S, Regan MM, et al. Selective detection of histologically aggressive prostate cancer: an Early Detection Research Network Prediction model to reduce unnecessary prostate biopsies

20. Klein EA, Thompson IM Jr, Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549-1556.

PART 11

RENO VASCULAR HYPERTENSIO N

GENITO URINARY/ RENAL

84 RENO VASCULAR HYPERTENSIO N Mad hab Lamichhane , MD

PATIENT STO RY A 50-year-old woman is admitted to the medical intensive care unit with complaints o severe shortness o breath that requires mechanical ventilation or acute respiratory ailure related to pulmonary edema. She has a history o dyslipidemia and a 20-pack-year history o smoking, but she denies any past medical history o hypertension, diabetes, or amily history o heart disease, hypertension, and stroke. Electrocardiogram is suggestive o le t ventricular hypertrophy (LVH). She has a mild troponin elevation with normal electrolytes. Her echocardiogram shows a normal ejection raction o 60% with no regional wall motion abnormality. Lisinopril is added or a newly diagnosed blood pressure (BP) elevation o 190/ 100 mm Hg. Her creatinine increased to 1.6 mg/ dL rom her baseline o 1.2 mg/ dL a ter starting lisinopril, and her renal unction normalized with its discontinuation. She subsequently underwent diagnostic cardiac catheterization with renal angiogram to evaluate the etiology o her acute pulmonary edema and hypertension; she is ound to have a hemodynamically signi cant stenosis o her right renal artery, or which she had percutaneous renal artery angioplasty with stent placement (Figure 84-1).

A

INTRO DUCTIO N Renovascular hypertension (RVH) is a type o secondary systemic hypertension caused mainly by occlusive disease o the renal arteries. Renal artery stenosis (RAS) is one cause o RVH that, when treated, can partially or completely cure hypertension.

SYNO NYMS Renovascular hypertension is also called renovascular disease.

EPIDEMIO LO GY • Renovascular hypertension is the most common cause o secondary hypertension and accounts or hypertension in 1% to 5% o all patients with hypertension. 1 • Incidence is higher in patients with severe or re ractory hypertension. • The prevalence o RAS was 6.8% in individuals 65 years or older in a community-based sample o subjects. 2 • Atherosclerotic RAS is seen in about 18% to 20% o individuals undergoing coronary angiography and 35% to 70% o those undergoing peripheral vascular angiography. 3 • O normotensive individuals, 3% to 6% have RAS. 4

B FIGURE 84-1 Hig h-g rad e rig ht re nal arte ry ste nosis d e monstrating imp rove d ow a te r ste nt p lace me nt. A. Be ore ste nt. B. Imp rove d ow a te r ste nt p lace me nt. (Re p rod uce d with p e rmission from Milind Karve , MD, FACC.)

ETIO LO GY Renovascular hypertension is most commonly caused by atherosclerotic disease and bromuscular dysplasia (FMD). Renovascular hypertension etiology can be classi ed as ollows2:

415

PART 11

416

GENITO URINARY/ RENAL

Ch a pt e r 84

• Atherosclerotic RAS • Fibromuscular disease rom medial, perimedial, intimal hyperplasia (Figure 84-2) • Extrinsic brous band • Renal trauma: arterial dissection, segmental renal in arction, Page kidney (perirenal brosis)2

°

• Aortic dissection

°

• Aortic endogra t occluding the renal artery °

• Arterial embolus • Other medical disorders ° Hypercoagulable state with renal in arction ° Takayasu arteritis ° Radiation-induced brosis ° Tumor encircling the renal artery ° Polyarteritis nodosa • Atherosclerosis RAS ° Atherosclerosis is the major cause involving 90% o all cases o RVH and usually involves the ostium and proximal third o the main renal and perirenal aorta. 4 ° It is a progressive disease, and total occlusion occurs in 39% over 12 to 60 months ollow-up when RAS is greater than 75% at the time o diagnosis. 5 • Fibromuscular dysplasia ° Fibromuscular dysplasia is the second-most-common cause o RAS and accounts or about 10% o the cases o RVH; it predominantly a ects younger emales. 6 ° It is a nonatherosclerotic and noninf ammatory disease o unclear etiology. A genetic actor may play a role, as suggested by a higher incidence in rst-degree relatives. 5 ° Medial broplasia is the histological nding in most cases (80%85%), and perimedial broplasia makes up most o the remaining

A

°

10% to 15%. Other mechanisms include intimal broplasia, medial brodysplasia, and adventitial broplasia. Renal arteries are the most commonly a ected arterial bed; however, other arteries can be a ected and include the carotid, vertebral, iliac, and mesenteric arteries. 5 Bilateral disease is seen in about 60% o patients with renal vascular bed involvement. 5 It usually involves the middle and distal two-thirds o main renal artery and may involve renal artery branches. 5 About 28% o individuals with FMD have involvement o multiple vascular beds. 6 There is good response to revascularization.

PATHO PHYSIO LO GY • Based on experimental models, RVH is caused by activation o the renin-angiotensin-aldosterone system (RAAS) in patients with unilateral RAS with a normal contralateral kidney. • The nonstenotic kidney receives higher per usion pressure, which leads to “pressure natriuresis” to lower the BP by excreting sodium. However, the all in BP decreases the per usion to the stenotic kidney, which in turn stimulates more renin release. The stenotic kidney ails to lower the BP with the pressure natriuresis because o angiotensin-IImediated aldosterone secretion, distal sodium reabsorption, and renal vasoconstriction. Renal vasoconstriction decreases renal plasma f ow, which promotes sodium reabsorption in both proximal and distal tubules. 3 • In bilateral renal arterial disease, or stenosis to a solitary unctioning kidney, angiotensin II increases the BP, but the kidney is unable to excrete sodium by natriuresis. This leads to volume-expansion-related hypertension rom sodium and water retention. 3

B

FIGURE 84-2 Ang iog rap hic imag e s o intimal f b rop lasia variant o f b romuscular d ysp lasia in the mid /d istal re na arte ry b e ore (A) and a te r (B) ang iop lasty. (Re p rod uce d with p e rmission from De an S, Satiani B. Color Atlas and Synop sis o Vascular Dise ase . Ne w York, NY: McGraw-Hill; 2014.)

PART 11

r e NO Va SCULa r h Ype r t e NSIO N

GENITO URINARY/ RENAL

• The activation o renin release occurs when the pressure gradient is above 10 to 20 mm Hg between the aorta and poststenotic segments, which is seen with greater than 70% to 75% lumen obstruction. 2

LABO RATO RY TESTING

• Increased sympathetic activity is common in this disorder, possibly rom the altered a erent signals rom the underper used kidney or augmentation o nerve signals in the presence o angiotensin II. 2,3

• Baseline renal unction—Worsening renal unction a ter initiation o angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocking agent can occur. Renin angiotensin inhibitors block angiotensin-II-induced e erent arteriolar vasoconstriction, which results in a decrease in transglomerular hydrostatic pressure and all in glomerular ltration rate (GFR). Use o these medications in patients with bilateral RAS or stenosis to a solitary kidney results in renal ailure.

• Endothelial dys unction with impaired relaxation also develops in RVH. 2 • The aldosterone level is higher in RVH. It has an important role in regulation o tissue brosis, LVH, and sodium retention.

• Complete blood cell count (CBC)—Values are normal in FMD, but anemia and thrombocytopenia can occur in arteritis-associated disease.

• Examination o urine or proteinuria assesses the severity o renal damage.

DIAGNO SIS/ SCREENING • The US Preventive Services Task Force has made no recommendations with regard to screening individuals or RVH. • The American Heart Association recommends screening with Doppler ultrasound in the appropriate clinical settings mentioned in the diagnostic section o this chapter. HISTO RY/ SYMPTO MS Speci cally ask about the ollowing: • Onset o hypertension be ore 35 years o age, which is suggestive o FMD • Severe hypertension (systolic BP ≥ 180 or diastolic pressure o 120 mm Hg) a ter the age o 55 years, which is suggestive o atherosclerotic RAS • Accelerated and resistant hypertension • Sudden and unexplained pulmonary edema, such as in the introductory case • Absent amily history o hypertension (except in FMD) PHYSICAL EXAMINATIO N Speci cally look or or establish the ollowing: • High BP—Note that wider variability in BP compared to essential hypertension during 24-hour ambulatory BP monitoring is seen because o increased sympathetic activity. 2 • Palpate and listen or carotid and peripheral pulse bruit. Positive ndings increase the possibility o a renovascular cause o hypertension. ° Epigastric area bruit—The presence o an abdominal bruit has sensitivity o 20% to 77.7% and speci city o about 63% to 90% or renovascular disease. ° Bruits are ound in7 77.7% to 86.9% o RVH cases with angiographically proven RAS. A systolic-diastolic bruit (audible in systolic phase with extension to the diastole) is more common in those with renovascular disease than in healthy people. Location, intensity, and pitch have questionable value. • Severe hypertension with signs o end-organ damage such as papilledema, retinal hemorrhage, heart ailure, or neurological de cits can occur. • Look or xanthomas and xanthelasma, which avor underlying hyperlipidemia and atherosclerotic disease (see Chapter 223, Hyperlipidemia). • Target organ damage ndings like LVH is more severe than that seen in essential hypertension or the same level o BP. 3 The apical impulse is sustained in LVH. • Some patients can have re ractory f uid retention o ten out o degree o myocardial pump ailure.

• Screening or atherosclerosis risk actors—Use asting glucose, asting lipid panel, level o hemoglobin A1C (HbA1C). IMAGING • Diagnostic imaging studies are recommended to evaluate or RAS in the ollowing clinical settings: 4,5 SO R B Onset o hypertension be ore 30 years o age ° 4,5 SO R B Severe hypertension a ter the age o 55 years ° ° Accelerated and resistant hypertension (sudden and persistent worsening o previously controlled hypertension)4,5 SO R C ° Malignant hypertension (hypertension with coexistent end-organ damage)4,5 SO R C ° Signi cant azotemia (greater than 50% rise in creatinine5 that persists or worsens even a ter correction o hypoper usion state a ter initiation o ACE inhibitor or angiotensin receptor blocking agent)4,5 SO R B

° Unexplained atrophic kidney or discrepancy in size between 2 kidneys o 1.5 cm4,5 SO R B 4,5 ° Sudden and unexplained pulmonary edema SO R B • Specif c imaging studies—The choice o diagnostic imaging technique depends on the availability o the diagnostic procedure, the operator’s experience, and the patient’s characteristics, such as body size, renal unction, contrast allergy, and presence o previous stents or metallic objects in the body. 5 ° Duplex ultrasonography is recommended as a screening test. SO R B

It has a sensitivity o 84% to 98% and speci city o 62% to 99% or detecting RAS. 5 ■ It is also used to monitor renal artery patency a ter endovascular treatment or surgical vascularization o RAS. ■ Limitations include operator skill, less visualization o accessory renal arteries, or inadequate images in obese patients or intervening bowel gas. ■ Parameters or diagnosis o RAS are (1) peak systolic velocity in the renal artery exceeding 1.8 or 2.0 m/ s and a renal artery/ aortic velocity ratio exceeding 3.5, with sensitivities varying rom 85% to 90% and about 90% speci city8; (2) an end diastolic velocity o greater than 150 cm/ s predicts more than 80% RAS. 5 ° Computed tomographic angiography (CTA) can be used. SO R B ■ Sensitivity and speci city or detecting RAS vary rom 59% to 96% and 82% to 99%, respectively. 2 ■ Metal stents and in-stent restenosis can be diagnosed. ■ Computed tomographic angiography is not indicated in patients with renal insu ciency caused by iodinated contrast. ■ Secondary signs on CTA—Poststenotic dilatation, renal parenchymal changes o atrophy, and decreased cortical enhancement. 8 ■

417

PART 11

418

GENITO URINARY/ RENAL

CHAPTER 84

B

A

FIGURE 84-3 Ang iog rams in a 70-ye ar-old man with a history o coronary arte ry d ise ase , p re vious coronary arte ry b yp ass g ra t surg e ry, and hyp e rte nsion; the man was taking 2 antihyp e rte nsive ag e nts and d e ve lop e d sud d e n worse ning o b lood p re ssure control, re q uiring 4 antihyp e rte nsive ag e nts with b lood p re ssure still g re ate r than 190/100 mm Hg . A. Ang iog ram re ve aling b ilate ral re nal arte ry ste nosis. B. A te r ste nting (arrows) o b ilate ral re nal ostial ste notic le sions. Blood p re ssure control imp rove d marke d ly, and the p atie nt now re q uire s only one antihyp e rte nsive ag e nt. (Re p rod uce d with p e rmission from Fuste r V, Walsh R, Harring ton R. Hurst’s The He art. 13th e d . Ne w York, NY: McGraw-Hill; 2011.)

2 Gadolinium-enhanced magnetic resonance angiography (MRA) °

SO R B

Magnetic resonance angiography has a sensitivity o 90% to 100% and speci cities o 76% to 94% or detection o RAS. 2 ■ It is less e ective in assessment o patients with more subtle beading and changes o FMD in the medial and distal segments. 3 ■ It is not use ul in patients with metallic stents. ■ Magnetic resonance angiography is contraindicated in patients with GFR less than 30% because o the enhanced risk o nephrogenic systemic brosis, which is seen in 1% to 6% o dialysis patients given gadolinium. 3 ° Catheter angiography (Figures 84-3 and 84-4) ■ It is the gold standard or diagnosis o RAS. ■ It is used mostly as a con rmatory diagnostic test when other noninvasive diagnostic procedures are inconclusive and concomitant angioplasty or stent placement is planned. SO R B ■ String-o -beads appearance with the diameter o the bead larger than the diameter o the artery is seen in medial broplasia. Long tubular areas o stenosis are seen in intimal broplasia or periadventitial broplasia. ■ Contrast-induced acute kidney injury incidence is seen in ewer than 3% o patients without diabetes or chronic kidney disease (CKD), 5% to 10% in diabetes, 10% to 20% in CKD, 20% to 50% in those with diabetes and CKD. 5 ■ Iso-osmolar nonionic contrast is associated with ewer nephrotoxic e ects. ■ The translesional pressure gradient can be measured across the stenosis to determine its signi cance in doubt ul cases. ° Captopril renography SO R C provides scintigraphic images and in ormation about renal size, per usion, and excretory capacity. ■ This is o limited value in patients with azotemia, bilateral RAS, or RAS to a single unctioning kidney. ■

Sensitivity is 74%, and speci city is about 59%. 5 ■ It is not help ul except in cases o RAS o borderline angiographic severity o unclear clinical signi cance. 2 ° Selective renal vein renin studies—These have limited value in diagnosis o RAS compared to noninvasive methods, which are highly reliable. SO R B ■

FIGURE 84-4. Rig ht re nal arte ry ste nosis rom athe roscle rosis. It usually involve s ostium and the p roximal se g me nt o the arte ry (re d arro w). (Re p rod uce d with p e rmission from Milind Karve , MD, FACC.)

RENO VASCULAR HYPERTENSIO N

° Plasma renin activity ■ Plasma renin level is measured at baseline and 60 minutes a ter a 50-mg dose o oral captopril administration. ■ Elevated plasma renin activity is seen in about 15% o patients with essential hypertension. ■ This test has sensitivity o 61% and speci city o 86% or the detection o renal artery disease. 5 ■ It is not recommended as a screening test or diagnosis o RAS. SOR B

DIFFERENTIAL DIAGNO SIS CAUSES O F SECO NDARY HYPERTENSIO N • Pheochromocytoma—Commonly associated with paroxysmal BP changes, palpitations, sweating, and headache • Primary aldosteronism—Associated with hypokalemia and adrenal adenomas • Cushing syndrome—Associated with moon-shaped acies, central obesity, striae, and easy bruising • Hyperthyroidism—Associated with heat intolerance, palpitations, weight loss (see Chapter 227, Hyperthyroidism) • Hyperparathyroidism—Associated with renal stones, hypercalcemia, and elevated parathyroid hormone levels • Coarctation o aorta—Causes pulse delay between radial and emoral artery, diminished pulse and BP distal to coarctation; may be associated with Turner syndrome • Parenchymal renal diseases—Associated with decreased GFR and protein or cellular elements in the urinalysis

MANAGEMENT • Antiplatelet agents based on the known bene t in atherosclerotic disease. • Antihypertensive therapy to optimize BP control—BP goal is 130/ 80 mm Hg in those with diabetes and CKD, 140/ 90 mm Hg in other patients. • Control BP ° Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers (ARBs), and calcium channel blockers slow the progression o renal disease. 4 SO R B ° RAAS blockers decrease the GFR and elevate the creatinine temporarily and require close monitoring. The GFR all o 30% or greater and a creatinine rise o more than 0.5 mg/ dL may be an indication or renal revascularization. ° Angiotensin-converting enzyme inhibitors are contraindicated in bilateral RAS and in RAS in a single unctional kidney. 3 SO R B ° Thiazide diuretics, hydralazine, and b-blockers are also e ective. ° Usually, multiple medications are required. ° No randomized controlled study has been done to evaluate di erent medical regimens. • Treat atherosclerotic risk actors (including tobacco abuse, dyslipidemia) and attain appropriate glycemic control in diabetic patients (see respective Chapters 237, Tobacco Addiction; 223, Hyperlipidemia; and 219, Diabetes). • Medical therapy is pre erred to revascularization or atherosclerotic RAS and advanced renal disease. • Two recent randomized trials (Angioplasty and STent or Renal Artery Lesions [ASTRAL] and STent placement and blood pressure

PART 11

GENITO URINARY/ RENAL and lipid-lowering or the prevention o progression o renal dys unction caused by Atherosclerotic ostial stenosis o the Renal artery [STAR]) compared stent angioplasty combined with medical therapy or medical therapy alone or atherosclerotic renovascular disease. Both trials did not show any di erence in renal events, cardiovascular morbidity, and mortality. 4,9,10 • Revascularization therapy ° It is controversial because o evolving in ormation and lack o clear bene t rom recent randomized controlled trials. ° Based on meta-analysis o 47 angioplasty studies (1616 patients) and 23 surgery studies (1014 patients), cure rates (BP o 140/ 90 mm Hg without treatment) are only 36% and 54% a ter angioplasty and surgery, respectively, in RAS caused by FMD. 11 ° In the ASTRAL study, no signi cant bene t in systolic BP reduction was seen in 806 patients with atherosclerotic renovascular disease who either underwent revascularization in addition to receiving medical therapy or received medical therapy alone. 12 ° Recommendations to consider revascularization should be based on the patient’s li e expectancy, comorbidities, quality o BP control, and renal unction. 4 ° Percutaneous revascularization is indicated in anatomically and unctionally signi cant RAS with the ollowing presentation SO R B : ■ Recurrent, unexplained congestive heart ailure or sudden, unexplained pulmonary edema. 5 ■ Percutaneous revascularization is reasonable or hemodynamically signi cant RAS with any o the ollowing: accelerated hypertension, resistant hypertension, malignant hypertension, hypertension with unexplained unilateral small kidney, and hypertension with intolerance to drug treatment. SO R B ■ Balloon angioplasty with stent placement is superior to balloon angioplasty in atherosclerotic lesions. 4 4 ■ Drug-eluting stents have not shown any better outcomes. bailout stent placement is rec° Balloon angioplasty with or without ommended or FMD lesions. 4,13 ■ Medical therapy is the pre erred treatment in well-controlled individuals who are compliant patients. 6 High rates o BP improvement are noted a ter angioplasty in FMD, unlike atherosclerotic RAD, or which it is less e ective. 12 ■ Meta-analysis o 7 studies (207 patients) did not show any di erence between baseline renal unction and ollow-up a ter revascularization. 9 6 ■ The rate o restenosis is 7% to 27% at 6-month to 2-year ollow-up. ° Complications o angioplasty include renal atheroembolization. ■ This occurs during diagnostic and direct manipulation o the renal artery during angioplasty or stenting. ■ The patient develops subacute renal ailure or eatures o embolization like blue toes and livedo reticularis (see Chapter 198, Erythema Ab Igne). ■ Preexisting renal insu ciency and long-standing hypertension are predictors o progression to end-stage renal disease (ESRD). No speci c therapy is available. Distal occlusion balloons or lter may reduce incidence. 14 ° Surgical revascularization is considered or patients requiring surgical repair o the aorta and patients with complex disease o renal arteries (eg, aneurysms or ailed endovascular procedures). 4 SO R C ■ Surgical procedures include aortorenal bypass gra ting using saphenous vein or a prosthesis, aortic implantation, resection anastomosis, and autotransplantation. 4 ■ Surgical revascularization has a 30-day mortality o 3.7% to 9.4%.

419

420

PART 11

GENITO URINARY/ RENAL PRO GNO SIS • Renal artery stenosis is associated with a signi cantly increased rate o CKD, 25% versus 2% among those without renal RAS, coronary artery disease (67% vs 25%), stroke (37% vs 12%), and peripheral vascular disease (56% vs 13%). 13 • Increased risk o cerebrovascular disease (CVD) in atherosclerotic RAS occurs rom activation o the RAAS and sympathetic nervous system and concomitant atherosclerotic disease in other organs. 4 • O those with RAS, 80% die rom cardiovascular events.

CHAPTER 84

PRO VIDER RESO URCES

• National Heart Lung and Blood Institute. Your Guide to Lowering High Blood Pressure—http:/ / www.nhlbi.nih.gov/ hbp/ index .html. • Society for Vascular Surgery: VascularWeb. Renovascular Conditions— http:/ / www.vascularweb.org/ vascularhealth/ Pages/ renovascular-conditions.aspx. REFERENCES

• Prevalence o LVH is 79% in RAS versus 46% in essential hypertension. LVH is associated with increased morbidity and mortality. 4

1. Bloch MJ, Basile J. The diagnosis and management o renovascular disease: a primary care perspective. Part II. Issues in management. J Clin Hypertens (Greenwich). 2003;5(4):261-268.

• Progression to high-grade stenosis or occlusion occurs in 1.3% to 11.1% o patients. 4

2. Stephen C, Textor, MD Textor SC. Current approaches to renovascular hypertension. Med Clin N Am. 2009;93:717-732.

• Atherosclerotic RAS leads to progressive renal unction loss, and 27% o patients will develop chronic renal ailure within 6 years. Patients with atherosclerotic RAS who progress to ESRD have high mortality rates. 2

3. Garovic V, Textor SC. Renovascular hypertension and ischemic nephropathy. Circulation. 2005;112:1362-1374.

• The 2-, 5-, and 10-year survival rates are 56%, 18%, and 5%, respectively, in atherosclerotic RAS. 5

4. European Stroke Organization; Tendera M, Aboyans V, et al. ESC guidelines on the diagnosis and treatment o peripheral artery diseases. Eur Heart J. 2011;32:2851-2906.

• Patients with FMD who achieve hypertension cure with angioplasty include those younger than 40 years at diagnosis, those with a duration o hypertension less than 5 years, and those with a systolic BP less than 160 mm Hg. 13

5. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/ AHA 2005 practice guidelines or the management o patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic). Circulation. 2006;113:e463.

FO LLO W-UP

6. Slovut DP, Olin JW. Fibromuscular dysplasia. N Engl J Med. 2004;350:1862-1871.

• Close ollow-up is indicated until adequate BP control is achieved. • Check creatinine and electrolytes values every 3 to 6 months and 2 to 4 weeks a ter adjustment o antihypertensive therapy, especially when using ACE inhibitors, ARBs, and diuretics. • For patients who are managed with medical therapy, ° Monitor serum creatinine level and BP every 3 months. ° Noninvasive imaging (such as duplex ultrasonography) should be obtained every 6 to 12 months to assess the progression o the disease or assess loss o renal volume. • Patients who have undergone revascularization need ollow-up with duplex ultrasonography soon a ter the procedure to assess the adequacy o intervention, then a ter 6 months and 12 months and yearly therea ter or whenever there is worsening o hypertension or unexplained elevation in creatinine. 6

PATIENT EDUCATIO N • Emphasize adherence to medical therapy. • Educate the patient on home BP monitoring and reporting to the physician i a signi cant increase in BP is noted. • Emphasize the continued need or risk actor reduction: diabetes, hypertension, dyslipidemia. PATIENT RESO URCES

• Vascular Disease Foundation. Renovascular Hypertension—http:/ / vasculardisease.org/ renovascular-hypertension-ras/ . • Vascular Disease Foundation. Fibromuscular Dysplasia—http:/ / www.vd .org/ diseasein o/ md/ .

7. Turnbull JM. The rational clinical examination. Is listening or abdominal bruits use ul in the evaluation o hypertension? JAMA. 1995;274:1299. 8. Hartman RP, Kawashima A. Radiologic evaluation o suspected renovascular hypertension. Department o Radiology, Mayo Clinic, Rochester, Minnesota. Am Fam Physician. 2009;80(3):273-279. 9. ASTRAL Investigators; Wheatley K, Ives N, et al. Revascularization versus medical therapy or renal-artery stenosis. N Engl J Med. 2009;361:1953-1962. 10. Bax L, Woittiez AJ, Kouwenberg HJ, et al. Stent placement in patients with atherosclerotic renal artery stenosis and impaired renal unction: a randomized trial. Ann Intern Med. 2009;150:840. 11. Trinquart L, Mounier-Vehier C, Sapoval M, Gagnon N, Plouin PF. E cacy o revascularization or renal artery stenosis caused by bromuscular dysplasia: a systematic review and meta-analysis. Hypertension. 2010;56:525-532. 12. Wheatley K, Ives N, Gray R, Kalra PA, et al. Revascularization versus medical therapy or renal-artery stenosis. N Engl J Med. 2009;361:1953-1962. 13. Dworkin LD, Cooper CJ. Renal-artery stenosis. N Engl J Med. 2009;361:1972-1978. 14. Rocha-Singh KJ, Eisenhauer AC, Textor SC, et al. Atherosclerotic Peripheral Vascular Disease Symposium II: intervention or renal artery disease. Circulation. 2008;118:2873-2878.

PART 11

RENAL CELL CARCINO MA

GENITO URINARY/ RENAL

85 RENAL CELL CARCINO MA Mind y A. Smith, MD, MS

PATIENT STO RY A 56-year-old man with hypertension presents with a 2-week history o le t-sided ank pain. Urinalysis shows microscopic hematuria and, a CT scan (Figures 85-1 and 85-2) demonstrates a solid le t renal mass. Work-up or metastatic disease was negative. A biopsy conf rmed renal cell carcinoma and a radical nephrectomy was per ormed.

INTRO DUCTIO N Renal tumors are a heterogeneous group o kidney neoplasms derived rom the various parts o the nephron. Each type o tumor possesses distinct genetic characteristics, histologic eatures, and, to some extent, clinical phenotypes that range rom benign (approximately 20% o small masses) to high-grade malignancy. Around 90% to 95% o kidney neoplasms are renal cell carcinomas (RCCs). 1,2

EPIDEMIO LO GY • RCC comprises 2% to 3% o all malignant diseases in adults and is the seventh most common cancer in men and ninth most common cancer in women. 2 • An estimated 60,920 cases were diagnosed and approximately 13,120 deaths occurred in 2011 rom kidney and renal pelvis cancer. 3 The ageadjusted incidence rate was 14.6 per 100,000 persons with a median age at diagnosis o 64 years. 3 • Li etime risk o kidney and renal pelvis cancer is 1.56% (1 in 63 people will be diagnosed during their li etime). 3 These cancers are more common in men than women (approximately 2:1). • Approximately 2% to 3% o cases are amilial (eg, von Hippel-Lindau syndrome). 2

FIGURE 85-2 CT wit contrast in t e same atie nt s ows t e solid y od e nse re nal ce ll carcinoma mass (arrow) in t e le ft kid ne y and contrasting normal are nc yma. T e contrast is take n u b e tte r b y t e re maining normal kid ne y tissue and t e tumor b e come s more visib le . (Re p rod uce d with p e rmission of Michae l Fre ckle ton, MD.)

• Metastatic disease at presentation occurs in 23% to 33%; the most common sites o distant metastases (in descending order) are lung (with or without mediastinal or hilar nodes), bone, upper abdomen (including the tumor bed, adrenal gland, contralateral kidney, and liver), brain, and other sites (eg, skin, spleen, heart, diaphragm, gut, connective tissue, and pancreas). 4

ETIO LO GY AND PATHO PHYSIO LO GY The majority o renal tumors all into the ollowing categories1,2: • Clear cell carcinoma ( rom high lipid content) (60%-80%). • Papillary carcinoma (5%-15%), urther delineated into type 1 and the more aggressive type 2. • Chromophobic tumors (3%-10%) and other rare subtypes, such as medullary, which occurs almost exclusively in patients with sickle cell trait.

RISK FACTO RS1,2 • Smoking (relative risk 2-3) • Obesity • Hypertension • Acquired cystic disease and end-stage renal disease, including dialysis treatment • Family history o the disease

DIAGNO SIS

FIGURE 85-1 Re nal ce ll carcinoma. CT s ows solid mass in t e le ft kid ne y (arrow). (Re p rod uce d with p e rmissio n of Michae l Fre ckle ton, MD.)

Most presentations are incidental (identif ed during other tests) and, consequently, although the incidence has increased, more cancers are diagnosed at early stages. 2 Despite this act, mortality rates have also increased.

421

PART 11

422

GENITO URINARY/ RENAL

Ch ApTER 85

CLINICAL FEATURES • Hematuria (40%) and ank pain (40%). • Weight loss and anemia (approximately 33%). • Flank mass (approximately 25%). • The classic triad o hematuria, ank pain, and ank mass occurs in 5% to 10% o patients. 1 • Other reported symptoms include night sweats, bone pain, atigue, and sudden onset o le t varicocele. • Systemic symptoms may be caused by metastases or paraneoplastic syndromes, such as parathyroid hormone-related protein (causing hypercalcemia and renal stones), renin (causing hypertension), or erythropoietin (causing erythrocytosis). 2 LABO RATO RY TESTING Potentially use ul studies: SO R C • Hemoglobin (anemia). • Liver chemistries (metastatic disease or paraneoplastic syndrome). • Urinalysis (hematuria—gross or microscopic). • Urine cytology (neoplastic cells). • The National Comprehensive Cancer Network (NCCN) also suggests a metabolic panel including lactate dehydrogenase (LDH) as part o the initial work-up. 5

FIGURE 85-4 patie nt wit tub e rous scle rosis. MRI s o ws multi le ang iomyoli omas in t e kid ne ys wit se ve ral le sions sus icious for re nal cance r. (Re p rod uce d with p e rmission of Karl T. Re w, MD.)

IMAGING • The work-up or indeterminate renal masses suggested by the American College o Radiology (ACR) includes either CT scan o the abdomen (Figures 85-1 to 85-3) (solid renal mass; signs suggestive o

renal vein or caval thrombus include f lling de ects, enlargement o the vessel, and rim enhancement) or abdominal MRI (slightly more sensitive and tends to upgrade cystic lesions; Figure 85-4); either scan should be done without and with contrast. 6 • An ultrasound (US) o the kidney retroperitoneal may help to clari y a mass that is probably a hyperdense cyst (the most common renal mass). • Angiography can be used to def ne vascular anatomy be ore nephronsparing surgery. 6 For the purpose o staging an RCC, ACR recommends6: • Multidetector CT without and with contrast. • Chest X-ray (CXR, tumor may extend into the hilar lymph nodes) or chest CT. • MRI i patient is unable to undergo CT with contrast. • Bone scans and brain MRI should be reserved or patients with abnormal blood chemistries, symptoms, or large and locally aggressive or metastatic primary renal cancers. BIO PSY A renal biopsy is only needed on occasion based on the appearance and size o the mass; US, CT, or MRI can be used or image guidance. 4 ACR indications or biopsy include the ollowing: • Conf rming an in ected cyst

FIGURE 85-3 CT in a 70-ye ar-old man d e monstrating a e te rog e ne ous solid mass in t e mid ortion to lowe r ole of t e rig t kid ne y (arrow), consiste nt wit a rimary re nal cance r. T e mass contains low-atte nuation, like ly ne crotic, com one nts and is e xo ytic. (Re p rod uce d with p e rmission o f Karl T. Re w, MD.)

• Identi ying lymphoma • Determining a metastasis • Conf rming RCC in certain circumstances, including prior to ablative therapies

PART 11

RENAL CELL CARCINO MA

DIFFERENTIAL DIAGNO SIS The di erential diagnosis o a renal mass includes the ollowing: • Simple cysts. • Renal calculi/ nephrolithiasis (see Chapter 80, Kidney Stones). • Benign neoplasms (in rarenal hematoma, adenoma, angiomyolipoma [see Figure 85-4], and oncocytoma). • In ammatory lesions ( ocal bacterial nephritis, abscess, pyelonephritis, and renal tuberculosis); patients o ten present with systemic signs and symptoms o in ection such as ever and chills.

GENITO URINARY/ RENAL epithelial growth actor agents (bevacizumab, sora enib, sunitinib, pazopanib, tivozanib, or axitinib) or mammalian target o rapamycin (mTOR) inhibitors (temsirolimus or everolimus) usually compared to inter eron-α . 8 No placebo-controlled trial has reported a benef t on health-related quality o li e. • The European Society o Medical Oncologists recommends either sunitinib or combination o bevacizumab and inter eron in good-risk and intermediate-risk patients, and temsirolimus in patients with poor-risk eatures and clear cell renal carcinoma. 9 The NCCN recommends any o these as f rst-line therapy or predominantly clear cell carcinoma and enrollment in a clinical trial as the pre erred strategy or non–clear cell cancers, although temsirolimus has shown some promise. 5

• Other primary or metastatic tumors (neoplastic tumors involving the kidney include squamous cell carcinoma o the collecting system, transitional cell carcinomas o the renal pelvis or collecting system, sarcoma, lymphoma, nephroblastoma, and melanoma).

• Presurgical treatment with sunitinib was reported in 1 case series; the drug decreased the size o primary RCC in 17 o 20 patients treated. 10

These can requently be di erentiated rom RCC on CT scan, but biopsy may be necessary.

• For localized disease, partial nephrectomy or small tumors and radical nephrectomy (complete removal o the kidney and Gerota ascia) or large tumors is the gold standard. 2,9 SO R B For T1 tumors (Table 85-1), the NCCN recommends either partial (pre erred) or radical nephrectomy, active surveillance or selected patients, or thermal ablation or nonsurgical candidates. 5

MANAGEMENT Because an increasing number o tumors are identif ed early (tumor size 30, loop diuretic i GFR < 30). ° A diuretic is the rst agent in nondiabetic kidney disease and when spot urine total protein-to-creatinine ratio is greater than 200 mg/ g; add amlodipine as needed. • Goal glycemic control is about 7.5%. • Other risk actor modi cations ° Smoking cessation ° Statin therapy to lower low-density lipoprotein (LDL) less than 100 mg/ dL ° Limit salt intake to less than 2.4 g/ day • Limit protein intake to less than 0.6 g/ kg/ day in patients with stage 4 or 5 CKD. • Correct phosphorus and vitamin D abnormalities—Provide dietary phosphate restriction and phosphate-binding agents, vitamin D supplementation to maintain serum calcium, phosphorus (2.7-4.6 mg/ dL) and parathyroid hormone levels (35-70 stage 3 or 70-110 stage 4) at goal range. • Correct acidosis with oral sodium bicarbonate therapy to maintain serum bicarbonate above 22 mmol/ L. • Correct hyperkalemia—Chronic correction with sodium polystyrene sul onate resin (Kayexalate) may be used. • Anemia—Once a GI source o blood loss is ruled out, provide iron to maintain adequate iron stores ( erritin levels > 100 mg/ dL, trans errin saturation > 20%). • Giving erythropoietin to achieve a hemoglobin level o about 13 is associated with worse outcomes than achieving about an 11 or the hemoglobin level. 4 • I a contrast study is needed, give 0.45% normal saline be ore and a ter the procedure. Also, consider intravenous N-acetylcysteine or sodium bicarbonate. 5,6 • Avoid MRI scans with gadolinium in patients with stage 4 or stage 5 CKD because o the enhanced risk o nephrogenic systemic brosis. 7 • Provide a nephrology consult or all patients with a GFR less than 30. • Dialysis indications include ° Volume overload not responsive to diuretics ° Pericarditis

Ch a pt e r 86

° Uremic encephalopathy ° HTN not responsive to treatment • Others can include metabolic abnormalities noted previously not responsive to treatment; atigue, nausea, and vomiting not otherwise responsive to treatment. PATIENT RESO URCES

• National Kidney Foundation. Clinical practice guidelines for CKD—http:/ / www.kidney.org/ professionals/ kdoqi/ guidelines_ckd/ toc.htm. PRO VIDER RESO URCES

• KDIGO 2012 Clinical Practice guideline for the Evaluation and Management of Chronic Kidney Disease—http:/ / www.kdigo.org/ clinical_practice_guidelines/ pdf/ CKD/ KDIGO_2012_ CKD_GL.pdf.

REFERENCES 1. National Kidney Foundation. KDOQI Clinical Practice Guidelines for Chronic Kidney Disease. 2002. http:/ / www.kidney.org/ pro essionals/ kdoqi/ guidelines_ckd/ toc.htm. 2. Hallan SI, Dahl K, Oien CM, et al. Screening strategies or chronic kidney disease in the general population: ollow-up o cross sectional health survey. BMJ. 2006;333(7577):1047. Epub 2006 Oct 24. 3. Ruzicka M, Burns KD, Culleton B, et al. Treatment o hypertension in patients with nondiabetic chronic kidney disease. Can J Cardiol. 2007;23(7):595-601. 4. Drüeke TB, Locatelli F, Clyne N, et al; and CREATE Investigators. Normalization o hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355(20):2071-2084. 5. Kelly AM, Dwamena B, Cronin P, et al. Meta-analysis: e ectiveness o drugs or preventing contrast-induced nephropathy. Ann Intern Med. 2008;148(4):284-294. 6. Merten GJ, Burgess WP, Gray LV, et al. Prevention o contrastinduced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004;291(19):2328-2334. 7. Agarwal R, Brunelli SM, Williams K, et al. Gadolinium-based contrast agents and nephrogenic systemic brosis: a systematic review and meta-analysis. Nephrol Dial Transplant. 2009;24(3):856-863. doi:10.1093/ ndt/ g n593. Epub 2008 Oct 24.

URINARY SEDIMENT

PART 11

GENITO URINARY/ RENAL

87 URINARY SEDIMENT

• One study o servicemen, conducted or a period o 10 years, ound an incidence o 38%. 1

Mind y A. Smith, MD, MS Richard P. Usatine , MD

• In 1 UK population study, rst episode o hematuria resulted in a noncancer or cancer diagnosis within 90 days in 17.5% o women (95% con dence interval [CI], 16.4%-18.6%) and 18.3% o men (95% CI, 17.4%-19.3%). 2

PATIENT STO RY A 47-year-old woman presents to the o ce with severe right f ank pain that does not radiate. Dipstick urinalysis shows hematuria, and microscopic examination con rms the presence o many red blood cells per high-power eld (Figure 87-1). There is no pyuria or bacteriuria. The physician gives her some pain medication and sends her to get a CT urogram. The CT urogram shows a stone in the right ureter and some mild hydronephrosis. Fortunately, the patient passes the stone when urinating a ter the imaging study is complete.

INTRO DUCTIO N Examination o the urinary sediment is a test requently done or evaluation o patients with suspected genetic/ intrinsic (eg, systemic lupus nephritis, renal sarcoidosis, sickle cell disease, glomerulonephritis, interstitial nephritis), anatomic (eg, arteriovenous mal ormation), obstructive (eg, kidney or bladder stones, benign prostatic hypertrophy), in ectious, metabolic (eg, coagulopathy), traumatic, or neoplastic disease o the urinary tract. Potential ndings o red or white blood cells, casts, bacteria, or neoplastic cells help in directing urther evaluation.

EPIDEMIO LO GY • A nding o hematuria (2-5 red blood cells [RBCs]/ high-power eld [HPF]) on a single urinalysis in an asymptomatic person is common and most o ten a result o menses, allergy, exercise, viral illness, or mild trauma. 1

• Persistent (> 3 RBCs/ HPF over 3 specimens) and signi cant hematuria (> 100 RBCs/ HPF or gross hematuria) was associated with signi cant lesions in 9.1% o more than 1000 patients. 1 • In a review o hematuria, approximately 5% o patients with signi cant microscopic hematuria (> 3 RBCs/ HPF on 2 o 3 properly collected specimens during a 2- to 3-week period)3 and up to 40% o patients with gross hematuria have a neoplasm. 4 • Isolated pyuria (> 2-10 white blood cells per high-power eld [WBCs/ HPF]) is uncommon, as inf ammatory processes in the urinary tract are usually associated with hematuria. 1 • In a laboratory study rom 88 institutions, 62.5% o urinalysis tests received a manual microscopic evaluation o the urinary sediment, usually triggered by an abnormal urinalysis. New in ormation was obtained 65% o the time as a result o the manual examination. 5

ETIO LO GY AND PATHO PHYSIO LO GY • Hematuria (Figure 87-1) has many causes including the ollowing:1 ° Idiopathic (increasing incidence in the young) ° Stones ° Neoplasms (increasing incidence with increase in age) ° Trauma ° In ection/ inf ammation including acute cystitis, urethritis, pyelonephritis, and prostatitis ° Benign prostatic hypertrophy ° Metabolic abnormalities, including hypercalcemia and hyperuricemia ° Glomerular diseases such as immunoglobulin (Ig) A nephropathy, hereditary nephritis, and thin basement membrane disease • Hematuria with dysmorphic RBCs or RBC casts (Figure 87-2) and excess protein excretion (> 500 mg/ dL) indicates glomerulonephritis. • Gross hematuria suggests a postrenal source in the collecting system. • Pyuria (Figure 87-3) is o ten the result o urinary tract in ection. 2 5 ° The presence o bacteria (>10 organisms per mL or > 10 using a midstream urine specimen) suggests in ection. A urinalysis with 10 bacteria per HPF is highly suggestive (speci city 99%) o in ection (positive likelihood ratio [LR+ ] 85). 2 ° Asymptomatic bacteruria is ound in 4% to 15% o pregnant women, usually Escherichia coli. ° The presence o WBC casts (Figure 87-4) with bacteria indicates pyelonephritis. • WBCs and/ or WBC casts can be seen in tubulointerstitial processes like interstitial nephritis, systemic lupus erythematosus, or transplant rejection. • Urinary casts are ormed only in the distal convoluted tubule (DCT) or in the collecting duct (distal nephron).

FIGURE 87-1 Re d b lood ce lls (RBCs) se e n in t e urine o a woman assing a kid ne y stone . Some o t e RBCs are cre nate d , and t e re is 1 e it e lial ce ll visib le . (Re p rod uce d with p e rmission of Richard P. Usatine , MD.)

• Hyaline casts are ormed rom mucoprotein secreted by the tubular epithelial cells within the nephrons. These translucent casts are the most common type o cast and can be seen in normal persons a ter vigorous exercise or with dehydration. Low urine f ow and concentrated

429

430

PART 11

GENITO URINARY/ RENAL

Ch ApTER 87

FIGURE 87-4 WBC casts se e n in ye lone ritis. T e se can b e d i e re ntiate d rom a clum o WBCs b y t e ir cylind rical s a e and t e re se nce o a yaline matrix. (Re p rod uce d with p e rmission of Ag ne s B. Fog o, MD, Vand e rb ilt Unive rsity.)

FIGURE 87-2 An RBC cast cause d b y b le e d ing into t e tub ule rom t e g lome rulus. T e se casts are se e n in g lome rulone ritis, Ig A ne ro at y, lu us ne ritis, Good asture synd rome , and We g e ne r g ranulomatosis. RBC casts are always at olog ic. (Re p ro d uce d with p e rmission of Ag ne s B. Fog o, MD, Vand e rb ilt Unive rsity.)

urine rom dehydration can contribute to the ormation o hyaline casts (Figure 87-5). • Granular casts are the second most common type o cast seen (Figure 87-6). These casts can result rom the breakdown o cellular casts or the inclusion o aggregates o albumin or immunoglobulin light chains. They can be classi ed as ne or coarse based on the size o the inclusions. There is no diagnostic signi cance to the classi cation o ne or coarse.

FIGURE 87-3 pyuria and b acte riuria in a woman wit a urinary tract in e ction. A sim le stain was ad d e d to t e we t mount o s un urine . Alt oug t e re are e it e lial ce lls re se nt, t e culture d e monstrate d a true urinary tract in e ction (UTI) and not me re ly a contaminate d urine . (Re p rod uce d with p e rmission of Richard P. Usatine , MD.)

FIGURE 87-5 h yaline casts are transluce nt and rote inace ous. T e se are t e most common casts ound in t e urine and can b e se e n in normal ind ivid uals. Conce ntrate d urine wit low f ow, usually cause d b y d e yd ration, e xe rcise , and /or d iure tics, can le ad to yaline cast o rmation. (Re p rod uce d with p e rmission of Ag ne s B. Fog o, MD, Vand e rb ilt Unive rsity.)

FIGURE 87-6 Coarse g ranular cast. All g ranular casts ind icate und e rlying re nal d ise ase . T e se are nons e ci c and may b e se e n in d ive rse re nal cond itions. (Re p rod uce d with p e rmission of Ag ne s B. Fog o, MD, Vand e rb ilt Unive rsity.)

URINARY SEDIMENT

RISK FACTO RS • Constipation ( or urinary tract in ection [UTI] in elderly). • Risk actors or cancer in patients with microscopic hematuria include the ollowing4: ° Smoking ° Age older than 40 years ° Medical history o gross hematuria, urologic disease, or pelvic radiation ° Occupational history o exposure to chemicals or dyes ° Analgesic abuse

DIAGNO SIS

PART 11

GENITO URINARY/ RENAL hematuria, a CT o the abdomen and pelvis without contrast and/ or an ultrasound o the kidneys and bladder is most appropriate. 7 For hematuria associated with trauma, obtain a CT o the abdomen and pelvis with contrast. ° I the above is negative or high risk or cancer, per orm cystoscopy. ° I the above is positive, an open renal biopsy may be indicated. ° I the above is negative, consider periodic ollow-up (6, 12, 24, and 36 months). • I RBC casts (Figure 87-2) are seen on UA in addition to proteinuria, also consider nephrotic syndrome caused by diabetes or amyloidosis. • Note that RBC casts are ragile and are best seen in a resh urine specimen (Figure 87-2).

MANAGEMENT

CLINICAL FEATURES

Treatment will depend on the underlying etiology:

• Other signs and symptoms o glomerular disease include various degrees o renal ailure, edema, oliguria, and hypertension.

• Cystitis is treated with appropriate antibiotics based on knowledge o the sensitivities o E. coli in your practice location (nitro urantoin [100 mg twice daily or 5 days], trimethoprim-sul amethoxazole [1 doublestrength tablet twice-daily or 3 days], or os omycin [3-g single dose] are rst-line agents). 8 Symptoms usually improve within 24 to 36 hours.

• Hematuria is o ten asymptomatic in patients with glomerular disease or metabolic abnormalities. Renal stones can cause pain in the ipsilateral f ank and/ or abdomen with radiation to the ipsilateral groin, testicle or vulva or irritative symptoms o requency, urgency, and dysuria, i located in the bladder. • Symptoms o UTI include dysuria, nocturia, urgency, requency, o ensive odor o urine, or a combination o these; positive likelihood ratios, however, are low (1.3-2.3). 6 • Symptoms o pyelonephritis include chills and rigor, ever, nausea and vomiting, and f ank pain; positive likelihood ratios are 1.5 to 2.5. • Family history o renal ailure or microscopic hematuria or history o trauma, weight loss, and changes in urine volume may be use ul.

• Uncomplicated pyelonephritis is treated with appropriate antibiotics as an outpatient (oral ciprof oxacin [500 mg twice daily] or 7 days with or without an initial 400-mg intravenous dose when resistance is not known to exceed 10%). 8 The urine should always be cultured in pyelonephritis to help guide therapy. Pregnant women may need hospitalization. • See Chapter 80 (Kidney Stones) or management o patients with kidney stones, Chapter 85 (Renal Cell Carcinoma) or renal cell carcinoma, and Chapter 78 (Bladder Cancer) or bladder cancer.

LABO RATO RY TESTING AND IMAGING The work-up or persistent or signi cant hematuria includes the ollowing1: • Urinary sediment looking or dysmorphic cells or RBC casts (Figure 87-2) and a 24-hour urine sample or proteinuria. ° I positive, suspect glomerular disease and consider blood cultures, antiglomerular basement membrane (GBM) antibody, antineutrophil cytoplasmic antibody (ANCA), complement, cryoglobulins, hepatitis serologies, Venereal Disease Research Laboratory (VDRL), HIV, and antistreptolysin O; a renal biopsy may be indicated. ° I negative and the sediment contains WBCs (Figure 87-3) or WBC casts (Figure 87-4), suspect in ection and obtain a urine culture and susceptibility test i pyelonephritis is suspected; E. coli is the most common organism (more than 80%) in uncomplicated cystitis. WBCs seen in conjunction with many epithelial cells, particularly in women, can indicate a contaminated specimen; and a new clean catch urine specimen should be obtained i possible. ° I negative and no WBCs, obtain a hemoglobin electrophoresis, urine cytology, urinalysis (UA) rom amily members looking or hematuria or signs o glomerular disease, and a 24-hour urine or calcium and uric acid. • In all adult patients with hematuria (except or those with generalized renal parenchymal disease or young women with hemorrhagic cystitis), the American College o Radiology (ACR) recommends obtaining CT urography. 7 In patients with generalized renal parenchymal disease, ultrasound o the kidneys and bladder is recommended. For pain ul

PREVENTIO N AND SCREENING The United States Preventive Services Task Force concluded that there was insu cient evidence to assess the balance o bene ts and harms o screening or bladder cancer in asymptomatic adults. 9 The positive predictive value o screening is less than 10% in asymptomatic persons, including higher-risk populations. PRO VIDER RESO URCES

• Urinalysis— http:/ / library.med.utah.edu/ WebPath/ TUTORIAL/ URINE/ URINE.html • Urine Sediment Atlas— https:/ / ahdc.vet.cornell.edu/ clinpath/ modules/ ua-sed/ ua-intro.htm

REFERENCES 1. Denker BM, Brenner BM. Azotemia and urinary abnormalities. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds. Harrison’s Principles of Internal Medicine, 16th ed. New York, NY: McGraw-Hill; 2005:250-251. 2. Jones R, Charlton J, Latinovic R, Gulli ord MC. Alarm symptoms and identi cation o non-cancer diagnoses in primary care: cohort study. BMJ. 2009;339:b3094. doi: 10.1136/ bmj.b3094.

431

432

PART 11

GENITO URINARY/ RENAL 3. Gross eld GD, Litwin MS, Wol JS, et al. Evaluation o asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy—part I: de nition, detection, prevalence, and etiology. Urology. 2001;57(4):599-603.

Ch ApTER 87

College o Radiology; 2008 [online publication]. http:/ / www .guideline.gov/ content.aspx?id= 15763&search=hematuria. Accessed July 2013.

5. Tworek JA, Wilkinson DS, Walsh MK. The rate o manual microscopic examination o urine sediment: a College o American Pathologists Q-Probes study o 11,243 urinalysis tests rom 88 institutions. Arch Pathol Lab Med. 2008;132(12):1868-1873.

8. Gupta K, Hooton TM, Naber KG, et al; In ectious Diseases Society o America, European Society or Microbiology and In ectious Diseases. International clinical practice guidelines or the treatment o acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the In ectious Diseases Society o America and the European Society or Microbiology and In ectious Diseases. Clin Infect Dis. 2011;52(5):e103-e120.

6. Bergus GR. Dysuria. In: Sloane PD, Slatt LM, Ebell MH, Smith MA, Power D, Viera AJ, eds. Essentials of Family Medicine, 6th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2012:327-336.

9. Moyer VA; U.S. Preventive Services Task Force. Screening or bladder cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2011;155(4):246-251.

4. Margulis V, Sagalowsky AI. Assessment o hematuria. Med Clin North Am. 2011;95:153-159.

7. Ramchandani P, Kisler T, Francis IR, et al; Expert Panel on Urologic Imaging. ACR Appropriateness Criteria® Hematuria. Reston, VA: American

Pa r t 12

WO MEN’S HEALTH

*

St re ng t h o Re co mme nd at io n (SO R)

De f nit io n

A

Re comme nd ation b ase d on consiste nt and g ood -q uality atie nt-orie nte d e vid e nce .*

B

Re comme nd ation b ase d on inconsiste nt or limite d -q uality atie nt-orie nte d e vid e nce .*

C

Re comme nd ation b ase d on conse nsus, usual ractice , o inion, d ise ase -orie nte d e vid e nce , or case se rie s or stud ie s o d iag nosis, tre atme nt, re ve ntion, or scre e ning .*

Se e A

e nd ix A on ag e s 1241-1244 or urthe r in ormation.

434

PART 12

WO MEN’S HEALTH

SECTIO N 1

CHApTER 88

VAGINITIS/CERVICITIS

88 O VERVIEW O F VAGINITIS E.J. Maye aux Jr, MD

PATIENT STO RY A 39-year-old woman presented to her physician with a malodorous vaginal discharge. On examination, a thin white discharge was seen covering the introitus (Figure 88-1). A speculum examination revealed a thin whitish gray discharge and a distinct f shy odor. The pH o the discharge was 4.6, and 40% o the epithelial cells on her wet prep were clue cells (Figure 88-2). She was diagnosed with bacterial vaginosis and treated with oral metronidazole.

INTRO DUCTIO N Vaginal discharge is a requent presenting complaint in primary care. The 3 most common causes are bacterial vaginosis, candidiasis, and trichomoniasis. However, a signif cant number o patients with vaginal discharge will have some other condition, such as atrophic vaginitis. Providers must re rain rom “diagnosing” a vaginitis based solely on the color and consistency o the discharge, as this may lead to misdiagnosis and may miss concomitant in ections. 1

FIGURE 88-2 A we t mount o vag inal d ischarg e in saline und e r hig h- owe r lig ht microsco y. Note the re se nce o vag inal e ithe lial ce lls, smalle r white b lood ce lls ( olymor honucle ocyte s), and b acte ria. The b acte ria are the coccob acilli o Gard ne re lla vag inalis cove ring the ce ll me mb rane s o the 2 vag inal e ithe lial ce lls ne ar the lowe r e nd o the e ld . The se are clue ce lls se e n in atie nts with b acte rial vag inosis. (Re p rod uce d with p e rmission of Richard P. Usatine , MD.)

EPIDEMIO LO GY The reported rates o chlamydia and gonorrhea are highest among emales ages 15 to 19 years. Adolescents are at greater risk or sexually transmitted diseases (STDs) because they requently have unprotected intercourse, are biologically more susceptible to in ection, are o ten engaged in partnerships o limited duration, and ace multiple obstacles to utilization o health care. 1

ETIO LO GY AND PATHO PHYSIO LO GY • The quantity and quality o normal vaginal discharge in healthy women vary. Physiologic leukorrhea re ers to generally nonmalodorous, mucousy, white, or yellowish vaginal discharge in the absence o a pathologic cause. It is not accompanied by signs and symptoms such as pain, pruritus, burning, erythema, or tissue riability. However, slight malodor and irritative symptoms can be normal or some women at certain times. 2 Physiologic leukorrhea is usually a result o estrogeninduced changes in cervicovaginal secretions. • Nonin ectious causes o vaginitis include irritants (eg, scented panty liners, spermicides, povidone-iodine, soaps and per umes, and some topical drugs) and allergens (eg, latex condoms, topical anti ungal agents, chemical preservatives) that produce hypersensitivity reactions. FIGURE 88-1 Thin white d ischarg e rom b acte rial vag inosis se e n cove ring the introitus rior to s e culum e xamination. (Re p rod uce d with p e rmission of Se attle STD/HIV Pre ve ntion Training Ce nte r, Unive rsity of Washing ton.)

• Be ore starting an examination, determine whether the patient douched recently, because this can lower the yield o diagnostic tests and increase the risk o pelvic in ammatory disease. 3 Patients who have

O VERVIEW O F VAGINITIS

FIGURE 88-3 Col osco ic vie w o the ce rvix in a atie nt in e cte d with trichomonas vag inalis. Note the rothy d ischarg e with visib le b ub b le s and the ce rvical e rythe ma. (Re p rod uce d with p e rmission of Se attle STD/HIV Pre ve ntion Training Ce nte r, Unive rsity of Washing ton.)

been told not to douche will sometimes start wiping the vagina with soapy washcloths, which also irritates the vagina and cervix and may cause a discharge. Douching is associated with increases in bacterial vaginosis and acquisition o sexually transmitted in ections when exposed. However, recent studies indicate that douching with plain water once a week or less did not disturb normal ora. 4,5 • There are many causes o vaginitis in humans. In ectious causes include bacterial vaginosis (40%-50% o cases) (see Figures 88-1 and 88-2), vulvovaginal candidiasis (20%-25%), and trichomonas (15%-20%) (Figure 88-3). 6 Less common causes include atrophic vaginitis, oreign body (especially in children), cytolytic or desquamative in ammatory vaginitis, streptococcal vaginitis, ulcerative vaginitis, and idiopathic vulvovaginal ulceration associated with HIV in ection. • Rarer nonin ectious causes include chemicals, allergies, hypersensitivity, contact dermatitis, trauma, postpuerperal atrophic vaginitis, erosive lichen planus, collagen vascular disease, Behçet syndrome, and pemphigus syndromes.

DIAGNO SIS

PART 12

WO MEN’S HEALTH

FIGURE 88-4 S e culum e xamination showing muco urule nt d ischarg e with a riab le a e aring ce rvix. (Re p rod uce d with p e rmission of Richard P. Usatine , MD.)

may show evidence o cervical, uterine, or adnexal tenderness. Table 88-1 shows diagnostic values or examination o vaginitis. • Vaginal pH testing can be help ul in the diagnosis o vaginitis. The pH can be checked by applying pH paper to the vaginal sidewall. Do not place the pH paper in contact with the cervical mucus. A pH above 4.5 is seen with menopausal patients, trichomonas in ection, or bacterial vaginosis. • Wet preps are obtained by applying a cotton-tipped applicator to the vaginal sidewall and placing the sample into normal saline. A drop o the suspension is then placed on a slide and examined or the presence and number o white blood cells (WBCs), trichomonads, candidal hyphae, or clue cells (Figure 88-1). • A KOH prep is made by adding a drop o KOH solution to a drop o saline suspension o the discharge. The KOH lyses epithelial cells in 5 to 15 minutes ( aster i the slide is warmed brie y) and allows easier visualization o candidal hyphae. The use o KOH with DMSO allows or quicker lyses o the epithelial cells and immediate examination o the smear. • Another diagnostic procedure is the “whi ” test, which is per ormed by placing a drop o KOH on a slide o the wet prep and smelling or a oul, f shy odor. The odor is indicative o anaerobic overgrowth or in ection. The “whi ” test is positive i the f shy amine odor is detected during the examination and it is then not necessary to add KOH and “whi ” again.

CLINICAL FEATURES • Examine the external genitalia or irritation or discharge (see Figure 88-2). Speculum examination is done to determine the amount and character o the discharge (Figure 88-4). A chlamydia and gonorrhea test should always be done in sexually active emales with a vaginal discharge. Look closely at the cervix or discharge and signs o in ection, dysplasia, or cancer (Figure 88-3). Bimanual examination

LABO RATO RY TESTING • Nucleic acid amplif cation tests are highly sensitive tests or Neisseria gonorrhoeae, Chlamydia, and Chlamydia trachomatis that can be per ormed on genital specimens or urine. Urine screening or gonorrhea, chlamydia, or both using nucleic acid amplif cation test can be used success ully in di f cult-to-reach adolescents. 7

435

PART 12

436

CHApTER 88

WO MEN’S HEALTH TABLE 88-1 Diag nostic Value s or Vag inal In e ctions

Diag no st ic Crit e ria

Bact e rial Vag ino sis

Tricho mo nas Vag init is

Cand id a Vulvo vag init is

No rmal

Vag inal H

3.8-4.2

>4.5

4.5

10/h

Bud d ing ye ast, hy hae , pse ud ohy hae

Data from E.J. Maye aux Jr, MD.

MANAGEMENT • Management is based on the identif cation o the causative agent. • Treatment or physiologic leukorrhea is unnecessary. • Management o vaginal irritants and allergens involves identi ying and eliminating the o ending agents. However, irritants and allergens can o ten be di f cult to identi y. • Health ood store lactobacilli are the wrong strain and do not adhere well to the vaginal epithelium. Ingestion o live-culture, nonpasteurized yogurt does not signif cantly change the incidence o candidal vulvovaginitis or bacterial vaginosis. 8 PATIENT RESO URCES

• Centers for Disease Control and Prevention. Sexually Transmitted Diseases page—http:/ / www.cdc.gov/ std/ . • Planned Parenthood—http:/ / www.plannedparenthood .org/ cameron-willacy/ images/ South-Texas/ What_ Every_Woman_Needs_to_Know_English.pdf. • Illinois Department of Public Health. Vaginitis—www.idph .state.il.us/ public/ hb/ hbvaginitis.htm. PRO VIDER RESO URCES

• Centers for Disease Control and Prevention. 2010 Guidelines for Treatment of Sexually Transmitted Diseases—http:/ / www.cdc.gov/ std/ treatment/ 2010/ STD-Treatment-2010-RR5912.pdf. • Centers for Disease Control and Prevention. Self-Study STD Module–Vaginitis—http:/ / www2a.cdc.gov/ STDTraining/ Self-Study/ vaginitis/ default.htm • Centers for Disease Control and Prevention. Vaginitis slides— http:/ / www2a.cdc.gov/ stdtraining/ ready-to-use/ Manuals/ Vaginitis/ vaginitis-slides-2010.pdf. • eMedicine. Vaginitis—http:/ / emedicine.medscape.com/ article/ 257141-overview. • American Family Physician. Diagnosis of Vaginitis—http:/ / www .aafp.org/ afp/ 20000901/ 1095.html.

REFERENCES 1. Centers or Disease Control and Prevention. SexuallyTransmitted Disease Surveillance 2001. Atlanta, GA: U.S. Department o Health and Human Services, CDC, 2002. 2. Anderson M, Karasz A, Friedland S. Are vaginal symptoms ever normal? A review o the literature. Med Gen Med. 2004;6:49. 3. Zhang J, Thomas AG, Leybovich E. Vaginal douching and adverse health e ects: a meta-analysis. Am J Public Health. 1997;87:1207-1211. 4. Hassan S, Chatwani A, Brovender H, et al. Douching or perceived vaginal odor with no in ectious cause o vaginitis: a randomized controlled trial. J Low Genit Tract Dis. 2011;15(2):128-133. 5. Zhang J, Hatch M, Zhang D, et al. Frequency o douching and risk o bacterial vaginosis in A rican-American women. Obstet Gynecol. 2004;104(4):756-760. 6. Sobel JD. Vaginitis. N Engl J Med. 1997;337:1896-1903. 7. Monroe KW, Weiss HL, Jones M, Hook EW 3rd. Acceptability o urine screening or Neisseria gonorrheae and Chlamydia trachomatis in adolescents at an urban emergency department. SexTransm Dis. 2003;30:850-853. 8. Pirotta M, Gunn J, Chondros P, et al. E ect o lactobacillus in preventing post-antibiotic vulvovaginal candidiasis: a randomised controlled trial. BMJ. 2004;329:548.

a t r O ph IC Va GINIt IS

89 ATRO PHIC VAGINITIS E.J. Maye aux Jr, MD

PATIENT STO RY A 60-year-old woman with vaginal dryness and irritation is seen to ollow-up on an in ammatory Pap smear. She denies discharge, odor, douching, and sexually transmitted disease (STD) exposure. She does admit to some postcoital bleeding. Her cervix has atrophic changes and an endocervical polyp (Figure 89-1). The polyp was removed easily with a ring orceps and no dysplasia was ound on pathology.

INTRO DUCTIO N Vaginal atrophy caused by estrogen def ciency is common and usually is asymptomatic except or vaginal dryness.

SYNO NYMS Vaginal atrophy, vulvovaginal atrophy, urogenital atrophy, senile vaginitis.

EPIDEMIO LO GY • The average age o menopause is 51 years in the United States.

PART 12

WO MEN’S HEALTH between the ages o 40 and 45 years (early menopause). This means that in the United States, most women will live a signif cant portion o their lives during menopause. Women who in menopause have surgical menopause or have ovarian suppression without estrogen supplementation (progestin-only contraceptives) are susceptible to atrophic changes in their lower genital tract. • Vaginal dryness occurs in approximately 3% o women o reproductive age, 4% to 21% o women in the menopausal transition, and 47% o women 3 years postmenopause. 1 Internationally, 39% o women experience menopause-related vaginal discom ort. 2

ETIO LO GY AND PATHO PHYSIO LO GY • A ter menopause, circulating estrogen levels dramatically decrease to a level at least one-sixth their premenopausal levels. 3 Changes that occur in the vaginal and cervical epithelium include proli eration o connective tissue, loss o elastin, thinning o the epithelium (Figure 89-2), and hyalinization o collagen. • A long-term decrease in estrogen is generally necessary be ore symptoms become apparent. Genital symptoms include decreased vaginal lubrication, dryness, burning, dyspareunia, leukorrhea, itching, and yellow malodorous discharge. • Urinary symptoms, such as requency, hematuria, urinary tract in ection, dysuria, and stress incontinence, are usually late symptoms. Over time, the lack o vaginal lubrication o ten results in sexual dys unction. • Cervical polyps (Figure 89-1) are pedunculated tumors that usually arise rom the endocervical canal mucosa, and are common in patients with atrophic vaginitis. Many will show squamous metaplasia, and they may develop squamous dysplasia. Polyps are most commonly asymptomatic unless they bleed.

• Approximately 5% o women experience menopause a ter age 55 years (late menopause), and another 5% experience the transition

• Menopause is the most common cause o atrophic vaginitis. In premenopausal women, radiation therapy, chemotherapy, immunologic disorders, and oophorectomy may greatly decrease production o ovarian estrogen and lead to atrophic vaginitis. Antiestrogen medications may also result in atrophic vaginitis. Women who are naturally premenopausally estrogen def cient, smoke cigarettes, or have not given vaginal birth tend to have more severe symptoms. 3

FIGURE 89-1 Col osco ic o og (sc nning ob j c iv wi 10× y i c ) d mons ing o ic v g ini is. No inn d w i i lium, i bl i lium wi b l d ing , nd c vic l oly . (Re p rod uce d with p e rmission of E.J. Maye aux Jr, MD.)

FIGURE 89-2 Col osco ic o og (sc nning ob j c iv wi 10× y i c ) d mons ing o ic c vicov g ini is. No in w i i lium, l iv d yn ss, nd b ly visib l c vic l os. (Re p ro d uce d with p e rmission of E.J. Maye aux Jr, MD.)

437

PART 12

438

WO MEN’S HEALTH RISK FACTO RS • Age • Family history o early menopause • Bilateral oophorectomy • Spontaneous premature ovarian ailure • Antiestrogenic medications e ects, such as tamoxi en, danazol, medroxyprogesterone acetate • Gonadotropin-releasing hormone agonists (leuprolide, na arelin, goserelin), or antagonists (ganirelix) • Prolactin elevation as a result o hypothalamic-pituitary disorders with secondary reduction o estrogen secretion • Certain chemotherapeutic agents • Pelvic radiation therapy • Severe systemic lupus erythematosus or rheumatoid arthritis (because o hypothalamic hypogonadism or primary ovarian insu f ciency) combined with glucocorticoid therapy cause combined suppression o ovarian and adrenal activity

DIAGNO SIS CLINICAL FEATURES • Diagnosis is clinical, based upon characteristic symptoms and f ndings. Many women with symptoms o vaginal atrophy do not discuss their condition with a health care provider because they believe their symptoms are a normal part o the aging process. 4 • Atrophic vaginal and cervical epithelium appears pale, smooth, relatively dry, and shiny (Figure 89-2). In ammation with patchy erythema, petechiae, and riability is common in more advanced cases. The external genitalia may demonstrate diminished elasticity, turgor o skin, sparsity o pubic hair, dryness o labia, erythema (Figure 89-3), and usion o the labia minora. 5 LABO RATO RY TESTING • Laboratory tests to conf rm hypoestrogenic f ndings are typically not necessary.

Ch a pt e r 89

• Serum estradiol levels o less than 20 pg/ mL support a clinical diagnosis o a low-estrogenic state. However, values are very laboratory dependent, and most assays are neither su f ciently sensitive nor reliable or diagnosis o hypoestrogenic states without clinical signs and symptoms. • A serum ollicle-stimulating hormone (FSH) level greater than 40 mIU/ mL is diagnostic o menopause. • A Papanicolaou smear can conf rm the presence o urogenital atrophy. Cytologic examination o smears rom the upper one-third o the vagina shows an increased proportion o parabasal cells and a decreased percentage o superf cial cells. • An elevated vaginal pH level (> 5), monitored by a pH strip in the vaginal vault, may also be a sign o vaginal atrophy. 3 IMAGING • Testing or associated osteoporosis should be considered i not previously per ormed.

DIFFERENTIAL DIAGNO SIS • Atrophic vaginitis symptoms can be mimicked or exacerbated by coinection o candidiasis, trichomoniasis, or bacterial vaginosis. These can be identif ed by wet prep, pH, and whi test (see Chapter 90, Bacterial Vaginosis). • Sexually transmitted diseases, including gonorrhea, trichomonas, and chlamydia, also may coexist with or mimic atrophic vaginitis. Cultures or nucleic acid amplif cation tests can identi y these in ections. It is important not to assume a diagnosis o solely atrophic vaginitis in the postmenopausal patient who presents with urogenital complaints. (Chapter 88, Overview o Vaginitis). • Contact dermatitis because o environmental agents (eg, per umes, deodorants, soaps, panty liners, perineal pads, spermicides, lubricants, or tight f tting/ synthetic clothing) may cause erythema, itching, burning, or pain. (Chapter 144, Contact Dermatitis). • Vulvovaginal lichen planus may produce labial usion. (Chapter 154. Lichen Planus). • Lichen sclerosus (LS) appears to cause atrophy o the vulva and can be mistaken or the atrophy o estrogen def ciency. It can be recognized by the hour-glass conf guration o the involvement around the vulva and perianal region (Figure 89-4). LS is treated with a high-potency steroid ointment rather than estrogen.

MANAGEMENT NO NPHARMACO LO GIC • Nonhormonal local vaginal moisturizers and lubricants may be used to help maintain natural secretions and com ort during intercourse. Sexual activity has been shown to encourage vaginal elasticity and pliability, and the lubricative response to sexual stimulation. An open-label study indicated that Replens, a bioadhesive vaginal moisturizer, was a sa e and e ective alternative to estrogen vaginal cream, with both therapies exhibiting statistically signif cant increases in vaginal moisture, vaginal uid volume, and vaginal elasticity. 6 SO R A FIGURE 89-3 t vulv o os m no us l wom n d mons ing inning o i nd inning nd y m o vulv skin ssoci d wi o ic vulvi is. (Re p ro d uce d with p e rmissio n o f Go rd o n Davis, MD, Arizona Vulva Clinic, Inc.)

• Water-based vaginal lubricants include the ollowing: ° Slippery Stu (polyoxyethylene, methylparaben, propylene glycol, isopropanol)

PART 12

a t r O ph IC Va GINIt IS

WO MEN’S HEALTH when compared to tablets causing uterine bleeding, breast pain, and perineal pain. Another trial ound signif cant endometrial overstimulation ollowing use o the conjugated equine estrogen cream when compared to the estrogen vaginal ring. Women appeared to avor the estradiol-releasing vaginal ring or ease o use, com ort o product, and overall satis action. 8 SO R A • The amount o estrogen and the duration o time required to eliminate symptoms depend on the degree o vaginal atrophy, and varies among patients. Progestin therapy should be considered in any woman with an intact uterus to avoid causing endometrial cancer. When oral estrogen is used at typical doses, atrophic symptoms will persist in 10% to 25% o patients. 9 • Topical administration o estrogen is an excellent treatment or genitourinary symptoms o atrophy, because exposure o other organs can be minimized i low doses o topical estrogens are used. Absorption rates with topical therapy increase with treatment duration because o the enhanced vascularity o the epithelium.

FIGURE 89-4 Lic n scl osus o vulv in is 53-y -old wom n. Lic n scl osus c n b cog niz d b y ou -g l ss conf g u ion o involv m n ound vulv nd i n l g ion. t m“ o icus” w sd o d om n m b c us cond i ion is c u lly scl o ic, no o ic. (Re p rod uce d with p e rmission o f Richard P. Usatine , MD.)

° Astroglide (glycerin, methylparaben, propylparaben, polypropylene glycol, polyquaternium, hydroxyethylcellulose) ° K-YJelly (glycerin, hydroxyethylcellulose, parabens, and chlorhexidine) ° Pre-Seed (hydroxyethylcellulose, arabinogalactan, paraben, and Pluronic copolymers), which is promoted or women who are trying to conceive • Silicone-based are as ollows: ° ID Millennium (cyclomethicone, dimethicone, and dimethiconol) ° Pjur Eros (cyclopentasiloxane, dimethicone, and dimethiconol) ° Pink (dimethicone, vitamin E, aloe vera, dimethiconol, and cyclomethicone) • Oil-based are as ollows: ° Elégance Women’s Lubricant ° Natural oils (such as olive oil) • Water-based and silicone-based vaginal lubricants are compatible with condom use. Oil-based lubricants may damage latex-based condoms. • Patients should stop smoking, as women who smoke cigarettes are relatively estrogen-def cient. 7 SO R A MEDICATIO NS • Estrogen replacement therapy relieves menopausal symptoms including atrophic vaginitis. 8 SO R A Routes o administration include oral, transdermal, and intravaginal. Risks associated with estrogen use include breast cancer, coronary heart disease, stroke, and venous thromboembolism. • A Cochrane review ound that estrogen creams, pessaries, vaginal tablets, and the estradiol vaginal ring appeared to be equally e ective or the symptoms o vaginal atrophy. 8 SO R A One trial ound signif cant side e ects ollowing conjugated equine estrogen cream administration

• Vaginal estrogen therapy available in the United States are conjugated estrogens cream (0.625 mg conjugated estrogens/ g, 0.5 g o cream intravaginally twice weekly) and estradiol cream (100 mcg estradiol/ g o cream, 2-4 g o cream intravaginally administered daily or 2 weeks, then decreased to 1 g o cream 1-3 times per week), tablet (10 mcg estradiol/ tablet intravaginally daily or 2 weeks then twice weekly), and ring (0.5 mcg estradiol/ day, released over 90 days). In Europe and some other countries, estriol cream is also available. • Vaginal estrogen therapy results in some estrogen absorption into the circulation, although to a lesser degree than oral or transdermal estrogen treatment. In 1 study, systemic absorption was 30% lower in a study o vaginal versus conjugated estrogen therapy. 10 SO R B • Progestin therapy is probably not necessary to protect against endometrial hyperplasia in women treated with the low-dose ring or intravaginal tablet when used as approved. The systemic estrogen absorption with use o the vaginal creams is di f cult to quanti y, so some experts recommend use o an opposing progestin or women treated with vaginal estrogen cream. 11 SO R C

FO LLO W-UP Follow-up is needed or all patients placed on estrogen therapy to monitor or estrogen-related side e ects. Otherwise, ollow-up can be as needed.

PATIENT EDUCATIO N Discuss the risks and benef ts o estrogen replacement therapy with patients interested in the use o estrogens. Vaginal lubricants (nonprescription) may sa ely help prevent pain during intercourse. PATIENT RESO URCES

• NCBI. Atrophic Vaginitis—www.ncbi.nlm.nih.gov. • MedlinePlus. Atrophic Vaginitis—www.nlm.nih.gov/ medlineplus/ ency/ article/ 000892.htm. • Harvard Medical School. Atrophic Vaginitis—www.health .harvard.edu/ fhg/ updates/ update0703c.shtml.

439

PART 12

440

WO MEN’S HEALTH PRO VIDER RESO URCES

• eMedicine. Vaginitis—http:/ / emedicine.medscape.com/ article/ 257141. • eMedicine. Vulvovaginitis in Emergency Medicine—http:/ / emedicine .medscape.com/ article/ 797497. • Bachmann GA, Nevadunsky NS. Diagnosis and treatment of atrophic vaginitis. Am Fam Physician. 2000;61(10):3090-3096.— http:/ / www.aafp.org/ afp/ 2000/ 0515/ p3090.html. • American Family Physician. Diagnosis and Treatment of Atrophic Vaginitis—http:/ / www.aafp.org/ afp/ 20000515/ 3090.html.

REFERENCES 1. Dennerstein L, Dudley EC, Hopper JL, et al. A prospective population-based study o menopausal symptoms. Obstet Gynecol. 2000;96:351. 2. Nappi RE, Kokot-Kierepa M. Women’s voices in the menopause: results rom an international survey on vaginal atrophy. Maturitas. 2010;67:233. 3. Pandit L, Ouslander JG. Postmenopausal vaginal atrophy and atrophic vaginitis. Am J Med Sci. 1997;314:228-231.

Ch a pt e r 89

4. Bachmann GA, Nevadunsky NS. Diagnosis and treatment o atrophic vaginitis. Am Fam Physician. 2000;61:3090. 5. Johnston SL, Farrell SA, Bouchard C, et al. The detection and management o vaginal atrophy. J Obstet Gynaecol Can. 2004;26:503. 6. Nachtigall Le. Comparative study: Replens versus local estrogen in menopausal women. Fertil Steril. 1994;61:178. 7. Tansavatdi K, McClain B, Herrington DM. The e ects o smoking on estradiol metabolism. Minerva Ginecol. 2004;56:105. 8. Suckling J, Lethaby A, Kennedy R. Local oestrogen or vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD001500. 9. Smith P, Heimer G, Lindskog M, Ulmsten U. Oestradiol-releasing vaginal ring or treatment o postmenopausal urogenital atrophy. Maturitas. 1993;16:145-154. 10. Dorr MB, Nelson AL, Mayer PR, et al. Plasma estrogen concentrations a ter oral and vaginal estrogen administration in women with atrophic vaginitis. Fertil Steril. 2010;94:2365. 11. Bachmann G, Bouchard C, Hoppe D, et al. E f cacy and sa ety o low-dose regimens o conjugated estrogens cream administered vaginally. Menopause. 2009;16:719.

PART 12

BACTERIAL VAGINO SIS

WO MEN’S HEALTH

90 BACTERIAL VAGINO SIS E.J. Maye aux Jr, MD Richard P. Usatine , MD

PATIENT STO RY A 31-year-old woman presents with a malodorous vaginal discharge or 3 weeks. There is no associated vaginal itching or pain. She is married and monogamous. She admits to douching about once per month to prevent odor but it is not working this time. On examination, her discharge is visible (Figure 90-1). It is thin and o -white. Wet prep examination shows that more than 50% o the epithelial cells are clue cells (Figure 90-2). The patient is treated with oral metronidazole 500 mg bid or 7 days with good results.

INTRO DUCTIO N Bacterial vaginosis (BV) is a clinical syndrome resulting rom alteration o the vaginal ecosystem. It is called a vaginosis, not a vaginitis, because the tissues themselves are not actually in ected, but only have super cial involvement. Women with BV are at increased risk or the acquisition o HIV, Neisseria gonorrhoeae, Chlamydia trachomatis, and herpes simplex virus (HSV)-2, and they have increased risk o complications a ter gynecologic surgery. 1 BV is associated with adverse pregnancy outcomes, including premature rupture o membranes, preterm labor, preterm birth, intraamniotic in ection, and postpartum endometritis. However, the only established

FIGURE 90-2 Clue ce ll and b acte ria se e n in b acte rial vag inosis. The lowe r ce ll is a clue ce ll cove re d in b acte ria while the u e r ce ll is a normal e ithe lial ce ll. Lig ht microsco e und e r hig h owe r. (Re p rod uce d with p e rmission o f E.J. Maye aux Jr, MD.)

bene t o BV therapy in pregnant women is the reduction o symptoms and signs o vaginal in ection. 1

SYNO NYMS • Vaginal bacteriosis • Corynebacterium vaginosis/ vaginalis/ vaginitis • Gardnerella vaginalis/ vaginosis • Haemophilus vaginalis/ vaginitis • Nonspeci c vaginitis • Anaerobic vaginosis

EPIDEMIO LO GY BV is e stimate d to b e the most re vale nt cause of vag inal d ischarg e or malod or in wome n re se nting for care in the Unite d State s. Howe ve r, more than 50% of wome n with BV are asym tomatic.1 It accounts for more than 10 million out atie nt visits e r ye ar.2 The world wid e re vale nce is unknown.

ETIO LO GY AND PATHO PHYSIO LO GY FIGURE 90-1 A 31-ye ar-old woman with homog e ne ous, thin white malod o rous vag inal d ischarg e . (Re p rod uce d with p e rmission of Richard P. Usatine , MD.)

• Hydrogen peroxide-producing Lactobacillus is the most common organism composing normal vaginal f ora. 1 In BV, normal vaginal lactobacilli are replaced by high concentrations o anaerobic bacteria

441

PART 12

442

WO MEN’S HEALTH

CHApTER 90

such as Mobiluncus, Prevotella, Gardnerella, Bacteroides, and Mycoplasma species. 1,2 • The hydrogen peroxide produced by the Lactobacillus may help in inhibiting the growth o atypical f ora. • The odor o BV is caused by the aromatic amines produced by the altered bacterial f ora in the vagina. These aromatic amines include putrescine and cadaverine—aptly named to describe their oul odor.

RISK FACTO RS • Multiple male or emale partners1,3 • A new sex partner1 • Douching4 • Lack o condom use1 • Lack o vaginal lactobacilli1 • Prior BV in ection1

DIAGNO SIS CLINICAL FEATURES • Symptomatic patients present with an unpleasant, “ shy smelling” discharge that is more noticeable a ter coitus (the basic pH o seminal f uid is like doing the whi test with KOH). There may be pruritus but not as o ten as seen with Candida vaginitis. The physical examination should include inspection o the external genitalia or irritation or discharge. Speculum examination is done to determine the amount and character o the discharge. A nucleic acid ampli cation test or N. gonorrhoeae, Chlamydia, and/ or C. trachomatis (or similar test) should be per ormed on genital specimens (urethral or cervical) or urine.

FIGURE 9 0 -3 A ho mo g e ne o us, o ff-white cre amy malo d o ro us d ischarg e that ad he re s to the vag inal walls and o o ls in the vag inal vault in a wo man with b acte rial vag ino sis. (Re p ro d uce d with p e rmissio n o f Richard P. Usatine , MD.)

• BV is usually clinically diagnosed by nding 3 o the ollowing 4 signs and symptoms: ° Homogeneous, thin, white discharge that smoothly coats the vaginal walls (Figure 90-3 and 90-4). ° Presence o clue cells on microscopic examination (Figure 90-2). ° pH o vaginal f uid > 4.5. be ore or a ter addition o 10% ° A shy odor o vaginal discharge KOH (ie, the whi test). 1 LABO RATO RY TESTING • Vaginal pH testing can be very help ul in the diagnosis o vaginitis. The normal vaginal pH is usually 3.5 to 4.5. A pH above 4.5 is seen with menopausal patients, Trichomonas in ection, or BV. A small piece o pH paper is touched to the vaginal discharge during the examination or on the speculum. Do not test a wet-prep sample i saline has been added because the saline alters the pH. • Wet preps are obtained using a cotton-tipped applicator applied to the vaginal sidewall, placing the sample o discharge into normal saline (not water). Observe or clue cells, number o white blood cells, trichomonads, and candidal hyphae. Clue cells are squamous epithelial cells whose borders are obscured by attached bacteria. More than 20% to 25% o epithelial cells seen in BV should be clue cells (Figure 90-2). • A proline aminopeptidase test card (Pip Activity Test Card), a DNA probe-based test or high concentrations o G. vaginalis (A rm VP III), and the OSOM BVBLUE test have shown acceptable per ormance

FIGURE 90-4 Close -u vie w of the ce rvix showing a ye llowish white homog e ne ous d ischarg e in a woman with b acte rial vag inosis. Note the lack of clum ing or “cottag e -che e se ” a e arance usually found with Cand id a infe ctions. (Re p ro d uce d with p e rmission of E.J. Maye aux Jr, MD.)

BACTERIAL VAGINO SIS

characteristics compared with Gram stain (gold standard). 1 However, they are more costly than traditional testing without clear advantages. • Although a test card is available or the detection o elevated pH and trimethylamine, it has low sensitivity and speci city and is not recommended by the Centers or Disease Control and Prevention (CDC). 1 • Culture o G. vaginalis is not recommended as a diagnostic tool because it is not speci c. • Pap tests are not use ul or the diagnosis o BV because o their low sensitivity. 1

DIFFERENTIAL DIAGNO SIS • Trichomonas also may have the odor o aromatic amines and, there ore, easily con used with BV at rst glance. Look or the strawberry cervix on examination and moving trichomonads on the wet prep (Chapter 84, Trichomonas Vaginitis). • Candida vaginitis tends to present with a cottage-cheese-like discharge and vaginal itching (Chapter 83, Candida Vulvovaginitis). • Gonorrhea and chlamydia should not be missed in patients with vaginal discharge. Consider testing or these sexually transmitted diseases (STDs) based on patients’ risk actors and the presence o purulence clinically and white blood cells on the wet prep (Chapter 85, Chlamydia Cervicitis).

MANAGEMENT • Treatment is recommended or women with symptoms. • Treatment o male sex partners has not been bene cial in preventing the recurrence o BV. 1 SO R A MEDICATIO NS • The established bene ts o therapy or BV in nonpregnant women are to (a) relieve vaginal symptoms and signs o in ection and (b) reduce the risk or in ectious complications a ter abortion or hysterectomy. 1 SO R A Other potential bene ts might include a reduction in risk or other sexually transmitted in ections (STIs). 1 SO R B Table 90-1 shows CDC recommended treatments. • Metronidazole, a 2-g single-dose therapy has the lowest e cacy or BV and is no longer a recommended or alternative regimen. Clindamycin cream is oil-based and might weaken latex condoms and diaphragms or 5 days a ter use. Topical clindamycin preparations should not be used in the second hal o pregnancy. 1 Multiple studies and metaanalyses have not demonstrated an association between metronidazole use during pregnancy and teratogenic or mutagenic e ects in newborns. 1 SO R A • The only established bene t o therapy or BV in pregnant women is to relieve vaginal symptoms and signs o in ection. 1 SO R A Additional potential bene ts o therapy include (a) reducing the risk or in ectious complications associated with BV during pregnancy and (b) reducing the risk or other in ections (eg, other STDs or HIV). Multiple studies and metaanalyses have not demonstrated an association between metronidazole use during pregnancy and teratogenic or mutagenic e ects in newborns. 5 • One randomized trial or persistent BV indicated that metronidazole gel 0.75% twice per week or 6 months a ter completion o a

PART 12

443

WO MEN’S HEALTH TABLE 90-1 CDC Re comme nd e d Re g ime ns SO R

A

Me tronid azole 500 mg orally twice a d ay for 7 d ays OR Me tronid azole g e l 0.75%, 1 full a nally, once a d ay for 5 d ays

licator (5 g ) intravag i-

OR Clind amycin cre am 2%, 1 full a at b e d time for 7 d ays

licator (5 g ) intravag inally

CDC Alte rnative Re g ime ns

SO R

A

Tinid azole 2 g orally once d aily for 3 d ays OR Tinid azole 1 g orally once d aily for 5 d ays OR Clind amycin 300 mg orally twice a d ay for 7 d ays OR Clind amycin ovule s 100 mg intravag inally once at b e d time for 3 d ays OR Me tronid azole 750-mg e xte nd e d -re le ase tab le ts once d aily for 7 d ays CDC Re comme nd e d Re g ime ns for Pre g nant Wome n SO R

A

Me tronid azole 500 mg orally twice a d ay for 7 d ays OR Me tronid azole 250 mg orally thre e time s a d ay for 7 d ays OR Clind amycin 300 mg orally twice a d ay for 7 d ays Data from Ce nte rs for Dise ase Control and pre ve ntion.1

recommended regimen was e ective in maintaining a clinical cure or 6 months. 6 SO R B • Limited data suggest that oral nitroimidazole ollowed by intravaginal boric acid and suppressive metronidazole gel or those women in remission might be an option in women with recurrent BV. 7 SO R B • Intravaginal clindamycin cream has been associated with adverse outcomes i used in the latter hal o pregnancy. 1 CO MPLEMENTARY AND ALTERNATIVE THERAPY • Extended ingestion o live culture, nonpasteurized yogurt may theoretically increase colonization by lactobacilli and decrease the episodes o BV. 8 SO R C However, health ood store lactobacilli are the wrong strain and are not well-retained by the vagina. • The e cacy o exogenous lactobacillus recolonization with probiotic lactobacilli vaginal gelatin capsules has been reported in 2 small trials. 9,10

PART 12

444

WO MEN’S HEALTH PREVENTIO N • Avoidance o risk actors is recommended, although asymptomatic BV is common. • The evidence is insu cient to assess the impact o screening or BV in pregnant women at high risk or preterm delivery. 1

FO LLO W-UP • Follow-up visits are unnecessary in nonpregnant women i symptoms resolve. 1 • Treatment o BV in asymptomatic pregnant women who are at high risk or preterm delivery might prevent adverse pregnancy outcomes. There ore, a ollow-up evaluation 1 month a ter completion o treatment should be considered to evaluate whether therapy was e ective. 1 SO R

C

• I symptoms do recur, consider a treatment regimen di erent rom the original regimen to treat recurrent disease. 1 SO R C

PATIENT EDUCATIO N Avoid consuming alcohol during treatment with metronidazole and or 24 hours therea ter. Women should be advised to return or additional therapy i symptoms recur because recurrence o BV is not unusual. PATIENT RESO URCES

• Centers for Disease Control and Prevention. Bacterial Vaginosis Fact Sheet—http:/ / www.cdc.gov/ std/ BV/ STDFact-BacterialVaginosis.htm. • MedicineNet.com. Bacterial Vaginosis—http:/ / www .medicinenet.com/ bacterial_vaginosis/ article.htm. PRO VIDER RESO URCES

• Centers for Disease Control and Prevention. 2010 Guidelines for Treatment of Sexually Transmitted Diseases—http:/ / www.cdc .gov/ std/ treatment/ 2010/ STD-Treatment-2010-RR5912 .pdf.

CHApTER 90

REFERENCES 1. Centers or Disease Control and Prevention. Guidelines forTreatment of Sexually Transmitted Diseases. http:/ / www.cdc.gov/ std/ treatment/ 2010/ STD-Treatment-2010-RR5912.pd . Accessed December 24, 2011. 2. Martius J, Krohn MA, Hillier SL, et al. Relationships o vaginal lactobacillus species, cervical chlamydia trachomatis, and bacterial vaginosis to preterm birth. Obstet Gynecol. 1988;71:89-95. 3. Gorgos LM, Marrazzo JM. Sexually transmitted in ections among women who have sex with women. Clin Infect Dis. 2011;53(3): S84-S91. 4. Klebano MA, Nansel TR, Brotman RM, et al. Personal hygienic behaviors and bacterial vaginosis. SexTransm Dis. 2010;37:94. 5. Burtin P, Taddio A, Ariburnu O, et al. Sa ety o metronidazole in pregnancy: a meta-analysis. Am J Obstet Gynecol. 1995;172 (2 Pt 1):525-529. 6. Sobel JD, Ferris D, Schwebke J, et al. Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis. Am J Obstet Gynecol. 2006;194:1283-1289. 7. Reichman O, Akins R, Sobel JD. Boric acid addition to suppressive antimicrobial therapy or recurrent bacterial vaginosis. SexTransm Dis. 2009;36:732-734. 8. Baylson FA, Nyirjesy P, Weitz MV. Treatment o recurrent bacterial vaginosis with tinidazole. Obstet Gynecol. 2004;104 (5 Pt 1):931-932. 9. Anukam KC, Osazuwa E, Osemene GI, et al. Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis. Microbes Infect. 2006;8:2772. 10. Ya W, Rei er C, Miller LE. E cacy o vaginal probiotic capsules or recurrent bacterial vaginosis: a double-blind, randomized, placebocontrolled study. Am J Obstet Gynecol. 2010;203:120.

PART 12

CANDIDA VULVO VAGINITIS

WO MEN’S HEALTH

91 CANDIDA VULVO VAGINITIS E.J. Maye aux Jr, MD Richard P. Usatine , MD

PATIENT STO RY A 35-year-old woman presents with severe vaginal and vulvar itching. She also complains o a thick white discharge. Figure 91-1 demonstrates the appearance o her vulva and introitus and Figure 91-2 shows her cervix. Figure 91-3 shows the wet prep with pseudohyphae. Treatment with a nonprescription intravaginal preparation was success ul.

INTRO DUCTIO N Vulvovaginal candidiasis (VVC) is a common ungal in ection in women o childbearing age. Pruritus is accompanied by a thick, odorless, white vaginal discharge. VVC is not a sexually transmitted disease. On the basis o clinical presentation, microbiology, host actors, and response-to-therapy, VVC can be classif ed as either uncomplicated or complicated. 1 Uncomplicated VVC is characterized by sporadic or in requent symptoms, mildto-moderate symptoms, and the patient is nonimmunocompromised. Complicated VVC is characterized by recurrent (4 or more episodes in 1 year) or severe VVC, non-albicans candidiasis, or the patient has uncontrolled diabetes, debilitation, or immunosuppression. 1

FIGURE 91-2 Cand id a vag initis visib le on the ce rvix. Note the thick, white , ad he re nt, “cottag e -che e se -like ” d ischarg e . (Re p ro d uce d with p e rmission from EJ Maye aux Jr, MD.)

SYNO NYMS Yeast vaginitis, yeast in ection, candidiasis, and moniliasis.

EPIDEMIO LO GY • VVC accounts or approximately one-third o vaginitis cases. 1 • Candida species are part o the lower genital tract ora in 20% to 50% o healthy asymptomatic women. 2 • Around 75% o all women in the United States will experience at least 1 episode o VVC. O these, 40% to 45% will have 2 or more episodes within their li etime. 3 Approximately 10% to 20% o women will have complicated VVC that necessitates diagnostic and therapeutic considerations. • It is a requent iatrogenic complication o antibiotic treatment, secondary to altered vaginal ora (Figure 91-4). • Nearly hal o all women experience multiple episodes, and up to 5% experience recurrent disease. 1

FIGURE 91-1 Cand id a on the vulva and introitus showing whitish p atche s with e rythe ma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Recurrent vulvovaginal candidiasis (RVVC) is def ned as 4 or more episodes o symptomatic VVC in 1 year. It a ects a small percentage o women (< 5%). 4 Recurrent yeast vaginitis is usually caused by relapse, and less o ten by rein ection. Recurrent in ection may be caused by Candida recolonization o the vagina rom the rectum. 5

445

446

PART 12

WO MEN’S HEALTH

Ch a pt e r 91

• The pathogenesis o recurrent VVC is poorly understood, and most women with these recurrences have no apparent predisposing or underlying conditions. 1

RISK FACTO RS8,9 • Diabetes mellitus • Recent antibiotic use (Figure 91-4) • Increased estrogen levels • Immunosuppression (Figure 91-5)

FIGURE 91-3 We t mount with KO H o Cand id a alb icans in a woman with Cand id a vag initis. Se e n und e r hig h p owe r d e monstrating b ranching p se ud ohyp hae and b ud d ing ye ast. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

ETIO LO GY AND PATHO PHYSIO LO GY • Most vulvovaginal Candidiasis is caused by Candida albicans (Figure 91-3). 1,6 Candida glabrata now causes a signif cant percentage o all Candida vulvovaginal in ections. This organism is resistant to the nonprescription imidazole creams. It can mutate out o the activity o treatment drugs much aster than albicans species. 7 • The disease is suggested by pruritus in the vulvar area, together with erythema o the vagina and vulva (Figures 91-1, 91-2, and 91-4). The amiliar reddening o the vulvar tissues is caused by an ethanol byproduct o the Candida in ection. This ethanol compound also produces pruritic symptoms. A scalloped edge with satellite lesions is characteristic o the erythema on the vulva. • VVC can occur concomitantly with sexually transmitted diseases (STDs).

FIGURE 91-4 Re d p ruritic rash in the vulva and ing uinal are as o this 46-year-old woman who su ere d a stroke with signif cant residual hemiparesis. Diag nosis was conf rme d with a KO H microscop ic e xamination. The case was p articularly se ve re se cond ary to he r use o an ad ult d iap e r or incontine nce and a p re ce d ing course o antib iotics. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

A

B FIGURE 91-5 A. Cand id a vulvovag initis in a 52-ye ar-old woman with p e mp hig us vulg aris on p re d nisone and mycop he nolate to control he r immunob ullous d ise ase . B. The p atie nt also has Cand id a thrush in he r mouth se cond ary to he r immunosup p re ssion. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 12

Ca NDIDa VULVO Va GINIt IS

WO MEN’S HEALTH

• Incontinence and adult diapers (Figure 91-4)

not ound to be sensitive enough to rule out yeast and avoid a culture. 6

• Contraceptive devices (vaginal sponges, diaphragms, and intrauterine devices)

SO R

• Genetic susceptibility • Behavioral actors—VVC may be linked to orogenital and, less commonly, anogenital sex • Spermicides are not associated with Candida in ection • There is no high-quality evidence showing a link between VVC and hygienic habits or wearing tight or synthetic clothing

DIAGNO SIS CLINICAL FEATURES The diagnosis is usually suspected by characteristic f ndings (Figures 91-1, 91-2, and 91-4). Typical symptoms include pruritus, vaginal soreness, dyspareunia, and external dysuria. Typical signs include vulvar edema, f ssures, excoriations, or thick, curdy vaginal discharge. 1 LABO RATO RY TESTING • Vaginitis solely caused by Candida generally has a normal vaginal pH o less than 4.5. • The wet prep, KOH smear, or Gram stain may demonstrate yeast and/ or pseudohyphae (Figures 91-3 and 91-6). Wet preps may also demonstrate white blood cells, trichomonads, candidal hyphae, or clue cells. • The KOH prep is made by adding a drop o KOH solution to a drop o saline suspension o the discharge. The KOH lyses epithelial cells in 5 to 15 minutes ( aster i the slide is warmed) and allows easier visualization o candidal hyphae or yeast. 1 Swartz-Lamkins stain (potassium hydroxide, a sur actant, and blue dye) may acilitate diagnosis by staining the yeast organisms a light blue. 10 • Rapid antigen testing is also available or Candida. The detection o vaginal yeast by rapid antigen testing is easible or o f ce practice and more sensitive than wet mount. A negative test result, however, was

A

• Fungal culture with Sabouraud agar, Nickerson medium, or MicrostixCandida medium should be considered in patients with symptoms and a negative KOH because C. glabrata does not orm pseudohyphae or hyphae and is not easily recognized on microscopy. I the wet mount is negative and Candida cultures cannot be done, empiric treatment can be considered or symptomatic women with any sign o VVC on examination. 1 SO R C Asymptomatic women should not be cultured as 10% to 20% o women harbor Candida species and other yeasts in the vagina. 1 SO R A • Vaginal cultures should be obtained rom patients with RVVC to conf rm the clinical diagnosis and to identi y unusual species, including non-albicans species, particularly C. glabrata (C. glabrata does not orm pseudohyphae or hyphae and is not easily recognized on microscopy). 1 SO R B C. glabrata and other non-albicans Candida sp. are observed in 10% to 20% o patients with RVVC. 1 • Given the requency at which RVVC occurs in the immunocompetent healthy population, the occurrence o RVVC alone should not be considered an indication or HIV testing. 1 SO R C

DIFFERENTIAL DIAGNO SIS • Trichomoniasis can be con used with candidiasis because patients may report itching and a discharge in both diagnoses. Look or the strawberry cervix on examination and moving trichomonads on the wet prep (Chapter 92, Trichomonas Vaginitis). • Bacterial vaginosis can be con used with candidiasis because patients may report a discharge and an odor in both diagnoses. The odor is usually much worse in bacterial vaginosis, and the quality o the discharge can be di erent. The wet prep should allow or di erentiation between these 2 in ections (Chapter 90, Bacterial Vaginosis). • Gonorrhea and Chlamydia should not be missed in patients with vaginal discharge. Consider testing or these STDs based on patients’ risk actors and the presence o purulence clinically and white blood cells on the wet prep (Chapter 93, Chlamydia Cervicitis). • Cytolytic vaginosis, or Döderlein cytolysis, can be con used with candidiasis. Cytolytic vaginosis is produced by a massive desquamation o epithelial cells related to excess lactobacilli in the vagina. The signs and symptoms are similar to Candida vaginitis, except no yeast are ound on wet prep. The wet prep will show an overgrowth o lactobacilli. The treatment is to discontinue all anti ungals and other agents or procedures that alter the vaginal ora.

MANAGEMENT NO NPHARMACO LO GIC • VVC is not usually acquired through sexual intercourse; treatment o sex partners is not recommended but may be considered in women who have recurrent in ection. Some male sex partners might have balanitis (Chapter 135, Candidiasis) and might benef t rom treatment. 1 SO R

FIGURE 91-6 We t mount with saline showing Cand id a in a woman with Cand id a vag initis. Note how the b ranching p se ud ohyp hae and b ud d ing ye ast can b e se e n e ve n thoug h the e p ithe lial ce lls have not b e e n lyse d b y KO H. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

A

• Any woman whose symptoms persist a ter using a nonprescription preparation or who has a recurrence o symptoms within 2 months should be evaluated with o f ce-based testing as they are not necessarily

447

PART 12

448

WO MEN’S HEALTH more capable o diagnosing themselves even with prior diagnosed episodes o VVC, and delay in the treatment o other vulvovaginitis etiologies can result in adverse clinical outcomes. 1 SO R A MEDICATIO NS • Women with typical symptoms and a positive test result should receive treatment. Short-courses o topical ormulations e ectively treat uncomplicated VVC (Table 91-1). 1 SO R A Topical azole drugs are more e ective than nystatin, and result in clinical cure and negative cultures in 80% to 90% o patients who complete therapy. SO R A The creams and suppositories in Table 91-1 are oil-based and might weaken latex condoms and diaphragms.1 • The cure rates with single-dose oral uconazole and all the intravaginal treatments are equal. 11 Fluconazole (Di ucan) 150-mg single dose has become very popular, but may have clinical cure rates o approximately only 70%. SO R A Systemic allergic reactions are possible with the oral agents. • The oral agents uconazole, ketoconazole, and itraconazole also appear to be e ective. 1 SO R B • VVC requently occurs during pregnancy. Only topical azole therapies, applied or 7 days, are recommended or use among pregnant women. 1 SO R

C

• The optimal treatment o non-albicans VVC remains unknown. Options include longer duration o therapy (7-14 days) with topical therapy or a 100-mg, 150-mg, or 200-mg oral dose o uconazole every third day or a total o 3 doses. 1 SO R C

TABLE 91-1 Ce nte rs or Dise ase Control and Pre ve ntion Re comme nd e d Tre atme nt Re g ime ns

Intravag inal Ag e nts: Butoconazole 2% cre am 5 g intravag inally or 3 d ays Butoconazole 2% cre am 5 g (Butaconazole 1-sustaine d re le ase ), sing le intravag inal ap p lication * Clotrimazole 1% cre am 5 g intravag inally or 7-14 d ays Clotrimazole 2% cre am 5 g intravag inally or 3 d ays Clotrimazole 100 mg vag inal sup p ositorie s, one intravag inally or 3 d ays Miconazole 2% cre am 5 g intravag inally or 7 d ays Miconazole 100 mg vag inal sup p ositorie s, 1 sup p ository or 7 d ays Miconazole 200 mg vag inal sup p ositorie s, 1 sup p ository or 3 d ays Miconazole 1200 mg vag inal suppositories, 1 sup pository or 1 d ay Nystatin 100,000-U vag inal tab le t, 1 tab le t or 14 d ays * Tioconazole 6.5% ointme nt 5 g intravag inally in a sing le ap p lication Te rconazole 0.4% cre am 5 g intravag inally or 7 d ays * Te rconazole 0.8% cre am 5 g intravag inally or 3 d ays * Te rconazole 80 mg vag inal sup p ositorie s, 1 sup p ository or 3 d ays * O ral Ag e nt: Fluconazole 150-mg oral tab le t, 1 tab le t in sing le d ose * *

Pre scrip tion only in the Unite d State s. Data rom the Ce nte rs or Dise ase Control and Pre ve ntion.1

Ch a pt e r 91

• Severe VVC (ie, extensive vulvar erythema, edema, excoriation, and f ssure ormation) is associated with lower clinical response rates in patients treated with short courses o topical or oral therapy. Either 7 to 14 days o topical azole or 150 mg o uconazole in 2 sequential doses (second dose 72 hours a ter initial dose) is recommended. 1 SO R

C

CO MPLEMENTARY AND ALTERNATIVE THERAPY • I recurrence VVC occurs, 600 mg o boric acid in a gelatin capsule is recommended, administered vaginally once daily or 2 weeks. This regimen has clinical and mycologic eradication rates o approximately 70%. 1 SO R B • Lactobacillus acidophilus does not adhere well to the vaginal epithelium, and it does not signif cantly change the incidence o candidal vulvovaginitis.5,12 • There is no evidence rom randomized trials that other complementary and alternative medicine (CAM) therapies, such as garlic, tea tree oil, yogurt, or douching, are e ective or the treatment or prevention o VVC caused by C. albicans. 13,14

PREVENTIO N MAINTENANCE REGIMENS • Oral uconazole (ie, 100-mg, 150-mg, or 200-mg dose) weekly or 6 months is the f rst line o treatment. I this regimen is not easible, some specialists recommend topical clotrimazole 200 mg twice a week, clotrimazole (500-mg dose vaginal suppositories once weekly), or other topical treatments used intermittently. 1 SO R C • Suppressive maintenance anti ungal therapies are e ective in reducing RVVC. 1 SO R A However, 30% to 50% o women will have recurrent disease a ter maintenance therapy is discontinued. Routine treatment o sex partners is controversial. C. albicans azole resistance is rare in vaginal isolates, and susceptibility testing is usually not warranted or individual treatment guidance.

PRO GNO SIS • Women with underlying debilitating medical conditions (eg, those with uncontrolled diabetes or those receiving corticosteroid treatments) do not respond as well to short-term therapies. E orts to correct modif able conditions should be made, and more prolonged (ie, 7-14 days) conventional antimycotic treatment is necessary. 1 SO R C • Symptomatic VVC is more requent in HIV-seropositive women and correlates with severity o immunodef ciency. In addition, among HIVin ected women, systemic azole exposure is associated with the isolation o non–C. albicans species rom the vagina. According to the available data, therapy or VVC in HIV-in ected women should not di er rom that or seronegative women. 1 SO R C

FO LLO W-UP Patients should be instructed to return or ollow-up visits only i symptoms persist or recur within 2 months o onset o initial symptoms. 1

PART 12

Ca NDIDa VULVO Va GINIt IS

PATIENT EDUCATIO N Studies show that women who were previously diagnosed with VVC are not necessarily more likely to be able to diagnose themselves. 1 Any woman whose symptoms persist a ter using a nonprescription preparation, or who has a recurrence o symptoms within 2 months, should be evaluated with o f ce-based testing. Explain that unnecessary or inappropriate use o nonprescription preparations can lead to a delay in the treatment o other vulvovaginitis etiologies, which can result in adverse clinical outcomes. 1 PATIENT RESO URCES

• FamilyDoctor.org from AAFP. Yeast Infections—http:/ / familydoctor.org/ online/ famdocen/ home/ women/ reproductive/ vaginal/ 206.htm. • MedicineNet. Vaginal Yeast Infection (Yeast Vaginitis)—http:/ / www.medicinenet.com/ yeast_vaginitis/ article.htm. • WebMD. Vaginal Yeast Infections—http:/ / women.webmd .com/ tc/ vaginal-yeast-infections-topic-overview. • Womenshealth.gov. Vaginal Yeast Infections Fact Sheet— http:/ / www.womenshealth.gov/ publications/ our-publications/ fact-sheet/ vaginal-yeast-infections.cfm. • MedLinePlus. Yeast Infections—http:/ / www.nlm.nih.gov/ medlineplus/ yeastinfections.html. • eMedicine Health. Candidiasis—http:/ / www.emedicinehealth .com/ candidiasis_yeast_infection/ article_em.htm. PRO VIDER RESO URCES

• Centers for Disease Control and Prevention. 2010 Guidelines for Treatment of Sexually Transmitted Diseases—http:/ / www.cdc .gov/ std/ treatment/ 2010/ STD-Treatment-2010-RR5912 .pdf. • American Family Physician. Management of vaginitis. Am Fam Physician. 2004;70:2125-2132.—http:/ / www.aafp.org/ afp/ 20041201/ 2125.html. • eMedicine. Candidiasis—http:/ / emedicine.medscape.com/ article/ 213853-overview. • eMedicine. Vulvovaginitis in Emergency Medicine—http:/ / emedicine.medscape.com/ article/ 797497-overview.

WO MEN’S HEALTH REFERENCES 1. Centers or Disease Control and Prevention. 2010 Guidelines for Treatment of SexuallyTransmitted Diseases. http:/ / www.cdc.gov/ std/ treatment/ 2010/ STD-Treatment-2010-RR5912.pd . Accessed November 2, 2011. 2. Goldacre MJ, Watt B, Loudon N, et al. Vaginal microbial ora in normal young women. Br Med J. 1979;1:1450. 3. Hurley R, De Louvois J. Candida vaginitis. Postgrad Med J. 1979;55:645. 4. Sobel JD. Epidemiology and pathogenesis o recurrent vulvovaginal candidiasis. Am J Obstet Gynecol. 1985;152:924. 5. Shalev E, Battino S, Weiner E, et al. Ingestion o yogurt containing acidophilus compared with pasteurized yogurt as prophylaxis or recurrent candidal vaginitis and bacterial vaginosis. Arch Fam Med. 1996;5:593-596. 6. Cohen DA, Nsuami M, Etame RB, et al. A school-based chlamydia control program using DNA amplif cation technology. Pediatrics. 1998;(1):101. 7. Horowitz BJ, Giaquinta D, Ito S. Evolving pathogens in vulvovaginal candidiasis: implications or patient care. J Clin Pharmacol. 1992;32:248. 8. Foxman B. The epidemiology o vulvovaginal candidiasis: risk actors. Am J Public Health. 1990;80:329. 9. Sobel JD. Candida vaginitis. Infect Dis Clin Pract (Baltim Md). 1994;3:334. 10. Swartz JH, Lamkins BE. A rapid, simple stain or ungi in skin, nail scrapings, and hair. Arch Dermatol. 1964 Jan;89:89-94. 11. Sobel JD, Brooker D, Stein GE, et al. Single oral dose uconazole compared with conventional clotrimazole topical therapy o candida vaginitis. Am J Obstet Gynecol. 1995;172:1263-1238. 12. Pirotta M, Gunn J, Chondros P, et al. E ect o lactobacillus in preventing post-antibiotic vulvovaginal candidiasis: a randomised controlled trial. BMJ. 2004;329:548. 13. Van Kessel K, Assef N, Marrazzo J, Eckert L. Common complementary and alternative therapies or yeast vaginitis and bacterial vaginosis: a systematic review. Obstet Gynecol Surv. 2003;58(5):351-358. 14. Boskey ER. Alternative therapies or bacterial vaginosis: a literature review and acceptability survey. AlternTher Health Med. 2005;11(5): 38-43.

449

PART 12

450

WO MEN’S HEALTH

Ch a pt e r 92

92 TRICHO MO NAS VAGINITIS E.J. Maye aux Jr, MD Richard P. Usatine , MD

PATIENT STO RY A 27-year-old woman presents with a vaginal itching, odor, and discharge for 1 week. She has one partner who is asymptomatic. Speculum examination shows a strawberry cervix seen with Trichomonas infections (Figure 92-1). This strawberry pattern is caused by in ammation and punctate hemorrhages on the cervix. There is a scant white discharge with a shy odor. Wet mount shows trichomonads swimming in saline (Figures 92-2 and 92-3). The trichomonads are larger than white blood cells (WBCs) and have visible agella and movement. She is diagnosed with trichomoniasis and treated with 2 g of metronidazole in a single dose. The patient is tested for other sexually transmitted diseases (STDs), and her partner is treated with the same regimen.

INTRO DUCTIO N Trichomonas vaginitis is a local infection caused by the protozoan Trichomonas vaginalis that is associated with vaginal discharge. The woman often has an itch and an odor along with the discharge but may be asymptomatic.

SYNO NYMS Trichomoniasis, trich, tricky monkeys.

FIGURE 92-2 We t mount showing Trichomonas in saline und e r low p owe r. The re are 2 visib le trichomonad s to the rig ht and ab ove the tip o the p ointe r. The larg e st ce lls are vag inal e p ithe lial ce lls with visib le nucle i. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

EPIDEMIO LO GY • An estimated 3 to 5 million cases of trichomoniasis occur each year in the United States. 1 • The worldwide prevalence of trichomoniasis is estimated to be 180 million cases per year; and these cases account for 10% to 25% of all vaginal infections. 2

ETIO LO GY AND PATHO PHYSIO LO GY • Trichomonas infection is caused by the unicellular protozoan T. vaginalis. 3 • The majority of men (90%) infected with T. vaginalis are asymptomatic, but many women (50%) report symptoms. 4

FIGURE 92-1 Sp e culum e xamination showing the strawb e rry ce rvix p atte rn se e n with Trichomonas in e ctions. This strawb e rry p atte rn is cause d b y inf ammation and p unctate he morrhag e s on the ce rvix. The re is a scant white d ischarg e . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 92-3 We t mount showing Trichomonas (arrows) in saline und e r hig h p owe r. The smalle r mo re g ranular ce lls are white b lood ce lls. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

t r ICh O MO Na S Va GINIt IS

PART 12

WO MEN’S HEALTH

• The infection is predominantly transmitted via sexual contact. The organism can survive up to 48 hours at 10°C (50°F) outside the body, making transmission from shared undergarments or from infected hot spas possible although extremely unlikely. • Trichomonas infection is associated with low-birth-weight infants, premature rupture of membranes, and preterm delivery in pregnant patients. 5 • In a person coinfected with HIV, the pathology induced by T. vaginalis infection can increase HIV shedding. Trichomonas infection may also act to expand the portal of entry for HIV in an HIV-negative person. Studies from Africa have suggested that T. vaginalis infection may increase the rate of HIV transmission by approximately 2 fold. 6

RISK FACTO RS3 • New or multiple partners • A history of STDs • Exchanging sex for payment or drugs • Injection drug use

DIAGNO SIS CLINICAL FEATURES • The physical examination should include inspection of the external genitalia for irritation or discharge. Speculum examination is done to determine the amount and character of the discharge and to look for the characteristic strawberry cervix (Figures 92-1 and 92-4). • Typically, women with trichomoniasis have a diffuse, malodorous, yellow-green or white discharge (Figure 92-5) with vulvar irritation (Figure 92-6). 3 Vaginal and vulvar itching and irritation are common. 3

FIGURE 92-4 Close -up o strawb e rry ce rvix in a Trichomonas in e ction d e monstrating inf ammation and p unctate he morrhag e s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 92-5 Sp e culum e xamination d e monstrating the thick ye llow-g re e n d ischarg e that may b e se e n in Trichomonas in e ction. The d ischarg e can also b e rothy white . (Re p rod uce d with p e rmissio n from E.J. Maye aux Jr, MD.)

• It should be determined whether the patient douched recently, because this can lower the yield of diagnostic tests. Patients who have been told not to douche will sometimes start wiping the vagina with soapy washcloths to “keep clean” as an alternative. This greatly irritates the vagina and cervix, lowers test sensitivity, and may cause a discharge.

FIGURE 92-6 Trichomonas in e ction in a 28-ye ar-old woman showing cop ious white d ischarg e and vulvar irritation. The woman had worke d as an “e scort” and ortunate ly he r othe r te sts or se xually transmitte d in e ctions we re ne g ative . (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

451

452

PART 12

WO MEN’S HEALTH TYPICAL DISTRIBUTIO N In women, T. vaginalis may be found in the vagina, urethra, and paraurethral glands of infected women. Other sites include the cervix and Bartholin and Skene glands. LABO RATO RY TESTING • Because of the high prevalence of trichomoniasis, testing should be performed in women seeking care for vaginal discharge. Screening should be considered for women with risk factors. 3 • Wet preps are obtained using a cotton-tipped applicator applied to the vaginal side-wall, placing the sample of discharge into normal saline (not water). A drop of the suspension is then placed on a slide, covered with a coverslip, and carefully examined with the low-power and highdry objective lenses. Under the microscope, observe for motile trichomonads, which are often easy to visualize because of their lashing agella (Figure 92-2). • Wet prep has a sensitivity of only approximately 60% to 70% and requires immediate evaluation of wet preparation slide for optimal results. 3 • The OSOM Trichomonas Rapid Test and the Af rm VP III are FDA cleared for trichomoniasis in women. Both tests are performed on vaginal secretions at the point of care and have a sensitivity greater than 83% and a speci city greater than 97%. The results of the OSOM Trichomonas Rapid Test are available in approximately 10 minutes, and results of the Af rm VP III are available within 45 minutes. False-positive tests might occur, especially in populations with a low prevalence of disease. 3 • An FDA-approved polymerase chain reaction (PCR) assay for detection of gonorrhea and chlamydial infection (Amplicor, manufactured by Roche Diagnostic Corp.) has been modi ed to test for T. vaginalis in vaginal or endocervical swabs and in urine from women and men, with sensitivity ranges from 88% to 97% and speci city from 98% to 99%. 7 • APTIMA T. vaginalis Analyte Speci c Reagents (ASR; manufactured by Gen-Probe, Inc.) also can detect T. vaginalis RNA using the same instrumentation platforms available for the FDA-cleared APTIMA Combo 2 assay for diagnosis of gonorrhea and chlamydial infection. Published validation studies found sensitivity ranging from 74% to 98% and speci city from 87% to 98%. 8 • A vaginal pH above 4.5 is seen with menopausal patients, Trichomonas infection, or bacterial vaginosis. 4 • Culture is a sensitive and highly speci c method of diagnosis. In women in whom trichomoniasis is suspected but not con rmed by microscopy, vaginal secretions should be cultured for T. vaginalis. 3 • A nucleic acid ampli cation test for Neisseria gonorrhoeae, and/ or Chlamydia trachomatis should be performed on all patients with Trichomonas.

DIFFERENTIAL DIAGNO SIS • Bacterial vaginosis and Trichomonas may have the odor of aromatic amines, and therefore may easily be confused with each other. Look for clue cells and trichomonads on the wet prep to differentiate between the 2 (Chapter 90, Bacterial Vaginosis). • Candida vaginitis tends to present with a cottage-cheese-like discharge and vaginal itching (Chapter 91, Candida Vaginitis). • Gonorrhea and Chlamydia should not be missed in patients with vaginal discharge. Consider testing for these STDs based on patients’ risk

Ch a pt e r 92

factors and the presence of purulence clinically and WBCs on the wet prep (Chapter 93, Chlamydia Cervicitis).

MANAGEMENT MEDICATIO NS • Table 92-1 shows treatments for T. vaginalis infections. Metronidazole 2 g orally as a single dose, or 500 mg bid for 7 days (including pregnant patients) are the best treatments by Cochrane analysis. 9 SO R A • Tinidazole (Tindamax), a second-generation nitroimidazole, is indicated as a 1-time dose of 2 g for the treatment of trichomoniasis (including metronidazole-resistant trichomoniasis). 3 SO R A It is effective therapy in nonresistant and resistant T. vaginalis. 10,11 The contraindications (including ethyl alcohol [ETOH]) to the use of tinidazole are similar to those for metronidazole. • Pregnant women may be treated with 2 g of metronidazole in a single dose. Metronidazole is pregnancy category B. Vaginal trichomoniasis is associated with adverse pregnancy outcomes, particularly premature rupture of membranes, preterm delivery, and low birth weight. Unfortunately, data do not suggest that metronidazole treatment results in a reduction in perinatal morbidity and treatment may even increase prematurity or low birth weight. 3 Treatment of T. vaginalis might relieve symptoms of vaginal discharge in pregnant women and might prevent respiratory or genital infection of the newborn and further sexual transmission. The Centers for Disease Control and Prevention (CDC) recommends that clinicians counsel patients regarding the potential risks and bene ts of treatment during pregnancy. 3 • Some strains of T. vaginalis can have diminished susceptibility to metronidazole. Low-level metronidazole resistance has been identi ed in 2% to 5% of cases of vaginal trichomoniasis. These infections should respond to tinidazole or higher doses or longer durations of metronidazole. High-level resistance is rare. • Metronidazole gel is 50% less ef cacious for the treatment of trichomoniasis than oral preparations and is not recommended. 3

PREVENTIO N • Patients should be instructed to avoid sex until they and their sex partners are cured (ie, when therapy has been completed and patient and partner[s] are asymptomatic). 3 • Spermicidal agents such as nonoxynol-9 reduce the rate of transmission of Trichomonas. 12 • The risk of acquiring infection can be reduced by consistent use of condoms and limiting the number of sexual partners. TABLE 92-1 Ce nte rs or Dise ase Control and Pre ve ntion Re comme nd e d Re g ime ns or Pre g nant and Nonp re g nant Patie nts. SO R

A

Me tronid azole 2 g orally in a sing le d ose OR Tinid azole 2 g orally in a sing le d ose CDC Alte rnative Re g ime n

SO R

A

Me tronid azole 500 mg orally twice a d ay or 7 d ays Data rom Ce nte rs or Dise ase Control and Pre ve ntion.2,3

t r ICh O MO Na S Va GINIt IS

FO LLO W-UP Because of the high rate of reinfection among patients in whom trichomoniasis was diagnosed, rescreening at 3 months following initial infection can be considered for sexually active women. 3

PATIENT EDUCATIO N Sexual partners of patients with Trichomonas should be treated. Patients can be sent home with a dose for a partner when it is believed that the partner will not come in on his own. PATIENT RESO URCES

• Centers for Disease Control and Prevention information— http:/ / www.dpd.cdc.gov/ dpdx/ HTML/ Trichomoniasis .htm.

PART 12

WO MEN’S HEALTH 3. Centers for Disease Control and Prevention. 2010 Guidelines forTreatment of SexuallyTransmitted Diseases. http:/ / www.cdc.gov/ std/ treatment/ 2010/ STD-Treatment-2010-RR5912.pdf. Accessed 1 December, 2011. 4. Gjerdngen D, Fontaine P, Bixby M, et al. The impact of regular vaginal pH screening on the diagnosis of bacterial vaginosis in pregnancy. J Fam Pract. 2000;49:3-43. 5. Cotch MF, Pastorek JG 2nd, Nugent RP, et al. Trichomonas vaginalis associated with low birth weight and preterm delivery: the Vaginal Infections and Prematurity Study Group. SexTransm Dis. 1997;24:353-360. 6. Sorvillo F, Smith L, Kerndt P, Ash L. Trichomonas vaginalis, HIV, and African-Americans. Emerg Infect Dis. 2001;7(6):927-932. 7. Van Der PB, Kraft CS, Williams JA. Use of an adaptation of a commercially available PCR assay aimed at diagnosis of chlamydia and gonorrhea to detect Trichomonas vaginalis in urogenital specimens. J Clin Microbiol. 2006;44:366-373.

• Centers for Disease Control and Prevention. STDs:Trichomoniasis— http:/ / www.cdc.gov/ std/ trichomonas/ default.htm.

8. Nye MB, Schwebke JR, Body BA. Comparison of APTIMA Trichomonas vaginalis transcription-mediated ampli cation to wet mount microscopy, culture, and polymerase chain reaction for diagnosis of trichomoniasis in men and women. Am J Obstet Gynecol. 2009;200: 188-197.

• PubMed Health. Trichomoniasis—http:/ / www.ncbi.nlm.nih .gov/ pubmedhealth/ PMH0002307/ .

9. Epling J. What is the best way to treat trichomoniasis in women? Am Fam Physician. 2001;64:1241-1244.

• MedlinePlus. Trichomoniasis—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 001331.htm.

• MedLinePlus. Trichomoniasis—http:/ / www.nlm.nih.gov/ medlineplus/ trichomoniasis.html. • eMedicine Health. Trichomoniasis—http:/ / www.emedicinehealth .com/ trichomoniasis/ article_em.htm. PRO VIDER RESO URCES

• Medscape. Trichomoniasis—http:/ / emedicine.medscape .com/ article/ 230617. • eMedicine. Trichomoniasis—http:/ / emedicine.medscape .com/ article/ 787722. • Centers for Disease Control and Prevention. 2010 Guidelines for Treatment of Sexually Transmitted Diseases—http:/ / www.cdc.gov/ std/ treatment/ 2010/ STD-Treatment-2010-RR5912.pdf. REFERENCES 1. Sutton M, Sternberg M, Koumans EH, et al. The prevalence of Trichomonas vaginalis infection among reproductive-age women in the United States, 2001-2004. Clin Infect Dis. 2007;45:1319. 2. Weinstock H, Berman S, Cates W Jr. Sexually transmitted diseases among American youth: incidence and prevalence estimates, 2000. Perspect Sex Reprod Health. 2004;36(1):6-10.

10. Mammen-Tobin A, Wilson JD. Management of metronidazoleresistant Trichomonas vaginalis—a new approach. Int J STD AIDS. 2005;16(7):488-490. 11. Hager WD. Treatment of metronidazole-resistant Trichomonas vaginalis with tinidazole: case reports of three patients. SexTransm Dis. 2004;31(6):343-345. 12. d’Oro LC, Parazzini F, Naldi L, La Vecchia C. Barrier methods of contraception, spermicides, and sexually transmitted diseases: a review. Genitourin Med. 1994;70:410.

453

454

PART 12

WO MEN’S HEALTH

93 CHLAMYDIA CERVICITIS E.J. Maye aux Jr, MD Richard P. Usatine , MD

PATIENT STO RY A young woman presents to her primary care physician with a vaginal discharge. On physical examination, there is cervical ectopy, in ammation, and some mucoid discharge (Figure 93-1). The cervix bled easily while obtaining discharge and cells for a wet mount and genetic probe test. The wet mount showed many white blood cells (WBCs) but no visible pathogens. She was sent to the laboratory for rapid plasma reagin (RPR) and HIV tests and given a follow-up appointment in 1 week. The genetic probe test was positive for Chlamydia and all the other examinations were negative. The patient was treated with 1 g of azithromycin taken in front of a clinic nurse. She was also counseled to discuss the result with her male partners and the importance of safe sex was emphasized.

INTRO DUCTIO N Chlamydia trachomatis causes genital infections that can result in pelvic in ammatory disease (PID), ectopic pregnancy, and infertility. Asymptomatic infection is common among both men and women so health care providers must rely on screening tests to detect disease. The Centers for Disease Control and Prevention (CDC) recommends annual screening of all sexually active women ages 25 years and younger, and of older women with risk factors, such as having a new sex partner or multiple sex partners. 1

Ch a pt e r 93

EPIDEMIO LO GY • A very common STD, Chlamydia is the most frequently reported infectious disease in the United States (excluding human papillomavirus [HPV]). 1 An estimated 1.2 million cases are reported to the CDC annually in the United States. 2 • The World Health Organization (WHO) estimates there are 140 million cases of Chlamydia trachomatis infection worldwide every year. 3 • The CDC estimates screening and treatment programs can be conducted at an annual cost of $175 million. Every dollar spent on screening and treatment saves $12 in complications that result from untreated Chlamydia. 4 • It is common among sexually active adolescents and young adults. 5 As many as 1 in 10 adolescent girls tested for Chlamydia is infected. Based on reports to the CDC provided by states that collect age-speci c data, teenage girls have the highest rates of chlamydial infection. In these states, 15- to 19-year-old girls represent 46% of infections and 20- to 24-year-old women represent another 33%. 4

ETIO LO GY AND PATHO PHYSIO LO GY • C. trachomatis is a small gram-negative bacterium with unique biologic properties among living organisms. Chlamydia is an obligate intracellular parasite that has a distinct life-cycle consisting of 2 major phases: The small elementary bodies attach and penetrate into cells, and the metabolically active reticulate bodies that form large inclusions within cells. • It has a long growth cycle, which explains why extended courses of treatment are often necessary. Immunity to infection is not long lived, so reinfection or persistent infection is common. • The infection may be asymptomatic and the onset often indolent. It can cause cervicitis, endometritis, PID, urethritis, epididymitis, neonatal conjunctivitis, and pediatric pneumonia. Of exposed babies, 50% develop conjunctivitis and 10% to 16% develop pneumonia. 1 • Chlamydia infections may lead to reactive arthritis, which presents with arthritis, conjunctivitis, and urethritis (Chapter 155, Reactive Arthritis). Past or ongoing C. trachomatis infection may be a risk factor for ovarian cancer. 6,7 • Up to 40% of women with untreated Chlamydia will develop PID. Undiagnosed PID caused by Chlamydia is common. Of those with PID, 20% will become infertile; 18% will experience debilitating, chronic pelvic pain; and 9% will have a life-threatening tubal pregnancy. Tubal pregnancy is the leading cause of rst-trimester, pregnancy-related deaths in American women. 4

RISK FACTO RS1,2,8 • Adolescents and young adults • Nonwhite populations • Multiple sexual partners • Poor socioeconomic conditions • Single marital status FIGURE 93-1 Chlamyd ia ce rvicitis in a p atie nt with a vag inal d ischarg e . A NAAT te st was p ositive or Chlamyd ia. The re st o he r work-up was ne g ative . (Re p rod uce d with p e rmissio n rom E.J. Maye aux Jr, M.D.)

• Nonbarrier contraceptive use • History of prior STD

Ch La MYDIa Ce r VICIt IS

PART 12

WO MEN’S HEALTH

FIGURE 93-4 Mucop urule nt d ischarg e on the le t swab rom a ce rvix in e cte d with Chlamyd ia (p ositive swab te st). (Re p rod uce d with p e rmission rom Connie Ce lum and Walte r Stamm, Se attle STD/HIV Pre ve ntion Training Ce nte r, Unive rsity o Washing ton.)

FIGURE 93-2 Chlamyd ial ce rvicitis with e ctop y, mucoid d ischarg e , and b le e d ing . The ce rvix is in ame d and riab le . (Re p rod uce d with p e rmission ro m Co nnie Ce lum and Walte r Stamm, Se attle STD/ HIV Pre ve ntio n Training Ce nte r, Unive rsity o Washing ton.)

DIAGNO SIS

• Swab test—A white cotton-tip applicator is placed in the endocervical canal and removed to view. A visible mucopurulent discharge constitutes a positive swab test for Chlamydia (Figure 93-4). This is not speci c for Chlamydia as other genital infections can cause a mucopurulent discharge, and it is not recommended for diagnosis. LABO RATO RY TESTING

CLINICAL FEATURES • The cervix is in amed, friable, and may bleed easily with manipulation. The cervix may show ectopy (columnar cells on the ectocervix). The discharge is usually mucoid or mucopurulent (Figure 93-2). • In many cases, the infected cervix may appear normal or mildly friable (Figure 93-3).

• A signi cant proportion of patients with Chlamydia are asymptomatic, providing a reservoir for infection. All pregnant women and sexually active women younger than 25 years of age should be screened with routine examinations. A wet prep is usually negative for other organisms. Only WBCs and normal ora are seen. • Chlamydia cannot be cultured on arti cial media because it is an obligate intracellular organism. Tissue culture is required to grow the live organism. When testing for Chlamydia, a wood-handled swab must not be used, as substances in wood may inhibit Chlamydia organism. Culture has sensitivity of 70% to 100% and a speci city of almost 100%, which makes it the gold standard. 1 • The enzyme-linked immunosorbent assay (ELISA) technique (Chlamydiazyme) has a sensitivity of 70% to 100% and a speci city of 97% to 99%. 5 Fluorescein-conjugated monoclonal antibodies test (MicroTrak) has a sensitivity of 70% to 100% and a speci city of 97% to 99%. 5 • C. trachomatis can be detected using nucleic acid ampli cation techniques (NAATs) on swabs or voided urine specimens. These tests are often used for testing to detect gonorrhea and Chlamydia. Nucleic acid ampli cation tests have been used successfully in dif cult-to-reach adolescents (“street kids”) as well as in pediatric emergency departments and school-based settings. 9,10 Screening in school-based settings was associated with signi cant reduction in Chlamydia rates during a 1-year period. Self-collected vaginal swab specimens perform at least as well as with other approved specimens using NAATs. 11

FIGURE 93-3 A normal ap p e aring ce rvix with minimal d ischarg e in a p atie nt ound to have g onorrhe a and chlamyd ia throug h lab te sting at the time o he r Pap te st. She was e nrolle d in a re sid e ntial d rug re hab ilitation p rog ram and had a history o unp rote cte d se x with multip le p artne rs. Hig h risk p atie nts should b e te ste d or chlamyd ia and g onorrhe a re g ard le ss o the f nd ing s on p hysical e xam. (Re p ro d uce d with p e rmission ro m Richard P. Usatine , MD.)

• Rectal and oropharyngeal C. trachomatis infection in persons engaging in anal or oral intercourse can be diagnosed by testing at the site of exposure. Although not FDA cleared for this use, NAATs have demonstrated improved sensitivity and speci city compared with culture for the detection at rectal sites12 and at oropharyngeal sites in men. 13

455

PART 12

456

Ch a pt e r 93

WO MEN’S HEALTH • Certain NAATs have been FDA-cleared for use on liquid-based cytology specimens, although test sensitivity using these specimens might be lower. 14 • Persons who undergo testing for Chlamydia should be tested for other STDs as well. 1

TABLE 93-1 Ce nte rs or Dise ase Control and Pre ve ntion Re comme nd e d Re g ime ns SO R

A

Azithromycin 1 g orally in a sing le d ose OR Doxycycline 100 mg orally twice a d ay or 7 d ays CDC Alte rnative Re g ime ns

DIFFERENTIAL DIAGNO SIS • Gonorrhea frequently coexists with Chlamydia and should be tested for when a patient is thought to have Chlamydia. The discharge of gonorrhea may be more purulent but this is not always the case (Chapter 213, Gonococcal Urethritis)

Erythromycin b ase 500 mg orally 4 time s a d ay or 7 d ays OR Erythromycin e thylsuccinate 800 mg orally 4 time s a d ay or 7 d ays

• Bacterial vaginosis—The aromatic amine odor and clue cells help to distinguish between these infections (Chapter 90, Bacterial Vaginosis). • Trichomoniasis—Look for the strawberry cervix and Trichomonas on the wet prep. There may also be a positive whiff test (see Chapter 92, Trichomonas Vaginitis).

OR O f oxacin 300 mg orally twice a d ay or 7 d ays OR Le vof oxacin 500 mg orally once d aily or 7 d ays CDC Re comme nd e d Re g ime ns in Pre g nancy

MANAGEMENT

Azithromycin 1 g orally in a sing le d ose OR

NO NPHARMACO LO GIC Patients diagnosed with Chlamydia cervicitis should be tested for other STDs. 1

Amoxicillin 500 mg orally 3 time s a d ay or 7 d ays

MEDICATIO NS

Erythromycin b ase 500 mg orally 4 time s a d ay or 7 d ays

• Table 93-1 shows CDC-recommended treatments for Chlamydia. Azithromycin (Zithromax) 1000 mg 1-time dose is easy and may be directly observed in the clinic. 1 SO R A It is the rst-line therapy for Chlamydia during pregnancy. • Other treatments include doxycycline 100 mg PO bid × 7 days. SO R A Avoid dairy products around time of dosing.

Alte rnative Re g ime ns in Pre g nancy

OR Erythromycin b ase 250 mg orally 4 time s a d ay or 14 d ays OR

1

• Erythromycin might be less ef cacious than either azithromycin or doxycycline, mainly because of the frequent occurrence of GI side effects that can lead to nonadherence. • O oxacin (Floxin) 300 mg PO bid × 7 days is an alternative that should be taken on an empty stomach. 1 SO R A It is contraindicated in children or pregnant and lactating women, but may also cover Neisseria gonorrhoeae infection. Levo oxacin 500 mg PO for 7 days is another uoroquinolone alternative. 1 SO R A • A metaanalysis of 12 randomized clinical trials of azithromycin versus doxycycline for the treatment of genital chlamydial infection demonstrated that the treatments were equally ef cacious, with microbial cure rates of 97% and 98%, respectively. 15 • Partners need treatment. If concern exists that sex partners will not seek evaluation and treatment, then delivery of antibiotic therapy (either a prescription or medication) to their partners is an option. 1 • Medications for chlamydial infections should be dispensed on site and the rst dose directly observed to maximize medication adherence. 1 REFERRAL O R HO SPITALIZATIO N With evidence of complications such as a tuboovarian abscess or severe PID.

Erythromycin e thylsuccinate 800 mg orally 4 time s a d ay or 7 d ays OR Erythromycin e thylsuccinate 400 mg orally 4 time s a d ay or 14 d ays Data rom the Ce nte rs or Dise ase Control and Pre ve ntion.1

PREVENTIO N Individuals who are sexually active should be aware of the risk of STDs and that ways of avoiding infection include mutual monogamy and appropriate barrier protection.

PRO GNO SIS Treatment failures with full primary therapies are quite rare. Reinfection is very common and is related to nontreatment of sexual partners or acquisition from a new partner.

Ch La MYDIa Ce r VICIt IS

FO LLO W-UP Test of cure (repeat testing 3-4 weeks after completing therapy) is not recommended for persons treated with the recommended or alterative regimens, unless therapeutic compliance is in question, symptoms persist, or reinfection is suspected. However, test of cure is recommended in pregnant women. 1

PATIENT EDUCATIO N

PART 12

WO MEN’S HEALTH 3. World Health Organization. ChlamydiaTrachomatis. Initiative forVaccine Research. http:/ / www.who.int/ vaccine_research/ diseases/ soa_std/ en/ index.html. Accessed December 2, 2011. 4. Centers for Disease Control and Prevention. http:/ / www.cdc.gov/ std/ Chlamydia/ STDFact-Chlamydia.htm. Accessed December 2, 2011. 5. Skolnik NS. Screening for Chlamydia trachomatis infection. Am Fam Physician. 1995;51:821-826. 6. Martius J, Krohn MA, Hillier SL, et al. Relationships of vaginal lactobacillus species, cervical Chlamydia trachomatis, and bacterial vaginosis to preterm birth. Obstet Gynecol. 1988;71:89-95.

• To minimize transmission, persons treated for Chlamydia should be instructed to abstain from sexual intercourse for 7 days after singledose therapy or until completion of a 7-day regimen.

7. Ness RB, Goodman MT, Shen C, Brunham RC. Serologic evidence of past infection with Chlamydia trachomatis, in relation to ovarian cancer. J Infect Dis. 2003;187:1147-1152.

• To minimize the risk for reinfection, patients also should be instructed to abstain from sexual intercourse until all their sex partners are treated. 1

8. Datta SD, Sternberg M, Johnson RE, et al. Gonorrhea and Chlamydia in the United States among persons 14 to 39 years of age, 1999 to 2002. Ann Intern Med. 2007;147:89.

PATIENT RESO URCES

• eMedicine Health. Cervicitis—http:/ / www.emedicinehealth .com/ cervicitis/ article_em.htm. • eMedicine Health. Chlamydia—http:/ / www.emedicinehealth .com/ chlamydia/ article_em.htm. • CDC. Chlamydia—http:/ / www.cdc.gov/ std/ Chlamydia/ STDFact-Chlamydia.htm.

9. Monroe KW, Weiss HL, Jones M, Hook EW 3rd. Acceptability of urine screening for Neisseria gonorrheae and Chlamydia trachomatis in adolescents at an urban emergency department. SexTransm Dis. 2003;30:850. 10. Rietmeijer CA, Bull SS, Ortiz CG, et al. Patterns of general health care and STD services use among high-risk youth in Denver participating in community-based urine Chlamydia screening. SexTransm Dis. 1998;25:457.

PRO VIDER RESO URCES

11. Doshi JS, Power J, Allen E. Acceptability of chlamydia screening using self-taken vaginal swabs. Int J STD AIDS. 2008;19:507-509.

• CDC. Sexually Transmitted Diseases (STDs) 2010: Diseases Characterized by Urethritis and Cervicitis—http:/ / www.cdc.gov/ std/ treatment/ 2010/ urethritis-and-cervicitis.htm.

12. Bachmann LH, Johnson RE, Cheng H, et al. Nucleic acid ampli cation tests for diagnosis of Neisseria gonorrhoeae and Chlamydia trachomatis rectal infections. J Clin Microbiol. 2010;48:1827-1832.

• Medscape. Chlamydial Genitourinary Infections—http:/ / emedicine .medscape .com/ article/ 214823-overview.

13. Bachmann LH, Johnson RE, Cheng H, et al. Nucleic acid ampli cation tests for diagnosis of Neisseria gonorrhoeae oropharyngeal infections. J Clin Microbiol. 2009;47:902-907.

• Medscape. Cervicitis—http:/ / emedicine.medscape.com/ article/ 253402. REFERENCES 1. Centers for Disease Control and Prevention. Sexually Transmitted Diseases (STDs) 2010: Diseases Characterized by Urethritis and Cervicitis. http:/ / www.cdc.gov/ std/ treatment/ 2010/ urethritis-and-cervicitis .htm. Accessed December 2, 2011. 2. Centers for Disease Control and Prevention. SexuallyTransmitted Disease Surveillance, 2009— Chlamydia. http:/ / www.cdc.gov/ std/ stats09/ default.htm. Accessed December 25, 2011.

14. Chernesky M, Freund GG, Hook E, 3rd, et al. Detection of Chlamydia trachomatis and Neisseria gonorrhoeae infections in North American women by testing SurePath liquid-based Pap specimens in APTIMA assays. J Clin Microbiol. 2007;45:2434-2438. 15. Lau C-Y, Qureshi AK. Azithromycin versus doxycycline for genital chlamydial infections: A meta-analysis of randomized clinical trials. SexTransm Dis. 2002;29:497-502.

457

458

PART 12

WO MEN’S HEALTH

SECTIO N 2

Ch a pt e r 94

BREAST

94 MASTITIS AND BREAST ABSCESS E.J. Maye aux, Jr., MD

PATIENT STO RY A 23-year-old woman, who is currently breast- eeding and 6 weeks postpartum presents with a hard, red, tender, indurated area medial to her right nipple (Figure 94-1). She also has a low-grade ever. There is a local area o f uctuance and so incision and drainage is recommended. The area is anesthetized with 1% lidocaine and epinephrine and drained with a No. 11 scalpel. A lot o purulence is expressed and the wound is packed. The patient is started on cephalexin 500 mg qid or 10 days to treat the surrounding cellulitis and seen in ollow-up the next day. The patient was already eeling better the next day and went on to ull resolution in the ollowing weeks.

FIGURE 94-2 Mastitis in a p ostp a tum b e ast-fe e d ing woman. The ig ht b e ast was wa m, te nd e , e nla g e d , and p ainful. E ythe ma is b a e ly visib le on the a e ola b e cause of the natu ally d a ke p ig me ntation of the skin. (Courte sy of Richard P. Usatine , MD.)

EPIDEMIO LO GY The prevalence o mastitis is estimated to be at least 1% to 3% o lactating women (Figure 94-2). Risk actors include a history o mastitis with a previous child, cracks and nipple sores, use o an anti ungal nipple cream in the same month, and use o a manual breast pump. 1 Breast abscess is an uncommon problem in breast- eeding women with an incidence o approximately 0.1%. 2 Risk actors include maternal age more than 30 years o age, primiparity, gestational age o 41 weeks, and mastitis. 2,3 Breast abscess develops in 5% to 11% o women with mastitis, o ten caused by inadequate therapy. 3

ETIO LO GY AND PATHO PHYSIO LO GY Mastitis, de ned as an in ection o the breast, and breast abscesses are typically ound in breast- eeding women (Figures 94-1 and 94-2). A breast abscess can occur in older women unrelated to pregnancy and breast- eeding (Figure 94-3). Mastitis is most commonly caused by Staphylococcus aureus, Streptococcus species, and Escherichia coli. Recurrent mastitis can result rom poor selection or incomplete use o antibiotic therapy, or ailure to resolve underlying lactation management problems. Mastitis that repeatedly recurs in the same location, or does not respond to appropriate therapy, may indicate the presence o breast cancer. 3

DIAGNO SIS CLINICAL FEATURES • Mastitis causes a hard, red, tender, swollen area on the breast (Figures 94-1 and 94-2). • Fever is common. • Pain usually extends beyond the indurated area. • It is o ten associated with other systemic complaints including myalgia, chills, malaise, and f u-like symptoms. • Breast abscess can occur with mastitis, except a f uctuant mass is palpable. (In Figure 94-3, the f uctuant mass is close to the midline with 2 openings o spontaneous drainage. The remainder o the erythema is cellulitis.) FIGURE 94-1 Localize d ce llulitis and b e ast ab sce ss in a b e ast-fe e d ing mo the . No te the Pe au d ’ o ang e ap p e a ance o f the e d e mato us b e ast tissue . (Re p rod uce d with p e rmission from Nicole tte De ve ne au, MD.)

• Breast abscesses, especially in the in ramammary area, may also be associated with hydradenitis suppurativa (Figure 94-4). 4 • Typical distribution is usually unilateral.

Ma St It IS a ND Br e a St a BSCe SS

PART 12

WO MEN’S HEALTH

FIGURE 94-3 B e ast ab sce ss and ce llulitis in a 40-ye a -old woman. Pus was al e ad y d aining at the time of p e se ntation, b ut a fu the incision and d ainag e th oug h the op e ning s yie ld e d anothe 30 cc of p us. The p atie nt was t e ate d with o al antib iotics and sche d ule d to g e t a mammog am whe n the infe ction is cle a e d . (Courte sy of Richard P. Usatine , MD.)

FIGURE 94-4 A b e ast ab sce ss in the le ft b e ast of a 43-ye a -old wome n with hid ade nitis sup pu ativa. Note the pe au d’o ange appe a ance of the le ft b e ast be fo e the absce ss was d aine d. Both b e asts and axillae have multiple old sca s f om p e vious incisions to d ain abscesse s and hid ade nitis in the past. He axillae have active ch onic dise ase but he acute p oble m is the b e ast ab scess. (Re produce d with pe rmission from Richard P. Usatine, MD.)

• Biopsy is unnecessary, but in persistent cases, a midstream milk sample may be cultured and antibiotics prescribed based upon the identi cation and sensitivity o the speci c pathogen.

• The management o a breast abscess consists o drainage o the abscess. 5 SO R A Antibiotic therapy should be considered and is especially important i there is surrounding cellulitis (Figures 94-2 and 94-3).

DIFFERENTIAL DIAGNO SIS • Mastitis should be distinguished rom plugged lacrimal ducts, which present as hard, locally tender, red areas without associated regional pain or ever. • Tinea corporis can cause erythema and scaling on any part o the body including breast. It is o ten annular and pruritic (see Chapter 132, Tinea Corporis).

• Drainage can usually be per ormed by needle aspiration, with the addition o ultrasound guidance i necessary. • I needle aspiration is not e ective, incision and drainage should be per ormed. Incision and drainage is o ten pre erred because it allows or continued drainage through the opening. In many cases a cotton wick is placed to keep the abscess open while the purulence drains in the ollowing days. • Breast- eeding may continue on both breasts i the incision isn’t too pain ul and it does not inter ere with the baby latching on. Otherwise a breast pump may be used on the a ected breast or 3 to 4 days until nursing can resume.

MANAGEMENT • Management o mastitis includes supportive measures such as continued breast- eeding and bed rest. SO R C I the in ant cannot relieve breast ullness during nursing, breast massage during nursing or pumping a terward may help reduce discom ort. • Acetaminophen or an anti-inf ammatory agent such as ibupro en may be used or pain control. • Antibiotic treatment should be initiated with dicloxacillin or cephalexin (500 mg PO 4 times daily) or 10 to 14 days. 5 SO R A Consider clindamycin i the patient is allergic to penicillin and/ or cephalosporins. 5 Clindamycin may be a good choice i methicillin-resistant S. aureus (MRSA) is suspected. All o the antibiotics recommended are sa e or the baby during pregnancy and lactation. Trimethoprim/ sul amethoxazole is an alternative or MRSA and/ or penicillin allergic patients but it should be avoided near term pregnancy and in the rst 2 months o breast- eeding because o a risk to the baby o kernicterus. Shorter courses o antibiotic therapy may be associated with higher relapse rates. SO R C

PATIENT EDUCATIO N • The patient may take acetaminophen or ibupro en or pain since these medications are sa e while breast- eeding and are indicated or use in children. • Warm compresses applied be ore and a ter eedings can provide some pain relie . A warm bath may also help. • Instruct the patient to nish the antibiotic prescription, even i they eel better in a ew days, to lower the risk o bacterial resistance or relapse. • Continue eedings and use a breast pump to completely empty the breast i necessary. • Educate the parents that the mastitis or the antibiotics will not harm the baby, and that the source o the in ection was probably the baby’s own mouth. • Continue to drink plenty o water and eat well-balanced meals.

459

PART 12

460

WO MEN’S HEALTH FO LLO W-UP • I no response is seen within 48 hours or i MRSA is a possibility, antibiotic therapy should be switched to trimethoprim/ sul amethoxazole 1 double strength PO twice a day, or Clindamycin 300 mg orally every 6 hours. Avoid trimethoprim/ sul amethoxazole in near-term pregnancy and in the rst 2 months o breast- eeding. • Hospitalization and intravenous antibiotics are rarely needed but should be considered i the patient is systemically ill and not able to tolerate oral antibiotics. PATIENT RESO URCES

• MedlinePlus. Breast infection—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 001490.htm. • National Health Service (Brittan) Direct Online Health Encyclopaedia—http:/ / www.nhsdirect.nhs.uk/ articles/ article.aspx?articleId=62. PRO VIDER RESO URCES

• eMedicine. Breast Abscess and Masses—http:/ / www.emedicine .com/ EMERG/ topic68.htm. • Andolsek KM and Copeland JA. Benign breast conditions and disease: Mastitis. In: Tayor RB ed. Family Medicine Principles and Practice. 6th ed. New York, NY: Springer, 2003:898.

CHAPTEr 94

REFERENCES 1. Foxman B, D’Arcy H, Gillespie B, et al. Lactation mastitis: Occurrence and medical management among 946 breast eeding women in the United States. Am J Epidemiol. 2002;155:103. 2. Kvist LJ, Rydhstroem H. Factors related to breast abscess a ter delivery: a population-based study. BJOG. 2005;112:1070. 3. Berens PD. Prenatal, intrapartum, and postpartum support o the lactating mother. Pediatr Clin North Am. 2001;48:365. 4. Dixon JM. ABC o breast diseases. Breast in ection. BMJ. Oct 8 1994;309(6959):946-949. 5. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines or the diagnosis and management o skin and so t-tissue in ections. Clin Infect Dis. 2005;41:1373-1406.

BREAST CANCER

PART 12

WO MEN’S HEALTH

95 BREAST CANCER E.J. Maye aux Jr, MD

PATIENT STO RY A 55-year-old woman presents for routine screening mammogram. The patient does not have any complaints but has a family history of breast cancer in a sister at age of 40 years. Her mammogram demonstrates an irregular mass with possible local spread (Figures 95-1 and 95-2). She is referred to a breast surgeon and the biopsy con rms the diagnosis of breast cancer.

INTRO DUCTIO N Breast cancer is a major health concern for all women. It is the most common female cancer in the United States, and the second most common cause of cancer death in women after lung cancer. 1

EPIDEMIO LO GY • In 2007, approximately 178,000 women in the United States were diagnosed with breast cancer. 1 Breast cancer incidence in the United States has doubled over the past 60 years. Since the early 1980s, most of the increase has been in early stage and in situ cancers because of mammogram screening (Figures 95-1 to 95-4).

FIGURE 95-2 A clo se -u mammo g ra ic vie w o t e b re ast cance r le sio n s o wn in Fig ure 95-1. (Re p rod uce d with p e rmission from John Braud , MD.)

• Globally, breast cancer is the most common cancer and the leading cause of cancer death in females. Breast cancer incidence rates are highest in North America, Australia-New Zealand, and Europe and lowest in Asia and sub-Saharan Africa. 2 • Locally advanced breast cancer (LABC) has been decreasing in frequency over the past several decades, at least partially as a result of

• Approximately 232,620 new cases of invasive breast cancer were expected to be diagnosed in the United States in 2011, and 39,970 were expected to die from the disease. 1

FIGURE 95-1 A mammog ram t at d e monstrate s an irre g ular mass wit ossib le local s re ad . Bio sy conf rme d t is to b e b re ast cance r. (Re p rod uce d with p e rmission from John Braud , MD.)

FIGURE 95-3 A scre e ning mammogram o a 55-ye ar-old woman w o is wit out b re ast com laints. T e mammog ram d e monstrate s a sig nif cant mass wit s e culations. Bio sy conf rme d t is to b e b re ast cance r. (Re p rod uce d with p e rmission from John Braud , MD.)

461

462

PART 12

WO MEN’S HEALTH

Ch a pt e r 95

FIGURE 95-6 T e woman wit b re ast cance r in Fig ure 95-5 s owing b re ast re traction and b rawny e d e ma o t e b re ast and arm. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

ETIO LO GY AND PATHO PHYSIO LO GY

FIGURE 95-4 Close -u mammog ra ic vie w o t e b re ast cance r s own in Fig ure 95-3 d e mo nstrating cle ar s iculations and microcalcif cations. (Re p rod uce d with p e rmission from John Braud , MD.)

earlier diagnosis because of better screening (Figures 95-5 to 95-8). It represents 30% to 50% of newly diagnosed breast cancers in medically underserved populations. 3 • Primary in ammatory breast cancer (IBC) is relatively rare, accounting for 0.5% to 2% invasive breast cancers. 4 However, it accounts for a greater proportion of cases presenting with more advanced disease. IBC is a clinical diagnosis. At presentation, almost all women with primary IBC have lymph node involvement and approximately one-third have distant metastases. 5

FIGURE 95-5 Woman wit ad vance d b re ast cance r and e au d ’orang e sig n. T e skin looks like t e skin o an orang e as a conse q ue nce o lym e d e ma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• The incidence of breast cancer increases with age. White women are more likely to develop breast cancer than black women. One percent of breast cancers occur in men. • Primary risk factors for the development of breast cancer include age older than 50 years, female sex, increased exposure to estrogen (including early menarche and late menopause), and a family history in a rstdegree maternal relative (especially if diagnosed premenopausally). • Approximately 8% of breast cancers are hereditary and of these one-half are associated with mutations in genes BRCA1 and BRCA2. It is more common in premenopausal women, multiple family generations, and bilateral breasts.6 Typically, several family members are affected over at least 3 generations and can include women from the paternal side of the family. • A history of a proliferative breast abnormality, such as atypical hyperplasia, may increase a woman’s risk for developing breast cancer.

FIGURE 95-7 Ad vance d b re ast cance r wit ung ating mass and d istortion o t e normal b re ast anatomy. (Re p rod uce d with p e rmission from Kriste n Sore nse n, MD.)

PART 12

Br e a St Ca NCe r

WO MEN’S HEALTH • Low physical activity levels. • High-fat diet. • Alcohol intake of 2 or more drinks daily.

DIAGNO SIS CLINICAL FEATURES

FIGURE 95-8 Et io ian woman wit b re ast cance r and 5 e nlarg e d f rm le t axillary lym no d e s. Note t e b re ast asymme try and t e e au d ’orang e skin on t e le t b re ast. T e d ark b lack are a was cause d b y a “trad itional e ale r” w o b urne d t e skin. Un ortunate ly t e wo man could not a ord to g e t care at t e local os ital, making e r rog nosis ve ry g rave . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• The selective estrogen receptor modulator tamoxifen (and possibly raloxifene) reduces the risk of developing breast cancer. • The American Cancer Society, American College of Radiology, American Medical Association, and American College of Obstetrics and Gynecology all recommend starting routine screening at age 40 years. 7 • The United States Preventive Services Task Force and the 2002 statement by the American Academy of Family Physicians recommend screening mammography every 1 to 2 years for women ages 40 years and older.8 • Women who have a family history of BRCA mutation should begin annual mammography between 25 and 35 years of age. 9 SO R A • MRI screening is more sensitive for detecting breast cancers than mammography and is being used to screen women with BRCA mutations. 10 It is not proven that surveillance regimens that include MRI will reduce mortality from breast cancer in high-risk women. 10 • Although the sensitivity of MRI is higher than that of conventional imaging. MRI has a lower speci city. One study suggests that unnecessary biopsies can be avoided with second-look ultrasound when MRI is positive and mammography is not. Second-look ultrasound can be used to recognize false-positive MRI results and guide biopsies. 11

• Detection of a breast mass is the most common presenting breast complaint. However, 90% of all breast masses are caused by benign lesions. Breast pain is also a common presenting problem. Physical examination of the breast should be performed in the upright (sitting) and supine positions. Inspect for differences in size, retraction of the skin or nipple (Figures 95-5 and 95-6), prominent venous patterns, and signs of in ammation (Figures 95-5 and 95-6). Palpate the breast tissue, axillary area, and supraclavicular areas for masses or adenopathy. Gently squeeze the nipple to check for discharge. • Most LABCs are both palpable and visible (Figures 95-7 and 95-8). Careful palpation of the skin, breasts, and regional lymph nodes is the initial step in diagnosis. The patient in Figure 95-8 had 5 palpable lymph nodes at the time of presentation. • IBC usually presents clinically as a diffuse brawny induration of the skin of the breast with an erythematous edge, and usually without an underlying palpable mass. Patients with de novo IBC typically present with pain and a rapidly enlarging breast. The skin over the breast is warm, and thickened, with a “peau d’orange” (skin of an orange) appearance (Figures 95-5 and 95-6). The skin color can range from a pink ushed discoloration to a purplish hue. TYPICAL DISTRIBUTIO N A mass that is suspicious for breast cancer is usually solitary, discrete, hard, unilateral, and nontender. It may be xed to the skin or the chest wall. IMAGING More than 90% of breast cancers are identi ed mammographically.12 When an abnormality is found, supplemental mammographic views and possibly ultrasound are usually done. Diagnostic mammography is associated with higher sensitivity but lower speci city as compared to screening mammography. 13 BIO PSY

RISK FACTO RS • Positive family history of breast and/ or ovarian cancer (especially with BRCA mutations). • Personal history of breast cancer. • Increasing age in women. • Early age at menarche and late menopause. • Prolonged exposure to and higher concentrations of endogenous or exogenous estrogen. • Exposure to ionizing radiation. • Dense breast tissue and atypical hyperplasia. • Women who have had no children or who had their rst child after age 30 have a slightly higher breast cancer risk.

Fine-needle aspiration biopsy generally uses a 20- to 23-gauge needle to obtain samples from a solid mass for cytology. Ultrasound or stereotactic guidance is used to assist in collecting a ne-needle aspiration from a nonpalpable lump. Core biopsy uses a 14-gauge or similar needle to remove cores of tissue from a mass. Excisional biopsy is done as the initial procedure or when needle biopsies are negative when the clinical suspicion is high. Guided biopsy and nonguided biopsy are also commonly used to make a de nitive diagnosis.

DIFFERENTIAL DIAGNO SIS • Fibroadenoma usually present as smooth, rounded, rubbery masses in women in their 20s and 30s. A clinically suspicious mass should be biopsied even if mammography ndings are normal.

463

PART 12

464

WO MEN’S HEALTH • Benign cysts are rubbery and hollow feeling in women in their 30s and 40s. A cyst can be diagnosed by ultrasound imaging. A simple cyst can be aspirated, but a residual mass requires further evaluation. Ultrasound is useful to differentiate between solid and cystic breast masses, especially in young women with dense breast tissue. • Bilateral mastalgia is rarely associated with breast cancer, but it does not eliminate the possibility. It is usually related to brocystic changes in premenopausal women that are associated with diffuse lumpy breasts. A unilateral breast lump with pain must be evaluated for breast cancer. • Nipple discharge may be from infection which is usually purulent, and from pregnancy, stimulation, or prolactinoma which produces a thin, milky, often bilateral discharge. A pregnancy test may be helpful. A suspicious discharge from a single duct can be evaluated with a ductogram. • Infectious mastitis and breast abscess, which typically occur in lactating women, appear similar to IBC but are generally associated with fever and leukocytosis (see Chapter 92, Breast Abscess and Mastitis). • Ductal ectasia with in ammation appears similar but is usually localized. • Leukemic involvement of the breast may mimic IBC, but the peripheral blood smear is typically diagnostic.

MANAGEMENT NO NPHARMACO LO GIC • Surgical resection is required in all patients with invasive breast cancer. Oncologic outcomes are similar with mastectomy and breast-conserving therapy (lumpectomy plus breast radiation therapy) in appropriately selected patients. For women undergoing mastectomy, breast reconstruction may be performed at the same time as the initial breast cancer surgery, or deferred to a later date. 14 SO R A • Long-term survival can be achieved in approximately 50% of women with LABC who are treated with a multimodality approach. 15 Prognostic factors include age, menopausal status, tumor stage and histologic grade, clinical response to neoadjuvant therapy, and estrogen receptor status. • In general, women with IBC are approached similarly to those with nonin ammatory LABC except that breast conservation therapy is generally considered inappropriate for these women. 16 SO R A MEDICATIO NS • Adjuvant systemic therapy consists of administration of hormone therapy, chemotherapy, and/ or trastuzumab (a humanized monoclonal antibody directed against HER-2/ neu) after de nitive local therapy for breast cancer. It bene ts most women with early stage breast cancer, but the magnitude of bene t is greatest for those with node-positive disease. 17 SO R A • The most common approach for advanced breast cancer is preoperative chemotherapy followed by surgery and radiotherapy. Questions regarding sequencing and choice of speci c chemotherapy regimens and extent of surgery (including the utility of the sentinel node biopsy) persist. SO R A • Preoperative (as opposed to postoperative) chemotherapy has several advantages for advanced breast cancer (Figure 95-7) treatment. It can reduce the size of the primary tumor, thus allowing

Ch a pt e r 95

for breast-conserving surgery, permits assessing an identi ed mass to determine the sensitivity of the tumor cells to drugs with discontinuation of ineffective therapy (thus avoiding unnecessary toxicity), and enables drug delivery through an intact tumor vasculature. 18 SO R A • Tamoxifen and aromatase inhibitors may be used in selective patients as neoadjuvant hormone therapy of decrease overall tumor volume. SO R A

REFERRAL O R HO SPITALIZATIO N With the emergence of breast-conserving therapy (BCT), many women now have the option of preserving a cosmetically acceptable breast without sacri cing survival for early stage invasive breast cancer.

PREVENTIO N • Healthy lifestyle choices can decrease the risk of breast cancer, including a low-fat diet, regular exercise, and no more than 1 drink daily. • Having children before age 30 years and prolonged breast-feeding may be of help in primary prevention, but will not be a commonly used strategy for most women. • Secondary prevention involves screening for breast cancer with physical examinations and mammography. There is a strong consensus based on consistent ndings from multiple randomized trials that routine screening mammography should be offered to women ages 50 to 69 years. Consensus is less strong for routine screening among women ages 40 to 49 years, women older than age 70 years, or for how frequently to screen. 19 20 The American Cancer Society, the National Cancer Institute, ° the American College of Obstetricians and Gynecologists, 21 and the National Comprehensive Cancer Network22 recommend starting routine screening at age 40 years. 23 The United States Preventive Services Task Force (USPSTF) and ° the Canadian Task Force on the Periodic Health Examination24 recommend beginning routine screening at age 50 years. • Prophylactic mastectomy is an effective and accepted method by some BRCA-positive women after childbearing when their risk of lifetime breast cancer without this intervention is high (eg, over 60%). • Chemoprevention with tamoxifen or raloxifene is an option for women who are at high risk for breast cancer.

FO LLO W-UP Regular follow-up will usually be maintained during treatment. After treatment, life-long regular follow-up for surveillance should be maintained. Metastases can present in many ways including dif culty breathing, back pain, or a new skin nodule (Figure 95-9). These complaints should be taken seriously and worked up carefully in any patient with a history of breast cancer.

PATIENT EDUCATIO N The contralateral breast is at increased risk of breast cancer and should be monitored. Patients on tamoxifen should be monitored for endometrial hyperplasia or cancer.

Br e a St Ca NCe r

PART 12

WO MEN’S HEALTH 6. Krainer M, Silva-Arrieta S, FitzGerald MG, et al. Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer. N Engl J Med. 1997;336(20):1416-1421. 7. Smith RA, Saslow D, Sawyer KA, et al. American Cancer Society guidelines for breast cancer screening: update 2003. CA Cancer J Clin. 2003;53(3):141-169. 8. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services, 3rd ed. http:/ / www.ahrq.gov/ clinic/ uspst x.htm. Accessed February 24, 2012. 9. Burke W, Daly M, Garber J, et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. JAMA. 1997;277(12):997-1003. 10. Warner E, Plewes DB, Hill KA, et al. Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA. 2004;292(11):1317-1325.

FIGURE 95-9 Me tastatic b re ast cance r wit f rm al ab le nod ule s on t e b ack. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

PATIENT RESO URCES

• Breast cancer support group for survivors—http:/ / bcsupport .org/ . • Breastcancer.org—http:/ / www.breastcancer.org/ . PRO VIDER RESO URCES

• American Academy of Family Physicians. Breast Cancer—http:/ / www.aafp.org/ online/ en/ home/ clinical/ exam/ breastcancer.html. • U.S. Preventive Services Task Force. Screening for Breast Cancer— http:/ / www.uspreventiveservicestaskforce.org/ uspstf/ uspsbrca.htm. • National Cancer Institute. Breast Cancer—http:/ / www.cancer .gov/ cancertopics/ types/ breast.

REFERENCES 1. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212-236. 2. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69-90. 3. Hortobagyi GN, Sinigletary SE, Strom EA. Treatment of locally advanced and in ammatory breast cancer. In: Harris JR, Lippman ME, Morrow M, Osborne CK, eds. Diseases of the Breast, 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2000:645-660. 4. Hance KW, Anderson WF, Devesa SS, et al. Trends in in ammatory breast carcinoma incidence and survival: The surveillance, epidemiology, and end results program at the national cancer institute. J Natl Cancer Inst. 2005;97(13):966-975. 5. Kleer CG, van Golen KL, Merajver SD. Molecular biology of breast cancer metastasis: inflammatory breast cancer: Clinical syndrome and molecular determinants. Breast Cancer Res. 2000;2(6): 423-429.

11. Trecate G, Vergnaghi D, Manoukian S, et al. MRI in the early detection of breast cancer in women with high genetic risk. Tumori. 2006;92(6):517-523. 12. Smart CR, Hartmann WH, Beahrs OH, Gar nkel L. Insights into breast cancer screening of younger women. Evidence from the 14-year follow-up of the Breast Cancer Detection Demonstration Project. Cancer. 1995;72(4 Suppl):1449-1456. 13. Barlow WE, Lehman CD, Zheng Y, et al. Performance of diagnostic mammography for women with signs or symptoms of breast cancer. J Natl Cancer Inst. 2002;94(15):1151-1159. 14. Vandeweyer E, Hertens D, Nogaret JM, Deraemaecker R. Immediate breast reconstruction with saline- lled implants: No interference with the oncologic outcome? Plast Reconstr Surg. 2001;107(6): 1409-1412. 15. Brito RA, Valero V, Buzdar AU, et al. Long-term results of combined-modality therapy for locally advanced breast cancer with ipsilateral supraclavicular metastases: The University of Texas M.D. Anderson Cancer Center experience. J Clin Oncol. 2001;19(3): 628-633. 16. Lyman GH, Giuliano AE, Somer eld MR, et al. American Society of Clinical Oncology. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol. 2005;23(30):7703-7720. 17. Goldhirsch A, Glick JH, Gelber RD, et al. Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol. 2005;16(10):1569-1583. 18. Fisher B, Gunduz N, Saffer EA. In uence of the interval between primary tumor removal and chemotherapy on kinetics and growth of metastases. Cancer Res. 1983;43(4):1488-1492. 19. Smith RA, Cokkinides V, Brawley OW. Cancer screening in the United States, 2009: a review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin. 2009;59(1):27-41. 20. National Cancer Institute. Breast Cancer Screening (PDQ). http:/ / www.cancer.gov/ cancertopics/ pdq/ screening/ breast/ HealthProfessional/ page2. Accessed February 24, 2012. 21. American College of Obstetricians-Gynecologists. Practice bulletin no. 122: breast cancer screening. Obstet Gynecol. 2011;118(2 Pt 1): 372-382.

465

466

PART 12

WO MEN’S HEALTH 22. Bevers TB, Anderson BO, Bonaccio E, et al. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer screening and diagnosis. J Natl Compr Canc Netw. 2009;7(10):1060-1096. 23. US Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151(10):716-726, W-236.

Ch ApTER 95

24. Canadian Task Force on the Periodic Health Examination. Screening for Breast Cancer. http:/ / www.canadiantaskforce.ca/ recommendations/ 2011_01_eng.html. Accessed February 24, 2012.

PAGET DISEASE O F THE BREAST

96 PAGET DISEASE O F THE BREAST

PART 12

WO MEN’S HEALTH • The peak incidence is between 50 and 60 years o age. 2 • It is associated with underlying in situ and/ or invasive breast cancer 85% to 88% o the time. 3

E.J. Maye aux, Jr., MD

ETIO LO GY AND PATHO PHYSIO LO GY PATIENT STO RY A 62-year-old woman presents with a 6-month history o an eczematous, scaly, rash near her nipple. It is mildly pruritic. On physical examination, the nipple and the areola are involved (Figure 96-1). Also, a hard mass is present in the lateral lower quadrant o the same breast. A 4-mm punch biopsy o the a ected area including the nipple demonstrates Paget disease. The mammogram is suspicious or breast cancer at the site o the mass and the patient is re erred to a breast surgeon.

INTRO DUCTIO N Paget disease o the breast is a low-grade malignancy o the breast that is o ten associated with other malignancies. It is an important consideration when working up a chronic persistent abnormality o the nipple.

SYNO NYMS Paget’s disease, Mammary Paget disease.

EPIDEMIO LO GY • The incidence o Paget disease o the breast is approximately 0.6% in women in the United States, according to National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) data. 1 Paget disease, like all breast cancers, is rare in men.

FIGURE 96-1 Pag e t d ise ase o the b re ast o a 62-ye ar-old woman that p re se nte d as a p e rsiste nt e cze matous le sion. (Re prod uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

• Most patients delay presentation, assuming the abnormality is a benign condition o some sort. The median duration o signs and symptoms prior to diagnosis is 6 to 8 months. 2 • Presenting symptoms are sometimes limited to persistent pain, burning, and/ or pruritus o the nipple (Figures 96-1 and 96-2). • A palpable breast mass is present in 50% o cases, but is o ten located more than 2 cm rom the nipple–areolar complex. 4 • Twenty percent o cases will have a mammographic abnormality without a palpable mass, and 25% o cases will have neither a mass nor abnormal mammogram, but will have an occult ductal carcinoma. • In less than 5% o cases, Paget disease o the breast is an isolated f nding. 4 • There are 2 theories regarding the pathogenesis o Paget disease o the breast, the choice o which a ects treatment choices. ° The more widely accepted epidermotropic theory proposes that the Paget cells arise rom an underlying mammary adenocarcinoma that migrates through the ductal system o the breast to the skin o the nipple. It is supported by the act that Paget disease is usually associated with an underlying ductal carcinoma, and both Paget cells and mammary ductal cells usually express similar immunochemical staining patterns and molecular markers. This could mean that there is a common genetic alteration and/ or a common progenitor cell or both Paget cells and the underlying ductal carcinoma. ° The less widely accepted trans ormation theory proposes that epidermal cells in the nipple trans orm into malignant Paget cells, and that Paget disease o the breast represents an independent epidermal carcinoma in situ. It is supported by the act that there is no parenchymal cancer identif ed in a small percentage o cases, and underlying breast carcinomas are o ten located at some distance to the nipple. Most pathologists disagree with the trans ormation theory.

FIGURE 96-2 Close -up o Pag e t d ise ase o the b re ast. Note the e rythe matous, e cze matous, scaly ap p e arance o the le sion. (Re p rod uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

467

PART 12

468

WO MEN’S HEALTH

Ch a pt e r 96

LABO RATO RY TESTING The diagnosis is made by f nding intraepithelial adenocarcinoma cells (Paget cells) either singly or in small groups within the epidermis o the nipple complex. IMAGING • Bilateral mammography is mandatory to asses or associated cancers. MRI may disclose occult cancer in some women with Paget disease o the breast and normal mammography and/ or physical examination. 5 • Polarized dermoscopy may also be use ul in diagnosis, especially in cases o pigmented mammary Paget disease. 6 BIO PSY FIGURE 96-3 Pag e t d ise ase o the b re ast in a 29-ye ar-o ld woman that p re se nte d as a p e rsiste nt e cze matous le sion or 8 months p rior to b iop sy. The p atie nt d id not have a p alp ab le b re ast mass. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIAGNO SIS CLINICAL FEATURES • Paget disease o the breast presents clinically in the nipple–areolar complex as a dermatitis that may be erythematous, eczematous, scaly, raw, vesicular, or ulcerated (Figures 96-1 to 96-4). The nipple is usually initially involved, and the lesion then spreads to the areola. Spontaneous improvement or healing o the nipple dermatitis can occur and should not be taken as an indication that Paget disease is not present. The diagnosis is made by f nding malignant, intraepithelial adenocarcinoma cells on pathology. Rarely, nipple retraction is ound. • Pain, burning, and/ or pruritus may be present or even precede clinically apparent disease develops on the skin.

The diagnosis is usually made by ull-thickness punch or wedge biopsy that shows Paget cells. Nipple scrape cytology can diagnose Paget disease and may be considered or screening eczematous lesion o the nipple.

DIFFERENTIAL DIAGNO SIS • Eczema o the areola is the most common cause o scaling o the breast (Figure 96-5). I the patient (Figure 96-5) had new nipple inversion with the onset o skin changes, this would be more suspicious or Paget disease. • Bowen disease is squamous cell carcinoma in situ and can di erentiate rom Paget disease by histology. Also, Bowen disease expresses highmolecular-weight keratins, whereas Paget disease expresses lowmolecular-weight keratins (see Chapter 166, Actinic Keratosis and Bowen Disease and Chapter 169, Squamous Cell Carcinoma). • Superf cial spreading malignant melanoma may be con used with Paget disease but histologic study and immunohistochemical staining can separate the 2 (Figure 96-6) (see Chapter 170, Melanoma).

TYPICAL DISTRIBUTIO N • Paget disease o the breast is almost always unilateral, although bilateral cases have been reported. • Work-up must also be directed toward identi ying any underlying breast cancer.

FIGURE 96-4 Close -up o Pag e t d ise ase o the b re ast in the young woman in Fig ure 96-3. Note the e rythe matous, scaly, and ulce rate d ap p e arance o the le sion. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 96-5 Ecze ma o the are ola in a 43-ye ar-old woman who has had an inve rte d nip p le he r whole ad ult li e . She re me mb e rs having d i f culty b re aste e d ing he r child re n. The curre nt e cze ma has b e e n p re se nt on the are ola on and o or more than 10 ye ars and always re sp ond s to top ical corticoste roid s. Bre ast e xamination and mammog rap hy are ne g ative . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 12

pa Ge t DISe a Se O F t h e Br e a St

WO MEN’S HEALTH acceptance. The surgically conservative approaches include excision o the complete nipple–areolar complex with margin evaluation. Sentinel lymph node biopsy should be per ormed to evaluate axillary lymph node status. 7 SO R B

PRO GNO SIS Patients with only noninvasive Paget disease o the nipple have excellent cancer outcome with conservative surgery, with survival rates similar to those achieved with mastectomy. 8,9 SO R B The prognosis o Paget disease with synchronous cancer is dependent upon the tumor stage o the underlying cancer. FIGURE 96-6 Sup e rf cial sp re ad ing me lano ma ad jace nt to the are ola. (Re p rod uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

PATIENT EDUCATIO N • All lesions o the breast that do not heal should be checked or cancer.

• Seborrheic keratoses and benign lichenoid keratoses can occur on and around the areola and be suspicious or Paget disease (Figure 96-7). A biopsy is the best way to make the diagnosis (see Chapter 156, Seborrheic Keratosis). • Nipple adenoma, which usually presents as an isolated mass with redness, can be diagnosed with biopsy.

• The patient’s prognosis is based on the underlying cancer, i present, not the Paget disease itsel .

PATIENT RESO URCES

• Breastcancer.org. Paget Disease of the Nipple—www.breastcancer .org/ symptoms/ types/ pagets/ . • Imaginis. Paget Disease of the Nipple—http:/ / imaginis.com/ breasthealth/ pagets_disease.asp.

MANAGEMENT SURGICAL The treatment and prognosis o Paget disease o the breast is f rst based on the stage o any underlying breast cancer. Simple mastectomy has traditionally been the standard treatment or isolated Paget disease o the breast, but breast-conserving treatment is being used more o ten. Breastconserving surgery combined with breast irradiation is gaining wider

• Macmillan Cancer Support. Paget Disease of the Breast—http:/ / www.macmillan.org.uk/ Cancerinformation/ Cancertypes/ Breast/ Aboutbreastcancer/ Typesandrelatedconditions/ Pagetsdisease.aspx. PRO VIDER RESO URCES

• Medscape. Mammary Paget Disease—http:/ / emedicine .medscape.com/ article/ 1101235-overview. • National Cancer Institute. Paget Disease of the Nipple—http:/ / www.cancer.gov/ cancertopics/ factsheet/ Sites-Types/ pagets-breast.

REFERENCES 1. SEER Brest Cancer. Cancer Statistics Review 1975-2008.Table 4.1. Cancer of the Female Breast (Invasive). http:/ / seer.cancer.gov/ csr/ 1975_2008/ results_merged/ sect_04_breast.pd . Accessed January 7, 2012. 2. Chaudary MA, Millis RR, Lane EB, Miller NA. Paget’s disease o the nipple: a ten year review including clinical, pathological, and immunohistochemical f ndings. Breast Cancer ResTreat. 1986;8(2):139-146. 3. Chen CY, Sun LM, Anderson BO. Paget disease o the breast: changing patterns o incidence, clinical presentation, and treatment in the U.S. Cancer. 2006;107(7):1448-1458. 4. Ashikari R, Park K, Huvos AG, Urban JA. Paget’s disease o the breast. Cancer. 1970;26(3):680-685. FIGURE 96-7 Be nig n liche noid ke ratosis on the are ola p rove n b y b iop sy. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

5. Morrogh M, Morris EA, Liberman L, et al. MRI identif es otherwise occult disease in select patients with Paget disease o the nipple. JAm Coll Surg. 2008;206(2):316-321.

469

470

PART 12

WO MEN’S HEALTH

CHAPTER 96

6. Crignis GS, Abreu Ld, Buçard AM, Barcaui CB. Polarized dermoscopy o mammary Paget disease. An Bras Dermatol. 2013;88(2): 290-292.

8. Marshall JK, Gri f th KA, Ha ty BG, et al. Conservative management o Paget disease o the breast with radiotherapy: 10- and 15-year results. Cancer. 2003;97(9):2142-2149.

7. Caliskan M, Gatti G, Sosnovskikh I, et al. Paget’s disease o the breast: the experience o the European institute o oncology and review o the literature. Breast Cancer ResTreat. 2008;112(3):513-521. http:/ / www. springerlink.com/ content/ 6270v27346461v08/ . Accessed February 25, 2008.

9. Pezzi CM, Kukora JS, Audet IM, et al. Breast conservation surgery using nipple-areolar resection or central breast cancers. Arch Surg. 2004;139(1):32-37.

Pa r t 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

*

St re ng t h o Re co mme nd at io n (SO R)

De f nit io n

A

Re comme nd ation b ase d on consiste nt and g ood -q uality p atie nt-orie nte d e vid e nce .*

B

Re comme nd ation b ase d on inconsiste nt or limite d -q uality p atie nt-orie nte d e vid e nce .*

C

Re comme nd ation b ase d on conse nsus, usual p ractice , op inion, d ise ase -orie nte d e vid e nce , or case se rie s or stud ie s o d iag nosis, tre atme nt, p re ve ntion, or scre e ning .*

Se e Ap p e nd ix A on p ag e s 1241-1244 or urthe r in ormation.

472

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch a pt e r 97

97 ARTHRITIS O VERVIEW He id i Chumle y, MD Richard P. Usatine , MD

PATIENT STO RY A 50-year-old woman presents with new complaint o pain in several ngers. She has had psoriasis or many years; however, she only developed joint pain last year. Her examination is signi cant or swelling and tenderness at the distal interphalangeal (DIP) joints o her second, third, and ourth ngers (Figure 97-1, A). She had an elevated erythrocyte sedimentation rate (ESR) and radiographs with erosive changes (Figure 97-1, B). Choices or therapy include methotrexate and the new biologic antitumor necrosis actor (TNF)-α medications.

INTRO DUCTIO N

A

Arthritis means inf ammation o the joints; however, the term is used or any disease or condition that a ects joints or the tissues around the joints. Joint pain can be classi ed as monoarticular or polyarticular and inf ammatory or noninf ammatory. Diagnosis is based on a combination o clinical presentation, synovial f uid analysis, other laboratory tests, and radiographic ndings. Management goals include minimizing joint damage, controlling pain, maximizing unction, and improving quality o li e.

EPIDEMIO LO GY • Fi ty million adults in the United States (22%) report doctor-diagnosed arthritis. 1 • Arthritis is the most common cause o disability in the United States. Twenty-one million adults have unctional limitations because o arthritis. 1 • Fi ty percent o adults age 65 years or older have been diagnosed with arthritis. 1 • In 2003, the total cost attributable to arthritic conditions was $128 billion. 2

A FIGURE 97-1 Psoriatic arthritis at initial p re se ntation in a 50-ye ar-old woman with p soriasis and ne w-onse t hand p ain. A. Note the p romine nt involve me nt o the d istal inte rp halang e al joints. B. Rad iog rap hy showing e arly p soriatic arthritis chang e s with p e riarticular e rosions se e n at the d istal inte rp halang e al joints. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

ETIO LO GY AND PATHO PHYSIO LO GY Arthritis can be caused by 1 o several mechanisms. • Noninf ammatory arthritis (ie, osteoarthritis) is caused by bony overgrowth (osteophytes) and degeneration o cartilage and underlying bone (Figures 97-2 and 97-3). • Autoimmune arthritis (ie, rheumatoid arthritis, systemic lupus erythematosus [SLE], psoriatic arthritis) is caused by an inappropriate immune response. • Crystalline arthritis (ie, gout, calcium pyrophosphate dehydrate deposition disease) is caused by deposition o uric acid crystals (gout) or

calcium pyrophosphate dehydrate crystals (CPPD) resulting in episodic f ares with periods o remission. • Septic arthritis is most commonly caused by bacteria (Neisseria gonorrhoeae, Staphylococcus, or Streptococcus; also gram-negative bacilli in immunocompromised patients and Salmonella in patients with sickle cell disease). Several viral illnesses may also have an associated arthritis. • Postin ectious (reactive) arthritis is caused by an immune reaction several weeks a ter a urethritis or enteric in ection. • Fibromyalgia has an unknown etiology but includes abnormal pain perception processing.

PART 13

a r t h r It IS O Ve r VIe W

FIGURE 97-2 O ste oarthritis in an e ld e rly woman with He b e rd e n nod e s at the d istal inte rp halang e al joints. The re is some swe lling b e g inning at the p roximal inte rp halang e al joints cre ating Bouchard nod e s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIAGNO SIS

MUSCULO SKELETAL/ RHEUMATO LO GIC

FIGURE 97-4 O ste oarthritis with visib le unilate ral kne e e usion. The e usion was tap p e d and the synovial uid was consiste nt with oste oarthritis. An intraarticular ste ro id inje ctio n was g ive n and p ro vid e d g re at re lie to the p ain and sti ne ss. (Re p ro d uce d with p e rmissio n fro m Richard P. Usatine , MD.)

° RA (see Chapter 99, Rheumatoid Arthritis)—Wrists, metacar-

CLINICAL FEATURES • Two eatures help limit the di erential diagnosis: mono- or polyarticular and inf ammatory or noninf ammatory. ° Monoarticular noninf ammatory—Osteoarthritis, trauma, avascular necrosis ° Monoarticular inf ammatory—In ectious (gonococcal, nongonococcal, Lyme disease) or crystalline (gout or CPPD) ° Polyarticular noninf ammatory—Osteoarthritis ° Polyarticular inf ammatory—Rheumatologic (rheumatoid arthritis [RA], SLE, psoriatic, ankylosing spondylitis [AS], and others) or in ectious (bacterial, viral, postin ectious) or crystalline later in the disease TYPICAL DISTRIBUTIO N • Most commonly a ected joints ° Osteoarthritis (see Chapter 98, Osteoarthritis)—Knees, hips, hands (DIP and proximal interphalangeal [PIP]), and spine (Figures 97-2 to 97-4).

FIGURE 97-3 O ste oarthritis with visib le He b e rd e n (DIP) and Bouchard (PIP) nod e s. (Re p rod uce d with p e rmission from Ricard o Zunig a-Monte s, MD.)

° ° ° ° °

pophalangeal (MCP), PIP, metatarsophalangeal (MTP) early in the disease with larger joints a ected later in the disease (Figures 97-5 and 97-6). Rheumatoid nodules may be ound over the ngers, hands, wrists, or elbows (Figures 97-6 and 97-7). SLE—Hands, wrists, and knees (see Chapter 178, Lupus: Systemic and Cutaneous) (Figure 97-8). AS—Lower back and hips, costosternal junctions, shoulders (see Chapter 101, Ankylosing Spondylitis). Psoriatic arthritis—Hands, eet, knees, spine, sacroiliac; typically with a personal or amily history or psoriasis (Figures 97-9 to 97-11); (see Chapter 100, Psoriatic arthritis). Gonococcal—Migratory with a single joint a ected, such as knee, wrist, ankle, hand, or oot. Lyme disease—Knee and/ or other large joints.

FIGURE 97-5 Rhe umatoid arthritis showing typ ical ulnar d e viatio n at the me tacarp op halang e al joints. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

473

474

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch a pt e r 97

FIGURE 97-8 Long -stand ing lup us e rythe matosus has cause d swan-ne ck d e ormitie s witho ut b one e rosions. This is calle d Jaccoud arthrop athy and is cause d b y synovitis and inïammatory cap sular f b rosis. (Re p rod uce d with p e rmission from Eve re tt Alle n, MD.) FIGURE 97-6 Rhe umatoid arthritis involving the whole up p e r-e xtre mity jo ints with nod ule s on the e lb ow, wrist, and hand joints. (Re p rod uce d with p e rmission from Ricard o Zunig a-Monte s, MD.)

° Gout (see Chapter 105, Gout)—Begins as monoarticular with MTP

joint o the rst toe; hands, ankles, tarsal joints, and knee may also be a ected (Figures 97-12 to 97-14); gout may be present with tophi over any joint; olecranon bursitis can also be the result o gout (Figure 97-15). ° CPPD—Knee, but also seen in shoulder, elbow, wrist, hands, and ankle joints; most patients have polyarticular disease. ° Septic arthritis can involve any joint; acute onset o pain, swelling, and joint immobility; ever may be present; must be recognized and treated immediately as joint destruction occurs within days (Figure 97-16).

FIGURE 97-9 Psoriatic arthritis o b oth kne e s. This p atie nt has asymme tric p soriatic arthritis in his hand s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 97-7 Rhe umatoid arthritis with rhe umatoid nod ule s ove r the PCP jo ints along with d e ormitie s o the d ig its. (Re p rod uce d with p e rmission from Ricard o Zunig a-Monte s, MD.)

FIGURE 97-10 Psoriatic arthritis with d actylitis and sig nif cant d istal inte rp halang e al joint involve me nt. Note the d e struction o the nails. Almost all p atie nts with p soriatic arthritis have nail involve me nt. (Re p rod uce d with p e rmission from Ricard o Zunig a-Monte s, MD.)

a r t h r It IS O Ve r VIe W

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

FIGURE 97-11 Psoriatic arthritis mutilans with se ve re d e struction o the f ng e rs. (Re p rod uce d with p e rmission from Ricard o Zunig a-Monte s, MD.) FIGURE 97-14 Se ve re top hace ous g out with larg e top hi and joint d e structio n o the hand s. (Re p ro d uce d with p e rmissio n fro m Ricard o Zunig aMo nte s, MD.)

FIGURE 97-12 An acute g outy arthritis attack o multip le f ng e r joints in a 75-ye ar-old man with g out. His joints have b e e n p ain ul or 3 we e ks. The e rythe ma o the acute in ammation is e vid e nt. (Re p rod uce d with p e rmission from R. Tre ad we ll, MD.) FIGURE 97-15 O le cranon b ursitis b ilate rally in a man with g out. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 97-13 Se ve re top hace ous g out with chronic g outy arthritis causing hand d e ormitie s and d isab ilitie s. (Re p rod uce d with p e rmission from Jack Re sne ck, Sr., MD.)

FIGURE 97-16 Se p tic le t kne e jo int in a g irl who p re se nte d with kne e p ain, e ve r, and limite d ab ility to amb ulate . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

475

476

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch a pt e r 97

LABO RATO RY TESTING • Not indicated or noninf ammatory arthritis. • In lammatory polyarthritis: Use laboratory tests to supplement the clinical impression. Initial tests to consider include the ollowing: ° ESR or C-reactive protein as a nonspeci c measure o inf ammation. ° Rheumatoid actor or anti-CCP (anti-cyclic citrullinated peptide) antibody when RA is expected. Anti-CCP antibody is more sensitive and speci c than rheumatoid actor. ° Antinuclear antibody (ANA), anti–double-stranded DNA (dsDNA) and anti-Ro when SLE is expected. ° Human leukocyte antigen (HLA)-B27 when AS is expected. ° Serum uric acid can be used, especially to ollow hypouricemic therapy in patients with gout; levels can be normal or low during an attack. • Joint aspiration: ° Synovial f uid analysis is critical when septic or crystalline arthritis are suspected. ° Assess or clarity/ color, cell count, crystals, and culture. Gram stain may give quick in ormation, but a culture should also be done. I there is clinical suspicion or septic arthritis, empiric antibiotics should be started even i the Gram stain is negative. ° White blood cell (WBC)—Normal < 200 cells/ µL; nonin lammatory arthritis < 2000 cells/ µL; in lammatory, crystalline, or septic arthritis > 2000 cells/ µL, o ten 30,000 to 50,000 cells/ µL. ° Crystals—Monosodium urate (gout) are needle shaped and negatively bire ringent; CPPD are rhomboid-shaped positively bire ringent. ° Culture—Gonococcal arthritis synovial f uid cultures can be negative in two-thirds o cases (synovial biopsy is positive); tuberculosis, ungal, and anaerobic in ections may also be di cult to identi y on culture. IMAGING • Osteoarthritis—Osteophytes, sclerosis, narrowed joint space (Figure 97-17).

FIGURE 97-17 Rad iog rap h showing o ste oarthritis o the kne e with asymme tric joint sp ace narrowing . (Re p rod uce d with p e rmissio n from Ricard o Zunig a-Monte s, MD.)

DIFFERENTIAL DIAGNO SIS • Bursitis is inf ammation o a bursa. Pain and tenderness is localized to the bursa. Common locations include subdeltoid, trochanteric, and olecranon. • Tendinitis is inf ammation o a tendon that produces a localized pain aggravated by stretching o the a ected tendon. • Inf ammatory myopathy or myositis is inf ammation o the muscle most commonly caused by an autoimmune or in ectious process. Pain is in the muscles instead o the joints.

• Rheumatoid arthritis—So t-tissue swelling, erosions, and loss o joint space; severe destruction and subluxation in advanced disease. MRI changes may appear rst and include synovitis, e usions, and bone marrow changes.

• Polymyalgia rheumatica is a systemic inf ammatory disease with aching and sti ness in the torso and proximal extremities. Pain is in the muscles, but synovitis or tenosynovitis may also be present. Passive joint range o motion is preserved. ESR is elevated. Normocytic anemia and thrombocytosis can be present.

• SLE—So t-tissue swelling; erosions are rare and joint de ormities are uncommon.

• Fibromyalgia—Widespread pain not limited to joints. Joint swelling is absent. Laboratory tests and imaging i obtained are normal.

• AS—Symmetric sacroiliitis, erosions, sclerosis; active sacroiliitis is best seen on MRI. • Psoriatic arthritis—Erosions with adjacent proli eration, “pencil-incup” de ormity, osteolysis, digit telescoping, asymmetric sacroiliitis.

MANAGEMENT

• Gout—Only so t-tissue swelling until advanced disease when erosions with sclerotic margins may be present.

The goals o treatment are to control pain, maximize unction, improve quality o li e, and, or inf ammatory causes, minimize joint damage.

• CPPD—Can mimic other types o arthritis; chondrocalcinosis, linear, or punctate radiodense deposits in cartilage or menisci may be present.

NO NPHARMACO LO GIC

Table 97-1 provides a comparison o psoriatic arthritis with RA, osteoarthritis, and AS.

• Recommend an exercise program. Aerobic exercise, strength training, or both improves pain and unction in arthritis and other rheumatic diseases. 3 SO R

a r t h r It IS O Ve r VIe W

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

TABLE 97-1 Comp arison o Psoriatic Arthritis with Rhe umatoid Arthritis, O ste oarthritis, and Ankylosing Sp ond ylitis

PsA

RA

OA

AS

Pe rip he ral d ise ase

Asymme tric

Symme tric

Asymme tric

No

Sacroiliitis

Asymme tric

No

No

Symme tric

Sti ne ss

In morning and /or with immob ility

In morning and /or with immob ility

With activity

Ye s

Fe male -to-male ratio

1:1

3:1

Hand / oot more common in e male p atie nts

1:3

Enthe sitis

Ye s

No

No

No

Hig h-tite r rhe umatoid actor

No

Ye s

No

No

HLA association

CW6, B27

DR4

No

B27

Nail le sions

Ye s

No

No

No

Psoriasis

Ye s

Uncommon

Uncommon

Uncommon

Ab b re viations: AS, ankylosing sp ond ylitis; O A, oste oarthritis; PsA, p soriatic arthritis; RA, rhe umatoid arthritis. Ad ap te d rom Gottlie b A, Korman NJ, Gord on KB, e t al. Guid e line s o care or the manag e me nt o p soriasis and p soriatic arthritis: Se ction 2. Psoriatic arthritis: ove rvie w and g uid e line s o care or tre atme nt with an e mp hasis on the b iolog ics. J Am Acad De rmatol. 2008;58(5):851-864.

• Splints or braces may be used to o f oad stress on a particular joint.

PATIENT RESO URCES

• Weight loss reduces joint load or weight-bearing joints.

• Centers for Disease Control and Prevention: Information on the Arthritis Sel -Management Program is available in English and Spanish—http:/ / www.cdc.gov/ arthritis/ interventions/ self_manage.htm# 1.

REFERRAL O R HO SPITALIZATIO N • Hospitalize patients with suspected septic arthritis and begin empiric therapy with appropriate intravenous antibiotics. • Re er patients in whom the diagnosis is unclear, especially i RA is suspected as early diagnosis and treatment improves outcomes. • Re er patients in whom surgical management is indicated.

PRO GNO SIS

PRO VIDER RESO URCES

• Centers for Disease Control and Prevention: Information on arthritis and other rheumatologic conditions—http:/ / www.cdc.gov/ arthritis/ . • American College of Rheumatology: Clinical support, including practice guidelines, classi cation criteria, and clinical orms— http:/ / www.rheumatology.org/ practice/ clinical/ index.asp.

Prognosis depends on the type o arthritis as well as psychosocial actors and socioeconomic status. REFERENCES

FO LLO W-UP Acute arthritis should be ollowed closely until resolution. Chronic arthritis is managed as other chronic diseases with the requency o ollow-up dependent upon the type o arthritis and the severity o the disease.

PATIENT EDUCATIO N For chronic arthritic conditions, the goals o treatment are to control pain, maximize unction, improve quality o li e, and minimize joint damage. Sel -management is an important part o chronic arthritic conditions.

1. Centers or Disease Control and Prevention (CDC). Prevalence o doctordiagnosed arthritis and arthritis-attributable activity limitation—United States, 2007-2009. MMWR Morb MortalWkly Rep. 2010;59(39):1261-1265. http:/ / www.cdc.gov/ mmwr/ preview/ mmwrhtml/ mm5939a1.htm?s_ cid=mm5939a1_w. Accessed May 1, 2014. 2. Yelin E, Murphy L, Cisternas MG, et al. Medical care expenditures and earnings losses among persons with arthritis and other rheumatic conditions in 2003, and comparisons to 1997. Arthritis Rheum. 2007;56(5): 1397-1407. 3. Kelley GA, Kelley KS, Hootman JM, Jones DL. E ects o community-deliverable exercise on pain and physical unction in adults with arthritis and other rheumatic diseases: a meta-analysis. Arthritis Care Res (Hoboken). 2011;63(1):79-93.

477

478

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

98 O STEO ARTHRITIS Jana K. Zaud ke , MD He id i Chumle y, MD

PATIENT STO RY A 70-year-old woman presents with pain and swelling in the joints o both hands, which impedes her normal activities. Her pain is better in the morning a ter resting and worse a ter she has been working with her hands. She denies sti ness. On examination, you nd bony enlargement o some distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints on both hands (Figure 98-1). Radiographs con rm the presence o Heberden and Bouchard nodes. She begins taking 1 g o acetaminophen twice a day and has signi cant improvement in her pain and unction.

INTRO DUCTIO N Osteoarthritis is the most common type o arthritis. It involves degeneration o the articular cartilage accompanied by osteophytes (hypertrophic bone changes) around the joints. Osteoarthritis leads to pain in the joints with movement and relie with rest.

Ch a pt e r 98

• In the Framingham cohort (mean age 71 years at baseline), women and men developed symptomatic knee osteoarthritis at the rate o 1% and 0.7% per year, respectively. 1 • Risk o developing osteoarthritis increases with knee injury in adolescence or adulthood (relative risk [RR] = 2.95) and obesity (RR = 1.51-2.07). 1 • Occupational physical activity and abnormal joint loading also increase the risk. 1,2

ETIO LO GY AND PATHO PHYSIO LO GY • Biomechanical actors and inf ammation upset the balance o articular cartilage biosynthesis and degradation. • Chondrocytes attempt to repair the damage; eventually, however, enzymes produced by the chondrocytes digest the matrix and accelerate cartilage erosion. • Inf ammatory molecules related to cytokine production, prostaglandin, and arachidonic acid metabolism may be involved in susceptibility to osteoarthritis. 3

RISK FACTO RS • Advanced age • Female gender • Genetics

SYNO NYMS Degenerative joint disease.

• Obesity • Knee injury in adolescence and adulthood • Abnormal joint loading • Occupational history

EPIDEMIO LO GY DIAGNO SIS • Osteoarthritis is the most common type o arthritis, a ecting 10% o men and 13% o women age 60 years or older. 1,2 • Incidence and prevalence will likely increase given the obesity epidemic and the aging o the population. 2

The American College o Rheumatology uses the ollowing criteria or the most common joints involved in osteoarthritis. • Knee—Knee pain, osteophytes on radiograph, and 1 o 3: age older than 50 years, sti ness less than 30 minutes, or crepitus on physical examination (sensitivity = 91%, speci city = 86%). 4 • Hip—Hip pain and 2 o 3: erythrocyte sedimentation rate (ESR) less than 20 mm/ h; emoral or acetabular osteophytes by radiograph; superior, axial, or medial joint space narrowing by radiograph (sensitivity = 89%, speci city = 91%). 5 • Hand—Hand pain, aching, or sti ness and 3 o 4: hard tissue enlargement o 2 or more DIP joints, ewer than 3 swollen metacarpophalangeal (MCP) joints, hand tissue enlargement o 2 or more selected joints, de ormity o 1 or more selected joints. Selected joints include second and third DIP, second and third PIP, rst carpometacarpal (CMC) on both hands (sensitivity = 94%, speci city = 87%). 6 CLINICAL FEATURES

FIGURE 98-1 Bony e nlarg e me nt o some d istal inte rp halang e al (DIP) and p roximal inte rp halang e al (PIP) joints consiste nt with He b e rd e n (DIP) and Bouchard (PIP) no d e s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Typically, joint pain is worsened with movement and relieved by rest. A small subset may demonstrate inf ammatory symptoms including prolonged sti ness. • Loss o unction (ie, impaired gait with knee or hip osteoarthritis, impaired manual dexterity with hand osteoarthritis).

O St e O a r t h r It IS

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

FIGURE 98-3 O ste oarthritis o the kne e causing joint sp ace narrowing , scle rosis, and b ony sp urring in all 3 comp artme nts o the rig ht kne e , most p ronounce d in the me d ial comp artme nt. (Re p rod uce d with p e rmission from He id i Chumle y, MD.)

FIGURE 98-2 Joint sp ace narrowing , marg inal oste op hyte s, and He b e rd e n nod e s at the d istal inte rp halang e al joints o the se cond throug h f th f ng e rs. (Re p rod uce d with p e rmission from He id i Chumle y, MD.)

• Radicular pain when vertebral column osteophytes impinge nerve roots. • Bony enlargement o the DIP joints (Heberden nodes) or PIP joints (Bouchard nodes) (Figure 98-1). TYPICAL DISTRIBUTIO N Most common joints a ected include knees, hands, hips, and back.

• Seronegative spondyloarthropathies—Asymmetric joint involvement, spine o ten involved (see Chapter 101, Ankylosing Spondylitis). • Reactive arthritis—History o in ection, sexually transmitted disease, or bowel complaints. The patient may have conjunctivitis, iritis, urethritis in addition to joint pain and arthritis (see Chapter 153, Reactive Arthritis). • Rheumatoid arthritis—Symmetric so t-tissue swelling in distal joints, sti ness a ter inactivity, positive rheumatoid actor. Ulnar deviation o the ngers at the MCP joints is a distinct nding in rheumatoid arthritis (Figure 98-6; Chapter 99, Rheumatoid Arthritis). • Bursitis—Pain at 1 site, o ten increased with direct pressure.

LABO RATO RY TESTING Not typically indicated. Normal ESR and synovial f uid white blood cell (WBC) count less than 2000/ mm. 3,4 IMAGING Loss o joint space or osteophytes on radiographs (Figures 98-2 to 98-5).

DIFFERENTIAL DIAGNO SIS Musculoskeletal pain can also be caused by: • Connective tissue diseases (scleroderma and lupus) that have other speci c systemic signs. • Fibromyalgia—Pain at trigger points instead o joints. • Polyarticular gout—Erythematous joints and crystals in joint aspirate (see Chapter 105, Gout). • Polymyalgia rheumatica—Proximal joint pain without de ormity, elevated ESR. (see Chapter 113, Polymyalgia rheumatic).

FIGURE 98-4 Articular sp ace narrowing , scle rosis, and sub chond ral cyst ormation o b oth hip s b e cause o oste oarthritis. (Re p ro d uce d with p e rmission from Che n MYM, Pop e TL Jr, O tt DJ. Basic Rad iolog y. McGraw-Hill; 2004:189, Fig ure 7-34.)

479

480

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch a pt e r 98

TABLE 98-1 Nonp harmacolog ic O p tions or O ste oarthritis

We ig ht loss (i ove rwe ig ht) Ae rob ic e xe rcise Rang e -o -motion e xe rcise s Muscle stre ng the ning Assistive d e vice s or walking Yog a and Tai Chi Sa e shoe s Late ral-we d g e d insole s ( or g e nu varum) b racing Physical and occup ational the rap y Joint p rote ction such as b race s Assistive d e vice s or activitie s o d aily living Arthritis Found ation Se l -Manag e me nt Prog ram Social sup p ort • Recommend weight loss or knee or hip osteoarthritis. Weight loss may not improve current pain, but may slow progression and can be recommended or numerous other health reasons. 8 SO R C • Consider a knee brace that alters knee mechanics (ie, Counter orce brace). 9 SO R B FIGURE 98-5 Loss o d isc sp ace and ace t arthrop athy at L5-S1 and small oste op hyte s, b e st se e n on L4 and L5. The se chang e s are cause d b y oste oarthritis. (Re p rod uce d with p e rmission from He id i Chumle y, MD.)

MANAGEMENT NO NPHARMACO LO GIC Table 98-1 lists the nonpharmacologic options or management o osteoarthritis. • Recommend therapeutic land-based or aquatic exercise to maintain range o motion and strengthen muscles surrounding a ected joints. 7,8 SO R

MEDICATIO NS Table 98-2 lists the pharmacologic therapy or osteoarthritis. • Prescribe acetaminophen (2-4 g/ day) or pain relie in patients at higher risk or GI complications. In a pooled analysis, acetaminophen improved pain by 5%, number needed to treat (NNT) 4 to 14. 10 SO R • Prescribe an NSAID or moderate-to-severe hip or knee osteoarthritis in patients who are at low risk or GI complications. GI bleeding is a signi cant risk to many elderly patients with osteoarthritis (see Table 98-3). A 2006 Cochrane review ound NSAIDs were slightly more e ective than acetaminophen, although more likely to produce adverse GI events. 10 SO R • I NSAIDs are to be used in patients with risk actors (see Table 98-3), consider giving misoprostol or a proton pump inhibitor or protection. 8 Note that H2-blockers may decrease gastric symptoms rom NSAIDs but are not protective against GI bleeding. • Consider opioid analgesics or patients with severe osteoarthritis who have not responded to NSAIDs (be care ul to not prescribe narcotics to patients in recovery rom substance abuse). 8 SO R C TABLE 98-2 Pharmacolog ic O p tions or O ste oarthritis

O ral • Ace taminop he n • CO X-2-sp e cif c inhib itor • NSAID p lus a p roton p ump inhib itor • O p ioid s (e g , hyd rocod one ) • Salsalate • Tramad ol Top ical • Me thylsalicylate • Top ical NSAID (e g , d iclo e nac g e l) FIGURE 98-6 Rhe umatoid arthritis showing ulnar d e viation o the f ng e rs at the me tacarp op halang e al joints. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

Intraarticular • Glucocorticoid s (e g , triamcinolone ) • Hyaluronic acid

O St e O a r t h r It IS

TABLE 98-3 Risk Facto rs o r Up p e r GI Ad ve rse E e cts in Pe rso ns Taking NSAIDs

• • • • • • •

Ag e 65 ye ars or old e r Anticoag ulants Comorb id me d ical cond itions History o p e p tic ulce r d ise ase History o up p e r g astrointe stinal b le e d ing O ral ste roid s Taking NSAIDs with an e mp ty stomach

• Consider a topical NSAID rather than an oral NSAID or hand or knee osteoarthritis, especially in patients 75 years o age or older. SO R C There is not yet enough data to recommend topical NSAID or hip osteoarthritis. 8 • Consider topical capsaicin 0.025% cream 4 times a day or hand osteoarthritis. 2 SO R B • Consider an intraarticular corticosteroid injection or acute pain related to knee or hip osteoarthritis. 8,11 SO R B • Consider an intra-articular hyaluronic injection or symptomatic chronic knee osteoarthritis. A 2006 Cochrane review o 76 clinical trials concluded that these injections were e ective or treating knee osteoarthritis. 11 SO R CO MPLEMENTARY AND ALTERNATIVE THERAPY • Consider participation in tai chi programs or knee or hip osteoarthritis. 8 • Consider traditional Chinese acupuncture or transcutaneous electrical stimulation or patients with knee osteoarthritis who choose not to have or are not candidates or a total-knee arthroplasty. 8 • In their newest guidelines, the American College o Rheumatology does not recommend use o chondroitin sul ate and glucosamine or osteoarthritis. 8 REFERRAL Re er patients who do not respond to conservative therapy to • Any physician with experience doing joint injections i this is not within your skill set • Rheumatologist or evaluation and treatment • Orthopedic surgeon or evaluation or arthroplasty or joint replacement

FO LLO W-UP There are no recommended intervals or ollow-up; however, it is reasonable to see patients periodically to assess pain management and unction.

PATIENT EDUCATIO N Osteoarthritis is a chronic, progressive disease. Nonpharmacologic and pharmacologic therapies can reduce pain and preserve unction.

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC PATIENT RESO URCES

• Arthritis Foundation. Osteoarthritis—http:/ / www.arthritis.org/ osteoarthritis.php. • PubMed Health. Osteoarthritis—http:/ / www.ncbi.nlm.nih.gov/ pubmedhealth/ PMH0001460/ . • FamilyDoctor.org. Osteoarthritis—http:/ / familydoctor.org/ familydoctor/ en/ diseases-conditions/ osteoarthritis.html. PRO VIDER RESO URCES

• American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the Medical Management of Osteoarthritis of the Hip and Knee—http:/ / www.rheumatology.org/ practice/ clinical/ guidelines/ oa-mgmt.asp.

REFERENCES

1. Sharma L, Kapoor D, Issa S. Epidemiology o osteoarthritis: an update [review]. Curr Opin Rheumatol. 2006;18(2):147-156. 2. Zhang Y, Jordan JM. Epidemiology o osteoarthritis. Clin Geriatr Med. 2010;26(3):355-369. 3. Valedez AM, Spector TD. The clinical relevance o genetic susceptibility to osteoarthritis. Best Pract Res Clin Rheumatol. 2010;24(1):3-14. 4. American College o Rheumatology. http:/ / www.rheumatology .org/ practice/ clinical/ classi cation/ oaknee.asp. Accessed April 6, 2012. 5. http:/ / www.rheumatology.org/ practice/ clinical/ classi cation/ oa-hip/ oahip.asp. Accessed April 6, 2012. 6. http:/ / www.rheumatology.org/ practice/ clinical/ classi cation/ oa-hand/ oshand.asp. Accessed April 6, 2012. 7. Ottawa panel evidence-based clinical practice guidelines or therapeutic exercises and manual therapy in the management o osteoarthritis [review] [178 re s]. PhysTher. 2005;85:907-971. 8. Hochberg MC, Altman RD, April KT, et al. American College o Rheumatology 2012 recommendations or the use o nonpharmacologic and pharmacologic therapies in osteoarthritis o the hand, hip and knee. Arthritis Care Res. 2012;64(4):465-474. 9. Barnes CL, Cawley PW, Hederman B. E ect o CounterForce brace on symptomatic relie in a group o patients with symptomatic unicompartmental osteoarthritis: a prospective 2-year investigation. Am J Orthop. 2002;31:396-401. 10. Towheed TE, Maxwell L, Judd MG, et al. Acetaminophen or osteoarthritis. Cochrane Database Syst Rev. 2006 Jan 25;(1): CD004257. 11. Sinusas, K. Osteoarthritis: diagnosis and treatment. Am Fam Physician. 2012;85(1):49-56.

481

482

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch a pt e r 99

99 RHEUMATO ID ARTHRITIS He id i Chumle y, MD

PATIENT STO RY A 79-year-old woman with late-stage rheumatoid arthritis comes or routine ollow-up (Figures 99-1 to 99-3). She began having hand pain and sti ness approximately 40 years ago. She took nonprescription medications or pain or approximately 10 years be ore seeing a physician. She was diagnosed with rheumatoid arthritis on the basis o combination o clinical, laboratory, and radiograph ndings. She was treated with prednisone and tried most o the disease-modi ying agents as they became available; however, her disease progression continued. Approximately 10 years ago, she began having increased oot pain and di culty walking. Today, she works with a multidisciplinary team to control pain and preserve hand unction and independence.

INTRO DUCTIO N Rheumatoid arthritis (RA) is a progressive chronic illness that causes signi cant pain and disability. RA is a polyarticular inf ammatory arthritis that causes symmetrical joint pain and swelling and typically involves the hands. Early recognition and treatment with nonbiologic and/ or biologic disease-modi ying antirheumatologic agents (DMARDs) can induce remission and preserve unction.

EPIDEMIO LO GY • RA is ound in 0.8% o the adult population worldwide. 1 • It is more than twice as common in women as compared to men (54 per 100,000 vs. 25 per 100,000). 1 • Typical age o onset is 30 to 50 years. 1

FIGURE 99-1 Ulnar d e viation at me tacarp op halang e al joints in ad vance d rhe umatoid arthritis. Also note the swe lling at the d istal inte rp halang e al jo ints, se e n b e st on the f rst f ng e r. (Re p ro d uce d with p e rmissio n fro m Richard P. Usatine , MD.)

FIGURE 99-2 Rhe umatoid arthritis in the o ot o a 79-ye ar-o ld wo man with sub luxatio n o the f rst me tatarso p halang e al jo int. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

ETIO LO GY AND PATHO PHYSIO LO GY • Genetic predisposition coupled with an autoimmune or in ectiontriggering incident. • Synovial macrophages and broblasts proli erate, leading to increased lymphocytes and endothelial cells. • Increased cellular material occludes small blood vessels, causing ischemia, neovascularization, and inf ammatory reactions. • Inf amed tissue grows irregularly, causing joint damage. • Damage causes urther release o cytokines, interleukins, proteases, and growth actors, resulting in more joint destruction and systemic complications including a higher risk or cardiovascular disease

FIGURE 99-3 De viation at the me tatarsop halang e al joints rom b ony d e struction in ad vance d rhe umatoid arthritis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

r h e UMa t O ID a r t h r It IS

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

RISK FACTO RS Genetic predisposition signi ed by a positive amily history.

DIAGNO SIS The 2010 American College o Rheumatology/ European League Against Rheumatism classi cation criteria uses a scoring system to designate patients as de nite RA. A score o 6 or greater out o 10 meets criteria or de nite RA. 2 • Joint involvement—1 large joint (0 points); 2 to 10 large joints (1 point); 1 to 3 small joints with or without large joints (2 points); 4 to 10 small joints with or without large joints (3 points); more than 10 joints with at least 1 small joint (5 points). • Serology—Negative rheumatoid actor (RF) and anti-cyclic citrullinated peptide (anti-CCP) (0 points); low positive RF or anti-CCP (2 points); high positive RF or ACPA (3 points). • Acute-phase reactants—Normal C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) (0 points); abnormal CRP or ESR (1 point). • Duration o symptoms—Less than 6 weeks (0 points); 6 or more weeks (1 point). American Rheumatism Association criteria (with positive likelihood ratio abbreviated as LR+ ):3

FIGURE 99-5 Rhe umatoid no d ule s in the hand s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Symmetrical involvement o 1 o these: wrist, PIP, MCP, elbow, knee, ankle, MTP (LR+1.2). • Subcutaneous nodules (LR+3.0) (Figures 99-5 and 99-6). • Positive serum RF (LR+ 8.4). • Osteopenia or erosion o surrounding joints on hand or wrist lms (LR+ 11) (Figures 99-7 and 99-8). CLINICAL FEATURES

• Sti ness around joint or 1 hour a ter inactivity (LR+ 1.9).

Joint pain and swelling, polyarticular and symmetrical.

• Three or more o these have so t-tissue swelling—Wrist, proximal interphalangeal (PIP), metacarpophalangeal (MCP), elbow, knee, ankle, metatarsophalangeal (MTP) (LR+ 1.4).

TYPICAL DISTRIBUTIO N

• Hand joints involved (LR+ 1.5) (Figures 99-1, 99-4, and 99-5).

• Commonly involved joints include wrist, PIP, MCP, elbow, knee, ankle, and MTP.

• Hands are typically involved (Figures 99-1, 99-4, and 99-5).

• Subcutaneous nodules (Figures 99-5 and 99-6).

FIGURE 99-4 Ulnar d e viation at me tacarp op halang e al joints se e n in a 64-ye ar-old woman with rhe umatoid arthritis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 99-6 Rhe umatoid no d ule s on the arm o a p atie nt with rhe umatoid arthritis. (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

483

484

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch a pt e r 99

DIFFERENTIAL DIAGNO SIS RA can mimic many systemic diseases and should be di erentiated rom the ollowing:1 • Connective tissue diseases (scleroderma and lupus), which have other speci c systemic signs. • Fibromyalgia—Pain at trigger points instead o joints. • Hemochromatosis—Abnormal iron studies and skin changes. • In ectious endocarditis—Heart murmurs, high ever, risk actors, such as IV drug use. • Polyarticular gout—Erythematous joints and crystals in joint aspirate. • Polymyalgia rheumatica—Proximal joint pain without de ormity. • Seronegative, spondyloarthropathies—Asymmetric joint involvement, spine o ten involved. FIGURE 99-7 Hand rad iog rap hs in long -stand ing rhe umatoid arthritis d e monstrating carp al d e struction, rad iocarp al joint narrowing , b ony e rosion (arrowhe ad s), and so t-tissue swe lling . (From Che n MYM, Pop e TL Jr, O tt DJ . Basic Rad io lo g y. Ne w Yo rk: McGraw-Hill; 2004:194, Fig ure 7-42. Co p yrig ht 2004.)

• Reactive arthritis—History o in ection, sexually transmitted disease, or bowel complaints.

MANAGEMENT LABO RATO RY TESTING • RF (negative in 30% o patients; positive in many connective tissue, neoplastic, and in ectious diseases). • Anti-CCP, high speci city, o ten presents be ore de nitive diagnosis can be made; presence predicts arthritis development. • CRP (> 0.7 pg/ mL) or ESR (> 30 mm/ h). • Complete blood count (normocytic or microcytic anemia, thrombocytosis). IMAGING Hand or wrist radiographs may show so t tissue swelling, osteopenia, erosions, subluxations, and de ormities (Figures 99-7 and 99-8).

Target outcome is remission through use o disease-modi ying agents. Monitor or complications: • Patients with RA are twice as likely to have serious GI complications; monitor care ully. • Anemia—25% will respond to iron therapy. • Cancer—Two- old increase risk o lymphomas and leukemias. • Cardiac complications such as pericarditis or pericardial e usion (30% at diagnosis). • Cervical spine disease—Atlas instability; care ul with intubation and avoid f exion lms a ter trauma until atlas visualized. NO NPHARMACO LO GIC • Use o multidisciplinary team improves outcomes. 4 SO R B • Exercise improves aerobic capacity and strength without increases in pain or disease activity. 5 SO R B MEDICATIO NS • NSAIDs can be used or pain control, 5 SO R progression and should not be used alone.

but do not alter disease

• Systemic corticosteroids relieve pain and slow progression, 5 SOR but have serious side e ects and should be used at lowest dose possible with added bone protection (eg, calcium and vitamin D or a bisphosphonate). • Nonbiologic DMARDs such as methotrexate, lef unomide, hydroxychloroquine, sul asalazine, and minocycline reduce disease progression and should be considered in all patients without contraindications. SOR

FIGURE 99-8 Se ve re chang e s o late rhe umatoid arthritis includ ing rad iocarp al joint d e struction, ulnar d e viation, e rosion o the ulnar styloid b ilate rally, d islocation o the le t thumb PIP jo int, and d islocatio n o the rig ht ourth and f th MCP joints. (Rep roduce d with pe rmission from Brunicardi CF, And e rsen DK, Billiar TR, e t al. Schwartz’s Princip le s o f Surg e ry. Ne w Yo rk: McGraw-Hill; 2005:1666, Fig ure 42-40. Cop yrig ht 2005.)

• Biologic DMARDs, such as antitumor necrosis actor (TNF) drugs, rituximab, abatacept, adalimumab, etanercept, and inf iximab, reduce disease progression and should be considered in patients with high disease activity and poor prognostic eatures. SO R C CO MPLEMENTARY AND ALTERNATIVE THERAPY Diet modi cations—Omega-3 polyunsaturated atty acids may decrease anti-inf ammatory medication use. 1 SO R B

r h e UMa t O ID a r t h r It IS

REFERRAL • Re er patients with new diagnosis o or with a suspicion o RA to a physician experienced in the use o nonbiologic and biologic DMARDs. Recommendations or initiating DMARDs are based on6 • Disease duration • Presence o poor prognostic actors ( unctional limitations, extraarticular disease, positive RF and/ or anti-CCP bony erosions) • Classi cation o low, moderate, or high disease activity, based on one o several validated instruments (eg, Rheumatoid Arthritis Disease Activity Index) DMARDs reduce disease progression, but have several contraindications and must be ollowed closely. • Do not start nonbiologic or biologic DMARDs when the patient has an active bacterial in ection, active or latent (be ore preventive therapy is initiated) tuberculosis (TB), acute hepatitis B or C, active herpes zoster, or a systemic ungal in ection. 6 • Avoid DMARDs i white blood cell (WBC) count is less than 3000/ mm3 or platelets are under 50,000/ mm3, New York Heart Association class III or IV heart ailure, or liver transaminases more than twice the normal value. 6 • Start methotrexate or lef unomide monotherapy or any disease duration, with or without poor prognostic actors, and any classi cation o disease activity. 6 • Combination DMARD therapy (eg, methotrexate [MTX] and sul asalazine) may be used in patients with any duration o disease, poor prognostic eatures, and moderate or high disease activity. 6 • Consider biologic DMARDs or patients with any disease duration, high disease activity, and poor prognostic eatures. Etanercept, inf iximab, and adalimumab improve unction and quality o li e as monotherapy or in combination with nonbiologic DMARDs. 6

PRO GNO SIS • Poor prognostic eatures include unctional limitations, extraarticular disease, positive RF and/ or anti-CCP, and bony erosions. 6 • RA patients have an increased risk o cardiovascular disease.

FO LLO W-UP Multidisciplinary ollow-up with primary care, rheumatologist, occupational and physical therapists, and patient educators improves outcomes.

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC PATIENT EDUCATIO N RA is a chronic illness. Twenty to 40 percent o patients will have remission with therapy. Early treatment can prevent complications and allow the person to maintain unction. It is best to stay active and exercise to the best o your ability. PATIENT RESO URCES

• Information on RA is available at http:/ / www .rheumatoidarthritis.com/ ra/ and http:/ / www.ra.com/ . • American College of Rheumatology. Rheumatoid Arthritis—http:/ / www.rheumatology.org/ practice/ clinical/ patients/ diseases_and_conditions/ ra.asp. PRO VIDER RESO URCES

• Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations or the use o nonbiologic and biologic disease-modi ying antirheumatic drugs in RA. Arthritis Rheum 2008;59(6):762-784—http:/ / www.rheumatology .org/ practice/ clinical/ guidelines/ recommendations .pdf.

REFERENCES 1. Rindf eisch JA, Muller D. Diagnosis and management o rheumatoid arthritis. Am Fam Physician. 2005;72(6):1037-1047, 1049-1050. 2. American College o Rheumatology/ European League Against Rheumatism. 2010 Rheumatoid arthritis classi cation criteria. Arthritis Rheum. 2010;62(9):2569-2581. 3. Saraux A, Berthelot JM, Chales G, et al. Ability o the American College o Rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classi cation o these patients two years later. Arthritis Rheum. 2001;44(11):2485-2491. 4. Vliet Vlieland TP, Breedveld FC, Hazes JM. The 2-year ollow-up o a randomized comparison o in-patient multidisciplinary team care and routine out-patient care or active rheumatoid arthritis. Br J Rheum. 1997;36(1):82-85. 5. American College o Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines or the management o rheumatoid arthritis: 2002 Update. [see comment]. Arthritis Rheum. 2002;46(2):328-346. 6. Saag KG, Teng GG, Patkar NM, et al. American College o Rheumatology 2008 recommendations or the use o nonbiologic and biologic disease-modi ying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59(6):762-784.

485

486

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

100 PSO RIATIC ARTHRITIS Gina R. Chacon, MD Richard P. Usatine , MD

PATIENT HISTO RY

Ch a pt e r 100

INTRO DUCTIO N Psoriatic arthritis (PsA) is common in patients with psoriasis and is associated with signi cant morbidity and decreased quality o li e. 1 PsA can be disabling, with radiographic damage noted in 7% to 47% o patients at a median interval o 2 years despite clinical improvement with standard disease-modi ying antirheumatic therapy. 2

A 19-year-old man presents with psoriatic plaques covering his body rom head to lower legs; he reports pain in his ngers, wrists, ankles, and eet or the past month. He states that it is pain ul to walk. On physical examination, it is noted that he has plaques covering 80% o his body sur ace area, nail pits, and swelling o his ankles and some ngers (Figure 100-1). There is no question that the patient has plaque psoriasis, so a skin biopsy is not needed. Plain lms o the hands, ankles, and eet show nothing more than so t-tissue swelling. The patient still has psoriatic arthritis (PsA) even though it is too early to see bone changes in the radiographs. The patient is initially treated with topical steroid ointments while baseline laboratory tests are made, and a puri ed protein derivative (PPD) antigen is used to test or tuberculosis. Methotrexate is started when the laboratory tests show no liver disease and there is a negative PPD test. The joint pains and plaque psoriasis improved over time.

B

A

C

FIGURE 100-1 A. Ne w-onse t p laq ue p soriasis in a 19-ye ar-old man. B. He has sig nif cant ankle and oot p ain with minimal joint swe lling on e xamination. C. The re is te nd e rne ss and swe lling in the f ng e r joints e ve n thoug h the rad iog rap hs d o not show p soriatic arthritis chang e s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

pSO r Ia t IC a r t h r It IS

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

EPIDEMIO LO GY • Psoriasis a ects approximately 2% to 3% o the population in the United States and over 125 million people worldwide. 3 • The exact proportion o patients with psoriasis who will develop PsA is an area o signi cant controversy, with studies demonstrating a range rom 6% to 10% in broadly representative population-based studies to as high as 42% o patients with psoriasis in clinic-based populations. 4 • The prevalence o PsA increases in patients with more extensive skin disease. In the general population o the United States, 5 it has been estimated to be 0.1% to 0.25%. • PsA can develop at any time rom childhood on, but or the majority o patients, it presents between the ages o 30 and 50 years. 4 • Caucasians are more requently a ected with PsA than any other racial or ethnic groups. 6 • PsA a ects men and women equally. 7

ETIO LO GY/ PATHO PHYSIO LO GY Psoriasis is an inf ammatory immune-based disorder with a genetic predisposition. 8,9

DIAGNO SIS • Clinicians can o ten diagnose psoriasis and PsA based on clinical history, physical examination, and radiography o joints (see Chapters 97, Arthritis Overview; 150, Psoriasis; 193, Psoriatic Nails). • In challenging cases, skin histopathology can be help ul in distinguishing psoriasis rom other types o skin diseases. • Full-body skin examination should include the nails and scalp. Common eatures o psoriasis may include the ollowing: ° characteristic morphology o erythema, scaling, and induration ° scalp involvement ° nail involvement (pitting, onycholysis, crumbling, or oil spots) olds ° involvement o the intertriginous 7 amily history o psoriasis °

FIGURE 100-2 Achille s e nthe sop athy in a mid d le -ag e d woman with long stand ing p soriasis. She p re se nte d with p ain, swe lling , and te nd e rne ss ove r the Achille s te nd on. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PHYSICAL EXAMINATIO N • Examine those joints that are reported to be pain ul or sti . Patients with PsA show tender and swollen joints. 4 • Dactylitis, or “sausage digit,” is a combination o enthesitis o the tendons and ligaments along with synovitis involving a whole digit (Figure 100-3). 4 • Plaque psoriasis appears as sharply marginated, erythematous patches or plaques with a characteristic silvery-white scale. 11 Lesions may initially mani est as erythematous, scaly papules that coalesce to orm plaques.

HISTO RY/ SYMPTO MS • A ected individuals with plaque psoriasis o ten present with chronic, recurrent, erythematous, scaly patches and plaques. PsA tends to persist or months to years, and intermittent f ares are common. 4,10 • Common skin symptoms associated with psoriasis include pruritus, irritation, burning, sensitivity, and pain. 7 • PsA is characterized by early morning sti ness lasting longer than 30 minutes, pain, swelling, and tenderness o the joints and the surrounding ligaments and tendons (eg, the Achilles tendons) (Figure 100-2) and ligamentous attachments to the ribs, spine, and pelvis. 4 • PsA may start slowly with mild symptoms and, on occasion, may be preceded by a joint injury. The course is variable and unpredictable, ranging rom mild and nondestructive to severe, debilitating, erosive arthropathy.4 • Flares and remissions usually characterize the course o PsA. Le t untreated, patients with PsA can have persistent inf ammation, progressive joint damage, severe physical limitations, and disability. 4

FIGURE 100-3 Dactylitis (sausag e f ng e rs) in a woman with p laq ue psoriasis and p so riatic arthritis. (Re p ro d uce d with p e rmissio n fro m Richard P. Usatine , MD.)

487

488

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

FIGURE 100-4 Psoriatic arthritis o the d istal inte rp halang e al p re d ominant (DIP) joint with p soriatic nail chang e s and p soriatic skin chang e s o the d istal d ig it. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• New psoriasis lesions can orm at sites o trauma, which is termed the Koebner phenomenon. Removal o scale o ten reveals pinpoint bleeding, which is called the Auspitz phenomenon. 7 • Psoriatic lesions are distributed symmetrically and can a ect any part o the body. The most commonly a ected sites are the scalp, torso, and extensor sur aces o the extremities, such as the knees and elbows. 12

Ch a pt e r 100

FIGURE 100-5 Arthritis mutilans in b oth hand s in a man with long -stand ing p soriasis and arthritis. (Re p rod uce d with p e rmission from Rob e rt Gilson, MD.)

• Nail pitting occurs as a result o psoriasis a ecting the nail matrix. Yellowish-brown nail discoloration or oil spots on the nail result rom psoriasis involvement o the nail bed. • Onycholysis occurs at the distal nail plate at the point o separation rom the hyponychium. 7

DIAGNO STIC TESTS

There are ve types o PsA: 1. Symmetric arthritis—Involves multiple symmetric pairs o joints in the hands and eet; resembles rheumatoid arthritis. It a ects approximately 15% o patients with PsA. 12 2. Asymmetric arthritis—Involves only 1 to 3 joints in an asymmetric pattern and may a ect any joint (eg, knee, hip, ankle, and wrist). Hands and eet may have enlarged sausage digits caused by dactylitis (Figure 100-4). As the most common type, it is ound in approximately 80% o patients. 12 3. Distal interphalangeal predominant (DIP)—Involves the distal joints o the ngers and toes. It may be con used with osteoarthritis, but nail changes are common in this type o PsA. The ngers with DIP involvement are most likely to have psoriatic nail changes, such as pitting (Figure 100-4). This “classic type” occurs in approximately 5% o patients. 12 4. Spondylitis (axial)—Inf ammation o the spinal column causes a sti neck and pain in the lower back and sacroiliac area. The arthritis may involve peripheral joints in the hands, arms, hips, legs, and eet. 12 5. Arthritis mutilans—A severe, de orming type o arthritis that usually a ects a ew joints in the hands and eet (Figure 100-5). It has been associated with pustular psoriasis. It a ects ewer than 5% o patients with PsA. 12

NAIL PSO RIASIS See Chapter 193, Psoriatic Nails, or more in ormation on the subject. • Nail disease is commonly ound in patients with PsA, especially those with distal interphalangeal joint involvement (Figure 100-4). 4 • Psoriatic nail disease occurs more commonly in the ngernails than the toenails and mani ests as pitting, onycholysis, oil spots, hyperkeratosis, or nail grooving. 3

• The erythrocyte sedimentation rate or the C-reactive protein level can be used to measure signs o systemic inf ammation. 4 • Skin biopsy is not routinely required or diagnosis o psoriasis. Histological ndings vary depending on the age o the lesions. 3 IMAGING Radiographs may show juxta-articular erosions (Figure 100-6), “pencil-incup” de ormity, osteolysis, digit telescoping, or asymmetric sacroiliitis.

MANAGEMENT • Inf ammation driven by T cells is responsible or keratinocyte growth and angiogenesis in the psoriatic plaque. 13 Many o the therapies or skin psoriasis are there ore devised to target T cells or their inf ammatory mediators. 13,14 • Indeed, many o the topical and systemic therapies and phototherapies also act at least in large part by inter ering with this same immune response. • For patients with moderate-to-severe skin psoriasis and PsA, systemic therapies should be used (Figure 100-7). 15 SO R • Patients with PsA may have skin psoriasis at the same time, and treatment should be or the joints and the skin at the same time. THERAPY FO R SKIN PSO RIASIS • Corticosteroids are the mainstay o treatment or symptomatic skin psoriasis. 9 • Topical steroids as monotherapy give ast relie o inf ammation and itching. Small, chronic plaques may be treated with intralesional steroid. 16 SO R • Vitamin D derivative–corticosteroid combination therapy is more e ective than vitamin D derivative monotherapy. 16 SO R

PART 13

pSO r Ia t IC a r t h r It IS

MUSCULO SKELETAL/ RHEUMATO LO GIC

A

A

B

B FIGURE 100-6 A. Symme trical p soriatic arthritis in b oth hand s o a 50-ye arold woman. B. This rad iog rap h o he r rig ht hand shows juxta-articular e rosions. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Acitretin is an antipsoriatic retinoid. The combination o acitretin with topical vitamin D, biological therapy, or phototherapy may increase rates o clearance but does not treat PsA. 16 SO R SYSTEMIC THERAPY • Patients with both chronic psoriasis and PsA may nd a major improvement in their quality o li e with systemic treatment. 16 SO R

FIGURE 100-7 A. Plaq ue p soriasis on b oth le g s in a 41-ye ar-old man with rig ht kne e p ain and p soriatic arthritis. B. The skin p soriasis is se e n on the d orsum o his le t hand along with joint d e ormitie s o the f ng e rs rom the ad vance d p so riatic arthritis. The ourth d ig it shows a swan-ne ck d e ormity. He is a g ood cand id ate or syste mic the rap y to tre at the skin and joints in an atte mp t to p re ve nt urthe r joint d e ormitie s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

e ects on T-cell gene expression patterns. It can be used continuously or many years with durable bene ts. • For patients with moderate-to-severe PsA, MTX, tumor necrosis actor a (TNF-a ) blockade, or the combination o these therapies is considered rst-line treatment. 4 SO R • The combination o orally administered MTX and cyclosporine can also be e ective in the treatment o PsA. 4 SO R

• Mild PsA is most o ten managed with nonsteroidal anti-inf ammatory drugs (NSAIDs) alone. I the PsA is unresponsive a ter 2 to 3 months o therapy with NSAIDs, treatment with methotrexate (MTX) should be considered. 4 SO R

BIO LO GICAL AGENTS

• Methotrexate is an inhibitor o olate biosynthesis and there ore impairs DNA replication. It is an anti-inf ammatory because o its

• All TNF-a inhibitors show similar e cacy or the signs and symptoms o PsA. There are, however, observed di erences in the e cacy o

• Immunomodulatory therapy interacts with speci c molecular targets in T-cell-mediated inf ammatory processes and exerts an anti-inf ammatory e ect, decreasing the progression o the disease. 15 SO R

489

490

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch a pt e r 100

these agents or the treatment o cutaneous psoriasis. Inf iximab clears cutaneous psoriasis in the highest proportion o patients and with the greatest rapidity. 4 SO R

• It is expected that control o the underlying inf ammatory process in patients with extensive psoriasis will make a signi cant di erence to their morbidity. 9

• All o the TNF-a inhibitors appear to diminish the likelihood o radiographic progression o PsA compared with MTX, but these ndings are derived rom comparing several di erent studies rather than one large comparator study. 4 SO R

• With correct diagnosis and proper management, most patients with psoriasis continue to lead a normal li e.

• Etanercept is a recombinant soluble TNF-a receptor used to the Fc portion o a human immunoglobulin G molecule. Etanercept binds soluble TNF-a , thus blocking its pro-inf ammatory e ects. SO R • Adalimumab is a TNF inhibitor that binds to TNF-a , preventing it rom activating TNF receptors. It o ers e ective control o plaque psoriasis. SO R • Inf iximab is a chimeric monoclonal antibody that blocks the proinf ammatory e ect o TNF-a . It o ers rapid and thorough suppression o psoriasis. SO R • Ustekinumab is a human monoclonal antibody to interleukin 12 (IL-12) and IL-23 that inhibits T-cell subsets involved in plaque psoriasis. SOR • In general, it is appropriate to initiate MTX treatment or patients with moderate-to-severe PsA who have no contraindications to MTX therapy. Check PPD rst and make sure that, i the test was positive, the patient has had at least 2 months o isoniazid (INH). ° I a ter 12 to 16 weeks o MTX therapy with appropriate dose escalation (maximum 25 mg/ week) there is minimal improvement in the signs and symptoms o PsA, it is appropriate to either add or switch to a TNF-a inhibitor, with all o the TNF-a inhibitors equally reasonable choices. 4 SO R

PRO GNO SIS/ CLINICAL CO URSE • The mani estations o PsA can be severe and widespread, with signs and symptoms that greatly a ect patients’ quality o li e. 7 • Some patients may have PsA involving only their hands, but it may have a devastating e ect on their ability to work and socialize (Figure 100-8).

MAJO R CO MPLICATIO NS O F PSO RIASIS • Psoriasis is associated with a number o serious systemic comorbidities, including PsA, anxiety, depression, obesity, hypertension, diabetes, hyperlipidemia, metabolic syndrome, smoking, cardiovascular disease, alcoholism, Crohn disease, lymphoma, and systemic multiple sclerosis. 17 • The associated comorbidities, which can be severe and debilitating, may complicate management and increase the risk o early death. 17,18

FO LLO W-UP • I a patient ails to respond to steroid therapy, then the clinician should reassess the need or additional or di erent treatment. SO R • Stable patients should be ollowed every 4 to 6 months.

PATIENT EDUCATIO N • Patients should see a physician i any new symptoms appear or the medication is not working. • Skin care measures—Psoriasis is made worse by scratching, rubbing, and picking; by excessively hot water; and by skin dryness. • Patients should avoid smoking. • Patient education is essential or optimizing psoriasis treatment or all categories o disease severity. A good physician-patient relationship osters con dence and trust, likely improving adherence to treatment. 4 • Patients should be ully in ormed o the bene ts and risks o their treatments and believe that they have signi cant input into their treatment plan. 4 PATIENT RESO URCES

• The National Psoriasis Foundation—http:/ / www.psoriasis.org. • The Psoriasis Association—https:/ / www.psoriasis-association .org.uk/ . PRO VIDER RESO URCES

• American Academy of Dermatology—http:/ / www.aad.org. • International Federation of Psoriasis Associations—http:/ / www .ifpa-pso.org.

FIGURE 100-8 Psoriatic arthritis in the hand s o a man with wid e sp re ad p soriasis. Multip le me tacarp op halang e al (MCP) and p roximal inte rp halang e al (PIP) joints are involve d . He also has p soriatic arthritis o the kne e s. He is a g ood cand id ate or syste mic the rap y. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Geneva Foundation for Medical Education and Research. Clearing house or many articles and guidelines or psoriasis—http:/ / www.gfmer.ch. • US National Library of Medicine. Psoriasis—http:/ / www.nlm .nih.gov.

pSO r Ia t IC a r t h r It IS

REFERENCES 1. Gottlieb AB, Lebwohl M, Totoritis MC, et al. Clinical and histologic response to single-dose treatment o moderate to severe psoriasis with an anti-CD80 monoclonal antibody. JAmAcad Dermatol. 2002;47(5):692-700. 2. Kane D, Sta ord L, Bresnihan B, FitzGerald O. A prospective, clinical and radiological study o early psoriatic arthritis: an early synovitis clinic experience. Rheumatology (Oxford). 2003;42(12):1460-1468. 3. Kurd SK, Gel and JM. The prevalence o previously diagnosed and undiagnosed psoriasis in US adults: results rom NHANES 2003-2004. JAmAcad Dermatol. 2009;60(2):218-224. 4. American Academy o Dermatology Work Group; Menter A, Korman NJ, Elmets CA, et al. Guidelines o care or the management o psoriasis and psoriatic arthritis: section 6. Guidelines o care or the treatment o psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. JAmAcad Dermatol. 2011;65(1):137-174.

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC 10. Nevitt GJ, Hutchinson PE. Psoriasis in the community: prevalence, severity and patients’ belie s and attitudes towards the disease. Br J Dermatol. 1996;135(4):533-537. 11. Meier M, Sheth PB. Clinical spectrum and severity o psoriasis. Curr Probl Dermatol. 2009;38:1-20. 12. Van Voorhees A, Feldman SR, Koo JYM, et al.; National Psoriasis Foundation. The Psoriasis and PsoriaticArthritis Pocket Guide:Treatment Algorithms and Management Options. 3rd ed. http:/ / www.psoriasis. org/ document.doc?id= 354. Accessed March 1, 2014. 13. Lowes MA, Kikuchi T, Fuentes-Duculan J, et al. Psoriasis vulgaris lesions contain discrete populations o Th1 and Th17 T cells. J Invest Dermatol. 2008 May;128(5):1207-1211. 14. Marble DJ, Gordon KB, Nickolo BJ. Targeting TNFalpha rapidly reduces density o dendritic cells and macrophages in psoriatic plaques with restoration o epidermal keratinocyte di erentiation. J Dermatol Sci. 2007;48(2):87-101.

5. Shbeeb M, Uramoto KM, Gibson LE, O’Fallon WM, Gabriel SE. The epidemiology o psoriatic arthritis in Olmsted County, Minnesota, USA, 1982-1991. J Rheumatol. 2000;27(5):1247-1250.

15. Hsu S, Papp KA, Lebwohl MG, et al. Consensus guidelines or the management o plaque psoriasis. Arch Dermatol. 2012;148(1): 95-102.

6. Koo J. Population-based epidemiologic study o psoriasis with emphasis on quality o li e assessment. Dermatol Clin. 1996;14(3):485-496.

16. Bailey EE, Ference EH, Alikhan A, Hession MT, Armstrong AW. Combination treatments or psoriasis: a systematic review and metaanalysis. Arch Dermatol. 2012;148(4):511-522.

7. Johnson MA, Armstrong AW. Clinical and histologic diagnostic guidelines or psoriasis: a critical review. Clin Rev Allergy immunol. 2013;44(2):166-172. 8. Ayala F. Clinical presentation o psoriasis. Reumatismo. 2007;59(suppl 1): 40-45. 9. Clarke P. Psoriasis. Aust Fam Physician. 2011;40(7):468-473.

17. Guenther L, Gulliver W. Psoriasis comorbidities. J Cutan Med Surg. 2009;13(suppl 2):S77-S87. 18. Han C, Lof and JH, Zhao N, Schenkel B. Increased prevalence o psychiatric disorders and health care-associated costs among patients with moderate-to-severe psoriasis. J Drugs Dermatol. 2011;10(8):843-850.

491

PART 13

492

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch a pt e r 101

101 ANKYLO SING SPO NDYLITIS He id i Chumle y, MD Richard P. Usatine , MD

PATIENT STO RY A 43-year-old man alls and presents with acute back and di use abdominal pain. He has had back pain on and o or years. Also, his wi e notes that he has become “stooped” orward in the last ew years. The radiographs show owing ligamentous ossif cation and syndesmophyte ormation about the cervical, thoracic, and lumbar spine consistent with ankylosing spondylitis (bamboo spine) (Figure 101-1). The KUB (kidneys, ureters, bladder) view f lm also shows usion o the sacroiliac (SI) joints consistent with ankylosing spondylitis (Figure 101-2). No racture, dislocation, or abdominal pathology is identif ed. The patient’s symptoms are treated and nonsteroidal anti-in ammatory drugs (NSAIDs) are started. On ollow-up a blood test reveals that he is human leukocyte antigen (HLA)-B27–positive. FIGURE 101-2 KUB vi w s owing b mb oo s in nd usion o b o s c oili c (SI) join s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

INTRO DUCTIO N Ankylosing spondylitis is an in ammatory disease o the axial spine associated with the HLA-B27 genotype. Symptoms o low back and/ or hip pain begin in late adolescence or early adulthood. Diagnosis is based on clinical eatures and radiographic f ndings.

EPIDEMIO LO GY • Prevalence in general population is approximately 0.2% to 0.5%. • Five percent o patients in primary care with low back pain have a spondyloarthritis, a spectrum o diseases that includes ankylosing spondylitis. 1 • More common in males than in emales (approximate ratio: 4:1). • Ninety percent o patients are HLA-B27–positive. 2 However, many people with HLA-B27 do not develop the disease.

ETIO LO GY AND PATHO PHYSIO LO GY • In ammatory arthritis with a poorly understood pathology. • Environment and genetic actors result in in ammation. • Chronic in ammation causes extensive new bone ormation.

RISK FACTO RS • Male gender • HLA-B27–positive genotype A

B

FIGURE 101-1 A. Fusion o v b l b od i s nd os io l m n s g iv s s in cl ssic “b mb oo” nc s n in nkylosing s ond yli is. B. No m k d ky osis nd synd smo y s in v ic l conn c ions b w n n io s c s o v b l b od i s. t y loc d in ou l y so nnulus f b osis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIAGNO SIS Mean delay o 7 to 8 years until diagnosis. Consider screening patients younger than 45 years o age with chronic low back pain or more than 3 months. 3

a NKYLO SING SpO NDYLIt IS

CLINICAL FEATURES • Younger patient (younger than 40 years o age at start o disease). • In ammatory (pain and sti ness worsen with immobility and improve with motion; symptoms are worse at night or early morning). • Good response to NSAIDs—Sensitivity = 77%, specif city = 85%, positive likelihood ratio (LR+ ) 5.1. 1 • Symptoms o in ammatory back pain have air sensitivity (75%) and specif city (75%). LR+ is 3.1. Number needed to screen is 7. 1,3 PHYSICAL EXAMINATIO N

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC classic bamboo spine described in ankylosing spondylitis (see Figures 101-1 and 101-2). • Magnetic resonance imaging (MRI)—Detects in ammation, such as acute sacroiliitis, which occurs prior to bony change visible by radiographs.

DIFFERENTIAL DIAGNO SIS The ollowing are causes o back pain in patients younger than age 45 years: • Lumbar strain or muscle spasm—Acute onset o ten with precipitating event.

• Limited range o motion o the spine. • Tenderness over the spine and sacroiliac joints. • In the advanced stages, kyphosis may occur with a stooped posture (see Figure 101-1). • Uveitis o the eye is the most common extra-articular mani estation occurring in 20% to 30% o patients. This can present with a red painul eye along with photophobia. The involved eye may have an irregular pupil and a 360-degree perilimbal injection (see Chapter 15, Uveitis and Iritis). TYPICAL DISTRIBUTIO N

• Herniated disc—Acute onset with pain radiating below the knee into lower leg or oot with numbness, weakness, and/ or loss o ankle jerk re ex. • Vertebral ractures—Risk actors are osteoporosis or signif cant trauma. • Abdominal pathology such as pancreatitis—Associated with gastrointestinal (GI) symptoms. • Kidney diseases—Nephrolithiasis (pain radiating into groin); pyelonephritis ( ever, nausea, and urinary symptoms). • Osteoarthritis—Worse a ter working; less commonly has in ammatory symptoms (see Chapter 98, Osteoarthritis).

Pain in lower back and/ or sacroiliac joints LABO RATO RY TESTING • HLA-B27 has good sensitivity (90%) and specif city (90%). LR+ is 9. Number needed to screen is 3. Test is expensive. 1,3

• Other spondyloarthritis (SpA) include psoriatic spondyloarthritis (Figure 101-4), SpA associated with in ammatory bowel disease, reactive SpA, and undi erentiated SpA.

• May also consider HLA-B27 or patients with in ammatory back pain only.1

MANAGEMENT

IMAGING • Radiologic f ndings conf rm the diagnosis; however, these may occur years a ter the onset o symptoms.

• NSAIDs and physical therapy reduce pain. Continuous NSAIDs reduce radiographic progression. 4 SO R

• Plain f lms—Typical spinal eatures include erosions, squaring, sclerosis, syndesmophytes, and ractures; may also see sacroiliac joint usion (Figure 101-3). Flowing ligamentous ossif cation and syndesmophyte ormation about the cervical, thoracic, and lumbar spine orm the

• Disease-modi ying antirheumatic drugs (methotrexate, le unomide) have not been demonstrated to have patient-oriented outcomes. 4

FIGURE 101-3 a nkylosing s ond yli is wi n usion o ig (SI) join nd s ud owid ning ( om osiv c ng s) o l (Re p rod uce d with p e rmission from Eve re tt Alle n, MD.)

s c oili c SI join .

SO R

• Tissue necrosis actor blockers are recommended or patients who ail NSAIDs and physical therapy. Consider treating or re erring or treatment with shorter duration o symptoms, elevated acute phase reactants (ie, C-reactive protein), or rapid radiographic progression. SO R

FIGURE 101-4 pso i ic i is s owing sw n-n ck d o mi i s, involv m n o oxim l in l ng l (pIp) nd d is l in l ng l (DIp) join s nd skin l q u s. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

493

494

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC ° In iximab improves pain scores and quality o li e within 2 weeks (61% vs 19% placebo). 4 SOR Many relapse; high cost, but economic analysis is avorable compared to estimated cost o loss o unction.4 ° Adalimumab improves quality o li e and unction scores by 12 weeks. Improvement continues or up to a year and remains stable through 3 years. 5 SO R 4 Relie comes ° Etanercept improves pain scores (60% vs 12%). SOR within 2 weeks. Many relapse; reinitiation works.4 Seventy-six percent o patients treated with etanercept, compared to 53% o patients treated with sul asalazine, improved by 20% within 4 months.6 Improvements in pain, unction, and mobility were sustained at 5 years.7

PRO GNO SIS Mortality is increased in male patients with ankylosing spondylitis. Leading cause o death was cardiovascular. Risk actors or reduced survival include absence o NSAID use (odds ratio [OR] 4.35), work disability (OR 3.65), increased C-reactive protein (OR 2.68), and diagnostic delay (OR 1.05).8

FO LLO W-UP Follow patients or progression o pain or decreased unction using standard ankylosing spondylitis, such as the Ankylosing Spondylitis Disease Activity Score or the Bath Ankylosing Spondylitis Disease Activity Index or Functional Index.

PATIENT EDUCATIO N Ankylosing spondylitis is a chronic disease. NSAIDs and physical therapy and exercise are important in controlling pain and slowing progression o disease. I these are ine ective, tissue necrosis actor blockers are e ective; however, these are expensive and pain recurs when they are stopped. PATIENT RESO URCES

• American College of Rheumatology. Patient education handout: Spondyloarthritis (Spondyloarthropathy)—http:/ / www .rheumatology.org/ practice/ clinical/ patients/ diseases_ and_conditions/ spondyloarthritis.asp. • The Spondylitis Association of America—http:/ / www .spondylitis.org. • PubMed Health. Ankylosing Spondylitis—http:/ / www.ncbi.nlm .nih.gov/ pubmedhealth/ PMH0001457/ .

Ch a pt e r 101

PRO VIDER RESO URCES

• Assessment o SpondyloArthritis International Society. Ankylosing Spondylitis Disease Activity Score Information and Online Calculator— http:/ / www.Asas-Group.Org/ Research.Php?Id=01# Null. • Medscape. Brent LH. Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy—http:/ / emedicine.medscape.com/ article/ 332945. • Assessment o SpondyloArthritis International Society (ASAS) and European League Against Rheumatism (EULAR); Zochling J, van der Heijde D, Burgos-Vargas R, et al. ASAS/ EULAR recommendations or the management o ankylosing spondylitis. Ann Rheum Dis. 2006;65(4):442-452.—http:/ / www.ncbi.nlm.nih.gov/ pmc/ articles/ PMC1798102/ . REFERENCES 1. Rudwaleit M, van der HD, Khan MA, et al. How to diagnose axial spondyloarthritis early. Ann Rheum Dis. 2004;63(5):535-543. 2. Kim Th, Uhm WS, Inman RD. Pathogenesis o ankylosing spondylitis and reactive arthritis [review] [73 re s]. Curr Opin Rheumatol. 2005;17(4):400-405. 3. Sieper J, Rudwaleit M. Early re erral recommendations or ankylosing spondylitis (including pre-radiographic and radiographic orms) in primary care [review]. Ann Rheum Dis. 2005;64(5):659-663. 4. Zochling J, Braun J. Management and treatment o ankylosing spondylitis [review]. Curr Opin Rheumatol. 2005;17(4):418-425. 5. Kimel M, Revicki D, Rao S, et al. Norms-based assessment o patientreported outcomes associated with adalimumab monotherapy in patients with ankylosing spondylitis. Clin Exp Rheumatol. 2011;29(4):624-632. 6. Braun J, van der Horst-Bruinsma IE, Huang F, et al. Clinical e f cacy and sa ety o etanercept versus sul asalazine in patients with ankylosing spondylitis: a randomized, double-blind trial. Arthritis Rheum. 2011;63(6):1543-1551. 7. Martin-Mola E, Sieper J, Leirisalo-Repo M, et al. Sustained e f cacy and sa ety, including patient-reported outcomes, with etanercept treatment over 5 years in patients with ankylosing spondylitis. Clin Exp Rheumatol. 2010;28(2):238-245. 8. Bakland G, Gran JT, Nossent JC. Increased mortality in ankylosing spondylitis is related to disease activity. Ann Rheum Dis. 2011;70(11):1921-1925.

BACK PAIN

102 BACK PAIN He id i Chumle y, MD

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC EPIDEMIO LO GY • Six percent o visits to primary care physicians are or back pain. 1 • Low back pain 1-year incidence is 20% and 1-year prevalence is 40% in adults. 2

PATIENT STO RY A 60-year-old woman presents with chronic low back pain (LBP) that began many years ago. Her back pain waxes and wanes and she has taken acetaminophen and ibupro en with some relie . About 3 months ago, she began to have daily pain. She recalls no trauma. Her examination is unremarkable other than some decreased exion. Straight leg raise test is negative. As the patient is older than 55 years o age, radiographs are ordered and they demonstrate degenerative changes in her lumbar spine (Figure 102-1). She is started on scheduled acetaminophen and ibupro en along with an exercise program.

• Thoracic back pain 1-year prevalence is 15% to 27% in adults. 3 • Treatment or back and neck problems accounted or approximately $86 billion in health care expenditures in the United States in 2005. 4 • Prevalence o malignancy in patients with LBP presenting to a primary care o f ce or emergency room is 0.1% to 1.5%. 5

ETIO LO GY AND PATHO PHYSIO LO GY • LBP can be caused by pain in the muscles, ligaments, joints, bones, discs, nerves, or blood vessels. 2 • In 90% o cases, the specif c cause o LBP is unclear. 2

INTRO DUCTIO N Back pain is one o the most common reasons that adults see their physician. Most acute back pain is a result o mechanical causes. Serious pathology can be recognized by the presence o red ags. Acute back pain is treated with reassurance, returning to activities, and acetaminophen with or without a nonsteroidal anti-in ammatory drug (NSAID). Psychological actors increase the risk o development o chronic pain. Chronic back pain is di f cult to treat and the best outcomes are typically achieved by an interpro essional team.

• In 10% o cases, a specif c cause such as an in ection, racture, or cancer is identif ed.

RISK FACTO RS • Older age—Prevalence o LBP increases with age into the sixth decade. 2 • Low educational status. 2 • Occupational actors—Manual labor, bending, twisting, and wholebody vibration. 2 • Psychosocial actors increase the risk o transition rom acute to chronic pain. 2 • Risk actors or cancer—Previous history o cancer (positive likelihood ratio [LR+ ] 23.7), elevated erythrocyte sedimentation rate (ESR) (LR+ 18), reduced hematocrit (LR+ 18.3). 5

DIAGNO SIS The diagnosis can be classif ed into 3 categories: 1. Nonspecif c back pain—Pain or less than 6 weeks (acute), 6 to 12 weeks (subacute), or more than 12 weeks (chronic); negative straight leg raise test; absence o red ags. 2. Radicular syndrome—LBP with radiation down leg; positive straight leg raise test; absence o red ags. 3. Serious pathology—Further workup required or presence o red ags, including age younger than 20 or older than 55 years; signif cant trauma; ever; unexplained weight loss; neurologic signs o cauda equina; progressive neurologic def cit. TYPICAL DISTRIBUTIO N Lumbar pain is about twice as common as thoracic pain. LABO RATO RY TESTING It is help ul in the presence o red ags: FIGURE 102-1 Lat ral vi w s ows g rad 1 d g n rativ sp ond ylolist sis at L4-L5 (arrow), mod rat fac t ost oart ritis of L5-S1. Mark d T12-L1 d isc d g n ration (arrowhe ad ) and mild L4-L5 d isc d g n ration.

• Complete blood count (CBC) to evaluate or anemia (malignancy) or leukocytosis (in ection).

495

496

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch APTe R 102

• Consider human leukocyte antigen (HLA)-B27 in younger patients with in ammatory symptoms. IMAGING • In acute back pain without red ags, imaging can be delayed or 6 weeks. • Radiographs may show degenerative joint disease changes in osteoarthritis; vertebral ractures; malignancies; and f ndings o ankylosing spondylitis including erosions, sclerosis, syndesmophytes (see Chapter 101, Ankylosing Spondylitis). • Magnetic resonance imaging (MRI) is the best imaging test or disc herniation and imaging o the spinal cord. Emergent MRI is indicated in patients with suspected spinal cord compromise or cauda equina syndrome. • Computerized tomography (CT) myelogram is a use ul alternative to evaluate disc herniation in patients who cannot undergo MRI.

DIFFERENTIAL DIAGNO SIS • Osteoporotic vertebral racture—Acute onset o pain, typically seen in older patients or those at risk or osteoporosis, point tenderness at the level o the racture, conf rmation by plain radiographs demonstrating compression or burst racture (Figure 102-2). • Spinal stenosis—Pain worse with extension, presence o unilateral or bilateral leg symptoms worse with walking and better with sitting, conf rmation by CT or MRI. • Herniated disc—Radicular pain that is worse with exion or sitting, may be accompanied by numbness or weakness o oot plantar exion

FIGURE 102-3 MRI s owing rniat d nucl us p ulp osus (arro w) at L5-S1 in a p ati nt wit rad icular p ain and a p oor r sp ons to 6 w ks of cons rvativ t rap y.

(L5/ S1) or dorsi exion (L4/ L5), MRI conf rms the level and shows the type o herniation (Figures 102-3 and 102-4). • Spinal in ection/ abscess—Most commonly seen in patients who use intravenous (IV) drugs, have diabetes mellitus, have cancer, or have a transplant; symptoms include ever, night pain, night sweats, and elevated ESR. MRI is the study o choice. I neurologic def cit is present, obtain an urgent MRI to evaluate or an abscess, which would require hospitalization and consultation with a spinal surgeon. • Ankylosing spondylitis (see Chapter 101, Ankylosing Spondylitis)— Pain, most commonly in the low back or sacroiliac joints, usually begins in late adolescence or early adulthood. Pain and sti ness worsen with immobility and improve with motion. HLA-B27 may be positive. Radiographic f ndings conf rm the diagnosis, but occur years a ter symptoms.

FIGURE 102-2 Lat ral vi w d monstrating t loss of v rt b ral b od y ig t s n wit a comp r ssion fractur d formity (arrow) of t sup rior nd p lat of t L2 v rt b ral b od y. T r is also a mild co ncav comp r ssion d formity of t sup rior nd p lat of t L5 v rt b ral b od y.

FIGURE 102-4 MRI cross-s ction d monstrat s t at t (arrow) is comp r ssing S1 n rv root.

rniat d d isc

BACK PAIN

• Malignancy—Typically seen in an older patient; symptoms o weight loss and night pain; signif cant anemia; history o cancer; nonresponse to therapy. O ten seen on plain radiographs. Bone scan is the most sensitive test. • Abdominal pathology such as pancreatitis, pyelonephritis, and cholecystitis can present as back pain or pain radiating to the back.

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC • Re erral or hospitalization ° Chronic pain is di f cult to treat. Use an interdisciplinary team to maximize e ectiveness i possible. ° Consider re erring patients who do not respond to conservative therapy to a pain management specialist or a spine surgeon.

PREVENTIO N MANAGEMENT ACUTE BACK PAIN Most national guidelines agree on the ollowing actors6: • Nonpharmacologic ° Reassure patients without red ags that they do not have a serious condition, advise them to remain active, discourage bed rest, and encourage an early return to work while back pain is still present. to normal ° Exercise is considered no more e ective than return activities or LBP within the f rst 4 to 6 weeks. 6 • Medications ° Acetaminophen. ° Add NSAID i needed (ask about gastrointestinal [GI] problems and protect against ulcers as needed). ° Consider a short course o opiates or muscle relaxers i pain is severe and inadequately treated with acetaminophen and NSAIDs. ° Consider amitriptyline or gabapentin or radicular pain. • Complementary and alternative therapy ° National guidelines di er; some recommend and some do not recommend spinal manipulative therapy or acute back pain. ° Spinal manipulative therapy has a similar7 e ect on pain relie and unctional status as other interventions. • Re erral or hospitalization ° Patients with cauda equina syndrome should have expedient imaging and urgent re erral to a spinal surgeon. ° Re er patients with serious pathology such as in ection, tumor, or racture to appropriate consultants. SUBACUTE (6-12 WEEKS) O R CHRO NIC (>12 WEEKS) BACK PAIN

Good posture, appropriate li ting techniques, maintaining a healthy weight, and enjoying an active li estyle may help prevent back pain. Adding yoga to an active li estyle has the potential to prevent recurrent back pain and diminish the pain o chronic back pain. 1-4 SO R

PRO GNO SIS • Patients with nonradicular acute back pain—By 12 months, 40% recover ully. 8 • Patients with acute back pain who have psychological actors at baseline are more likely to develop chronic LBP. 9

FO LLO W-UP Follow-up is determined by etiology. Patients with acute back pain, without red ags, especially those at risk to develop chronic pain, should be ollowed closely. Patients with chronic pain benef t rom ongoing treatment by an interpro essional team.

PATIENT EDUCATIO N • Reassure patients without red ags that most acute back pain is not a result o a serious cause and can be treated conservatively. • Advise patients with chronic back pain that a comprehensive approach to pain management is more likely to result in pain improvement than medications alone. • Yoga and stretching can be a valuable adjunct to other treatments. 1-4

Most national guidelines agree on the ollowing recommendations6: • Nonpharmacologic ° Encourage an exercise program. ° Recommend cognitive-behavioral therapy. ° Discourage ultrasound or electrotherapy. • Medications ° National guidelines vary on medication recommendations. ° Start with acetaminophen, then add NSAIDs i needed. ° Consider adding one o these medications: tramadol, an antidepressant, a benzodiazepine, or an opiate. • Complementary and alternative therapy ° Yoga—There have been a number o randomized controlled trials (RCTs) and meta-analyses that have ound yoga to be an excellent treatment or chronic and recurrent LBP. 1-4 SO R A 12-week yoga program or adults with chronic or recurrent LBP led to greater improvements in back unction than did usual care. 4 Yoga classes were more e ective than a sel -care book, but not more e ective than stretching classes, in improving unction and reducing symptoms caused by chronic LBP, with lasting benef ts. 3

PATIENT RESO URCES

• Written and auditory patient information is available in English and Spanish at Family Doctor.org—http:/ / familydoctor.org/ familydoctor/ en/ diseases-conditions/ low-back-pain .html. • Yoga therapy for back pain. Audio and visual instructions for patients wanting to use yoga—http:/ / www.samata.com/ video4.php. • YouTube. Gentle yoga routine for lower back relief—http:/ / www .youtube.com/ watch?v= u0BLxSY2L3Y. PRO VIDER RESO URCES

• A comprehensive list of red ags for back pain can be found in amily practice notebook—http:/ / www.fpnotebook.com/ Ortho/ Sx/ LwBckPnRdFlg.htm. • WebMD Back Pain Health Center. Useful for patients and providers—http:/ / www.webmd.com/ back-pain/ default.htm.

497

498

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC REFERENCES 1. Jordan KP, Kadam UT, Hayward R, et al. Annual consultation prevalence o regional musculoskeletal problems in primary care: an observational study. BMC Musculoskelet Disord. 2010;11:144. 2. Hoy D, Brooks P, Blyth F, Buchbinder R. The epidemiology o low back pain. Best Pract Res Clin Rheumatol. 2010;24(6):769-781. 3. Briggs AM, Smith AJ, Straker LM, Bragge P. Thoracic spine pain in the general population: prevalence, incidence and associated actors in children, adolescents and adults. A systematic review. BMC Musculoskelet Disord. 2009;10:77. 4. Martin BI, Deyo RA, Mirza SK, et al. Expenditures and health status among adults with back and neck problems. JAMA. 2008;299:656-664. 5. Henschke N, Maher CG, Re shauge KM. Screening or malignancy in low back pain patients: a systematic review. Eur Spine J. 2007;16(10):1673-1679.

Ch APTe R 102

6. Koes BW, van Tulder M, Lin CW, et al. An updated overview of clinical guidelines or the management o non-specif c low back pain in primary care. Eur Spine J. 2010;19(12):2075-2094. 7. Rubinstein SM, van Middelkoop M, Assendelft WJ, et al. Spinal manipulative therapy or chronic low-back pain. Cochrane Database Syst Rev. 2011:CD008112. 8. Costa Lda C, Maher CG, McAuley JH, et al. Prognosis or patients with chronic low back pain: inception cohort study. BMJ. 2009;339:b3829. 9. Mello M, El ering A, Egli Presland C, et al. Predicting the transition rom acute to persistent low back pain. Occup Med (Lond). 2011;61(2):127-131.

LUMBAR SPINAL STENO SIS

103 LUMBAR SPINAL STENO SIS Gary Fe re nchick, MD

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC neurogenic claudication. Palliative eatures commonly include symptomatic relie with orward f exion, sitting and/ or recumbency.”1

SYNO NYMS Synonyms or LSS are lumbar degenerative spinal stenosis and central canal stenosis.

PATIENT STO RY An 82-year-old man presents with a 12-month history o lower-back, bilateral buttock, and leg pain, which was worse with walking. The leg pain extended to the knees and was elt both posteriorly and anteriorly. The pain was only present while ambulating and with prolonged standing and was not present at rest. The pain was described as an achy quality, which made it di cult or the patient to carry objects, per orm house- or yard work, or climb and descend stairs. His physical examination reveals negative straight-leg raising (SLR) bilaterally, and his range-o -motion at the lumbosacral (LS) spine reveals pain with lumbar extension and lateral motion. His lower-extremity ref exes and muscle strength are normal as are his pedal pulses. A magnetic resonance imaging (MRI) scan reveals spinal stenosis at L2-3, L3-4, and L4-5 with normal lordotic curvature, patent oramina, and the absence o spondylolisthesis (Figure 103-1).

INTRO DUCTIO N • According to the North American Spine Society, degenerative lumbar spinal stenosis (LSS) is “a condition in which there is diminished space available or the neural and vascular elements in the lumbar spine secondary to degenerative changes in the spinal canal. When symptomatic, this causes a variable clinical syndrome o gluteal and/ or lower extremity pain and/ or atigue which may occur with or without back pain. Symptomatic lumbar spinal stenosis has certain characteristic provocative and palliative eatures … including upright exercise such as walking or positionally-induced

EPIDEMIO LO GY • For patients over 65, LSS is the most requent indication or spinal surgery.2 • Lower-extremity pain coexisting with low-back pain occurs in 12% to 21% o older adults. 3

ETIO LO GY/ PATHO PHYSIO LO GY • Compression o nerve roots rom congenital (less common) or degenerative (more common) changes leads to symptoms o LSS. ° Short pedicles lead to a narrow canal in congenital disease, whereas loss o disk height, changes in the ligamentum f avum, and osteophyte ormation lead to canal narrowing in degenerative disease. • Less-common causes o LSS include the ollowing3: ° Spondylolisthesis ° Prior spinal surgery ° Paget disease ° Cushing syndrome

DIAGNO SIS/ SCREENING HISTO RY/ SYMPTO MS Gluteal or lower-extremity symptoms are exacerbated with walking, prolonged standing, or spinal extension and show improvement with sitting or orward f exion (eg, neurogenic claudication). 1 • I symptoms are not worsened with ambulation, there is a low likelihood o LSS. 1 • Some patients have more subtle symptoms, such as subjective weakness or atigue o the legs or gait disturbances and sensory loss. 3 • Low-back pain is present in the majority o patients with LSS. PHYSICAL EXAMINATIO N • Unsteadiness and a wide-based gait • Wide-based stance with the Romberg test • Discom ort with extension and relie with f exion at the LS spine weakness that inter eres with normal ° Note that lower-extremity activity is uncommon3 IMAGING

FIGURE 103-1 Spinal canal stenosis wit moderate diffuse disk bulging at L2-3, L3-4, and L4-5 (arrows). T e anteroposterior diameter of t e spinal canal measures 6.5 mm. (Reproduced with permission from Gary Ferenchick, MD.)

• Order an MRI o the LS spine1 (Figures 103-1 and 103-2). SO R ° Sensitivity o MR imaging or LSS is greater than 70%. ■ Up to 19% to 47% o patients between the ages o 60 and 69 have radiographic LSS (depending on the degree o stenosis, < 12 mm vs < 10 mm); however, most o these patients have no symptoms. 4 ■ Computed tomography (CT) or CT myelography is an alternative test in patients in whom an MRI cannot be accomplished or is inconclusive. 1 SO R

499

500

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch APTER 103

• There is insu cient evidence to recommend or or against spinal manipulation, education, traction, or electrical stimulation (transcutaneous electrical nerve stimulation, TENS) or LSS. 1 • Epidural corticosteroid injections may be help ul or up to 6 months or symptom relie in patients with LSS. 1 SO R • A ter 2 to 10 years, 50% to 70% o patients managed nonoperatively will have their symptoms improved, and 20% to 40% o patients will require surgery to manage symptoms. 1 O PERATIVE MANAGEMENT • Decompressive surgery to eliminate pressure on the spinal nerve roots improves outcomes in patients with moderate-to-severe symptoms o LSS and is associated with good or excellent results at 4 years. 1 SO R ° Up to 80% o patients with LSS have symptomatic relie with surgery; a ter 7 to 10 years, a third o these patients have recurrent symptoms, and reoperation rates o 23% have been reported. 2 • In patients with spondylolisthesis, decompression and usion are more e ective than decompression alone. 2 FIGURE 103-2 Se ve re sp inal ste nosis se e n on comp ute d tomog rap ic scan of t e lumb osacral sp ine in a p atie nt wit ac ond rop lasia. (Re p rod uce d with p e rmission from Skinne r HB. Curre nt Diag nosis and Tre atme nt in O rt op e d ics. 4th e d . Ne w York, NY: McGraw Hill; 2006.)

° In patients in whom LSS is clinically suspected but not con rmed with MRI or CT scanning, axial loading o the spine (imaging upright or imaging in both f exion and extension) will increase the sensitivity o the image. 1 SO R • Plain lms o the LS spine are not as use ul as CT or MRI, but they may show predisposing pathology, such as loss o height o the disk space, osteophyte ormation, and spondylolisthesis. 3 • Electromyography is not commonly needed in the diagnosis o LSS but may be help ul in patients with neuropathy (eg, diabetes). 1,2

DIFFERENTIAL DIAGNO SIS • Vascular claudication is not altered by changes in position such as f exion and will be associated with an abnormal ankle-brachial index (ABI). • Compression racture o the LS spine causes pain that is more acute in onset and is not associated with lower-extremity pain unless there is secondary nerve root impingement. • Radicular pain rom a herniated disk is commonly unilateral and associated with a positive SLR test.

MANAGEMENT NO NO PERATIVE MANAGEMENT • Nonoperative management includes exercises that occur during f exion (including bicycling) and strengthening o the abdominal musculature. 2 • Lumbar support corsets worn or short periods may help with posture and provide some pain relie . 1,2

PRO GNO SIS/ CLINICAL CO URSE • The natural history o mild-to-moderate LSS is “ avorable” in 33% to 50%, and there are no reports o “rapid or catastrophic” neurological decline in such patients. 1 • The majority o patients ollowed or 1 year report no major change in the characteristics o their pain. 5 PATIENT RESO URCES

• American Association o Neurological Surgeons (AANS). Lumbar Spinal Stenosis—http:/ / www.aans.org/ Patient%20Information/ Conditions%20and%20Treatments/ Lumbar%20Spinal%20Stenosis.aspx. • MedlinePlus. Lumbar Spinal Stenosis— http:/ / www.nlm.nih. gov/ medlineplus/ spinalstenosis.html. PRO VIDER RESO URCES

• The North American Spine Society. Evidence-Based Clinical Guidelines for Multidisciplinary Spine Care— https:/ / www.spine.org/ Documents/ ResearchClinicalCare/ Guidelines/ LumbarStenosis.pdf. REFERENCES 1. The North American Spine Society. Evidence-Based Clinical Guidelines for Multidisciplinary Spine Care. http:/ / www.spine.org/ Documents/ LumbarStenosis11.pd . Accessed September 12, 2012. 2. Katz JN, Harris MB. Lumbar spinal stenosis. N Engl J Med. 2008;358:818-825. 3. Suri P, Rainville J, Kalichman L, Katz JN. Does this older adult with lower extremity pain have the clinical syndrome o lumbar spinal stenosis? JAMA. 2012;304:2628-2636

• Acetaminophen or nonsteroidal anti-inf ammatory drugs (NSAIDs) are given or pain treatment.

4. Kalichman L, Cole R, Kim DH, et al. Spinal stenosis prevalence association with symptoms: the Framingham Study. Spine J. 2009;9: 545-950.

• Physical therapy (stretching, strengthening, and cycling at low intensities and ultrasound) may improve pain and disability scores. 1 SO R

5. Benoist M. The natural history o lumbar degenerative spinal stenosis. Joint Bone Spine. 2002;69:450.

PART 13

CO MPRESSIO N FRACTURES

MUSCULO SKELETAL/ RHEUMATO LO GIC

104 CO MPRESSIO N FRACTURES Gary Fe re nchick, MD

PATIENT STO RY A previously healthy 75-year-old woman presents with a 3-day history o midthoracic back pain. The pain started shortly a ter she bent over to pick up her grandchild. The pain was not relieved with one gram o acetaminophen 3 times daily. Her examination reveals percussion tenderness over the thoracic spine, and a subsequent thoracic spine radiograph reveals compression ractures o T5 and T8 (Figure 104-1A and 104-1B). She is started on 600 mg ibupro en three times daily (with ood) and 200 IU o calcitonin nasal spray to treat her pain. A subsequent bone mineral density study (dual-energy X-ray absorptiometry [DXA] scan) reveals a spinal T score o -2.9, consistent with osteoporosis. Her physician chooses to start her on oral ibandronate (a bisphosphonate) 2.5 mg daily to treat her osteoporosis.

INTRO DUCTIO N Compression ractures re er to vertebral collapse, o ten at the midthoracic (T7-T12) or lumbar (L1) spine regions, resulting rom osteoporosis. About 66% o osteoporotic vertebral compression ractures (OVCFs) are asymptomatic and are o ten discovered on chest or abdominal radiographs obtained or other reasons or because o the sel -report o loss o height. The remaining 33% o compression ractures are discovered as a result o a sudden onset o back pain, commonly rom atraumatic events such as bending, li ting, coughing, or alling rom a standing height or less.

A

SYNO NYMS Other terms or compression raction are ragility racture, insu ciency racture, and low-trauma racture.

EPIDEMIO LO GY • O Americans, 10 million are estimated to have osteoporosis. 1 • Among Canadians, 1 in 4 women and 1 in 8 men have a li etime risk o a vertebral compression racture. 2 • More than 70% o ractures in those over the age o 70 are caused by osteoporosis. 1 • In Rochester, Minnesota, the incidence o vertebral compression ractures in women is 145 and in men 73 per 100,000 adults per year. 3

ETIO LO GY/ PATHO PHYSIO LO GY • Osteoporosis (see Chapter 225, Osteoporosis and Osteopenia). • Paget disease. • Celiac disease prevalence is increased in patients with compression ractures.

B FIGURE 104-1 A. Comp re ssion fracture s of T5 and T8 in a p ostme nop ausal woman with oste op orosis. B. Close -up of comp re ssion fracture (ye llow arrow) in the same p atie nt. (Re p rod uce d with p e rmission from Gary Fe re nchick, MD.)

• Risk actors include the ollowing: ° Age greater than 50 ° Trauma ° Corticosteroid use ° Previous racture ° Low body weight ( 3 months) pain rom a remote OVCF and only a slight decrease in pain with mobility at 6 months. 6 ° Calcitonin may be given as an intranasal spray, injectable (subcutaneous or intramuscular), or a rectal suppository. • Use an L2 nerve root block in a patient who presents with a symptomatic acute L3 or L4 osteoporotic racture. SO R C • Kyphoplasty (placement o inf atable bone tamp to restore height o collapsed vertebral body ollowed by injection o bone cement into the vertebral body) is an option or treating symptomatic but neurologically intact osteoporotic spinal compression ractures. SO R C • The ollowing have neither a positive nor a negative recommendation: ° Bed rest ° Complementary and alternative medicines ° Opioids ° Bracing ° Exercise programs ° Electrical stimulation ° Any speci c treatment in patients with an osteoporotic racture who are not neurologically intact • The AAOS recommends against vertebroplasty (percutaneous injection o bone cement in ractured vertebral body). 7 SO R • Ibandronate can be given or the prevention o additional osteoporotic ractures. SO R C

PRO GNO SIS/ CLINICAL CO URSE • Acute episodes o pain resolve in 4 to 6 weeks; mild pain may last longer. • About 75% o patients with an OVCF have chronic pain. • A single osteoporotic racture is a strong risk actor or subsequent osteoporotic ractures. a single OVCF, 19.2% will have another ° O women who develop OCVF within 1 year. 8 ° The presence o an OVCF increases the risk o subsequent OVCF by 5- old and the risk o hip and nonvertebral ractures 2.8- old over 8 years. 9 • OVCFs are associated with a decreased quality o li e and unctional impairments and mortality similar to those with hip ractures. 10

PATIENT EDUCATIO N • Treatment with bisphosphonates is commonly required to prevent uture osteoporotic ractures, and adequate intake o vitamin D and calcium should be maintained.

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC • Following a precise dosing regimen or bisphosphonates is important, including rein orcing that the medications should be taken on an empty stomach and the patient should remain upright or at least 30 minutes. • Adequate weight-bearing exercises are also important in preventing urther ractures.

PATIENT RESO URCES

• MedlinePlus. Compression Fractures of the Back—http:/ / www. nlm.nih.gov/ medlineplus/ ency/ article/ 000443.htm. PRO VIDER RESO URCES

• American Academy of Orthopaedic Surgeons. The Treatment of Symptomatic Osteoporotic Spinal Compression Fractures: Guideline and Evidence Report. 2010. http:/ / www.aaos.org/ research/ guidelines/ SCFguideline.pdf. • National Guideline Clearinghouse. ACR Appropriateness Criteria Management of Vertebral Compression Fractures.—http:/ / guidelines.gov/ content.aspx?id=32646.

REFERENCES 1. Holroyd C, Cooper C, Dennison E. Epidemiology o osteoporosis. Best Pract Res Clin Endocrinol Metab. 2008;22(5):671-685. 2. Esses SI, McGuire R, Jenkins J, et al. The treatment o symptomatic osteoporotic spinal compression ractures. JAmAcad Orthop Surg. 2011;19(3):176-182. 3. Cooper C, Atkinson EJ, O’Fallon WM, Melton LJ. Incidence o clinically diagnosed vertebral ractures: a population-based study in Rochester, Minnesota, 1985-1989. J Bone Miner Res. 1992;7(2):221-227. 4. Bartynski WS, Heller MT, Grahovac SZ, Roth us WE, Kurs-Lasky M. Severe thoracic kyphosis in the older patient in the absence o vertebral racture: association o extreme curve with age. AJNR Am J Neuroradiol. 2005;26(8):2077-2085. 5. Tannenbaum C, Clark J, Schwartzman K, et al. Yield o laboratory testing to identi y secondary contributors to osteoporosis in otherwise healthy women. J Clin Endocrinol Metab. 2002;87(10): 4431-4437. 6. Knopp-Sihota JA, Newburn-Cook CV, Homik J, Cummings GG, Voaklander D. Calcitonin or treating acute and chronic pain o recent and remote osteoporotic vertebral compression ractures: a systematic review and meta-analysis. Osteoporos Int. 2012;23(1): 17-38. 7. American Academy o Orthopaedic Surgeons. TheTreatment of Symptomatic Osteoporotic Spinal Compression Fractures: Guideline and Evidence Report. 2010. http:/ / www.aaos.org/ research/ guidelines/ SCFguideline.pd . Accessed August 24, 2012. 8. Lindsay R, Silverman SL, Cooper C, et al. Risk o new vertebral racture in the year ollowing a racture. JAMA. 2001;285(3):320-323. 9. Black DM, Arden NK, Palermo L, Pearson J, Cummings SR. Prevalent vertebral de ormities predict hip ractures and new vertebral de ormities but not wrist ractures. Study o Osteoporotic Fractures Research Group. J Bone Miner Res. 1999;14(5):821-828. 10. Papaioannou A, Watts NB, Kendler DL, Yuen CK, Adachi JD, Ferko N. Diagnosis and management o vertebral ractures in elderly adults. Am J Med. 2002;113(3):220-228.

503

504

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch ApTe r 105

105 GO UT Mind y A. Smith, MD He id i Chumle y, MD

PATIENT STO RY A 91-year-old woman arrives by ambulance to the emergency department because she was experiencing severe pain in her right middle nger (Figure 105-1). History reveals that she has had swelling o her nger or approximately 1 year. Palpation o the distal interphalangeal joint demonstrated rmness rather than f uctuance. A radiograph o the nger was ordered (Figure 105-2). The radiograph and physical examination are consistent with acute gouty arthritis superimposed on tophaceous gout. The diagnosis was con rmed by an aspirate o the nger that demonstrated negatively bire ringent, needle-like crystals, both intracellularly and extracellularly. She was given 1.2 mg o colchicine ollowed by a second dose o 0.6 mg a ter 1 hour. Her pain was markedly decreased in 4 hours. Her serum uric acid level was determined to be 10.7 mg/ dL. The colchicine was used in this case because the risk o using nonsteroidal anti-inf ammatory drugs (NSAIDs) was considered to be high because o her previous history o gastric bleeding secondary to NSAIDs.

INTRO DUCTIO N Gout is an inf ammatory crystalline arthritis. Elevated uric acid leads to deposition o monosodium urate (MSU) crystals in the joints resulting in a red, hot, swollen joint. Gout typically begins as a monoarthritis, but

FIGURE 105-2 T is X- ay o t ng in Fig ure 105-1 s ows s v al to i (monosod ium u at [MSU] d osits) in t so t tissu ov t t i d d istal int alang al joint. Not t ty ical unc d out l sions und t to i. T is is sub c ond al b on d st uction. (Re p rod uce d with p e rmission rom Ge id e rman JM. An e ld e rly woman with a warm, p ain ul f ng e r. W st J M d . 2000;172(1):51-52.)

can become polyarthritic. Treatment o acute episodes includes NSAIDs, colchicine, or intra-articular steroids. Chronic therapy includes lowering the uric acid level using dietary modi cations and urate-lowering drugs.

EPIDEMIO LO GY • Gout a ects 1% to 2% o the US population and approximately 6% o men older than 80 years o age. 1 • Gout is more prevalent in men than women. • Gout usually begins a ter age 30 years in men and a ter menopause in women; it is amilial in approximately 40% o patients. 1

ETIO LO GY AND PATHO PHYSIO LO GY • De ective uric acid metabolism with ine cient renal urate excretion leads to underexcretion o uric acid and an elevated serum uric acid level. • Overproduction o uric acid, instead o underexcretion, occurs in approximately 10% o patients with gout, and also leads to elevated serum uric acid levels. • Elevated serum uric acid leads to deposition o MSU crystals in the joints and the kidneys. FIGURE 105-1 Acut g outy a t itis su im os d on to ac ous g out. (Re p rod uce d with p e rmission rom Ge id e rman JM. An e ld e rly woman with a warm, p ain ul f ng e r. W st J M d . 2000;172(1):51-52.)

• Crystals trigger proinf ammatory cytokines, which cause local inf ammation, tissue necrosis, brosis, and subchondral bone destruction.

PART 13

GO UT

MUSCULO SKELETAL/ RHEUMATO LO GIC

RISK FACTO RS • Medications that cause hyperuricemia—Thiazide diuretics, cyclosporine, aspirin (< 1 g/ d). 2 • Conditions associated with gout—Insulin resistance, obesity, hypertension, hypertriglyceridemia, hypercholesterolemia, congestive heart ailure, renal insu ciency, early menopause, organ transplant. 2,3 • Dietary—Increased intake o meat and sea ood, alcohol, so t drinks, and ructose. 2

DIAGNO SIS Following are the diagnostic characteristics use ul in predicting gout, based on the 1977 criteria developed by the American College o Rheumatology:

A

• Monoarthritis • Redness over the joints • First metatarsophalangeal (MTP) joint involved (Figure 105-3) • Unilateral rst MTP joint attack • Unilateral tarsal joint attack • Tophi identi ed (Figures 105-1, 105-4, and 105-5) • Hyperuricemia • Asymmetric swelling in joint on radiograph • Subcortical cysts on radiograph • MSU crystals in joint f uid (Figure 105-6) • Joint f uid culture negative The presence o 6 o these 11 criteria helps con rm gout (positive likelihood ratio [LR+ ] 20, negative likelihood ratio [LR− ] 0.02). 4 CLINICAL FEATURES

B

• Gout usually begins at night as an acute attack over several hours.

FIGURE 105-4 A. A 52-y a -old om l ss man wit acut monoa ticula g outy a t itis s nting wit kn ain and sw lling . Kn as i ation v al d a st aw-colo d usion. B. Wit lig t mic osco y num ous actil n d l -s a d c ystals o u ic acid w visualiz d in t joint f uid . T arrow oints to a clust o n d l -s a d u ic acid c ystals. (Top : Re p rod uce d with p e rmission rom Usatine RP, Sacks B, Sorci J. A swolle n kne e . J Fam p act. 2003;52(1):53-55. Bottom: Re p rod uce d with p e rmission rom Frontline Me d ical Communications.)

• Fever, chills, and arthralgias sometimes precede gout. • The a ected joint is swollen, red, hot, and pain ul to touch and movement (see Figures 105-1, 105-3, and 105-6). Symptoms subside in 3 to 10 days. • Dietary or alcohol excess, trauma, surgery, and serious medical illness can precipitate gout attacks.

TYPICAL DISTRIBUTIO N Initially, only one joint may be a ected, but other joints commonly involved are ngers and toes (75%) and knees and ankles (50%). • The most common site is the rst MTP joint and the name or gout at this site is podagra (see Figure 105-3). • Joint involvement is o ten asymmetric. • Tophi may be seen at the MTP joint, elbow, hands, and ears (see Figures 105-1, 105-4, and 105-5). LABO RATO RY TESTING

FIGURE 105-3 pod ag a. Ty ical inf ammato y c ang s o g out at jo int. (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

st MTp

• Serum uric acid is o ten elevated, but is variable rom week to week and normal in 25% o patients with gout. • Measure 24-hour urine or excretion o uric acid.

505

506

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch ApTe r 105

• Rheumatic arthritis—Symmetric joint involvement (usually hands); slow onset; synovial culture is negative (see Chapter 99, Rheumatoid Arthritis). • Pseudogout—Findings like gout; synovial f uid with short rods; crystal re raction blue on red background (calcium pyrophosphate dihydrate).

MANAGEMENT ACUTE GO UT

FIGURE 105-5 S v to ac ous g out causing majo d o miti s in t and s. (Re p rod uce d with p e rmission rom Eric Kraus, MD.)

• On microscopy, the presence o MSU crystals rom synovial f uid or a tophus that are negatively bire ringent in polarized light (yellow against a red background) helps to con rm the diagnosis, but there are limited data on the accuracy o crystal identi cation. • Even with light microscopy re ractile needle-shaped crystals o uric acid can be visualized in the joint f uid (see Figure 105-6). IMAGING Although radiographs are negative early in the disease, punched-out erosions (“rat bites”) are seen later and can be diagnostic, especially i seen adjacent to tophi (see Figure 105-2).

DIFFERENTIAL DIAGNO SIS In addition to gout, the di erential diagnosis o inf ammatory monoarthritis includes the ollowing: • Cellulitis—Joint motion is not pain ul; synovial culture is negative (see Chapter 122, Cellulitis). • Septic arthritis—Fever; pain ul motion; synovial f uid has many white blood cells and a positive culture.

FIGURE 105-6 To ac ous d osits on b ot lb ows and on ng in a man wit g out. (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

• Prescribe an NSAID, such as indomethacin 50 to 75 mg every 6 to 8 hours, in patients without renal impairment (serum creatinine should be < 2) or peptic ulcer disease. 5 SO R • Colchicine can be used in patients who cannot take NSAIDs. Colchicine 1.2 mg ollowed by 0.6 mg a ter 1 hour has equivalent e cacy and lower side e ects compared to a high dose o 4.8 mg given over 6 hours. One-third o patients will respond. 6 SO R • In monoarticular gout, consider an intra-articular injection with longacting steroid (eg, triamcinolone acetonide, 10-40 mg, depending on the size o the joint). 5 SO R CHRO NIC GO UT The treatment o chronic gout includes modi cations in diet and existing medications (i possible) and lowering urate levels. Treatment measures include the ollowing1: • Nonpharmacologic ° Reduce the intake o purine-rich oods (eg, organ meats, red meats, and sea ood). ° Increase f uid intake to 2000 mL/ d. ° Lower alcohol intake. 1 Consume dairy products as these may be protective against gout. ° • Medications ° Change medications—Discontinue aspirin (low dose up to 2 g/ d causes uric acid retention) and consider stopping a thiazide diuretic. Calcium channel blockers and losartan are associated with a lower risk o gout in patients with hypertension. 7 ° Lower urate levels with xanthine oxidase inhibitors (eg, allopurinol), uricosuric agents (eg, probenecid), or uricase agents (eg, pegloticase). ° The level o urinary uric acid helps to determine which medication should be used with levels greater than or equal to 600 mg/ 24 h indicating a need to halt production with xanthine oxidase inhibitors and levels less than 600 mg/ 24 h indicating a need or uricosuric drugs. ° Allopurinol (100-300 mg/ d or mild gout; or patients with moderate-to-severe tophaceous gout give 400-600 mg/ d with a maximum daily dose o 800 mg/ d). Titrate allopurinol to a serum uric acid level less than 6. 8 SO R ° Give colchicine (0.6 mg twice daily or the rst 6 months o therapy) concomitantly during initiation o allopurinol to reduce the requency and severity o acute f ares. 9 SO R ° Consider uricosuric agents (probenecid, 250 mg twice daily increasing to 2-3 g/ d or sul npyrazone, 50-100 mg twice daily increasing to 200-400 twice daily) in patients with uric acid excretion o less than 600 mg/ 24 h, with normal renal unction, younger than age 60 years, and no history o renal calculi. 5 SO R

GO UT

° Consider oral potassium citrate (10-20 mEq 3-4 times a day) to prevent crystal precipitation in the urine as uricosuric agents increase urinary uric acid excretion. ° Pegloticase, a mammalian recombinant uricase, is a medication that degrades urate when administered by intravenous in usion. Early randomized controlled trials show improvements in pain and quality o li e; however, adverse events are high. This may be an option or patients with severe gout, allopurinol intolerance or re ractoriness, and serum uric acid greater than 8 mg/ dL despite conventional therapy. 10 • Complementary and alternative therapy ° A number o Chinese and Vietnamese medicinal plants and herbs have xanthine oxidase inhibitory activity, but ew have been tested or clinical e ectiveness.

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC PATIENT RESO URCES

• The Arthritis Foundation. Gout Living—http:/ / www.arthritis .org/ goutliving-basics.php. • MedlinePlus. Gout—http:/ / www.nlm.nih.gov/ medlineplus/ goutandpseudogout.html. • The American College of Rheumatology. Gout—http:/ / www .rheumatology.org/ practice/ clinical/ patients/ diseases_and_conditions/ gout.asp. PRO VIDER RESO URCES

• Medscape. Gout and Pseudogout—http:/ / emedicine.medscape .com/ article/ 329958. REFERENCES

PREVENTIO N • Intake o dairy products, olate, and co ee lowers the risk o gout. 3 • In a patient with a prior episode o gout, avoid medications that cause hyperuricemia—Thiazide diuretics, cyclosporine, aspirin (< 1 g/ d). 2

PRO GNO SIS • Untreated, recurrent, and more severe attacks are common with 60% o patients experiencing a recurrence in the rst year and 25% in the second year. • Colchicine 0.5 mg up to 3 times a day decreases attacks, but may not decrease joint destruction. 8 SO R

FO LLO W-UP Follow patients with an acute f are through resolution and initiation o prophylactic therapy i indicated.

PATIENT EDUCATIO N Advise patients to lose weight, minimize alcohol use, eat less meat and sea ood, and obtain more protein rom dairy. 5

1. Choi HK, Curhan G. Gout: epidemiology and li estyle choices. Curr Opin Rheumatol. 2005;17(3):341-345. 2. Neogi T. Gout. N Engl J Med. 2011;362:443-452. 3. Singh JA, Reddy SG, Kundukulam J. Risk actors or gout and prevention: a systematic review o the literature. Curr Opin Rheumatol. 2011;23(2):192-202. 4. Silman AJ, Hochberg MC. Epidemiology of the Rheumatic Diseases. New York, NY: Ox ord University Press; 1993. 5. Wortmann RL. Recent advances in the management o gout and hyperuricemia. Curr Opin Rheumatol. 2005;17(3):319-324. 6. Terkeltaub RA, Furst DE, Bennett K, et al. High versus low dosing o oral colchicine or early acute gout f are: twenty- our-hour outcome o the rst multicenter, randomized, double-blind, placebocontrolled, parallel-group, dose-comparison colchicine study. Arthritis Rheum. 2010;62(4):1060-1080. 7. Choi HK, Soriano LC, Zhang Y, Rodriguez LA. Antihypertensive drugs and risk o incident gout among patients with hypertension: population based case-control study. BMJ. 2012;344:d8190. 8. Winklerprins VJ, Weismantel AM, Trinh TH. Clinical inquiries. How e ective is prophylactic therapy or gout in people with prior attacks? J Fam Pract. 2004;53(10):837-838. 9. Borstad GC, Bryant LR, Abel MP, et al. Colchicine or prophylaxis o acute f ares when initiating allopurinol or chronic gouty arthritis. J Rheumatol. 2004;31(12):2429-2432. 10. Sundy JS, Bara HS, Yood RA, et al. E cacy and tolerability o pegloticase or the treatment o chronic gout in patients re ractory to conventional treatment. JAMA. 2011;306(7):711-720.

507

508

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

106 O LECRANO N BURSITIS He id i Chumle y, MD

PATIENT STO RY

Ch a pTe r 106

EPIDEMIO LO GY Prevalence o aseptic olecranon bursitis is unknown, but is estimated to be twice as common as septic olecranon bursitis. 1 • Prevalence o septic olecranon bursitis is at least 10 per 100,000 in the general population. 2 • Peak age o onset is 40 to 50 years.

A 60-year-old man presents with swelling in his elbow or the last 2 months. He does not have pain unless he leans on his elbow. He denies any trauma. Figure 106-1 demonstrates a “goose egg” swelling over the olecranon bursa that is not warm and is tender only to palpation. He has ull range o motion. His olecranon bursitis was treated with ice, rest, and nonsteroidal anti-in ammatory drugs (NSAIDs) and he was told to avoid leaning on his elbow.

INTRO DUCTIO N Olecranon bursitis can be aseptic, rom repetitive trauma or systemic disease, or septic, most commonly rom gram-positive bacteria. Di erences in clinical presentation help di erentiate aseptic rom septic olecranon bursitis; however, analysis o uid may be necessary. Aseptic olecranon bursitis is treated with an elbow pad, NSAIDs, and ice. Septic olecranon bursitis is treated with drainage and antibiotics.

SYNO NYMS Olecranon bursitis is also known as popeye elbow, student elbow, or baker elbow.

• Eighty-one percent are male. • Fi ty percent have antecedent trauma.

ETIO LO GY AND PATHO PHYSIO LO GY In ammation or degeneration o the sac overlying the olecranon bursa occurs because o the ollowing actors: • Repetitive motion or trauma, such as direct pressure on the elbow • Systemic diseases such as gout, pseudogout, and rheumatoid arthritis • In ection, typically by Staphylococcus aureus or another gram-positive organism

RISK FACTO RS • Aseptic bursitis—Occupation-related activities such as leaning on the elbow • Septic bursitis—Immunocompromised state

DIAGNO SIS The diagnosis o olecranon bursitis is made clinically, by its typical appearance (Figures 106-1 and 106-2). When necessary, joint aspiration verif es the diagnosis and separates septic rom aseptic bursitis. CLINICAL FEATURES O F SEPTIC BURSITIS • Common symptoms2—Pain (87%), redness (77%), and subjective ever or chills (45%) • Common signs—Erythema (92%), swelling (85%), edema (75%), tenderness (59%), and uctuance (50%) • Less common signs—Decreased range o motion (27%) and temperature greater than or equal to 37.8°C (100.04°F) (20%) CLINICAL FEATURES O F ASEPTIC BURSITIS • Swelling with minimal pain and tenderness. • Erythema may be present (see Figure 106-2). • Fever is typically absent. LABO RATO RY TESTING • Erythrocyte sedimentation rate (ESR) and C-reactive protein may be elevated in both septic and aseptic presentations. 3

FIGURE 106-1 C onic s tic ol c non b u sitis in 60-y -old m n s owing ty ic l sw lling ov t ol c non. T is no yt m o t nd n ss. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Bursal uid f ndings that help di erentiate septic rom aseptic olecranon bursitis are as below3: ° White blood cell (WBC) count is greater than 30,000 in septic bursitis and less than 28,000 in aseptic bursitis; however, elevated WBC count is also seen in rheumatoid arthritis or gout.

O Le LECRANO Cr a NO N BUr BURSITIS SITIS

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

FIGURE 106-3 a s i tion o n ol c non b u sitis od uc d st w-colo d uid wit no WBCs o b ct i s n und mic osco . T is conf m d t clinic l im ssion t t t ti nt d id not v s tic ol c non b u sitis. h lso d li o sym toms wit t uid s i tion. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 106-2 a s tic ol c non b u sitis s cond y to titiv lb ow l ning in t is com ut og mm . T is som yt m nd minim l t nd n ss. T s i t d uid w s cl . Most ti nts (70%) t in ull xt nsion in t lb o w d s it sw lling ov t ol c no n. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

° Neutrophils are seen in septic bursitis; monocytes are seen in aseptic bursitis. ° Glucose less than 50% o serum glucose is ound in septic bursitis and greater than 70% o serum glucose is ound in aseptic bursitis. ° Gram-positive organisms are seen on Gram stain in septic bursitis. IMAGING

Other causes o elbow pain typically without swelling include the ollowing actors: • Lateral or medial epicondylitis (pain lateral or medial, not over olecranon) • Ulnar nerve entrapment (concurrent numbness in f ngers)

MANAGEMENT SEPTIC BURSITIS • Identi y organism using Gram stain and culture (Figure 106-4). • I the WBC is slightly elevated and no organisms are seen on Gram stain, treat empirically with oral antibiotics active against gram

• Usually not indicated. • In traumatic bursitis, radiographs may identi y a oreign body. • In atypical cases, magnetic resonance imaging (MRI) may be needed to determine the extent o so t tissue involvement. ASPIRATIO N Aspirate when there is suspicion o in ection or crystal disease (moderate pain, ever, warmth over the olecranon)4 or or discom ort caused by extensive swelling (Figures 106-3 and 106-4). 5

DIFFERENTIAL DIAGNO SIS Pain and swelling around the elbow joint may be caused by the ollowing actors: • Gout or pseudogout (acute pain with signs o in ammation), prior history o gout (pseudogout) • Rheumatoid arthritis (pain, in ammation, loss o range o motion, o ten involves other joints) • Septic joint (acute pain, loss o range o motion, ever) • Hemorrhage into the bursa (history o trauma, bruising)

FIGURE 106-4 S tic ol c non b u sitis in n immunosu ss d ti nt wit m ig us vulg is. a s i tion s ow d g m- ositiv cocci on G m st in nd Mr Sa g w out o t cultu . p ti nt w s t t d in t os it l wit IV v ncomycin nd t n d isc g d on o l d oxycyclin w n t s nsitiviti s w v il b l nd t ti nt w s st b l . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

509

510

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC positives until culture results are available (ie, cephalexin 500 mg twice a day or levo oxacin 500 mg/ d). 6 SO R • I WBCs are moderately elevated and organisms are seen on Gram stain, use intravenous (IV) medications such as oxacillin or na cillin 2 g every 6 hours or ce azolin 1 to 2 g every 8 hours. 6 SO R • Vancomycin can be considered or penicillin- or cephalosporin-allergic patients or in communities with high rates o methicillin-resistant S. aureus (MRSA). 6 SO R • Home IV therapy is sa e and e ective or immunocompetent patients. 2 SO R

• Hospitalize immunosuppressed patients or those who do not respond to therapy. 6 SO R • Aspirate a ter several days o treatment and continue antibiotics or 5 days a ter uid is sterile. 6 SO R • Re er to an orthopedic specialist i incision and debridement o the bursa is needed. SO R ASEPTIC BURSITIS • The f rst line o treatment should be wearing an elbow pad at all times in addition to modif cation o activities (no leaning on elbows) and NSAIDs as tolerated.

Ch a pTe r 106

FO LLO W-UP Follow septic bursitis until uid is sterile. Reaspirate a ter 4 to 5 days o antibiotics and continue antibiotics or 5 days a ter uid is sterile.

PATIENT EDUCATIO N Limit bursa aggravation by not leaning on elbows or pushing o on elbows when arising. Aseptic and septic bursitis may require multiple aspirations. PATIENT RESO URCES

• Patient.co.uk. Olecranon Bursitis—http:/ / www.patient.co.uk/ health/ Olecranon-Bursitis.htm. PRO VIDER RESO URCES

• American Academy o Family Physicians. Diagnostic and Therapeutic Injection of the Elbow Region (includes a description o aspiration technique)—http:/ / www.aafp.org/ afp/ 2002/ 1201/ p2097 .html.

• Patient education about aggravating actors. • Ice and rest.

REFERENCES

• Consider corticosteroid injection or severe pain, persistent, or recurrent uid accumulation. 6 SO R Because there is a risk o converting an aseptic olecranon bursitis to a septic one with aspiration and steroid injection, the treatment options noted above should be exhausted prior to consideration o steroid injection.

1. Stell IM. Septic and non-septic olecranon bursitis in the accident and emergency department–an approach to management. JAccid Emerg Med. 1996;13(5):351-353.

• Consider surgical re erral or recalcitrant uid accumulation. ASPIRATIO N When indicated, aspirate uid as ollows5: • Flex elbow to 45 degrees. • Locate triangle ormed by lateral olecranon, the head o the radius, and the lateral epicondyle. • Using sterile technique, insert needle into the so t tissue in the middle o the triangle, pointing toward the medial epicondyle. (I there is a signif cant amount o uid, it is hard to miss the uid regardless o the direction o the needle as long as the needle gauge is su f cient or aspiration. Consider a 20- to 22-gauge needle, and i an 18-gauge needle is to be used, give the patient some local anesthetic f rst. • Aspirate luid and send or complete blood count (CBC), Gram stain, culture, and evaluate or crystals i gout or pseudogout is expected. • Consider injecting with steroid (see below) only i aspirate is clear and history does not suggest in ection.

PRO GNO SIS • Aseptic olecranon bursitis o ten resolves with conservative therapy. 7 • Septic bursitis has a recurrence rate o 15% in hospitalized patients treated with surgical interventions and antibiotics. 7

2. Laupland KB, Davies HD. Calgary home parenteral therapy program study group. Olecranon septic bursitis managed in an ambulatory setting. The Calgary home parenteral therapy program study group. Clin Invest Med. 2001;24:171-178. 3. Wasserman AR, Melville LD, Birkhahn RH. Septic bursitis: a case report and primer or the emergency clinician. J Emerg Med. 2009;37(3):269-272. 4. Work Loss Data Institute. Elbow (Acute and Chronic). National Guidelines Institute. http:/ / guidelines.gov/ content.aspx?id= 33179. Updated April 28, 2011. Accessed November 21, 2011. 5. Cardone DA, Tallia AF. Diagnostic and therapeutic injection o the elbow region. Am Fam Physician. 2002;66(11):2097-2100. 6. Sheon RP, Kotton CN. Septic Bursitis. UpToDate. http:/ / www.utdol. com/ utd/ content/ topic.do?topicKey=skin_in / 12648. Accessed February 24, 2008. 7. Perez C, Huttner A, Assal M, et al. In ectious olecranon and patellar bursitis: short-course adjuvant antibiotic therapy is not a risk actor or recurrence in adult hospitalized patients. JAntimicrob Chemother. 2010;65(5):1008-1014.

CLa VICULa r Fr a Ct Ur e

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

107 CLAVICULAR FRACTURE He id i Chumle y, MD

PATIENT STO RY A 22-year-old man presents a ter alling and landing directly on his lateral shoulder. He had immediate pain and swelling in the middle o his clavicle. His examination revealed a bump in the middle o his clavicle. A radiograph con rmed a midclavicular racture (Figure 107-1). He was treated conservatively with a sling, which he wore or approximately one o the recommended 3 weeks. A ollow-up radiograph demonstrated good healing. The bump on his clavicle is still palpable; however, this does not bother him.

INTRO DUCTIO N Clavicular ractures are common and are usually caused by accidental trauma. The clavicle most commonly ractures in the midsha t (Figures 107-1 to 107-3), but can also racture distally (Figure 107-4). Many ractures can be treated conservatively. Re er patients with signi cant displacement or distal ractures or surgical evaluation.

EPIDEMIO LO GY Clavicular ractures account or 2.6% o all ractures in adults, with an overall incidence o 64 per 100,000 people per year; midsha t ractures account or approximately 69% to 81% o all clavicle ractures. 1,2

FIGURE 107-2 Mid s cl vicl cu p e rmission from John De lze ll, MD.)

wi

ng ul ion. (Re p ro d uce d with

ETIO LO GY AND PATHO PHYSIO LO GY • Most are caused by accidental trauma rom all against the lateral shoulder or an outstretched hand or direct blow to the clavicle; however, stress ractures in gymnasts and divers have been reported. • Pathologic ractures (uncommon) can result rom lytic lesions, bony cancers, or metastases, or radiation. • Physical assaults or intimate partner violence can cause clavicular ractures.

DIAGNO SIS CLINICAL FEATURES • History o trauma with a mechanism known to result in clavicle ractures (ie, all on an outstretched hand or lateral shoulder, or direct blow)

FIGURE 107-1 Mid s cl vicl c u . Cl vicl cu s d sig n d mid s (in mid d l i d ), d is l (d is l i d ), o m d i l (m d i l i d ). (Re p rod uce d with p e rmission from John De lze ll, MD.)

FIGURE 107-3 Mid s cl vicul c u wi oxim l g m n d is l c d su io ly om ull o s nocl id om s oid muscl . (Re p rod uce d with p e rmissio n from Simon RR, She rman SC, Koe nig skne cht SJ. e m g ncy O o d ics e x mi i s. Ne w York, NY: McGraw-Hill; 2007:283, Fig ure 11-32. Cop yrig ht 2007.)

511

512

PART 13

Ch a pt e r 107

MUSCULO SKELETAL/ RHEUMATO LO GIC

FIGURE 107-4 Dis l cl vicul c u . (Re p rod uce d with p e rmission from Simon RR, She rman SC, Koe nig skne cht SJ. e m g ncy O e x mi i s. Ne w York, NY: McGraw-Hill; 2007:286, Fig ure 11-35. Cop yrig ht 2007.)

• Pain and swelling at the racture site

o

d ics

MANAGEMENT

• Gross de ormity at the site o racture

Initial assessment includes the ollowing:

TYPICAL DISTRIBUTIO N For the typical distribution and classi cation o clavicular ractures, see Table 107-1. IMAGING Obtain plain lms o the clavicle or radiographic evidence o racture.

• Assess neurovascular status o injured extremity. • Assess or damage to lungs (pneumothorax or hemothorax). • Determine the classi cation and amount o displacement by radiograph (see Figure 107-1; see also Table 107-1). NO NPHARMACO LO GIC Most clavicular ractures can be treated nonoperatively, other options include xation with plates or pins.

DIFFERENTIAL DIAGNO SIS • Acromioclavicular (AC) separation (Figure 107-5)—Fall directly on the “point” o the shoulder or a direct blow, pain with overhead movement, tenderness at the AC joint, and AC joint separation on radiographs • Sternoclavicular dislocation—Fall on the shoulder, chest and shoulder pain exacerbated by arm movement or when lying down, and a prominence rom the superomedial displacement o the clavicle (uncommon) • Pseudoarthrosis o the clavicle—Painless mass in the middle o the clavicle rom ailure o the central part o the clavicle to ossi y (extremely rare)

Mid clavicular fract ure s • Treat adults with non- or minimally displaced midsha t clavicular ractures nonoperatively. SO R • Place adults in a sling instead o a gure-o -8 bandage. Patients treated with a sling had higher treatment satis action than those treated with a gure-o -8 bandage. 3 SO R • Midclavicular ractures can be treated with a clavicle brace; treat until radiographic evidence o healing has occurred. SO R Wearing the brace rees the upper extremities or activities o daily living. The clavicle brace may improve the alignment o the midclavicular racture.

TABLE 107-1 t y ic l Dis ib u ion/Cl ssif c ion

Gro up (Ap p ro x. %)

Fract ure Lo cat io n Rad io g rap hic Ap p e arance

G ou I (80%)

Mid d l

G ou II (15%)

Dis l

id id

U w d d is l c m n (s M d i l sid o

g m n is d is l c d u w d (s

ty

I

Minim l d is l c m n

ty

II

F cu

ty

III

F cu aCs

G ou III (5%)

M di l

id

Fig ure s 107-1 to 107-3)

m d i l o co cocl vicul icul

su

c o

lig m n s; som ov l c omiocl vicul

ion

M d i l sid o

Fig ure 107-4)

g m n u ; d is l sid d own

ing o

gm n s

(a C) join ; c n look lik

CLa VICULa r Fr a Ct Ur e

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC • Patients with distal clavicle ractures treated nonoperatively had nonunion rates o 21%; however, there was no di erence in unction between those who healed and those with a nonunion. 6 SO R

FO LLO W-UP Monitor with examination and radiographs until pain has resolved, any lost unction has returned, and there is radiographic evidence o healing. Initially, repeat X-ray every 1 to 2 weeks to evaluate or any change in alignment. I the racture is stable, repeat X-ray every 4 to 6 weeks until the clavicle has healed. I there is no evidence o healing a ter 2 to 3 months, re erral should be considered.

PATIENT EDUCATIO N FIGURE 107-5 a c omiocl vicul (a C) join s ion ( i d d g ) wi wid a C join nd cl vicl d is l c d om c omion. (Re p rod uce d with p e rmission from Simon RR, She rman SC, Koe nig skne cht SJ. e m g ncy O o d ics e x mi i s. Ne w York, NY: McGraw-Hill; 2007:297, Fig ure 11-54. Cop yrig ht 2007.)

• Re er patients with initial racture shortening over 2 cm to discuss operative and conservative options. SO R These patients have a higher risk o a nonunion associated with poor unctional outcomes. 4 Dist al clavicular fract ure s • Treat patients with nondisplaced distal clavicle ractures conservatively. • Distal clavicle ractures are commonly treated by wearing a sling or 6 weeks to minimize the weight o the arm pulling on the distal clavicle ragment. • Some patients with displaced distal clavicle racture may bene t rom surgery. Re er patients, other than the very elderly, to discuss risks and bene ts o operative and nonoperative options. 5

Most clavicle ractures heal without surgery, especially i the racture is not displaced. Fractures in adults take 6 to 8 weeks to heal. O ten, there will be a bump at the site o the healed racture, which typically does not inter ere with any activities.

PATIENT RESO URCES

• American Academy of Orthopedic Surgeons. Patient information handout under Broken Collarbone—http:/ / orthoinfo.aaos.org/ topic.cfm?topic=A00072. PRO VIDER RESO URCES

• Medscape. Clavicle Fractures—http:/ / emedicine.medscape .com/ article/ 1260953. • Duke University online. Wheeless’ Textbook of Orthopaedics— http:/ / www.wheelessonline.com/ ortho/ clavicle_ fractures.

MEDICATIO NS Treat pain as needed with acetaminophen or nonsteroidal anti-inf ammatory drugs (NSAIDs). REFERRAL • Re er or surgical evaluation, patients with impingement o so t tissue/ muscle, instability o shoulder girdle, displacement with skin per oration/ necrosis, or risk to mediastinal structures. 2 SO R

REFERENCES 1. Zlowodzki M, Zelle BA, Cole PA, et al; Evidence-Based Orthopaedic Trauma Working Group. Treatment o acute midsha t clavicle ractures: systematic review o 2144 ractures: on behal o the Evidence-Based Orthopaedic Trauma Working Group. J Orthop Trauma. 2005;19(7):504-507.

• Consider re erring patients with displaced ractures. Nonoperative treatment has a 15.1% nonunion rate, whereas operative rates are 0% to 2%.1

2. Kubiak R, Slongo T. Operative treatment o clavicle ractures in children: a review o 21 years. J Pediatr Orthop. 2002;22:736-739.

• Consider consulting with a physician skilled in managing clavicular ractures in patients with a distal clavicle racture. These ractures have a high rate o nonunion; however, only a portion o nonunions are pain ul or inhibit unction. I the patient continues to have a symptomatic nonunion a ter many months, surgery may be considered.

4. Preston CF, Egol KA. Midsha t clavicle ractures in adults. Bull NYU Hosp Jt Dis. 2009;67(1):52-57.

PRO GNO SIS • Midclavicular displaced ractures treated nonoperatively have a nonunion rate o up to 15% and a poor unctional outcome in up to 5%. Operative nonunion rates are 0% to 2%. 1

3. Andersen K, Jensen PO, Lauritzen J. Treatment o clavicular ractures. Figure-o -eight bandage versus a simple sling. Acta Orthop Scand. 1987;58(1):71-74.

5. Khan LA, Bradnock TJ, Scott C, Robinson CM. Fractures o the clavicle. J Bone Joint Surg Am. 2009;91(2):447-460. 6. Robinson CM, Cairns DA. Primary nonoperative treatment o displaced lateral ractures o the clavicle. J Bone Joint Surg Am. 2004; 86-A(4):778-782.

513

514

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch ApTER 108

108 DISTAL RADIUS FRACTURE He id i Chumle y, MD Richard P. Usatine , MD

PATIENT STO RY A 65-year-old woman tripped on a rug in her home and ell on her outstretched hand with her wrist dorsi exed (extended). She elt immediate pain in her wrist and has di f culty in moving her wrist or hand. She has been postmenopausal or 15 years and has never taken hormone replacement therapy or bisphosphonates. She presented with pain and swelling in her wrist. Her arm had a “dinner- ork” de ormity. Radiographs showed a distal radius racture with dorsal angulation on the lateral view (Figure 108-1).

INTRO DUCTIO N Distal radius ractures are common, especially in postmenopausal women. Patients present with wrist pain and a “dinner- ork” de ormity. Diagnosis is conf rmed by radiographs. Treatment is either operative or nonoperative, based on the degree o displacement and the age o the patient.

A

SYNO NYMS Colles racture is the most common type. Other types o distal radius ractures include Smith racture, Barton racture, and Hutchinson racture.

EPIDEMIO LO GY • More common in older women—Female-to-male ratio o 3.2:1. 1 • Prevalence—In a community study o 452 people older than age 40 years in the United Kingdom, 10.8% o women and 2.6% o men had a prior distal radius racture. 2 • Incidence—In Sweden, the incidence is 115 per 100,000 women and 29 per 100,000 men. 1

ETIO LO GY AND PATHO PHYSIO LO GY B

• Classic history is a all on an outstretched hand. • In patients older than 40 years o age, there is a strong association with osteoporosis. Patients with low-impact distal radius ractures have higher rates o osteoporosis than age-matched controls without ractures by bone density measured at the wrist (60% vs 35%; p < 0.001; odds ratio [OR], 5.7; 95% conf dence interval [CI], 1.227.2) and lumbar spine (47% vs 20%; p < 0.005; OR, 3.9; 95% CI, 1.1-14.3). 3

FIGURE 108-1 Colle s racture . T is occurre d a te r a all on an e xte nd e d wrist. A. Late ral vie w s ows a d istal rad ius racture wit d orsal ang ulation. B. Ante rior- oste rior vie w d e monstrating a transve rse d istal rad ius racture . (Re p rod uce d with p e rmission from Re b e cca Lore d o-He rnand e z, MD.)

• Postmenopausal women and older men with distal radius ractures have an increased risk or a uture hip racture (relative risk [RR] = 1.53; 95% CI, 1.34-1.74; p 10 cm laxity), place in a hinged brace, initially non– weight bearing, advancing to weight bearing over 4 weeks. Grade III LCL tears o ten require surgery.

PRO GNO SIS 6

Most young active adults have an excellent prognosis rom knee injuries. Nonsurgical management o ACL tears has a good prognosis rom 1 to 5 years, but patients reduce their activity level by 21%. 14

t h e KNe e

FO LLO W-UP Timing o ollow-up is determined by the orthopedic surgeon, sports medicine specialist, or other provider skilled in acute knee injury management.

PATIENT EDUCATIO N

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC 2. Owens BD, Mountcastle SB, Dunn WR, et al. Incidence o anterior cruciate ligament injury among active duty U.S. military servicemen and servicewomen. Mil Med. 2007;172(1):90-91. 3. Cimino PM. The incidence o meniscal tears associated with acute anterior cruciate ligament disruption secondary to snow skiing accidents. Arthroscopy. 1994;10(2):198-200. 4. Bhattacharya T, Gale D, Dewire P, et al. The clinical importance o meniscal tears demonstrated by magnetic resonance imaging in osteoarthritis o the knee. J Bone Joint Surg Am. 2003;85-A:4-9.

• ACL tears o ten require surgery, take 4 to 6 months to heal, and require a commitment to rehabilitation or the best results.

5. Ebell MH. Evaluating the patient with a knee injury. Am Fam Physician. 2005;71(6):1169-1172.

• Meniscal tears may require surgery when mechanical symptoms are present. The location o the tear determines how likely surgical repair is to be e ective because o the blood supply available or healing.

6. Bachmann KM, Haberzeth S, Steurer J, Ter Riet G. The accuracy o the Ottawa knee rule to rule out knee ractures: a systematic review. Ann Intern Med. 2004;140(2):121-124.

• Meniscal tears are commonly seen on MRI in patients with osteoarthritis who do not have pain and meniscal tears seen on MRI may not be contributing to arthritic pain.

7. David K, Frank B. Anterior cruciate ligament rupture. Br J Sports Med. 2005;39:324-329.

• Collateral tears can o ten be treated conservatively, while protecting the knee in a brace and preserving range o motion. Complete tears to the LCL o ten require surgery. PATIENT RESO URCES

8. New Zealand Guidelines Group (NZGG). The Diagnosis and Management of Soft Tissue Knee Injuries: Internal Derangements. Wellington, NZ: New Zealand Guidelines Group (NZGG), 2003:100. 9. Legnani C, Terzaghi C, Borgo E, Ventura A. Management o anterior cruciate ligament rupture in patients aged 40 years and older. J OrthopTraumatol. 2011;12(4):177-184.

• The American Academy of Family Physicians has a patient algorithm or knee pain—http:/ / familydoctor.org/ familydoctor/ en/ health-tools/ search-by-symptom/ knee-problems.html.

10. Greis PE, Bardana DD, Holmstrom MC, Burks RT. Meniscal injury I: basic science and evaluation. JAmAcad Orthop Surg. 2002;10(2):168-176.

• The National Institute of Health through the National Institute or Arthritis and Musculoskeletal and Skin Diseases has patient in ormation on several types o knee problems—http:/ / www .niams.nih.gov/ Health_Info/ Knee_Problems/ default .asp.

11. Suter LG, Fraenkel L, Losina E, et al. Medical decision making in patients with knee pain, meniscal tear, and osteoarthritis. Arthritis Rheum. 2009;61(11):1531-1538.

PRO VIDER RESO URCES

• The Ottawa and Pittsburgh Knee Rules are available in an online calculator—http:/ / www.mdcalc.com/ ottawa-andpittsburg-knee-rules. • Dr. Hutchinson’s Knee Exam from the University of British Columbia—http:/ / www.youtube.com/ user/ BJSMVideos. REFERENCES 1. Walden M, Hagglund M, Werner J, Ekstrand J. The epidemiology o anterior cruciate ligament injury in ootball(soccer): a review o the literature rom a gender-related perspective. Knee Surg Sports Traumatol Arthrosc. 2011;19(1):3-10.

12. Barber-Westin SD, Noyes FR, Smith ST, Campbell TM. Reducing the risk o noncontact anterior cruciate ligament injuries in the emale athlete. Phys Sportsmed. 2009;37(3):49-61. 13. Olsen OE, Myklebust G, Engebretsen L, Holme I, Bahr R. Exercises to prevent lower limb injuries in youth sports: cluster randomised controlled trial. BMJ. 2005;330(7489):449. 14. Muaidi QI, Nicholson LL, Re shauge KM, et al. Prognosis o conservatively managed anterior cruciate ligament injury: a systematic review. Sports Med. 2007;37(8):703-716.

529

530

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch a pt e r 112

112 DUPUYTREN DISEASE John E De lze ll Jr, MD, MSPH He id i Chumle y, MD

PATIENT STO RY A 53-year-old man presented with sti ness in his hands. He said his hands began to eel sti several years ago, and now he nds that he cannot straighten many o his ngers (Figure 112-1). He delayed seeing a physician because he did not eel any pain in his hands. He recently began having di culty holding his woodworking tools and wants to regain the unction he has lost in his hands. The physician diagnosed him with Dupuytren contracture and discussed the disease with him along with his options or treatment.

INTRO DUCTIO N Dupuytren contracture is a f exion contracture o one or more o the ngers in the hand. Patients develop a progressive thickening o the palmar ascia, which causes the ngers to bend in toward the palm and limits extension. Diagnosis is clinical and the palpable nodules in the palm are considered diagnostic. Treatment has historically been surgical, but a new nonsurgical treatment with a collagenase has been approved.

SYNO NYMS Dupuytren disease is also known as Dupuytren contractures, palmar bromatosis, morbus Dupuytren, or Ledderhose disease.

FIGURE 112-2 Du uy n con ac u in a 60-y a -old man s owing a xion con ac u o f d ig i and a alma co d . All o is b o s av Du uy n con ac u s. (Re p ro d uce d with p e rmissio n fro m Richard P. Usatine , MD.)

• Higher prevalence is among whites, particularly o Northern European descent. There is an increasing incidence related to aging. 1 • It is more common in men than women (approximately 6:1). 2,3 • Incidence in the United States is estimated to be approximately 3 per 10,000 adults with an estimated prevalence o 7%. • Higher incidence is ound in people who use tobacco and alcohol or who have diabetes mellitus or epilepsy. 4

ETIO LO GY AND PATHO PHYSIO LO GY Dupuytren contractures orm in ollowing 3 stages: • Myo broblasts in the palmar ascia proli erate to orm nodules. • Myo broblasts then align along the lines o tension, orming cords.

EPIDEMIO LO GY • Dupuytren contracture is an autosomal dominant disease with incomplete penetrance (Figure 112-2).

• Tissue becomes acellular leaving thick cords o collagen that tighten resulting in f exion contractures at the metacarpal phalangeal joint, the proximal interphalangeal joint, and, occasionally, the distal interphalangeal joint.

RISK FACTO RS • Tobacco use • Alcohol consumption • Epilepsy • Diabetes mellitus • Carpal tunnel syndrome • History o manual labor • History o hand injury

DIAGNO SIS CLINICAL FEATURES • Clinical diagnosis is based on the history and physical examination. FIGURE 112-1 Du uy n con ac u in a 53-y a -old man s owing xion con ac u s a oximal in alang al join s o i d d ig i and a alma co d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Patients complain o a slowly progressive tightness in the hands and a lack o the ability to ully extend their ngers.

DUpUYt r e N DISe a Se

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC • Ganglion cysts and palmar nodules. • Occupational hyperkeratosis and callous ormation. • Hand tumors including epithelioid sarcomas and so t tissue giant cell tumors.

MANAGEMENT The treatment goal o Dupuytren contracture is to maintain or restore hand unction by increasing range o motion at involved joints. NO NPHARMACO LO GIC • Physical therapy with splinting does not seem to be help ul as a sole treatment. SO R C • Radiation therapy has been used but there is little evidence to support it and signi cant potential side e ects o the treatment. SO R C • Hyperbaric oxygen is being studied with mixed results. SO R C FIGURE 112-3 Du uy n con ac u in a 58-y a -old man s owing xion con ac u s o ou and f d ig i s and a alma co d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Typically painless.

MEDICATIO NS • Intralesional injection o corticosteroids is only mildly success ul and may place the patient at risk or tendon rupture. SO R C

• Examination ndings—Nodules with f exion contractures are considered diagnostic, particularly in older white males; however, nodules may disappear late in the disease. 4

• Collagenase injection, a nonsurgical treatment, reduced contractures to 0 to 5 degrees in 44% to 64% o patients. Thirty- ve percent o contractures recur by 3 years and most contractures will recur by 8 years. 5,6

TYPICAL DISTRIBUTIO N

REFERRAL FO R SURGERY

• Either hand can be a ected

• Surgical correction is considered when there is at least 30 degrees o contracture at the metacarpophalangeal (MCP) joint. SO R C

• More commonly seen in the ourth and th digits (Figure 112-3) LABO RATO RY TESTING Not indicated

• Surgical asciotomy decreases the degree o f exion de ormity and results in modest improvements in hand unction. Studies indicated that improvements in unction are best correlated to changes at the proximal interphalangeal joint. 1 SO R B

IMAGING Magnetic resonance imaging (MRI) o the contractures may be help ul prior to surgical intervention, but is not needed to con rm a clinical diagnosis.

PRO GNO SIS

BIO PSY

• Recurrence rate is related to the amount o ascia that is removed on surgery.

• Typically not indicated.

• There is an increased risk or recurrence with time.

• Early diagnosis or diagnosis in atypical populations, such as children, may require histologic con rmation.

DIFFERENTIAL DIAGNO SIS Consider the other causes o hand contractures and palmar nodules including the ollowing: • Intrinsic joint contractures—Loss o range o motion rom any primary joint disease. • Trigger nger, stenosing tenosynovitis—Localized swelling o the f exor tendon limits movement within the sheath with resulting “triggering”; digit catches, but can be straightened. • Rheumatoid arthritis—Bony de ormities resulting in ulnar deviation at the metacarpophalangeal joints and/ or the wrist.

FO LLO W-UP Postoperative ollow-up should include hand therapy with a goal o increasing extension in the a ected digits.

PATIENT EDUCATIO N • Modi ying risk actors (eg, smoking, alcohol intake) that are known to contribute to the development o Dupuytren contracture is prudent, but are not shown to alter the course o the disease. • A ter surgery, postoperative hand therapy may improve unction and use o the hand. However, initial decreases in joint de ormity and improvements in hand unction may be lost over time.

531

532

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

Ch Apt e r 112

PATIENT RESO URCES

REFERENCES

• PubMed Health. Dupuytren’s Contracture—http:/ / www.ncbi .nlm.nih.gov/ pubmedhealth/ PMH0002213/ .

1. Draviaraj KP, Chakrabarti I. Functional outcome after surgery for Dupuytren’s contracture: a prospective study. J Hand Surg Am. 2004;29(5):804-808.

• American Family Physician (AAFP). Dupuytren’s Disease: What You Should Know—http:/ / www.aafp.org/ afp/ 2007/ 0701/ p90 .html. PRO VIDER RESO URCES

• Mayo Clinic. Dupuytren’s Contracture—http:/ / www .mayoclinic.com/ health/ dupuytrens-contracture/ DS00732. • American Family Physician (AAFP). Trojian TH, Chu SM. Dupuytren’s disease: diagnosis and treatment Am Fam Physician. 2007;76(1):86-89—http:/ / www.aafp.org/ afp/ 2007/ 0701/ p86.html. • Medscape. Dupuytren Contracture—http:/ / emedicine.medscape .com/ article/ 329414.

2. Gudmundsson KG, Arngrimsson R, Sig usson N, et al. Epidemiology o Dupuytren’s disease: clinical, serological, and social assessment. The Reykjavik study. J Clin Epidemiol. 2000;53(3):291-296. 3. Hindocha S, McGrouther DA, Bayat A. Epidemiological evaluation o Dupuytren’s disease incidence and prevalence rates in relation to etiology. Hand (NY). 2009;4(3):256-269. 4. Saar JD, Grothaus PC. Dupuytren’s disease: an overview. Plast Reconstr Surg. 2000;106(1):125-134. 5. Lo S, Pick ord M. Current concepts in Dupuytren’s disease. Curr Rev Musculoskeletal Med. 2013;6(1):26-34. 6. Peimer CA, Blazar P, Coleman S, et al. Dupuytren contracture recurrence ollowing treatment with collagenase clostridium histolyticum (CORDLESS study): 3-year data. J Hand Surg Am. 2013;38(1):12-22.

PO LYMYALGIA RHEUMATICA AND TEMPO RAL ARTERITIS

113 PO LYMYALGIA RHEUMATICA AND TEMPO RAL ARTERITIS Gary Fe re nchick, MD

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC more systemic symptoms o low-grade ever, weight loss, and atigue and is commonly associated with an elevated sedimentation rate or elevated C-reactive protein (CRP). 1 Temporal arteritis (TA) is chronic vasculitis o unknown etiology o medium and large vessels. TA should be considered a medical emergency because o increased risk o stroke and vision loss.

SYNO NYMS PATIENT STO RY A 65-year-old male presents to the clinic with atigue and a slowly progressive onset o pain in his shoulders or the past 3 months. The shoulder pain is worse in the morning and while working with his arms over his head. Over the past 2 weeks, he required help rom his wi e getting dressed in the morning. He also described pain in his calves and buttock muscles. He denies any symptoms in his small joints and denies headache or visual disturbance. Blood tests reveal a platelet count o 411 and an erythrocyte sedimentation rate (ESR) o 54 mm/ h. A diagnosis o polymyalgia rheumatica (PMR) is made based on the clinical picture (Figure 113-1). The patient is started on 15 mg o prednisone daily. Within 7 days, he is 95% improved, and a ollow-up sedimentation rate is 10 mm/ h 4 weeks later. Over several months, he is weaned o prednisone and remains asymptomatic.

Temporal arteritis is also known as giant cell arteritis (GCA).

EPIDEMIO LO GY • Polymyalgia rheumatica is the most common systemic in ammatory problem aced by the elderly and a common reason or long-term corticosteroid therapy. It is 3 times more common than TA. • Temporal arteritis is the most common medium-/ large-vessel vasculitis and may cause acute blindness (20% o patients with TA experience visual loss). 2 • Mean age o onset or TA is 70, and it is rare be ore age 50. • Temporal arteritis is more common in Caucasians. • Temporal arteritis is accompanied by PMR about 50% o the time.

INTRO DUCTIO N Polymyalgia rheumatica is a condition o unknown etiology associated with bilateral shoulder, pelvic girdle, and neck aching along with morning sti ness in patients over 50 years o age. It may be associated with

FIGURE 113-1 Typ ical are as o p ain and sti ne ss in p atie nts p re se nting with PMR.

ETIO LO GY/ PATHO PHYSIO LO GY • Temporal arteritis mostly involves the proximal cranial vessels arising rom the aortic arch and is associated with granulomatous in ammation with multinucleated giant cells on histology3 (Figures 113-2 and 113-3).

FIGURE 113-2 Giant ce ll arte ritis. Te mp oral arte ry biopsy showing e ndothe lial proli e ration, ragmentation o inte rnal elastic lamina, and in ltration o the adve ntitia and me d ia by inf ammatory ce lls. Giant ce lls show e spe cially we ll in the inse t. (Re produce d with pe rmission from He llmann DB. Vasculitis. In: Stobo J, Traill TA, He llmann DB, Lade nson PW, Pe tty BG. Principles and Practice o Me dicine . Ne w York, NY: Ap p le ton & Lang e ; 1996:215.)

533

534

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

FIGURE 1 13-3 Te mp o ral arte ry b io p sy in g iant ce ll arte ritis. This te mp o ral arte ry b io p sy d e mo nstrate s a p anmural in ltratio n o mo no nucle ar ce lls and lymp ho cyte s that are p articularly se e n in the me d ia and ad ve ntitia. Scatte re d g iant ce lls are also p re se nt. (Re p rod uce d with p e rmission fro m Lo ng o DL, Fauci A, Kasp e r D, Hause r S, Jame so n J , Lo scalzo J . Harriso n’s Princip le s o Inte rnal Me d icine . 18th e d . Ne w York, NY: McGraw-Hill.)

Ch a pt e r 113

FIGURE 113-5 Up p e r-e xtre mity arte riog ram d e monstrating a long ste notic le sion o the axillary arte ry in a 75-ye ar-old e male with g iant ce ll arte ritis. (Re p rod uce d with p e rmission from Long o DL, Fauci A, Kasp e r D, Hause r S, Jame son J, Loscalzo J. Harriso n’s Princip le s o Inte rnal Me d icine . 18th e d . Ne w Yo rk, NY: McGraw-Hill.)

RISK FACTO RS • The arteritis may involve the aorta and its branches and be complicated by dissection and occlusion (Figures 113-4 and 113-5, respectively). • Polymyalgia rheumatica is associated with a synovitis that includes vascular proli eration along with macrophage and T-lymphocyte inf ltration on histology. 4

• Age greater than 50 • Female gender • Northern European ancestry

DIAGNO SIS/ SCREENING CLINICAL FEATURES—HISTO RY AND PHYSICAL

FIGURE 113-4 Mag ne tic re sonance imag ing d e monstrating e xte nsive ane urysmal d ise ase o the thoracic aorta in an 80-ye ar-old e male . The p atie nt had b e e n d iag nose d with b iop sy-p rove n g iant ce ll arte ritis 10 ye ars p rior to p re se nting with this ane urysm. (Re p rod uce d with p e rmission from Long o DL, Fauci A, Kasp e r D, Hause r S, Jame son J, Loscalzo J. Harrison’s Princip le s of Inte rnal Me d icine . 18th e d . Ne w York, NY: McGraw-Hill.)

• Diagnostic criteria or PMR—Guidelines are not specif c on the number o these “core inclusion criteria” that are required to make the diagnosis. 5 ° Age greater than 50; symptoms present or more than 2 weeks. ° Bilateral shoulder or pelvic girdle aching or both. ° Morning sti ness lasting longer than 45 minutes. ° Evidence o an acute-phase response (elevated ESR or CRP). ° The diagnosis o PMR can be made in the absence o an elevated ESR (or CRP) i there are classic symptoms and there is a rapid response to corticosteroids (initial dose commonly 15 mg/ day). ■ A 70% clinical response within 7 days is consistent with PMR. ° Normalization o ESR or CRP within 4 weeks o starting prednisone. ° Hips are involved in up to 70% o patients with PMR. ° Up to 30% o patients with PMR lack shoulder symptoms. ° Peripheral/ constitutional symptoms occur in up to 50% o patients with PMR. ° Exclude ■ Active in ection or cancer as the management o PMR typically includes corticosteroids ■ Temporal arteritis as the management o this condition is di erent rom that o PMR ■ Other in ammatory rheumatic diseases, such as rheumatoid arthritis ■ Drug-induced myalgias, such as that seen with statins ■ Chronic pain syndromes, such as f bromyalgia ■ Endocrine disease, such as hypothyroidism, which may present with myopathy ■ Parkinson disease

PART 13

pO LYMYa LGIa r h e UMa t ICa a ND t e MpO r a L a r t e r It IS

• Clinical mani estations o TA vary rom subtle to dramatic. use 3 o the ollowing 5 (93% sensitivity ° For the diagnosis o TA, and 91% specif city)6: ■ Age o onset past 50 years (mean age 70) ■ Abrupt onset o a new headache (temporal is common) and temporal tenderness, but tenderness can occasionally be di use or bilateral ■ Temporal artery tenderness (and prominent beading or diminished pulse on the temporal artery not related to atherosclerosis) or decreased pulsation ■ Erythrocyte sedimentation rate more than 50 mm/ h ■ Temporal artery biopsy (showing vasculitis with granulomatous in ammation and multinucleated giant cells) ° Other eatures that may be associated with TA include jaw or tongue claudication, blurring or diplopia, scalp tenderness, ever, atigue, weight loss, cranial nerve palsies, and bruits over the upper-limb arteries. A high index o suspicion or TA is needed in the presence o jaw/ tongue claudication or visual symptoms in the absence o headache. LABO RATO RY TESTING • A complete blood cell count (CBC), although nonspecif c, may help identi y a systemic disease or in ection. • Core diagnostic tests or the presence o both TA and PMR are ESR and CRP. • Complete a comprehensive prof le prior to starting corticosteroids to assess or glycemic control and liver and renal unction. • Parathyroid hormone and 25-hydroxy-vitamin D level—Vitamin D def ciency and hyperparathyroidism are secondary causes o osteopenia and osteoporosis, which can be worsened with the anticipated prednisone therapy or both PMR and TA. • Bence-Jones protein (in urine and plasma) helps to exclude the presence o multiple myeloma, which can present with musculoskeletal pain and is a disease primarily o the elderly. • Thyrotropin (TSH)—Hypothyroidism can be associated with myopathy. • Testing or creatine kinase should be ordered to help exclude the presence o in ammatory muscle disease, such as polymyositis. • Rheumatoid actor (RF) testing (a blood test or anti-cyclic citrullinated peptide [anti-CCP] antibody should be considered as it is more sensitive) will help exclude the diagnosis o rheumatoid arthritis. • Antinuclear antibody (ANA) will evaluate or systemic lupus erythematosus (SLE) or overlap syndromes. IMAGING • Ultrasound, demonstrating edema in the temporal artery along with stenosis has 69% sensitivity and 82% specif city or the diagnosis o TA. However, it is not a replacement or TA biopsy. 7 • Chest radiography can check or aortic aneurysm in patients with TA (consider an echocardiogram or computed tomographic [CT] angiography). • Biopsy o the temporal artery or a diagnosis o TA should be completed within 1 week o starting corticosteroids. However, do not delay the initiation o corticosteroid therapy while arranging or the biopsy. 8 DIFFERENTIAL DIAGNO SIS • Di erential diagnosis o PMR includes the ollowing: ° Rheumatoid arthritis, lupus, or other vasculidities—Sti ness, pain swelling, tenderness, and warmth are more common in the distal

MUSCULO SKELETAL/ RHEUMATO LO GIC

°

° °

°

joints (hands and eet) (see Chapters 99, Rheumatoid Arthritis; and 178, Lupus: Systemic and Cutaneous). In ammatory myopathies—Dermatomyositis and polymyositis are associated with muscle weakness and an increase in serum muscle enzymes. In addition, dermatomyositis is associated with a rash (see Chapter 179, Dermatomyositis). Osteoarthritis—Pain is worse with use and better with rest (see Chapter 98, Osteoarthritis). Primary shoulder disease, including rotator cu lesions or capsulitis—Pain is worse with use and better with rest and is more commonly unilateral. Fibromyalgia—This is commonly associated with widespread pain in the musculoskeletal system and multiple trigger points and is most common in women.

• Di erential diagnosis o TA includes the ollowing: ° Headache di erential (see Chapter 230, Headache) ■ Migraine—Onset o migraine a ter the age o 50 is unusual, and migraine is associated with pulsatile pain, nausea/ vomiting, and photophobia and phonophobia. ■ Cluster headache—This is most common in males, and the pain o cluster headaches has a typical duration o 15 minutes to 3 hours with symptom- ree intervals o up to 2 days. ■ Herpes zoster (shingles)—Localized pain, including a headache, is ollowed by a vesicular rash in a dermatomal distribution (see Chapters 126, Zoster; and 127, Zoster Ophthalmicus). ■ Cervical spine disease—Pain o cervical spine disease is commonly worse with movement o the cervical spine. ■ Sinus disease—This presents with pain over the sinus, rhinorrhea, and pus in the nasal cavity (see Chapter 28, Sinusitis). ° Acute vision loss. ■ Transient ischemic attack (TIA) ( or acute vision loss)—This causes abrupt onset o visual loss in the absence o headache. ° Jaw claudication. ■ Temperomandibular joint (TMJ) pain may be con used with jaw claudication but is commonly associated with audible clicking and crepitus during jaw movement.

MANAGEMENT MEDICATIO NS • Polymyalgia rheumatica—Urgently starting corticosteroids is not necessary in PMR (as opposed to TA) and can be delayed to initiate a complete assessment. ° Prednisone 15 mg daily or 3 weeks, then 12.5 mg or 3 weeks, then 10 mg or 4 to 6 weeks, then reduction by 1 mg every 4 to 8 weeks until discontinuation. 1,9 SO R A ■ Less than 1% o patients initially treated with 15 mg prednisone subsequently required higher doses to control symptoms; there ore, a 15-mg starting dose is an e ective initial dose in most patients.1 ■ Follow-up 3 times in the f rst 4 months; the f rst visit should be within several weeks, then every 3 months or 1 year. ■ Some patients benef t rom a more rapid steroid-tapering regimen. ° Duration o treatment is commonly 1 to 2 years (discontinue when asymptomatic rom their in ammatory condition and ESR and CRP levels normalize). ° In the case o a relapse, increase corticosteroid to the previous higher dose (or use intramuscular injections o methylprednisolone 120 mg every 3-4 weeks, decreasing by 20 mg every 2-3 months). 5

535

536

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC • For TA, begin corticosteroid therapy immediately. 3,10 SO R A ° Prednisone 1 mg/ kg/ d or 40 to 60 mg daily until symptoms disappear and laboratory abnormalities (eg, ESR) normalize, commonly 4 weeks. ° Reduce dose by 10 mg every 2 weeks to 20 mg, then by 2.5 mg every 2 to 4 weeks to 10 mg, then 1 mg every 1 to 2 months. 3 ° I visual evolving loss or amaurosis ugax, use3 methylprednisolone 500 mg to 1 g intravenously daily or 3 days. • Osteoporosis prevention—Start a bisphosphonate with vitamin D and calcium to prevent osteoporosis in patients with high- racture risk (age > 65 and prior ragility racture). In patients without a high- racture risk start calcium and vitamin D when starting steroid therapy; in these patients, obtain a dual-energy X-ray absorptiometry (DXA) scan and i the T score is less than - 1.0, start a bisphosphonate. 11 • Initiate low-dose aspirin 160 mg/ d in patients with TA in the absence o contraindications. 3 SO R C ° The aspirin decreases visual loss and cerebrovascular ischemic events by about 20%. • Consider a proton pump inhibitor or gastrointestinal protection in those on corticosteroids. SO R C • Steroid-sparing drugs (to reduce the potential risk o long-term steroid use) have been studied in PMR. ° Methotrexate (10 mg/ week) added to 10 mg o prednisone per day appears to have an e ect on decreasing relapses, reducing prednisone requirements, and decreasing prednisone-related adverse e ects and may be o most benef t in those at high risk o steroid complications. 1,12 SO R B • In iximab demonstrated no benef cial e ect (and possible harm) in newly diagnosed patients with PMR treated with prednisone. 13 SO R B REFER O R HO SPITALIZE • Re er patients with atypical eatures such as lack o shoulder involvement, prominent systemic symptoms, or normal or very high acutephase reactants. • Re er patients with therapeutic dilemmas, including nonresponse or inability to reduce corticosteroids or contraindications to corticosteroids.

Ch a pt e r 113

PATIENT EDUCATIO N • Educate patients on eatures o relapse, including new ever, headache, scalp tenderness, visual symptoms, jaw or tongue claudication, PMR, or cerebrovascular symptoms. • Osteoporosis prevention is more than taking medications. Other li estyle issues should be discussed, including diet and exercise (see Chapter 225, Osteoporosis and Osteopenia). PATIENT RESO URCES

• American College of Rheumatology ° Giant Cell Arteritis—http:/ / www.rheumatology.org/ practice/ clinical/ patients/ diseases_and_conditions/ giantcellarteritis.asp. ■ Spanish version—http:/ / www.rheumatology.org/ practice/ clinical/ patients/ diseases_and_conditions/ giantcellarteritis-esp.asp. ° Polymyalgia Rheumatica—http:/ / www.rheumatology.org/ practice/ clinical/ patients/ diseases_and_conditions/ polymyalgiarheumatica.asp. ■ Spanish version—http:/ / www.rheumatology.org/ practice/ clinical/ patients/ diseases_and_conditions/ polymyalgiarheumatica-esp.asp. PRO VIDER RESO URCES

• Dasgupta B, Borg FA, Hassan N, et al. BSR and BHPR guidelines or the management o polymyalgia rheumatica. Rheumatology. 2010;49(1):186-190. http:/ / rheumatology.oxfordjournals .org/ content/ 49/ 1/ 186.long. • Dasgupta B, Borg FA, Hassan N, et al. BSR and BHPR guidelines or the management o giant cell arteritis. Rheumatology. 2010;49(8): 1594-1597. http:/ / rheumatology.oxfordjournals.org/ content/ 49/ 8/ 1594.long. • Grossman JM, Gordon R, Ranganath VK, et al. American College o Rheumatology 2010 recommendations or the prevention and treatment o glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken). 2010;62(11):1515-1526. http:/ / www.rheumatology .org/ practice/ clinical/ guidelines/ GIOP_Guidelines_ Nov_2010.pdf.

PRO GNO SIS • Risk o vision loss is up to 50% in the contralateral eye in the presence o vision loss in one eye. • About 27% o patients with TA are at risk or the late complications o aortic aneurysm, dissection, or stenosis. 14

FO LLO W-UP • For PMR, ollow up patients in 1 to 3 weeks, then 4 to 6 weeks depending on the response to treatment. • Assess or proximal muscle pain (hips and shoulders), morning sti ness, and atigue. • For TA, ollow up more requently, including within 1 week, 4 times within the f rst 3 months, and every 3 months a terward within the f rst year.

REFERENCES 1. Hernandez-Rodriguez J, Cid MC, Lopez-Soto A, Espigol-Frigole G, Bosch X. Treatment o polymyalgia rheumatic: a systematic review. Arch Intern Med. 2009;169:1839-1850. 2. Smeeth L, Cook C, Hall AJ. Incidence o diagnosed polymyalgia rheumatica and temporal arteritis in the United Kingdom, 1990-2001. Ann Rheum Dis. 2006;65(8):1093-1098. Epub 2006 Jan 13. 3. Dasgupta B, Borg FA, Hassan N, et al. or the BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guidelines or the management o giant cell arteritis. Rheumatology (Oxford). 2010;49(8):1594-1597. Epub 2010 Apr 5. 4. Meliconi R, Pulsatelli L, Uguccioni M, et al. Leukocyte inf ltration in synovial tissue rom the shoulder o patients with polymyalgia rheumatica. Quantitative analysis and in uence o corticosteroid treatment. Arthritis Rheum. 1996;39(7):1199-1207.

pO LYMYa LGIa r h e UMa t ICa a ND t e MpO r a L a r t e r It IS

PART 13

MUSCULO SKELETAL/ RHEUMATO LO GIC

5. Dasgupta B, Borg FA, Hassan N, et al. or the BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guidelines or the management o polymyalgia rheumatica. Rheumatology (Oxford). 2010;49(1):186-190. Epub 2009 Nov 12.

11. Grossman JM, Gordon R, Ranganath VK, et al. American College of Rheumatology 2010 recommendations or the prevention and treatment o glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken). 2010;62(11):1515-1526.

6. Hunder GG, Bloch DA, Michel BA, et al. The American College o Rheumatology 1990 criteria or the classif cation o giant cell arteritis. Arthritis Rheum. 1990;33(8):1122-1128.

12. Ferraccioli G, Sala f F, De Vita S, et al. Methotrexate in polymyalgia rheumatica: preliminary results o an open, randomized study. Rheumatology. 1996;23(4):624-628.

7. Karassa FB, Matsagas MI, Schmidt WA, Ioannidis JP. Meta-analysis: test per ormance o ultrasonography or giant-cell arteritis. Ann Intern Med. 2005;142(5):359-369.

13. Salvarani C, Macchioni P, Manzini C, et al. In iximab plus prednisone or placebo plus prednisone or the initial treatment o polymyalgia rheumatica: a randomized trial. Ann Intern Med. 2007;146(9): 631-639.

8. Mukhtyar C, Guillevin L, Cid MC, et al. or the European Vasculitis Study Group. EULAR recommendations or the management o large vessel vasculitis. Ann Rheum Dis. 2009;68(3):318-323. Epub 2008 Apr 15. 9. Salvarani C, Cantini F, Hunder GG. Polymyalgia rheumatic and giant-cell arteritis. Lancet. 2008;372:234. 10. Mukhtyar C, Guillevin L, Cid MC, et al. EULAR recommendations or the management o large vessel vasculitis. Ann Rheum Dis. 2009;68:318-323.

14. Nuenningho DM, Hunder GG, Christianson TJ, et al. Incidence and predictors o large-artery complication (aortic aneurysm, aortic dissection, and/ or large-artery stenosis) in patients with giant cell arteritis: a population-based study over 50 years. Arthritis Rheum. 2003;48(12):3522-3531.

537

This page intentionally left blank

Pa r t 14

DERMATO LO GY

*

St re ng t h o Re co mme nd at io n (SO R)

De f nit io n

A

Re comme nd ation b ase d on consiste nt and g ood -q uality p atie nt-orie nte d e vid e nce .*

B

Re comme nd ation b ase d on inconsiste nt or limite d -q uality p atie nt-orie nte d e vid e nce .*

C

Re comme nd ation b ase d on conse nsus, usual p ractice , op inion, d ise ase -orie nte d e vid e nce , or case se rie s or stud ie s o d iag nosis, tre atme nt, p re ve ntion, or scre e ning .*

Se e Ap p e nd ix A on p ag e s 1241-1244 or urthe r in ormation.

PART 14 DERMATO LO GY

540

SECTIO N 1

Ch Apt ER 114

ACNEIFO RM DISO RDERS

114 ACNE VULGARIS Richard P. Usatine , MD

PATIENT STO RY A 20-year-old man (Figure 114-1a) with severe nodulocystic acne and scarring presents or treatment. A ter trying oral antibiotics, topical retinoids, and topical benzyl peroxide with no signi cant bene t, the patient requests isotretinoin. A ter 6 months o isotretinoin, the nodules and cysts cleared (Figure 114-1b). He is much happier and more con dent about his appearance.

INTRO DUCTIO N Acne is an obstructive and inf ammatory disease o the pilosebaceous unit that can occur at any age. While it is typically associated with the teenage years, many adults su er with acne severe enough to a ect their sel esteem and well-being (Figure 114-2).

EPIDEMIO LO GY

A

Acne vulgaris a ects more than 80% o teenagers, and persists beyond the age o 25 years in 3% o men and 12% o women. 1

ETIO LO GY AND PATHO PHYSIO LO GY The 4 most important steps in acne pathogenesis are as below: 1. Sebum overproduction related to androgenic hormones and genetics 2. Abnormal desquamation o the ollicular epithelium (keratin plugging) 3. Propionibacterium acnes proli eration 4. Follicular obstruction, which can lead to inf ammation and ollicular disruption Acne can be precipitated by medications such as phenytoin and lithium (Figure 114-3). There are some studies that suggest that consumption o large quantities o milk (especially skim milk) increase the risk or acne in teenagers and young adults. 2,3 Recent studies suggest that a high glycemic load diet contributes to acne and changing to a low glycemic load diet can reduce acne lesions. 3-5

DIAGNO SIS CLINICAL FEATURES Morphology o acne includes comedones, papules, pustules, nodules, and cysts.

B FIGURE 114-1 A. Se ve re nod ulocystic acne with scarring in a 20-ye ar-old man. B. Exce lle nt re sults a te r 6 months o isotre tinoin. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

ACNE VULGARIS

PART 14 DERMATO LO GY

FIGURE 114-4 Come d onal acne with larg e op e n come d one s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

LABO RATO RY STUDIES

FIGURE 114-2 Se ve re inf ammatory acne in a 24-ye ar-old woman who has aile d all top ical tre atme nts and oral antib iotics. She is a p e r e ct cand id ate or isotre tinoin as long as she has no contraind ications and will ad he re to the use o 2 contrace p tive me thod s or ab stine nce . (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

• Obstructive acne = comedonal acne = noninf ammatory acne and consists o only comedones (Figure 114-4). • Open comedones are blackheads and closed comedones are called whiteheads and look like small papules.

None unless you suspect androgen excess and/ or polycystic ovarian syndrome (PCOS). 6 SOR Obtain testosterone and dehydroepiandrosterone sul ate (DHEA-S) levels i you suspect androgen excess and/ or PCOS. Consider ollicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels i you suspect PCOS.

DIFFERENTIAL DIAGNO SIS • Acne conglobata is an uncommon and unusually severe orm o acne characterized by multiple comedones, cysts, sinus tracks, and

• Inf ammatory acne has papules, pustules, nodules, and cysts in addition to comedones (Figures 114-5 and 114-6). TYPICAL DISTRIBUTIO N The parts a ected with acne vulgaris are ace, back, chest, and neck.

FIGURE 114-3 Se ve re inf ammatory acne in a young ad ult. His acne worse ne d whe n he was starte d on p he nytoin or his se izure d isord e r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 114-5 Inf ammatory acne in a 20-ye ar-old woman. It is ve ry common or the jaw line to b e involve d in wome n su e ring with acne at this ag e . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

541

542

PART 14 DERMATO LO GY

Ch Apt ER 114

A

FIGURE 114-6 Inf ammatory acne in an old e r woman. She is tire d o having p ain ul cysts on he r ace and choose s to have some acne inje ctions that d ay. Knowing this is only a te mp orary tre atme nt, isotre tinoin is d iscusse d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

abscesses. The inf ammatory lesions and scars can lead to signi cant dis gurement. 7 Sinus tracks can orm with multiple openings that drain oul-smelling purulent material (Figures 114-7, 114-8, and 114-9). The comedones and nodules are usually ound on the chest, the shoulders, the back, the buttocks, and the ace. In some cases acne conglobata is part o a ollicular occlusion triad including hidradenitis and dissecting cellulitis o the scalp (see Figure 114-9). • Acne ulminans is characterized by sudden-onset ulcerative crusting cystic acne, mostly on the chest and back (Figures 114-10 and 114-11). 8 Fever, malaise, nausea, arthralgia, myalgia, and weight loss are common. Leukocytosis and elevated erythrocyte sedimentation rate are usually ound. There may also be ocal osteolytic lesions. The term acne ulminans may also be used in cases o severe aggravation o acne without systemic eatures. 8 • Rosacea can resemble acne by having papules and pustules on the ace. It is usually seen in older adults with prominent erythema and telangiectasias. Rosacea does not include comedones and may have ocular or nasal mani estations (see Chapter 115, Rosacea). Rosacea ulminans or pyoderma aciale has eatures o severe acne and rosacea (Figure 114-12). • Folliculitis on the back may be con used with acne. Look or hairs centrally located in the inf ammatory papules o olliculitis to help distinguish it rom acne. Acne on the back usually accompanies acne on the ace as well (see Chapter 119, Folliculitis). • Acne keloidalis nuchae consists o papules, pustules, nodules, and keloidal tissue ound at the posterior hairline. It is most o ten seen in men o color a ter shaving the hair at the nape o the neck (see Chapter 116, Pseudo olliculitis and Acne Keloidalis Nuchae). • Actinic comedones (blackheads) are related to sun exposure and are seen later in li e (Figure 114-13).

B FIGURE 114-7 A. Acne cong lob ata in a 16-ye ar-old b oy. He has se ve re cysts on his ace with sinus tracks b e twe e n the m. He re q uire d many we e ks o oral p re d nisone b e ore isotre tinoin was starte d . His acne cle are d comp le te ly with his tre atme nt. B. Acne cong lob ata cle are d with minimal scarring a te r oral p re d nisone and 5 months o isotre tinoin the rap y. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

MANAGEMENT Treatment is based on type o acne and severity. Medical therapy categories to choose rom are topical retinoids, topical antimicrobials, systemic antimicrobials, hormonal therapy, oral isotretinoin, and injection therapy.

ACNE VULGARIS

FIGURE 114-8 Acne cong lob ata in a 42-ye ar-old woman showing communicating sinus tracks b e twe e n cysts. The re is p us d raining rom o ne o the sinus tracts on the rig ht sid e o the ne ck. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

Discussion o diet is reasonable or all patients as a low glycemic load diet and weight loss may be bene cial or many patients. DIETARY CHANGES • Take a brie diet history asking about milk intake and whether the diet contains high glycemic load oods such as simple sugars. • Suggest that excessive milk intake be decreased. 2,3SO R B • Discuss the role a healthy lower glycemic load diet substituting oods with more complex carbohydrates (eg, whole-grain bread, pasta, and ruit) or those with simple sugars. Also including more oods higher in protein (eg, lean meat, poultry, beans, or sh) and not relying on a high carbohydrate diet alone. 4,5SO R B • In one randomized controlled trial (RCT) o a low glycemic load diet in 43 male patients with acne, total lesion counts and weight decreased

FIGURE 114-9 Acne cong lob ata in a 53-ye ar-old man cove re d with op e n come d one s and cysts on his b ack. He has the ollicular occlusion triad includ ing hid rad e nitis, d isse cting ce llulitis o the scalp , and acne cong lob ata. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

FIGURE 114-10 Acne ulminans in a 17-ye ar-old b oy. He was on isotre tinoin whe n he d e ve lop e d worse ning o his acne with p olymyalg ia and arthralg ia. He p re se nte d with nume rous nod ule s and cysts cove re d b y he morrhag ic crusts on his che st and b ack. (Re p rod uce d with p e rmission from Grunwald MH, Amichai B. Nod ulocystic e rup tion with musculoske le tal p ain. J Fam Pract. 2007;56:205-206, re p rod uce d with p e rmission from Frontline Me d ical Communications.)

more in the experimental group compared with the control group. 5 Part o the bene t may have been secondary to weight loss. Certainly, suggesting that obese patients lose weight as part o their acne treatment can only be bene cial or the skin and general health o the patients. 5SO R B MEDICATIO NS FO R ACNE THERAPY In a review o 250 comparisons, the Agency or Healthcare Research and Quality ound 14 had evidence o level A. 9 These comparisons demonstrated the e cacy over vehicle or placebo control o topical clindamycin, topical erythromycin, benzoyl peroxide, topical tretinoin, oral tetracycline, and norgestimate/ ethinyl estradiol. 9 Level A conclusions demonstrating equivalence include benzoyl peroxide at various strengths was equally e cacious in mild or moderate acne; adapalene and tretinoin were equally e cacious. 9SO R

FIGURE 114-11 Acne ulminans with se ve re rap id ly worse ning truncal acne in a 15-ye ar-old ad ole sce nt b oy. He d id not have e ve r or b one p ain b ut had a white b loo d ce ll count o 17,000. He re sp ond e d rap id ly to p re d nisone and was starte d on isotre tinoin. The ulce rs and g ranulation tissue worse ne d initially on isotre tinoin b ut p re d nisone he lp e d to g e t this und e r control. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

543

544

PART 14 DERMATO LO GY

Ch Apt ER 114

Topical • Benzoyl peroxide—Antimicrobial e ect (gel, cream, lotion) (2.5%, 5%, 10%) 10% causes more irritation and is not more e ective. 1 SO R

• Topical antibiotics—Clindamycin and erythromycin are the mainstays o treatment. • Erythromycin—Solution, gel. 6 SO R • Clindamycin—Solution, gel, lotion. 6 SO R • Benzamycin gel—Erythromycin 3%, benzoyl peroxide 5%. 6 SO R • BenzaClin gel—Clindamycin 1%, benzoyl peroxide 5%. 6 SO R • Dapsone 5% gel. 10 SO R B Retinoids • Tretinoin (Retin-A) gel, cream, liquid, micronized. 1 SO R • Adapalene gel—Less irritating than tretinoin. 1 SO R • Tazarotene—Strongest topical retinoid with greatest risk o irritation. 11 SO R Topical retinoids will o ten result in skin irritation during the rst 2 to 3 months o treatment, but new systematic reviews do not demonstrate that they worsen acne lesion counts during the initial period o use. 2 FIGURE 114-12 Pyod e rma aciale is almost e xclusive ly se e n in ad ult wome n. It can p re se nt with se ve re cystic acial acne o te n in a malar d istrib ution. It also is calle d rosace a ulminans. It starte d ab rup tly 6 months b e ore and he r antinucle ar antib od y was normal. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

• Azelaic acid—Use ul to treat spotty hyperpigmentation and acne (Figure 114-14). 6 SO R B Systemic • Oral antibiotics. • Tetracycline 500 mg qd bid—Inexpensive, absorbed best on an empty stomach. 6 SO R • Doxycycline 40 to 100 mg qd bid—Inexpensive, well tolerated, can take with ood and increases sun sensitivity. 6 SO R • Minocycline 50 to 100 mg qd bid—More expensive, not proven to be better than other systemic antibiotics including tetracycline. 6,12 SO R • Erythromycin 250 to 500 mg bid—Inexpensive, requent gastrointestinal (GI) disturbance but can be used in pregnancy. 6 SO R • Trimethoprim/ sul amethoxazole DS bid—E ective but risk o Stevens-Johnson syndrome is real. Reserve or short courses in particularly severe and resistant cases. 6 SO R

FIGURE 114-13 Actinic come d one s re late d to sun e xp osure in an old e r man. The se are typ ically se e n on the sid e o the ace cluste ring around the e ye s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 114-14 O b structive or come d onal acne with sp otty hyp e rp ig me ntation. Aze laic acid was he lp ul to tre at the acne and the hyp e rp ig me ntation. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

ACNE VULGARIS

PART 14 DERMATO LO GY

Oral azithromycin has been prescribed in pulse dosing or acne in a number o small poorly done studies and has not been ound to be better than oral doxycyline. 13 • Isotretinoin (o ten re erred to as Accutane even though this brand name is o the market) is the most power ul treatment or acne. It is especially use ul or cystic and scarring acne that has not responded to other therapies. 6 SO R Dosed at approximately 1 mg/ kg per day or 5 months. Women o childbearing age must use 2 orms o contraception. Monitor or depression. • The US Food and Drug Administration (FDA) requires that prescribers o isotretinoin, patients who take isotretinoin, and pharmacists who dispense isotretinoin all must register with the iPLEDGE system (www.ipledgeprogram.com). • Hormonal treatments ° Oral contraceptives only or emales—Choose ones with low androgenic e ect. 6 SO R FDA-approved oral contraceptives are Ortho Tri-Cyclen, Yaz, and Estrostep. Other oral contraceptives with similar ormulations also help acne in women even though these have not received FDA approval or this indication. Note Yaz and Yasmin have progestin drospirenone, which is derived rom 17α -spironolactone. It shares an antiandrogenic e ect with spironolactone. There may be an increased risk o venous thromboembolism with drospirenone versus other progestins. 14 may be used or adult women when other therapies ° Spironolactone 3,15,16 ail. This may be especially use ul i the patient has hirsutism. Standard dosing is 50 to 200 mg/ d. May start with 50 mg daily and monitor or hyperkalemia. The risk o hyperkalemia increases with a higher dose. Titrate up as needed and tolerated. 6 SO R B A recent systematic review ailed to show a bene t or spironolactone in acne even though it was ound to decrease hirsutism. 17 Note that acne is not an FDA-approved indication or spironolactone. ° One small prospective study o 27 women with severe papular and nodulocystic acne used a combination o EE/ DRSP (Yasmin) and spironolactone 100 mg daily. Eighty- ive percent o subjects were entirely clear o acne lesions or had excellent improvement and there was no signi icant elevation o serum potassium. 18 STERO ID INJ ECTIO N THERAPY This therapy is used or pain ul nodules and cysts. SO R C Be care ul to avoid producing skin atrophy by diluting the steroid and ollowing the directions below: ° Dilute 0.1 cc o 10 mg/ cc triamcinolone acetonide (Kenalog) with 0.4 cc o sterile saline or a 2 mg/ cc suspension. ° Inject 0.1 cc with a 1-cc tuberculin syringe into each nodule using a 30-gauge needle (Figure 114-15). CO MPLEMENTARY AND ALTERNATIVE THERAPY Tea tree oil 5% gel19 SO R B ACNE THERAPY BY SEVERITY Comedonal acne (see Figure 114-6) • Topical retinoid or azelaic acid. • Consider benzoyl peroxide as a wash or leave-on product. • No need or antibiotics—No need to kill Propionibacterium acnes.

FIGURE 114-15 Inje ction o acne nod ule s with 2 mg /cc triamcinolone ace tonid e . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• May add oral antibiotics i topical agents are not working. Papulopustular or nodulocystic acne—moderate to severe—inf ammatory • Topical antibiotic, benzoyl peroxide, and oral antibiotic. • Oral antibiotics are o ten essential at this stage. • Topical retinoid or azelaic acid (titrate up to more potent retinoids as needed) • Steroid injection therapy—For pain ul nodules and cysts. Severe cystic or scarring acne • Isotretinoin i there are no contraindications. This is the most e ective therapy (Figure 114-16). • Steroid injection therapy—For pain ul nodules and cysts. Acne ulminans (see Figures 114-9 to 114-11) • Start with systemic steroids (prednisone 40-60 mg/ d—approximately 1 mg/ kg per day). 20 SO R C • Systemic steroid treatment rapidly controls the skin lesions and systemic symptoms. The duration o steroid treatment in one Finnish series was 2 to 4 months to avoid relapses. 20 SO R C • Therapy with isotretinoin, antibiotics, or both was o ten combined with steroids, but the use o these agents combined is not proven. 20 SOR C I an antibiotic is used with isotretinoin, avoid any in the tetracycline class as the combination o the 2 increases the risk o pseudotumor cerebri. • One British series used oral prednisolone 0.5 to 1 mg/ kg daily or 4 to 6 weeks (therea ter slowly reduced to zero). 21 SO R C • Oral isotretinoin was added to the regimen at the ourth week, initially at 0.5 mg/ kg daily and gradually increased to achieve complete clearance. 21 SO R C • Consider introducing isotretinoin at approximately 4 weeks into the oral prednisone i there are no contraindications. SO R C Acne conglobata and pyoderma aciale may be treated like acne ulminans but the course o oral prednisone does not need to be as long. SOR C

Mild papulopustular

CO MBINATIO N THERAPIES

• Topical antibiotics and benzoyl peroxide.

• Combination therapy with multiple topical agents can be more e ective than single agents. 6 SO R B

• Topical retinoid or azelaic acid.

545

PART 14 DERMATO LO GY

546

Ch Apt ER 114

• The adjunctive use o clindamycin/ benzoyl peroxide gel with tazarotene cream promotes greater e cacy and may also enhance tolerability. 22 • Combination therapy with topical retinoids and oral antibiotics can be help ul at the start o acne therapy. However, maintenance therapy with combination tazarotene and minocycline therapy showed a trend or greater e cacy but no statistical signi cance versus tazarotene alone. 23 MEDICATIO N CO ST The most a ordable medications or acne include topical benzoyl peroxide, erythromycin, clindamycin, and oral doxycycline. The most expensive acne medications are the newest brand name combination products o existing topical medication. These medications are convenient or those with insurance that covers them (Epiduo contains benzoyl peroxide and adapalene; Ziana contains clindamycin and tretinoin). NEWER EXPENSIVE MO DES O F THERAPY

A

Intense pulsed light and photodynamic therapy (PDT) use lasers, special lights, and topical chemicals to treat acne. 24-26 These therapies are very expensive and the data do not suggest that these should be rst-line therapies at this time. Light and laser treatments have been shown to be o short-term bene t i patients can a ord therapy and tolerate some discom ort. These therapies have not been shown to be better than simple topical treatments. 2 One comparative trial demonstrated that PDT was less e ective than topical adapalene in the short-term reduction o inf ammatory lesions. 2

FO LLO W-UP Isotretinoin requires monthly ollow-up visits but other therapies can be monitored every ew months at rst and then once to twice a year. Keep in mind that many treatments or acne take months to work, so quick ollow-up visits may be disappointing.

PATIENT EDUCATIO N Adherence with medication regimens is crucial to the success o the therapy. Adequate ace washing twice a day is su cient. Do not scrub the ace with abrasive physical or chemical agents. I benzoyl peroxide is not being used as a leave-on product, it can be purchased to use or ace washing.

PATIENT RESO URCES

B FIGURE 114-16 A. A young man p re se nts with se ve re cystic acne unre sp onsive to top ical me d icine s and oral antib iotics. He is starte d on isotre tinoin. B. Exce lle nt cosme tic re sults le ad to a hap p y p atie nt 6 months late r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Topical retinoids and topical antibiotics are more e ective when used in combination than when either is used alone. 6 SO R B • Benzoyl peroxide and topical antibiotics used in combination are e ective treatment or acne by helping to minimize antibiotic resistance.6 SOR B

• PubMed Health. Acne—http:/ / www.ncbi.nlm.nih.gov/ pubmedhealth/ PMH0001876/ . PRO VIDER RESO URCES

• Usatine R, Pfenninger J, Stulberg D, Small R. Dermatologic and Cosmetic Procedures in O f ce Practice. Philadelphia, PA: Elsevier; 2012— Covers how to do acne surgery, steroid injections or acne, chemical peels, PDT and laser treatment or acne. It is also available as an app at www.usatinemedia.com.

ACNE VULGARIS

REFERENCES 1. Purdy S, de Berker D. Acne vulgaris. Clin Evid (Online). 2011;2011:1714. 2. Smith EV, Grindlay DJ, Williams HC. What’s new in acne? An analysis o systematic reviews published in 2009-2010. Clin Exp Dermatol. 2011;36:119-122. 3. Ismail NH, Mana ZA, Azizan NZ. High glycemic load diet, milk and ice cream consumption are related to acne vulgaris in Malaysian young adults: a case control study. BMC Dermatol. 2012;12:13. 4. Kwon HH, Yoon JY, Hong JS, Jung JY, Park MS, Suh DH. Clinical and histological e ect o a low glycaemic load diet in treatment o acne vulgaris in Korean patients: a randomized, controlled trial. Acta DermVenereol. 2012;92(3):241-246. 5. Smith RN, Mann NJ, Braue A, Mäkeläinen H, Varigos GA. The e ect o a high-protein, low glycemic-load diet versus a conventional, high glycemic-load diet on biochemical parameters associated with acne vulgaris: a randomized, investigator-masked, controlled trial. JAmAcad Dermatol. 2007;57(2):247-256. 6. Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines o care or acne vulgaris management. JAmAcad Dermatol. 2007;56:651-663. 7. Shirakawa M, Uramoto K, Harada FA. Treatment o acne conglobata with inf iximab. JAmAcad Dermatol. 2006;55:344-346. 8. Grunwald MH, Amichai B. Nodulo-cystic eruption with musculoskeletal pain. J Fam Pract. 2007;56:205-206. 9. AHRQ. Management o Acne. http:/ / www ahrq gov/ clinic/ epcsums/ acnesum htm [serial online]. 2001. 10. Draelos ZD, Carter E, Maloney JM, et al. Two randomized studies demonstrate the e cacy and sa ety o dapsone gel, 5% or the treatment o acne vulgaris. JAmAcad Dermatol. 2007;56:439-410. 11. Webster GF, Guenther L, Poulin YP, et al. A multicenter, doubleblind, randomized comparison study o the e cacy and tolerability o once-daily tazarotene 0.1% gel and adapalene 0.1% gel or the treatment o acial acne vulgaris. Cutis. 2002;69(suppl 2):4-11. 12. Garner SE, Eady EA, Popescu C, Newton J, Li WA. Minocycline or acne vulgaris: e cacy and sa ety. Cochrane Database Syst Rev. 2003;(1):CD002086. 13. Maleszka R, Turek-Urasinska K, Oremus M, et al. Pulsed azithromycin treatment is as e ective and sa e as 2-week-longer daily doxycycline treatment o acne vulgaris: a randomized, double-blind, nonin eriority study. Skinmed. 2011;9:86-94. 14. Wu CQ, Grandi SM, Filion KB, Abenhaim HA, Joseph L, Eisenberg MJ. Drospirenone-containing oral contraceptive pills and the risk o venous and arterial thrombosis: a systematic review. BJOG. 2013;120(7):801-810.

PART 14 DERMATO LO GY 15. Shaw JC. Low-dose adjunctive spironolactone in the treatment o acne in women: a retrospective analysis o 85 consecutively treated patients. JAmAcad Dermatol. 2000;43:498-502. 16. Sato K, Matsumoto D, Iizuka F, et al. Anti-androgenic therapy using oral spironolactone or acne vulgaris in Asians. Aesthetic Plast Surg. 2006;30:689-694. 17. Brown J, Farquhar C, Lee O, et al. Spironolactone versus placebo or in combination with steroids or hirsutism and/ or acne. Cochrane Database Syst Rev. 2009;CD000194. 18. Krunic A, Ciurea A, Scheman A. E cacy and tolerance o acne treatment using both spironolactone and a combined contraceptive containing drospirenone. JAmAcad Dermatol. 2008;58:60-62. 19. Enshaieh S, Jooya A, Siadat AH, Iraji F. The e cacy o 5% topical tea tree oil gel in mild to moderate acne vulgaris: a randomized, double-blind placebo-controlled study. Indian J DermatolVenereol Leprol. 2007;73:22-25. 20. Karvonen SL. Acne ulminans: report o clinical ndings and treatment o twenty- our patients. JAmAcad Dermatol. 1993;28:572-579. 21. Seukeran DC, Cunli e WJ. The treatment o acne ulminans: a review o 25 cases. Br J Dermatol. 1999;141:307-309. 22. Tanghetti E, Dhawan S, Green L, et al. Randomized comparison o the sa ety and e cacy o tazarotene 0.1% cream and adapalene 0.3% gel in the treatment o patients with at least moderate acial acne vulgaris. J Drugs Dermatol. 2010;9:549-558. 23. Leyden J, Thiboutot DM, Shalita AR, et al. Comparison o tazarotene and minocycline maintenance therapies in acne vulgaris: a multicenter, double-blind, randomized, parallel-group study. Arch Dermatol. 2006;142:605-612. 24. Yeung CK, Shek SY, Bjerring P, et al. A comparative study o intense pulsed light alone and its combination with photodynamic therapy or the treatment o acial acne in Asian skin. Lasers Surg Med. 2007;39:1-6. 25. Wiegell SR, Wul HC. Photodynamic therapy o acne vulgaris using 5-aminolevulinic acid versus methyl aminolevulinate. JAmAcad Dermatol. 2006;54:647-651. 26. Hor elt C, Funk J, Frohm-Nilsson M, et al. Topical methyl aminolaevulinate photodynamic therapy or treatment o acial acne vulgaris: results o a randomized, controlled study. Br J Dermatol. 2006;155:608-613.

547

548

PART 14 DERMATO LO GY

Ch a pt e r 115

115 RO SACEA Richard P. Usatine , MD

PATIENT STO RY A 34-year-old woman with extensive papulopustular rosacea (Figures 115-1 to 115-3) has a history o easy acial ushing since her teen years. Her ace has been persistently redder in the past 5 years and she is bothered by this. She acknowledges that her mom has similar redness in her ace and that she is rom northern European heritage. In the last 6 months, since her daughter was born, she has developed many “pimples.” Physical examination reveals papules, pustules, and telangiectasias. No comedones are seen. She knows that the sun makes it worse but f nds that many sunscreens are irritating to her skin. The patient is started on oral tetracycline daily and 0.75% metronidazole cream to use once daily. She agrees to wear a hat and stay out o the sun during the middle o the day. She will continue to look or a sunscreen she can tolerate. She knows that precipitating actors or her include hot and humid weather, alcohol, hot beverages, and spicy oods. She will do her best to avoid those actors.

Fig u r e 1 1 5 -2 Clo se -up o p a p ule s a nd p ustule s in the sa m e wo m a n. No te the a b se nce o co m e d o ne s. This is no t a cne . This is p a p ulo p ustula r ro sa ce a . (Re p ro d uce d with p e rm issio n fro m Richa rd P. Usa tine , MD.)

SYNO NYMS Rosacea is also called acne rosacea.

INTRO DUCTIO N Rosacea is an in ammatory condition o the ace and eyes that mostly a ects adults. Most commonly the ace becomes reddened over the cheeks and nose and this is o ten accompanied by telangiectasias and a papulopustular eruption.

Fig u r e 115-1 Rosace a in a 34-ye ar-old woman showing e rythe ma, p ap ule s, and p ustule s cove ring much o the ace . Note he r air skin and b lue e ye s rom he r northe rn Europ e an he ritag e . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

EPIDEMIO LO GY • Rosacea is common in air-skinned people o Celtic and northern European heritage. • Women are more o ten a ected than men.

Fig u r e 115-3 Close -up showing te lang ie ctasias on the nose and p ap ule s around the mouth and chin. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

r O Sa Ce a

Fig u r e 1 15 -4 Rhinop hymatous rosace a with hyp e rtrop hy o the skin o the no se o a 51-ye ar-o ld Hisp anic man. The p atie nt ackno wle d g e s p re vio us he avy alco ho l intake . (Re p ro d uce d with p e rmissio n from Richard P. Usatine , MD.)

• Men are more prone to the extreme orms o hyperplasia, which causes rhinophymatous rosacea (Figures 115-4 and 115-5).

ETIO LO GY AND PATHO PHYSIO LO GY • Although the exact etiology is unknown, the pathophysiology involves nonspecif c in ammation ollowed by dilation around ollicles and hyperreactive capillaries. These dilated capillaries become telangiectasias (Figures 115-6 and 115-7).

PART 14 DERMATO LO GY

Fig u r e 115-6 Erythe matote lang ie ctatic sub typ e o rosace a in a mid d le ag e d Hisp anic woman. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

• As rosacea progresses, di use hypertrophy o the connective tissue and sebaceous glands ensues (see Figures 115-4 and 115-5). • Alcohol may accentuate erythema, but does not cause the disease. Rosacea runs in amilies. • Sun exposure may precipitate an acute rosacea are, but are-ups can happen without sun exposure. • A signif cant increase in the hair ollicle mite Demodex olliculorum is sometimes ound in rosacea. 1 It is theorized that these mites play a role because they incite an in ammatory or allergic reaction by mechanical blockage o ollicles.

RISK FACTO RS Risk actors include genetics, Demodex in estation, 1 sun exposure.

Fig u r e 115-5 Rhinop hymatous rosace a in an old e r man who d oe s not d rink alcohol. Althoug h this is o te n calle d a W. C. Fie ld nose , it is not ne ce ssarily re late d to he avy alcohol use . (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

Fig u r e 115-7 Rosace a in a mid d le -ag e d man showing d e e p e rythe ma and many te lang ie ctasias. (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

549

PART 14 DERMATO LO GY

550

Ch a pt e r 115

DIAGNO SIS CLINICAL FEATURES Rosacea has ollowing 4 stages or subtypes: 1. Erythematotelangiectatic rosacea (see Figures 115-6 and 115-7)—This stage is characterized by requent mild-to-severe ushing with persistent central acial erythema. 2. Papulopustular rosacea (see Figures 115-1 to 115-3, 115-8 and 115-9)—This is a highly vascular stage that involves longer periods o ushing than the f rst stage, o ten lasting rom days to weeks. Minute telangiectasias and papules start to orm by this stage, and some patients begin having very mild ocular complaints such as ocular grittiness or conjunctivitis. These patients may have many unsightly pustules with severe acial erythema. They are more prone to develop a hordeolum (stye) (see Chapter 10, Hordeolum and Chalazion). 3. Phymatous or rhinophymatous rosacea (see Figures 115-4 and 115-5)—Characterized by hyperplasia o the sebaceous glands that orm thickened con uent plaques on the nose known as rhinophyma. This hyperplasia can cause signif cant disf gurement to the orehead, eyelids, chin, and nose. The nasal disf guration is seen more commonly in men than women. W. C. Fields is amous or his rhinophyma and intake o alcohol. Rhinophyma can occur without any alcohol use, as seen in the patient in Figure 115-5. 4. Ocular rosacea (Figures 115-10 to 115-12)—An advanced subtype o rosacea that is characterized by impressive, severe ushing with persistent telangiectasias, papules, and pustules. The patient may complain o watery eyes, a oreign-body sensation, burning, dryness, vision changes, and lid or periocular erythema. The eyelids are most commonly involved with telangiectasias, blepharitis, and recurrent

Fig u r e 115-9 Pap ulop ustular rosace a in a woman who has a history o re curre nt hord e o la. (Courte sy of Richard P. Usatine , MD.)

hordeola and chalazia (see Figures 115-10 and 115-11). Conjunctivitis may be chronic. Although corneal involvement is least common, it can have the most devastating consequences. Corneal f ndings may include punctate erosions, corneal inf ltrates, and corneal neovascularization. In the most severe cases, blood vessels may grow over the cornea and lead to blindness (see Figure 115-12). TYPICAL DISTRIBUTIO N Rosacea occurs on the ace, especially on the cheeks and nose. However, the orehead, eyelids, and chin can also be involved (Figure 115-13).

Fig u r e 115-8 Pap ulop ustular rosace a in a mid d le -ag e d woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Fig u r e 115-10 O cular rosace a sho wing b le p haritis, conjunctival hyp e re mia, and te lang ie ctasias o the lid . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

r O Sa Ce a

PART 14 DERMATO LO GY

Fig u r e 115-11 O cular rosace a with b le p haritis, conjunctivitis, and crusting around the e ye lashe s. This p atie nt has me ib omian g land d ys unction. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Fig u r e 115-13 Rosace a in a young woman with a b utte rf y p atte rn along with chin involve me nt. This is not lup us. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

LABO RATO RY STUDIES

• Seborrheic dermatitis tends to produce scale, whereas rosacea does not. Although both cause central acial erythema, papules and telangiectasias are present in rosacea and are not part o seborrheic dermatitis (see Chapter 149, Seborrheic Dermatitis).

It is not needed when the clinical picture is clear. I you are considering lupus or sarcoid, an antinuclear antibody (ANA), chest X-ray, or punch biopsy may be needed.

DIFFERENTIAL DIAGNO SIS • Acne–The age o onset or rosacea tends to be 30 to 50 years, much later than the onset or acne vulgaris. Comedones are prominent in most cases o acne and generally absent in rosacea (see Chapter 114, Acne Vulgaris). • Sarcoidosis on the ace is much less common than rosacea, but the in amed plaques can be red and resemble the in ammation o rosacea (see Chapter 173, Sarcoidosis o the skin).

• Systemic lupus erythematosus (SLE) can be scarring, does not usually produce papules or pustules, and it spares the nasolabial olds and nose (see Chapter 178, Lupus: Systemic and Cutaneous). The patient in Figure 115-13 has a butter y distribution o her rosacea, but her right nasolabial old is involved along with her chin. The ollowing 3 diagnoses were once considered variants o rosacea but a recent classif cation system identif ed these as separate entities2: • Rosacea ulminans (known as pyoderma aciale) is characterized by the sudden appearance o papules, pustules, and nodules, along with uctuating and draining sinuses that may be interconnecting. The condition appears primarily in women in their 20s, and intense redness and edema also may be prominent (Figure 115-14). 2 • Steroid-induced acnei orm eruption is not a variant o rosacea and can occur as an in ammatory response in any patient during or a ter chronic corticosteroid use. The same in ammatory response may also occur in patients with rosacea (Figure 115-15). • Perioral dermatitis without rosacea symptoms should not be classi ied as a variant o rosacea. Perioral dermatitis is characterized by microvesicles, scaling, and peeling around the mouth (Figure 115-16).

MANAGEMENT

Fig u r e 115-12 Ne ovascularization involving the corne a in a 30-ye ar-old woman with se ve re ocular rosace a. This typ e o corne al involve me nt has cause d a d e cre ase in vision. The woman is hop ing or a corne al transp lant in the uture . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• A Cochrane Database systematic review examined the e icacy o rosacea interventions. 3 Oral doxycycline appeared to be signi icantly more e ective than placebo and there was no statistically signi icant di erence in e ectiveness between the 100-mg and 40-mg doses. 3 SO R A They ound some evidence to support the e ectiveness o topical metronidazole (0.75% or 1%), azelaic acid (15% or 20%) or the treatment o moderate-to-severe rosacea. 3 SO R A Cyclosporine ophthalmic emulsion was signi icantly more

551

552

PART 14 DERMATO LO GY

Fig u r e 115-14 Rosace a ulminans (known as p yod e rma aciale ) is characte rize d b y the sud d e n ap p e arance o p ap ule s, p ustule s, and nod ule s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

e ective than arti icial tears or treating ocular rosacea ( or all outcomes). 3 SO R A • When there are a limited number o papules and pustules, start with topical metronidazole (0.75% or 1%) or topical azelaic acid (15% or 20%). 3 ° There are no substantial di erences between topical metronidazole o 0.75% and 1%, or between once daily and twice daily

Ch a pt e r 115

Fig u r e 115-16 Pe rioral d e rmatitis in this 23-ye ar-old woman with microve sicle s, scaling , and p e e ling around the mouth. Note the sp aring o the skin imme d iate ly around the lip s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

regimens. 4 Metronidazole cream, gel, and lotion have similar e f cacies as well. 4 • Azelaic acid in a 15% gel applied bid appeared to o er some modest benef ts over 0.75% metronidazole gel in a manu acturer-sponsored study. 4 Azelaic acid was not as well tolerated, so both medications are reasonable options with the choice depending on patient pre erence and tolerance. 3 SO R B One study ound that once-daily azelaic acid 15% gel was as e ective as twice-daily application, which can translate into a signif cant cost saving. 5 • I the skin lesions are more extensive, oral antibiotics, such as doxycycline (40 mg or 100 mg daily) is recommended. 3 SO R A When attempting to avoid the photosensitivity side e ects o doxycycline it is reasonable to prescribe oral tetracycline (250-500 mg daily) or oral metronidazole (250-500 mg daily). SO R C • Patients who are started on oral antibiotics alone and improve may be switched to topical agents such as metronidazole or azelaic acid or maintenance. • The Demodex mite may be one causative agent in rosacea. One study ound permethrin 5% cream to be as e ective as metronidazole 0.75% gel and superior to placebo in the treatment o rosacea. 5 SO R

B

• Severe papulopustular disease re ractory to antibiotics and topical treatments can be treated with oral isotretinoin at a low dose o 0.3 mg/ kg per day. 6 SO R B • Simple electrosurgery or laser without anesthesia can be used to treat the telangiectasias associated with rosacea. SO R C • Rhinophyma can be excised with radio requency electrosurgery or laser. Isotretinoin is also used to treat rhinophyma. 6 SO R B

Fig u r e 115-15 Ste roid -ind uce d acne i orm e rup tion cause d b y the use o top ical f uocinonid e d aily in this woman who p rob ab ly had some und e rlying rosace a. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Traditional therapies or mild ocular rosacea include oral tetracyclines, lid hygiene, and warm compresses. 1 SO R C Topical ophthalmic cyclosporine 0.05% (Restasis) is more e ective than artif cial tears or the treatment o rosacea-associated lid and corneal changes. 7 SO R B Ocular rosacea that involves the cornea should be immediately re erred to an ophthalmologist to prevent blindness (see Figure 115-12).

PART 14 DERMATO LO GY

r O Sa Ce a

FO LLO W-UP Follow-up can be done in 1 to 3 months as needed.

PATIENT EDUCATIO N Sun protection, including use o a hat and daily application o sunscreen, should be emphasized. Choose a sunscreen that is nonirritating and protects against UVA and UVB rays. Advise patients to keep a diary to identi y and avoid precipitating actors such as hot and humid weather, alcohol, hot beverages, spicy oods, and large hot meals. PATIENT RESO URCES

• National Rosacea Society. Its mission is to improve the lives of people with rosacea by raising awareness, providing public health in ormation, and supporting medical research—http:/ / www .rosacea.org/ . PRO VIDER RESO URCES

• The National Rosacea Society also has an excellent set of materials that are geared or physicians—http:/ / www.rosacea.org/ .

REFERENCES 1. Zhao YE, Wu LP, Peng Y, Cheng H. Retrospective analysis o the association between Demodex in estation and rosacea. Arch Dermatol. 2010;146:896-902. 2. Wilkin J, Dahl M, Detmar M, et al. Standard classif cation o rosacea: report o the National Rosacea Society Expert Committee on the Classif cation and Staging o Rosacea. JAmAcad Dermatol. 2002;46:584-587. 3. van Zuuren EJ, Kramer S, Carter B, et al. Interventions or rosacea. Cochrane Database Syst Rev. 2011;(3):CD003262. 4. Yoo J, Reid DC, Kimball AB. Metronidazole in the treatment o rosacea: do ormulation, dosing, and concentration matter? J Drugs Dermatol. 2006;5:317-319. 5. Kocak M, Yagli S, Vahapoglu G, Eksioglu M. Permethrin 5% cream versus metronidazole 0.75% gel or the treatment o papulopustular rosacea. A randomized double-blind placebo-controlled study. Dermatology. 2002;205:265-270. 6. Gollnick H, Blume-Peytavi U, Szabo EL, et al. Systemic isotretinoin in the treatment o rosacea- doxycycline- and placebo-controlled, randomized clinical study. J Dtsch Dermatol Ges. 2010;8:505-515. 7. Schechter BA, Katz RS, Friedman LS. E f cacy o topical cyclosporine or the treatment o ocular rosacea. AdvTher. 2009;26:651-659.

553

PART 14 DERMATO LO GY

554

Ch a pt e r 116

116 PSEUDO FO LLICULITIS AND ACNE KELO IDALIS NUCHAE E.J. Maye aux, Jr, MD

PATIENT STO RY A young A rican American man comes to the o ce because he has been bothered by the uncom ortable bumps on the back o his neck and scalp. (Figure 116-1). He likes to wear his hair short but notices that every times he shaves his scalp the bumps on his scalp get irritated. He is diagnosed with acne keloidalis nuchae. It was suggested that he minimize shaving the scalp and let the hair grow out a bit longer. Additional treatment consisted o 0.025% tretinoin cream and 0.1% triamcinolone cream once to twice daily to the involved area.

INTRO DUCTIO N Pseudo olliculitis is a common skin condition a ecting the hair-bearing areas o the body that are shaved (Figures 116-2 to 116-4). Potential complications include postinf ammatory hyperpigmentation, bacterial superin ection, and keloid ormation.

SYNO NYMS • Pseudo olliculitis—Razor bumps, shave bumps • Acne keloidalis nuchae—Folliculitis keloidalis

EPIDEMIO LO GY • Pseudo olliculitis is most common in black men, with at least 50% o black men who shave being prone to the condition. 1 In the beard area

FIGURE 116-1 Acne ke loid alis nuchae in a young A rican Ame rican man. He like s to we ar his hair short b ut notice s that e ve ry time s he shave s his scalp the b ump s on his scalp g e t irritate d . (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 116-2 Pse ud o olliculitis b arb ae along the jawline and ne ck in a young man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

it is called pseudofolliculitis barbae, and when it occurs a ter pubic hair is shaved, it is re erred to as pseudofolliculitis pubis. It may also occur in the neck area. • Acne keloidalis nuchae occurs most o ten in black men but can be seen in all ethnicities (Figures 116-1, 116-5, and 116-6). The lesions are o ten pain ul and cosmetically dis guring. • Both conditions are seen in women but ar less o ten than in men (Figure 116-7).

ETIO LO GY AND PATHO PHYSIO LO GY • Pseudo olliculitis develops when, a ter shaving, the ree end o tightly coiled hair reenters the skin, causing a oreign-body–like in lammatory reaction. Shaving produces a sharp ree end below the skin sur ace. Tightly curled hair has a greater tendency or the

FIGURE 116-3 Pse ud o olliculitis b arb ae in a Dominican man. Note the active p ustule s on the ne ck. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

pSe UDO FO LLICULIt IS a ND a CNe Ke LO IDa LIS NUCh a e

FIGURE 116-4 Pse ud o olliculitis b arb ae on the ace o a 28-ye ar-old A rican man who works p rovid ing aid to Dar ur re ug e e s. The p ain ul nod ule s b e come wo rse e ve ry time he shave s. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

tip to pierce the sur ace o the skin and orm ingrown hairs. This explains the relative predominance o this condition in patients o A rican ethnicity. The hair eventually orms a loop and i the embedded tip is pulled out there may be spontaneous resolution o symptoms. • The exact cause o acne keloidalis is uncertain. It o ten develops in areas o pseudo olliculitis or olliculitis. It may be associated with haircuts where the posterior hairline is shaved with a razor and with tightly curved hair sha ts. Other possible etiologies include irritation rom shirt collars, chronic bacterial in ections, and an autoimmune process. It is a orm o primary scarring alopecia. 2 As such, multiple hairs can be seen growing rom single ollicle (hair tu ts) in the midst o the keloidal scarring (see Figure 116-6).

FIGURE 116-6 Acne ke loid alis nuchae with larg e ke loid al mass in a Hisp anic man. Note multip le hairs can b e se e n g rowing rom sing le ollicle s (hair tu ts). Surg e ry is the only tre atme nt that can re move this ke loid al mass. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

RISK FACTO RS • Pseudo olliculitis ° A rican ethnicity ° Curly hair • Acne keloidalis nuchae ° Shaving the hair on the neck ° Pseudo olliculitis

DIAGNO SIS CLINICAL FEATURES • The diagnosis o pseudo olliculitis is based on clinical appearance. A piece o hair o ten may be identi ed protruding rom a lesion. Inf ammation results in the ormation o rm, skin-colored, erythematous or hyperpigmented papules that occur a ter shaving (see Figures 116-2 to 116-4). Pustules may develop secondarily. The severity varies rom a ew papules or pustules to hundreds o lesions. • Patients with acne keloidalis initially develop a olliculitis or pseudo olliculitis, which heals with keloid-like lesions, sometimes with discharging sinuses. It starts a ter puberty as 2- to 4-mm rm, ollicular papules (see Figure 116-2). More papules appear and enlarge over time (see Figure 116-5). Papules may coalesce to orm keloid-like plaques, which are usually arranged in a band-like distribution along the posterior part o the hairline (Figures 116-6 and 116-8). TYPICAL DISTRIBUTIO N • Pseudo olliculitis a ects the hair-bearing areas o the body that are shaved, especially the ace, neck, and pubic area (see Figures 116-2 to 116-4). • Acne keloidalis occurs on the occipital scalp and the posterior part o the neck (see Figures 116-1, 116-5, and 116-6). BIO PSY

FIGURE 116-5 Acne ke loid alis with multip le f rm ke loid al p ap ule s in a Hisp anic man who p re e rs to ke e p his hair short. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Histologic evaluation o a biopsy may con rm either diagnosis but is usually not necessary.

555

556

PART 14 DERMATO LO GY

Ch a pt e r 116

these men to go without shaving. In mild cases, shaving should be discontinued or a month. The beard can be coarsely trimmed with scissors or electric clippers during this time. Shaving should not resume until all inf ammatory lesions have resolved. Warm Burow solution compresses may be applied to the lesions or 10 minutes, 2 times per day. Instruct the patient to search or ingrown hairs each day using a magni ying mirror and release them gently using a sterilized needle or tweezers. The hairs should not be plucked as this may cause recurrence o symptoms with hair regrowth (see Figure 116-7). SO R

FIGURE 116-7 Pse ud o olliculitis b arb ae in a b lack woman with hirsutism. The scarring is re late d to p lucking and shaving the hairs o n the ne ck. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIFFERENTIAL DIAGNO SIS • True olliculitis, which is an acute pustular in ection o a hair ollicle with more localized inf ammation (see Chapter 119, Folliculitis) • Impetigo, which presents with yellowish pustules or bullae that rupture and develop honey crusts, sometimes with adenopathy (see Chapter 118, Impetigo) • Acne vulgaris, which presents with comedones and pustules usually including the orehead (see Chapter 114, Acne Vulgaris)

MANAGEMENT NO NPHARMACO LO GIC • Avoid close shaving, avoid all shaving, or permanently remove hair. 3 Some occupations, however, such as the military and law en orcement, require acial shaving. Occasionally, a doctor’s note will allow

• Chemical depilatories (Ali, Royal Crown, Magic Shave, and others) cause ewer symptoms than shaving. 4 SO R B However, these creams can cause severe irritation, so testing a small amount on the orearm is important. They work by breaking the disul de bonds in hair, which results in the hair being bluntly broken at the ollicular opening instead o sharply cut below the sur ace. They should be used every second or third day to avoid skin irritation, although this can be controlled with hydrocortisone cream. Barium sul de 2% powder depilatories can be made into a paste with water, applied to the beard, and removed a ter 3 to 5 minutes. Calcium thioglycolate preparations are le t on 10 to 15 minutes, but the ragrances can cause an allergic reaction and chemical burns can result i it is le t or too long. • People who have acne keloidalis nuchae should avoid anything that causes olliculitis or pseudo olliculitis, such as getting their neck or hairline shaved with a razor. MEDICATIO NS • Topical ef ornithine HCL 13.9% cream (Vaniqa; by prescription only) may be used to inhibit hair growth. It decreases the rate o hair growth and may make the hair ner and lighter. Un ortunately, this medication is expensive and requires daily application or continued e cacy. SO R • Twice-daily treatment with a class 2 or 3 corticosteroid may be su cient to shrink pseudo olliculitis lesions and relieve symptoms (see Appendix B: Topical and Intralesional Corticosteroids). SO R • When pustules, crust ormation, or drainage is present, use topical clindamycin or erythromycin. Unresponsive patients may be changed to a systemic antibiotic. SO R • Topical erythromycin, clindamycin, and combination clindamycin– benzoyl peroxide (BenzaClin, Duac) and erythromycin–benzoyl peroxide (Benzamycin) may be used once or twice daily. 5 SO R B • Oral doxycycline 100 mg bid, tetracycline 500 mg bid, or erythromycin 500 mg bid may be used or patients with more severe secondary inf ammation. SO R • Tretinoin cream, 0.025%, may be use ul in patients with mild disease, but is rarely help ul in moderate-to-severe cases. 6 It is applied nightly or a week then reduced to every second or third night. Tretinoin may be used in conjunction with a mid-potency topical corticosteroid applied each morning. The mechanism o action is thought to be by relieving hyperkeratosis and “toughening” the skin. Topical combination cream (tretinoin 0.05%, luocinolone acetonide 0.01%, and hydroquinone 4%) (Tri-Luma) adds an additional postin lammatory hyperpigmentation treatment. SO R

FIGURE 116-8 Acne keloidalis nuchae a ter injection with intralesional triamcinolone. Although the keloid is smaller and so ter, some hypopigmentation has occurred. (Reproduced with permission from Richard P. Usatine, MD.)

• Intralesional steroid injections (10-20 mg/ mL) may be used to so ten and shrink keloids. Warn patients that this therapy may cause hypopigmentation (see Figure 116-8). SO R

PART 14 DERMATO LO GY

pSe UDO FO LLICULIt IS a ND a CNe Ke LO IDa LIS NUCh a e

PATIENT EDUCATIO N • For those who must shave, have the patient clip hairs no shorter than needed or maintenance. Use ne scissors or acial hair clippers i possible. When shaving, have the patient rinse with warm tap water or several minutes, use generous amounts o a highly lubricating shaving gel, and allow it to so ten the skin or 5 to 10 minutes be ore shaving. The patient should always use sharp razors and shave in the direction o hair growth. Specialized guarded razors (eg, PFB Bump Fighter) are available in pharmacies and by mail order. A ter shaving rinse the ace with tap water, and then apply cold water compresses. • With acne keloidalis, instruct males who play ootball to make sure their helmets t properly and do not cause irritation on the posterior part o the scalp. They should avoid having the posterior part o the hairline shaved with a razor as part o a haircut, and discontinue wearing garments that rub or irritate the posterior parts o the scalp and the neck. FIGURE 116-9 Hyp e rtrop hic scarring a te r the e xcision o acne ke loid alis nuchae . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PATIENT RESO URCES

SURGICAL • The only de nitive cure or pseudo olliculitis is permanent hair removal. Electrolysis is expensive, pain ul, and sometimes unsuccess ul. Laser hair removal is airly success ul or treating pseudo olliculitis.7 SO R B Diode laser (810 nm) treatments have been proven sa e and e ective in patients with skin phototypes I to IV. 8 • Excision o acne keloidalis lesions may be attempted. Recalcitrant keloidal lesions may be treated with removing individual papules with a small punch, or large keloids (Figure 116-9) with an elliptical excision closed with sutures. A ter removal, the wound edges should be injected with a mixture o equal amount o triamcinolone acetonide 40 mg/ mL and sterile saline. Remove the sutures in 1 to 2 weeks and inject the edges every month with the above mixture or 3 to 4 times. SO R Excision should extend into the subcutaneous tissue and the wound edges can be injected with 10 to 40 mg/ mL o triamcinolone acetonide and be reapproximated. SO R Recurrence is common, especially with shallow excisions or not treating with steroids. • Other therapies that may be considered are laser therapy (carbon dioxide or Nd:YAG [neodymium:yttrium-aluminum-garnet]) ollowed by intralesional triamcinolone injections or cryotherapy or two 20-second bursts that are allowed to thaw and are then applied again a minute later. These methods may produce more pain and hypopigmentation. SOR

PREVENTIO N Termination o shaving prevents the development o pseudo olliculitis.

PRO GNO SIS No speci c cure exists. I the patient is able to stop shaving, the problem usually disappears (except or any scar ormation).

FO LLO W-UP Instruct patients to return i any complications occur. Otherwise have them return or possible initiation o intralesional steroid injections or topical steroid/ retinoic acid therapy once the area has healed.

• American Osteopathic College of Dermatology. Pseudofolliculitis— http:/ / aocd.org/ skin/ dermatologic_diseases/ pseudofolliculitis.html. • Skin Channel. Acne Keloidalis Nuchae—http:/ / skinchannel .com/ acne/ acne-keloidalis-nuchae/ . PRO VIDER RESO URCES

• eMedicine. Pseudofolliculitis—http:/ / emedicine.medscape .com/ article/ 1071251. • eMedicine. Acne Keloidalis—http:/ / emedicine.medscape .com/ article/ 1072149. • DermNet NZ. Acne Keloidalis—http:/ / dermnetnz.org/ acne/ keloid-acne.html.

REFERENCES 1. Coquilla BH, Lewis CW. Management o pseudo olliculitis barbae. Mil Med. 1995;160(5):263-269. 2. Sperling LC, Homoky C, Pratt L, Sau P. Acne keloidalis is a orm o primary scarring alopecia. Arch Dermatol. 2000;136(4):479-484. 3. Chui CT, Berger TG, Price VH, Zachary CB. Recalcitrant scarring ollicular disorders treated by laser-assisted hair removal: a preliminary report. Dermatol Surg. 1999;25(1):34-37. 4. Hage JJ, Bowman FG. Surgical depilation or the treatment o pseudoolliculitis or local hirsutism o the ace: experience in the rst 40 patients. Plast Reconstr Surg. 1991;88:446-451. 5. Cook-Bolden FE, Barba A, Halder R, Taylor S. Twice-daily applications o benzoyl peroxide 5% clindamycin 1% gel versus vehicle in the treatment o pseudo olliculitis barbae. Cutis. 2004;73(suppl 6):18-24. 6. Brown LA Jr. Pathogenesis and treatment o pseudo olliculitis barbae. Cutis. 1983;32(4):373-375. 7. Ross EV, Cooke LM, Timko AL, et al. Treatment o pseudo olliculitis barbae in skin types IV, V, and VI with a long-pulsed neodymium: yttrium aluminum garnet laser. JAmAcad Dermatol. 2002;47(2): 263-270. 8. Kauvar AN. Treatment o pseudo olliculitis with a pulsed in rared laser. Arch Dermatol. 2000;136(11):1343-1346.

557

PART 14 DERMATO LO GY

558

117 HIDRADENITIS SUPPURATIVA Richard P. Usatine , MD

PATIENT STO RY A 25-year-old woman presents with new tender lesions in her axilla (Figure 117-1). She admits to years o similar outbreaks in both axilla and occasional pain ul bumps in the groin. She states that it is pain ul to have them opened and just wants to get some relie without surgery. We elected to inject the nodules with triamcinolone and start the patient on doxycycline 100 mg twice daily. Smoking cessation was emphasized and the patient agreed to start on a nicotine patch that evening. She had relie within 24 hours rom the steroid injection.

Ch a pt e r 117

EPIDEMIO LO GY • Occurs a ter puberty in approximately 1% o the population. 1 • Incidence is higher in emales, in the range o 4:1 to 5:1. Flare-ups may be associated with menses. 1

ETIO LO GY AND PATHO PHYSIO LO GY • Disorder o the terminal ollicular epithelium in the apocrine gland-bearing skin1 • Starts with occlusion o hair ollicles that lead to occlusion o surrounding apocrine glands • Chronic relapsing in ammation with mucopurulent discharge (Figures 117-2 to 117-7) • Can lead to sinus tracts, draining f stulas, and progressive scarring (see Figures 117-2 to 117-7)

INTRO DUCTIO N Hidradenitis suppurativa (HS) is an in ammatory disease o the pilosebaceous unit in the apocrine gland-bearing skin. HS is most common in the axilla and inguinal area, but may be ound in the in ramammary area as well. It produces pain ul in ammatory nodules, cysts, and sinus tracks with mucopurulent discharge and progressive scarring.

SYNO NYMS It is called acne inversa because it involves intertriginous areas and not the regions a ected by acne (similar to inverse psoriasis).

RISK FACTO RS Obesity, smoking, and tight-f tting clothing are the risk actors o HS.

DIAGNO SIS CLINICAL FEATURES • Most common presentation is pain ul, tender, f rm, nodular lesions in axillae (see Figures 117-1 to 117-3). • Nodules may open and drain pus spontaneously and heal slowly, with or without drainage, over 10 to 30 days. 1 • Nodules may recur several times yearly, or in severe cases new lesions orm as old ones heal. • Surrounding cellulitis may be present and require systemic antibiotic treatment.

FIGURE 117-1 Mild hid rad e nitis sup p urativa in the axilla o a young woman. She has a history o re curre nt le sions in he r axilla. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 117-2 Mod e rate hid rad e nitis sup p urativa in a young woman. The le sions are d e e p e r and the re have b e e n some chronic chang e s with scarring and b rosis rom p re vio us le sio ns. (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

h IDr a De NIt IS SUppUr a t IVa

PART 14 DERMATO LO GY

FIGURE 117-5 Se ve re d isab ling hid rad e nitis sup p urativa in a 34-ye ar-old white man who is morb id ly ob e se . He nd s it p ain ul to walk. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

TYPICAL DISTRIBUTIO N

FIGURE 117-3 A 33-ye ar-old Hisp anic woman with sinus tracts, d raining stulas, and scarring se cond ary to he r chronic hid rad e nitis sup p urativa. Note the mucop urule nt d ischarg e . (Re p rod uce d with p e rmissio n fro m Richard P. Usatine , MD.)

• Chronic recurrences result in thickened sinus tracts, which may become draining f stulas (see Figures 117-3 to 117-7). • HS can cause disabling pain, diminished range o motion, and social isolation (see Figure 117-5).

FIGURE 117-4 Long-standing pain ul severe hidradenitis suppurativa between the breasts o a 45-year-old woman. (Reproduced with permission from Richard P. Usatine, MD.)

Axillary, inguinal, periareolar, intermammary zones, pubic area, in raumbilical midline, gluteal olds, top o the anterior thighs, and the perianal region. 1 LABO RATO RY STUDIES Culture o purulence is likely to yield staphylococci and streptococci and is usually unnecessary to determine treatment. Culture may be use ul i you suspect methicillin-resistant Staphylococcus aureus (MRSA).

FIGURE 117-6 Se ve re hid rad e nitis sup p urativa in the vulva and on the mons p ub is. The skin is thicke ne d and hyp e rp ig me nte d rom the ong oing inf ammatory le sions p re se nt in the are a. (Re p rod uce d with p e rmission from Suraj Re d d y, MD.)

559

560

PART 14 DERMATO LO GY

Ch a pt e r 117

° Combination o systemic clindamycin (300 mg twice daily) and ri ampin (600 mg daily) is recommended or patients with more severe HS. 2,3 In a series o 116 patients, parameters o severity improved, as did the quality-o -li e score. 2 In another study, 28 o 34 patients (82%) experienced at least partial improvement, and 16 (47%) showed a total remission. 3 The maximum e ect o treatment appeared within 10 weeks. Following total remission, 8 o 13 (61.5%) patients experienced a relapse a ter a mean period o 5 months. Nonresponders were predominantly patients with severe disease. The most requent side e ect is diarrhea. 2,3 ° Oral dapsone may be considered in milder cases. In one study, only 38% o patients experienced improvement. 4 SO R B Rapid recurrence a ter stopping treatment suggests that anti-in ammatory e ects may predominate over antimicrobial e ects. The total e ect appears to be smaller than that reported with combination therapy using clindamycin and ri ampicin. • Isotretinoin can reduce the severity o attacks in some patients but is not a reliable cure or HS. 5 SO R

FIGURE 117-7 Thirty-ye ar history o se ve re hid rad e nitis in a 54-ye ar-old woman. Note the scars rom p re vious p lastic surg e rie s. Note the d raining cysts, stulas, and the acute ab sce ss on he r le t b uttocks. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIFFERENTIAL DIAGNO SIS • Bacterial in ections, including olliculitis, carbuncles, uruncles, abscess, and cellulitis, may resemble HS but are less likely to be recurrent in the intertriginous areas. • Epidermal cysts in the intertriginous regions may resemble HS. Theses cysts contain malodorous keratin contents. • Granuloma inguinale and lymphogranuloma venereum are sexually transmitted in ections that can produce inguinal ulcers and adenopathy that could be mistaken or HS.

MANAGEMENT • Li estyle changes are recommended, including weight loss i obesity is present. SO R • Smoking is a risk actor or HS and cessation is highly recommended or many reasons. 1 See SOR B or HS and SOR A or other health reasons. • Frequent bathing and wearing loose-f tting clothing may help. Medical treatment is similar to acne treatment. • Oral antibiotics are used in acute and chronic treatment. Oral tetracyclines, clindamycin, ri ampin, and dapsone have been touted as benef cial. I MRSA is present there, trimethoprim/ sul amethoxazole or clindamycin should be used. • Tetracycline 500 mg bid and doxycycline 100 mg bid can be used acutely and to prevent new lesions in the mildest o cases. Many patients do not f nd these antibiotics to be o great help. SO R • Topical clindamycin bid may be used in the mildest o cases. In one randomized controlled trial (RCT), systemic therapy with tetracyclines did not show better results than topical therapy with clindamycin. 1 SO R B

• Acitretin can be an e ective treatment or re ractory HS. In one study, all 12 patients achieved remission and experienced a signif cant decrease in pain. Long-lasting improvement was observed in 9 patients, with no recurrence o lesions a ter 6 months (n = 1), 1 year (n = 3), more than 2 years (n = 2), more than 3 years (n = 2), and more than 4 years (n = 1). 5 SO R B • Antitumor necrosis actor (TNF) agents are being studied or severe, recalcitrant HS (Figure 117-8). In one series, in iximab therapy (weight based) was shown to be e ective and well tolerated in 6 o 7 patients with HS who were resistant to previous therapy. 6 This was in agreement with preexisting literature showing that 52 o 60 patients (87%) were improved a ter in iximab therapy. 6 SO R B Adalimumab helps in the short term, but no long-term curative e ect was uni ormly seen. 7 • Intense pulsed light (IPL) with laser may be worth considering or patients who can a ord the cost and time or treatment. In one study o 18 patients who were randomized to treatment o one axilla, groin, or in ramammary area with IPL 2 times per week or 4 weeks, there was a signif cant improvement in the mean examination score, which was maintained at 12 months. Patients reported high levels o satis action with the IPL treatment. 8 SO R B Surgical treatments include the ollowing: • Intralesional steroids with 5 to 10 mg/ mL o triamcinolone may help to decrease in ammation and pain within 24 to 48 hours. SO R

• Incision and drainage o acute lesions are suggested or the large luctuant abscesses that can occur in HS. Although this may give some relie o the pressure, the surgical treatment and repacking o the wound is pain ul, and there is no evidence that it speeds healing. SO R • Lancing small nodules is more pain ul than help ul and is not recommended. • Surgical excision o a ected area with or without skin gra ting is used or recalcitrant disabling disease and should be individualized based on the stage and location o the disease. 9 SO R B One surgical group has been using a medial thigh li t or immediate de ect closure a ter radical excision o localized inguinal hidradenitis. 10

PART 14 DERMATO LO GY

h IDr a De NIt IS SUppUr a t IVa

PATIENT RESO URCES

• Medline Plus. Hidradenitis Suppurativa—http:/ / www.nlm .nih.gov/ medlineplus/ hidradenitissuppurativa.html. PRO VIDER RESO URCES

• Medscape. Hidradenitis Suppurativa—http:/ / emedicine .medscape.com/ article/ 1073117-overview.

REFERENCES 1. Jemec GB, Wendelboe P. Topical clindamycin versus systemic tetracycline in the treatment o hidradenitis suppurativa. JAmAcad Dermatol. 1998;39:971-974. 2. Gener G, Canoui-Poitrine F, Revuz JE, et al. Combination therapy with clindamycin and ri ampicin or hidradenitis suppurativa: a series o 116 consecutive patients. Dermatology. 2009;219:148-154. A

3. van der Zee HH, Boer J, Prens EP, Jemec GBE. The e ect o combined treatment with oral clindamycin and oral ri ampicin in patients with hidradenitis suppurativa. Dermatology. 2009;219:143-147. 4. Yazdanyar S, Boer J, Ingvarsson G, et al. Dapsone therapy or hidradenitis suppurativa: a series o 24 patients. Dermatology. 2011;222(4):342-346. 5. Boer J, Nazary M. Long-term results o acitretin therapy or hidradenitis suppurativa. Is acne inversa also a misnomer? Br J Dermatol. 2011;164:170-175. 6. Delage M, Samimi M, Atlan M, et al. E f cacy o in iximab or hidradenitis suppurativa: assessment o clinical and biological in ammatory markers. Acta DermVenereol. 2011;91:169-171. 7. Miller I, Lynggaard CD, Lophaven S, et al. A double-blind placebocontrolled randomized trial o adalimumab in the treatment o hidradenitis suppurativa. Br J Dermatol. 2011;165:391-398.

B FIGURE 117-8 Se ve re re calcitrant hid rad e nitis in this 42-ye ar-old woman with sinus tracts and scarring . She has e xp e rie nce d sig ni cant symp tomatic re lie with inf iximab in usions. A. Axillary involve me nt. B. In ramammary involve me nt. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FO LLO W-UP I there is cellulitis or a large abscess was drained, ollow-up should be within days. Chronic relapsing disease can ultimately be managed with appointments every 3 to 6 months depending on the treatment and its success.

PATIENT EDUCATIO N Smoking cessation, weight loss i overweight, and avoidance o tightf tting clothes should be emphasized.

8. Highton L, Chan WY, Khwaja N, Laitung JK. Treatment o hidradenitis suppurativa with intense pulsed light: a prospective study. Plast Reconstr Surg. 2011;128:459-466. 9. Kagan RJ, Yakubo KP, Warner P, Warden GD. Surgical treatment o hidradenitis suppurativa: a 10-year experience. Surgery. 2005;138:734-740. 10. Rieger UM, Erba P, Pierer G, Kalbermatten DF. Hidradenitis suppurativa o the groin treated by radical excision and de ect closure by medial thigh li t: aesthetic surgery meets reconstructive surgery. J Plast Reconstr Aesthet Surg. 2009;62:1355-1360.

561

562

PART 14 DERMATO LO GY

SECTIO N 2

Ch a PTEr 118

BACTERIAL

118 IMPETIGO Richard P. Usatine , MD

PATIENT STO RY A young woman presented to the o ce with a 3-day history o an uncom ortable rash on her lip and chin (Figure 118-1). She denied any trauma or previous history o oral herpes. This case o impetigo resolved quickly with oral cephalexin.

INTRO DUCTIO N Impetigo is the most super cial o bacterial skin in ections. It causes honey crusts, bullae, and erosions.

EPIDEMIO LO GY

Fig u r e 118-2 Bullous imp e tig o se cond ary to me thicillin-re sistant Stap hyloco ccus aure us (MRSA) on the le g . Note the surround ing ce llulitis. (Re p rod uce d with p e rmission from Stud d iford J, Stone house A. Bullous e rup tion on the p oste rior thig h 1. J Fam Pract. 2005;54:1041-1044. Re p rod uce d with p e rmission from Frontline Me d ical Communications.)

• It is most requent in children ages 2 to 6 years, but it can be seen in patients o any age.

• Bullous impetigo (Figure 118-2) is almost always caused by S. aureus and is less common than the typical crusted impetigo. 1

• It is common among homeless people living on the streets.

• Impetigo may occur a ter minor skin injury, such as an insect bite, abrasion, or dermatitis.

• It is o ten seen in third world countries in persons living without easy access to clean water and soap. • Contagious and can be spread within a household.

ETIO LO GY AND PATHO PHYSIO LO GY • Impetigo is caused by Staphylococcus aureus and/ or group A β-hemolytic Streptococcus (GABHS).

DIAGNO SIS CLINICAL FEATURES Vesicles, pustules, honey-colored (see Figure 118-1), brown or dark crusts, erythematous erosions (Figure 118-3), ulcers in ecthyma (Figure 118-4), and bullae in bullous impetigo (Figures 118-5 to 118-7) TYPICAL DISTRIBUTIO N Face (see Figures 118-1, 118-4 to 118-6, and 118-8) is most common, ollowed by hands, legs (see Figure 118-2), trunk, and buttocks. CULTURE Culture should be considered in severe cases because o the rising incidence o methicillin-resistant S. aureus (MRSA)-causing impetigo.

DIFFERENTIAL DIAGNO SIS Many o the conditions below can become impetigo a ter being secondarily in ected with bacteria. This process is called impetiginization.

Fig u r e 118-1 Typ ical hone y-cruste d p laq ue on the lip o an ad ult with imp e tig o. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Atopic dermatitis—A common inf ammatory skin disorder characterized by itching and inf amed skin. It can become secondarily in ected with bacteria (Figure 118-9) (see Chapter 143, Atopic Dermatitis).

IMPETIGO

PART 14 DERMATO LO GY

Fig u r e 118-3 Widespread impetigo with honey-crusted erythematous lesions on the back. (Reproduced with permission from Richard P. Usatine, MD.)

Fig u r e 118-6 Bullous imp e tig o on the ace . Me thicillin-re sistant Stap hylococcus aure us (MRSA) was culture d rom the imp e tig o. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Herpes simplex virus in ection anywhere on the skin or mucous membranes can become secondarily in ected (see Chapter 128, Herpes Simplex). • Eczema herpeticum is eczema superin ected with herpes rather than bacteria. • Scabies—Pruritic contagious disease caused by a mite that burrows in skin (see Chapter 141, Scabies). Fig u r e 118-4 Imp e tig o on the ace and hand o a home le ss man. Note the e cthyma (ulce rate d imp e tig o) on the d orsum o the hand . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Fig u r e 118-5 Bullous imp e tig o around the mo uth that p rog re sse d to d e sq uamation o the skin o the hand s and e e t. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Folliculitis—Inf ammation and/ or in ection o hair ollicles that may be bacterial (see Chapter 119, Folliculitis). • Tinea corporis—A cutaneous ungal in ection caused by dermatophytes, requently with ring-like scale (see Chapter 136, Tinea Corporis).

Fig u r e 118-7 Bullous imp e tig o on the ab d ome n. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

563

564

PART 14 DERMATO LO GY

Ch a PTEr 118

Fig u r e 118-10 Se cond ary imp e tig inization o a se cond -d e g re e sunb urn in a home le ss man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.) Fig u r e 118-8 Imp e tig o on the nose o a young woman as p art o the initial p re se ntatio n o syste mic lup us e rythe mato sus. No te the sub tle b utte rf y hyp e rp ig me ntation on the che e ks. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Pemphigus vulgaris—Somewhat rare bullous autoimmune condition with f accid vesicles and bullae that rupture easily, a ecting people between 40 and 60 years o age (see Chapter 183, Pemphigus). • Bullous pemphigoid—An autoimmune condition with multiple tense bullae that primarily a ects people older than 60 years o age (see Chapter 182, Bullous Pemphigoid). • Acute allergic contact dermatitis—Dermatitis rom direct cutaneous exposure to allergens such as poison ivy. Acute lesions are erythematous papules and vesicles in a linear pattern (see Chapter 144, Contact Dermatitis). • Insect bites—Scratched, open lesions can become secondarily in ected with bacteria (impetiginized). • Second-degree burn or sunburn—The blisters when opened leave the skin susceptible to secondary in ection (Figure 118-10). • Staphylococcal scalded skin syndrome—Li e-threatening syndrome o acute ex oliation o the skin caused by an exotoxin rom a

staphylococcal in ection. This condition is seen almost entirely in in ants and young children.

MANAGEMENT • There is good evidence that topical mupirocin is equally or more e ective than oral treatment or people with limited impetigo. SO R A Mupirocin also covers MRSA. 2 • Extensive impetigo could be treated or 7 days with antibiotics that cover GABHS and S. aureus, such as cephalexin or dicloxacillin. 3 SOR A • Community-acquired MRSA can present as bullous impetigo (see Figures 118-2 and 118-6). • I you suspect MRSA, culture the lesions and start one o the ollowing oral antibiotics: trimethoprim-sul amethoxazole, clindamycin, tetracycline, or doxycycline.4 SOR A Trimethoprim-sul amethoxazole achieved 100% clearance in the treatment o impetigo in children cultured with MRSA and GABHS in one small randomized controlled trial (RCT).5 • I there are recurrent MRSA in ections, one might choose to prescribe intranasal mupirocin ointment and chlorhexidine bathing to decrease MRSA colonization. 6 SO R B

PREVENTIO N Practice good hygiene with soap and water. Avoid sharing towels and wash clothes.

FO LLO W-UP Arrange ollow-up based on severity o case and the age and immune status o the patient.

PATIENT EDUCATIO N Fig u r e 118-9 Imp e tig o se cond ary to p ap ular e cze ma on the ne ck. Note the hone y crusting o the le sions close to the hairline . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Discuss hygiene issues and how to avoid spread within the household or other living situations such as homeless shelters.

IMPETIGO

REFERENCES 1. Studdi ord J, Stonehouse A. Bullous eruption on the posterior thigh 1. J Fam Pract. 2005;54:1041-1044. 2. Koning S, Verhagen AP, van-Suijlekom-Smit LWA, et al. Interventions or impetigo. Cochrane Database Syst Rev. 2012;CD003261. 3. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines or the diagnosis and management o skin and so t-tissue in ections. Clin Infect Dis. 2005;41:1373-1406. 4. Naimi TS, LeDell KH, Como-Sabetti K, et al. Comparison o community- and health care-associated methicillin-resistant Staphylococcus aureus in ection. JAMA. 2003;290:2976-2984.

PART 14 DERMATO LO GY 5. Tong SY, Andrews RM, Kearns T, et al. Trimethoprim-sul amethoxazole compared with benzathine penicillin or treatment o impetigo in aboriginal children: a pilot randomised controlled trial. J Paediatr Child Health. 2010;46(3):131-133. 6. Wendt C, Schinke S, Württemberger M, et al. Value o whole-body washing with chlorhexidine or the eradication o methicillin-resistant Staphylococcus aureus: a randomized, placebo-controlled, double-blind clinical trial. Infect Control Hosp Epidemiol. 2007;28(9):1036-1043.

565

566

PART 14 DERMATO LO GY

Ch a pTe r 119

119 FO LLICULITIS Richard P. Usatine , MD Khalilah Hunte r-And e rson, MD

PATIENT STO RY A 42-year-old woman is seen or multiple papules and pustules on her back (Figure 119-1). Further questioning demonstrates that she was in a riend’s hot tub twice over the previous weekend. The outbreak on her back started a ter she went into the hot tub the second time. This is a case o Pseudomonas olliculitis or “hot tub” olliculitis. The patient avoided this hot tub and the olliculitis disappeared spontaneously. Another option is to treat with an oral uoroquinolone that covers Pseudomonas. FIGURE 119-2 Close-up o b acte rial olliculitis showing hairs coming through pustule s. (Re produce d with pe rmission from Richard P. Usatine, MD.)

INTRO DUCTIO N Folliculitis is an in ammation o hair ollicles usually rom an in ectious etiology. Multiple species o bacteria have been implicated, as well as ungal organisms.

EPIDEMIO LO GY • Folliculitis is a cutaneous disorder that a ects all age groups and races, and both genders.

• It can be in ectious or nonin ectious. It is most commonly o bacterial origin (Figures 119-2 and 119-3). • Pseudo olliculitis or sycosis barbae is most requently seen in men o color and made worse by shaving (Figure 119-4). 1 • Acne keloidalis nuchae or keloidal olliculitis is commonly seen in black patients, but can be seen in patients o any ethnic background (Figures 119-5 and 119-6). 2 • Eosinophilic olliculitis is described in patients with HIV in ection (Figure 119-7). • Methicillin-resistant Staphylococcus aureus (MRSA) can pose a challenge to the treatment o olliculitis (Figure 119-8).

ETIO LO GY AND PATHO PHYSIO LO GY • Folliculitis is an in ection o the hair ollicle and can be superf cial, in which it is conf ned to the upper hair ollicle, or deep, in which in ammation spans the entire depth o the ollicle.

FIGURE 119-1 ”Hot-tub ” olliculitis rom Pse ud omonas ae rug ino sa in a hot tub . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 119-3 Chronic bacterial olliculitis on the b ack with scarring and hyperpigmentation. (Reproduced with pe rmission from E.J. Mayeaux, Jr, MD.)

FO LLICULITIS

FIGURE 119-4 Pse ud o olliculitis b arb ae in a b lack man. Shaving make s it worse and he note s many p rob le ms with ing rown hairs. (Re p rod uce d with p e rmission from Jonathan Karne s, MD.)

PART 14 DERMATO LO GY

FIGURE 119-7 Eosinop hilic o lliculitis on the b ack o an HIV-p ositive man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• In ection can be o bacterial, viral, or ungal origin. S. aureus is by ar the most common bacterial causative agent. • The nonin ectious orm o olliculitis is o ten seen in adolescents and young adults who wear tight-f tting clothes. Folliculitis can also be caused by chemical irritants or physical injury. • Topical steroid use, ointments, lotions, or makeup can swell the opening to the pilosebaceous unit and cause olliculitis. • Bacterial olliculitis or Staphylococcus olliculitis typically presents as in ected pustules most prominent on the ace, buttocks, trunk, or extremities. It can progress to a deeper in ection with the development o uruncles or boils (Figure 119-9). In ection can occur as a result o mechanical injury or via local spread rom nearby in ected wounds. An area o desquamation is requently seen surrounding in ected pustules in S. aureus olliculitis. 1-3 FIGURE 119-5 Acne ke loid alis nuchae with inf ame d p ap ule s and p ustule s on the b ack o the ne ck o a young Hisp anic man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 119-6 Acne ke loid alis nuchae in a woman d e monstrating the olliculitis around the hair ollicle s and the scarring alop e cia that has occurre d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Parasitic olliculitis usually occurs as a result o mite in estation (Demodex). These are usually seen on the ace, nose, and back and typically cause an eosinophilic pustular-like olliculitis. 1

FIGURE 119-8 MRSA olliculitis in the axilla o a 29-ye ar-old woman. The le sions we re p re se nt or 4 we e ks in the axilla, le t ore arm, and rig ht thig h. The MRSA was se nsitive to te tracycline s and re solve d with oral d oxycycline . (Re p rod uce d with p e rmission from Alisha N. Plotne r, MD, and Rob e rt T. Brode ll, MD, and used with pe rmission from Plotne r AN, Brode ll RT. Bilateral axillary p ustule s. J Fam Pract. 2008;57(4):253-255. Re p ro d uce d with p e rmission from Frontline Me d ical Communicatio ns.)

567

568

PART 14 DERMATO LO GY

FIGURE 119-9 Isolate d sing le uruncle in an ad ult woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Folliculitis decalvans is a chronic orm o olliculitis involving the scalp, leading to hair loss or alopecia (Figure 119-10). Staphylococci in ection is the usual causative agent, but there also has been a suggested genetic component to this condition. 1 It is also called tu ted olliculitis because some o the hair ollicles will have many hairs growing rom them simultaneously (Figure 119-11) (see Chapter 187, Scarring Alopecia). • Acne keloidalis nuchae is a chronic orm o olliculitis ound on the posterior neck that can be extensive and lead to keloidal tissue and alopecia. 1-3 Although it is o ten thought to occur almost exclusively in black men, it can be seen in men o all ethnic backgrounds and occasionally in women (see Figures 119-5 and 119-6) (see Chapter 116, Pseudo olliculitis and Acne Keloidalis Nuchae). • Fungal olliculitis is epidermal ungal in ections that are seen requently. Tinea capitis in ections are a orm o dermatophytic olliculitis. Pityrosporum olliculitis is caused by yeast in ection (Malassezia species) and is seen in a similar distribution as bacterial olliculitis on

Ch a pTe r 119

FIGURE 119-11 Tu te d olliculitis with visib le tu ts o hair (multip le hairs rom one ollicle ) g rowing rom a numb e r o ab normal ollicle s. This is one e xamp le o scarring alop e cia. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

the back, chest, and shoulders (Figure 119-12) (see Chapter 139, Tinea Versicolor). Candidal in ection is less common and is usually seen in individuals who are immunosuppressed, present in hairy areas that are moist, and unlike most cases o olliculitis, may present with systemic signs and symptoms. 1-4 • Pseudomonas olliculitis or “hot tub” olliculitis is usually a sel -limited in ection that ollows exposure to water or objects that are contaminated with Pseudomonas aeruginosa (see Figure 119-1). This occurs when hot tubs are inadequately chlorinated or brominated. This also occurs when loo ah sponges or other items used or bathing become a host or pseudomonal growth. Onset o symptoms is usually within 6 to 72 hours a ter exposure, with the complete resolution o symptoms in a couple o days, provided that the individual avoids urther exposure. 4 • Gram-negative olliculitis is an in ection with gram-negative bacteria that most typically occurs in individuals who have been on long-term antibiotic therapy, usually those taking oral antibiotics or acne. The most requently encountered in ective agents include Klebsiella, Escherichia coli, Enterobacter, and Proteus. 5 • Pseudo olliculitis barbae (razor bumps) is most commonly seen in black males who shave. Papules develop when the sharp edge o the hair sha t reenters the skin (ingrown hairs), and is seen on the cheeks and neck as a result o curled ingrown hair. 2 It can also occur in women with hirsutism who shave or pluck their hairs (see Figure 119-4) (see Chapter 116, Pseudo olliculitis and Acne Keloidalis Nuchae). 6 • Viral olliculitis is primarily caused by herpes simplex virus and molluscum contagiosum. 4 Herpetic olliculitis is seen primarily in individuals with a history o herpes simplex in ections type I or II. But most notably, it may be a sign o immunosuppression, as is the case with HIV in ection. 7 The expression o herpes olliculitis in HIV in ection ranges rom simple to necrotizing olliculitis and ulcerative lesions. Molluscum is a pox virus and molluscum contagiosum has been well documented in similar patient populations (ie, HIV and AIDS) and in children (see Chapters 128, Herpes Simplex and 129, Molluscum Contagiosum). 7-9

FIGURE 119-10 Early olliculitis d e calvans showing scalp inf ammation, p ustule s around hair ollicle s, and scarring alop e cia. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Actinic super icial olliculitis is a sterile orm o olliculitis seen predominantly in warm climates or during hot or summer months. Pustules occur primarily on the neck, over the shoulders, upper trunk, and upper arms, usually within 6 to 36 hours a ter sun exposure. 10

FO LLICULITIS

PART 14 DERMATO LO GY erythema or in ammation. Look or a hair at the center o the lesions (see Figure 119-2). There is usually an absence o systemic signs and patients’ symptoms range rom mild discom ort and pruritus to severe pain with extensive involvement. TYPICAL DISTRIBUTIO N Any area o the skin may be a ected and o ten location may be related to the pathogen or cause o olliculitis. The ace, scalp, neck, trunk, axillae, extremities, and groin are some o the more common areas a ected. LABO RATO RY TESTS

A

Laboratory testing may be unnecessary in simple super icial olliculitis and where the history is clear and quick resolution occurs. Clinical diagnosis o herpes and ungal olliculitis may be di icult and diagnosis may be made based on strong clinical suspicion or as a result o ailed antimicrobial therapy. Potassium hydroxide (KOH) preps can be used to look or tinea versicolor or other ungal organisms. Herpes culture or a quick test or herpes can be used when herpes is suspected. 1 SO R

DIFFERENTIAL DIAGNO SIS • Grover disease is a very pruritic condition o unknown cause that produces reddish papules and slight scale on the backs o middleaged men. It is also called “transient acantholytic dermatosis” and may resolve spontaneously in a period o years. It resembles olliculitis but the papules are not centered on hair ollicles (Figure 119-13). • Miliaria is blockage o the sweat glands that can resemble the small papules o olliculitis. The eccrine sweat glands become blocked so that

B FIGURE 119-12 A.Pityrosp orum olliculitis on the che st, should e rs, and arms o a young man; b iop sy p rove n. B. Pityrosp orum olliculitis on the che st o a young woman. KO H p re p aration showe d Pityrosp orum looking like ziti and me atb alls. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

• Eosinophilic olliculitis is associated with HIV in ection and can occur as a result o the viral in ection itsel , in which case the exact mechanism by which this occurs is uncertain (though thought to be autoimmune) (see Figure 119-7). 9,11-14 It is associated with diminished CD4 cell counts. Eosinophilic olliculitis generally improves with the initiation o highly active antiretroviral therapy (HAART), but can occur during the restoration o immune unction with HAART. 12

DIAGNO SIS O ten the diagnosis o olliculitis is based on a good history and physical. CLINICAL FEATURES Folliculitis has its characteristic presentation as the development o papules or pustules that are thin-walled and surrounded by a margin o

FIGURE 119-13 Grove r d ise ase on the b ack o a mid d le -ag e d man. This is also calle d “transie nt acantholytic d e rmatosis.” It is ve ry p ruritic with re d d ish p ap ule s and slig ht scale . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

569

570

PART 14 DERMATO LO GY sweat leaks into the dermis and epidermis. Clinically, skin lesions may range rom clear vesicles to pustules. These skin lesions primarily occur in times o increased heat and humidity, and are sel -limited. 1 • Impetigo is a bacterial in ection o the skin that a ects the superf cial layers o the epidermis as opposed to hair ollicles. It is contagious, unlike olliculitis. It has a bullous and nonbullous orm, and honeycrusted lesions requently predominate as opposed to the usual pustules seen in olliculitis (see Chapter 118, Impetigo). 4,6 • Keratosis pilaris consists o papules that occur as a result o a buildup o keratin in the openings o hair ollicles, especially on the lateral upper arms and thighs. It is not an in ection but can develop into olliculitis i lesions become in ected (see Chapter 143, Atopic Dermatitis). 1,6 • Acne vulgaris is characterized by the presence o comedones, papules, pustules, and nodules that are a result o ollicular hyperproli eration and plugging with excessive sebum. In ammation occurs when Propionibacterium acnes and other in ammatory substances get extruded rom the blocked pilosebaceous unit. 15 Although acne on the ace is rarely con used with olliculitis, acne on the trunk can resemble olliculitis. To distinguish between them look or acial involvement and comedones seen in acne (see Chapter 114, Acne Vulgaris).

MANAGEMENT

Ch a pTe r 119

retinoids, and UV light therapy. 11 Topical steroids and nonsteroidal anti-in ammatory drugs (NSAIDs) and isotretinoin are treatments o choice or HIV-associated eosinophilic olliculitis. 9-13 SO R B Relie with systemic antihistamines are variable and UV therapy is time consuming and expensive. 11,12 SO R C

FO LLO W-UP Most cases o olliculitis are superf cial and resolve easily with treatment. Dermatologic and surgical consultation may be required in cases o chronic olliculitis with scarring.

PATIENT EDUCATIO N Prevention is most important, and centers on good personal hygiene and proper laundering o clothing. Patients should be encouraged to avoid tight-f tting clothing. Hot tubs should be properly cleaned and the chemicals should be maintained appropriately. Electric razors or shaving can help prevent pseudo olliculitis barbae and should be cleaned regularly with alcohol. Patients with acne keloidalis nuchae should avoid shaving the hair in the involved area. PATIENT RESO URCES

• Management o olliculitis varies by causative agent and underlying pathophysiology.

• PubMed Health. Folliculitis—http:/ / www.ncbi.nlm.nih.gov/ pubmedhealth/ PMH0001826/ .

• Antivirals, antibiotics, and anti ungals are used as topical and/ or systemic agents. Approaches to nonpharmacologic therapy include patient education on the prevention o chemical and mechanical skin irritation. 16 Glycemic control in diabetic patients may help treat olliculitis. 1-3 Good hygiene helps to control symptoms and prevent recurrence.

PRO VIDER RESO URCES

• With superf cial bacterial olliculitis, treatment with topical preparations such as mupirocin (Bactroban) or usidic acid may be su f cient. 1 SO R Additionally, topical clindamycin may be considered in the mildest cases in which MRSA is involved. 1 SO R • Deep or extensive bacterial olliculitis warrants oral therapy with f rstgeneration cephalosporins (cephalexin), penicillins (amoxicillin/ clavulanate and dicloxacillin), macrolides, or uoroquinolones. 1,4,6 SO R • Pseudomonas or “hot tub” olliculitis usually resolves untreated within a week o onset (see Figure 119-1). For severe cases, treatment with cipro oxacin provides adequate antipseudomonal coverage. 1,4 SO R B Application o a warm compress to a ected areas also provides symptomatic relie . • Pityrosporum olliculitis and/ or tinea versicolor can be treated with systemic anti ungals, topical azoles, and/ or with shampoos containing azoles, selenium, or zinc (see Figure 119-12) (see Chapter 139, Tinea Versicolor). • Candidal olliculitis in immunosuppressed persons may be treated with oral itraconazole (see Chapter 135, Candidiasis). 1 SO R • Demodex olliculitis can be treated with ivermectin or topically with 5% permethrin cream. 4 SO R B • Herpes olliculitis can be treated with acyclovir, valacyclovir, and amciclovir. Regimens may requently include acyclovir 200 mg 5 times a day or 5 days (see Chapter 128, Herpes Simplex). 1 SO R • Eosinophilic olliculitis associated with HIV is treated with HAART, topical steroids, antihistamines, itraconazole, metronidazole, oral

• Medscape. Folliculitis.—http:/ / emedicine.medscape.com/ article/ 1070456. REFERENCES 1. Luelmo-Aguilar J, Santandreu MS. Folliculitis recognition and management. Am J Clin Dermatol. 2004;5(5):301-310. 2. Habi T. Clinical Dermatology. 5th ed. Philadelphia, PA: Saunders Elsevier; 2010. 3. Levy AL, Simpson G, Skinner RB Jr. Medical pearl: circle o desquamation, a clue to the diagnosis o olliculitis and urunculosis caused by Staphylococcus aureus. J Am Acad Dermatol. 2006;55(6):1079-1080. 4. Stulberg DL, Penrod MA, Blatny RA. Common bacterial skin in ections. Am Fam Physician. 2002;66(1):119-124. 5. Neubert U, Jansen T, Plewig G. Bacteriologic and immunologic aspects o Gram-negative olliculitis: a study o 46 patients. Int J Dermatol. 1999;38(4):270-274. 6. Ferri FF. Ferri’s Clinical Advisor 2012. , Philadelphia, PA: Elsevier; 2012. 7. Boer A, Herder N, Winter K, Falk T. Herpes olliculitis: clinical histopathological, and molecular pathologic observations. Br J Dermatol. 2006;154(4):743-746. 8. Weinberg JM, Mysliwiec A, Turiansky GW, et al. Viral olliculitis. Atypical presentations o herpes simplex, herpes zoster, and molluscum contagiosum. Arch Dermatol. 1997;133(8):983-986. 9. Fearf eld LA, Rowe A, Francis N, et al. Itchy olliculitis and human immunodef ciency virus in ection: clinicopathological and immunological eatures, pathogenesis and treatment. Br J Dermatol. 1999;141(1):3-11.

FO LLICULITIS

10. Labandeira J, Suarez-Campos A, Toribio J. Actinic superf cial olliculitis. Br J Dermatol. 1998;138(6):1070-1074. 11. Nervi SJ, Schwartz RA, Dmochowski M. Eosinophilic pustular olliculitis: a 40 year retrospect. JAmAcad Dermatol. 2006;55(2):285289. 12. Rajendran PM, Dolev JC, Heaphy MR Jr, Maurer T. Eosinophilic olliculitis: be ore and a ter the introduction o antiretroviral therapy. Arch Dermatol. 2005;141(10):1227-1231. 13. Jang KA, Kim SH, Choi JH, et al. Viral olliculitis on the ace. Br J Dermatol. 2000;142(3):555-559.

PART 14 DERMATO LO GY 14. Toutous-Trellu L, Abraham S, Pechère M, et al. Topical tacrolimus or e ective treatment o eosinophilic olliculitis associated with human immunodef ciency virus in ection. Arch Dermatol. 2005;141(10):1203-1208. 15. Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines o care or acne vulgaris management. JAm Acad Dermatol. 2007;56(4):651-663. 16. Gupta AK, Batra R, Bluhm R, et al. Skin diseases associated with Malassezia species. JAmAcad Dermatol. 2004;51(5):785-798.

571

572

PART 14 DERMATO LO GY

Ch APTER 120

120 PITTED KERATO LYSIS Michae l Bab cock, MD Richard P. Usatine , MD

PATIENT STO RY A young man comes to the o f ce with a terrible oot odor problem. He is wearing cowboy boots and he says that his eet are always sweaty. He is embarrassed to remove his boots, but when his mother convinces him to do so the odor is unpleasant. The clinician sees the typical pits o pitted keratolysis and notes that the boy’s socks are moist. His oot has many crateri orm pits on the heel (Figure 120-1). He is prescribed topical erythromycin solution or the pitted keratolysis and topical aluminum chloride or the hyperhidrosis. It is suggested that he wear a lighter and more breathable shoe until this problem improves.

INTRO DUCTIO N Pitted keratolysis is a superf cial oot in ection caused by gram-positive bacteria. These bacteria degrade the keratin o the stratum corneum leaving visible pits on the soles o the eet.

EPIDEMIO LO GY

FIGURE 120-2 Pitt d k tolysis on t p ssu -b ing s of t to s nd t b ll of t foo t. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Proteases produced by the bacteria degrade keratins to give the clinical appearance. 4 • The associated malodor is likely secondary to the production o sul ur by-products. 3

• Seen more commonly in males. • O ten a complication o hyperhidrosis.

DIAGNO SIS

• Seen more o ten in hot and humid climates. • Prevalence can be as high as 42.5% among paddy f eld workers. 1

CLINICAL FEATURES

• May be common in athletes with moist, sweaty eet. 2

Pitted keratolysis usually presents as painless, malodorous, crateri orm pits coalescing into larger superf cial erosions o the stratum corneum (Figures 120-1 to 120-4). It may be associated with itching and a burning sensation in some patients (see Figure 120-3).

ETIO LO GY AND PATHO PHYSIO LO GY • Kytococcus sedentarius ( ormerly Micrococcus spp.), Corynebacterium species, and Dermatophilus congolensis have all been shown to cause pitted keratolysis.3

TYPICAL DISTRIBUTIO N Pitted keratolysis usually involves the callused pressure-bearing areas o the oot, such as the heel, ball o the oot, and plantar great toe. It can also be ound in riction areas between the toes. 5

LABO RATO RY STUDIES Typically a clinical diagnosis but biopsy will reveal keratin pits lined by bacteria.

DIFFERENTIAL DIAGNO SIS • Characteristic clinical eatures make the diagnosis easy, but it is possible to have other diseases causing plantar pits, which can be included in the di erential. These other diseases include plantar warts, basal cell nevus syndrome, and arsenic toxicity. FIGURE 1 20-1 M ny c t ifo m p its o n t l o f t fo ot wit p itt d k to lysis nd yp id osis. (Re p ro d uce d with p e rmissio n from Richard P. Usatine , MD.)

• Plantar warts are typically not as numerous. They have a f rm callus ring around a so t core with small black dots rom thrombosed capillaries (see Chapter 133, Plantar Warts).

PART 14 DERMATO LO GY

PITTED KERATO LYSIS

• Arsenic toxicity can result in pits on the palms and soles, but it can also have hyperpigmentation, many skin cancers, Mees lines (white lines on the f ngernails), or other nail disorders.

MANAGEMENT • Treatment is based on bacterial elimination and reducing the moist environment in which the bacteria thrive. Various topical antibiotics are e ective or pitted keratolysis. • Topical erythromycin or clindamycin solution or gel can be applied twice daily until the condition resolves. SO R C Generic 2% erythromycin solution with an applicator top is a very inexpensive and e ective preparation. It may take 3 to 4 weeks to clear the odor and skin lesions. • Topical mupirocin is more expensive but also e ective. SO R C • Oral erythromycin is e ective and may be considered i topical therapy ails. SO R C

FIGURE 120-3 Pitt d k tolysis wit yp p ig m nt d c t ifo m p its on t p ssu -b ing s of t foot. T p ti nt comp l in d of itc ing nd b u ning on t f t. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

• Basal cell nevus syndrome typically has pits involving the palms and soles, bone abnormalities, a history o many basal cell carcinomas, and a characteristic acies with rontal bossing, hypoplastic maxilla, and hypertelorism (wide-set eyes) (see Chapter 168, Basal Cell Carcinoma).

• Treating underlying hyperhidrosis is also important to prevent recurrence. This can be done with topical aluminum chloride o varying concentrations. SO R C Drysol is 20% aluminum chloride solution and can be prescribed with an applicator top. • Botulinum toxin injection is an expensive and e ective treatment or hyperhidrosis. 6 SO R C It should be reserved or treatment ailures because o the cost, the discom ort o the multiple injections, and the need to repeat the treatment every 3 to 4 months.

FO LLO W-UP Follow-up is needed or treatment ailures, recurrences, and the treatment o underlying hyperhidrosis i present. Follow-up can be per ormed annually or prescription aluminum chloride or approximately every 4 months or botulinum toxin injections.

PATIENT EDUCATIO N Patients should be taught about the etiology o this disorder to help avoid recurrence. Help ul preventive strategies include avoiding occlusive ootwear and using moisture-wicking socks or changing sweaty socks requently. PATIENT RESO URCES

• International Hyperhidrosis Society—http:/ / www.sweathelp.org. PRO VIDER RESO URCES

• Medscape. Pitted Keratolysis—http:/ / emedicine.medscape .com/ article/ 1053078-overview. REFERENCES 1. Shenoi SD, Davis SV, Rao S, et al. Dermatoses among paddy f eld workers—a descriptive, cross-sectional pilot study. Indian J Dermatol Venereol Leprol. 2005;71:254-258. FIGURE 120-4 Pitt d k tolysis wit m ny c t ifo m p its on t (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

l.

2. Conklin RJ. Common cutaneous disorders in athletes. Sports Med. 1990;9:100-119.

573

574

PART 14 DERMATO LO GY 3. Bolognia J, Jorizzo J, Rapini R. Dermatology. 2nd ed. Philadelphia, PA: Mosby; 2008:1088-1089. 4. Takama H, Tamada Y, Yano K, et al. Pitted keratolysis: clinical maniestations in 53 cases. Br J Dermatol. 1997;137(2):282-285.

Ch a PTe r 120

5. Longshaw C, Wright J, Farrell A, et al. Kytococcus sedentarius, the organism associated with pitted keratolysis, produces two keratindegrading enzymes. JAppl Microbiol. 2002;93(5):810-816. 6. Vadoud-Seyedi J. Treatment o plantar hyperhidrosis with botulinum toxin type A. Int J Dermatol. 2004;43(12):969-971.

PART 14 DERMATO LO GY

ERYTHRASMA

121 ERYTHRASMA Richard P. Usatine , MD Anna Allre d , MD Mind y A. Smith, MD, MS

EPIDEMIO LO GY • The incidence o erythrasma is approximately 4%. 1 • Both sexes are equally a ected. • The inguinal location is more common in men.

PATIENT STO RY A 59-year-old woman (with obesity and type 2 diabetes) presents with a 6-month history o a brown, somewhat pruritic, rash in both axillae (Figure 121-1a). She has been seen by multiple physicians and many anti ungal creams and topical steroids have been tried with no results. She had stopped wearing deodorant or ear that she was allergic to all deodorants. The rash demonstrated the classic coral red uorescence o erythrasma (Figure 121-1b). The patient was given a prescription or oral erythromycin and the erythrasma cleared to the great delight o the patient.

ETIO LO GY AND PATHO PHYSIO LO GY • Corynebacterium minutissimum, a lipophilic gram-positive non–sporeorming rod-shaped organism, is the causative agent. • Under avorable conditions, such as heat and humidity, this organism invades and proli erates the upper one-third o the stratum corneum. • The organism produces porphyrins that result in the coral red luorescence seen under a Wood lamp (Figures 121-1 and 121-2).

RISK FACTO RS INTRO DUCTIO N Erythrasma is a chronic superf cial bacterial skin in ection that usually occurs in a skin old.

A

• Warm climate1 • Diabetes mellitus • Immunocompromised states

B

FIGURE 121-1 A. Erythrasma in the axilla o 59-ye ar-old woman with ob e sity and d iab e te s. B. Coral re d f uore sce nce se e n with a Wood lamp . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

575

PART 14 DERMATO LO GY

576

FIGURE 121-2 Coral re d f uore sce nce se e n with a Wood lamp he ld in the axilla o a p atie nt with e rythrasma. (Re p rod uce d with p e rmissio n from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

• Obesity • Hyperhidrosis • Poor hygiene • Advanced age

DIAGNO SIS CLINICAL FEATURES • Erythrasma is a sharply delineated, dry, red-brown patch with slightly scaling patches. Some lesions appear redder, whereas others have a browner color (Figures 121-3 and 121-4).

FIGURE 121-3 Re d d ish b rown e rythrasma in the axilla o an ob e se woman with d iab e te s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

CHApTER 121

FIGURE 121-4 Brown e rythrasma in the g roin o a man with d iab e te s. (Re p rod uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

• The lesions may appear with central clearing and be slightly raised rom the surrounding skin (Figure 121-5). • The lesions are typically asymptomatic; however, patients sometimes complain o itching and burning when lesions occur in the groin (Figure 121-6). TYPICAL DISTRIBUTIO N Erythrasma is characteristically ound in the intertriginous areas, especially the axilla and the groin (Figure 121-7). Patches o erythrasma may also be ound in the interspaces o the toes, intergluteal cle t, perianal skin, and in ramammary area.

FIGURE 121-5 Pinkish e rythrasma in the axilla o a 32-ye ar-old man with some ce ntral cle aring and e le vate d b ord e rs. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

ERYTHRASMA

FIGURE 121-6 Pinkish e rythrasma in the g roin o the man in Fig ure 121-5. Me n are more like ly to have e rythrasma in the crural re g ion. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

A

LABO RATO RY STUDIES • Illumination o the plaque with a Wood lamp reveals coral red uorescence (Figure 121-8). It should be noted that washing the area be ore examination may eliminate the uorescence. • The diagnosis may be conf rmed by applying Gram stain or methylene blue stain to scrapings rom the skin to reveal gram-positive rods and dark blue granules, respectively. However, i the presentation is typical and the plaque reveals uorescence then microscopic examination and cultures are not needed. • Microscopic examination is use ul i erythrasma is suspected but the plaque does not uoresce.

DIFFERENTIAL DIAGNO SIS • Psoriasis—Inverse psoriasis occurs in the same areas as erythrasma and also causes pink-to-red plaques with well-demarcated borders. The best way to distinguish psoriasis rom erythrasma is to look or other clues o psoriasis in the patient, including nail pitting or onycholysis and hyperkeratotic plaques on the elbows, knees, or scalp. Also, inverse psoriasis may be seen in the intergluteal cle t as well as below the breasts or pannus in overweight individuals (see Chapter 150, Psoriasis). The Wood lamp may help di erentiate between these diagnoses. • Dermatophytosis—Cutaneous ungal in ections also closely resemble erythrasma when they occur in the axillary and inguinal areas. Tinea in ections also have well-demarcated borders that can be raised with central clearing. This distinctive ringworm look is more obvious with tinea than erythrasma but a scraping or microscopic examination

B FIGURE 121-7 Erythrasma in the axilla and g roin o a mid d le -ag e d woman with d iab e te s. A. Axilla B. Groin. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

should be able to distinguish between the 2 conditions. Examination o the eet will requently show tinea pedis and onychomycosis when there are tinea in ections elsewhere on the body (see Chapters 136, Tinea Corporis and 137, Tinea Cruris).

577

PART 14 DERMATO LO GY

578

CHApTER 121

• Intertrigo—This is a term or in ammation in intertriginous areas (skin olds). It is caused or exacerbated by heat, moisture, maceration, riction, and lack o air circulation. It is requently made worse by in ection with Candida, bacteria, or dermatophytes, and there ore overlaps with the erythrasma, Candida, and dermatophytosis. Obesity and diabetes especially predispose to this condition. All e orts should be made to f nd coexisting in ections and treat them. • Contact dermatitis to deodorants can mimic erythrasma. The history and Wood lamp should help to di erentiate the 2 conditions (see Chapter 144, Contact Dermatitis).

MANAGEMENT NO NPHARMACO LO GIC • It has been advocated that the areas should be vigorously washed with soap and water prior to application o topical antibiotics. SO R • Consider loose-f tting cotton undergarments during treatment and to help prevent recurrence. SO R MEDICATIO NS A

• Although the bacteria responds to a variety o antibacterial agents (eg, penicillins, f rst-generation cephalosporins), the treatment o choice is oral erythromycin 250 mg 4 times a day or 14 days. Erythromycin shows cure rates as high as 100%. 2-4 SO R B • However, some advocate that oral erythromycin is only required or the treatment o extensive or resistant cases and topical antibiotic treatment may be su f cient. 5 SO R • Topical therapy (antibacterial, anti ungal, and benzoic acid 6%) has been recommended in addition to oral therapy in patients with hidden reservoirs o in ection (ie, interdigital involvement). SO R • Topical clindamycin may be applied once daily during the course o oral erythromycin therapy and or 2 weeks a ter physical clearance o the lesions or treatment and prophylaxis. 3,6 SO R • Topical erythromycin 2% solution applied twice daily or 2 weeks is one option. 4,5,7 SO R • In a Turkish study, topical usidic acid was more e ective than erythromycin or single-dose clarithromycin based on Wood light re ection scores.8 • Optimal blood glucose control is recommended in the management o a diabetic patient with erythrasma. 2 SO R

PRO GNO SIS

B FIGURE 121-8 A. Erythrasma in the axilla with 2 sate llite are as o involve me nt on the up p e r arm. B. Close -up o coral re d f uore sce nce with Wood lamp in the same p atie nt. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Candidiasis—Look or satellite lesions to help distinguish candidiasis rom erythrasma. Candidiasis will not uoresce and a microscopic examination o a Candida in ection should show branching pseudohyphae (see Chapter 135, Candidiasis).

• Usually it is a benign condition; however, in immunocompromised individuals, Corynebacterium can cause abscess ormation, bacteremia, endocarditis, pyelonephritis, cellulitis, and meningitis. 1 • The condition tends to recur i the predisposing condition is not addressed.

FO LLO W-UP Have the patient to ollow up in 2 to 4 weeks as needed to determine i erythrasma has resolved.

ERYTHRASMA

PATIENT EDUCATIO N Reassure the patient that erythrasma is curable with antibiotic treatment. PATIENT RESO URCES

• PubMed Health. Erythrasma—http:/ / www.ncbi.nlm.nih.gov/ pubmedhealth/ PMH0002441/ . • Dermnet NZ. Erythrasma—http:/ / www.dermnetnz.org/ bacterial/ erythrasma.html. PRO VIDER RESO URCES

• Medscape. Erythrasma—http:/ / emedicine.medscape.com/ article/ 1052532. REFERENCES 1. Kibbi AG, Bahhady RF, Saleh Z, Haddad FG. Erythrasma. http:/ / emedicine.medscape.com/ article/ 1052532-overview# a0199. Accessed April 2, 2012.

PART 14 DERMATO LO GY 2. Ahmed I, Goldstein B. Diabetes mellitus. Clin Dermatol. 2006;24(4):237-246. 3. Holdiness MR. Management o cutaneous erythrasma. Drugs. 2002;62(8):1131-1141. 4. James WD, Berger TG, Elston DM. Andrew’s Diseases of the Skin Clinical Dermatology. 10th ed. London, UK: Saunders/ Elsevier; 2006. 5. Karakatsanis G, Vakirlis E, Kastoridou C, Devliotou-Panagiotidou D. Coexistence o pityriasis versicolor and erythrasma. Mycoses. 2004;47(7):343-345. 6. Holdiness MR. Erythrasma and common bacterial skin in ections. Am Fam Physician. 2003;15:67(2):254. 7. Miller SD, David-Bajar K. Images in clinical medicine. A brilliant case o erythrasma. N Engl J Med. 2004;14:351(16):1666. 8. Avci O, Tanyildizi T, Kusku E. A comparison between the e ectiveness o erythromycin, single-dose clarithromycin and topical usidic acid in the treatment o erythrasma. J DermatologTreat. 2013;24(1):70-74.

579

580

PART 14 DERMATO LO GY

Ch a pTEr 122

122 CELLULITIS Richard P. Usatine , MD

PATIENT STO RY A 63-year-old man presents to his internist with a pain ul red swollen le t leg or 3 days. He has a known history o venous stasis and stasis dermatitis. He ran out on his topical steroid and could not resist scratching the very itchy lower leg. On physical examination the patient is noted to have a temperature o 100.4°F and signi cant erythema rom his oot up to his knee. The le t leg is swollen and there is scaling o the skin consistent with the stasis dermatitis. There are excoriations in the skin where the bacteria may have entered to initiate the cellulitis. Because o his coexisting diabetes it was decided to admit the patient to the hospital and treat him with intravenous (IV) antibiotics.

INTRO DUCTIO N Cellulitis is an acute in ection o the skin that involves the dermis and subcutaneous tissues. FIGURE 122-1 Ce llulitis in an old e r man with ve nous stasis d e rmatitis. (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

EPIDEMIO LO GY • Facial cellulitis occurs more o ten in adults ages 50 years or older, or in children ages 6 months to 3 years. • Perianal cellulitis occurs more commonly in young children but can be seen in adults as well.

DIAGNO SIS CLINICAL FEATURES The clinical eatures include rubor (red), calor (warm), tumor (swollen), and dolor (pain ul).

ETIO LO GY AND PATHO PHYSIO LO GY • O ten begins with a break in the skin caused by trauma, a bite, or an underlying skin disease (eg, tinea pedis, stasis dermatitis, psoriasis) (Figures 122-1 to 122-4). • It is most o ten caused by group A β-hemolytic Streptococcus (GABHS) or Staphylococcus aureus. The most common etiology o cellulitis with intact skin, when it has been determined through needle aspiration and/ or punch biopsy, is S. aureus, outnumbering GABHS by a ratio o nearly 2:1. 1 There are increasing concerns about the role o community-acquired methicillin-resistant S. aureus (CAMRSA) in all so t tissue in ections including cellulitis. 2-5 • A ter a cat or dog bite, cellulitis is o ten caused by Pasteurella multocida. • Cellulitis can be secondary to Vibrio vulnif cus ound in saltwater and sea ood. A V. vulnif cus in ection can start with raw oyster ingestion in an immunosuppressed person leading to sepsis and secondary cutaneous involvement (Figure 122-5). • Erysipelas is a speci c type o super cial cellulitis with prominent lymphatic involvement and leading to a sharply de ned and elevated border (Figure 122-6).

FIGURE 122-2 Ce llulitis and ab sce ss o the ng e r a te r a cle nche d st injury in which the p atie nt cut his ng e r on the tooth o the man he assaulte d . (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

CELLULITIS

PART 14 DERMATO LO GY

FIGURE 122-3 Ce llulitis o the oot o a d iab e tic p e rson in which the re is p ossib le ne crosis and g ang re ne o the se cond toe , re q uiring hosp italization and a p od iatry consult. (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

TYPICAL DISTRIBUTIO N Can occur on any part o the body, but is most o ten seen on the extremities and ace (Figures 122-1 to 122-8). Periorbital cellulitis can be li e threatening (Figure 122-9). Cellulitis can also occur around the anus. This is called perianal cellulitis (Figure 122-10).

FIGURE 122-5 Fatal Vib rio vulnif cus se p sis in a man with cirrhosis who ate raw oyste rs. The b acte re mia le d to wid e sp re ad ce llulitis and cutane ous b ullae . The violace ous b ullae should b e a re d f ag or this in e ction and /or ne crotizing asciitis. Eve n tho ug h the in e ction was id e nti e d e arly, the ove rwhe lming se p sis re sulte d in d e ath. (Re p rod uce d with p e rmission rom Donna Ng uye n, MD.)

LABO RATO RY TESTS • Aspiration—I there is f uctuance within the area o erythema, a needle aspiration or incision and drainage should be per ormed. I pus is aspirated, per orm a culture to guide antibiotic use. • Blood cultures—Results are positive in only 5% o cases and the results o culture o needle aspirations o the inf amed skin are variable and not recommended. 4

FIGURE 122-6 Erysip e las o the ce ntral ace that re sp ond e d we ll to oral antib iotic the rap y. (Re p rod uce d with p e rmission rom Erne sto Samano Ayon, MD.)

FIGURE 122-4 Ce llulitis that occurre d on the le g o a 50-ye ar-old woman with se ve re p soriasis b e ing tre ate d with me thotre xate and ad alimumab . (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

FIGURE 122-7 Ce llulitis o the le g in a 55-ye ar-old man that d e ve lop e d a te r a minor ab rasion and a long p lane f ig ht. Pe te chiae and e cchymose s are visib le and not in re q ue ntly se e n in ce llulitis. (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

581

582

PART 14 DERMATO LO GY

Ch a pTEr 122

DIFFERENTIAL DIAGNO SIS • Thrombophlebitis—Inf ammation o a vein caused by a blood clot. The pain and tenderness are over the involved vein. • Venous stasis—Swelling, discoloration, and pain o the lower extremities that can lead to cellulitis. Venous stasis dermatitis can add erythema and scaling to the picture and resemble cellulitis (see Figure 122-4) (see Chapter 51, Venous Stasis). • Allergic reactions—Allergic reactions to vaccines or bug bites may resemble cellulitis because o the erythema and swelling (Figure 122-11). • Acute gout—May resemble cellulitis i there is signi cant cutaneous inf ammation beyond the involved joint (see Chapter 105, Gout).

FIGURE 122-8 Asce nd ing lymp hang itis characte rize d b y lymp hatic stre aking up the le g in the p atie nt o Fig ure 122-7. (Re p rod uce d with p e rmissio n rom Richard P. Usatine , MD.)

• Necrotizing asciitis—Deep in ection o the subcutaneous tissues and ascia with di use swelling, severe pain, and bullae in a toxic-appearing patient. It is important to recognize the di erence between standard cellulitis and necrotizing asciitis. Imaging procedures can detect gas in the so t tissues. Rapid progression rom mild erythema to violaceous or necrotic lesions and/ or bullae in a number o hours is a red f ag or necrotizing asciitis. The toxicity o the patient and the other physical ndings should encourage rapid surgical consultation (see Chapter 124, Necrotizing Fasciitis).

MANAGEMENT • The rst decision is whether or not the patient needs hospitalization and IV antibiotics. It is o ten best to hospitalize any immunocompromised patients (eg, HIV, transplant recipient, chronic renal or liver disease, on prednisone, diabetes out o control) with cellulitis because they may decompensate quickly. SO R • Evidence comparing di erent durations o treatment, oral versus intravenous antibiotics is lacking. 6 Randomized controlled trials (RCTs) comparing di erent antibiotic regimens ound clinical cure in 50% to 100% o people, but provided insu cient in ormation on di erences between regimens. 6 SO R A FIGURE 122-9 Li e -thre ate ning stap hylococcal p e riorb ital ce llulitis re q uiring op e rative inte rve ntion. (Re p rod uce d with p e rmission rom Frank Mille r, MD.)

FIGURE 122-10 Se ve re p e rianal ce llulitis in an ad ult man. (Re p rod uce d with p e rmission rom Jack Re sne ck Sr., MD.)

FIGURE 122-11 Re d ne ss and swe lling a te r a p ne umococcal vaccine the d ay b e ore in a 66-ye ar-old woman. This alle rg ic re action looks like b acte rial ce llulitis. It re solve d with oral d ip he nhyd ramine . (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

CELLULITIS

• One quasi-randomized trial in 73 hospitalized people with erysipelas, but excluding patients with clinical signs o septicemia, compared oral versus intravenous penicillin and ound no signi cant di erence in clinical e cacy. 6 SO R B • Standard oral therapy or cellulitis not requiring hospitalization (in the pre-MRSA era) involves covering GABHS and S. aureus with cephalexin or dicloxacillin. 4 SO R A The standard dose is 500 mg orally every 6 hours or each antibiotic and the typical duration is 7 to 10 days. SO R • Penicillin-allergic patients may be treated with clindamycin rather than erythromycin because o macrolide resistance and increasing MRSA prevalence. 4 SO R A • Parenteral treatment is usually done with penicillinase-resistant penicillins or rst-generation cephalosporins such as ce azolin, or, or patients with li e-threatening penicillin allergies, clindamycin, or vancomycin. 4 SO R A • In cases o uncomplicated cellulitis, 5 days o antibiotic treatment with levof oxacin is as e ective as a 10-day course. 7 SO R B This is not a good choice i MRSA is suspected. Two recent studies (published in 2009 and 2010) addressed concerns over CAMRSA in cellulitis and came up with di erent conclusions: • An electronic chart review o patients seen in a Texas emergency department with cellulitis in 2000 and 2005 was per ormed. Exclusion criteria were incision and drainage, surgery, or admission on initial visit. Treatment ailure was de ned as a repeat visit in the subsequent 30 days and a change in antibiotics, admission to the hospital, incision and drainage o abscess, or surgical intervention. There was a signi cant decrease in β-lactam antibiotics and an increase in CAMRSAe ective antibiotics prescribed in 2005 versus 2000. The di erence in treatment ailure rates o the β-lactams and CAMRSA antibiotics was statistically insigni cant. The β-lactam antibiotics per ormed as well as “CAMRSA antibiotics” in their setting. 5 SO R B • A 3-year retrospective cohort study o outpatients with cellulitis empirically treated in Hawaii was per ormed. Exclusion criteria included patients who received more than one oral antibiotic or were hospitalized. The overall treatment success rate o trimethoprimsul amethoxazole was signi cantly higher than the rate o cephalexin (91% vs 74%; p < 0.001). Clindamycin success rates were higher than those o cephalexin in patients who had subsequently culture-con rmed MRSA in ections (p = 0.01), had moderately severe cellulitis (p = 0.03), and were obese (p = 0.04). MRSA was recovered in 72 o 117 positive culture specimens rom 405 included patients. The researchers concluded that trimethoprim-sul amethoxazole and clindamycin are pre erred empiric therapy or outpatients with cellulitis in the CAMRSA-prevalent setting.2 SOR B • Although MRSA is increasing in its prevalence in skin and so t tissue in ections, 3 the di culty in obtaining microbiologic cultures or cellulitis still makes it di cult to know how much MRSA is a problem in cellulitis with intact skin. I there is a coexisting abscess or crusting lesion, it is best to obtain a culture to guide therapy and start empiric therapy with trimethoprim-sul amethoxazole and clindamycin. 2 SO R B • Do not miss necrotizing asciitis. Patients with severe pain, bullae, crepitus, skin necrosis, or signi cant toxicity merit imaging and immediate surgical consultation (see Chapter 124, Necrotizing Fasciitis). • Treat underlying conditions (eg, tinea pedis, lymphedema) that predispose the patient to the in ection. SO R

PATIENT EDUCATIO N Recommend that the patient should take rest and elevate the involved extremity. I outpatient therapy is ollowed, then provide precautions (eg, vomiting and unable to hold medicine down) or which the patient should seek more immediate ollow-up.

FO LLO W-UP I prescribing oral outpatient therapy, consider ollow-up in 1 to 2 days to assess response to the antibiotic and to determine the adequacy o outpatient therapy. PATIENT RESO URCES

• Medline Plus for patients—http:/ / www.nlm.nih.gov/ medlineplus/ cellulitis.html. PRO VIDER RESO URCES

• Guidelines on the management of cellulitis in adults from Ireland—http:/ / www.gain-ni.org/ Library/ Guidelines/ cellulitis-guide.pdf. • Practice Guidelines for the Diagnosis and Management of Skin and So t Tissue In ections rom the In ectious Diseases Society o America—http:/ / cid.oxfordjournals.org/ content/ 41/ 10/ 1373.full.

REFERENCES 1. Chira S, Miller LG. Staphylococcus aureus is the most common identied cause o cellulitis: a systematic review. Epidemiol In ect. 2010;138:313-317. 2. Khawcharoenporn T, Tice A. Empiric outpatient therapy with trimethoprim-sul amethoxazole, cephalexin, or clindamycin or cellulitis. Am J Med. 2010;123:942-950. 3. Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S. aureus in ections among patients in the emergency department. N Engl J Med. 2006;355:666-674. 4. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines or the diagnosis and management o skin and so t-tissue in ections. Clin In ect Dis. 2005;41:1373-1406. 5. Wells RD, Mason P, Roarty J, Dooley M. Comparison o initial antibiotic choice and treatment o cellulitis in the pre- and post-community-acquired methicillin-resistant Staphylococcus aureus eras. Am J Emerg Med. 2009;27:436-439. 6. Morris AD. Cellulitis and erysipelas. Clin Evid (Online). 2008 Jan 2;2008:1708. 7. Hepburn MJ, Dooley DP, Skidmore PJ, et al. Comparison o shortcourse (5 days) and standard (10 days) treatment or uncomplicated cellulitis. Arch Intern Med. 2004;164:1669-1674.

583

584

PART 14 DERMATO LO GY

Ch Apt Er 123

123 ABSCESS Richard P. Usatine , MD

PATIENT STO RY A young man is seen in a shelter in San Antonio a ter being evacuated rom New Orleans a ter the devastating oods o hurricane Katrina (Figure 123-1). He has acial pain and swelling and noticeable pus near the eye. His vision is normal. The area is anesthetized with lidocaine and epinephrine. The abscess is drained with a # 11 blade. The patient is started on an oral antibiotic because o the proximity to the eye and the local swelling that could represent early cellulitis. A culture to look or methicillin-resistant Staphylococcus aureus (MRSA) was not available in the shelter, but close ollow-up was set or the next day and the patient was doing much better.

INTRO DUCTIO N An abscess is a collection o pus in the in ected tissues. The abscess represents a walled-o in ection in which there is a pocket o purulence. In abscesses o the skin the o ending organism is almost always S. aureus.

FIGURE 1 2 3 -2 Ne ck a b sce ss se co nd a ry to d e nta l a b sce ss in a ho me le ss m an. This wa s d raine d in the o p e rating ro o m b y an ENT sp e cia list. (Re p ro d uce d with p e rmissio n fro m Richard P. Usa tine , MD.)

EPIDEMIO LO GY • MRSA was the most common identif able cause o skin and so t tissue in ections among patients presenting to emergency departments in 11 US cities. S. aureus was isolated rom 76% o these in ections and 59% were community-acquired MRSA (CAMRSA). 1 • Risk actors or MRSA in ection and other abscesses—Intravenous drug abuse, homelessness, dental disease, contact sports, incarceration, and high prevalence in the community (Figure 123-2).

ETIO LO GY AND PATHO PHYSIO LO GY • Most cutaneous abscesses are caused by S. aureus. • Risk actors or developing an abscess with MRSA include patients who work or are exposed to a health care system, intravenous drug use, previous MRSA in ection and colonization, recent hospitalization, being homeless, A rican American, and having used antibiotics within the last 6 months. 2 • CAMRSA has become so prevalent in our community that both the patients shown in Figures 123-3 and 123-4 had no special risk actors and both had abscesses that grew out MRSA. One study that evaluated management o skin abscesses drained in the emergency department showed that there was no signif cant association between amount o surrounding cellulitis or abscess size with the likelihood o MRSApositive cultures. 2 • A dental abscess can spread into tissue outside the mouth, as in the homeless person in Figure 123-2.

DIAGNO SIS CLINICAL FEATURES

FIGURE 123-1 Ab sce ss se e n on the ace o a man a te r e vacuation rom the f ood wate rs o Ne w O rle ans ollowing hurricane Katrina. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Clinical eature indicates collection o pus in or below the skin. Patients o ten eel pain and have tenderness at the involved site. There is swelling, erythema, warmth, and uctuance in most cases (Figures 123-1 to 123-5). Determine i the patient is ebrile and i there is surrounding cellulitis.

ABSCESS

PART 14 DERMATO LO GY

FIGURE 123-3 MRSA ab sce ss on the b ack o the ne ck that p atie nt thoug ht was a sp id e r b ite . Note that a ring b lock was d rawn around the ab sce ss with a surg ical marke r to d e monstrate ho w to p e r orm this b lock. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

TYPICAL DISTRIBUTIO N Skin abscesses can be ound anywhere rom head to eet. Frequent sites include the hands, eet, extremities, head, neck, buttocks, and breast (see Figure 123-5).

FIGURE 123-5 Ab sce ss in the arm o d e ntal stud e nt, cause unknown. The p us that d raine d rom the ab sce ss g re w out MRSA. He was starte d on trime thop rim-sul ame thoxazole (TMP-SMX) to cove r the surround ing ce llulitis at the time o incision and d rainag e . The in e ction re solve d q uickly. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

LABO RATO RY STUDIES Clinical cure is o ten obtained with incision and drainage alone so the benef ts o pathogen identif cation and sensitivities are low in low-risk patients. 2 Most clinical studies have excluded patients who were immunocompromised, diabetic, or had other signif cant comorbidities. 2 Consequently, it may be reasonable to obtain wound cultures in high-risk patients, those with signs o systemic in ection, and in patients with history o high recurrence rates. 2,3

DIFFERENTIAL DIAGNO SIS • Epidermal inclusion cyst with in ammation or in ection—These cysts (also known as sebaceous cysts) can become in amed, swollen, and superin ected. Although the initial erythema may be sterile in ammation, these cysts can become in ected with S. aureus. The treatment consists o incision and drainage and antibiotics i cellulitis is also present. I these are removed be ore they become in amed, the cyst may come out intact (Figure 123-6). • Cellulitis with swelling and no pocket o pus—When it is unclear i an area o in ected skin has an abscess, needle aspiration with a large-gauge needle may be help ul to determine whether to incise the skin. Cellulitis alone should have no area o uctuance (see Chapter 122, Cellulitis). • Hidradenitis suppurativa—Recurrent in ammation surrounding the apocrine glands o the axilla and inguinal areas (see Chapter 117, Hidradenitis Suppurativa). • Furuncles and carbuncles—A uruncle or boil is an abscess that starts in hair ollicle or sweat gland. A carbuncle occurs when the uruncle extends into the subcutaneous tissue. • Acne cysts—More sterile in ammation than true abscess, o ten better to inject with steroid rather than incise and drain (see Chapter 114, Acne Vulgaris).

MANAGEMENT FIGURE 1 23 -4 Larg e MRSA ab sce ss on the le g in a 62-ye ar-old man b e g inning to d rain sp o ntane o usly. The ab sce ss cavity was larg e and the p atie nt was p lace d o n trime tho p rim-sul ame tho xazo le (TMP-SMX) to co ve r the surro und ing ce llulitis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• The evidence strongly supports the incision and drainage o an abscess. 2,4 SO R Inject 1% lidocaine with epinephrine into the skin at the site you plan to open using a 27-gauge needle. A ring block can

585

586

PART 14 DERMATO LO GY

Ch Apt Er 123

tetracycline, or doxycycline. Local sensitivity data should be consulted when available. 2 SO R B There is no current data to support the use o an antimicrobial medication (mupirocin or ri ampin) in the eradication o MRSA colonization. 2 SO R C

PATIENT EDUCATIO N Patients may shower daily 24 to 48 hours a ter incision and drainage and then reapply dressings. Patients should be given return precautions or worsening o symptoms or continued redness, pain, or pus.

FO LLO W-UP In patients or wounds at higher risk or complications, ollow-up should be scheduled in 24 to 48 hours. I packing was placed, it can be removed by the patient or a amily member. PATIENT RESO URCES

• Skinsight. Abscess—http:/ / www.skinsight.com/ adult/ abscess.htm. FIGURE 123-6 Ep id e rmal inclusion cyst re move d intact. The re is no ne e d or antib iotics in this case . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

be help ul rather than injecting into the abscess itsel (see Figure 123-3). Open the abscess with a linear incision using a # 11 blade scalpel ollowing skin lines i possible. 5 Although many physicians still pack a drained abscess with ribbon gauze, there is limited data on whether or not packing o an abscess cavity improves outcomes. A small study concluded that routine packing o simple cutaneous abscesses is pain ul and probably unnecessary. 6 SO R C The author o this chapter o ten packs abscesses lightly and has the patient remove the packing in the shower 2 days later, avoiding additional visits and pain ul repacking o the healing cavity. SO R C However, i a large abscess is not packed it can seal over and the pus may reaccumulate. Routine use o antibiotics or an initial abscess in addition to incision and drainage is not supported by current evidence. 2,7-9 SO R Three randomized controlled trials (RCTs) are per ormed since the emergence o CAMRSA have demonstrated that antibiotics do not signif cantly improve healing rates o superf cial skin abscesses, but 2 o these studies suggest that antibiotics do decrease short-term rates o new lesion development. 7-9 Consider the use o oral antibiotics to treat an abscess with suspected CAMRSA in patients who are ebrile or have systemic symptoms, have signif cant surrounding cellulitis, have ailed incision and drainage alone, have requent recurrences, or have a history o close contacts with abscesses. 2 SO R C I an antibiotic is to be used, CAMRSA is close to 100% sensitive to trimethoprim-sul amethoxazole (TMP-SMX). 2 SO R B Although standard dosing o oral TMP-SMX or an in ection in adults is 1 DS tablet bid, one study suggests that 2 DS tablets should be used bid or 7 days. 10 SO R B Alternative antibiotics include oral clindamycin,

PRO VIDER RESO URCES

• Gillian R. How do you treat an abscess in the era of increased community-associated MRSA (MRSA)? JEmerg Med. 2011;41:276-281. • ScienceDirect. How Do You Treat an Abscess in the Era o Increased Community-associated Methicillin-resistant Staphylococcus Aureus (MRSA)?— http:/ / www.sciencedirect.com/ science/ article/ pii/ S0736467911004252.

REFERENCES 1. Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S. aureus in ections among patients in the emergency department. N Engl J Med. 2006;355:666-674. 2. Gillian R. How do you treat an abscess in the era of increased community-associated methicillin-resistant Staphylococcus aureus (MRSA)? J Emerg Med. 2011;41:276-281. 3. Abrahamian FM, Shro SD. Use o routine wound cultures to evaluate cutaneous abscesses or community-associated methicillinresistant Staphylococcus aureus. Ann Emerg Med. 2007;50:66-67. 4. Sorensen C, Hjortrup A, Moesgaard F, Lykkegaard-Nielsen M. Linear incision and curettage vs. deroof ng and drainage in subcutaneous abscess. A randomized clinical trial. Acta Chir Scand. 1987;153:659-660. 5. Usatine R, Pfenninger J, Stulberg D, Small R. Dermatologic and Cosmetic Procedures in O f ce Practice. Philadelphia, PA: Elsevier; 2012. 6. O’Malley GF, Dominici P, Giraldo P, et al. Routine packing of simple cutaneous abscesses is pain ul and probably unnecessary. Acad Emerg Med. 2009;16:470-473. 7. Duong M, Markwell S, Peter J, Barenkamp S. Randomized, controlled trial o antibiotics in the management o community-acquired skin abscesses in the pediatric patient. Ann Emerg Med. 2010;55:401-407. 8. Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial o trimethoprim-sul amethoxazole or uncomplicated skin abscesses

ABSCESS

in patients at risk or community-associated methicillin-resistant Staphylococcus aureus in ection. Ann Emerg Med. 2010;56:283-287. 9. Rajendran PM, Young D, Maurer T, et al. Randomized, doubleblind, placebo-controlled trial o cephalexin or treatment o uncomplicated skin abscesses in a population at risk or community-

PART 14 DERMATO LO GY acquired methicillin-resistant Staphylococcus aureus in ection. Antimicrob Agents Chemother. 2007;51:4044-4048. 10. Markowitz N, Quinn EL, Saravolatz LD. Trimethoprim-sul amethoxazole compared with vancomycin or the treatment o Staphylococcus aureus in ection. Ann Intern Med. 1992;117:390-398.

587

PART 14 DERMATO LO GY

588

Ch ApTER 124

124 NECRO TIZING FASCIITIS Richard P. Usatine , MD Je re my A. Franklin, MD

PATIENT STO RY A 54-year-old woman with diabetes was brought to the emergency department with right leg swelling, ever, and altered mental status. 1 The patient noted a pimple in her groin 5 days earlier and over the past ew days had increasing leg pain. Her right leg was tender, red, hot, and swollen (Figure 124-1). Large bullae were present. Her temperature was 38.9°C (102°F) and her blood sugar was 573. The skin had a “woody” eel and a radiograph o her leg showed gas in the muscles and so t tissues (Figure 124-2). She was taken to the operating room or debridement o her necrotizing asciitis (NF). Broad-spectrum antibiotics were also started but the in ection continued to advance quickly. The patient died the ollowing day; her wound culture later grew Escherichia coli, Proteus vulgaris, Corynebacterium, Enterococcus, Staphylococcus sp., and Peptostreptococcus.1

FIGURE 124-2 Rad iog rap h o the p atie nt’s le g showing g as in the so t tissue s and muscle s. (Re p rod uce d with p e rmission from Dufe l S, Martino M. Simp le ce llulitis or a more se rious infe ction? J Fam Pract. 2006;55(5): 396-400. Re p rod uce d with p e rmission from Frontline Me d ical Communications.)1

INTRO DUCTIO N Necrotizing asciitis is a rapidly progressive in ection o the deep ascia, with necrosis o the subcutaneous tissues. It usually occurs a ter surgery or trauma. Patients have erythema and pain disproportionate to the physical ndings. Immediate surgical debridement and antibiotic therapy should be initiated.2

SYNO NYMS NF is also known as f esh-eating bacteria, necrotizing so t tissue in ection (NSTI), suppurative asciitis, hospital gangrene, and necrotizing erysipelas. Fournier gangrene is a type o NF or NSTI in the genital and perineal region. 3

EPIDEMIO LO GY • Incidence in adults is 0.40 cases per 100,000 population. 4 • NF caused by Streptococcus pyogenes is the most common orm. 4

ETIO LO GY AND PATHO PHYSIO LO GY • Type I NF is a polymicrobial in ection with aerobic and anaerobic bacteria: ° Frequently caused by enteric gram-negative pathogens including Enterobacteriaceae organisms and Bacteroides. ° Can occur with gram-positive5 organisms such as non–group A streptococci and Peptostreptococcus. ° Saltwater variant can occur with penetrating trauma or an open wound contaminated with saltwater containing marine vibrios. Vibrio vulnif cus is the most virulent. 6 ° Up to 15 pathogens have been isolated in a7 single wound. ° Average o 5 di erent isolates per wound. • Type II NF occurs rom common skin organisms: ° Generally a monomicrobial in ection caused by S. pyogenes: ■ May occur in combination with Staphylococcus aureus. ■ Methicillin-resistant S. aureus (MRSA) is no longer a rare cause o NF. 5 ■ S. pyogenes strains may produce pyrogenic exotoxins, which act as superantigens to stimulate production o tumor necrosis actor (TNF)-α , TNF-β, interleukin (IL)-1, IL-6, and IL-2. 7

RISK FACTO RS FIGURE 124-1 Ne crotizing asciitis on the le g and g roin showing e rythe ma, swe lling , and b ullae . (Re p rod uce d with p e rmission from Dufe l S, Martino M. Simp le ce llulitis or a more se rious infe ction? J Fam Pract. 2006;55(5):396-400. Re p rod uce d with p e rmission from Frontline Me d ical Communications.)

• Risk actors or type I NF (polymicrobial) include the ollowing: ° Diabetes mellitus ° Severe peripheral vascular disease ° Obesity

NECRO TIZING FASCIITIS

FIGURE 124-3 Ne crotizing asciitis that starte d whe n the p atie nt ste p p e d on a nail. Note the p uncture wound and the d raining f uid . (Re p ro d uce d with p e rmission from Sub ramaniam R, Shirle y O B. O ozing p uncture wound on fo ot. J Fam Pract. 2009 Jan;58(1):37-39. Re p rod uce d with p e rmission from Frontline Me d ical Communicatio ns.)

° Alcoholism and cirrhosis ° Intravenous drug use ° Decubitus ulcers ° Poor nutritional status ° Postoperative patients or those with penetrating trauma ° Abscess o the emale genital tract • Risk actors o type II NF (group A β-hemolytic Streptococcus [GABHS] and S. aureus) include the ollowing: ° Diabetes mellitus ° Severe peripheral vascular disease ° Recent parturition (Figure 124-3) ° Trauma 5 ° Varicella

PART 14 DERMATO LO GY

FIGURE 124-4 Ne crotizing asciitis with violace ous color o the skin on the a e cte d skin ab ove the C-se ction. Exte nsive d e b rid e me nt was p e r orme d in the op e rating room to save the p atie nt’s li e . (Re p rod uce d with p e rmission from Michae l Bab cock, MD.)

• Crepitus occurs when there is gas in the so t tissues. • Unresponsive to empiric antimicrobial therapy. TYPICAL DISTRIBUTIO N • May occur at any anatomic location. • Majority o cases occur on the lower extremities (Figures 124-5 and 124-7) but can occur on the upper extremities. • Also common on abdominal wall (see Figure 124-4) and in perineum (Fournier gangrene). LABO RATO RY AND IMAGING • Routine laboratory tests are nonspeci c but common ndings include an elevated white blood cell count (WBC), a low serum sodium, and a high blood urea nitrogen (BUN).

DIAGNO SIS Early recognition based on signs and symptoms is potentially li esaving. Although laboratory tests and imaging studies can con rm ones’ clinical impression, rapid treatment with antibiotics and surgery are crucial to improving survival. CLINICAL FEATURES • Rapid progression o erythema to bullae (Figures 124-4 and 124-5), ecchymosis, and necrosis or gangrene (Figure 124-6). • The erythematous skin may develop a dusky blue discoloration. Vesicular and bullous lesions orm over the erythematous skin, with some serosanguineous drainage. The bullae may become violaceous. The skin can become gangrenous and develop a black eschar. 2 • Edematous, wooden eel o subcutaneous tissues extending beyond the margin o erythema. • High evers and severe systemic toxicity. • Unrelenting intense pain out o proportion to cutaneous ndings. • Pain progresses to cutaneous anesthesia as disease evolves. Anesthesia o the skin develops as a result o in arction o cutaneous nerves. 2

FIGURE 1 2 4 -5 Ne cro tizing a sciitis tha t sta rte d whe n the p a tie nt ste p p e d o n a na il. A la rg e la ccid b ulla is visib le a lo ng with swe lling a nd e rythe m a . A ra p id b e lo w-the -kne e a m p uta tio n a llo we d this p a tie nt to survive . (Re p ro d uce d with p e rm issio n fro m Sub ra m a nia m R, Shirle y O B. O o zing p uncture wo und o n fo o t. J Fa m Pra ct. 2009 J a n;58(1):3739. Re p ro d uce d with p e rm issio n fro m Fro ntline Me d ica l Co m m unica tio ns.)

589

PART 14 DERMATO LO GY

590

Ch ApTER 124

DIFFERENTIAL DIAGNO SIS • Cellulitis—Acute spreading in ection o skin and so t tissues characterized by erythema, edema, pain, and calor. Rapid progression o disease despite antibiotics, systemic toxicity, intense pain, and skin necrosis suggest NF rather than cellulitis (see Chapter 122, Cellulitis). • Pyomyositis—Suppuration within individual skeletal muscle groups. Synergistic necrotizing cellulitis is a NSTI that involves muscle groups in addition to super cial tissues and ascia. 7 Although pyomyositis may occur with NF, it can occur independent o cutaneous and so t tissue in ections. Imaging o the muscle con rms the diagnosis. • Clostridial myonecrosis—Acute necrotizing in ection o muscle tissue caused by clostridial organisms. Surgical exploration and cultures are required to di erentiate rom NF. FIGURE 124-6 Ne crotizing asciitis with g ang re ne . Eve n with a rad ical he mip e lve ctomy this p atie nt d id not survive . (Re p ro d uce d with p e rmission from Fre d Bong ard , MD.)

• Histology and culture o deep tissue biopsy are essential; sur ace cultures cannot be relied on alone. Gram staining o the exudate may provide clues about the pathogens while the physician awaits culture results. 2 • Standard radiographs are o little value unless air is demonstrated in the tissues (see Figure 124-2). • Radiography, computed tomography (CT), ultrasonography, and magnetic resonance imaging (MRI) can be used to detect gas within so t tissues or muscles. 2 • Although imaging may help delineate the extent o disease, it should not delay surgical consultation. BIO PSY • Gross examination reveals swollen, dull, gray ascia with stringy areas o necrosis. 6 • Necrosis o super cial ascia and at produces watery, oul-smelling “dishwater pus.”2 • Histology demonstrates subcutaneous at necrosis, vasculitis, and local hemorrhage. 2

FIGURE 124-7 Ne crotizing asciitis with violace ous color o the skin on the a e cte d le g . (Re p rod uce d with p e rmission from Fre d Bo ng ard , MD.)

• Erythema induratum—Tender, erythematous subcutaneous nodules occurring on the lower legs (especially the calves). Lack o ever, systemic toxicity, and skin necrosis suggest erythema induratum rather than NF. Lesions o erythema induratum may have a chronic, recurrent course and the patient requently has a history o tuberculosis or a positive puri ed protein derivative (PPD) test. • Streptococcal or staphylococcal toxic shock syndrome—Systemic inf ammatory response to a toxin-producing bacteria characterized by ever, hypotension, generalized erythroderma, myalgia, and multisystem organ involvement. NF may occur as part o the toxic shock syndrome.

MANAGEMENT Start by maintaining a high index o suspicion or NF. I the rst debridement occurs within 24 hours rom the onset o symptoms, there is a signi cantly improved chance o survival. 8 • Surgical debridement is the primary therapeutic modality. 2,3,5,7-10 SOR ° Extensive, de nitive debridement should be the goal with the rst surgery. This may require amputation o an extremity to control the disease. Surgical debridement is repeated until all in ected devitalized tissue is removed. • Antibiotics are the main adjunctive therapy to surgery. Broad-spectrum empiric antibiotics should be started immediately when NF is suspected and should include coverage o gram-positive, gram-negative, and anaerobic organisms. 7 SO R ° Antimicrobial therapy must be directed at the known or suspected pathogens and used in appropriate doses until repeated operative procedures are no longer needed, the patient has demonstrated obvious clinical improvement, and ever has been absent or 48 to 72 hours. 7 SO R ° Ampicillin is use ul or coverage o susceptible enteric aerobic organisms, such as E. coli, as well as or gram-positive organisms, such as Peptostreptococcus species, group B, C, or G streptococci, and some anaerobes. 7 SO R ° Clindamycin is use ul or coverage o anaerobes and aerobic grampositive cocci, including most S. aureus serogroups. ° Clindamycin should be considered in initial coverage or its e ects on exotoxin production in group A Streptococcus (GAS) in ections. NF and/ or streptococcal toxic shock syndrome caused by group A streptococci should be treated with clindamycin and penicillin. 7 SO R

PART 14 DERMATO LO GY

NECRO TIZING FASCIITIS

The rationale or clindamycin is based on in vitro studies demonstrating both toxin suppression and modulation o cytokine (ie, TNF) production, on animal studies demonstrating superior e cacy versus that o penicillin, and on 2 observational studies demonstrating greater e cacy or clindamycin than or β-lactam antibiotics. 7 SO R Metronidazole has the greatest anaerobic spectrum against the enteric gram-negative anaerobes, but it is less e ective against the gram-positive anaerobic cocci. Gentamicin or a f uorinated quinolone, ticarcillin-clavulanate, or piperacillin-sulbactam is use ul or coverage against resistant gram-negative rods. 7 The best choice o antibiotics or community-acquired mixed in ections is a combination o ampicillin-sulbactam plus clindamycin plus ciprof oxacin. 7 SO R Another commonly used combination is a continuous in usion o penicillin G in combination with clindamycin and an aminoglycoside i renal unction permits. 10 Empiric vancomycin should be considered during pending culture results to cover or the increasing incidence o community-acquired MRSA (CAMRSA). 5,7 One pre erred antimicrobial therapy or V. vulnif cus is doxycycline in combination with ce tazidime and surgery or NSTI. 6 Hyperbaric oxygen (HBO2) may have bene cial e ects when used postoperatively in NSTIs. One recent study demonstrated decreased morbidity (amputations 50% vs 0%) and mortality (34% vs 11.9%) with the use o postoperative HBO2. 11 SO R B ■

°

°

°

°

° °

• Aggressive f uid resuscitation is o ten necessary because o massive capillary leak syndrome. Supplemental enteral nutrition is o ten necessary or patients with NSTIs. • Vacuum-assisted closure devices may be help ul in secondary wound management a ter debridement o NSTIs. 10 • A recommendation to use intravenous immunoglobulin (IVIG) to treat NF or toxic shock syndrome cannot be made with certainty. 7 SO R

B

• United States Centers for Disease Control and Prevention. Necrotizing Fasciitis—http:/ / www.cdc.gov/ features/ necrotizingfasciitis/ . PRO VIDER RESO URCES

• Practice Guidelines for the Diagnosis and Management of Skin and So t Tissue In ections—http:/ / cid.oxfordjournals.org/ content/ 41/ 10/ 1373.full# sec-6.

REFERENCES 1. Du el S, Martino M. Simple cellulitis or a more serious in ection? J Fam Pract. 2006;55:396-400. 2. Usatine RP, Sandy N. Dermatologic emergencies. Am Fam Physician. 2010;82:773-780. 3. Koukouras D, Kallidonis P, Panagopoulos C, et al. Fournier’s gangrene, a urologic and surgical emergency: presentation o a multiinstitutional experience with 45 cases. Urol Int. 2011;86:167-172. 4. Trent JT, Kirsner RS. Diagnosing necrotizing asciitis. Adv Skin Wound Care. 2002;15:135-138. 5. Cheng NC, Chang SC, Kuo YS, et al. Necrotizing asciitis caused by methicillin-resistant Staphylococcus aureus resulting in death. A report o three cases. J Bone Joint Surg Am. 2006;88:1107-1110. 6. Horseman MA, Surani S. A comprehensive review o Vibrio vulnif cus: an important cause o severe sepsis and skin and so t-tissue in ection. Int J In ect Dis. 2011;15:e157-e166. 7. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines or the diagnosis and management o skin and so t-tissue in ections. Clin In ect Dis. 2005;41:1373-1406. 8. Cheung JP, Fung B, Tang WM, Ip WY. A review o necrotising asciitis in the extremities. Hong Kong Med J. 2009;15:44-52. 9. Angoules AG, Kontakis G, Drakoulakis E, et al. Necrotising asciitis o upper and lower limb: a systematic review. Injury. 2007;38 (suppl 5):S19-S26.

PRO GNO SIS AND FO LLO W-UP • Overall case atality rate remains 20% to 47% despite aggressive, modern therapy. 5,6 ° However, in a retrospective chart review o patients with NSTIs treated at 6 academic hospitals in Texas between 2004 and 2007 mortality rates varied between hospitals rom 9% to 25% (n = 296). 12 • Early diagnosis and treatment can reduce case atality rate to 12%.

PATIENT RESO URCES

5

• Carrying out the rst asciotomy and radical debridement within 24 hours o symptom onset is associated with signi cantly improved survival. 8

PATIENT EDUCATIO N The serious li e-threatening nature o NF should be explained to the patient and amily when in ormed consent is given prior to surgery. The risk o losing li e and limb should be explained while giving hope or recovery. For those patients who survive but have lost a limb, counseling should be o ered to help them deal with the psychological e ects o the amputation.

10. Endor FW, Cancio LC, Klein MB. Necrotizing so t-tissue in ections: clinical guidelines. J Burn Care Res. 2009;30:769-775. 11. Escobar SJ, Slade JB Jr, Hunt TK, Cianci P. Adjuvant hyperbaric oxygen therapy (HBO2) or treatment o necrotizing asciitis reduces mortality and amputation rate. Undersea Hyperb Med. 2005;32:437-443. 12. Kao LS, Lew DF, Arab SN, et al. Local variations in the epidemiology, microbiology, and outcome o necrotizing so t-tissue in ections: a multicenter study. Am J Surg. 2011;202:139-145.

591

PART 14 DERMATO LO GY

592

SECTIO N 3

Ch a pt e r 125

VIRAL

125 CHICKENPO X E.J. Maye aux, Jr, MD

PATIENT STO RY A 48-year-old man developed a rash, low ever, and a cough. Because he had no medical insurance he posted a photograph o his rash on Facebook hoping that someone would give him some good advice. A riend working in a community clinic suggested that he could be seen at a reasonable price based on their sliding scale. The man presented to the clinic with the rash and upper respiratory symptoms. On history he acknowledged that he never had varicella as a child. On physical examination he was ound to have multiple vesicles, papules, pustules, and crusting lesions rom his scalp down to his legs (Figures 125-1 and 125-2). A close-up o lesions showed a “dewdrop on a rose petal” pattern o single vesicles on red bases (Figure 125-3). The physician diagnosed the patient with chickenpox (varicella) and o ered him a prescription or generic acyclovir. The patient stated that he was already beginning to eel better and since his ever was gone he might not ll the prescription. One week later he posted on Facebook that he was eeling well and appreciated the physician or seeing him without insurance.

INTRO DUCTIO N Chickenpox is a highly contagious viral in ection that can become reactivated in the orm o zoster.

SYNO NYMS Chickenpox is also called as varicella

FIGURE 125-1 Chicke np ox in a 48-ye ar-old man who ne ve r had varice lla as a child . Note le sions in various stag e s (p ap ule s, intact ve sicle s, p ustule s, and cruste d p ap ule s) cause d b y multip le crop s o le sions. (Re p rod uce d with p e rmission from Ryan O ’Q uinn, MD.)

• As the vaccination rates steadily increased in the United States, there has been a corresponding 4- old decrease in the number o cases o chickenpox cases down to disease rates o rom 0.3 to 1 per 1000 population in 2001. 3 • Less than 2% o cases o varicella in ections occur among adults over the age o 20 years (see Figures 125-1 to 125-3), almost a quarter o all VZV-related mortality occurs among this age group. 4 • I the mother acquires varicella in ection be ore 20 weeks’ gestation, the etus is at risk or developing congenital varicella syndrome, characterized by limb hypoplasia, skin lesions, neurologic abnormalities, and structural eye damage. Herpes zoster may also develop during in ancy. 5 • I the mother acquires varicella in the peripartum period, the baby is at risk or neonatal varicella, which may present with mild rash to disseminated in ection. 5

EPIDEMIO LO GY • Varicella-zoster virus (VZV) is distributed worldwide. • The rate o secondary household attack is more than 90% in susceptible individuals. 1 • Adults and immunocompromised patients generally develop more severe disease than normal children. For every 100,000 individuals who develop chickenpox, between 4 and 9 will die due to the in ection and 81% to 85% o these will be adults. It is 5 times more likely to be atal in pregnancy than in the nonpregnant adult. 2 • Traditionally, primary in ection with VZV occurred during childhood. In childhood, it is usually a benign, sel -limited illness in immunocompetent hosts. It occurs throughout the year in temperate regions, but the incidence peaks in the late spring and summer months. • Prior to the introduction o the varicella vaccine in 1995, the yearly incidence o chickenpox in the United States was approximately 4 million cases with approximately 11,000 hospital admissions and 100 deaths. 3

FIGURE 125-2 Chicke np ox in the scalp o the same man in Fig ure 125-1. (Re p rod uce d with p e rmission from Ryan O ’Q uinn, MD.)

PART 14 DERMATO LO GY

Ch ICKe NpO X

FIGURE 125-3 Clo se -up p icture o chicke np o x in the same man in Fig ure 125-1. No te the le sions are p re se nt in various stag e s. The ve sicle s or p ustule s are on a re d b ase . (Re p rod uce d with p e rmission from Ryan O ’Q uinn, MD.)

ETIO LO GY AND PATHO PHYSIO LO GY • Chickenpox is caused by a primary in ection with the VZV, which is a double-stranded, linear DNA herpesvirus. • Transmission occurs via contact with aerosolized droplets rom nasopharyngeal secretions or by direct cutaneous contact with vesicle f uid rom skin lesions. • The incubation period or VZV is approximately 15 days, during which the virus undergoes replication in regional lymph nodes, ollowed by 2 viremic phases, the second o which persists through the development o skin lesions generally by day 14. 6 • The vesicular rash appears in crops or several days. The lesions start as vesicle on a red base, which is classically described as a dewdrop on a rose petal (Figure 125-4). The lesions gradually develop a pustular component (Figure 125-5) ollowed by the evolution o crusted papules (see Figure 125-5). The period o in ectivity is generally considered to last rom 48 hours prior to the onset o rash until skin lesions have ully crusted. • The most requent complication is bacterial skin superin ection. Lesscommon skin complications (seen more requently in immunosup-

FIGURE 125-5 Pustule s and cruste d le sions on the ace o a home le ss man with varice lla. Note how varice lla has le sions simultane ously visib le at d i e re nt stag e s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

pressed hosts) include bullous varicella, purpura ulminans, and necrotizing asciitis. • Encephalitis is a serious potential complication o chickenpox that develops toward the end o the rst week o the exanthema. One orm, acute cerebellar ataxia, occurs mostly in children and is generally ollowed by complete recovery. A more di use encephalitis most o ten occurs in adults and may produce delirium, seizures, and ocal neurologic signs. It has signi cant rates o long-term neurologic sequelae and death. • Pneumonia is rare in healthy children but accounts or the majority o hospitalizations in adults, where it has up to a 30% mortality rate. 7 It usually develops insidiously within a ew days a ter the rash has appeared with progressive tachypnea, dyspnea, and dry cough. Chest X-rays reveal di use bilateral in ltrates. Treat with prompt administration o intravenous acyclovir. The use o adjunctive steroid therapy is controversial. • Varicella hepatitis is rare, and typically only occurs in immunosuppressed individuals. It is requently atal. • Reactivation o latent VZV results in herpes zoster or shingles.

RISK FACTO RS • Preexisting lung disease2 • Smoking • Immunocompromise including immunosuppressive drug therapy • HIV in ection • Malignancy

DIAGNO SIS CLINICAL FEATURES

FIGURE 125-4 De wd rop on a rose p e tal is the classic d e scrip tion o a varice lla ve sicle on a re d b ase . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• The typical clinical mani estations o chickenpox include a prodrome o ever, malaise, or pharyngitis, ollowed in 24 hours by the development o a generalized vesicular rash. • The lesions are pruritic and appear as successive crops o vesicles more than 3 to 4 days.

593

594

PART 14 DERMATO LO GY

Ch a pt e r 125

rapid than tissue culture. Latex agglutination blood testing may be used to determine exposure and immunity to VZV. • Women o childbearing potential who acquire the in ection should also be tested or pregnancy.

DIFFERENTIAL DIAGNO SIS • Pemphigus and bullous pemphigoid (see Chapters 182, Bullous Pemphigoid and 183, Pemphigus) present with larger bullae or erosions, and varicella vesicles are smaller. 2 • Dermatitis herpeti ormis is characterized by pruritic papulovesicles over the extremities and on the trunk, and granular immunoglobulin (Ig) A deposits on the basement membrane (see Chapter 184, Other Bullous Disease). FIGURE 125-6 Varice lla on the trunk o a nonimmunize d man d e monstrating the simultane ous ap p e arance o p ap ule s, p ustule s, and cruste d le sions. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Coexisting lesions in di erent stages o development on the ace, trunk, and extremities are common (Figure 125-6). • New lesions stop orming in approximately 4 days, and most lesions have ully crusted by 7 days.

• Herpes simplex in ection presents with similar lesions, but is generally restricted to the genital and oral areas. The vesicles o herpes simplex tend to be more clustered in a group rather than the wide distribution o varicella (see Chapter 128, Herpes Simplex). • Impetigo can have bullous or crusted lesions anywhere on the body. The lesions o ten have mild erythema and a yellowish color to the crusts (see Chapter 118, Impetigo). • Insect bites are o ten suspected by history and can occur on the entire body.

TYPICAL DISTRIBUTIO N Body wide—No laboratory tests are needed unless the diagnosis is uncertain. For children or adults in which there is uncertainty about previous disease and it is important to establish a quick diagnosis, a direct f uorescent antibody test can be done on a scraping o a lesion. In many laboratories, a result can be obtained within 24 hours (Figure 125-7). LABO RATO RY TESTING • Diagnosis is usually based on classic presentation. Culture o vesicular f uid provides a de nitive diagnosis, but is positive in less than 40% o cases. Direct immunof uorescence has good sensitivity and is more

MANAGEMENT NO NPHARMACO LO GIC • Pruritus can be treated with calamine lotion, pramoxine gel, or powdered oatmeal baths. • Fingernails should be closely cropped to avoid signi cant excoriation and secondary bacterial in ection. MEDICATIO NS • Antihistamines are help ul in the symptomatic treatment o pruritus. • Acetaminophen should be used to treat ever in children, as aspirin use is associated with Reye syndrome in the setting o viral in ections. 8 SOR • Superin ection may be treated with topical or oral antibiotics. • Prophylactic use o varicella zoster immune globulin (125 U/ 10 kg, up to 625 U intramuscular [IM]) in recently exposed susceptible individuals can prevent or attenuate the disease. However, the immune globulin is extremely hard to obtain at times. 9 • For adults, acyclovir 20 mg/ kg PO 4 times daily (800 mg maximum) or 7 days may be used or treatment i started in the rst 24 hours o the rash. 9 SO R • Early treatment with intravenous acyclovir may be e ective or treatment o varicella hepatitis and pneumonia, and may also be use ul in the treatment o immunosuppressed patients.2 SOR C It is pregnancy class Bdrug. • Valacyclovir 1 g 3 times daily has enhanced bioavailability when compared with acyclovir.

FIGURE 125-7 A 29-ye ar-old woman with mild case o varice lla. He r p re vious history o varice lla in child hood was unce rtain, so a d ire ct scrap ing o a le sion was p e r orme d and the varice lla virus was id e nti e d q uickly with a d ire ct f uo re sce nt antib o d y te st. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Famciclovir 500 mg 3 times daily also has enhanced bioavailability when compared with acyclovir. • Adults who get varicella should be assessed or neurologic and pulmonary disease.

PART 14 DERMATO LO GY

Ch ICKe NpO X

PREVENTIO N • Varicella immunization (Varivax) can be used to prevent chickenpox. SOR It is contraindicated in individuals allergic to gelatin or neomycin and in immunosuppressed individuals (it is a live vaccine). In 2006, and again in 2010, the Advisory Committee on Immunization Practices recommended that all children younger than 13 years o age should be routinely administered 2 doses o varicella-containing vaccine, with the rst dose administered at 12 to 15 months o age and the second dose at 4 to 6 years o age (ie, be ore rst grade). The second dose can be administered at an earlier age provided the interval between the rst and second dose is at least 3 months. 10 The Centers or Disease Control and Prevention (CDC) also recommends that all adults without evidence o immunity to varicella should receive 2 doses o single-antigen varicella vaccine or a second dose i they have received only 1 dose. Evidence o immunity to varicella in adults includes documentation o 2 doses o varicella vaccine at least 4 weeks apart, US-born be ore 1980 except health care personnel and pregnant women, history o varicella based on diagnosis or veri cation o varicella disease by a health care provider, history o herpes zoster, or laboratory evidence o immunity or laboratory con rmation o disease. Extra consideration or vaccination should be given to those who have close contact with persons at high risk or severe disease (eg, health care personnel and amily contacts) or are at high risk or exposure or transmission (eg, people with regular exposure to children, college students, military personnel, nonpregnant women o childbearing age, and international travelers). • Pregnant women should be assessed or evidence o varicella immunity. Women who do not have evidence o immunity should receive the rst dose o varicella vaccine upon completion or termination o pregnancy and be ore discharge rom the health care acility. The second dose should be administered 4 to 8 weeks a ter the rst dose. • Passive immunization with VZV-speci c antibodies reduces the risk o varicella in ection and attenuates the severity o in ection in those who seroconvert. The US Advisory Committee on Immunization Practices recommends VariZIG in all nonimmune pregnant women who have been exposed to persons with VZV 125 U/ 10 kg (1 vial) body weight given IM, with a maximum dose o 625 units (5 vials) within 96 hours o exposure. 4 SO R B For pregnant women who cannot receive VariZIG within 96 hours o exposure, a single dose o intravenous immunoglobulin (IVIG) at 400 mg/ kg may be used, or the patient may be closely monitor or signs and symptoms o varicella and treatment started with acyclovir i illness occurs. 11 Postexposure prophylaxis is not needed among women who have a history o chickenpox or were immunized with varicella vaccine in the past.

FO LLO W-UP Follow-up is unnecessary or immunocompetent children and adults who are having no complications. All patients or parents should report any respiratory or neurologic problems immediately.

PATIENT EDUCATIO N • Avoid scratching the blisters and keep ngernails short. Scratching may lead to superin ection. • Calamine lotion and oatmeal (Aveeno) baths may help relieve itching.

• Do not use aspirin or aspirin-containing products to relieve ever. The use o aspirin is associated with development o Reye syndrome, which may cause death. PATIENT RESO URCES

• KidsHealth. Chickenpox—http:/ / www.kidshealth.org/ parent/ infections/ skin/ chicken_pox.html. • MedlinePlus. Chickenpox—http:/ / www.nlm.nih.gov/ medlineplus/ chickenpox.html. PRO VIDER RESO URCES

• Centers for Disease Control and Prevention. Varicella (Chickenpox) Vaccination—http:/ / www.cdc.gov/ vaccines/ vpd-vac/ varicella/ default.htm. • Centers or Disease Control and Prevention. Slide Set: Overview of VZV Disease &Vaccination for Healthcare Professionals—http:/ / www.cdc.gov/ vaccines/ vpd-vac/ shingles/ downloads/ VZV_clinical_slideset_Jul2010.ppt.

REFERENCES 1. Wharton M. The epidemiology o varicella-zoster in ections. Infect Dis Clin North Am. 1996;10(3):571-581. 2. Tunbridge AJ, Breuer J, Jeffery KJ; British Infection Society. Chickenpox in adults—clinical management. J Infect. 2008 Aug;57(2):95-102. 3. Centers or Disease Control and Prevention (CDC). Decline in annual incidence o varicella—selected states, 1990-2001. MMWR Morb MortalWkly Rep. 2003;52(37):884-885. 4. Marin M, Güris D, Chaves SS, Schmid S, Seward JF; Advisory Committee on Immunization Practices, Centers or Disease Control and Prevention. Prevention o varicella: recommendations o the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007 Jun;56(RR-4):1-40. CDC. http:/ / www.cdc.gov/ mmwr/ preview/ mmwrhtml/ rr5604a1.htm. Accessed January 30, 2014. 5. Enders G, Miller E, Cradock-Watson J, et al. Consequences o varicella and herpes zoster in pregnancy: prospective study o 1739 cases. Lancet. 1994;343:1548. 6. Grose C. Variation on a theme by Fenner: the pathogenesis o chickenpox. Pediatrics. 1981;68(5):735-737. 7. Schlossberg D, Littman M. Varicella pneumonia. Arch Intern Med. 1988;148(7):1630-1632. 8. Belay ED, Bresee JS, Holman RC, et al. Reye’s syndrome in the United States rom 1981 through 1997. N Engl J Med. 1999;340(18):1377-1382. 9. Ogilvie MM. Antiviral prophylaxis and treatment in chickenpox. A review prepared for the UK advisory group on chickenpox on behal o the british society or the study o in ection. J Infect. 1998;36(suppl 1):31-38. 10. Centers or Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommended immunization schedules or persons aged 0 through 18 years and adults aged 19 years and older—United States, 2013. MMWR Surveill Summ. 2013 Feb;62(suppl 1):1. 11. VariZIG or prophylaxis a ter exposure to varicella. Med Lett Drugs Ther. 2006 Aug 14;48(1241):69-70.

595

PART 14 DERMATO LO GY

596

Ch a pt e r 126

126 ZO STER E.J. Maye aux, Jr, MD Richard P. Usatine , MD

PATIENT STO RY A 75-year-old woman presented with a severely pain ul case o herpes zoster in a lower abdominal/ or lower extremity distribution. Groups o vesicles were becoming bullae and leading to erosions (Figure 126-1). The woman was treated with oral analgesics and an oral antiviral medication. Her primary care physician treated her pain aggressively in an attempt to prevent postherpetic neuralgia. FIGURE 126-2 Close -up of he rp e s zoste r le sions. Note g roup e d ve sicle s on a re d b ase . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

INTRO DUCTIO N Herpes zoster (shingles) is a syndrome characterized by a pain ul, usually unilateral vesicular eruption that develops in a restricted dermatomal distribution (Figures 126-1 and 126-2). 1-3

SYNO NYMS Zoster is also known as shingles.

EPIDEMIO LO GY

A

• According to the Centers or Disease Control and Prevention (CDC), 32% o persons in the United States will experience zoster during their li etimes accounting or about 1 million cases annually. 4 Older age groups account or the highest incidence o zoster. Approximately 4% o patients will experience a second episode o herpes zoster. 5 • More zoster cases have been observed among women, even when controlling or age. 6 • Herpes zoster occurs more requently and more severely in immunosuppressed patients, including transplantation patients.

ETIO LO GY AND PATHO PHYSIO LO GY • A ter primary in ection with either chickenpox or vaccine-type varicella-zoster virus (VZV), a latent in ection is established in the sensory dorsal root ganglia. Reactivation o this latent VZV in ection results in herpes zoster (shingles).

B

• Both sensory ganglia neurons and satellite cells surrounding the neurons serve as sites o VZV latent in ection. During latency, the virus only expresses a small number o viral proteins.

FIGURE 126-1 A 75-ye ar-old woman with se ve re case of he rp e s zoste r in a lo we r ab d ominal and lowe r e xtre mity d istrib ution. A. Note the e rosions on the up p e r thig hs in ad d ition to the ve sicle s and b ullae . B. Close -up of the zoste r le sions showing g roup e d ve sicle s and b ullae on a re d b ase . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• How the virus emerges rom latency is not clearly understood. Once reactivated, virus spreads to other cells within the ganglion. The dermatomal distribution o the rash corresponds to the sensory elds o the in ected neurons within the speci c ganglion. 3

PART 14 DERMATO LO GY

ZO St e r

• Loss o VZV-speci c cell-mediated immune response is responsible or reactivation. 3 • The pain associated with zoster in ections and postherpetic neuralgia (PHN) is thought to result rom injury to the peripheral nerves and altered central nervous system processing. • The most common complications are PHN and bacterial superin ection that can delay healing and cause scarring o the zoster lesions. • Approximately 19% o patients develop complications that may include the ollowing7: 7 PHN—The most common complication is seen in 10% at 90 days ° (see below). 7 ° Ocular complications, including uveitis and keratitis (seen in 4%) (see Chapter 127, Zoster Ophthalmicus). (seen in 3%). 7 ° Bell palsy and other motor nerve plastic 7 ° Bacterial skin in ection (seen in 2%). ° Meningitis caused by central extension o the in ection. ° Herpes zoster oticus (Ramsay Hunt syndrome) (Figure 126-3) includes the triad o ipsilateral acial paralysis, ear pain, and vesicles in the auditory canal and auricle. 8 Disturbances in taste perception, hearing (tinnitus, hyperacusis), lacrimation, and vestibular unction (vertigo) may occur. ° Other rare complications may include acute retinal necrosis, transverse myelitis, encephalitis, leukoencephalitis, contralateral thrombotic stroke syndrome, and granulomatous vasculitis. 9 • Immunosuppressed patients are at increased risk or complications, including severe complications such as broader dermatomal involvement, disseminated in ection, visceral involvement, pneumonitis, and/ or meningoencephalitis. • PHN is the persistence o pain, numbness, and/ or dysesthesias precipitated by movement or in response to nonnoxious stimuli in the a ected dermatome or more than 1 month a ter the onset o zoster. The incidence o PHN in the general population is 1.38 per 1000 person-years, and it occurs more commonly in individuals older than age 60 years and in immunosuppressed individuals. 3 • In a large study, rates o zoster-associated pain (PHN) persisting at least 90 days were as below: ° Ten percent overall, 12% in women and 7% in men ° Ages 22 to 59 years—5% overall, 6% in women and 5% in men

FIGURE 126-3 He rp e s zoste r oticus (Ramsay Hunt synd rome ) with the classic p re se ntation of re d ne ss and ve sicle s on the auricle . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

° Ages 60 to 69 years—10% overall, 14% in women and 5% in men ° Ages 70 to 79 years—17% overall, 18% in women and 15% in men7 ° Age 80 years and older—20% overall, 23% in women and 13% in men

RISK FACTO RS ZO STER • Older age3 • Underlying malignancy • Disorders o cell-mediated immunity • Chronic lung or kidney disease • Autoimmune disease PHN • Age older than 60 years • Negative vaccine status

DIAGNO SIS CLINICAL FEATURES A deep burning pain and sometimes redness in a dermatomal pattern is the most common rst symptom and can precede the rash by days to weeks (Figure 126-4). A prodrome o ever, dysesthesias, malaise, and headache leads in several days to a dermatomal vesicular eruption. The rash starts as grouped vesicles or bullae which evolve into pustular or hemorrhagic lesions within 3 to 4 days (Figures 126-1 to 126-6). The lesions typically crust in approximately a week, with complete resolution within 3 to 4 weeks. 5 TYPICAL DISTRIBUTIO N Generally limited to one dermatome in immunocompetent patients, but sometimes a ects neighboring dermatomes. Rarely, a ew scattered vesicles located away rom the involved dermatome as a result o release o

FIGURE 126-4 He rp e s zoste r in the axilla of a young woman with g roup e d ve sicle s on a p ink b ase . Notice the e rythe ma in the d e rmatome that has starte d p rod ucing b liste rs. (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

597

598

PART 14 DERMATO LO GY

Ch a pt e r 126

• Scabies may present as a pustular rash that is not con ned to dermatomes and usually has characteristic lesions in the webs o the ngers (see Chapter 141, Scabies). • Insect bites are o ten suspected by history and can occur over the entire body. • Folliculitis presents with characteristic pustules arising rom hair sha ts (see Chapter 119, Folliculitis). • Zoster mimics coronary artery disease when it presents with chest pain be ore the vesicles are visible. • Herpes simplex in ection presents with similar lesions but is usually restricted to the perioral region, genital area, buttocks, and ngers (see Chapter 128, Herpes Simplex). FIGURE 126-5 He rp e s zoste r on the arm that follows a d e rmatomal p atte rn. (Re p ro d uce d with p e rmission fro m E.J. Maye aux Jr, MD.)

MANAGEMENT NO NPHARMACO LO GIC

VZV rom the in ected ganglion into the bloodstream. 3 I there are more than 20 lesions distributed outside the dermatome a ected, the patient has disseminated zoster. The thoracic and lumbar dermatomes are the most commonly involved. Occasionally zoster will be seen on the extremities (see Figure 126-5). LABO RATO RY TESTING Meningitis associated with VZV in ection can be diagnosed by cerebrospinal f uid showing pleocytosis.

DIFFERENTIAL DIAGNO SIS • Pemphigus and other bullous diseases present with blisters, but not the classic dermatomal distribution (see Chapters 181, Overview o Bullous Disease and 183, Pemphigus). • Molluscum contagiosum presents with white or yellow f at-topped papules with central umbilication caused by a pox virus. The lesions are more rm and unless irritated do not have a red base as seen with zoster (see Chapter 129, Molluscum Contagiosum).

Calamine lotion and topically administered lidocaine may be used to reduce pain and itching. SO R C MEDICATIO NS • The objectives o treatment o herpes zoster include (a) hastening the resolution o the acute viral in ection, (b) treatment o the associated pain, and (c) prevention o PHN. • Antiviral agents used in the treatment o herpes zoster include acyclovir (Zovirax), amciclovir (Famvir), and valacyclovir (Valtrex), all started within 72 hours o the onset o the rash (Table 126-1). 10 SO R • Adding corticosteroids to acyclovir therapy may accelerate times to crusting and healing, return to uninterrupted sleep, resumption o ull activity, and discontinuation o analgesic. Data are lacking or combining corticosteroids with other antivirals. • Pain can be managed with nonprescription analgesics or narcotics. Pain should be treated aggressively. This may actually prevent or lessen the severity o PHN. Narcotic analgesics with hydrocodone are appropriate when needed. SO R C • Treatment o herpes zoster with steroids does not reduce the prevalence o PHN. • Treatment o herpes zoster early with valacyclovir, amciclovir, or amitriptyline does reduce pain o PHN at 6 months. • Treatment o PHN includes tricyclic antidepressants, gabapentin (Neurontin), pregabalin (Lyrica), and/ or opioid analgesics (Table 126-2). TABLE 126-1 Tre atme nts for He rp e s Zoste r

FIGURE 126-6 He rp e s zoste r of the C4-C5 d e rmatomal d istrib ution. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Me d icat io n

Do sag e

Acyclovir (Zovirax)

800 mg orally 5 time s d aily for 7 to 10 d ays or 10 mg /kg intrave nously e ve ry 8 hours for 7 to 10 d ays

Famciclovir (Famvir)

500 mg orally 3 time s d aily for 7 d ays

Valacyclovir (Valtre x)

1000 mg orally 3 time s d aily for 7 d ays

Pre d nisone (De ltasone )

30 mg orally twice d aily for 1 we e k followe d b y a tap e ring d ose for ap p roximate ly 2 we e ks

PART 14 DERMATO LO GY

ZO St e r

TABLE 126-2 Effe ctive Tre atme nts for Posthe rp e tic Ne uralg ia

NNT o r ê 50% Pain Re d uct io n

Tre at me nt

Be ne f t / Risk

Risks

Do se / Durat io n

Lid ocaine p atch 5%

Re d uce s p ain and acts as me chanical b arrie r

Ap p lication site se nsitivity

2

Ap p ly up to 3 p atche s for up to 12 hours

Tricyclic antid e p re ssants (includ ing amitrip tyline ) (strong e st e vid e nce )

Re d uce s p ain, b e tte r sle e p , d e cre ase s anxie ty and d e p re ssion

Multip le sid e e ffe cts, includ ing se d ation and d ry mouth

2.7

25 to 150 mg q hs

Gab ap e ntin (Ne urontin) (strong e st e vid e nce )

Re d uce s p ain, imp rove s sle e p, mood, and q uality of life

Somnole nce , d izzine ss, d e cre ase d me mory

2.8 to 5.3

300 to 600 mg tid (can g o as hig h as 1200 mg tid )

Pre g ab alin (Lyrica)

May re d uce p ain

Pe rip he ral e d e ma and we ig ht g ain

5

75 mg b id

O p ioid s (morp hine , oxycod one , me thad one )

Re d uce s p ain

Somnole nce , constip ation, tole rance

Variab le

Start low and titrate to e ffe ctive d ose

Tramad ol

Re d uce s p ain and is not a true narcotic

Dizzine ss, nause a, somnole nce , constip ation

4.8

50 to 100 mg q id

NNT, numb e r ne e d e d to tre at. Data from Garroway N, Chhab ra S, Land is S, Skolnik DC. Clinical inq uirie s: what me asure s re lie ve p osthe rp e tic ne uralg ia?J Fam Pract. 2009;58(7):384 and Tyring SK. Manag e me nt of he rp e s zoste r and p osthe rp e tic ne uralg ia. J Am Acad De rmatol. 2007;57(sup p l 6):S136-S142.

PREVENTIO N • Use o varicella (chickenpox) vaccine has not led to an increase in vaccine-associated herpes zoster in immunized patients or in the general population, and has led to an overall decrease in herpes zoster. 8 • The herpes zoster vaccine contains a much higher dose o the liveattenuated virus than the varicella vaccine. In adults 60 years o age or older, immunization reduces the incidence o herpes zoster by 51% compared with placebo. 3 In those who do develop zoster, the duration o pain and discom ort is shorter and the incidence o PHN is greatly reduced. It reduces the incidence o PHN rom 1.38 to 0.46 per 1000 person-years. 3

FO LLO W-UP Follow-up is based on the severity o the case and the immune status o the patient.

PATIENT EDUCATIO N • Herpes zoster in an immunocompetent host is only contagious rom contact with open lesions. • Patients with disseminated zoster or with zoster and are immunocompromised should be isolated rom nonimmune individuals with primary varicella in ection (in which airborne spread is possible).

• Individuals who have not had varicella and are exposed to a patient with herpes zoster are only at risk o developing primary varicella and not herpes zoster. PATIENT RESO URCES

• Centers for Disease Control and Prevention. Vaccine Information Statements—http:/ / www.cdc.gov/ vaccines/ pubs/ vis/ . • Medinfo UK. Shingles (Herpes Zoster)—http:/ / www.medinfo .co.uk/ conditions/ shingles.html. • The Skin Site. Herpes Zoster (Shingles)—http:/ / www.skinsite .com/ info_herpes_zoster.htm. • MedlinePlus. Shingles—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000858.htm. PRO VIDER RESO URCES

• MedlinePlus. Shingles—http:/ / emedicine.medscape.com/ article/ 218683. • Stankus SJ, Dlugopolski M, Packer D. Management o herpes zoster (shingles) and PHN. Am Fam Physician. 2000;61:2437-2444— http:/ / www.aafp.org/ afp/ 20000415/ 2437.html. REFERENCES 1. Usatine RP, Clemente C. Is herpes zoster unilateral? West J Med. 1999;170(5):263. 2. Gnann JW Jr, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med. 2002;347(5):340-346.

599

600

PART 14 DERMATO LO GY

CHAPTER 126

3. Oxman MN. Immunization to reduce the requency and severity o herpes zoster and its complications. Neurology. 1995;45(12 suppl 8):S41-S46.

7. Yawn BP, Saddier P, Wollan PC, et al. A population-based study o the incidence and complication rates o herpes zoster be ore zoster vaccine introduction. Mayo Clin Proc. 2007;82(11):1341-1349.

4. Harpaz R, Ortega-Sanchez IR, Seward JF; Advisory Committee on Immunization Practices (ACIP) Centers or Disease Control and Prevention (CDC). Prevention o herpes zoster: recommendations o the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008;57(RR-5):1-30.

8. Adour KK. Otological complications of herpes zoster. Ann Neurol. 1994;35(suppl):S62-S64.

5. Stankus SJ, Dlugopolski M, Packer D. Management o herpes zoster (shingles) and postherpetic neuralgia. Am Fam Physician. 2000;61(18):2437-2444, 2447-2448. 6. Opstelten W, Van Essen GA, Schellevis F, et al. Gender as an independent risk actor or herpes zoster: a population-based prospective study. Ann Epidemiol. 2006;16(9):692-695.

9. Arvin AM, Pollard RB, Rasmussen LE, Merigan TC. Cellular and humoral immunity in the pathogenesis o recurrent herpes viral in ections in patients with lymphoma. J Clin Invest. 1980;65(4): 869-878. 10. Tyring SK, Beutner KR, Tucker BA, et al. Antiviral therapy for herpes zoster: randomized, controlled clinical trial o valacyclovir and amciclovir therapy in immunocompetent patients 50 years and older. Arch Fam Med. 2000;9(9):863-869.

PART 14 DERMATO LO GY

ZO STER O PHTHALMICUS

127 ZO STER O PHTHALMICUS E.J. Maye aux Jr, MD Richard P. Usatine , MD

PATIENT STO RY A 44-year-old HIV-positive Hispanic man presented with pain ul herpes zoster o his right orehead (Figure 127-1). He was particularly worried because his right eye was red, pain ul, and very sensitive to light (Figure 127-2). On physical examination there was signi cant conjunctival injection, corneal punctate epithelial erosions, and clouding, and a small layer o blood in the anterior chamber (hyphema). The pupil was somewhat irregular. Along with the hyphema and ciliary f ush, this indicated an anterior uveitis. The patient had a unilateral ptosis on the right side with limitations in elevation, depression, and adduction o the eye secondary to cranial nerve III palsy rom the zoster. The patient was immediately re erred to ophthalmology and the anterior uveitis, corneal involvement, and cranial nerve III palsy were con rmed. The ophthalmologist started the patient on topical ophthalmic preparations o erythromycin, moxif oxacin, prednisolone, and atropine. Oral acyclovir was also prescribed. Un ortunately, the patient did not return or ollow-up until 6 months later, when he returned to the ophthalmologist with signi cant corneal scarring (Figure 127-3). The patient is currently on a waiting list or a corneal transplantation.

INTRO DUCTIO N

FIGURE 127-2 Acute zoste r op hthalmicus o the same p atie nt with conjunctival inje ction, corne al p unctation (ke ratitis), and a small laye r o b lood in the ante rior chamb e r (hyp he ma). A d iag nosis o ante rior uve itis was susp e cte d b ase d on the irre g ularly shap e d p up il, the hyp he ma, and ciliary ush. A slit-lamp e xamination conf rme d the ante rior uve itis (iritis). (Re p rod uce d with p e rmission from Paul Come au).

SYNO NYMS Zoster ophthalmicus is also known as ocular herpes zoster.

EPIDEMIO LO GY • Incidence rates o HZO complicating herpes zoster range rom 8% to 56%. 1

Herpes zoster is a common in ection caused by varicella-zoster virus (VZV), the same virus that causes chickenpox. Reactivation o the latent virus in neurosensory ganglia produces the characteristic mani estations o herpes zoster (shingles). Herpes zoster outbreaks may be precipitated by aging, poor nutrition, immunocompromised status, physical or emotional stress, and excessive atigue. Although zoster most commonly involves the thoracic and lumbar dermatomes, reactivation o the latent virus in the trigeminal ganglia may result in herpes zoster ophthalmicus (HZO) (Figures 127-1 to 127-7).

• Ocular involvement is not correlated with age, gender, or severity o disease.

FIGURE 127-1 A 44-ye ar-old HIV-p ositive Hisp anic man with p ain ul he rp e s zoste r o his rig ht ore he ad . (Re p rod uce d with p e rmission from Paul Come au).

FIGURE 127-3 Corne al scarring and conjunctival inje ction o the same p atie nt 6 months late r a te r b e ing lost to ollow-up . (Re p ro d uce d with p e rmission from Paul Come au).

ETIO LO GY AND PATHO PHYSIO LO GY • Serious sequelae may occur including chronic ocular inf ammation, vision loss, and disabling pain. Early diagnosis is important to prevent progressive corneal involvement and potential loss o vision. 2

601

PART 14 DERMATO LO GY

602

Ch a pt e r 127

A FIGURE 127-5 He rp e s zoste r op hthalmicus involving the f rst and se cond b ranch o the trig e minal ne rve and the e ye lid s. The re is co njunctival hyp e re mia and p urule nt le t e ye d ischarg e . The naso ciliary b ranch o the o p hthalmic b ranch o the trig e minal ne rve is invo lve d , p ro d ucing the b lack crusting on the tip o the nose . (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

B FIGURE 127-4 A. He rp e s zoste r op hthalmicus showing a V1 d istrib ution in this 55-ye ar-old woman that is immunosup p re sse d with p re d nisone and azathiop rine or he r d e rmatomyositis. She had tre me nd ous e ye and acial p ain and d e ve lop e d sig nif cant b le p haro sp asm se cond ary to this p ain. B. It b e g an with e ye p ain with no f nd ing s e vid e nt to the op hthalmolog ist. A e w d ays late r the re we re ve sicle s on the up p e r lid and conjunctival inje ction with d ischarg e . In this p hotog rap h the uore sce in staining is still visib le a te r se e ing the op hthalmolog ist e arlie r that d ay. The re is no corne al d amag e and the mate rial at 1:00 is just uore sce in and d ischarg e on the sur ace o the corne a. (Re p rod uce d with p e rmission from Richard P. Usatine , MD).

• Because the nasociliary branch o the rst (ophthalmic) division o the trigeminal ( th cranial) nerve innervates the globe (see Figure 127-7), the most serious ocular involvement develops i this branch is involved. • Classically, involvement o the side o the tip o the nose (Hutchinson sign) has been thought to be a clinical predictor o ocular involvement

FIGURE 127-6 He rp e s zoste r op hthalmicus causing e ye lid swe lling and p tosis. Note the p ositive Hutchinson sig n. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

ZO St e r O ph t h a LMICUS

• Conjunctivitis, usually with Staphylococcus aureus, is a common complication o HZO. S upra orbita l n.

RISK FACTO RS S upra trochle a r n. Infra orbita l n. Exte rna l Na s a l n. (V2) Exte rna l Na s a l Br. of Na s ocilia ry n. (V1) FIGURE 127-7 Diag ram d e monstrating the se nsory d istrib ution o the trig e minal (f th cranial) ne rve , and major p e rip he ral ne rve s o the f rst (op hthalmic) d ivision that may b e involve d with he rp e s zoste r op hthalmicus. The in raorb ital ne rve rom the se cond d ivision is also shown. (Re p rod uce d with p e rmission from E.J. Maye aux Jr, MD.)

via the external nasal nerve (see Figures 127-5 and 127-6). The Hutchinson sign is a power ul predictor o ocular inf ammation and corneal denervation with relative risks o 3.35 and 4.02, respectively. In one study, the mani estation o herpes zoster skin lesions at the dermatomes o both nasociliary branches (at the tip, the side, and the root o the nose) was invariably associated with the development o ocular inf ammation. 3 • Epithelial keratitis is the earliest potential corneal nding (see Figure 127-2). On slit-lamp examination, it appears as multiple, ocal, swollen spots on the cornea that stain with f uorescein dye. They may either resolve or progress to dendrite ormation. Herpes zoster virus dendrites orm branching or rond-like patterns that have tapered ends and stain with f uorescein dye. These lesions can lead to anterior stromal corneal in ltrates. • Stromal keratitis occurs in 25% to 30% o patients with HZO, and is characterized by multiple ne granular in ltrates in the anterior corneal stroma. The in ltrates probably arise rom antigen-antibody reaction and may be prolonged and recurrent. 4 • Anterior uveitis evolves to in lammation o the iris and ciliary body and occurs requently with HZO (see Figure 127-2). The in lammation is usually mild, but may cause a mild intraocular pressure elevation. The course o disease may be prolonged, especially without timely treatment, and may lead to glaucoma and cataract ormation.

Immunocompromised persons, especially when caused by human immunode ciency virus in ection, have a much higher risk o developing zoster complications, including HZO.

DIAGNO SIS CLINICAL FEATURES • The syndrome usually begins with a prodrome o low-grade ever, headache, and malaise that may start up to 1 week be ore the rash appears. • Unilateral pain or hypesthesia in the a ected eye, orehead, top o the head, and/ or nose may precede or ollow the prodrome. The rash starts with erythematous macules along the involved dermatome, then rapidly progresses over several days to papules, vesicles and pustules (see Figures 127-4 to 127-6). The lesions rupture and typically crust over, requiring several weeks to heal completely. • With the onset o a vesicular rash along the trigeminal dermatome, hyperemic conjunctivitis, episcleritis, and lid droop (ptosis) can occur (see Figure 127-6). • Approximately two-thirds o patients with HZO develop corneal involvement (keratitis). 1 The epithelial keratitis may eature punctate or dendriti orm lesions (see Figure127-2). Complications o corneal involvement can lead to corneal scarring (see Figure 127-3). 6 • Iritis (anterior uveitis) occurs in approximately 40% o patients and can be associated with hyphema and an irregular pupil (see Figure 127-2). 1 • Rarely, zoster can be associated with cranial nerve palsies. TYPICAL DISTRIBUTIO N • The rontal branch o the rst division o the trigeminal nerve (which includes the supraorbital, supratrochlear, and external nasal branch o the anterior ethmoidal nerve) is most requently involved, and 50% to 72% o patients experience direct eye involvement. 1 • Although HZO most o ten produces a classic dermatomal rash in the trigeminal distribution, a minority o patients may have only cornea ndings.

• Herpes zoster virus is the most common cause o acute retinal necrosis. Symptoms include blurred vision and/ or pain in one or both eyes and signs include peripheral patches o retinal necrosis that rapidly coalesce, occlusive vasculitis, and vitreous inf ammation. It commonly causes retinal detachment. Bilateral involvement is observed in onethird o patients, but may be as high as 70% in patients with untreated disease. Treatment includes long courses o oral and intravenous acyclovir (Zovirax), and corticosteroids. 5

• Bacterial or viral conjunctivitis presents as eye pain and oreign body sensation associated with discharge but no rash (see Chapter 13, Conjunctivitis).

• Varicella-zoster virus is a member o the same amily (Herpesviridae) as herpes simplex virus, Epstein-Barr virus, and cytomegalovirus.

• Glaucoma presents as inf ammation, pain, and injection, but without the rash or conjunctival ndings (see Chapter 16, Glaucoma).

• The virus damages the eye and surrounding structures by neural and secondary perineural inf ammation o the sensory nerves. This o ten results in corneal anesthesia.

• Traumatic abrasions usually present with a history o trauma and corneal ndings but no other zoster ndings (see Chapter 12, Corneal Foreign Body and Abrasion).

DIFFERENTIAL DIAGNO SIS

• Trigeminal neuralgia presents with acial pain but without the rash or conjunctival ndings.

603

PART 14 DERMATO LO GY

604

• Pemphigus and other bullous diseases present with blisters, but not in a dermatomal distribution (see Chapter 181, Overview o Bullous Disease).

MANAGEMENT MEDICATIO NS • The standard treatment or HZO is to initiate antiviral therapy with acyclovir (800 mg, 5 times daily or 7-10 days), valacyclovir (1000 mg 3 times daily or 7-14 days), or amciclovir (500 mg orally 3 times a day or 7 days), as soon as possible so as to decrease the incidence o dendritic and stromal keratitis as well as anterior uveitis. 7 SO R • Oral acyclovir, valacyclovir, and amciclovir in patients with ophthalmic involvement have comparable outcomes. Treatment is most commonly oral acyclovir but intravenous acyclovir (10 mg/ kg 3 times daily or 7 days) may be considered in immunocompromised patients or the rare patient who is extremely ill. 8 SO R • Topical steroid ophthalmic drops are applied to the involved eye, a ter examination by the ophthalmologist, to reduce the inf ammatory response and control immune keratitis and iritis. 1,2 SO R B • The ophthalmologist may prescribe a topical cycloplegic (such as atropine) to treat the ciliary muscle spasm that is pain ul in iritis. SO R C • Topical ophthalmic antibiotics may also be prescribed to prevent secondary in ection o the eye. SO R C • As in all cases o zoster, pain should be treated e ectively with oral analgesics and other appropriate medications. Early and e ective treatment o pain may help to prevent postherpetic neuralgia (see Chapter 126, Zoster). • Topical anesthetics should never be used with ocular involvement because o their corneal toxicity. SO R B

Ch a pt e r 127

FO LLO W-UP Early diagnosis is critical to prevent progressive corneal involvement and potential loss o vision. Patients with herpes zoster should be in ormed that they should present or medical care with any zoster involving the rst (ophthalmic) division o the trigeminal nerve or the eye itsel .

PATIENT EDUCATIO N • Zoster o the eye is a very serious vision-threatening illness that requires strict adherence to medical therapy and close ollow-up. • Viral transmission to nonimmune individuals rom patients with herpes zoster can occur, but it is less requent than with chickenpox. Virus can be transmitted through contact with secretions.

PATIENT RESO URCES

• American Family Physician. What You Should Know About HZO— http:/ / www.aafp.org/ afp/ 2002/ 1101/ p1732.html. • EyeMDLink.com. Eye Herpes (Ocular Herpes)—http:/ / www .eyemdlink.com/ Condition.asp?ConditionID=223. PRO VIDER RESO URCES

• Medscape. Herpes Zoster Ophthalmicus—http:/ / emedicine .medscape.com/ article/ 783223. • Shaikh S, Ta CN. Evaluation and management o HZO. Am Fam Physician. 2002;66:1723-1730—http:/ / www.aafp.org/ afp/ 20021101/ 1723.html.

• Secondary in ection, usually S. aureus, may develop and should be treated with broad-spectrum topical and/ or systemic antibiotics. REFERRAL O R HO SPITALIZATIO N • Re erral to an ophthalmologist urgently should be initiated when eye involvement is seen or suspected. • Hospital admission should be considered or patients with loss o vision, severe symptoms, immunosuppression, involvement o multiple dermatomes, or with signi cant acial bacterial superin ection.

PREVENTIO N The herpes zoster vaccine reduces the incidence o herpes zoster by 51% compared with placebo. 9 In those who do develop zoster, the duration o pain and discom ort is shorter and the incidence o postherpetic neuralgia (PHN) is greatly reduced. It reduces the incidence o PHN rom 1.38 to 0.46 per 1000 person-years. 9

PRO GNO SIS

REFERENCES 1. Pavan-Langston D. Herpes zoster ophthalmicus. Neurology. 1995;45(12 suppl 8):S50-S51. 2. Severson EA, Baratz KH, Hodge DO, Burke JP. Herpes zoster ophthalmicus in Olmsted County, Minnesota: have systemic antivirals made a di erence? Arch Ophthalmol. 2003;121(3):386-390. 3. Zaal MJ, Völker-Dieben HJ, D’Amaro J. Prognostic value of Hutchinson’s sign in acute herpes zoster ophthalmicus. Graefes Arch Clin Exp Ophthalmol. 2003;241(3):187-191. 4. Liesegang TJ. Corneal complications from herpes zoster ophthalmicus. Ophthalmology. 1985;92(3):316-324. 5. Liesegang TJ. Herpes zoster ophthalmicus natural history, risk factors, clinical presentation, and morbidity. Ophthalmology. 2008;115(suppl 2):S3-S12. 6. Albrecht Ma. Clinical Features ofVaricella-ZosterVirus Infection: Herpes Zoster. http:/ / www.uptodate.com/ contents/ clinical-mani estations-o -varicella-zoster-virus-in ection-herpes-zoster. Accessed September 3, 2012.

• HZO can become chronic or relapsing. Recurrence is a characteristic eature o HZO.

7. McGill J, Chapman C, Mahakasingam M. Acyclovir therapy in herpes zoster in ection. A practical guide. Trans Ophthalmol Soc U K. 1983;103(pt 1):111-114.

• Approximately 50% o patients with HZO develop complications. Systemic antiviral therapy can lower the emergence o complications. 10,11

8. Gnann JW Jr, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med. 2002;347(5):340-346.

ZO St e r O ph t h a LMICUS

9. Oxman MN. Immunization to reduce the frequency and severity of herpes zoster and its complications. Neurology. 1995;45(12 suppl 8): S41-S46. 10. Miserocchi E, Waheed NK, Dios E, et al. Visual outcome in herpes simplex virus and varicella zoster virus uveitis: a clinical evaluation and comparison. Ophthalmology. 2002;109(8):1532-1537.

PART 14 DERMATO LO GY 11. Zaal MJ, Volker-Dieben HJ, D’Amaro J. Visual prognosis in immunocompetent patients with herpes zoster ophthalmicus. Acta Ophthalmol Scand. 2003;81(3):216-220.

605

606

PART 14 DERMATO LO GY

Ch a pt e r 128

128 HERPES SIMPLEX E.J. Maye aux Jr, MD Ke vin Carte r, MD

PATIENT STO RY A 32-year-old man presents with complains o a 1-week history o multiple pain ul vesicles on the sha t o his penis associated with tender groin adenopathy (Figure 128-1). The vesicles broke 2 days ago and the pain has increased. He had similar lesions 1 year ago but never went or health care examination at that time. He has had 3 di erent emale sexual partners in the last 2 years but has no knowledge o them having any sores or diseases. He was given the presumptive diagnosis o genital herpes and a course o acyclovir. His herpes culture came back positive and his rapid plasma reagin (RPR) and HIV tests were negative.

INTRO DUCTIO N Herpes simplex virus (HSV) in ection can involve the skin, mucosa, eyes, and central nervous system (CNS). HSV establishes a latent state ollowed by viral reactivation and recurrent local disease. Perinatal transmission o HSV can lead to signi cant etal morbidity and mortality.

EPIDEMIO LO GY HSV a ects more than one-third o the world’s population, with the 2 most common cutaneous mani estations being genital (Figures 128-1 to 128-4) and orolabial herpes (Figures 128-5 to 128-7). 1 The Centers or Disease Control and Prevention (CDC) reports that at least 50 million persons in the United States have genital HSV-2 in ection. Over the past decade, the percentage o Americans with genital herpes in ection in the United States has remained stable. Most persons in ected with HSV-2 have not been diagnosed with genital herpes. 2

FIGURE 128-1 R curr nt g nital h rp s simp l x virus on th p nis showing g ro up d ulc rs (d roo d v sicl s). (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 128-2 H rp s simp l x on th p nis with intact v sicl s and visib l crusts. (Re p rod uce d with p e rmission from Jack Re zne ck, Sr., MD.)

Genital HSV-2 in ection is more common in women (approximately 1 out o 5 women 14-49 years o age) than in men (approximately 1 out o 9 men 14-49 years o age). Transmission rom an in ected male to his emale partner is believed to be more likely than rom an in ected emale to her male partner.

FIGURE 128-3 Vulvar h rp s simp l x virus at th introitus showing small p unch d out ulc rs. (Re p rod uce d with p e rmissio n fro m the Ce nte rs for Dise ase Control and Pre ve ntion and Susan Lind sle y.)

h e r pe S SIMpLe X

FIGURE 128-4 R curr nt h rp s simp l x virus on th b uttocks o a woman in th ulc rativ stag . Wom n ar p ron to g tting b uttocks involv m nt owing to sl p ing with p artn rs that hav g nital involv m nt. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Orolabial herpes is the most prevalent orm o herpes in ection and o ten a ects children younger than 5 years o age (see Figure 121-7) although all age groups are a ected. The duration o the illness is 2 to 3 weeks, and oral shedding o virus may continue or as long as 23 days. 1 Herpetic whitlow is an intense pain ul in ection o the hand involving the terminal phalanx o one or more digits. In the United States, the estimated annual incidence is 2.4 cases per 100,000 persons. 3

ETIO LO GY AND PATHO PHYSIO LO GY • HSV belongs to the amily Herpesviridae and is a double-stranded DNA virus. • HSV exists as 2 separate types (types 1 and 2), which have a nities or di erent epithelia. 3 Ninety percent o HSV-2 in ections are genital, whereas 90% o those caused by HSV-1 are oral-labial.

FIGURE 128-5 Primary h rp s g ing ivostomatitis p r s nting with multip l ulc rs on th tong u and low r lip . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

FIGURE 128-6 Clos -up o r curr nt h rp s simp l x virus-1 (HSV-1) showing v sicl s on a r d b as at th v rmilion b ord r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• HSV enters through abraded skin or intact mucous membranes. Once in ected, the epithelial cells die, orming vesicles and creating multinucleated giant cells. • Retrograde transport into sensory ganglia leads to li elong latent in ection. 1 Reactivation o the virus may be triggered by immunode ciency, trauma, ever, and UV light. • Genital HSV in ection is usually transmitted through sexual contact. When it occurs in a preadolescent, the possibility o abuse must be considered. • Evidence indicates that 21.9% o all persons in the United States, 12 years or older, have serologic evidence o HSV-2 in ection, which is more commonly associated with genital in ections. 4 • As many as 90% o those in ected are unaware that they have herpes in ection and may unknowingly shed virus and transmit in ection. 5 • Primary genital herpes has an average incubation period o 4 days, ollowed by a prodrome o itching, burning, or erythema (Figure 128-8).

FIGURE 128-7 O rolab ial h rp s simp l x virus in an ad ult woman showing d ro o d b list rs (ulc r). (Re p ro d uce d with p e rmissio n fro m Richard P. Usatine , MD.)

607

PART 14 DERMATO LO GY

608

Ch a pt e r 128

FIGURE 128-9 H rp tic whitlow l sion on d istal ind x f ng r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIAGNO SIS FIGURE 128-8 Primary g nital h rp s in a 51-y ar-old woman with p romin nt ryth ma and v ry small v sicl s. Th woman was in a lot o p ain. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• With both types, systemic symptoms are common in primary disease and include ever, headache, malaise, abdominal pain, and myalgia. 6 Recurrences are usually less severe and shorter in duration than the initial outbreak. 1,6 • Maternal- etal transmission o HSV is associated with signi cant morbidity and mortality. Mani estations o neonatal HSV include localized in ection o the skin, eyes, and mouth, CNS disease, or disseminated multiple organ disease. The CDC and the American College o Obstetricians and Gynecologists recommend that cesarean delivery should be o ered as soon as possible to women who have active HSV lesions or, in those with a history o genital herpes, symptoms o vulvar pain, or burning at the time o delivery.

CLINICAL FEATURES • The diagnosis o HSV in ection may be made by clinical appearance. Many patients have systemic symptoms, including ever, headache, malaise, and myalgias. • Orolabial herpes typically takes the orm o pain ul vesicles and ulcerative erosions on the tongue, palate, gingiva, buccal mucosa, and lips (see Figures 128-5 to 128-7). • Genital herpes presents with multiple transient, pain ul vesicles that appear on the penis (see Figures 128-1 and 128-2), vulva

• Herpetic whitlow occurs as a complication o oral or genital HSV in ection and in medical personnel who have contact with oral secretions (Figures 128-9 and 128-10). • Toddlers and preschool children are susceptible to herpetic whitlow i they have herpes labialis and engage in thumb-sucking or nger-sucking behavior. • Like all HSV in ections, herpetic whitlow usually has a primary in ection, which may be ollowed by subsequent recurrences. The virus migrates to the peripheral ganglia and Schwann cells where it lies dormant. Recurrences observed in 20% to 50% o cases are usually milder and shorter in duration.

RISK FACTO RS • Multiple sexual partners • Female gender • Low socioeconomic status • HIV in ection

FIGURE 128-10 S v r ly p ain ul h rp tic whitlow on th thumb . (Re p rod uce d with p e rmission from Eric Kraus, MD.)

h e r pe S SIMpLe X

PART 14 DERMATO LO GY • I the herpes was acquired by sexual contact, screening should be perormed or other sexually transmitted diseases (STDs), such as syphilis and HIV. • Biopsy is usually unnecessary unless no in ectious etiology is ound or a genital lesion and a malignancy is suspected.

DIFFERENTIAL DIAGNO SIS • Syphilis produces a painless or mildly pain ul, indurated, clean-based ulcer (chancre) at the site o exposure. It is best to investigate or syphilis or coexisting syphilis in any patient presenting or the rst time with a genital ulcer o unproven etiology (see Chapter 218, Syphilis). • Chancroid produces a pain ul deep, undermined, purulent ulcer that may be associated with pain ul inguinal lymphadenitis (see Chapter 218, Syphilis). FIGURE 128-11 R curr nt h rp s simp l x virus on th b uttocks o a woman. Not th v sicl s and crusts in a unilat ral clust r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

(see Figure 128-3), buttocks (Figures 128-4 and 128-11), perineum, vagina or cervix, and tender inguinal lymphadenopathy. 6 The vesicles break down and become ulcers that develop crusts while these are healing. • Recurrences typically occur 2 to 3 times a year. The duration is shorter and less pain ul than in primary in ections. The lesions are o ten single and the vesicles heal completely by 8 to 10 days. • UV radiation in the orm o sunlight may trigger outbreaks. Another reason to use sun protection when outdoors triggers recurrence o orolabial HSV-1, an e ect which is not ully suppressed by acyclovir.

• Drug eruptions produce pruritic papules or blisters without associated viral symptoms (see Chapter 201, Cutaneous Drug Reactions). • Behçet disease produces ulcerative disease around the mouth and genitals, possibly be ore onset o sexual activity (Figure 128-12). • Acute paronychia which presents as a localized abscess in a nail old and is the main di erential diagnosis in the consideration o herpetic whitlow (see Chapter 192, Paronychia). • Felon—A red, pain ul in ection, usually bacterial, o the ngertip pulp. It is important to distinguish whitlow rom a elon (where the pulp space usually is tensely swollen) as incision and drainage o a elon is needed, but should be avoided in herpetic whitlow because it may lead to an unnecessary secondary bacterial in ection.

MANAGEMENT

LABO RATO RY STUDIES • The gold standard o diagnosis is viral isolation by tissue culture and polymerase chain reaction (PCR) testing. 2 ° The culture sensitivity rate is only 70% to 80% and depends on the stage at which the specimen is collected. The sensitivity is highest at rst in the vesicular stage and declines with ulceration and crusting. The tissue culture assay can be positive within 48 hours but may take longer. ° PCR is extremely sensitive (96%) and speci c (99%). PCR testing is generally used or cerebrospinal f uid (CSF) testing in suspected HSV encephalitis or meningitis. 2

NO NPHARMACO LO GIC Women with active primary or recurrent genital herpetic lesions at the onset o labor should deliver by cesarean section to lower the chance o neonatal HSV in ection. 2 SO R

• Older type-speci c HSV serologic assays that do not accurately distinguish HSV-1 rom HSV-2 antibody are still on the market. Both laboratory-based assays and point-o -care tests that provide results or HSV-2 antibodies rom capillary blood or serum with sensitivities o 80% to 98% are available. Because nearly all HSV-2 in ections are sexually acquired, the presence o type-speci c HSV-2 antibody implies anogenital in ection. Type-speci c HSV serologic assays might be useul in patients with recurrent symptoms and negative HSV cultures and an asymptomatic patient with a partner with genital herpes. Screening or HSV-1 and HSV-2 in the general population is not indicated. 2 • The Tzanck test and antigen detection tests have lower sensitivity rates than viral culture and should not be relied on or diagnosis. 2 • The CDC does not currently recommend routine type 2 HSV testing in someone with no symptoms suggestive o herpes in ection (ie, or the general population). 7

FIGURE 128-12 Young man with B hç t synd rom p r s nting with a p ainul p nil ulc r and ap hthous ulc rs in his mouth. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

609

PART 14 DERMATO LO GY

610

Ch a pt e r 128

TABLE 128-1 Dosag s o Tr atm nts or G nital H rp s In ction 2

Chro nic Sup p re ssive The rap y

Drug

Primary Infe ct io n Do sag e

Re curre nt Infe ct io n Do sag e

Acyclovir (Zovirax)

400 mg 3 tim s d aily or 7 to 10 d ays or 200 mg 5 tim s d aily

400 mg 3 tim s d aily or 5 d ays or 800 mg twic d aily or 5 d ays or 800 mg 3 tim s d aily or 2 d ays

400 mg twic d aily

Famciclovir (Famvir)

250 mg 3 tim s d aily or 10 d ays *

125 mg twic d aily or 5 d ays or 1 g twic d aily or 1 d ay or 500 mg onc , ollow d b y 250 mg twic d aily or 2 d ays

250 mg PO twic d aily

Valacyclovir (Valtr x)

1 g twic d aily or 10 d ays

500 mg twic d aily or 3 d ays or 1 g d aily or 5 d ays

500 mg to 1 g onc d aily

*

Famciclovir is not FDA-lab l d or this ind ication.

MEDICATIO NS Acyclovir is a guanosine analog that acts as a DNA chain terminator which, when incorporated, ends viral DNA replication. Valacyclovir is the l-valine ester prodrug o acyclovir that has enhanced absorption a ter oral administration and high oral bioavailability. Famciclovir is the oral orm o penciclovir, a purine analog similar to acyclovir. They must be administered early in the outbreak to be e ective, but are sa e and extremely well tolerated. 6 SO R Ge nital he rp e s • Antiviral therapy is recommended or an initial genital herpes outbreak. Table 128-1 shows the dosages or antiherpes drugs. Although systemic antiviral drugs can partially control the signs and symptoms o herpes episodes, they do not eradicate latent virus. • Acyclovir, amciclovir, and valacyclovir are equally e ective or episodic treatment o genital herpes, but amciclovir appears somewhat less e ective or suppression o viral shedding. 2 SO R B • E ective episodic treatment o herpes requires initiation o therapy during the prodrome period or within 1 day o lesion onset. Providing the patient with a prescription or the medication with instructions to initiate treatment immediately when symptoms begin improves e cacy. 2 SO R B • IV acyclovir therapy at 5 to 10 mg/ kg IV every 8 hours or 2 to 7 days ollowed by oral antiviral therapy to complete at least 10 days o total therapy should be provided or patients who have severe HSV disease or complications. 2 SO R C • HSV strains resistant to acyclovir have been detected in immunocompromised patients so that other antivirals (eg, amciclovir) need to be considered in these patients. SO R C • Topical medication or HSV in ection is generally not e ective. Topical penciclovir applied every 2 hours or 4 days, reduces clinical healing time by approximately 1 day. 1,2 • All patients with a rst episode o genital herpes should receive antiviral therapy as even with mild clinical mani estations initially, they can develop severe or prolonged symptoms. • Toxicity o these 3 antiviral drugs is rare, but in patients who are dehydrated or who have poor renal unction, the drug can crystallize in the renal tubules, leading to a reversible creatinine elevation or, rarely, acute tubular necrosis. Adverse e ects, usually mild, include nausea,

vomiting, rash, and headache. Lethargy, tremulousness, seizures, and delirium have been reported rarely in studies o renally impaired patients. 8 O ral he rp e s Table 128-2 provides an overview o treatments or herpes labialis. • In the treatment o primary orolabial herpes, oral acyclovir (200 mg 5 times daily or 5 days) accelerates healing by 1 day and can reduce the mean duration o pain by 36%. 9 SO R • The oral lesions in primary herpes gingivostomatitis can lead to poor oral intake especially in children (Figure 128-13) and the elderly. To prevent dehydration, the ollowing medications may be considered. Topical oral anesthetics such as 2% viscous lidocaine by prescription or 20% topical benzocaine OTC may be used to treat pain ul oral ulcers. SOR C A solution combining aluminum and magnesium hydroxide (liquid antacid) and 2% viscous lidocaine has been reported as help ul when swished and spit out several times a day as needed or pain. SOR C • Docosanol cream (Abreva) is available without prescription or oral herpes. One randomized controlled trial (RCT) o 743 patients with herpes labialis showed a aster healing time in patients treated with docosanol 10% cream compared with placebo cream (4.1 vs 4.8 days), as well as reduced duration o pain symptoms (2.2 vs 2.7 days). 10 More than 90% o patients in both groups healed completely within 10 days. 10 Treatment with docosanol cream, when applied 5 times per day and within 12 hours o episode onset, is sa e and somewhat e ective. 11

PREVENTIO N • Barrier protection using latex condoms is recommended to minimize exposure to genital HSV in ections (see “Patient Education” below). • Suppressive therapy with antiviral drugs reduces the requency o genital herpes recurrences by 70% to 80% in patients with requent recurrences. 2 SO R Traditionally this is reserved or use in patients who have more than 4 to 6 outbreaks per year (see Table 128-1). • Short-term prophylactic therapy with acyclovir or orolabial HSV may be used in patients who anticipate intense exposure to UV light. Early treatment o recurrent orolabial HSV in ection with amciclovir 250 mg 3 times daily or 5 days can markedly decrease the size and duration o lesions. 12 SO R

PART 14 DERMATO LO GY

h e r pe S SIMpLe X

611

TABLE 128-2 Tr atm nts or H rp s Lab ialis

Drug

Evid e nce Rat ing *

Do se o r Do sag e

Re fe re nce s

Ep isod ic oral tre atme nt for re curre nce s † Acyclovir (Zovirax)

200 mg 5 tim s p r d ay or 400 mg 3 tim s p r d ay or 5 d ays

A

13, 14

Famciclovir (Famvir)

1500 mg onc

B

15

Valacyclovir (Valtr x)

2 g twic

B

16

or 1 d ay

or 1 d ay

Ep isod ic top ical tre atme nt for re curre nce s † Acyclovir cr am

Ap p ly 5 tim s p r d ay or 4 d ays

B

19

Docosanol cr am (Ab r va)

Ap p ly 5 tim s p r d ay until h al d

B

18

P nciclovir cr am (D navir)

Ap p ly v ry 2 hours whil awak

B

17

or 4 d ays

Tre atme nt to p re ve nt re curre nce s Acyclovir

400 mg twic p r d ay (ong oing )

A

14, 20

Valacyclovir

500 mg onc p r d ay (ong oing )

B

21

*

A, consist nt, g ood -q uality, p ati nt-ori nt d vid nc ; B, inconsist nt or limit d -q uality, p ati nt-ori nt d vid nc ; C, cons nsus, d is as ori nt d vid nc , usual p ractic , xp rt op inion, or cas s ri s. † Most ctiv i tr atm nt is start d at th ons t o symp toms. Data rom Usatin RP, Tinitig an R. Nong nital h rp s simp l x virus. Am Fam Physician. 2010;82(9):1075-1082.

FO LLO W-UP The patient should return or ollow-up i pain is uncontrolled or superinection is suspected. The patient should be periodically evaluated or the need or suppressive therapy based on the number o recurrences per year.

PATIENT EDUCATIO N Following are measures to prevent genital HSV in ection: • Abstain rom sexual activity or limit number o sexual partners to prevent exposure to the disease.

• Use condoms to protect against transmission, but this is not oolproo as ulcers can occur on areas not covered by condoms. • Prevent autoinoculation by patting dry a ected areas, not rubbing with towel. • Studies show that patients may shed virus when they are otherwise asymptomatic. A link between HSV genital ulcer disease and sexual transmission o HIV has been established. Sa er sex practices should be strongly encouraged to prevent transmission o HSV to others and acquiring HIV by the patient. PATIENT RESO URCES

• National Institute of Allergy and Infectious Diseases. Genital Herpes—http:/ / www.niaid.nih.gov/ topics/ genitalherpes/ Pages/ default.aspx. • Centers for Disease Control and Prevention. Genital Herpes–CDC Fact Sheet—http:/ / www.cdc.gov/ std/ Herpes/ STDFact-Herpes.htm. • Skinsight. Herpetic Whitlow–Information for Adults—http:/ / www .skinsight.com/ adult/ herpeticWhitlow.htm. PRO VIDER RESO URCES

• Medscape. Herpes Simplex—http:/ / emedicine.medscape .com/ article/ 218580. • Medscape. Dermatologic Manifestations of Herpes Simplex—http:/ / emedicine.medscape.com/ article/ 1132351. • Usatine RP, Tinitigan R. Nongenital HSV. Am Fam Physician. 2010;82:1075-1082—http:/ / www.aafp.org/ afp/ 2010/ 1101/ p1075.html. FIGURE 128-13 Primary h rp s g ing ivostomatitis in a 4-y ar-old g irl. Not th clust r o ulc rs insid th low r lip typ ical o h rp s simp l x virus. Th pati nt also had involv m nt o h r g ing iva, which w r swoll n and pain ul. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Emmert DH. Treatment o common cutaneous HSV in ections. Am Fam Physician. 2000;61:1697-1704—http:/ / www.aafp.org/ afp/ 20000315/ 1697.html.

PART 14 DERMATO LO GY

612

CHAPTe R 128

1. Whitley RJ, Kimberlin DW, Roizman B. Herpes simplex viruses. Clin Infect Dis. 1998;26:541-555.

13. Amir J, Harel L, Smetana Z, Varsano I. Treatment o herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study. BMJ. 1997;314(7097):1800-1803.

2. Centers or Disease Control and Prevention. 2010 Guidelines for Treatment of Sexually Transmitted Diseases. http:/ / www.cdc.gov/ std/ treatment/ 2010/ STD-Treatment-2010-RR5912.pd . Accessed December 1, 2011.

14. Glenny AM, Fernandez Maule nch LM, Pavitt S, Walsh T. Interventions or the prevention and treatment o herpes simplex virus in patients being treated or cancer. Cochrane Database Syst Rev. 2009;(1):CD006706.

3. Gill MJ, Arlette J, Buchan K. Herpes simplex virus in ection o the hand. A pro le o 79 cases. Am J Med. 1988;84:89-93.

15. Spruance SL, Bodsworth N, Resnick H, et al. Single-dose, patientinitiated amciclovir: a randomized, double-blind, placebo-controlled trial or episodic treatment o herpes labialis. JAmAcad Dermatol. 2006;55(1):47-53.

REFERENCES

4. Fleming DT, McQuillan GM, Johnson RE, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med. 1997;337:1105-1111. 5. Mertz GJ. Epidemiology o genital herpes in ections. Infect Dis Clin North Am. 1993;7:825-839. 6. Clark JL, Tatum NO, Noble SL. Management o genital herpes. Am Fam Physician. 1995;51:175-182, 187-188. 7. Centers or Disease Control and Prevention (CDC). Seroprevalence o herpes simplex virus type 2 among persons aged 14-49 years— United States, 2005-2008. MMWR Morb MortalWkly Rep. 2010;59(15):456-459. 8. Emmert DH. Treatment o common cutaneous herpes simplex virus in ections. Am Fam Physician. 2000;61(6):1697-1706, 1708. 9. Spruance SL, Stewart JC, Rowe NH, et al. Treatment o recurrent herpes simplex labialis with oral acyclovir. J Infect Dis. 1990;161:185-190. 10. Sacks SL, Thisted RA, Jones TM, et al. Docosanol 10% Cream Study Group. Clinical e cacy o topical docosanol 10% cream or herpes simplex labialis: a multi-center, randomized, placebo-controlled trial. JAmAcad Dermatol. 2001;45(2):222-230. 11. Usatine RP, Tinitigan R. Nongenital herpes simplex virus. Am Fam Physician. 2010;82(9):1075-1082. 12. Spruance SL, Rowe NH, Raborn GW, et al. Perioral amciclovir in the treatment o experimental ultraviolet radiation-induced herpes simplex labialis: a double-blind, dose-ranging, placebo-controlled, multicenter trial. J Infect Dis. 1999;179:303-310.

16. Hull C, McKeough M, Sebastian K, Kriesel J, Spruance S. Valacyclovir and topical clobetasol gel or the episodic treatment o herpes labialis: a patient-initiated, double-blind, placebo-controlled pilot trial. J Eur Acad DermatolVenereol. 2009;23(3):263-267. 17. Spruance SL, Rea TL, Thoming C, Tucker R, Saltzman R, Boon R. Penciclovir cream or the treatment o herpes simplex labialis. A randomized, multicenter, double-blind, placebo-controlled trial. Topical Penciclovir Collaborative Study Group. JAMA. 1997;277(17):1374-1379. 18. Sacks SL, Thisted RA, Jones TM, et al.; Docosanol 10% Cream Study Group. Clinical e icacy o topical docosanol 10% cream or herpes simplex labialis: a multi-center, randomized, placebocontrolled trial. JAm Acad Dermatol. 2001;45(2):222-230. 19. Spruance SL, Nett R, Marbury T, Wol R, Johnson J, Spaulding T. Acyclovir cream or treatment o herpes simplex labialis: results o two randomized, double-blind, vehicle-controlled, multicenter clinical trials. Antimicrob Agents Chemother. 2002;46(7):2238-2243. 20. Rooney JF, Straus SE, Mannix ML, et al. Oral acyclovir to suppress requently recurrent herpes labialis. A double-blind, placebo-controlled trial. Ann Intern Med. 1993;118(4):268-272. 21. Baker D, Eisen D. Valacyclovir or prevention o recurrent herpes labialis: 2 double-blind, placebo-controlled studies. Cutis. 2003;71(3):239-242.

MO LLUSCUM CO NTAGIO SUM

PART 14 DERMATO LO GY

129 MO LLUSCUM CO NTAGIO SUM E.J. Maye aux Jr, MD

PATIENT STO RIES An 18-year-old young man came to the o ce because o an outbreak o bumps on his lower abdomen and groin area or a couple o weeks (Figure 129-1). He admits to being sexually active and has recent partners whom he does not know well. He is diagnosed with molluscum contagiosum and elects treatment with cryotherapy, which was per ormed using liquid nitrogen in a Cryogun (Figure 129-2). The molluscum disappeared without scarring or hypopigmentation. FIGURE 129-2 C yoth ap y o th p ati nt shown in Fig ure 129-1. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

INTRO DUCTIO N Molluscum contagiosum is a viral skin in ection that produces pearly papules that o ten have a central umbilication. It is seen most commonly in children, but can also be transmitted sexually among adults.

EPIDEMIO LO GY • Molluscum contagiosum in ection has been reported worldwide. An Australian seroepidemiology study ound a seropositivity rate o 23%. 1 • Up to 5% o children in the United States have clinical evidence o molluscum contagiosum in ection. 2 It is a common, nonsexually transmitted condition in children. • In adults, molluscum occurs most commonly in the genital region (Figure 129-1 to 129-4). In this case, it is considered a sexually transmitted disease. Subclinical cases may occur and may be more common in the general community than is generally recognized.

FIGURE 129-1 Molluscum contag iosum on th low ab d om n o a young man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• The number o cases in US adults increased in the 1980s, probably as a result o the HIV/ AIDS epidemic. Since the introduction o highly active antiretroviral therapy (HAART), the number o molluscum contagiosum cases in HIV/ AIDS patients has decreased substantially. 3 However, the prevalence o molluscum contagiosum in patients who are HIV-positive may still be as high as 5% to 18% (Figures 129-5 and 129-6). 4,5

ETIO LO GY AND PATHO PHYSIO LO GY • Molluscum contagiosum is a benign condition that is o ten transmitted through close contact in children and through sexual contact in adults. • It is a large DNA virus o the Poxviridae amily o poxvirus. It is related to the orthopoxviruses (variola, vaccinia, smallpox, and monkeypox viruses).

FIGURE 129-3 Molluscum contag iosum on and a ound th p nis. His g i li nd has th s on th b uttocks. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

613

614

PART 14 DERMATO LO GY

Ch a pt e r 129

FIGURE 129-6 Giant and wid sp ad molluscum on th ac p omp t d an HIV t st that tu n d out p ositiv . (Re p rod uce d with p e rmission from Ghosh SK, Band yop ad hyay D, Mand al RK. Multip le facial b ump s with we ig ht loss. J Fam P act. 2010 De c;59(12):703-705.)

FIGURE 129-4 Molluscum contag iosum und th y with c nt al umb ilication. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIAGNO SIS CLINICAL FEATURES

• Molluscum replicates in the cytoplasm o epithelial cells. It causes a chronic localized skin in ection consisting o dome-shaped pearly papules on the skin. Like most o the viruses in the poxvirus amily, molluscum is spread by direct skin-to-skin contact. It can also spread by autoinoculation when scratching, touching, or treating lesions. • Any one single lesion is usually present or approximately 2 months, but autoinoculation o ten causes continuous crops o lesions.

RISK FACTO RS • Molluscum contagiosum may be more common in patients with atopic dermatitis. 2 • The disease also may be spread by participation in contact sports. 2 • It is also associated with immunode cient states such as in HIV in ection (see Figures 129-5 and 129-6) and with immunosuppressive drug treatment.

• Firm, multiple, 2- to 5-mm dome-shaped papules are seen with a characteristic shiny sur ace and umbilicated center (Figure 129-7). Not all the papules have a central umbilication, so it helps to take a moment and look or a papule that has this characteristic morphology. I all eatures point to molluscum and no single lesion has central umbilication, do not rule out molluscum as the diagnosis. • The lesions range in color rom pearly white, to f esh-colored, to pink or yellow. • Pruritus may be present or absent. TYPICAL DISTRIBUTIO N The lesions may appear anywhere on the body except the palms and soles. The number o lesions may be greater in an HIV-in ected individual. In adults, they are o ten ound around the genitalia, inguinal area, buttocks, or inner thighs (see Figure 129-3). In children, the lesions are o ten on the trunk or ace. LABO RATO RY TESTING • Laboratory testing is not typically indicated. • Sexually active adolescents and adults with genital lesions should be evaluated or other sexually transmitted diseases, including or HIV in ection.

FIGURE 129-5 Molluscum contag iosum on th ac o a woman with human immunod f ci ncy vi us. Not th la g molluscum on th scalp . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 129-7 Clos -up o a molluscum l sion showing a d om -shap d p a ly p ap ul with a cha act istic umb ilicat d c nt . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

MO LLUSCUM CO Nt a GIO SUM

BIO PSY I con rmation is needed, smears o the caseous material expressed rom the lesions can be examined directly under the microscope looking or molluscum bodies (enlarged keratinocytes that are engorged with viral inclusion bodies). Hematoxylin and eosin (H&E) staining rom a shave biopsy usually reveals keratinocytes that contain eosinophilic cytoplasmic inclusion bodies. 5 I a single lesion is suspicious or basal cell carcinoma (BCC), per orm a shave biopsy.

DIFFERENTIAL DIAGNO SIS • Scabies is caused by Sarcoptes scabiei mite and can be transmitted through close or sexual contact. Early lesions are f esh-colored to red papules that produce signi cant itching. The itching and excoriations are greater than seen with molluscum. Scabies lesions also usually appear in the nger webs, ventral wrist old, and underneath the breasts in women (see Chapter 141, Scabies). • Dermato bromas—Firm to hard nodules ranging in color rom f esh to black that typically dimple downward when compressed laterally. Usually do not seen in crops as in molluscum. These nodules are deeper in the dermis and do not appear stuck on like molluscum (see Chapter 158, Dermato broma). • BCCs are also pearly and raised. Usually not seen in crops as in molluscum. I a single lesion could be a BCC or molluscum, a biopsy is warranted (see Chapter 168, Basal Cell Carcinoma). • Genital warts may be f at and grossly resemble molluscum but they lack the characteristic shiny sur ace and central umbilication (see Chapter 132, Genital Warts).

MANAGEMENT NO NPHARMACO LO GIC • Treatment o nongenital lesions is usually not medically necessary as the in ection is usually sel -limited and spontaneously resolves a ter a ew months. Treatment may be per ormed in an attempt to decrease autoinoculation. Patients and parents o children o ten want treatment or cosmetic reasons and when watch ul waiting ails. • A 2009 Cochrane Database systematic review investigated the e cacy o treatments or nongenital molluscum contagiosum in healthy individuals and ound insu cient evidence to conclude that any treatment was de nitively e ective. 6 SO R • In the HIV-in ected patient, molluscum may resolve a ter control o HIV disease with HAART. 3 SO R B

FIGURE 129-8 Blist s that o m d th n xt d ay a t t ating molluscum contag iosum with cantha id in. Th b list s a not always so la g b ut a sup p os d to o m as th cantha id in is d iv d om th b list b tl . Th b list ing h lp s ad icat th molluscum. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

shown not to have systemic or toxic e ects in children. 9 In one study, 23 children ranging in age rom 1 to 9 years with molluscum contagiosum in ection were randomized to either imiquimod cream 5% (12 patients) or vehicle (11 patients). Parents applied the study drug to the patient’s lesions 3 times a week or 12 weeks. Complete clearance at week 12 was noted in 33.3% (4/ 12) o imiquimod patients and in 9.1% (1/ 11) o vehicle patients. 10 • Tretinoin cream11 0.1% or gel 0.025% applied daily are commonly used but not FDA approved or this indication. SO R B • Cantharidin12 and trichloroacetic acid13 are topical chemicals that can be applied by the physician in the o ce (Figure 129-8). SO R B Many children will ear treatment with a curette or with any orm o cryotherapy. SURGICAL Curettage and cryotherapy are physical methods used to eradicate molluscum. 14,15 SO R B CO MPLEMENTARY AND ALTERNATIVE THERAPY ZymaDerm is a nonprescription, topical, homeopathic agent that is marketed or the treatment o molluscum contagiosum, but no published studies have evaluated its e cacy or sa ety.

PREVENTIO N

MEDICATIO NS

• Molluscum contagiosum is a common childhood disease.

• Podophyllotoxin 0.5% (Condylox) is an antimitotic agent that is indicated or the treatment o genital warts. The e cacy o podophyllotoxin was established in a randomized trial o lesions located on the thighs or genitalia. SO R B Local erythema, burning, pruritus, inf ammation, and erosions can occur with the use o this agent. The sa ety and e cacy o this drug has not been established in young children. 7

• Limiting sexual exposure or number o sexual contact may help prevent exposure.

• Topical imiquimod 5% (Aldara) cream has been shown (not FDA approved) to be better than vehicle alone to treat molluscum. 8,9 SO R B It can be well tolerated, although application site irritation can be uncom ortable and lead to discontinuation o therapy. It has been

• Genital lesions should be treated to prevent spread by sexual contact.

PRO GNO SIS In immunocompetent patients, lesions usually spontaneously resolve within several months. In a minority o cases, disease persists or a ew years. 16

615

PART 14 DERMATO LO GY

616

FO LLO W-UP Have patients watch or complications that may include irritation, inf ammation, and secondary in ections. Lesions on eyelids may be associated with ollicular or papillary conjunctivitis, so eye irritation should prompt a visit to an eye care specialist.

PATIENT EDUCATIO N Instruct patients to avoid scratching to prevent autoinoculation. PATIENT RESO URCES

• Centers for Disease Control and Prevention. Molluscum (Molluscum Contagiosum)—http:/ / www.cdc.gov/ ncidod/ dvrd/ molluscum/ . • Pubmed Health. Molluscum Contagiosum—http:/ / www.ncbi.nlm .nih.gov/ pubmedhealth/ PMH0001829/ . • American Academy of Dermatology. Molluscum Contagiosum— http:/ / www.aad.org/ skin-conditions/ dermatology-a-to-z/ molluscum-contagiosum.

CHAPTe r 129

(HAART) in patients with AIDS. Eur J Dermatol. 1999;9(3): 211-213. 4. Schwartz JJ, Myskowski PL. Molluscum contagiosum in patients with human immunode ciency virus in ection. JAmAcad Dermatol. 1992;27(4):583-588. 5. Cotell SL, Roholt NS. Images in clinical medicine. Molluscum contagiosum in a patient with the acquired immunode ciency syndrome. N Engl J Med. 1998;338(13):888. 6. van der Wouden JC, van der Sande R, van Suijlekom-Smit LW, et al. Interventions or cutaneous molluscum contagiosum. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD004767. 7. Syed TA, Lundin S, Ahmad M. Topical 0.3% and 0.5% podophyllotoxin cream or sel -treatment o molluscum contagiosum in males. A placebo-controlled, double-blind study. Dermatology. 1994;189(1):65-68. 8. Hengge UR, Esser S, Schultewolter T, et al. Sel -administered topical 5% imiquimod or the treatment o common warts and molluscum contagiosum. Br J Dermatol. 2000;143(5):1026-1031. 9. Barba AR, Kapoor S, Berman B. An open label sa ety study o topical imiquimod 5% cream in the treatment o Molluscum contagiosum in children. Dermatol Online J. 2001;7(1):20.

• eMedicine Health. Molluscum Contagiosum—http:/ / www .emedicinehealth.com/ molluscum_contagiosum/ article_em.htm.

10. Theos AU, Cummins R, Silverberg NB, Paller AS. E ectiveness o imiquimod cream 5% or treating childhood molluscum contagiosum in a double-blind, randomized pilot trial. Cutis. 2004;74 (2):134-138, 141-142.

• MedlinePlus. Molluscum Contagiosum—http:/ / www.nlm.nih .gov/ medlineplus/ ency/ article/ 000826.htm.

11. Papa CM, Berger RS. Venereal herpes-like molluscum contagiosum: treatment with tretinoin. Cutis. 1976;18(4):537-540.

PRO VIDER RESO URCES

12. Silverberg NB, Sidbury R, Mancini AJ. Childhood molluscum contagiosum: experience with cantharidin therapy in 300 patients. JAm Acad Dermatol. 2000;43(3):503-507.

• eMedicine. Molluscum Contagiosum—http:/ / emedicine.medscape .com/ article/ 910570. • Centers or Disease Control and Prevention. Clinical Information: Molluscum Contagiosum—http:/ / www.cdc.gov/ ncidod/ dvrd/ molluscum/ clinical_overview.htm.

REFERENCES 1. Konya J, Thompson CH. Molluscum contagiosum virus: antibody responses in persons with clinical lesions and seroepidemiology in a representative Australian population. J Infect Dis. 1999;179(3):701-704. 2. Dohil MA, Lin P, Lee J, et al. The epidemiology o molluscum contagiosum in children. JAmAcad Dermatol. 2006;54(1):47-54. 3. Calista D, Boschini A, Landi G. Resolution o disseminated molluscum contagiosum with highly active anti-retroviral therapy

13. Yoshinaga IG, Conrado LA, Schainberg SC, Grinblat M. Recalcitrant molluscum contagiosum in a patient with AIDS: combined treatment with CO(2) laser, trichloroacetic acid, and pulsed dye laser. Lasers Surg Med. 2000;27(4):291-294. 14. Hanna D, Hatami A, Powell J, et al. A prospective randomized trial comparing the e cacy and adverse e ects o our recognized treatments o molluscum contagiosum in children. Pediatr Dermatol. 2006;23(6):574-579. 15. Wetmore SJ. Cryosurgery or common skin lesions. Treatment in amily physicians’ o ces. Can Fam Physician. 1999;45:964-974. 16. Lee R, Schwartz RA. Pediatric molluscum contagiosum: ref ections on the last challenging poxvirus in ection, part 1. Cutis. 2010;86(5):230-236.

PART 14 DERMATO LO GY

CO MMO N WARTS

130 CO MMO N WARTS E.J. Maye aux Jr, MD

PATIENT STO RY A young adult presents with a verrucous growth under the eye or 3 months. He does not like the way it looks and he wants it o as soon as possible. Based on the verrucous appearance the physician believed that this growth was nothing more than a common wart (Figure 130-1). Treatment options were discussed with the patient and it was decided to shave the growth o a ter providing local anesthesia. The specimen was sent to pathology and the nal diagnosis was verruca vulgaris (common wart).

INTRO DUCTIO N Human papillomaviruses (HPVs) are DNA viruses that in ect skin and mucous membranes. In ection is usually con ned to the epidermis and does not result in disseminated systemic in ection. The most common clinical mani estation o these viruses is warts (verrucae). There are more than 100 distinct HPV subtypes based on DNA testing. Some tend to in ect speci c body sites or types o epithelium. Some HPV types have a potential to cause malignant change but trans ormation is rare on keratinized skin.

FIGURE 130-2 Many common warts on th hand o an HIV-n g ativ young ad ult. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

EPIDEMIO LO GY • Nongenital cutaneous warts are widespread worldwide and are more common in children, with a peak incidence in the teenage years and a sharp decline therea ter. 1 • They are most commonly caused by HPV types 1 to 5, 7, 27, 29. 1

SYNO NYMS HPVs are also known as verrucae, verruca vulgaris, or common warts.

• Common warts account or approximately 70% o nongenital cutaneous warts. 2 • Common warts occur most commonly in children and young adults (Figures 130-1 and 130-2). 3

ETIO LO GY AND PATHO PHYSIO LO GY • In ection with HPV occurs by skin-to-skin contact. It starts with a break in the integrity o the epithelium caused by maceration or trauma that allows the virus to in ect the basal layers. • Warts may in ect the skin on opposing digits causing “kissing warts” (Figure 130-3). • Individuals with subclinical in ection may serve as a reservoir or HPVs. • An incubation period ollowing inoculation lasts or approximately 2 to 6 months.

RISK FACTO RS • Young age1 • Disruption to the normal epithelial barrier • More common among meat handlers • Atopic dermatitis FIGURE 130-1 Common wart und r th y o a young ad ult. Th g rowth was r mov d with a shav b io sy and th atholog y show d v rruca vulg aris. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Nail biters more commonly have multiple periungual warts • Conditions that decrease cell-mediated immunity such as HIV (Figure 130-4) and immunosuppressant drugs (Figure 130-5)

617

PART 14 DERMATO LO GY

618

Ch a pt e r 130

FIGURE 130-5 Bio sy- rov n warts o n th n ck and ch st o a wo man on azathio rin a t r a r nal trans lantation. Human a illomavirus l sions can roli rat as a r sult o immunosu r ssiv m d ications. This ati nt is also b ing monitor d or sq uamous c ll carcinoma, as this is a mor sig nif cant risk in osttrans lantation ati nts. (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

TYPICAL DISTRIBUTIO N

FIGURE 130-3 Warts may in ct th skin on o osing d ig its causing “kissing warts.” (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Common anatomic locations include the dorsum o the hand, between the ngers, f exor sur aces, and adjacent to the nails (periungual) (see Figures 130-1 and 130-2). LABO RATO RY TESTING

DIAGNO SIS

• HPV testing is not use ul or this condition. 4

CLINICAL FEATURES

• HIV testing may be use ul i the warts are severe and there are risk actors present (see Figure 130-4).

• The diagnosis o warts is based on clinical appearance. The wart will obscure normal skin markings.

BIO PSY

• Common warts are well demarcated, rough, hard papules with irregular papillary sur ace. They are usually asymptomatic unless located on a pressure point.

Paring the sur ace with a surgical blade may expose punctate hemorrhagic capillaries, or black dots, which are thrombosed capillaries. I the diagnosis is in doubt, a shave biopsy is indicated to con rm the diagnosis.

• Warts may orm cylindrical o li orm projections (Figure 130-6).

FIGURE 130-4 Larg wart on th f th d ig it o an HIV- ositiv man. Th wart was b io si d to mak sur it had not b com sq uamous c ll carcinoma. Th most ctiv tr atm nt so ar is cryoth ra y b ut th wart has still not ully r solv d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 130-6 Fili orm warts ar id ntif d b y th ir multi l roj ctions as o os d to a unif d a ul . This wart was on th ac o an ld rly woman and was r mov d b y shav xcision and s nt or atholog y. It was rov n to b a wart and not sq uamous c ll carcinoma. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

CO MMO N Wa r t S

DIFFERENTIAL DIAGNO SIS • Seborrheic keratosis are usually more darkly pigmented, have a stuckon appearance, and “horn cysts” may be visible on close examination. They also have a wide distribution on the body (see Chapter 156, Seborrheic Keratosis). Typical dermoscopic patterns include comedolike openings and milia-like cysts (see Appendix C, Dermoscopy) • Acrochordon (skin tags) are pedunculated f esh-colored papules that are more common in obese persons. They lack the sur ace roughness o common warts. Fili orm warts also may be pedunculated, but typically have a characteristic li orm appearance (see Chapter 155, Skin Tag). • Squamous cell carcinoma (SCC) should be considered when lesions have irregular growth, pigmentation, ulceration, or resist therapy, particularly in sun-exposed areas and in immunosuppressed patients (see Chapter 169, Squamous Cell Carcinoma). The patient in Figure 130-7 had a wart that was not going away and a biopsy demonstrated SCC in situ with in an HPV-induced lesion.

FIGURE 130-8 A n w g rowth on th l g o an old r woman turn d out to b a wart a t r it was shav d o and s nt to atholog y. Th clinician was conc rn d that it could hav b n a k ratoacanthoma b as d on th c ntral k ratin cor . (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

Observational studies show that one-hal o cutaneous warts resolve spontaneously within 1 year, and about two-thirds within 2 years. 6

• Amelanotic melanoma—Although rare, lesions that are treatment resistant or atypical should be monitored closely or biopsied to establish the diagnosis (see Chapter 170, Melanoma).

• Treatment does not decrease transmissibility o the virus. 7

• Early warts may appear similar to actinic keratosis in sun-exposed areas (see Chapter 164, Actinic Keratosis and Bowen Disease)

MEDICATIO NS

• Advanced warts may appear similar to a keratoacanthoma to casual inspection. The characteristic ndings o the keratoacanthoma and biopsy will separate the 2 conditions (Figure 130-8) (see Chapter 165, Keratoacanthoma).

• Therapies or common warts do not speci cally treat the HPV virus. They work by destruction o virus-containing skin while preserving uninvolved tissue. This usually exposes the blood and its immune cells to the virus, which may promote an immune response against the virus. • The least-pain ul methods should be used rst, especially in children.

MANAGEMENT NO NPHARMACO LO GIC • Because spontaneous regression occurs in two-thirds o warts within 2 years, observation without treatment is always an option. In 17 trials, the average reported cure rate was 30% within 10 weeks. 5

SO R C

• A Cochrane review ound that there is a considerable lack o evidence on which to base the rational use o the local treatments or common warts. 5 The trials are highly variable in method and quality. There is evidence that simple topical treatments containing salicylic acid have a therapeutic e ect. 5 SO R There is less evidence or the e cacy o cryotherapy and no convincing evidence that it is any more e ective than simple topical treatments. • Seventeen percent salicylic acid is a use ul rst-line agent, especially or thick or multiple warts. 5 SOR It is sa e in children. Combined results rom 5 randomized controlled trials (RCTs) showed a 73% cure rate with 6 to 12 weeks o salicylic acid treatment, compared with a 48% cure rate with placebo (number needed to treat [NNT] = 4). 5 A number o preparations are available without a prescription. Topical 17% salicylic acid is applied overnight and is now the most commonly used orm or this type o wart. Soak the wart area with warm water or 5 minutes, then gently le down any thick skin with a pumice stone or emery board. The salicylic acid product should be applied to the wart. Repeat the rst 2 steps daily with liquid or gel preparations, or every other day with the patch. Tape may be used to cover the wart a ter application o salicylic acid liquid. Repeat treatment until the wart has cleared, or or up to 12 weeks. Discontinue the treatment i severe redness or pain occurs in the treated area. Do not use salicylic acid on the ace because o an increased risk o hypopigmentation. 1

FIGURE 130-7 Sq uamous c ll carcinoma in situ that start d rom a human a illomavirus- ositiv l sion. Wh n cryoth ra y is not working on what a ars to b a wart, consid r r orming a b io sy. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Forty percent salicylic acid plasters (Mediplast) are available over the counter or larger and thicker warts. The plasters are cut to t and then applied a ew millimeters beyond the wart or 48 hours.

619

620

PART 14 DERMATO LO GY

FIGURE 130-9 Cand id a antig n is b ing inj ct d into a clust r o warts on th kn o a t nag b oy. His warts d id not r s ond to multi l th ra i s, includ ing to ical salicylic acid and cryoth ra y. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Then the patch is removed; the wart pared down with a nail ile, pumice stone, or scalpel; and the process repeated as needed. • Imiquimod 5% is an expensive topical immunomodulator that is indicated or treatment o anogenital warts but is also used on nongenital warts. 8-10 SO R B It is nonscarring and painless, although local irritation is common. Debriding heavily keratinized warts may enhance penetration o the medication. The cream is applied in a thin layer to the lesions 3 times a week (every other night) and covered with an adhesive bandage or tape. The medication is removed with soap and water in the morning. It can also be used as adjunctive therapy. A lower concentration o imiquimod (3.75% cream) is also available, but data or common warts is lacking. • Intralesional injections with Candida antigen induces a localized, cellmediated, and HPV-speci c response that may target the injected wart as well as more distant warts (Figure 130-9). This method has moderate e ectiveness (60% cure rates) or treatment o recalcitrant warts in patients with a positive skin antigen pretest. 1 SO R B The Candida antigen must be diluted be ore used (see Table 131-1). Inject 0.1 to 0.3 mL into the largest warts using a 30-gauge needle and up to 1 mL per treatment. Warn the patient to expect itching in the area, burning, or peeling. Repeat every 4 weeks, up to 3 treatments or until warts are gone.

Ch a pt e r 130

FIGURE 130-10 Cantharid in is b ing a li d to riung ual warts. Not th us o th wood n stick o a cotton-ti d a licator. I th cotton ti is us d , th cantharid in stays within th cotton and th a lication is insu f ci nt. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Intralesional injection with bleomycin can be considered or treatment o recalcitrant warts, although the e ectiveness is unproven. 1 SO R B • Early open-label, uncontrolled studies indicate cimetidine might be use ul in treating warts. However, 3 placebo-controlled, double-blind studies and 2 open-label comparative trials demonstrate that its e cacy is equal to placebo. 11 SO R SURGICAL • Cryotherapy, most commonly with liquid nitrogen, is use ul but is somewhat pain ul or younger children. 5 SO R B Chemical cryogens are now available over the counter but are not as cold or e ective as liquid nitrogen. Most trials comparing cryotherapy with salicylic acid ound similar e ectiveness, with overall cure rates o 50% to 70% a ter 3 or 4 treatments. 1 Aggressive cryotherapy (10-30 seconds) is more e ective than less-aggressive cryotherapy, but may increase complications. 1 SO R B Anesthesia is usually unnecessary but may be achieved with 1% lidocaine or eutectic mixture o local anesthetics (EMLA) cream. Liquid nitrogen is applied or 10 to 20 seconds via a Cryogun or a cotton swab so that the reeze ball extends 2 mm beyond the lesion (Figure 130-11). Two reeze cycles may

• Photodynamic therapy with aminolevulinic acid plus topical salicylic acid is a moderately e ective option or treatment o recalcitrant warts. 1 SO R B Although it is likely to be bene cial, it is expensive and o ten requires re erral. • Cantharidin 0.7% is an extract o the blister beetle that is applied to the wart, a ter which blistering occurs on the ollowing day. It may be used in resistant cases. It is also use ul in young children because application is painless in the o ce. However, pain ul blisters o ten occur within a day a ter application. Be care ul not to overtreat with cantharidin because the blistering can be quite severe. Care ully apply to multiple lesions using the wooden end o a cotton-tipped applicator (Figure 130-10). SO R C • Contact immunotherapy using dinitrochlorobenzene, squaric acid dibutylester, and diphenylcyclopropenone may be applied to the skin to sensitize the patient and then to the lesion to induce an immune response. SO R C

FIGURE 130-11 Cryoth ra y showing an ad q uat r zon (halo) around th wart. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

CO MMO N Wa r t S

• Simple excision is used or small or li orm warts (see Figures 130-1 and 130-7). The area is injected with lidocaine and the wart is excised with sharp scissors or a scalpel blade. SO R C • Pulsed-dye laser can be considered or treatment o recalcitrant warts, although the e ectiveness is unproven. 1 SO R B CO MPLEMENTARY AND ALTERNATIVE THERAPY Although preliminary studies were promising, duct tape is o uncertain e cacy or wart treatment. 1 A randomized controlled trial in adults showed it to be no better than moleskin and both groups only had a 21% to 22% success rate. 13 SO R B FIGURE 130-12 Ring wart that r sult d rom inad q uat cryoth ra y o a common wart. (Re p ro d uce d with p e rmission fro m Richard P. Usatine , MD.)

PREVENTIO N improve resolution, but it is better to under reeze than over reeze as over reezing may lead to permanent scarring or hypopigmentation. Best results o cryotherapy can be achieved when the patient is treated every 2 or 3 weeks. There is no therapeutic bene t beyond 3 months. 1 SO R B Because HPV can survive in liquid nitrogen, cotton swabs and residual liquid nitrogen should be properly discarded to avoid spreading the virus to other patients or contaminating the liquid nitrogen reservoir. 12 A ter cryotherapy, the skin shows erythema and may progress to hemorrhagic blistering. Healing occurs in approximately a week and hypopigmentation may occur. Ring warts may result rom an inadequate margin o treatment o a common wart (Figure 130-12). Common adverse e ects o cryotherapy include pain, blistering, and hypoor hyperpigmentation. Cryotherapy must be used cautiously where nerves are located super cially (such as on the ngers) to prevent pain and neuropathy. Over reezing in the periungual region can result in permanent nail dystrophy. • Cryotherapy can be combined with other modalities. In Figure 130-13, a man with warts on his lips was rustrated that the cryotherapy was not working so his treatment was modi ed to include topical trichloroacetic acid applied to the warts a ter the cryotherapy.

• Tools used or paring down warts, such as nail les and pumice stones, should not be used on normal skin or by other people. • Hair-bearing areas with warts should be shaved with depilatories, electric razors, or not at all to help limit spread o warts.

PRO GNO SIS • Sixty percent to 70% o cutaneous warts resolve in 3 to 24 months without treatment. 14,15 • New warts may appear while others are regressing. This is not a treatment ailure but part o the natural disease process with HPV.

FO LLO W-UP • Schedule patients or return visits a ter treatment to limit loss o ollow-up and to assess therapy. • Follow-up visits can be le t to the patient’s discretion when sel applied therapy is being used.

PATIENT EDUCATIO N Therapy o ten takes weeks to months, so patience and perseverance are essential or success ul therapy. PATIENT RESO URCES

• AFP Patient Information. Am Fam Physician. 2011;84(3): 296—http:/ / www.aafp.org/ afp/ 2011/ 0801/ p296.html. • eMedicine Health—http:/ / www.emedicinehealth.com/ warts/ article_em.htm. • BUPA. Warts and Verrucas Patient In ormation—http:/ / www .bupa.co.uk/ individuals/ health-information/ directory/ w/ warts-and-verrucas?tab=Resources. FIGURE 130-13 Common warts on th li o a young man a t r cryoth ra y and trichloroac tic acid (TCA) w r a li d . Th TCA was ad d d to th tr atm nt wh n th cryoth ra y alon was not working . Th warts d id r solv a t r a w comb ination tr atm nts. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• FamilyDoctor.org. American Academy of Family Physicians. Warts—http:/ / familydoctor.org/ 209.xml. • MayoClinic.com. Common Warts—http:/ / www.mayoclinic .com/ health/ common-warts/ DS00370.

621

PART 14 DERMATO LO GY

622

PRO VIDER RESO URCES

• eMedicine. Nongenital Warts—http:/ / emedicine.medscape .com/ article/ 1133317. • For information on treating warts including how to dilute Candida antigen: Usatine R, Pfenninger J, Stulberg D, Small R. Dermatologic and Cosmetic Procedures in O f ce Practice. Philadelphia, PA: Elsevier; 2012. This can also be purchased as an electronic application at www.usatinemedia.com. • Cutaneous warts: An evidence-based approach to therapy. Am Fam Physician. 2005;72:647-652. http:/ / www.aafp.org/ afp/ 20050815/ 647.html. • Medline Plus. Warts—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000885.htm. • Cochrane review. Topical Treatments or Cutaneous Warts—http:/ / www.cochrane.org/ reviews/ en/ ab001781.html.

REFERENCES 1. Mulhem E, Pinelis S. Treatment o nongenital cutaneous warts. Am Fam Physician. 2011;84(3):288-293. 2. Micali G, Dall’Oglio F, Nasca MR, et al. Management o cutaneous warts: an evidence-based approach. Am J Clin Dermatol. 2004;5(5):311-317. 3. Kilkenny M, Marks R. The descriptive epidemiology o warts in the community. Australas J Dermatol. 1996;37:80-86. 4. Sterling JC, Hand eld-Jones S, Hudson PM; British Association o Dermatologists. Guidelines or the management o cutaneous warts. Br J Dermatol. 2001;144(1):4-11.

CHApTe R 130

5. Gibbs S, Harvey I, Sterling JC, Stark R. Local treatments or cutaneous warts. Cochrane Database Syst Rev. 2001;(2):CD001781. 6. Massing AM, Epstein WL. Natural history o warts. A two-year study. Arch Dermatol. 1963;87:306-310. 7. Rivera A, Tyring SK. Therapy o cutaneous human papillomavirus in ections. Dermatol Ther. 2004;17(6):441-448. 8. Micali G, Dall’Oglio F, Nasca MR. An open label evaluation o the e cacy o imiquimod 5% cream in the treatment o recalcitrant subungual and periungual cutaneous warts. J DermatologTreat. 2003;14:233-236. 9. Hengge UR, Esser S, Schultewolter T, et al. Self-administered topical 5% imiquimod or the treatment o common warts and molluscum contagiosum. Br J Dermatol. 2000;143:1026-1031. 10. Grussendor -Conen EI, Jacobs S. E cacy o imiquimod 5% cream in the treatment o recalcitrant warts in children. Pediatr Dermatol. 2002;19:263-266. 11. Yilmaz E, Alpsoy E, Basaran E. Cimetidine therapy or warts: a placebo-controlled, double-blind study. JAmAcad Dermatol. 1996;34(6):1005-1007. 12. Tabrizi SN, Garland SM. Is cryotherapy treating or in ecting? Med J Aust. 1996;164(5):263. 13. Wenner R, Askari SK, Cham PM, et al. Duct tape or the treatment o common warts in adults: a double-blind randomized controlled trial. Arch Dermatol. 2007;143(3):309-313. 14. Allen AL, Sieg ried EC. What’s new in human papillomavirus in ection. Curr Opin Pediatr. 2000;12:365-369. 15. Sterling JC, Hand eld-Jones S, Hudson PM. Guidelines or the management o cutaneous warts. Br J Dermatol. 2001;144:4-11.

PART 14 DERMATO LO GY

FLAT WARTS

131 FLAT WARTS E.J. Maye aux Jr, MD

PATIENT STO RY A young woman presents with multiple at lesions surrounding her le t eyebrow (Figure 131-1). It started with just a ew lesions but has spread over the past 3 months. The lesions are unilateral. She is diagnosed with at warts and various treatment methods are discussed. The patient chose to try topical tretinoin cream.

INTRO DUCTIO N Flat warts are characterized as at or slightly elevated esh-colored papules. They may be smooth or slightly hyperkeratotic. They range in size rom 1 to 5 mm or more, and numbers range rom a ew to hundreds o lesions, which may become grouped or con uent. They occur most commonly on the ace, hands, and shins. They may appear in a linear distribution as a result o scratching, shaving, or trauma (Koebner phenomenon) (Figure 131-2).

A

SYNO NYMS Flat warts are also known as plane warts, verruca plana, and verruca plana juvenilis.

EPIDEMIO LO GY • Flat warts (verruca plana) are most commonly ound in children and young adults (Figures 131-1 to 131-5).

B

• Flat warts are the least common variety o wart, but are generally numerous on an individual. 1

FIGURE 131-2 A. and B. Two d i e re nt young wome n with f at warts around the kne e s sp re ad b y shaving . (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

• Flat warts are usually caused by human papillomavirus (HPV) types 3, 10, 28, and 29. 2

ETIO LO GY AND PATHO PHYSIO LO GY • Like all warts, at warts are caused by HPV. 2 • Flat warts may spread in a linear pattern secondary to spread by scratching or trauma, such as shaving. • Flat warts present a special treatment problem because they persist or a long time; they are generally located in cosmetically important areas, and they are resistant to therapy.

RISK FACTO RS FIGURE 131-1 Flat warts on a p atie nt’s e ye b row skin. (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

• Shaving next to in ected areas (see Figures 131-2 and 131-3) • HIV in ection or other types o immunosuppression (see Figure 131-3)

623

624

PART 14 DERMATO LO GY

Ch a pt e r 131

DIAGNO SIS CLINICAL FEATURES at warts are multiple small, at-topped papules that may be pink, light-brown, or light-yellow colored. They may be polygonal in shape (see Figure 131-4). TYPICAL DISTRIBUTIO N Flat warts typically appear on the orehead (see Figure 131-1), around the mouth, the backs o the hands, and shaved areas, such as the lower ace and neck in men (see Figures 131-3 and 131-5) and the lower legs in women (see Figure 131-2). LABO RATO RY TESTING HPV testing is not use ul or this condition. 3 FIGURE 131-3 Flat warts on the ne ck o an HIV-p ositive man. The warts have b e e n sp re ad b y shaving . Cryothe rap y and imiq uimod we re not succe ss ul b ut intrale sional Cand id a antig e n inje ctions cle are d all the warts. (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

BIO PSY Although usually not necessary, a shave biopsy can conf rm the diagnosis.

DIFFERENTIAL DIAGNO SIS • Lichen planus produces at-topped papules that may be con used with at warts. Look or characteristic signs o lichen planus such as the symmetric distribution, purplish coloration, and oral lacy lesions. (Wickham striae are white, f ne, reticular scale seen on the lesions.) The distribution o lichen planus is di erent, with the most common sites being the ankles, wrists, and back (see Chapter 152, Lichen Planus). • Seborrheic keratoses are o ten more darkly pigmented and have a stuck-on appearance; “horn cysts” may be visible on close examination (see Chapter 156, Seborrheic Keratosis).

FIGURE 131-4 Close -up o a f at wart. Note typ ical small, f at-top p e d p ap ule . (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

• Squamous cell carcinoma should be considered when lesions have irregular growth or pigmentation, ulceration, or resist therapy, particularly in sun-exposed areas and in immunosuppressed patients (see Chapter 169, Squamous Cell Carcinoma).

MANAGEMENT NO NPHARMACO LO GIC • Regression o these lesions may occur, which usually is heralded by in ammation. • There are no current therapies or HPV that are virus specif c. MEDICATIO NS • Topical salicylic acid treatments by topical liquid or patch are the most e ective treatment or all types o warts with a success rate average o 73% rom 5 pooled placebo-controlled trials. 4 Number needed to treat (NNT) = 4. SO R Salicylic acid may be more acceptable on the legs 2 than the ace. O ten, 17% salicylic acid topicals are applied overnight daily until the warts resolve. FIGURE 131-5 Flat warts on the ace o a man on p re d nisone or sarcoid osis. (Re p rod uce d with p e rmissio n rom Richard P. Usatine , MD.)

• Fluorouracil (E udex 5% cream, Fluoroplex 1%) may be used to treat at warts. Apply the cream to a ected areas twice daily or 3 to 4 weeks. Sun protection is essential because the drug is

PART 14 DERMATO LO GY

FLa t Wa r t S

photosensitizing. Persistent hypo- or hyperpigmentation may occur ollowing use, but applying it with a cotton-tipped applicator to individual lesions instead o to the area may minimize this adverse reaction. 5,6 SO R B • Imiquimod 5% cream is an expensive topical immunomodulator that has shown some e f cacy in treating at warts. 7,8 It is nonscarring and painless to apply. There are rare reports o systemic side e ects. The cream is applied to the lesions 3 times a week (every other day). The cream may be applied to the a ected area, not strictly to the lesion itsel . 9 It can be used on all external HPV-in ected sites, but not on occluded mucous membranes. Therapy can be temporarily halted i symptoms become problematic. Imiquimod has the advantage o having almost no risk o scarring. 7,8 SO R B A lower concentration o imiquimod (3.75% cream) is also available, but data or its use with at or common warts are lacking. • Tretinoin cream, 0.025%, 0.05%, or 0.1%, applied at bedtime over the entire involved area is one accepted treatment. The requency o application is then adjusted so as to produce a mild, f ne scaling and erythema. Sun protection is important. Treatment may be required or weeks or months and may not be e ective. No published studies were ound to support this treatment. SO R C • Intralesional injections with Candida antigen induce a localized, cellmediated, and HPV-specif c response that may target the injected wart as well as more distant warts. This method has moderate e ectiveness (60% cure rates) or treatment o recalcitrant warts (Figures 131-3 and 131-6). 2 The Candida antigen must be diluted be ore used (see Table 131-1). Inject 0.1 to 0.3 mL into the largest warts using a 30-gauge needle and up to 1 mL per treatment. Warn the patient to expect itching in the area, burning, or peeling. Repeat every 4 weeks, up to 3 treatments or until warts are gone. 10 SO R B • Photodynamic therapy with aminolevulinic acid plus topical salicylic acid is a moderately e ective option or treatment o recalcitrant warts. Although it is likely to be benef cial, it is expensive and o ten requires dermatologic re erral. 2 SO R B • Cantharidin 0.7% is an extract o the blister beetle that is applied to the wart a ter which blistering occurs. It may be used in resistant cases. 11 It is also use ul in young children because application is painless in the o f ce. However, pain ul blisters o ten occur within a day a ter

TABLE 131-1 Cand id a Dilutions

Cre at ing 1 mL fo r Inje ct io n

Cand id a Ant ig e n (mL)

2% Lid o caine (No Ep ine p hrine ) (mL)

Ge ne ric 1:1000

0.25

0.75

Cand in 1:500

0.5

0.5

Data rom Usatine RP, P e nning e r J, Stulb e rg D, Small R. De rmatolog ic and Cosme tic Proce d ure s in O f ce Practice . Philad e lp hia, PA: Else vie r Inc.; 2012.

application. Be care ul not to overtreat with cantharidin because the blistering can be quite severe. Care ully apply to multiple lesions using the wooden end o a cotton-tipped applicator. SO R C SURGICAL • Cryotherapy, most commonly with liquid nitrogen, is use ul but is somewhat pain ul or younger children. 6 SO R B Chemical cryogens are now available over the counter but are not as cold or e ective as liquid nitrogen. Most trials comparing cryotherapy with salicylic acid ound similar e ectiveness. 2 Liquid nitrogen is applied or 5 to 10 seconds via a Cryogun or a cotton swab so that the reeze ball extends 1 to 2 mm beyond the lesion. Because at warts are thinner than common warts, the reeze times needed are shorter. Two reeze cycles may improve resolution, but it is better to under reeze than over reeze since over reezing may lead to permanent scarring or hypopigmentation. Best results o cryotherapy can be achieved when the patient is treated every 2 or 3 weeks. There is no therapeutic benef t beyond 3 months.2 SOR B Because HPV can survive in liquid nitrogen, cotton swabs and residual liquid nitrogen should be properly discarded to avoid spreading the virus to other patients or contaminating the liquid nitrogen reservoir.12 A ter cryotherapy, the skin shows erythema and may progress to hemorrhagic blistering. Healing occurs in approximately a week and hypopigmentation may occur. Common adverse e ects o cryotherapy include pain, blistering, and hypo- or hyperpigmentation. • Pulsed-dye laser can be considered or treatment o recalcitrant warts, although the e ectiveness is unproven. 2 SO R B

PREVENTIO N Hair-bearing areas with warts should be shaved with depilatories, electric razors, or not at all to help limit spread o warts.

FO LLO W-UP Schedule patients or a return visit in 2 to 3 weeks a ter therapy to assess e f cacy.

PATIENT EDUCATIO N • To help avoid spreading warts, patients should avoid touching or scratching the lesions. FIGURE 131-6 The same man in Fig ure 131-3 a te r succe ss ul tre atme nt with Cand id a antig e n. (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

• Razors that are used in areas where warts are located should not be used on normal skin or by other people to prevent spread.

625

PART 14 DERMATO LO GY

626

PATIENT RESO URCES

• KidsHealth. Warts—http:/ / www.kidshealth.org/ parent/ infections/ skin/ wart.html. • American Academy of Dermatology. Warts—http:/ / www.aad .org/ public/ Publications/ pamphlets/ Warts.htm. • MedlinePlus. Warts—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000885.htm.

CHAPTER 131

3. Sterling JC, Handf eld-Jones S, Hudson PM; British Association o Dermatologists. Guidelines or the management o cutaneous warts. Br J Dermatol. 2001;144(1):4-11. 4. Gibbs S, Harvey I. Topical treatments or cutaneous warts. Cochrane Database Syst Rev. 2006;(3):CD001781. 5. Lockshin NA. Flat acial warts treated with uorouracil. Arch Dermatol. 1979;115:929-1030.

PRO VIDER RESO URCES

6. Lee S, Kim J-G, Chun SI. Treatment o verruca plana with 5% 5- uorouracil ointment. Dermatologica. 1980;160:383-389.

• Bacelieri R, Johnson SM. Cutaneous warts. An evidence-based approach to therapy. Am Fam Physician. 2005;72:647-652. http:/ / www.aafp.org/ afp/ 20050815/ 647.html.

7. Cutler K, Kagen MH, Don PC, et al. Treatment o acial verrucae with topical imiquimod cream in a patient with human immunodef ciency virus. Acta DermVenereol. 2000;80:134-135.

• Cochrane Review. Topical Treatments or Cutaneous Warts—http:/ / www.cochrane.org/ reviews/ en/ ab001781.html.

8. Kim MB. Treatment o at warts with 5% imiquimod cream. J Eur Acad DermatolVenereol. 2006;20(10):1349-1350.

• Treatment of warts is covered extensively in Usatine R, Pfenninger J, Stulberg D, Small R. Dermatologic and Cosmetic Procedures in O f ce Practice. Philadelphia, PA: Elsevier Inc.; 2012. This can also be purchased as an electronic application at www.usatinemedia.com.

9. Schwab RA, Elston DM. Topical imiquimod or recalcitrant acial at warts. Cutis. 2000;65:160-162.

REFERENCES 1. Williams H, Pottier A, Strachan D. Are viral warts seen more commonly in children with eczema? Arch Dermatol. 1993;129:717-720. 2. Mulhem E, Pinelis S. Treatment o nongenital cutaneous warts. Am Fam Physician. 2011;84(3):288-293.

10. Ritter SE, Me ert J. Success ul treatment o at warts using intralesional Candida antigen. Arch Dermatol. 2003;139(4):541-542. 11. Kartal Durmazlar SP, Atacan D, Eskioglu F. Cantharidin treatment or recalcitrant acial at warts: a preliminary study. J Dermatolog Treat. 2009;20(2):114-119. 12. Tabrizi SN, Garland SM. Is cryotherapy treating or in ecting? Med J Aust. 1996;164(5):263.

PART 14 DERMATO LO GY

GENITAL WARTS

132 GENITAL WARTS E.J. Maye aux, Jr, MD Richard P. Usatine , MD

SYNO NYMS Genital warts are also known as condyloma acuminata.

EPIDEMIO LO GY PATIENT STO RY An 18-year-old woman presents with a concern that she might have genital warts (Figure 132-1). She never had a sexually transmitted disease (STD) but admits to 2 new sexual partners in the last 6 months. She has not been vaccinated against human papillomavirus (HPV). The patient is told that her concern is accurate and she has condyloma caused by HPV (an STD). The treatment options are discussed and she chooses to have cryotherapy with liquid nitrogen ollowed by imiquimod sel -applied beginning 2 weeks a ter cryotherapy. A urine test or gonorrhea and Chlamydia is per ormed and the patient is sent to the laboratory to have blood tests or syphilis and HIV. Fortunately, all the additional tests are negative. Further patient education is per ormed and ollow-up is arranged.

INTRO DUCTIO N More than 100 types o HPV exist, with more than 40 that can in ect the human genital area. Most HPV in ections are asymptomatic, unrecognized, or subclinical. Low-risk HPV types (eg, HPV types 6 and 11) cause genital warts, although coin ection with HPV types associated with squamous intraepithelial neoplasia can occur. Asymptomatic genital HPV in ection is common and usually sel -limited. 1

• Anogenital warts are the most common viral STD in the United States. There are approximately 1 million new cases o genital warts per year in the United States. 2 • Most in ections are transient and cleared within 2 years. 2 • Some in ections persist and recur and cause much distress or the patients.

ETIO LO GY AND PATHO PHYSIO LO GY • Genital warts are caused by HPV in ection. HPV encompasses a amily o primarily sexually transmitted double-stranded DNA viruses. The incubation period a ter exposure ranges rom 3 weeks to 8 months.

RISK FACTO RS • Sexual intercourse and oral sex3 • Other types o sexual activity including digital–anal, oral–anal, and digital–vaginal contact • Immunosuppression, especially HIV (Figure 132-2)

DIAGNO SIS CLINICAL FEATURES • Diagnosis o genital warts is usually clinical based on visual inspection. 1 • Genital warts are usually asymptomatic, and typically present as eshcolored, exophytic lesions on the genitalia, including the penis, vulva, vagina, scrotum, perineum, and perianal skin.

FIGURE 132-1 Multip le vulvar e xop hytic cond yloma in an 18-ye ar-old woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 132-2 Multip le e xop hytic cond yloma on the p e nis o a man with AIDS. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

627

628

PART 14 DERMATO LO GY

Ch a pt e r 132

FIGURE 132-5 Smooth-top p e d cond yloma on the we ll-ke ratinize d skin o a circumcise d man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

TYPICAL DISTRIBUTIO N

FIGURE 132-3 Cond yloma around the clitoris, lab ia minor, and op e ning o the vag ina. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• In women, the most common sites o in ection are the vulva (85%) (see Figure 132-1), perianal area (58%), and the vagina (42%) (see Figure 132-3). • In men, the most common sites o in ection are the penis (Figures 132-4 and 132-5) and scrotum.

• External warts can appear as small bumps, or they may be at, verrucous, or pedunculated (Figures 132-2 to 132-4).

• Perianal warts (Figure 132-6) can occur in men or women who have a history o anal intercourse and in those who do not have any such history (Figure 132-7). 1

• Less commonly, warts can appear as reddish or brown, smooth, raised papules or as dome-shaped lesions on keratinized skin.

• Condyloma acuminata may be seen on the abdomen or upper thighs in conjunction with genital warts (Figure 132-8).

FIGURE 132-4 Cond yloma acuminata d e monstrating a cauli owe r ap p e arance with typ ical p ap illary sur ace se e n whe n the ore skin is re tracte d in an uncircumcise d man. Note that the top wart is p e d unculate d with a narrow b ase . (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

FIGURE 132-6 Pe rianal warts in a g ay man with history o anal-re ce p tive inte rcourse . The se le sions re sp ond e d to cryothe rap y. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Ge NIt a L Wa r t S

FIGURE 132-7 Exte nsive p e rianal warts in a 17-ye ar-old ad ole sce nt b oy who d e nie s se xual ab use and anal inte rcourse . Patie nt aile d imiq uimod the rap y and was re e rre d to surg e ry. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

• Condyloma caused by HPV can be seen in obese individuals within the olds o the pannus (Figure 132-9). • A rapid plasma reagin (RPR) or Veneral Disease Research Laboratory (VDRL) test should be ordered to screen or syphilis and a HIV test should be ordered as well. Genital warts are a sexually transmitted disease and patients who have one STD should be screened or others. LABO RATO RY TESTING HPV viral typing is not recommended because test results would not alter clinical management o the condition. The application o 3% to 5% acetic acid to detect mucosal changes attributed to HPV in ection is not recommended. 1 BIO PSY • Diagnosis may be conf rmed by shave or punch biopsy i necessary. 1 Biopsy is indicated or the ollowing reasons: ° The diagnosis is uncertain. ° The patient has a poor response to appropriate therapy.

FIGURE 132-8 Condyloma that started on the penis and spre ad up the abdomen and on to the thighs. Note how these warts are hyp e rp ig m e nte d in this Latino man. (Reproduced with permission from Richard P. Usatine, MD.)

PART 14 DERMATO LO GY

FIGURE 132-9 Panus cond yloma rom HPV g rowing b e twe e n the old s o he avy ad ip ose tissue in this ob e se woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

° Warts are atypical in appearance (unusually pigmented, indurated, f xed, or ulcerated). ° The patient has compromised immunity and squamous cell carcinoma is suspected (one type o HPV-related malignancy).

DIFFERENTIAL DIAGNO SIS • Pearly penile papules (PPPs), which are small papules around the edge o the glans penis (Figure 132-10). • Common skin lesions, such as seborrheic keratoses and nevi—These are rare in the genital area (Figure 132-11) (see Chapters 156, Seborrheic Keratosis and 160, Nevus). • Giant condyloma or Buschke-Lowenstein tumor is a low-grade, locally invasive malignancy that can appear as a ungating condyloma (Figure 132-12). Persons with HIV/ AIDS have a higher risk o giant condyloma and malignant trans ormation (Figure 132-13).

FIGURE 132-10 Cond yloma coe xisting with p e arly p e nile p ap ule s (PPPs), which are a normal variant on the e d g e o the corona. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

629

630

PART 14 DERMATO LO GY

Ch a pt e r 132

FIGURE 132-11 Two larg e cond ylomas that re se mb le se b orrhe ic ke ratose s. Shave b iop sy was p ositive or HPV. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Molluscum contagiosum—Waxy umbilicated papules around the genitals and lower abdomen (see Chapter 129, Molluscum Contagiosum).

FIGURE 132-13 Giant cond ylomata acuminata in a man with AIDS. (Re p rod uce d with p e rmission from Jack Re sne ck, Sr., MD.)

• Malignant neoplasms, such as basal cell carcinoma and squamous cell carcinomas (see Chapters 168, Basal Cell Carcinoma and 169, Squamous Cell Carcinoma). • Condyloma lata is caused by secondary syphilis in ection; lesions appear at and velvety (see Chapter 218, Syphilis). A ull workup or other STDs, including syphilis, should be done or any patient with genital warts (Figure 132-14). • Micropapillomatosis o the vulva is a normal variant and appears as distinct individual papillary projections rom the labia in a symmetrical pattern.

FIGURE 132-12 Buschke -Lowe nste in tumor (g iant co nd ylomata acuminata) at the b ase o the p e nis. This was tre ate d with surg ical re se ction. The marg ins we re cle ar and the re was no sq uamous ce ll carcinoma ound . (Re p rod uce d with p e rmission from Suraj Re d d y, MD.)

FIGURE 1 32-14 This 22-ye ar-o ld wo man with an ad d iction to IV he ro in p re se nte d with many cond yloma in the ano g e nital re g ion. An RPR was p ositive o r syp hilis. The p atie nt was tre ate d with p e nicillin as we ll as cryo the rap y. The visib le cond ylo mas in this imag e are mo st like ly HPV and not co nd ylo ma lata b ase d on the ir ve rrucous mo rp ho log y. (Re p ro d uce d with p e rmissio n from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

Ge NIt a L Wa r t S

631

MANAGEMENT • The primary reason or treating genital warts is the amelioration o symptoms and ultimately removal o the warts. 1 • The choice o therapy is based on the number, size, site, and morphology o lesions, as well as patient’s pre erence, treatment cost, convenience, adverse e ects, and physician’s experience. • Although available therapies or genital warts are likely to reduce HPV in ectivity, they probably do not eradicate transmission. 1 MEDICATIO NS AND SURGICAL METHO DS • Treatments or external genital warts include topical medications, cryotherapy (Figure 132-15), and surgical methods, and are shown in Table 132-1. • Cryotherapy is best applied with a bent-tipped spray applicator that allows or precise application with a less pain ul attenuated ow (see Figure 132-15).4 Application may be repeated every 2 weeks i necessary.

FIGURE 132-15 Cryothe rap y o p e nile warts using a liq uid nitrog e n sp ray te chniq ue and a b e nt-tip p e d ap p licator.

• Treatment with 5% uorouracil cream (E udex) is no longer recommended because o severe local side e ects and teratogenicity. 1

TABLE 132-1 Tre atme nts or Exte rnal Ge nital Warts

Tre at me nt

Po ssib le Ad ve rse Effe ct s

Cle arance (%)

Re curre nce (%)

Patie nt-Ap p lie d The rap y Imiq uimod (Ald ara) is ap p lie d at b e d time or 3 d ays, the n re st 4 d ays; alte rnative ly, ap p ly e ve ry othe r d ay or 3 ap p lications; may re p e at we e kly cycle s or up to 16 we e ks 5 SO R

Erythe ma, irritation, ulce ration, p ain, and p ig me ntary chang e s; minimal syste mic ab sorp tion

30-50

15

Sine cate chins 15% ointme nt—Ap p ly a 0.5-cm strand o ointme nt to e ach wart 3 time s d aily6 SO R

Erythe ma, p ruritus/b urning , p ain, ulce ration, e d e ma, ind uration, and ve sicular rash

53-57

3.7

Pod of lox (Cond ylox) is ap p lie d twice d aily or 3 d ays, the n re st 4 d ays; may re p e at or 4 cycle s 7 SO R

Burning , p ain, in ammation; low risk or syste mic toxicity unle ss ap p lie d to occlud e d me mb rane s

45-80

5-30

Cryothe rap y p e r orme d with liq uid nitrog e n or a cryop rob e 6 SO R

Pain or b liste rs at ap p lication site , scarring

60-90

20-40

Pod op hyllin re sin is ap p lie d to e ach wart and allowe d to d ry, and is re p e ate d we e kly as ne e d e d 6,7 SO R

Local irritation, e rythe ma, b urning , and sore ne ss at ap p lication site ; ne urotoxic and oncog e nic i ab sorb e d

30-80

20-65

35-70

5-50

50-80

35

Provid e r-Ap p lie d The rap y

Surg ical tre atme nt or warts involve s Pain, b le e d ing , scarring ; risk or b urnre moval to the d e rmal–e p id e rmal junction; ing and alle rg ic re action rom local op tions includ e scissor e xcision, shave e xciane sthe tic; lase r and LEEP have risk sion, lase r vap orization, and loop e le ctrosuror sp re ad ing HPV in p lume g ical e xcision p roce d ure (LEEP) e xcision 6 SO R

Trichloroace tic acid (TCA) and b ichlorace tic acid (BCA) are ap p lie d to e ach wart and allowe d to d ry; re p e ate d we e kly6 SO R

Local p ain and irritation; no syste mic sid e e e cts

PART 14 DERMATO LO GY

632

CHAPTER 132

REFERRAL O R HO SPITALIZATIO N

PRO VIDER RESO URCES

Consider consultation or patients with very large or recalcitrant lesions.

• Centers for Disease Control and Prevention. Genital Warts— http:/ / www.cdc.gov/ std/ treatment/ 2010/ genital-warts.htm.

PREVENTIO N A bivalent vaccine (Cervarix) containing HPV types 16 and 18 and a quadrivalent vaccine (Gardasil) containing HPV types 6, 11, 16, and 18 are licensed in the United States. The quadrivalent HPV vaccine protects against the HPV types that cause 90% o genital warts (ie, types 6 and 11) in males and emales when given prophylactically. Both vaccines o er protection against the HPV types that cause 70% o cervical cancers (ie, types 16 and 18). In the United States, the quadrivalent (Gardasil) HPV vaccine can also be used in males and emales ages 9 to 26 years to prevent genital warts. 8

PRO GNO SIS Many genital warts will eventually resolve without treatment. Resolution can usually be hastened with therapy (see Table 132-1).

FO LLO W-UP Patients should be o ered a ollow-up evaluation 2 to 3 months a ter treatment to check or new lesions. 1 SO R

PATIENT EDUCATIO N HPV is transmitted mainly by skin-to-skin contact. Although condoms may decrease the levels o transmission, they are imper ect barriers at best as they can ail, and they do not cover the scrotum or vulva, where in ection may reside. PATIENT RESO URCES

• eMedicineHealth. Genital Warts (HPV In ection)—http:/ / www .emedicinehealth.com/ genital_warts/ article_em.htm. • PubMed Health. Genital Warts—http:/ / www.ncbi.nlm.nih.gov/ pubmedhealth/ PMH0001889/ . • American Academy of Dermatology. Genital Warts—http:/ / www .aad.org/ skin-conditions/ dermatology-a-to-z/ genital-warts. • MedlinePlus. Genital Warts—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000886.htm.

• Medscape. Genital Warts—http:/ / emedicine.medscape.com/ article/ 1133201. • Medscape. Genital Warts in Emergency Medicine—http:/ / emedicine.medscape.com/ article/ 763014. REFERENCES 1. Centers or Disease Control and Prevention. 2010 Guidelines or Treatment o SexuallyTransmitted Diseases. http:/ / www.cdc.gov/ std/ treatment/ 2010/ STD-Treatment-2010-RR5912.pd . Accessed December 1, 2011. 2. Burk RD, Kelly P, Feldman J, et al. Declining prevalence o cervicovaginal human papillomavirus in ection with age is independent o other risk actors. SexTransm Dis. 1996;23:333-341. 3. Pale sky JM. Cutaneous and genital HPV-associated lesions in HIV-in ected patients. Clin Dermatol. 1997;15:439-447. 4. Usatine R, Stulberg D. Cryosurgery. In: Usatine R, P enninger J, Stulberg D, Small R, eds. Dermatologic and Cosmetic Procedures in O f ce Practice. Philadelphia, PA: Elsevier; 2012:182-198. 5. Gotovtseva EP, Kapadia AS, Smolensky MH, Lairson DR. Optimal requency o imiquimod (Aldara) 5% cream or the treatment o external genital warts in immunocompetent adults: a meta-analysis. SexTransm Dis. 2008;35(4):346-351. 6. Mayeaux EJ Jr, Dunton C. Modern management o external genital warts. J Low Genit Tract Dis. 2008;12:185-192. 7. Langley PC, Tyring SK, Smith MH. The cost e ectiveness o patientapplied versus provider-administered intervention strategies or the treatment o external genital warts. Am J Manag Care. 1999;5(1):69-77. 8. Centers or Disease Control and Prevention (CDC). FDA licensure o quadrivalent human papillomavirus vaccine (HPV4, Gardasil) or use in males and guidance rom the Advisory Committee on Immunization Practices (ACIP). MMWR Morb MortalWkly Rep. 2010;59(20):630-632.

PART 14 DERMATO LO GY

PLANTAR WARTS

133 PLANTAR WARTS E.J. Maye aux Jr, MD

PATIENT STO RY A young man presents to the clinic with a “growth” on the side o his oot. It had been present or about a year and was unresponsive to over-the-counter therapies (Figure 133-1). It is pain ul to walk on and he would like it to be treated. He was diagnosed with plantar warts. The lesions were treated with gentle paring using a scalpel and liquid nitrogen therapy over 2 sessions.

INTRO DUCTIO N Plantar warts (verruca plantaris) are human papilloma virus (HPV) lesions that occur on the soles o the eet (Figures 133-1 to 133-5) and palms o the hands (Figure 133-6).

FIGURE 133-2 Close -up o p lantar wart on the sid e o the he e l. Note the d isrup tion o skin line s and b lack d ots. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

SYNO NYMS Plantar warts are also known as palmoplantar warts and myrmecia.

EPIDEMIO LO GY • Plantar warts a ect mostly adolescents and young adults, a ecting up to 10% o people in these age groups. 1 • Prevalence studies demonstrate a wide range o values, rom 0.84% in the United States2 to 3.3% to 4.7% in the United Kingdom, 3 to 24% in 16- to 18-year-olds in Australia. 4

ETIO LO GY AND PATHO PHYSIO LO GY

bones (see Figure 133-5), but may appear anywhere on the plantar sur ace including the tips o the f ngers and toes (Figure 133-7). • A thick, pain ul callus orms in response to the pressure that is induced as the size o the lesion increases. Even a minor wart can cause a lot o pain. • A cluster o many warts that appear to use is re erred to as a mosaic wart (see Figure 133-4).

RISK FACTO RS • Young age • Decreased immunity

• Plantar warts are caused by HPV. • They usually occur at points o maximum pressure, such as on the heels (see Figures 133-2 to 133-4) or over the heads o the metatarsal

FIGURE 133-1 Plantar wart on the sid e o the oot. It had b e e n p re se nt or ab o ut a ye ar and was unre sp onsive to ove r-the -counte r the rap ie s. (Re p rod uce d with p e rmission from E.J. Maye aux, Jr, MD.)

FIGURE 133-3 Close -up o a p lantar wart d e monstrating d isrup tion o normal skin line s. Corns and callus d o not d isrup t normal skin line s. The b lack d ots are thromb ose d ve sse ls, which are re q ue ntly se e n in p lantar warts. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

633

PART 14 DERMATO LO GY

634

Ch a pt e r 133

FIGURE 133-6 Multip le p lantar warts on the p alms o an HIV-p ositive man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.) FIGURE 133-4 A mosaic wart is orme d whe n se ve ral p lantar warts b e come conf ue nt. This man was HIV p ositive and this wart was ve ry re sistant to tre atme nt. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• May have centrally located black dots (thrombosed vessels) that may bleed with paring (see Figures 133-2 to 133-7) TYPICAL DISTRIBUTIO N

DIAGNO SIS CLINICAL FEATURES Plantar warts present as thick, pain ul endophytic plaques located on the soles and/ or palms. Warts have the ollowing eatures: • Begin as small shiny papules • Lack skin lines crossing their sur ace (see Figure 133-3) • Have a highly organized mosaic pattern on the sur ace when examined with a hand lens • Have a rough keratotic sur ace surrounded by a smooth collar o callused skin

They occur on the palms o the hands and soles o the eet. They are more commonly ound on weight-bearing areas, such as under the metatarsal heads or on the heel. 5 BIO PSY I the diagnosis is doubt ul, a shave biopsy is indicated to conf rm the diagnosis. 6

DIFFERENTIAL DIAGNO SIS • Corns and calluses are pressure-induced skin thickenings that occur on the eet and can be mistaken or plantar warts. Calluses are generally ound on the sole and corns are usually ound on the toes. Calluses and

• Pain ul when compressed laterally

FIGURE 133-5 Multip le p lantar warts on the b all o the o ot and to e s. The thromb ose d ve sse ls within the warts ap p e ar as b lack d ots. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 133-7 Close -up o p lantar wart on a ng e r that also shows d isrup tion o skin line s and b lack d ots. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

pLa Nt a r Wa r t S

corns have skin lines crossing the sur ace, and are painless with lateral pressure (see Chapter 205, Corn and Callus). • Black heel presents as a cluster o blue-black dots that result rom ruptured capillaries. They appear on the plantar sur ace o the heel ollowing the shearing trauma o sports that involve sudden stops or position changes. Examination reveals normal skin lines, and paring does not cause additional bleeding. The condition resolves spontaneously in a ew weeks. • Black warts are plantar warts undergoing spontaneous resolution, which may turn black and eel so t when pared with a blade. 7 • Squamous cell carcinoma should be considered when lesions have irregular growth or pigmentation, ulceration, or resist therapy, particularly in immunosuppressed patients (see Chapter 169, Squamous Cell Carcinoma). • Amelanotic melanoma, although extremely rare, can look similar to HPV lesions. Lesions that are treatment resistant or atypical, particularly on the palms or soles, should be monitored closely. A biopsy is required to establish the diagnosis (see Chapter 170, Melanoma).

A

• Palmoplantar keratoderma describes a rare heterogeneous group o disorders characterized by thickening o the palms and the soles that can also be an associated eature o di erent syndromes. They can be classif ed as having uni orm involvement versus ocal hyperkeratosis located mainly on pressure points and sites o recurrent riction (Figure 133-8). This latter type can be di erentiated rom plantar warts by the more di use locations on the palmoplantar sur aces, the mainly epidermal involvement, and biopsy, i necessary (Figure 133-9).

MANAGEMENT NO NPHARMACO LO GIC • Painless plantar warts do not require therapy. Minimal discom ort can be relieved by periodically removing the hyperkeratosis with a blade or pumice stone. • Pain ul warts should be treated using a technique that causes minimal scarring as scars on the soles o the eet are usually permanent and pain ul. • Patients with diabetes must be treated with the utmost care to minimize complications. MEDICATIO NS • Topical salicylic acid solutions are available in nonprescription orm and provide conservative keratolytic therapy. These preparations are nonscarring, minimally pain ul, and relatively e ective, but require persistent application o medication once each day or weeks to months. The wart is f rst pared with a blade, pumice stone, or emery board, and the area soaked in warm water. The solution is then applied, allowed to dry, reapplied, and occluded with adhesive tape. 8 White, pliable, keratin orms and should be pared away care ully until pink skin is exposed. 9 SO R B • Seventeen percent to 50% salicylic acid solution and plasters are available in nonprescription and prescription orms. However, the 17% solutions are more prevalent and easier to f nd in nonprescription orm. The treatment is similar to the previous process, except that with plasters the salicylic acid has been incorporated into a pad. They are particularly use ul in treating mosaic warts covering a large area. Pain is quickly relieved in plantar warts, because a large amount o

B FIGURE 133-8 Focal p almop lantar ke ratod e rma o the p alms (A) and sole s (B). This is an inhe rite d g e nod e rmatosis. Note le sions are locate d mainly on hig he r p re ssure are as. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

keratin is removed during the f rst ew days o treatment. 9 SO R B A recent multicenter, open-label, randomized, controlled trial ound that 50% salicylic acid and the cryotherapy were equally e ective or clearance o plantar warts. 10 SO R A • Acid chemotherapy with trichloroacetic acid (TCA) or bichloracetic acid (BCA) is commonly employed to treat plantar warts in the o f ce. They are considered sa e during pregnancy or external lesions.

635

PART 14 DERMATO LO GY

636

Ch a pt e r 133

The excess keratin is f rst pared with a scalpel, then the entire lesion is coated with acid, and the acid is worked into the wart with a sharp toothpick. The process is repeated every 7 to 10 days. SO R • Cryotherapy with liquid nitrogen therapy is commonly used, but plantar warts are more resistant than other HPV lesions. The liquid nitrogen is applied to orm a reeze ball that covers the lesion and 2 mm o surrounding normal tissue, usually 10 to 20 seconds per reeze. SO R There is no evidence that 2 reezing episodes are better than one, other than it allows or more reeze time in a way that is more acceptable to the patient. It is always better to under reeze than to over reeze in areas where scarring can produce permanent disability. • Treatments or resistant lesions are o ten carried out in re erral practices that have a high enough volume to use more expensive or specialized therapy. Cantharidin is an extract o the blister beetle that is applied to the wart a ter which blistering occurs. Intralesional immunotherapy with skin-test antigens (ie, mumps, Candida, or Trichophyton antigens) may lead to the resolution both o the injected wart and other warts that were not injected. Contact immunotherapy using dinitrochlorobenzene, squaric acid dibutylester, and diphenylcyclopropenone may be applied to the skin to sensitize the patient and then to the lesion to induce an immune response. Intralesional bleomycin or laser therapy is also use ul or recalcitrant warts. SO R A

CO MPLEMENTARY AND ALTERNATIVE THERAPY Although many complementary and alternative therapies are promoted or wart therapy, there is no signif cant data supporting their use in the treatment o plantar warts.

PREVENTIO N Tools used or paring down warts, such as nail f les and pumice stones should not be used on normal skin or by other people.

PRO GNO SIS Most plantar warts will spontaneously disappear without treatment. Treatment o ten hastens resolution o lesions.

FO LLO W-UP Regular ollow-up to assess treatment e f cacy, adverse reactions, and patient tolerance are recommended to minimize treatment dropouts.

PATIENT EDUCATIO N B FIGURE 133-9 Di use p almop lantar ke ratod e rma o the p alms (A) and sole s (B) in an 11-ye ar-old g irl. This is an inhe rite d g e nod e rmatosis with se ve re unctional conse q ue nce s. (Re p ro d uce d with p e rmission fro m Richard P. Usatine , MD.)

• Because spontaneous regression occurs, observation o painless lesions without treatment is pre erable. • Therapy o ten takes weeks to months, so patience and perseverance are essential or success ul therapy.

pLa Nt a r Wa r t S

PATIENT RESO URCES

• MayoClinic. Plantar Warts—http:/ / www.mayoclinic.com/ health/ plantar-warts/ DS00509. • MedlinePlus. Warts—http:/ / www.nlm.nih.gov/ medlineplus/ warts.html. • Fort Drum Medical Activity. Patient Education Handouts: Warts and Plantar Warts—http:/ / www.drum.amedd.army.mil/ pt_info/ handouts/ warts_Plantar.pdf. PRO VIDER RESO URCES

• Bacelieri R, Johnson SM. Cutaneous warts: an evidence-based approach to therapy. Am Fam Physician. 2005;72:647-652— http:/ / www.aafp.org/ afp/ 20050815/ 647.html. • Medscape. Nongenital Warts—http:/ / emedicine.medscape .com/ article/ 1133317.

REFERENCES 1. Laurent R, Kienzler JL. Epidemiology o HPV in ections. Clin Dermatol. 1985;3(4):64-70. 2. Johnson ML, Roberts J. Skin conditions and related need or medical care among persons 1-74 years. Rockville, MD: US Department o Health, Education, and Wel are; 1978:1-26.

PART 14 DERMATO LO GY 3. Williams HC, Pottier A, Strachan D. The descriptive epidemiology o warts in British schoolchildren. Br J Dermatol. 1993;128:504-511. 4. Kilkenny M, Merlin K, Young R, Marks R. The prevalence o common skin conditions in Australian school students: 1. Common, plane and plantar viral warts. Br J Dermatol. 1998;138:840-845. 5. Holland TT, Weber CB, James WD. Tender periungual nodules. Myrmecia (deep palmoplantar warts). Arch Dermatol. 1992;128(1):105-106, 108-109. 6. Beutner, KR. Nongenital human papillomavirus in ections. Clin Lab Med. 2000;20:423-430. 7. Berman A, Domnitz JM, Winkelmann RK. Plantar warts recently turned black. Arch Dermatol. 1982;118:47-51. 8. Landsman MJ, Mancuso JE, Abramow SP. Diagnosis, pathophysiology, and treatment o plantar verruca. Clin Podiatr Med Surg. 1996;13(1):55-71. 9. Gibbs S, Harvey I. Cochrane Summaries. Topical Treatments for Cutaneous Warts. http:/ / www.cochrane.org/ reviews/ en/ ab001781.html. Accessed April 1, 2008. 10. Cockayne S, Hewitt C, Hicks K, et al. Cryotherapy versus salicylic acid or the treatment o plantar warts (verrucae): a randomized controlled trial. BMJ. 2011;342:d3271.

637

PART 14 DERMATO LO GY

638

SECTIO N 4

Ch a pt e r 134

FUNGAL

134 FUNGAL O VERVIEW Richard P. Usatine , MD

PATIENT STO RY A 55-year-old woman presents with a red pruritic area on her ace or 3 months (Figure 134-1). The annular distribution immediately is suspicious or a dermatophyte in ection. Further investigation demonstrates that the patient has severe tinea pedis in a moccasin distribution. The patient is treated with an oral anti ungal agent and her ungal in ection clears over the coming month. INTRO DUCTIO N Fungal in ections o the skin and mucous membranes are ubiquitous and common. There are many types o ungus that grow on humans but they all share a predilection or warm and moist areas. Consequently, hot and humid climates promote ungal in ections, but many areas o the skin can get warm and sweaty even in cold climates, such as the eet and groin.

SYNO NYMS Pityriasis versicolor equals tinea versicolor.

PATHO PHYSIO LO GY Mucocutaneous ungal in ections are caused by the ollowing:

FIGURE 134-2 Annular p ruritic le sion with conce ntric ring s in the axilla o a young woman cause d b y tine a corp oris. The conce ntric ring s have a hig h sp e ci city or tine a in e ctions. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

and these ungi cause tinea pedis and manus, tinea capitis, tinea corporis, tinea cruris, tinea aciei, and onychomycosis (Figures 134-1 to 134-6). • Yeasts in the genera o Candida and Pityrosporum (Malassezia)—There are multiple species o Candida that can cause mucocutaneous in ections with Candida albicans as the most common one involved (Figure 134-7). Pityrosporum causes seborrhea and tinea versicolor (Figure 134-8). Although tinea versicolor has the name tinea in it, it is not a true dermatophyte and may be best called pityriasis versicolor.

• Dermatophytes are caused by 3 genera: Microsporum, Epidermophyton, and Trichophyton. There are approximately 40 species in the 3 genera

DIAGNO SIS CLINICAL FEATURES O F TINEA INFECTIO NS Clinical eatures include scaling, erythema, pruritus, central clearing, concentric rings, and maceration (Table 134-1). Changes in pigmentation are not uncommon in various types o tinea especially tinea versicolor. • Figure 134-1 shows tinea aciei on the ace with typical scaling and ring-like pattern, hence, the name ringworm. There is also erythema and central clearing. The patient was experiencing pruritus. • Figure 134-2 shows annular pruritic lesion with concentric rings in the axilla o a young woman caused by tinea corporis. The concentric rings have a high speci city (80%) or tinea in ections. • Note that tinea in ections will not show central clearing in 58% o cases, as in Figure 134-3 in which tinea cruris has no central clearing. FIGURE 134-1 Tine a acie i on the ace o a 55-ye ar-old woman with typ ical scaling and ring -like p atte rn (ring worm). Note the we ll-d e marcate d raise d b ord e r and ce ntral cle aring . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Hyperpigmentation is common in dark-skinned individuals, as seen in Figure 134-4 on the f ank o this Hispanic woman. • Hypopigmentation is requently seen in tinea versicolor (see Figure 134-8).

FUNGa L O Ve r VIe W

FIGURE 134-3 Tine a cruris with we ll-d e marcate d raise d b ord e r and no ce ntral cle aring . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

FIGURE 134-6 Two- oot, 1-hand synd rome with tine a manus o 1 hand and tine a p e d is o b oth e e t. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 134-4 Tine a corp oris on the rig ht f ank o a woman b e nd ing orward . Note the p ostinf ammatory hyp e rp ig me ntation, annular p atte rns in are as o ce ntral sp aring . (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

FIGURE 134-7 Thrush in the mouth o a p atie nt with d iab e tic ke toacid osis. This mucosal Cand id a in e ctio n was con rme d with a KO H p re p aration. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 134-5 Recurrent tinea cruris in a woman with a well-demarcated raised scaling border. (Reproduced with permission from Richard P. Usatine, MD.)

FIGURE 134-8 Tine a ve rsicolor showing hyp op ig me ntation on the che st. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

639

PART 14 DERMATO LO GY

640

Ch a pt e r 134

TABLE 134-1 Diag nostic Value o Se le cte d Sig ns and Symp toms in Tine a In e ction *

Sig n/ Symp t o m

Se nsit ivit y (%)

Sp e cif cit y (%)

PV+ (%)

PV– (%)

LR+

LR–

Scaling

77

20

17

80

0.96

1.15

Erythe ma

69

31

18

83

1.00

1.00

Pruritus

54

40

16

80

0.90

1.15

Ce ntral cle aring

42

65

20

84

1.20

0.89

Conce ntric ring s

27

80

23

84

1.35

0.91

Mace ration

27

84

26

84

1.69

0.87

LR–, ne g ative like lihood ratio; LR+ , p ositive like lihood ratio; PV–, ne g ative p re d ictive * Sig ns and symp toms we re comp ile d b y 27 g e ne ral p ractitione rs p rior to sub mission 148 conse cutive p atie nts with e rythe matosq uamous le sions o g lab rous skin. Culture e vid e nce = 2b . Data rom J Fam Pract. 1999;48:611-615. Re p rod uce d with p e rmission rom Frontline

TYPICAL DISTRIBUTIO N • Fungal in ections can be seen rom the head down to the toes. Fungus especially likes warm and moist areas, so intertriginous areas (see Figure 134-5) and mucus membranes are very commonly a ected. • The 2- oot, 1-hand syndrome is a curious phenomenon with tinea manus o one hand and tinea pedis o both eet (see Figure 134-6). It is not clear why only one hand is involved in these cases. In this case, it was the nondominant hand. LABO RATO RY STUDIES Creating a potassium hydroxide (KOH) prep • Scrape the leading edge o the lesion on to a slide using the side o a # 15 scalpel or another microscope slide (Figure 134-9). • Use your coverslip to push the scale into the center o the slide.

value ; PV+ , p ositive p re d ictive value . o skin or ung al culture . Sp e cime ns we re take n rom re sults we re consid e re d the g old stand ard ; le ve l o Me d ical Communications.

• DMSO acts as a sur actant that helps to break up the cell membranes o the epithelial cells without heating. Fungal stains that come with KOH and a sur actant in the solution are very simple to use. These inexpensive stains come conveniently in small plastic squeeze bottles that have a shel li e o 1 to 3 years. Two use ul stains that can make it easier to identi y ungus are chlorazol and Swartz-Lamkins stains. Swartz-Lamkins stain has a longer shel li e and is my pre erred stain. • Examine with microscope starting with 10 power to look or the cells and hyphae and then switch to 40 power to con rm your ndings (Figures 134-10 to 134-13). The ungal stain helps the hyphae to stand out among the epithelial cells. • It helps to start with 10 power to nd the clumps o cells and look or groups o cells that appear to have ungal elements within them (see Figure 134-10).

• Gently heat with f ame rom an alcohol lamp or lighter i you are using plain KOH without dimethyl sul oxide (DMSO). Avoid boiling.

• Do not be ooled by cell borders that look linear and branching. True ungal morphology at 40 power should con rm that you are looking at real ungus and not arti act. The ungal stains bring out these characteristics including cell walls, nuclei, and arthroconidia (see Figures 134-11 to 134-13).

FIGURE 134-9 Making a KO H p re p aration b y scrap ing in are a o scale with a #15 b lad e . This was a case o tine a ve rsicolor. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 134-10 Trichop hyton rub rum rom tine a cruris visib le among skin ce lls using lig ht microscop y at 10 p owe r and Swartz-Lamkins ung al stain. Start your se arch o n 10 p owe r and move to 40 p owe r to con rm your nd ing s. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

• Add 2 drops o KOH (or ungal stain) to the slide and place coverslip on top.

PART 14 DERMATO LO GY

FUNGa L O Ve r VIe W

• KOH test characteristics1 (without ungal stains)—Sensitivity 77% to 88%, speci city 62% to 95% (Table 134-2). The sensitivity and specicity should be higher with ungal stains and the experience o the person per orming the test.

O THER LABO RATO RY STUDIES • Fungal culture—Send skin scrapings, hair, or nail clippings to the laboratory in a sterile container such as a urine cup. These will be plated out on ungal agar and the laboratory can report the species i positive. • Biopsy specimens can be sent in ormalin or periodic acid-Schi (PAS) staining when KOH and ungal cultures seem to be alsely negative.

FIGURE 134-11 Trichop hyton rub rum rom tine a cruris using SwartzLamkins ung al stain at 40 p owe r. Straig ht hyp hae with visib le se p tae . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• UV light (Wood lamp) is used to look or f uorescence. The Microsporum species are most likely to f uoresce. However, the majority o tinea in ections are caused by Trichophyton species that do not f uoresce.

MANAGEMENT There is a wide variety o topical anti ungal medications (Table 134-3). A Cochrane systematic review o 70 trials o topical anti ungals or tinea pedis showed good evidence or e cacy compared to placebo2 or the ollowing: • Allylamines (na ti ne, terbina ne, butena ne). • Azoles (clotrimazole, miconazole, econazole). • Allylamines cure slightly more in ections than azoles but are more expensive. 2 • No di erences in e cacy ound between individual topical allylamines or individual azoles. 2 SO R A

FIGURE 134-12 Arthroconid ia visib le rom tine a cruris using SwartzLamkins ung al stain at 40 p owe r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Evidence or the management onychomycosis by topical treatments is sparse. There is some evidence that ciclopirox and butena ne are both marginally e ective, but they both need to be applied daily or at least 1 year. 3 Oral anti ungals are needed or all tinea capitis in ections and or more severe in ections o the rest o the body. 4 True dermatophyte in ections that do not respond to topical anti ungals may need an oral agent. • A Cochrane systematic review o 12 trials o oral anti ungals or tinea pedis showed oral terbina ne or 2 weeks cures 52% more patients than oral griseo ulvin. 5 SO R A • Terbina ne is equal to itraconazole in patient outcomes. 5 • No signi cant di erences in comparisons between a number o other oral agents. 5 Oral anti ungals used or ungal in ections o the skin, nails, or mucous membranes include the ollowing:

FIGURE 134-13 Trichop hyton rub rum rom tine a cruris using chlorazol b lack ung al stain at 40 p owe r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• • • • •

Itraconazole (Sporanox) Fluconazole (Dif ucan) Griseo ulvin Ketoconazole (Nizoral) Terbina ne (Lamisil)

641

PART 14 DERMATO LO GY

642

Ch a pt e r 134

TABLE 134-2 Diag nostic Value o Clinical Diag nosis and KO H Pre p in Tine a In e ction

Te st

Se nsit ivit y (%)

Sp e cif cit y (%)

PV+ (%)

PV– (%)

LR+

LR–

Clinical d iag nosis *

81

45

24

92

1.47

0.42

KO H p re p (stud y 1)†

88

95

73

98

17.6

0.13

KO H p re p (stud y 2)†

77

62

59

79

2.02

0.37

LR–, ne g ative like lihood ratio; LR+ , p ositive like lihood ratio; PV–, ne g ative p re d ictive value ; PV+ , p ositive p re d ictive value . * The clinical d iag nosis se t was comp ile d b y 27 g e ne ral p ractitione rs p rior to sub mission o skin or ung al culture . Sp e cime ns we re take n rom conse cutive p atie nts with e rythrosq uamous le sions. Culture re sults we re consid e re d the g old stand ard ; stud y q uality = 2b . † Both stud ie s o KO H p re p s we re op e n analyse s o p atie nts with susp icious le sions. Paire d ung al culture was initiate d simultane ously with KO H p re p and was consid e re d the g old stand ard ; stud y q uality = 2b . Data rom Thomas B. Cle ar choice s in manag ing e p id e rmal tine a in e ctions. J Fam Pract. 2003;52(11):850-862. Re p rod uce d with p e rmission rom Frontline Me d ical Communications.

One meta-analysis suggests that terbina ne is more e cacious than griseo ulvin in treating tinea capitis caused by Trichophyton species, whereas griseo ulvin is more e cacious than terbina ne in treating tinea capitis caused by Microsporum species. 6 SO R A Details o treatments or multiple types o ungal skin in ections are supplied in the ollowing chapters. PATIENT RESO URCES

• Doctor fungus—http:/ / www.doctorfungus.org/ .

PRO VIDER RESO URCES

• Fungal skin—http:/ / www.dermnetnz.org/ fungal/ . • Doctor fungus—http:/ / www.doctorfungus.org/ . • World of dermatophytes—http:/ / www.provlab.ab.ca/ mycol/ tutorials/ derm/ dermhome.htm. • Swartz-Lamkins fungal stain can be easily purchased online— http:/ / www.delasco.com/ pcat/ 1/ Chemicals/ Swartz_ Lamkins/ dlmis023/ .

TABLE 134-3 Top ical Anti ung al Pre p arations

Ge ne ric Name

Brand Name

O TC o r Rx

Class

Bute na ne

Me ntax Lotrimin Ultra

Rx O TC

Allylamine

Ciclop irox

Lop rox

Rx

Pyrid one

Clotrimazole

Lotrimin AF Cre am Lotrimin AF Sp ray

O TC

Azole

Econazole

Sp e ctazole

Rx

Azole

Ke toconazole

Nizoral

2% Rx

Azole

Miconazole

Micatin Ge ne ric

O TC

Azole

Na ti ne

Na tin

Rx

Allylamine

O xiconazole

O xistat

Rx

Azole

Se rtaconazole

Ertaczo

Rx

Azole

Te rb ina ne

Lamisil AT

O TC

Allylamine

Tolna tate *

Tinactin cre am Lamisil AF d e e nse and Tinactin p owd e r sp ray Ge ne ric cre am

O TC

Misce llane ous

O TC, ove r the counte r. * All the ab ove anti ung als will tre at d e rmatop hyte s and Cand id a. Tolna tate is e e ctive only or d e rmatop hyte s and not Cand id a. Nystatin is e e ctive only or Cand id a and not the d e rmatop hyte s.

FUNGa L O Ve r VIe W

REFERENCES 1. Thomas B. Clear choices in managing epidermal tinea in ections. J Fam Pract. 2003;52:850-862. 2. Craw ord F, Hart R, Bell-Syer S, et al. Topical treatments or ungal in ections o the skin and nails o the oot. Cochrane Database Syst Rev. 2000;(2):CD001434. 3. Craw ord F, Hollis S. Topical treatments or ungal in ections o the skin and nails o the oot. Cochrane Database Syst Rev. 2007 Jul 18;(3): CD001434.

PART 14 DERMATO LO GY 4. Gonzalez U, Seaton T, Bergus G, et al. Systemic anti ungal therapy or tinea capitis in children. Cochrane Database Syst Rev. 2007 Oct 17;(4): CD004685. 5. Bell-Syer SE, Hart R, Craw ord F, et al. Oral treatments or ungal in ections o the skin o the oot. Cochrane Database Syst Rev. 2002;(2):CD003584. 6. Tey HL, Tan AS, Chan YC. Meta-analysis o randomized, controlled trials comparing griseo ulvin and terbina ne in the treatment o tinea capitis. JAmAcad Dermatol. 2011;64:663-670.

643

644

PART 14 DERMATO LO GY

Ch a pt e r 135

135 CANDIDIASIS Richard P. Usatine , MD

PATIENT STO RY A 42-year-old man (Figure 135-1) was admitted to the hospital or community-acquired pneumonia and type 2 diabetes out o control. On the second day o admission, when he was eeling a bit better, he asked about the itching he was having on his penis. Physical examination revealed an uncircumcised penis with white discharge on the glans and inside the oreskin consistent with Candida balanitis. Potassium hydroxide (KOH) prep was positive or the pseudohyphae o Candida. The patient was treated with a topical azole and the balanitis resolved.

A

INTRO DUCTIO N Cutaneous and mucosal Candida in ections are seen commonly in in ants with thrush and diaper rash. Also children and teens with obesity, diabetes, hyperhidrosis, and/ or immunode ciency are at higher risk o developing these in ections.

EPIDEMIO LO GY • Candida thrush is common in immunosuppressed adults (HIV and during chemotherapy). • Candida thrush can also occur in adults wearing dentures or a ter a course o antibiotics. (Figure 135-2). • Candida balanitis is more common in uncircumcised men than in them who have been circumcised (see Figure 135-1).

ETIO LO GY AND PATHO PHYSIO LO GY • In ections caused by Candida species are primarily Candida albicans. 1 • C. albicans has the ability to exist in both hyphal and yeast orms (termed dimorphism). I pinched cells do not separate, a chain o cells is produced and is termed pseudohyphae. 1

B FIGURE 135-2 Thrush and a Cand id a g roin rash in a 46-ye ar-old woman who was g ive n antib io tics o r a urinary tract in e ctio n. The wo man had p re viously su e re d a stroke and was we aring an ad ult d iap e r to d e al with he r urinary incontine nce . A. Note the white coating on the tong ue . A KO H p re p aration was p ositive or Cand id a. B. Note the sate llite le sions which are typ ical in a Cand id a in e ction o the g roin. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

RISK FACTO RS Obesity, diabetes, hyperhidrosis, immunode ciency, HIV, heat, use o oral antibiotics, and use o inhaled or systemic steroids are the risk actors.1

DIAGNO SIS CLINICAL FEATURES FIGURE 135-1 Cand id a b alanitis in a man with uncontrolle d d iab e te s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Typical distribution—Groin, glans penis, vulva, in ramammary, under abdominal pannus, between ngers, in the creases o the neck, corners o mouth, nail olds in chronic paronychia.

Ca NDIDIa SIS

PART 14 DERMATO LO GY

FIGURE 135-3 Cand id a rash with sup e rimp ose d contact d e rmatitis in a b re ast- e e d ing woman. He r b ab y has thrush and b oth ne e d tre atme nt to e rad icate the in e ctio n. The co ntact d e rmatitis was to the ne o mycinco ntaining top ical antib iotic she ap p lie d to he r sore b re asts. (Re p ro d uce d with p e rmission from Jack Re sne ck, Sr., MD.)

• Morphology—Macules, patches, plaques that are pink to bright red with small peripheral satellite lesions. • Candidiasis o the nipple in the nursing mother is associated with in antile thrush (Figures 135-3). Nipple candidiasis is almost always bilateral, with the nipples appearing bright red and inf amed. In this case, the inf ammation was made worse by the application o a topical antibiotic that caused a secondary contact dermatitis. • The Candida in ection in the corners o the mouth is called perlèche or angular cheilitis (Figure 135-4). When accompanied by thrush it may be a sign o HIV/ AIDS. • Thrush can be caused by Candida growing on the upper plate o a denture and the roo o the mouth (Figure 135-5). • Ask about recent antibiotic use i there is a new onset o a rash with satellite lesions. In Figure 135-6, the man with diabetes had a course o antibiotics be ore he developed a Candida in ection in his groin. LABO RATO RY STUDIES Scrape involved area and add to a slide with KOH (dimethyl sul oxide [DMSO] optional). C. albicans exist in both hyphal and yeast orms (dimorphism). Look or pseudohyphae and/ or budding yeast (Figure 135-7).

FIGURE 135-4 Thrush and p e rlè che in a man with AIDS. The Cand id a in e ction in the corne rs o the mouth is calle d p e rlè che o r ang ular che ilitis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 135-5 Cand id a on the roo o the mouth in an e ld e rly woman using d e nture s. This is a common comp lication o d e nture use and should b e susp e cte d i a p atie nt p re se nts with ne w-onse t p ain und e r the d e nture s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIFFERENTIAL DIAGNO SIS • Intertrigo is a nonspeci c inf ammatory condition o the skin olds. It is induced or aggravated by heat, moisture, maceration, and riction. The condition is requently worsened by in ection with Candida or dermatophytes (Figures 135-8 and 135-9). In Figure 135-8 there is signi cant hyperpigmentation secondary to the inf ammation. • Tinea corporis or cruris—Can be distinguished rom Candida when you see an annular pattern or concentric circles in the tinea (Figure 135-9).

FIGURE 135-6 Cand id a ing uinal e rup tion in a 61-ye ar-old man a te r a course o antib iotics or b ronchitis. Note the sate llite le sions. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

645

PART 14 DERMATO LO GY

646

A

Ch a pt e r 135

FIGURE 135-9 Tine a corp oris und e r the b re asts o a 55-ye ar-old woman. Note the annular p atte rn with we ll-d e marcate d b ord e rs. KO H was p ositive or d e rmatop hyte s and not Cand id a. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

There is no scrotal involvement in tinea cruris. Candida intertrigo may have scrotal involvement (see Chapters 136, Tinea Corporis and 137, Tinea Cruris). • Erythrasma—May be brown and glows a coral red with ultraviolet (UV) light (see Chapter 121, Erythrasma). • Inverse psoriasis—Psoriasis in the intertriginous areas as seen in Figure 135-10 (see Chapter 150, Psoriasis). • Seborrhea—In lammation related to overgrowth o Pityrosporum, a yeast-like organism (see Chapter 149, Seborrheic Dermatitis). B FIGURE 135-7 A. and B. The b ranching p se ud ohyp hae o Cand id a rom thrush und e r the microscop e . Note the b ud d ing ye ast. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 135-8 Cand id a und e r the b re asts o an ove rwe ig ht Hisp anic woman showing hyp e rp ig me ntation. The b ord e r is not we ll d e marcate d and the re are sate llite le sions. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 135-10 Inve rse p soriasis that close ly re se mb le s Cand id a inte rtrig o in the sub mammary old s. This p atie nt d id not imp rove with top ical anti ung als and f nally a b iop sy showe d that this was inve rse p soriasis. Inve rse p soriasis is o te n mistake n or a ung al in e ction unle ss the p hysician is aware o this cond ition. Fre q ue ntly the re are othe r clue s to the d iag nosis o p soriasis in the skin and nails so that a b io p sy is no t ne e d e d . (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

Ca NDIDIa SIS

MANAGEMENT PRIMARY CANDIDAL SKIN INFECTIO NS • Topical azoles, including clotrimazole, miconazole, and nystatin (polyenes) are e ective. 2,3 SO R B • Keeping the in ected area dry is important. 2 SO R C • For more details o the topical anti ungals, see Table 134-3 in Chapter 134, Fungal Overview. • In one study, miconazole ointment was well tolerated and signi cantly more e ective than the zinc oxide/ petrolatum vehicle control or treatment o diaper dermatitis complicated by candidiasis. 3 • Do not use tolna tate, which is active against dermatophytes but not Candida. • I recurrent or recalcitrant, consider f uconazole 150 mg weekly × 2 or ketoconazole 200 mg daily or 1 to 2 weeks. O RO PHARYNGEAL CANDIDIASIS • Treat initial episodes with clotrimazole troches (one 10-mg troche 5 times per day or adults) or nystatin (available as a suspension o 100,000 U/ mL [dosage, 4-6 mL qid] or as f avored 200,000 units pastilles [dosage, 1 or 2 pastilles 4-5 times per day or 7-14 days]). 2 SOR B

• Oral f uconazole (100 mg/ d or 7-14 days) is as e ective as—and, in some studies, superior to—topical therapy. 2 SO R • Itraconazole solution (200 mg/ d or 7-14 days) is as e ective as f uconazole. 2 SO R • Ketoconazole and itraconazole capsules are less e ective than f uconazole, because o variable absorption. 2 SO R • Fluconazole-re ractory oropharyngeal candidiasis will respond to oral itraconazole therapy (>200 mg/ d, pre erably in solution orm) approximately two-thirds o the time. 2 SO R • Children with thrush are usually treated with oral nystatin suspension. 2 SO R B

• HIV/ AIDS patients with oral candidiasis may be treated with clotrimazole troches. I unresponsive to topical therapy, f uconazole may be needed. 2 SO R • Denture-related disease may require extensive and aggressive disin ection o the denture or de nitive cure. 2 SO R C MAMMARY CANDIDIASIS IN BREAST-FEEDING • Most mammary candidiasis does not present with the red breasts seen in Figure 135-3. • Nipple pain and discom ort along with thrush are adequate data to treat the mother and child. • Topical nystatin and oral f uconazole are sa e or in ants and the mother. 2 CHRO NIC MUCO CUTANEO US CANDIDIASIS • Chronic mucocutaneous candidiasis (Figure 135-11) requires a longterm approach that is analogous to that used in patients with AIDS. 2

FIGURE 135-11 Se ve re chronic cutane ous cand id iasis in a 22-ye ar-old man with immunosup p re ssion. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Systemic therapy is needed, and azole anti ungal agents (ketoconazole, f uconazole, and itraconazole) have been used success ully. 2 • As with HIV-in ected patients, development o resistance to these agents has been described. 2

PATIENT EDUCATIO N Keep the in ected area clean and dry. For thrush in a baby, treat sources o in ection such as the mother’s breasts and bottle nipples. I the baby is bottle ed, boil the nipples between uses.

PATIENT AND PRO VIDER RESO URCES

• Medscape. Cutaneous Candidiasis—http:/ / emedicine .medscape.com/ article/ 1090632. • Medscape. Intertrigo—http:/ / emedicine.medscape.com/ article/ 1087691.

REFERENCES 1. Schein eld N. Cutaneous Candidiasis. Updated August 2, 2011. http:/ / emedicine.medscape.com/ article/ 1090632. Accessed September 5, 2011. 2. Pappas PG, Rex JH, Sobel JD, et al. Guidelines or treatment o candidiasis. Clin Infect Dis. 2004;38:161-189. 3. Spraker MK, Gisoldi EM, Sieg ried EC, et al. Topical miconazole nitrate ointment in the treatment o diaper dermatitis complicated by candidiasis. Cutis. 2006;77(2):113-120.

647

PART 14 DERMATO LO GY

648

136 TINEA CO RPO RIS Richard P. Usatine , MD Ad e liza Jime ne z, MD

Ch a pt e r 136

Swartz-Lamkins ungal stain is added to the slide and branching hyphae are seen (Figure 136-1C). Tinea corporis is diagnosed but the previous use o a topical steroid allows one to call this a case o tinea incognito. The patient was treated with terbina ne 250 mg daily or 2 weeks with ull clearing.

INTRO DUCTIO N

PATIENT STO RY A 45-year-old woman presents to her internist with a rash that has been itching under her breast or the past 6 months (Figure 136-1A). She had gone to an urgent care center and received a topical steroid which only partially relieved the itching. On physical examination there is erythema and scale under the breast with a well-demarcated partial annular border (see Figure 136-1A). The erythema and scale are most prominent on the edge creating a clinical suspicion or tinea corporis. There are no satellite lesions that may be seen with candidiasis and the patient does not have a history o psoriasis. The physician scrapes the leading edge to create a potassium hydroxide (KOH) preparation (Figure 136-1B).

Tinea corporis is a common super cial ungal in ection o the body, characterized by well-demarcated, annular lesions with central clearing, erythema, and scaling o the periphery.

A

B

EPIDEMIO LO GY Dermatophytes are the most prevalent agents causing ungal in ections in the United States, with Trichophyton rubrum causing the majority o cases o tinea corporis, tinea cruris, tinea manuum, and tinea pedis.

C FIGURE 136-1 A. Tine a corp oris with scaling , e rythe ma, and ce ntral sp aring und e r the b re ast. B. Scrap ing the e d g e or a KO H p re p aration to con rm the clinical imp re ssion. C. Branching hyp hae e asily se e n at 40× p owe r using ung al stain (Swartz-Lamkins) rom a scrap ing o tine a corp oris. Note how the hyp hae stand out with the b lue ink color. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

t INe a CO r pO r IS

PART 14 DERMATO LO GY

• Excessive heat and humidity make a good environment or ungal growth. • Dermatophytes spread by exposure to in ected animals or persons and contact with contaminated items.

ETIO LO GY AND PATHO PHYSIO LO GY Tinea corporis is caused by ungal species rom any one o the ollowing 3 dermatophyte genuses: Trichophyton, Microsporum, and Epidermophyton. T. rubrum is the most common causative agent o tinea corporis. • Dermatophytes produce enzymes such as keratinase that penetrate keratinized tissue. Their hyphae invade the stratum corneum and keratin and spread centri ugally outward.

RISK FACTO RS • Participation in daycare centers • Living in a nursing home • Poor personal hygiene • Living conditions with poor sanitation • Warm, humid environments • Conditions that cause weakening o the immune system (eg, AIDS, cancer, organ transplantation, diabetes)

FIGURE 136-2 Tine a acie i in a 42-ye ar-old woman who had wid e sp re ad tine a corp o ris. It re so lve d with o ral te rb ina ne . (Re p ro d uce d with p e rmission from O lvia Re ve lo, MD.)

LABO RATO RY STUDIES

DIAGNO SIS The diagnosis can be made rom history, clinical presentation, culture, and direct microscopic observation o hyphae in in ected tissue and hairs a ter KOH preparation.

• KOH preparation o skin scraping can be very use ul to con rm a clinical impression or when the diagnosis is not certain. Scrape the skin with the side o a slide or scalpel, making sure to scrape the periphery and the erythematous part. Scrape hard enough to get some stratum corneum without causing signi cant bleeding. False negatives can occur secondary to inadequate scraping, patient using topical anti ungals, or an inexperienced microscopist.

CLINICAL FEATURES • Pruritus o a ected area. • Well-demarcated, annular lesions with central clearing, erythema, and scaling o the periphery. Concentric rings are highly speci c (80%) or tinea in ections (see Figure 136-1). • Central clearing is not always present (Figure 136-2). • Although scale is the most prominent morphologic characteristic, some tinea in ections will actually cause pustules rom the inf ammatory response (Figure 136-3). TYPICAL DISTRIBUTIO N It occurs on any part o the body including the ace and axilla (Figures 136-1 to 136-4). Tinea incognito is a type o tinea in ection that was previously not recognized by the physician or patient and topical steroids were used on the site. While applying the steroid, the dermatophyte continues to grow and orm concentric rings (Figures 136-5 and 136-6). Tinea corporis can cover large parts o the body as in Figures 136-7 to 136-9. In some cases the in ection may cause hyperpigmentation (see Figures 136-7 to 136-9).

FIGURE 136-3 Tine a corp oris with p ustule s and scale . KO H p re p aration was p ositive or b ranching hyp hae . The p ustule s are a mani e station o an inf ammatory re sp onse to the d e rmatop hyte in e ction. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

649

PART 14 DERMATO LO GY

650

Ch a pt e r 136

prep is negative and this does not t the clinical picture, wait a ew hours and look at the KOH prep again as the ungi may become more visible over time (see Figure 136-11). • Skin scraping and culture—Gold standard, but more costly and may take up to 2 weeks or the culture to grow. Consider culture i the KOH prep is negative but tinea is still suspected, or when a microscope is not available. • Skin biopsy sent in ormalin or periodic acid-Schi (PAS) staining when the KOH and culture remain negative but the clinical picture is consistent with a ungal in ection.

DIFFERENTIAL DIAGNO SIS • Granuloma annulare—Inf ammatory, benign dermatosis o unknown cause, characterized by both dermal and annular papules (Figure 136-12) (see Chapter 171, Granuloma Annulare). • Psoriasis—Plaque with scale on extensor sur aces and trunk. Occasionally, the plaques can have an annular appearance (Figure 136-13). Inverse psoriasis in intertriginous areas can also mimic tinea corporis (see Chapter 150, Psoriasis). FIGURE 136-4 Exte nsive tine a corp o ris in the axilla and arm o this old e r ad ult. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

• Erythema annulare centri ugum (EAC)—Scaly red rings with normal skin in the center o the rings. The scale is trailing the erythema as the ring expands while the scale is leading in tinea corporis (Figure 136-14) (see Chapter 204, Erythema Annulare Centri ugum).

• Use KOH (plain, with dimethyl sul oxide [DMSO], or in a ungal stain) to break up the epithelial cells more rapidly without heating (Figure 136-10). It is easy to purchase a small bottle o SwartzLamkins ungal stain that includes KOH, a sur actant, and blue ink. The blue ink allows the hyphae to stand out, thereby saving time and decreasing the chance o a alse-negative result (Figure 136-11). I the epithelial cells are not breaking up su ciently, use a f ame under the slide or approximately 5 seconds to speed up the process. I the KOH

• Cutaneous larva migrans has serpiginous burrows made by the hookworm larvae, and these burrows can look annular and be con used with tinea corporis (see Chapter 142, Cutaneous Larva Migrans).

A

B

• Nummular eczema—Round coin-like red scaly plaques without central clearing (see Chapter 143, Atopic Dermatitis). • Erythrasma—Found in the axilla and groin without an annular con guration and central clearing. Coral red f uorescence is seen under a UV lamp (see Chapter 121, Erythrasma).

FIGURE 136-5 Tine a incog nito on the che st and arm o this b lack woman. This tine a in e ction continue d to g row as the p atie nt ap p lie d the top ical ste roid s g ive n to he r b y he r p hysician. The re is an e xte nsive amount o p ostinf ammatory hyp e rp ig me ntation. A. Tine a incog nito on the arm with conce ntric ring s as this d e rmatop hyte in e ction continue d to g ro w und e r the inf ue nce o the top ical ste roid s. B. Tine a incog nito on the che st. (Re p ro d uce d with p e rmission fro m Richard P. Usatine , MD.)

t INe a CO r pO r IS

PART 14 DERMATO LO GY

FIGURE 136-6 Tine a incog nito in the axillary re g ion o a young man who was p re scrib e d top ical ste roid s. Althoug h the re is some hyp e rp ig me ntation, e rythe ma is mo st p romine nt. (Re p rod uce d with p e rmissio n from Chris We nne r, MD.)

MANAGEMENT • Use topical anti ungal medications or tinea corporis that involves small areas o the body such as seen in Figures 136-1 and 136-2. • Although all the topical anti ungal agents may be e ective, the evidence supports the greater e ectiveness o the allylamines (terbina ne)

FIGURE 136-7 Tine a co rp o ris co ve ring the b ack and sho wing we lld e marcate d b o rd e rs. (Re p ro d uce d with p e rmissio n from Richard P. Usatine , MD.)

FIGURE 136-8 Tine a co rp o ris o n the b ack, sho uld e r, and arm with e rythe ma and hyp e rp ig me ntatio n. (Re p ro d uce d with p e rmissio n fro m Richard P. Usatine , MD.)

over the less-expensive azoles or tinea pedis and corporis. Allylamines cure slightly more in ections than azoles and are now available over the counter. 1,2 SO R • Studies show that terbina ne 1% cream or solution applied once daily or 7 days is highly e ective or tinea corporis/ cruris. 3,4 The 1% cream

FIGURE 136-9 Tine a corp oris rom the trunk d own b oth le g s with sig ni cant hyp e rp ig me ntation. (Re p ro d uce d with p e rmissio n from Richard P. Usatine , MD.)

651

652

PART 14 DERMATO LO GY

FIGURE 136-10 Branching hyp hae at 40× p owe r rom KO H p re p aration o tine a corp oris. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Ch a pt e r 136

FIGURE 136-13 Wid e sp re ad annular le sions cause d b y p soriasis. Not all le sions that are annular with scale are tine a corp oris. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

(which is available over the counter as Lamisil AF) produced a mycologic cure o 84.2% versus 23.3% with placebo. Number needed to treat (NNT) = 1.6. 3 SO R • Oral anti ungal agents should be considered or rst-line therapy or tinea corporis covering large areas o the body, as seen in Figures 136-6 and 136-7. However, it is not wrong to attempt topical treatment i the size o the area in ected is on the borderline. The patient with tinea incognito in Figures 136-4 and 136-5 did need oral therapy to resolve her in ection. Un ortunately, the postinf ammatory hyperpigmentation did not resolve well. • One randomized controlled trial (RCT) showed that oral itraconazole 200 mg daily or 1 week is similarly e ective, equally well tolerated, and at least as sa e as itraconazole 100 mg or 2 weeks in the treatment o tinea corporis or cruris. 5 SO R B FIGURE 136-11 Branching se p tate hyp hae e asily se e n at 40× p owe r using ung al stain (Swartz-Lamkins) rom a scrap ing o tine a corp oris. The KO H pre p was p ositive the d ay b e ore . This p hotomicrog rap h was take n the ollowing d ay whe n the skin ce lls we re le ss visib le and the hyp hae had maximally take n up the b lue ink color. This is to hig hlig ht how waiting a e w hours or e ve n 1 d ay can b ring out a p ositive KO H e ve n whe n it orig inally ap pe are d ne g ative . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 136-12 Multip le annular le sions cause d by g ranuloma annulare . No scale is visib le . (Re prod uce d with pe rmission from Richard P. Usatine , MD.)

• In one study, patients with mycologically diagnosed tinea corporis and tinea cruris were randomly allocated to receive either 250 mg o oral

FIGURE 136-14 Erythe ma annulare ce ntri ug um (EAC) in the axilla o a 28-ye ar-old man. A te r multip le aile d trials o anti ung al me d icine s, a p unch b iop sy showe d this to b e EAC. Note the trailing scale rathe r than le ad ing scale se e n in tine a corp oris. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

t INe a CO r pO r IS

terbina ne once daily or 500 mg o griseo ulvin once daily or 2 weeks. The cure rates were higher or terbina ne at 6 weeks. 6 SO R B • In summary, i an oral agent is needed, the evidence is greatest or the use o the ollowing: 6 Terbina ne 250 mg daily or 2 weeks. SO R B (Terbina ne is avail° able as an inexpensive generic prescription on the $4 and $5 plans in the United States. It also has less drug interactions than itraconazole. For these reasons it is usually the pre erred treatment when an oral agent is needed.) 5 Itraconazole 200 mg daily or 1 week. SO R B (More expensive ° with more drug interactions than terbina ne.) 5 ° Itraconazole 100 mg daily or 2 weeks. SO R B

PATIENT RESO URCES

• VisualDxHealth. Ringworm—http:/ / www.visualdxhealth.com/ adult/ tineaCorporis.htm. • Medline Plus Medical Encyclopedia—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000877.htm. PRO VIDER RESO URCES

• eMedicine topic—http:/ / www.emedicine.com/ DERM/ topic421.htm. • Doctor Fungus—http:/ / www.doctorfungus.org/ . • Swartz-Lamkins fungal stain can be easily purchased online—http:/ / www.delasco.com/ pcat/ 1/ Chemicals/ Swartz_Lamkins/ dlmis023/ .

PREVENTIO N Tinea corporis and cruris are dermatophyte in ections that are particularly common in areas o excessive heat and moisture. A dry, cool environment may play a role in reducing in ection. In addition, avoiding contact with arm animals and other individuals in ected with tinea corporis and cruris may help in preventing in ection. Preventative measures or tinea in ections include practicing good personal hygiene; keeping the skin dry and cool at all times; and avoiding sharing towels, clothing, or hair accessories with in ected individuals. 7 In individuals involved in contact sports such as wrestling, a comprehensive skin disease prevention protocol includes some combination o the ollowing: washing o wrestling mats be ore and a ter each practice and competition; showers be ore and a ter each practice; use o clean clothing be ore each practice; and exclusion o in ected athletes. 8

PATIENT EDUCATIO N Keep the skin clean and dry. In ected pets should be treated.

FO LLO W-UP Consider ollow-up appointments in 4 to 6 weeks or di cult and more widespread cases. I there are concerns about bacterial superin ection, ollow-up should be sooner.

REFERENCES 1. Thomas B. Clear choices in managing epidermal tinea in ections. J Fam Pract. 2003;52:850-862. 2. Craw ord F, Hollis S. Topical treatments or ungal in ections o the skin and nails o the oot. Cochrane Database Syst Rev. 2007;3: CD001434. 3. Budimulja U, Bramono K, Urip KS, et al. Once daily treatment with terbina ne 1% cream (Lamisil) or one week is e ective in the treatment o tinea corporis and cruris. A placebo-controlled study. Mycoses. 2001;44:300-306. 4. Lebwohl M, Elewski B, Eisen D, Savin RC. E cacy and sa ety o terbina ne 1% solution in the treatment o interdigital tinea pedis and tinea corporis or tinea cruris. Cutis. 2001;67:261-266. 5. Boonk W, de Geer D, de Kreek E, et al. Itraconazole in the treatment o tinea corporis and tinea cruris: comparison o two treatment schedules. Mycoses. 1998;41:509-514. 6. Voravutinon V. Oral treatment o tinea corporis and tinea cruris with terbina ne and griseo ulvin: A randomized double blind comparative study. J Med AssocThai. 1993;76:388-393. 7. Gupta AK, Chaudhry M, Elewski B. Tinea corporis, tinea cruris, tinea nigra, and piedra. Dermatol Clin. 2003;21(3):395-400. 8. Hand JW, Wroble RR. Prevention o tinea corporis in collegiate wrestlers. JAthl Train. 1999;34(4):350-352.

653

PART 14 DERMATO LO GY

654

Ch a pt e r 137

137 TINEA CRURIS Richard P. Usatine , MD Mind y A. Smith, MD, MS

PATIENT STO RY A 59-year-old man presents with itching in the groin (Figure 137-1). On examination, he was ound to have scaly erythematous plaques in the inguinal area. A skin scraping was treated with Swartz-Lamkins stain and the dermatophyte was highly visible under the microscope (Figure 137-2). He was treated with a topical anti ungal medicine until his tinea cruris resolved.

INTRO DUCTIO N Tinea cruris is an intensely pruritic super cial ungal in ection o the groin and adjacent skin.

SYNO NYMS Tinea cruris is commonly known as crotch rot and jock itch to the lay public.

EPIDEMIO LO GY • Using data rom the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey (NHAMCS)

FIGURE 137-2 Micro scop ic vie w o the scrap ing o the g roin in a man with tine a cruris. The hyp hae are e asy to se e und e r 40 p owe r with SwartzLamkins stain. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

(1995-2004), there were more than 4 million annual visits or dermatophytoses and 8.4% were or tinea cruris. 1 • Tinea cruris is more common in men than women (3- old) and rare in children.

ETIO LO GY AND PATHO PHYSIO LO GY • Most commonly caused by the dermatophytes Trichophyton rubrum, Epidermophyton f occosum, Trichophyton mentagrophytes, and Trichophyton verrucosum. T. rubrum is the most common organism. 2 • Can be spread by omites, such as contaminated towels. • The ungal agents cause keratinases, which allow invasion o the cornied cell layer o the epidermis. 2 • Autoinoculation can occur rom ungus on the eet or hands.

RISK FACTO RS • Wearing tight- tting or wet clothing or underwear has traditionally been suggested; however, in a study o Italian soldiers, none o the risk actors analyzed (eg, hyperhidrosis, swimming pool attendance) were signi cantly associated with any ungal in ection. 3 • Obesity and diabetes mellitus may be risk actors. 4

DIAGNO SIS CLINICAL FEATURES

FIGURE 137-1 Tine a cruris in a 59-ye ar-old Hisp anic man p re se nt or 1 ye ar. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

The cardinal eatures are scale and signs o inf ammation. In light-skinned persons inf ammation o ten appears pink or red and in dark-skinned persons the inf ammation o ten leads to hyperpigmentation (Figures 137-3 and 137-4). Occasionally, tinea cruris may show central sparing with an annular pattern as in Figure 137-5, but most o ten is homogeneously distributed as in Figures 137-3 and 137-4.

t INe a Cr Ur IS

PART 14 DERMATO LO GY

FIGURE 137-5 An 18-ye ar-old woman with tine a cruris showing e rythe ma and scale in an annular p atte rn. Ce ntral cle aring is le ss common in tine a cruris than tine a corp oris b ut can occur. (Re p ro d uce d with p e rmission fro m Richard P. Usatine , MD.)

FIGURE 137-3 Tine a cruris in an old e r b lack man with hyp e rp ig me ntation se cond ary to the in ammatory re sp onse . A silve ry scale is also se e n and p soriasis should b e consid e re d in the d i e re ntial d iag nosis. In such a case , p e r orming a p otassium hyd roxid e (KO H) p re p aration is crucial to making an accurate d iag nosis as it is not p ossib le to know the d iag nosis b y ap p e arance only. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

TYPICAL DISTRIBUTIO N By de nition tinea cruris is in the inguinal area. However, the ungus can grow outside o this area to involve the abdomen and thighs (Figures 137-4 and 137-6). Tinea can be present in multiple locations, as in the patient in Figure 137-7 who had tinea in the groin, on her eet and ace, and under her breasts.

FIGURE 137-4 Tine a cruris that has e xp and e d b e yond the ing uinal are a in this 35-ye ar-old b lack man. Postin ammatory hyp e rp ig me ntation is visib le throug hout the in e cte d are a. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 137-6 A 54-ye ar-old man with tine a cruris and corp oris or de cad e s de sp ite multip le tre atme nts with oral anti ung al me d ications. His culture s show T. rub rum se nsitive to all the typ ical oral anti ung al me d ications, b ut his tine a ne ve r comple te ly cle ars. He d oe s not have a known immunod e f cie ncy but his immune syste m ap pe ars not to re cog nize the T. rub rum as ore ign. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 137-7 A 55-ye ar-old woman with tine a cruris showing e rythe ma and scale . Althoug h le ss common in wome n, wome n d o g e t tine a cruris. This p atie nt had tine a on he r e e t, ace , and und e r he r b re asts. She was tre ate d with oral te rb inaf ne or 3 we e ks. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

655

656

PART 14 DERMATO LO GY

Ch a pt e r 137

FIGURE 137-8 Erythrasma in the g ro in can b e mistake n or tine a cruris. This e rythrasma uore sce d coral re d with a ultraviole t lig ht. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

LABO RATO RY STUDIES Diagnosis is o ten made based on clinical presentation, but a skin scraping treated with KOH and a ungal stain analyzed under the microscope can be help ul (see Figure 137-2). False negatives may occur i scraping is inadequate, patient is using topical anti ungals, or the viewer is inexperienced. Skin scraping and culture is de nitive but expensive, and may take up to 2 weeks or the culture to grow. Ultraviolet (UV) lamp can be used to look or the coral red f uorescence o erythrasma (see Chapter 121, Erythrasma). Most tinea cruris is caused by T. rubrum so will not f uoresce.

DIFFERENTIAL DIAGNO SIS • Cutaneous Candida in the groin can become red and have scaling that extends to the thigh and scrotum. Tinea cruris does not o ten involve the scrotum. Candida o ten has satellite lesions. However, tinea cruris can also have a ew satellite lesions (see Chapter 135, Candidiasis). • Erythrasma in the groin appears similar to tinea cruris. It is less common than tinea cruris and may show coral red f uorescence with a UV light (Figure 137-8) (see Chapter 121, Erythrasma). • Contact dermatitis can occur anywhere on the body. I the contact is near the groin this can be mistaken or tinea cruris (see Chapter 144, Contact Dermatitis). • Inverse psoriasis causes inf ammation in the intertriginous areas o the body. It does not have the thick plaques o plaque psoriasis. Inverse psoriasis is requently misdiagnosed as a ungal in ection until an astute clinician recognizes the pattern or does a biopsy (Figure 137-9; see Chapter 150, Psoriasis). • Intertrigo is an inf ammatory condition o the skin olds. It induced or aggravated by heat, moisture, maceration, and riction. 5 The condition requently is worsened by in ection with Candida or dermatophytes so there is some overlap with tinea cruris.

MANAGEMENT • Tinea cruris is best treated with a topical allylamine or an azole antiungal (SO R , based on multiple randomized controlled trials [RCTs]). 6 Di erences in current comparison data are insu cient to

FIGURE 137-9 Inve rse p soriasis in a man who also has the nail chang e s o p soriasis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

strati y the 2 groups o topical anti ungals. 7 In one RCT, cure rates were higher at 1 week with butena ne (once daily or 2 weeks) versus clotrimazole (twice daily or 4 weeks) (26.5% vs 2.9%, respectively), but were not signi cantly di erent at 4 or 8 weeks. 8 • The ungicidal allylamines (na ti ne and terbina ne) and butena ne (allylamine derivative) are a more costly group o topical tinea treatments, yet they are more convenient as they allow or a shorter duration o treatment compared with ungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole). 7 • Topical azoles should be continued or 4 weeks and topical allylamines or 2 weeks or until clinical cure. 6-8 SO R • Fluconazole 150 mg once weekly or 2 to 4 weeks appears to be e ective in the treatment o tinea cruris. 9 SO R B • One RCT showed that itraconazole 200 mg or 1 week is similarly e ective, equally well tolerated, and at least as sa e as itraconazole 100 mg or 2 weeks in the treatment o tinea corporis or cruris (clinical response: 73% and 80% at the end o ollow-up, respectively).10 SOR B • Patients with mycologically diagnosed tinea corporis and tinea cruris were randomly allocated to receive either 250 mg o oral terbina ne once daily or 500 mg o griseo ulvin once daily or 2 weeks. The cure rates were higher or terbina ne at 6 weeks. 11 SO R B • I there are multiple sites in ected with ungus, treat all active areas o in ection simultaneously to prevent rein ection o the groin rom other body sites. I the tinea is widespread as in the patient in Figure 137-7 an oral agent is warranted. • Some patients will have been treated incorrectly with topical steroids allowing the tinea cruris to grow and spread (Figure 137-10). In these cases an oral anti ungal will be needed to eradicate the tinea incognito.

PART 14 DERMATO LO GY

t INe a Cr Ur IS

REFERENCES 1. Panackal AA, Halpern EF, Watson AJ. Cutaneous ungal in ections in the United States: analysis o the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS), 1995-2004. Int J Dermatol. 2009;48(7): 704-712. 2. Wiederkehr M, Schwartz RA. Tinea Cruris. http:/ / emedicine. medscape.com/ article/ 1091806-overview. Accessed April 2, 2012. 3. Ingordo V, Naldi L, Fracchiolla S, Colecchia B. Prevalence and risk actors or super cial ungal in ections among Italian Navy cadets. Dermatology. 2004;209(3):190-196. 4. Patel GA, Wiederkehr M, Schwartz RA. Tinea cruris in children. Cutis. 2009;84(3):133-137. 5. Selden ST. Intertrigo. http:/ / emedicine.medscape.com/ article/ 1087691-overview. Accessed April 2, 2012. FIGURE 137-10 Tine a incog nito that occurre d whe n a woman with tine a cruris was tre ate d with a to p ical ste roid rathe r than an anti ung al me d ication. (Re p rod uce d with p e rmission from O lvia P. Re ve lo, MD.)

FO LLO W-UP Follow-up should be done as needed.

PATIENT EDUCATIO N • Advise patients with tinea pedis to put on their socks be ore their undershorts to reduce the possibility o direct contamination. SO R C • Dry the groin completely a ter bathing. SO R C PATIENT RESO URCES

• Medline Plus. Jock Itch—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000876.htm. PRO VIDER RESO URCES

• DermNet NZ. Fungal Skin In ections—http:/ / www.dermnetnz .org/ fungal/ . • Doctor Fungus—http:/ / www.doctorfungus.org/ . • Medscape. Tinea Cruris—http:/ / emedicine.medscape.com/ article/ 1091806.

6. Drake LA, Dinehart SM, Farmer ER, et al. Guidelines o care or super cial mycotic in ections o the skin: tinea corporis, tinea cruris, tinea aciei, tinea manuum, and tinea pedis. Guidelines/ Outcomes Committee. American Academy o Dermatology. J Am Acad Dermatol. 1996;34(2 pt 1):282-286. 7. Nadalo D, Montoya C, Hunter-Smith D. What is the best way to treat tinea cruris? J Fam Pract. 2006;55:256-258. 8. Singal A, Pandhi D, Agrawal S, Das S. Comparative e cacy o topical 1% butena ne and 1% clotrimazole in tinea cruris and tinea corporis: a randomized, double-blind trial. J DermatologTreat. 2005;16(506):331-335. 9. Nozickova M, Koudelkova V, Kulikova Z, Malina L, Urbanowski S, Silny W. A comparison o the e cacy o oral f uconazole, 150 mg/ week versus 50 mg/ day, in the treatment o tinea corporis, tinea cruris, tinea pedis, and cutaneous candidosis. Int J Dermatol. 1998;37:703-705. 10. Boonk W, de Geer D, de Kreek E, Remme J, van Huystee B. Itraconazole in the treatment o tinea corporis and tinea cruris: comparison o two treatment schedules. Mycoses. 1998;41:509-514. 11. Voravutinon V. Oral treatment o tinea corporis and tinea cruris with terbina ne and griseo ulvin: a randomized double blind comparative study. J Med AssocThai. 1993;76:388-393.

657

PART 14 DERMATO LO GY

658

Ch a pt e r 138

138 TINEA PEDIS Richard P. Usatine , MD Katie Re p p a, MD

PATIENT STO RY A 38-year-old man presents with an itchy rash on his hands and blisters on his eet or 1 week duration (Figure 138-1). Vesicular tinea pedis with bullae were present. The papules and vesicles between the ngers were typical o an autoeczematization reaction (Id reaction) (Figure 138-2). The patient was treated with an oral anti ungal medication and a short burst o oral prednisone or the Id reaction.

INTRO DUCTIO N Tinea pedis is a common cutaneous in ection o the eet caused by dermatophyte ungus. The clinical mani estation presents in 1 o 3 major patterns: interdigital, moccasin, and inf ammatory. Concurrent ungal in ection o the nails (onychomycosis) occurs requently.

FIGURE 138-2 The hand shows an autoe cze matization re action to the in ammatory tine a p e d is in Fig ure 138-1. The ve sicle s b e twe e n the f ng e rs are typ ical o an autoe cze matization re action, also known as an Id re action. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

ETIO LO GY AND PATHO PHYSIO LO GY • A cutaneous ungal in ection most commonly caused by Trichophyton rubrum.1 • Trichophyton mentagrophytes and Epidermophyton f occosum ollow in that order.

SYNO NYMS

• T. rubrum causes most tinea pedis and onychomycosis. Tinea pedis is also known as athlete’s oot.

RISK FACTO RS EPIDEMIO LO GY

• Male gender

• Tinea pedis is thought to be the world’s most common dermatophytosis.1

• Use o public showers, baths, or pools2

• About 70% o the population will be in ected with tinea pedis at some time. 1

• Household member with tinea pedis in ection2

• More commonly a ects males than emales.

1

• Prevalence increases with age and it is rare be ore adolescence. 1

• Certain occupations (miners, armers, soldiers, meat actory workers, marathon runners)2 • Use o immunosuppressive drugs

DIAGNO SIS TYPICAL DISTRIBUTIO N AND MO RPHO LO GY Three types o tinea pedis are as ollow: • Interdigital type—most common (Figure 138-3) • Moccasin type (Figure 138-4 and 138-5) • Inf ammatory/ vesicular type—least common (see Figure 138-1) Some authors describe an ulcerative type (Figure 138-6). CLINICAL FEATURES • Interdigital—White or green ungal growth between toes with erythema, maceration, cracks, and ssures—especially between ourth and th digits (see Figure 138-3). The dry type has more scale and the moist type becomes macerated. FIGURE 138-1 Ve sicular tine a p e d is with b ullae p re se nt. This is an in ammatory re action to the tine a p e d is. (Re p ro d uce d with p e rmissio n fro m Richard P. Usatine , MD.)

• Moccasin—Scale on sides and soles o eet (see Figures 138-4 and 138-5). • Vesicular—Vesicles and bullae on eet (see Figure 138-6).

t INe a pe DIS

PART 14 DERMATO LO GY

FIGURE 138-5 Tine a p e d is in a moccasin d istrib ution that has sp re ad up the le g . (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.) FIGURE 138-3 Tine a p e d is se e n in the inte rd ig ital sp ace b e twe e n the ourth and f th d ig its. This is the most common are a to se e tine a p e d is. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Ulcerative tinea pedis is characterized by rapidly spreading vesiculopustular lesions, ulcers, and erosions, typically in the web spaces (Figure 138-7). It is accompanied by a secondary bacterial in ection. This can lead to cellulitis or lymphangitis. • Autosensitization (dermatophytid reaction; Id reaction) is a hypersensitivity response to the ungal in ection causing papules on the hands (see Figure 138-2). • Examine nails or evidence o onychomycosis—Fungal in ections o nails may include subungual keratosis, yellow or white discolorations, dysmorphic nails (see Chapter 191, Onychomycosis). • Examine to exclude cellulitis that may show erythema, swelling, tenderness with red streaks tracking up the oot and lower leg (see Chapter 122, Cellulitis). TYPICAL DISTRIBUTIO N It occurs between the toes, on the soles, and lateral aspects o the eet.

FIGURE 138-6 Ve sicular tine a p e d is with ve sicle s and b ullae ove r the arch re g ion o the oot. The arch is a typ ical lo cation o r ve siculob ullous tine a p e d is. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

LABO RATO RY STUDIES Diagnosis is o ten made based on clinical presentation but a skin scraping treated with potassium hydroxide (KOH) and a ungal stain analyzed under the microscope can be help ul (Figure 138-8).

FIGURE 138-4 Tine a p e d is in the moccasin d istrib ution. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 138-7 Ulce rative tine a p e d is with sp re ad ing ve sicle s re late d to a b acte rial sup e rin e ctio n. The p atie nt was tre ate d with anti ung als and antib iotics. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

659

660

PART 14 DERMATO LO GY

Ch a pt e r 138

FIGURE 138-8 Microscop ic vie w o the scrap ing o the oot in the man with tine a incog nito in Fig ure 138-9. The hyp hae have p roli e rate d and are e asy to se e und e r 40 p o we r with Swartz-Lamkins stain. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

In the patient with tinea incognito on his oot and lower leg, the physicians were set astray by his diagnosis o systemic lupus erythematosus (SLE) (Figure 138-9). It took a skin scraping to demonstrate that this was tinea and not lupus to get the patient the treatment he needed (see Figure 138-8). Skin scraping and culture is de nitive but expensive, and may take up to 2 weeks or the culture to grow.

DIFFERENTIAL DIAGNO SIS • Pitted keratolysis—Well-demarcated pits or erosions in the sole o the oot caused by bacteria (Figure 138-10) (see Chapter 120, Pitted Keratolysis).

FIGURE 138-10 Pitte d ke ratolysis on the sole o the oot with some inte rd ig ital tine a p e d is. The p its are cause d b y b acte ria and i not tre ate d with an antib iotic will not re so lve . (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

• Contact dermatitis—Tends to be seen on the dorsum and sides o the oot (Figure 138-11) (see Chapter 144, Contact Dermatitis). • Keratodermas—Thickening o the soles o the eet that can be caused by a number o etiologies, including menopause (Figure 138-12). This condition looks a lot like tinea pedis in the moccasin distribution. • Dyshidrotic eczema is characterized by scale and tapioca-like vesicles on the hands and eet (Figure 138-13) (see Chapter 145, Hand Eczema). • Friction blisters—Blisters on the eet o persons leading an active athletic li estyle. • Psoriasis—Can mimic tinea pedis but will usually be present in other areas as well (Figure 138-14) (see Chapter 150, Psoriasis).

FIGURE 138-9 Tine a incog nito on the oot o a 63-ye ar-old b lack man with lup us. He was g ive n top ical ste roid s that allowe d this ung us to sp re ad and thrive . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 138-11 Co ntact d e rmatitis to an alle rg e n in te nnis sho e s with typ ical d istrib utio n that cro sse s the d o rsum o the o ot. (Re p ro d uce d with p e rmissio n from Richard P. Usatine , MD.)

t INe a pe DIS

PART 14 DERMATO LO GY

661

FIGURE 138-12 Ke ratod e rma climacte ricum, which starte d whe n this woman e nte re d me nop ause . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 138-14 Plantar p soriasis in a p atie nt with othe r are as o p soriasis also p re se nt. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

MANAGEMENT Table 138-1 discusses management o tinea pedis. TO PICAL ANTIFUNGALS

FIGURE 138-13 Dyshid rotic e cze ma on the oot showing tap ioca ve sicle s with p e e ling o skin on the tip o the se cond toe . The p atie nt also has typ ical tap ioca ve sicle s b e twe e n the f ng e rs. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Systematic review o 70 trials o topical anti ungals showed good evidence or e cacy compared to placebo or the ollowing: 3 ° Allylamines (na ti ne, terbina ne, butena ne). SO R 3 ° Azoles (clotrimazole, miconazole, econazole). SO R ° Allylamines cure slightly more in ections than azoles but are more expensive. 3 SO R ° No di erences in e cacy ound between individual allylamines or individual azoles (Table 138-2). SO R ° In one meta-analysis, topical terbina ne was ound to be equally e ective as other topical anti ungals but the average duration o treatment was shorter. (1 week instead o 2 weeks). Additionally, terbina ne is e ective as a single-application lm- orming solution. 4 SOR O RAL ANTIFUNGALS • Systematic review o 12 trials, involving 700 participants: Oral terbina ne or 2 weeks cures 52% more patients than oral griseo ulvin.5 SOR

TABLE 138-1 Manag e me nt o Tine a Pe d is

Tine a Pe d is Typ e

Tre at me nt fo r Mild Case s

Tre at me nt fo r Re calcit rant Case s

Inte rd ig ital typ e

Top ical anti ung al

Anothe r top ical anti ung al or an oral anti ung al

A

Moccasin typ e

Top ical anti ung al

O ral anti ung al

A

In ammatory/ve sicular typ e

O ral anti ung al

O ral anti ung al

A

Re p rinte d with p e rmissio n ro m Thomas B. Cle ar cho ice s in manag ing e p id e rmal tine a in e ctio ns. J Fam Pract. 2003;52(11):857. Re p ro d uce d with p e rmission rom Frontline Me d ical Communications.

SO R

PART 14 DERMATO LO GY

662

Ch a pt e r 138

TABLE 138-2 Top ical Anti ung al Me d ications

Fo rmulat io n

Fre q ue ncy*

Durat io n* (We e ks)

NNT†

Clotrimazole

1% cre am 1% solution 1% swab s

Twice d aily

2-4

2.9

Econazole

1% cre am

Twice d aily

2-4

2.6

Ke toconazole

2% cre am

O nce d aily

2-4

No d ata availab le

Miconazole

2% cre am 2% sp ray 2% p owd e r

Twice d aily

2-4

2.8 (at 8 wk)

O xiconazole

1% cre am 1% lotion

O nce to twice d aily

2-4

2.9

Sulconazole

1% cre am 1% solution

O nce to twice d aily

2-4

2.5

Na tif ne

1% cre am 1% g e l

O nce to twice d aily

1-4

1.9

Te rb inaf ne

1% cre am 1% solution

O nce to twice d aily

1-4

1.6 (1.7 or tine a cruris/tine a corp oris at 8 wk)

1% cre am

O nce to twice d aily

1-4

1.9 (1.4 or tine a corp oris and 1.5 or tine a cruris)

Ciclop irox

0.77% cre am 0.77% lotion

Twice d aily

2-4

2.1

Tolna tate

1% p owd e r 1% sp ray 1% swab s

Twice d aily

4

3.6 (at 8 wk)

Ag e nt Imid azole s

Allylamine s

Be nzylamine Bute naf ne O the r

*

Manu acture r g uid e line s. NNT, numb e r ne e d e d to tre at. NNT is calculate d rom syste matic re vie w o all rand omize d controlle d trials or tine a p e d is at 6 we e ks a te r the initiation o tre atme nt e xce p t whe re othe rwise note d . Re p rinte d with p e rmission rom Thomas B. Cle ar choice s in manag ing e p id e rmal tine a in e ctions. J Fam Pract. 2003;52(11):857. Re p rod uce d with p e rmission rom Frontline Me d ical Communications. †

• Terbina ne is equal to itraconazole in patient outcomes. 5 SO R

ALTERNATIVE THERAPY

• No signi cant di erences in comparisons between a number o oral agents. 5 SO R

One small pilot study with 56 participants showed signi cant improvement or resolution o symptoms in patients treated by wearing socks containing copper oxide bers daily or a minimum o 8 to 10 days. 7 SOR B

Dosing or tinea pedis needing oral therapy includes the ollowing: • Itraconazole two 100 mg tablets daily or 1 week6 • Terbina ne 250 mg PO daily or 1 to 2 weeks6 Patients with onychomycosis may have recurrences o the skin in ection related to the ungus that remains in the nails and, there ore, may need oral treatment or 3 months to achieve better results. Topical urea (Carmol, Keralac), available in 10% to 40% concentrations, may be use ul to decrease scaling in patients with hyperkeratotic soles. 5

PATIENT EDUCATIO N • Do not go bare oot in public showers and locker rooms. SO R C • Keep eet dry and clean, and use clean socks and shoes that allow the eet to get resh air. SO R C • Use the topical medication beyond the time in which the eet look clear to prevent relapse.

t INe a pe DIS

PATIENT RESO URCES

• eMedicineHealth. Athlete’s Foot—http:/ / www.emedicinehealth .com/ athletes_foot/ article_em.htm. PRO VIDER RESO URCES

• Medscape. Tinea Pedis—http:/ / emedicine.medscape.com/ article/ 1091684.

REFERENCES 1. Robbins C. Tinea Pedis. http:/ / www.emedicine.com/ DERM/ topic470.htm. Accessed June 24, 2007. 2. Seebacher C, Bouchara JP, Mignon B. Updates on the epidemiology o dermatophyte in ections. Mycopathologia. 2008;166(5-6):335-352.

PART 14 DERMATO LO GY 3. Craw ord F, Hart R, Bell-Syer S, Torgerson D, Young P, Russell I. Topical treatments or ungal in ections o the skin and nails o the oot. Cochrane Database Syst Rev. 2000;CD001434. 4. Kienke P, Korting HC, Nelles S, Rychlik R. Comparable e cacy and sa ety o various topical ormulations o terbina ne in tinea pedis irrespective o the treatment regimen: results o a meta-analysis. Am J Clin Dermatol. 2007;8(6):357-364. 5. Bell-Syer SE, Hart R, Craw ord F, Torgerson DJ, Tyrrell W, Russell I. Oral treatments or ungal in ections o the skin o the oot. Cochrane Database Syst Rev. 2002;CD003584. 6. Thomas B. Clear choices in managing epidermal tinea in ections. J Fam Pract. 2003;52:850-862. 7. Zatco RC, Smith MS, Borkow G. Treatment o tinea pedis with socks containing copper-oxide impregnated bers. Foot (Edinb). 2008;18(3):136-141.

663

PART 14 DERMATO LO GY

664

139 TINEA VERSICO LO R Richard P. Usatine , MD Me lissa M. Chan, MD

Ch a pt e r 139

ETIO LO GY AND PATHO PHYSIO LO GY • Tinea versicolor is caused by Pityrosporum (M. furfur), which is a lipophilic yeast that can be normal human cutaneous f ora. • Pityrosporum exists in 2 shapes—Pityrosporum ovale (oval) and Pityrosporum orbiculare (round).

PATIENT STO RY A young black man presents to the o ce with a 5-year history o white spots on his trunk (Figure 139-1). He denies any symptoms but worries i this could spread to his girl riend. These spots get worse during the summer months but never go away completely. He was relieved to receive a treatment or his tinea versicolor and to nd out that it rarely spread to others through contact.

INTRO DUCTIO N Tinea versicolor is a common super cial skin in ection caused by the dimorphic lipophilic yeast Pityrosporum (Malassezia furfur). The most typical presentation is a set o hypopigmented macules and patches with ne scale over the trunk in a cape-like distribution.

SYNO NYMS Pityriasis versicolor is actually a more accurate name as “tinea” implies a dermatophyte in ection. Tinea versicolor is caused by Pityrosporum and not a dermatophyte.

EPIDEMIO LO GY • Seen more commonly in men than in women. • Seen more o ten during the summer, and is especially common in warm and humid climates.

FIGURE 139-1 Tine a ve rsicolor showing are as o hyp op ig me ntation. (Re p rod uce d with p e rmission from Usatine RP. What is in a name ? We st J Me d . 2000;173(4):231-232.)

• Tinea versicolor starts when the yeast that normally colonizes the skin changes rom the round orm to the pathologic mycelial orm and then invades the stratum corneum. 1 • Pityrosporum is also associated with seborrhea and Pityrosporum olliculitis. • The white and brown colors are secondary to damage caused by the Pityrosporum to the melanocytes, while the pink is an inf ammatory reaction to the organism. • Pityrosporum thrives on sebum and moisture; they tend to grow on the skin in areas where there are sebaceous ollicles secreting sebum.

DIAGNO SIS CLINICAL FEATURES Tinea versicolor consists o hypopigmented, hyperpigmented, or pink macules and patches on the trunk that are nely scaling and well demarcated. Versicolor means a variety o or variation in colors; tinea versicolor tends to come in white, pink, and brown colors (Figures 139-1 to 139-5). TYPICAL DISTRIBUTIO N Tinea versicolor is ound on the chest, abdomen, upper arms, and back, whereas seborrhea tends to be seen on the scalp, ace, and anterior chest. LABO RATO RY STUDIES A scraping o the scaling portions o the skin may be placed onto a slide using the side o another slide or a scalpel. Potassium hydroxide (KOH) with dimethyl sul oxide (DMSO) (DMSO helps the KOH dissolve the

FIGURE 139-2 Patche s o hyp op ig me ntation across the b ack cause d b y tine a ve rsicolor in a young Latino man. Vitilig o is on the d i e re ntial d iag nosis in this case . A KO H p re p aration conf rme d tine a ve rsicolor. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

t INe a Ve r SICO LO r

PART 14 DERMATO LO GY

FIGURE 139-3 Pink scaly p atche s cause d b y tine a ve rsicolor. Se b orrhe a may b e se e n in this location, b ut te nd s to b e worse in the p re ste rnal re g ion. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

keratinocytes aster and reduces the need or heating the slide) is placed on the slide and covered with a coverslip. Microscopic examination reveals the typical “spaghetti-and-meatballs” pattern o tinea versicolor. The “spaghetti,” or more accurately “ziti,” is the short mycelial orm and the “meatballs” are the round yeast orm (Figures 139-6 and 139-7). Fungal stains such as the Swartz-Lamkins stain help make the identi cation o the ungal elements easier.

DIFFERENTIAL DIAGNO SIS • Pityriasis rosea has a ne collarette scale around the border o the lesions and is requently seen with a herald patch. Negative KOH (see Chapter 151, Pityriasis Rosea). • Secondary syphilis is usually not scaling and tends to have macules on the palms and soles. Negative KOH (see Chapter 218, Syphilis). • Tinea corporis is rarely as widespread as tinea versicolor and each individual lesion usually has central clearing and a well-de ned, raised, scaling border. The KOH preparation in tinea corporis shows hyphae

FIGURE 139-4 Larg e are as o p ink tine a ve rsicolor on the should e r in a cap e -like d istrib ution. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 139-5 Hyp e rp ig me nte d variant o tine a ve rsicolor in a Hisp anic woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

with multiple branch points and not the “ziti-and-meatballs” pattern o tinea versicolor (see Chapter 136, Tinea Corporis). • Vitiligo—The degree o hypopigmentation is greater and the distribution is requently di erent with vitiligo involving the hands and ace (see Chapter 196, Vitiligo). • Pityriasis alba—Lightly hypopigmented areas with slight scale that tend to be ound on the ace and trunk o children with atopy. These patches are requently smaller and rounder than tinea versicolor (see Chapter 143, Atopic Dermatitis).

FIGURE 139-6 Microscop ic e xamination o scrap ing s d one rom p re vious p atie nt showing short myce lial orms and round ye ast orms sug g e stive o sp ag he tti and me atb alls. Swartz-Lamkins stain was use d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

665

PART 14 DERMATO LO GY

666

Ch a pt e r 139

typical regimen involves applying the lotion or shampoo to the involved areas or 10 minutes and then washing it o in the shower. SOR C • One study used ketoconazole 2% shampoo (Nizoral) as a single application or daily or 3 days and ound it sa e and highly e ective in treating tinea versicolor. 3 SO R B • Topical anti ungal creams or smaller areas o involvement can include ketoconazole and clotrimazole. SO R C

O RAL TREATMENT AND PREVENTIO N • A single-dose 400-mg oral f uconazole provided the best clinical and mycological cure rate, with no relapse during 12 months o ollow-up. 4 SO R B

FIGURE 139-7 Close -up o Malasse zia furfur (Pityrosp orum) showing the ziti-and -me atb all ap p e arance a te r Swartz-Lamkins stain was ap p lie d to the scrap ing o tine a ve rsicolor in a young woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Pityrosporum olliculitis is caused by the same organism but presents with pink or brown papules on the back. The patient complains o itchy rough skin and the KOH is positive (Figure 139-8).

MANAGEMENT

• A single dose o 300 mg o oral f uconazole repeated weekly or 2 weeks was equal to 400 mg o ketoconazole in a single dose repeated weekly or 2 weeks. No signi cant di erences in e cacy, sa ety, and tolerability between the 2 treatment regimens were ound. 5 SO R B • A single-dose 400-mg oral ketoconazole to treat tinea versicolor is sa e and cost-e ective compared to using the newer, more expensive, oral anti ungal agents, such as itraconazole. 6,7 SO R B • Oral itraconazole 200 mg given twice a day or 1 day a month has been shown to be sa e and e ective as a prophylactic treatment or tinea versicolor. 8 SO R B • There is no evidence that establishes the need to sweat a ter taking oral anti ungals to treat tinea versicolor.

TO PICAL • Because tinea versicolor is usually asymptomatic, the treatment is mostly or cosmetic reasons. • The mainstay o treatment has been topical therapy using antidandru shampoos, because the same Pityrosporum species that cause seborrhea and dandru also cause tinea versicolor. 1,2 • Patients may apply selenium sul de 2.5% lotion or shampoo, or zinc pyrithione shampoo to the involved areas daily or 1 to 2 weeks. Various amounts o time are suggested to allow the preparations to work, but there are no studies that show a minimum exposure time needed. A

PATIENT EDUCATIO N Patients should be told that the change in skin color will not reverse immediately. The rst sign o success ul treatment is the lack o scale. The yeast acts like a sunscreen in the hypopigmented macules. Sun exposure will hasten the normalization o the skin color in patients with hypopigmentation.

FO LLO W-UP None needed unless it is a stubborn or recurrent case. Recurrent cases can be treated with monthly topical or oral therapy. PATIENT RESO URCES

• Skin Sight. Tinea Versicolor— http:/ / www.skinsight.com/ adult/ tineaVersicolor.htm. PRO VIDER RESO URCES

• Medscape. Tinea Versicolor— http:/ / emedicine.medscape .com/ article/ 1091575.

REFERENCES 1. Bolognia J, Jorizzo J, Rapini R. Dermatology. St. Louis, MO: Mosby; 2003. FIGURE 139-8 Pityrosp orum olliculitis on the b ack o a man with p ruritus. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

2. Hu SW, Bigby M. Pityriasis versicolor: a systematic review o interventions. Arch Dermatol. 2010;146(10):1132-1140.

t INe a Ve r SICO LO r

3. Lange DS, Richards HM, Guarnieri J, et al. Ketoconazole 2% shampoo in the treatment o tinea versicolor: a multicenter, randomized, double-blind, placebo-controlled trial. JAmAcad Dermatol. 1998;39(6):944-950. 4. Bhogal CS, Singal A, Baruah MC. Comparative e cacy o ketoconazole and f uconazole in the treatment o pityriasis versicolor: a one year ollow-up study. J Dermatol. 2001;28(10):535-539. 5. Farschian M, Yaghoobi R, Samadi K. Fluconazole versus ketoconazole in the treatment o tinea versicolor. J DermatologTreat. 2002;13(2):73-76.

PART 14 DERMATO LO GY 6. Gupta AK, Del Rosso JQ. An evaluation o intermittent therapies used to treat onychomycosis and other dermatomycoses with the oral anti ungal agents. Int J Dermatol. 2000;39(6):401-411. 7. Wahab MA, Ali ME, Rahman MH, et al. Single dose (400 mg) versus 7 day (200 mg) daily dose itraconazole in the treatment o tinea versicolor: a randomized clinical trial. Mymensingh Med J. 2010;19(1):72-76. 8. Faergemann J, Gupta AK, Mo adi AA, et al. E cacy o itraconazole in the prophylactic treatment o pityriasis (tinea) versicolor. Arch Dermatol. 2002;138:69-73.

667

PART 14

668

DERMATO LO GY

SECTIO N 5

Ch a pt e r 140

INFESTATIO NS

140 LICE Richard P. Usatine , MD E.J. Maye aux, MD

PATIENT STO RY A 64-year-old homeless woman with schizophrenia presented to a homeless clinic or itching all over her body. She stated that she could see creatures eed on her and move in and out o her skin. The physical examination revealed that she was unwashed and had multiple excoriations over her body (Figure 140-1). Body lice and their progeny were visible along the seams o her pants (Figure 140-2). Treatment o this lousy in estation required giving her new clothes and a shower. 1

INTRO DUCTIO N Lice are ectoparasites that live on or near the body. They will die o starvation within 10 days o removal rom their human host. Lice have coexisted with humans or at least 10,000 years. 2 Lice are ubiquitous and remain a major problem throughout the world. 3

SYNO NYMS It is also known as pediculosis or crabs (pubic lice).

EPIDEMIO LO GY • Human lice (pediculosis corporis, pediculosis pubis, and pediculosis capitis) are ound in all countries and climates. 3

FIGURE 140-2 Ad ult b od y lic and nymp s visib l along t p ant s ams of t woman in Fig ure 140-1 (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Head lice are most common among school-age children. Each year, approximately 6 to 12 million children, ages 3 to 12 years, are in ested. 4 • Head lice in estation is seen across all socioeconomic groups and is not a sign o poor hygiene. 5 • In the United States, black children are a ected less o ten as a result o their oval-shaped hair sha ts that are di cult or lice to grasp. 4 • Body lice in est the seams o clothing (see Figure 140-2) and bed linen. In estations are associated with poor hygiene and conditions o crowding. • Pubic lice are most common in sexually active adolescents and adults. Young children with pubic lice typically have in estations o the eyelashes. Although in estations in this age group may be an indication o sexual abuse, children generally acquire the crab lice rom their parents. 6

ETIO LO GY AND PATHO PHYSIO LO GY

FIGURE 140-1 Bod y lic in a 64-y a -old om l ss wo man wit sc izop nia. (Re p rod uce d with p e rmission from Richard P. Usatine , MD and Usatine RP, Hale m L. A te rrib le itch. J Fam P act. 2003;52(5):377-379. Re p rod uce d with p e rmission from Frontline Me d ical Communications.)

• Lice are parasites that have 6 legs with terminal claws that enable them to attach to hair and clothing. There are 3 types o lice responsible or human in estation. All 3 kinds o lice must eed daily on human blood and can only survive 1 to 2 days away rom the host. The 3 types o lice are as ollows: ° Head lice (Pediculus humanus capitis)—Measure 2 to 4 mm in length (Figure 140-3). ° Body lice (Pediculus humanus corporis)—Body lice similarly measure 2 to 4 mm in length (Figure 140-4). ° Pubic or crab lice (Phthirus pubis)—Pubic lice are shorter, with a broader body and have an average length o 1 to 2 mm (Figure 140-5).

LICe

PART 14

DERMATO LO GY

A FIGURE 140-5 T c ab lous as a s o t b od y and its la g claws a sp onsib l fo t “c ab ” in its nam . (Re p roduce d with p e rmission from Ce nte rs for Dise ase Control and Pre ve ntion and World He alth O rg anization.)

• Female lice have a li e span o approximately 30 days and can lay approximately 10 eggs (nits) a day. 4 • Nits are rmly attached to the hair sha t or clothing seams by a gluelike substance produced by the louse (Figures 140-6 and 140-7). • Nits are incubated by the host’s body heat. • The incubation period rom laying eggs to hatching o the rst nymph is 7 to 14 days (see Figure 140-7). • Mature adult lice capable o reproducing appear 2 to 3 weeks later (Figure 140-8). 5

B FIGURE 140-3 A. Ad ult ad lous wit long at d b od y. (Re p rod uce d with p e rmission from Ce nte rs for Dise ase Control and Pre ve ntion and De nnis D. Jurane k.) B. Ad ult ad lous ang ing on to t ai on t n ck of a man inf st d wit ad lic . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 140-4 A b od y lous f d ing on t b lood of t p otog ap . T d a k mass insid t ab d om n is a p viously ing st d b lood m al. (Re p rod uce d with p e rmissio n from Ce nte rs for Dise ase Contro l and Pre ve ntion and Frank Collins, PhD.)

• Transmission o head lice occurs through direct contact with the hair o in ested individuals. The role o omites (eg, hats, combs, brushes) in transmission is negligible. 6 Head lice do not serve as vectors or transmission o disease among humans. • Transmission o body lice occurs through direct human contact or contact with in ested material. Unlike head lice, body lice are well-recognized vectors or transmission o the pathogens responsible or epidemic typhus, trench ever, and relapsing ever.5

FIGURE 140-6 P a ly nits on t ai of a man wit p oo yg i n . T nits a fo und b ind t a s and at t nap of t n ck. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

669

PART 14

670

DERMATO LO GY

FIGURE 140-7 A massiv inf station of ad lic on t ai of a m ntally ill om l ss p son. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Pubic or crab lice are transmitted primarily through sexual contact. In addition to pubic hair (Figure 140-9), in estations o eyelashes, eyebrows, beard, upper thighs, abdominal, and axillary hairs may also occur.

RISK FACTO RS • Contact with an in ected individual • Living in crowded quarters such as homeless shelters • Poor hygiene and mental illness

DIAGNO SIS CLINICAL FEATURES • Nits can be seen in active disease or treated disease. Nits closer to the base o the hairs are generally newer and more likely to be live and unhatched. Un ortunately, nits that were not killed by pediculicides can hatch and start the in estation cycle over again. Note that nits are

Ch a pt e r 140

FIGURE 140-9 C ab lic inf sting pubic ai . (Re produce d with p ermission from the Unive rsity of Te xas He alth Scie nces Ce nte r, Division of De rmatology.)

glued to the hairs and are hard to remove, whereas f akes o dandru can be easily brushed o . • Pruritus is the hallmark o lice in estation. It is the result o an allergic response to louse saliva. 7 Head lice are associated with excoriated lesions that appear on the scalp, ears, neck, and back. • Occipital and cervical adenopathy may develop, especially when lesions become superin ected. • Body lice result in small maculopapular eruptions that are predominantly ound on the trunk (see Figure 140-1) and the clothing (see Figure 140-2). • Chronic in estations o ten result in hyperpigmented, licheni ed plaques known as “vagabond’s skin.”8 • Pubic lice produce bluish-gray spots (macula cerulea) that can be ound on the chest, abdomen, and thighs. 8 TYPICAL DISTRIBUTIO N • Head lice—Look or nits and lice in the hair especially above the ears, behind the ears, and at the nape o the neck. There are many more nits present than live adults. Finding nits without an adult louse does not mean that the in estation has resolved (see Figures 140-6 and 140-7). Systematically combing wet or dry hair with a ne-toothed nit comb (teeth o comb are 0.2 mm apart) better detects active louse in estation than visual inspection o the hair and scalp alone. 9 • Body lice—Look or the lice and larvae in the seams o the clothing (see Figure 140-2). • Pubic lice—Look or nits and lice on the pubic hairs (see Figure 140-9). These lice and their nits may also be seen on the hairs o the upper thighs, abdomen, axilla, beard, eyebrows, and eyelashes. Little specks o dried blood may be seen in the underwear as a clue to the in estation. LABO RATO RY TESTING • Direct visualization and identi cation o live lice or nits are su cient to make a diagnosis (see Figures 140-2 to 140-7 and 140-9). • The use o a magni cation lens may aid in the detection or con rmation o lice in estation. • Under Wood light the head lice nits f uoresce a pale blue.

FIGURE 140-8 Mic oscop ic vi w of a nit c m nt d to t ai and ab out to atc . (Re p rod uce d with p e rmission from Dan Stulb e rg , MD.)

• I you nd an adult louse put it on a slide with a coverslip loosely above it. Look at it under the microscope on the lowest power (see Figures 140-4

PART 14

LICe

and 140-5). You will see the internal workings o the live organs. I the louse was not ound in a typical location, you can use the morphology o the body and legs to determine the type o louse causing the in estation.

DERMATO LO GY

°

• In cases o pubic lice in estations, individuals should be screened or other sexually transmitted diseases. 5

DIFFERENTIAL DIAGNO SIS • Dandru , hair casts, and debris should be ruled out in cases o suspected lice in estations. Unlike nits, these particles are easily removed rom the hair sha t. In addition, adult lice are absent. • Scabies is also characterized by intense pruritus and papular eruptions. Unlike lice in estations, scabies may be associated with vesicles, and the presence o burrows is pathognomonic. Diagnosis is con rmed by microscopic examination o the scrapings rom lesions or the presence o mites or eggs (see Chapter 141, Scabies).

MANAGEMENT

°

° °

°

NO NPHARMACO LO GIC In young children or others who wish to avoid topical pediculicides or head lice, mechanical removal o lice by wet combing is an alternative therapy. A 1:1 vinegar:water rinse (le t under a conditioning cap or towel or 15-20 minutes) or 8% ormic acid crème rinse may enhance removal o tenacious nits. 8 Combing is per ormed until no lice are ound or 2 weeks. SO R B • Nits are also removed with a ne-toothed comb ollowing the application o all treatments. This step is critical in achieving resolution. • Combs and hairbrushes should be discarded, soaked in hot water (at a temperature o at least 55°C [130°F]) or 5 minutes, or treated with pediculicides. 10 MEDICATIO NS • Pediculus humanus capitis (head lice) ° Nonprescription 1% permethrin cream rinse (Nix), pyrethrins with piperonyl butoxide (which inhibits pyrethrin catabolism; RID) shampoo, or permethrin 1% is applied to the hair and scalp and le t on or 10 minutes then rinsed out. 11 SO R ° Pyrethrins are only pediculicidal, whereas permethrin is both pediculicidal and ovicidal. It is important to note that treatment ailure is common with these agents owing to the emergence o resistant strains o lice. ° A ter 7 to 10 days repeating the application is optional when permethrin is used, but is necessary or pyrethrin. Lice persisting a ter treatment with a pyrethroid may be an indication o resistance. ° Malathion 0.5% (Ovide) is available by prescription only, and is a highly e ective pediculicidal and ovicidal agent or resistant lice. Malathion may have greater e cacy than pyrethrins. 12 It is approved or use in children age 6 years and older. The lotion is applied to dry hair or 8 to 12 hours and then washed. Repeat application is recommended a ter 7 to 10 days i live lice are still present. When used appropriately, malathion is 78% to 95% e ective. 12 SO R ° Benzyl alcohol 5% lotion (Ules a) is a newer treatment option in patients 6 months o age and older. It works by asphyxiating the

°

°

parasite. It is applied or 10 minutes with saturation o the scalp and hair, and then rinsed o with water. The treatment is repeated a ter 7 days. 13 SO R Spinosad (Natroba) is a new topical prescription medication approved by the Food and Drug Administration (FDA) in 2011 or the treatment o lice. Spinosad is a ermentation product o the soil bacterium Saccharopolyspora spinosa that compromises the central nervous system o lice. It is approximately 85% e ective in lice eradication, usually a ter one application. It is applied to completely cover the dry scalp and hair, and rinsed o a ter 10 minutes. Treatment should be repeated i live lice remain 7 days a ter the initial application. 14 SO R In February 2012, the US FDA approved ivermectin 0.5% lotion or the treatment o head lice. It is applied as a single 10-minute topical application. The sa ety o ivermectin in in ants younger than age 6 months has not been established. 15 SO R Hair conditioners should not be used prior to the application o pediculicides; these products may result in reduced e cacy. 16 A Cochrane review ound no evidence that any one pediculicide was better than another; permethrin, synergized pyrethrin, and malathion were all e ective in the treatment o head lice. 17 SO R Other therapeutic options include permethrin 5% cream and lindane 1% shampoo. Permethrin 5% is conventionally used to treat scabies; however, it is anecdotally recommended or treatment o recalcitrant head lice. 5 SO R C Lindane is considered a second-line treatment option owing to the possibility o central nervous system toxicity, which is most severe in children. Oral therapy options include a 10-day course o trimethoprimsul amethoxazole or 2 doses o ivermectin (200 µg/ kg) 7 to 10 days apart. SO R C Trimethoprim-sul amethoxazole is postulated to kill the symbiotic bacteria in the gut o the louse. 4 Combination therapy with 1% permethrin and trimethoprim-sul amethoxazole is recommended in cases o multiple treatment ailure or suspected cases o resistance to therapy. 5,10 SO R C

• Pediculus humanus corporis (body lice) ° Improving hygiene, and laundering clothing and bed linen at temperatures o 65°C (149°F) or 15 to 30 minutes will eliminate body lice. 8 ° In settings where individuals cannot change clothing (eg, indigent population), a monthly application o 10% lindane powder can be used to dust the lining o all clothing. 8 ° Additionally, lindane lotion or permethrin cream may be applied to the body or 8 to 12 hours to eradicate body lice. • Phthirus pubis (pubic lice) ° Pubic lice in estations are treated with a 10-minute application o the same topical pediculicides used to treat head lice. ° Retreatment is recommended 7 to 10 days later. ° Petroleum ointment applied 2 to 4 times a day or 8 to 10 days will eradicate eyelash in estations. ° Clothing, towels, and 8bed linen should also be laundered to eliminate nit-bearing hairs.

PREVENTIO N Washing clothing and linen used by the head or pubic lice-in ested person during 2 days prior to therapy in hot water and/ or drying the items on a high-heat dryer cycle (54.5°C [130°F]). Items that cannot be washed may be dry cleaned or stored in a sealed plastic bag or 2 weeks.

671

PART 14

672

DERMATO LO GY FO LLO W-UP Patients should be reexamined upon completion o therapy to con rm eradication o lice.

PATIENT EDUCATIO N • Patients should be instructed to wash potentially contaminated articles o clothing, bed linen, combs, brushes, and hats. • Nit removal is important in preventing continued in estation as a result o new progeny. Care ul examination o close contacts, with appropriate treatment or in ested individuals is important in avoiding recurrence. • In cases o pubic lice, all sexual contacts should be treated.

PATIENT RESO URCES

• eMedicineHealth. Lice—http:/ / www.emedicinehealth.com/ lice/ article_em.htm. • Centers for Disease Control and Prevention. Parasites–Lice— http:/ / www.cdc.gov/ parasites/ lice/ index.html. PRO VIDER RESO URCES

• Centers for Disease Control and Prevention. Parasites—http:/ / www.cdc.gov/ ncidod/ dpd/ parasites/ lice/ default.htm. • Medscape. Pediculosis (Lice)—http:/ / emedicine.medscape .com/ article/ 225013.

REFERENCES 1. Usatine RP, Halem L. A terrible itch. J Fam Pract. 2003;52(5): 377-379. 2. Araujo A, Ferreira LF, Guidon N, et al. Ten thousand years o head lice in ection. Parasitol Today. 2000;16(7):269.

Ch APTe r 140

5. Pickering LK, Baker CJ, Long SS, McMillan JA. Red Book: 2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL: American Academy o Pediatrics; 2006:488-493. 6. Maguire JH, Pollack RJ, Spielman A. Ectoparasite in estations and arthropod bites and stings. In: Kasper DL, Fauci AS, Longo DL, Braunwald EB, Hauser SL, Jameson JL, eds. Harrison’s Principles of Internal Medicine, 16th ed. New York, NY: McGraw-Hill; 2005:2601-2602. 7. Flinders DC, De Schweinitz P. Pediculosis and scabies. Am Fam Physician. 2004;69(2):341-348. 8. Darmstadt GL. Arthropod bites and in estations. In: Behrman RE, Kliegman RM, Jenson HB, eds. NelsonTextbook of Pediatrics, 16th ed. Philadelphia, PA: Saunders; 2000:2046-2047. 9. Jahnke C, Bauer E, Hengge UR, Feldmeier H. Accuracy o diagnosis o pediculosis capitis: visual inspection vs wet combing. Arch Dermatol. 2009;145(3):309-313. 10. Hipolito RB, Mallorca FG, Zuniga-Macaraig ZO, et al. Head lice in estation: single drug versus combination therapy with one percent permethrin and trimethoprim/ sul amethoxazole. Pediatrics. 2001; 107(3):E30. 11. Meinking TL, Clineschmidt CM, Chen C, et al. An observer-blinded study o 1% permethrin creme rinse with and without adjunctive combing in patients with head lice. J Pediatr. 2002;141(5):665-670. 12. Meinking TL, Serrano L, Hard B, et al. Comparative in vitro pediculicidal e cacy o treatments in a resistant head lice population in the United States. Arch Dermatol. 2002;138(2):220-224. 13. Meinking TL, Villar ME, Vicaria M, et al. The clinical trials supporting benzyl alcohol lotion 5% (Ules a): a sa e and e ective topical treatment or head lice (pediculosis humanus capitis). Pediatr Dermatol. 2010;27(1):19-24. 14. Stough D, Shellabarger S, Quiring J, Gabrielsen AA Jr. E cacy and sa ety o spinosad and permethrin creme rinses or pediculosis capitis (head lice). Pediatrics. 2009;124(3):e389-e395. 15. Ivermectin Lotion 0.5% (Sklice) Clinical Review (NDA). http:/ / www . da.gov/ downloads/ Drugs/ DevelopmentApprovalProcess/ DevelopmentResources/ UCM295584.pd . Accessed April 13, 2012.

3. Roberts RJ. Clinical practice. Head lice. N Engl J Med. 2002;346:1645.

16. Lebwohl M, Clark L, Levitt J. Therapy or head lice based on li e cycle, resistance, and sa ety considerations. Pediatrics. 2007;119(5):965-974.

4. Frankowski BL, Weiner LB. Head Lice. Pediatrics. 2002;110(3): 638-643.

17. Dodd CS. Interventions or treating head lice. Cochrane Database Syst Rev. 2006;(4):CD001165.

SCABIES

PART 14

DERMATO LO GY

141 SCABIES Richard P. Usatine , MD Pie rre Chanoine , MD Mind y A. Smith, MD, MS

PATIENT STO RY A 32-year-old man is seen with severe itching and crusting o his hands and eet (Figures 141-1 and 141-2). He also has a pruritic rash over the rest o his body. Dermoscopy revealed the scabies mites in various burrows. A scraping was done and scabies mites and scybala ( eces) were seen (Figures 141-3 and 141-4). The man was treated with oral ivermectin (0.2 mg/ kg) once with a repeat dose to be taken in 10 days. The yellow crusting wheeping o yellow uid is evidence o secondary bacterial in ection or impetiginization, so the patient was also given a short course o an oral antibiotic. The scabies cleared.

FIGURE 141-2 Imp e tig inize d scab ie s on the oot o the 32-ye ar-old man o Fig ure 141-1. The ye llow crusting and whe e p ing o ye llow f uid is e vid e nce o se co nd ary b acte rial in e ction. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

SYNO NYMS Scabies is also known as 7-year itch.

EPIDEMIO LO GY • Three hundred million cases per year are estimated worldwide. 1 In many developing tropical countries, scabies is endemic. 1 • Studies in resource-poor countries show an association between scabies and overcrowding, especially in sleeping quarters. 1 • In developed nations the rates o scabies in estation are similar across age ranges. While in developing countries the highest rates are among children and the elderly. 1

FIGURE 141-3 Microscop ic vie w o the scab ie s mite rom a p atie nt with cruste d scab ie s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 141-1 Scab ie s in e station d e monstrate d b y typ ical line ar b urrows b e twe e n the ng e rs o this 32-ye ar-old man. De rmoscop y re ve ale d a p ositive arrowhe ad sig n o the scab ie s mite at the e nd o a b urrow. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 141-4 Scrap ing o the p atie nt’s hand p rod uce d a g ood vie w o the scyb ala (the mite s’ e ce s). (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

673

674

PART 14

DERMATO LO GY

Ch a pt e r 141

• The highest rates o crusted scabies are in immunocompromised patients including medical immunosuppression, as well as in those with developmental disability, including Down syndrome. 1 • The medical burden o scabies is associated with increased rates o impetigo and complications o secondary bacterial in ection with group A streptococci and Staphylococcus aureus. 1

ETIO LO GY AND PATHO PHYSIO LO GY • Human scabies is caused by the mite Sarcoptes scabiei, an obligate human parasite (see Figure 141-3). 2,3 • Adult mites spend their entire li e cycle, around 30 days, within the epidermis. A ter copulation the male mite dies and the emale mite burrows through the superf cial layers o the skin excreting eces (see Figure 141-4) and laying eggs (Figure 141-5). • Mites move through the superf cial layers o skin by secreting proteases that degrade the stratum corneum. • In ected individuals usually have less than 100 mites. In contrast, immunocompromised hosts can have up to 1 million mites, and are susceptible to crusted scabies also called Norwegian scabies (see Figures 141-6 to 141-8). 2 • Transmission usually occurs via direct skin contact. Scabies in adults is requently sexually transmitted. 4 Scabies mites can also be transmitted rom animals to humans. 2 • Mites can also survive or 3 days outside o the human epidermis allowing or in requent transmission through bedding and clothing. • The incubation period is on average 3 to 4 weeks or an initial in estation. Sensitized individuals can have symptoms within hours o reexposure.

RISK FACTO RS

FIGURE 141-6 Cruste d scab ie s on the hand s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIAGNO SIS CLINICAL FEATURES • Pruritus is a hallmark o the disease. 2 • Skin f ndings include papules (see Figure 141-8), burrows (Figure 141-9 and 141-10), nodules (Figures 141-11), and vesiculopustules (see Figure 141-10). • Burrows are the classic morphologic f nding in scabies and the best location to f nd the mite (see Figures 141-9 and 141-10). • Pruritic papules/ nodules around the axillae, umbilicus, areola, or on the penis and scrotum (Figure 141-11 and 141-12) are highly suggestive o scabies.

• Scabies is more common in homeless and impoverished persons, and individuals who are immunocompromised or su ering rom dementia.2 • Institutionalized individuals and those living in crowded conditions also have a higher incidence o the in estation. 2

FIGURE 141-5 Scab ie s e g g s rom a scrap ing . (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

FIGURE 141-7 Cruste d scab ie s rom head to toe in a man with HIV/AIDS. The in e station was so massive that it cause d him to be come e rythrode rmic and d ehydrate d. Note the crusting on the hands. (Re p roduced with pe rmission from Richard P. Usatine , MD.)

SCa BIe S

FIGURE 141-8 Cruste d scab ie s on the oot o a d isab le d man who had e xp e rie nce d a stroke p re vio usly. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14

DERMATO LO GY

FIGURE 141-11 Pruritic p ap ule s on the g lans o the p e nis and no d ule s on the scrotum se cond ary to se xually transmitte d scab ie s in a g ay man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

TYPICAL DISTRIBUTIO N • Classic distribution in scabies includes the interdigital spaces (Figures 141-9, 141-10, and 141-13), wrists, ankles, waist (Figures 141-14), groin, axillae, palms, and eet (see Figures 141-7 and 141-8). • Genital involvement can also occur (see Figures 141-11 and 141-12). LABO RATO RY STUDIES AND IMAGING

FIGURE 141-9 Scab ie s in e station on the hand . De rmoscop y re ve ale d scab ie s mite s within b urrows (arrow). (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Light microscopy o skin scrapings provides a def nitive diagnosis when mites, eggs, or eces are identif ed (see Figures 141-3 to 141-5). This can be challenging and time consuming, even when mites, eggs, or eces are present. Packing tape stripping o skin has also been used instead o a scalpel to f nd mites or examination under the microscope. 5 The inability to f nd these items should not be used to rule out scabies in a clinically suspicious case. In what is believed to be a recurrent case, it is help ul to f nd def nitive evidence that your diagnosis is correct.

FIGURE 141-10 Burrows p romine ntly visib le b e twe e n the ng e rs o this home le ss man with scab ie s. Burrows are a classic mani e station o scab ie s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 141-12 Pruritic p ap ule s o scab ie s on the ore skin o the p e nis, hand s, and g ro in acq uire d as a se xually transmitte d d ise ase . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

675

676

PART 14

DERMATO LO GY

Ch a pt e r 141

FIGURE 141-13 Scab ie s ound in the classic location b e twe e n the ng e rs in this inte rd ig ital we b sp ace . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Dermoscopy is a use ul and rapid technique or identi ying a scabies mite at the end o a burrow (see Appendix C, Dermoscopy). 6 The mite has been described as an arrowhead or a jet plane in its appearance (Figure 141-15). The advantage o the dermoscope is that multiple burrows can be examined quickly without causing any pain to the patient. Children are more likely to stay still or this than scraping with a scalpel or skin stripping with tape. • I a dermoscope is available, start with this noninvasive examination. I the f ndings are typical, then a microscopic examination is not needed. I the f ndings are not convincing, or a dermoscope is not available, per orm a scraping. It is best to scrape the skin at the end o a burrow. Use a # 15 scalpel that has been dipped into mineral oil or microscope immersion oil. Scrape holding the blade perpendicular to the skin until the burrow (or papule) is opened (some slight bleeding is usual). Trans er the material to a slide and add a coverslip. • Tips or microscopic examination—Start by examining the slide with the lowest power available as mites may be seen under 4 power and

FIGURE 141-15 Two scab ie s mite s visib le with d e rmoscop y. Note how the d arke st most visib le asp e ct o the mite looks like an arrowhe ad or je t p lane . In this case the oval b od ie s o the mite s are also visib le . The up p e r rig ht inse t shows the same b urrows without d e rmoscop y. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

the slide can be scanned most quickly with the lowest power. I no mites are seen switch to 10 power and scan the slide again looking or mites, eggs, and eces. Forty power may be used to conf rm f ndings under 10 power. • In one study comparing dermoscopic mite identif cation with microscopic examination o skin scrapings, ound the ormer technique to be o comparable sensitivity (91% and 90%, respectively) with specif city o 86% (vs 100% by def nition), even in inexperienced hands. 7 Another study reported sensitivity o dermoscopy at 83% (95% conf dence interval, 0.70-0.94). 8 In this study, the negative-predictive value was identical or dermoscopy and the adhesive tape test (0.85), making the latter a good screening test in resource-poor areas. • Videodermatoscopy can also be used to diagnose scabies. 9 Videodermatoscopy allows or skin magnif cation with incidental lighting at high magnif cations or viewing mites and eggs. The technique is noninvasive and does not cause pain. • S. scabiei recombinant antigens have diagnostic potential and are under investigation or identi ying antibodies in individuals with active scabies. 10 BIO PSY Rarely necessary unless there are reasons to suspect another diagnosis.

DIFFERENTIAL DIAGNO SIS FIGURE 141-14 Scab ie s around the waist with multip le p ap ule s and nod ule s in this incarce rate d young woman. Incarce ration is a risk actor or scab ie s. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

• Atopic dermatitis—Itching is a prominent symptom in atopic dermatitis and scabies. The distribution o involved skin can help to di erentiate the 2 diagnoses. Look or burrows in scabies and the history o

SCa BIe S

PART 14

DERMATO LO GY

involved amily members. In children, atopic dermatitis is o ten conf ned to the exural and extensor sur aces o the body. In adults, the hands are a primary site o involvement (see Chapter 143, Atopic Dermatitis). • Contact dermatitis—Characterized by vesicles and papules on bright red skin, which are rare in scabies. Chronic contact dermatitis o ten leads to scaling and lichenif cation and may not be as pruritic as scabies (see Chapter 144, Contact Dermatitis). • Seborrheic dermatitis—A papulosquamous eruption with scales and crusts that is limited to the sebum-rich areas o the body; namely, the scalp, the ace, the postauricular areas, and the intertriginous areas. Pruritus is usually mild or absent (see Chapter 149, Seborrheic Dermatitis). • Impetigo—Honey-crusted plaques are a hallmark o impetigo. Scabies can become secondarily in ected, so consider that both diagnoses can occur concomitantly with papules and pustules present (see Chapter 118, Impetigo). • Bedbugs have become more prevalent in the United States (Figure 141-16). Bedbug bites tend to appear in the morning a ter sleeping on the in ested bed. The skin mani estations o these bites can appear anywhere on the body especially in skin not covered by clothing. The typical description o the bites includes clusters o 3 bites in a linear pattern (Figure 141-17). The mnemonic or this is break ast, lunch, and dinner. Scabies lesions do not ollow this pattern and the scabies mite is not visible as is the bedbug. • Other arthropod bites—Bites may exhibit puncta that allow or di erentiation rom scabies.

FIGURE 141-17 Be d b ug b ite s on the arm o a 42-ye ar-old woman. Note the re is a line ar p atte rn o 3 b ite s on the ore arm. O ne way to re me mb e r this p atte rn is to think the b e d b ug e ating b re ak ast, lunch, and d inne r. Scab ie s d oe s not cre ate this p atte rn. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Tinea—All kinds o tinea in ections can be pruritic with scales and linear or curvilinear borders. In Figure 141-18, an immunosuppressed man being treated or polymyositis was ound to have tinea corporis and scabies. When his pruritus did not resolve during treatment or his tinea corporis, close examination with the dermatoscope revealed a scabies in estation. Skin scrapings or microscopy in most cases will distinguish between tinea and scabies.

FIGURE 141-16 Ad ult b e d b ug s are on ave rag e 5-mm long , oval-shap e d , and d orsove ntrally f atte ne d . The y p osse ss p ie rcing -sucking mouthp arts and are virtually wing le ss. Nymp hs look like smalle r, p ale r ve rsions o the ad ults. (Re p rod uce d with p e rmission from Ce nte rs fo r Dise ase Control and Pre ve ntio n/Blaine Mathison.)

FIGURE 141-18 Scab ie s and tine a corp oris in a 55-ye ar-old man b e ing tre ate d or p olymyositis with p re d nisone . The scab ie s was initially misse d and whe n the p ruritus d id not re so lve with oral te rb ina ne o r the tine a se e n ne ar his waist (KO H p rove n), close r look with d e rmoscop y re ve ale d scab ie s mite s in some o the p ruritic p ap ule s. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

677

PART 14

678

DERMATO LO GY MANAGEMENT NO NPHARMACO LO GIC Environmental decontamination is a standard component o all therapies. SO R B Clothing, bed linens, and towels should be machine washed in hot water. Clothing or other items (eg, stu ed animals) that cannot be washed may be dry cleaned or stored in sealed bags or at least 72 hours. 11 MEDICATIO NS Treatment includes administration o an antiscabicide and an antipruritic.2,12

Ch a pt e r 141

PREVENTIO N • Avoid direct skin-to-skin contact with an in ested person or with items such as clothing or bedding used by an in ested person. • Treat members o the same household and other potentially exposed persons at the same time as the in ested person to prevent possible reexposure and rein estation.

PRO GNO SIS

• Permethrin 5% cream (Elimite, Acticin) is the most e ective treatment based on a systematic review in the Cochrane Database. 12 SO R A The cream is applied rom the neck down (include the head when it is involved) and rinsed o 8 to 14 hours later. Usually, this is done overnight. Repeating the treatment in 1 to 2 weeks may be more e ective. SO R C In patients with crusted scabies, use o a keratolytic cream may acilitate the breakdown o skin crusts and improve penetration o the cream. 13 Un ortunately, scabies resistance to permethrin is increasing.

• The prognosis with proper diagnosis and treatment is excellent unless the patient is immunocompromised; rein estation, however, o ten occurs i environmental risk actors continue. 1

• Ivermectin is an oral treatment or resistant or crusted scabies. Studies have demonstrated its sa ety and e f cacy. Most studies used a single dose o ivermectin at 200 µg/ kg. 13 SO R A Taking the drug with ood may enhance drug penetration into the epidermis. 13 Some experts advocate repeating a dose 1 week later. It is worth noting that the Food and Drug Administration (FDA) has not labeled this drug or use in children weighing less than 15 kg. Ivermectin is currently available only in 3- and 6-mg tablets, so dosing o ten needs to be rounded up to accommodate the use o whichever tablets are available. As there is no oral suspension available, tablets may need to be cut and given with ood or use in children.

• Consider an immunologic workup or individuals with crusted scabies.

• Diphenhydramine, hydroxyzine, and mid-potency steroid creams can be used or symptomatic relie o itching. SO R C . It is important to note that pruritus may persist or 1 to 2 weeks a ter success ul treatment because the dead scabies mites and eggs still have antigenic qualities that may cause persistent in ammation. • All household or amily members living in the in ested home and sexual contacts should be treated. SO R C Failure to treat all involved individuals o ten results in recurrences within the amily. Use o insecticide sprays and umigants is not recommended. • Other less-e ective medications include topical benzyl benzoate, crotamiton, lindane (no longer used in the United States because o concerns regarding neurotoxicity), and synergized natural pyrethrins. 8 SO R A Topical agents used more commonly in other countries include 5% to 10% sul ur in para f n (widely in A rica and South America), 10% to 25% benzyl benzoate (o ten used in Europe and Australia), and malathion. 13 In in ants younger than 2 months o age, crotamiton or a sul ur preparation is recommended by one author instead o permethrin because o theoretical concerns o systemic absorption o permethrin. 13 • Antibiotics are needed i there is evidence o a bacterial superin ection. SO R C

CO MPLEMENTARY AND ALTERNATIVE THERAPY Tea tree oil contains oxygenetic terpenoids, ound to have rapid scabicidal activity. 14

• Postin ammatory hyper- or hypopigmentation can occur. 1

FO LLO W-UP • Routine ollow-up is indicated when symptoms do not resolve.

PATIENT EDUCATIO N • Patients should avoid direct contact including sleeping with others until they have completed the f rst application o the medicine. • Patients may return to school and work 24 hours a ter f rst treatment. • Patients should be warned that itching may persist or 1 to 2 weeks a ter success ul treatment but that i symptoms are still present by the third week, the patient should return or urther evaluation.

PATIENT RESO URCES

• Centers or Disease Control and Prevention. Scabies— http:/ / www.cdc.gov/ parasites/ scabies/ . • PubMed Health. Scabies— http:/ / www.ncbi.nlm.nih.gov/ pubmedhealth/ PMH0001833/ . PRO VIDER RESO URCES

• Medscape. Scabies— http:/ / emedicine.medscape.com/ article/ 1109204. • DermNet NZ. Scabies— http:/ / dermnetnz.org/ arthropods/ scabies.html.

REFERENCES 1. Hay RJ, Steer AC, Engelman D, Walton S. Scabies in the developing world—its prevalence, complications, and management. Clin Microbiol Infect. 2012 Apr;18(4):313-323. 2. Hengge UR, Currie B, Jäger G, et al. Scabies: a ubiquitous neglected skin disease. Lancet Infect Dis. 2006;6(12):769-779. 3. Paller AS, Mancini AJ. Scabies. In: Paller AS, Mancini AJ, eds. Hurwitz Clinical Pediatric Dermatology:ATextbook of Skin Disorders of Childhood and Adolescence. Philadelphia, PA: Saunders; 2006:479-488.

SCa BIe S

PART 14

DERMATO LO GY

4. Centers or Disease Control and Prevention. Scabies: Epidemiology and Risk Factors. http:/ / www.cdc.gov/ parasites/ scabies/ epi.html. Accessed April 2012.

10. Walton SF, Currie BJ. Problems in diagnosing scabies, a global disease in human and animal populations. Clin Microbiol Rev. 2007; 20(2):268-279.

5. Albrecht J, Bigby M. Testing a test. Critical appraisal o tests or diagnosing scabies. Arch Dermatol. 2011;147(4):494-497.

11. Centers or Disease Control and Prevention. Scabies:Treatment. http:/ / www.cdc.gov/ parasites/ scabies/ treatment.html. Accessed April 2012.

6. Fox GN, Usatine RP. Itching and rash in a boy and his grandmother. J Fam Pract. 2006;55(8):679-684. 7. Dupuy A, Dehen L, Bourrat E, et al. Accuracy o standard dermoscopy or diagnosing scabies. JAmAcad Dermatol. 2007;56(1):53-62. 8. Walter B, Heukelbach J, Fengler G, et al. Comparison o dermoscopy, skin scraping, and the adhesive tape test or the diagnosis o scabies in a resource-poor setting. Arch Dermatol. 2011;147(4): 468-473. 9. Lacarrubba F, Musumeci ML, Caltabiano R, et al. High-magnif cation videodermatoscopy: a new noninvasive diagnostic tool or scabies in children. Pediatr Dermatol. 2001;18(5):439-441.

12. Strong M, Johnstone PW. Interventions or treating scabies. Cochrane Database Syst Rev. 2007;3:CD000320. 13. Currie BJ, McCarthy JS. Permethrin and ivermectin or scabies, N Engl J Med. 2010;362(8):717-725. 14. Carson CF, Hammer KA, Riley TV. Melaleuca alternifolia (Tea Tree) oil: a review o antimicrobial and other medicinal properties. Clin Microbiol Rev. 2006;19(1):50-62.

679

PART 14 DERMATO LO GY

680

Ch ApTER 142

142 CUTANEO US LARVA MIGRANS Je nnife r A. Ke e hb auch, MD Richard P. Usatine , MD

PATIENT STO RY A 29-year-old man noted pruritic lesions on the dorsum o both eet a ter returning rom vacation in Mexico. A serpiginous, linear, raised, tunnellike erythematous lesion outlining the path o migration o the larva. Lesions were present bilaterally, arising in the 4 and 5 webspace at sites o tinea pedis. He was treated success ully with oral ivermectin. 1

SYNO NYMS Cutaneous larva migrans (CLM) is also known as creeping eruption, plumber’s itch.

EPIDEMIO LO GY • Endemic in developing countries, particularly Brazil, India, South A rica, Somalia, Malaysia, Indonesia, and Thailand. 2,3 • Peak incidence in the rainy seasons. 3 • During peak rainy seasons, the prevalence in children is as high as 15% in resource-poor areas, but much less common in a uent communities in these same countries with only 1 to 2 per 10,000 individuals per year. 4 • In the United States, it is ound predominantly in Florida, southeastern Atlantic states, and the Gul Coast. 2 • Children are more requently a ected than adults. 4

FIGURE 142-1 Cutan ous la va mig ans (CLM) on th d o sum of th foot in a 29-y a -old man. H not d u itic l sions on th d o sum of b oth f t aft tu ning f om vacation in M xico. A s ig inous, lin a , ais d , tunn llik yth matous l sion outlin s th ath of mig ation of th la va. L sions w s nt b ilat ally, a ising in th 4 and 5 w b s ac at sit s of tin a d is. H was t at d succ ssfully with iv m ctin. (Re p rod uce d with p e rmission from Wolff K and Johnson RA. Fitz at ick’s Colo Atlas & Syno sis of Clinical D matolog y. 6th e d . McGraw-Hill, 2009.)

TYPICAL DISTRIBUTIO N • Feet and lower extremities (73%), buttocks (13%-18%), and abdomen (16%)6,7 • Areas that come in contact with contaminated skin 3 Most commonly the eet, buttocks, and thigh ° LABO RATO RY AND IMAGING Not indicated, but rarely blood tests show eosinophilia or elevated immunoglobulin E levels. 5

DIFFERENTIAL DIAGNO SIS It may be con used with the ollowing conditions: • Cutaneous ungal in ections—Lesions are typically scaling plaques and annular macules with central clearing. I the serpiginous track o CLM

ETIO LO GY AND PATHO PHYSIO LO GY • Most commonly caused by dog and cat hookworms (ie, Ancylostoma braziliense, Ancylostoma caninum, Uncinaria stenocephala). 4 • Eggs are passed in cat or dog eces. 2 • Larvae are hatched in moist, warm sand or soil. 2 • In ective stage larvae penetrate the skin. 2

DIAGNO SIS The diagnosis is based on history and clinical f ndings. CLINICAL FEATURES • Elevated, serpiginous, or linear reddish-brown tracks 1 to 5 cm long (Figures 142-1 to 142-5). 2,5 • Intense pruritus, which o ten disrupts sleep. 3 • Symptoms last or weeks to months, and, rarely, years. Most cases are sel -limiting. 5

FIGURE 142-2 Clos -u of a b u ow f om cutan ous la va mig ans on th foot of a ca nt who was d oing wo k und a hous . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

CUTANEO US LARVA MIGRANS

PART 14 DERMATO LO GY

FIGURE 142-5 Long s ig inous b u ow f om cutan ous la va mig ans on th d o sum of th foot in a young woman tu ning f om a holid ay at th b ach. (Re p rod uce d with p e rmission from Sand ra O sswald , MD.)

FIGURE 142-3 S ig inous b u ow f om cutan ous la va mig ans on th l g . Th actual la va is 2 to 3 cm b yond th visib l t acks. (Re p rod uce d with p e rmission from John Gonzale z, MD.)

is circular, this can lead to the incorrect diagnosis o “ringworm.” The irony is that ringworm is a dermatophyte ungus whereas CLM really is a worm (see Chapter 136, Tinea Corporis). • Contact dermatitis—Di erentiate by distribution o lesions, presence o vesicles, and absence o classical serpiginous tracks (see Chapter 144, Contact Dermatitis). • Erythema migrans o Lyme disease—Lesions are usually annular macules or patches and are not raised and serpiginous (see Chapter 215, Lyme Disease). • Phytophotodermatitis—The acute phase o phytophotodermatitis is erythematous with vesicles; this later develops into postin ammatory hyperpigmented lesions. This may be acquired while preparing drinks

with lime on the beach and not rom the sandy beach in ested with larvae (see Chapter 197, Photosensitivity).

MANAGEMENT • Oral thiabendazole was the f rst proven therapy with Food and Drug Administration (FDA) approval. It was removed rom the market in 2010. • Albendazole has been success ully prescribed or more than 25 years, and is the Centers or Disease Control and Prevention (CDC) drug o choice. 3,5 Albendazole lacks FDA approval or this indication. 3,5 SO R The recommended dose is 400 mg daily or 3 days. B ° with albendazole exceed 92%, but are less with single ° Cure rates dosage. 3 • Ivermectin (Stromectol) has been well studied and is an appropriate alternative as per the CDC with dosing o 0.2 mg/ kg daily or 1 to 2 days. 3,5 It also lacks FDA approval or this indication. 3 SOR B ° A single dose o ivermectin 0.2 mg/ kg is also recommended. 3 Cure rates o 77% to 100% with a single dose. ° ° Ivermectin has3 been used worldwide on millions with an excellent sa ety prof le. is contraindicated in pregnancy and breast- eeding ° Ivermectin 3 mothers. • Cryotherapy is ine ective and harm ul and should be avoided. 3 SO R B ADJ UNCT THERAPY • Antihistamines may relieve itching. • Antibiotics may be used i secondary in ection occurs.

PATIENT EDUCATIO N FIGURE 142-4 Cutan ous la va mig ans (CLM) on th l g of an 18 y a -old man. H d v lo d this u itic s ig inous ash s v al d ays aft tu ning f om th b ach. It xt nd d s v al millim t in l ng th ach d ay and a b list d v lo d at th d istal oint of th b u ow in th ast 24 hou s. (Re p rod uce d with p e rmission from Rob e rt T. Brod e ll, MD.)

• Wear shoes on beaches where animals are allowed. • Keep covers on sand boxes. • Pet owners should keep pets o the beaches, deworm pets, and dispose o eces properly.

681

PART 14 DERMATO LO GY

682

FO LLO W-UP Follow up i lesions persist. PATIENT AND PRO VIDER RESO URCES

• eMedicine. Dermatology—http:/ / emedicine.medscape.com/ article/ 1108784. • eMedicine. Pediatrics—http:/ / emedicine.medscape.com/ article/ 998709. • CDC—http:/ / www.cdc.gov/ parasites/ zoonotichookworm/ health_professionals/ index.html REFERENCES 1. Wol K and Johnson RA. Fitzpatrick’s Color Atlas &Synopsis of Clinical Dermatology. 6th ed. New York, NY: McGraw-Hill; 2009. 2. Bowman D, Montgomery S, Zajac A, et al. Hookworms o dogs and cats as agents o cutaneous larva migrans. Trends Parasitol. 2010;26(4):162-167.

CHApTe r 142

3. Heukelbach J, Feldmeier H. Epidemiological and clinical characteristics o hookworm-related cutaneous larva migrans. Lancet Infect Dis. 2008;8(5):302-309. 4. Feldmeier H, Heukelbach J. Epidermal parasitic skin diseases: a neglected category o poverty-associated plagues. BullWorld Health Organ. 2009;87(2):152-159. 5. Montgomery S. Cutaneous larva migrans. In: Infectious Disease Related toTravel. CDCYellow Book. 2012. http:/ / wwwnc.cdc.gov/ travel/ yellowbook/ 2012/ chapter-3-in ectious-diseases-related-to-travel/ cutaneous-larva-migrans.htm. Accessed October 26, 2012. 6. Hotez P, Brooker S, Bethony J, et al. Hookworm in ection. N Engl J Med. 2004;351(8):799-807. 7. Jelinek T, Maiwald H, Nothdur t H, Loscher T. Cutaneous larva migrans in travelers: synopsis o histories, symptoms and treating 98 patients. Clin Infect Dis. 1994;19:1062-1066.

PART 14 DERMATO LO GY

ATO PIC DERMATITIS

SECTIO N 6

DERMATITIS/ALLERGIC

143 ATO PIC DERMATITIS Richard P. Usatine , MD Lind se y B. Finkle a, MD

PATIENT STO RY A 41-year-old woman with asthma, allergic rhinitis, and atopic dermatitis (the atopic triad) presents with a are-up o her atopic dermatitis (AD). Her neck is severely involved with erythema, scaling, cracking, and weeping o yellow uid, indicating a superin ection (Figure 143-1A). The hands and antecubital ossae are also signif cantly involved (Figure 143-1B). The patient is started on oral cephalexin along with topical corticosteroids. A ter months o trying to control her atopic dermatitis with topical steroids and other conservative measures unsuccess ully, her primary care physician re ers her to dermatology. The patient tells the dermatologists that she is unable to sleep at night and the pain in her skin makes it di f cult or her to care or her children. They decide to proceed with a short course o oral cyclosporine. Two days later the patient is already eeling better (Figure 143-1C) but it is not until 2 weeks that her skin becomes markedly improved.

B

C A FIGURE 143-1 A. Exace rb ation o atop ic d e rmatitis (AD) on the ne ck and hand o this 41-ye ar-old woman with asthma, alle rg ic rhinitis, and AD (the atop ic triad ). He r ne ck is se ve re ly involve d with e rythe ma, scaling , cracking , and we e p ing o ye llow uid ind icating a sup e rin e ction.

FIGURE 143-1 (Continue d ) B. The hand s and ante cub ital ossae are also sig nif cantly involve d . C. Months late r she was starte d on oral cyclosp orine b y the d e rmatolog ist. This p hoto was take n only 2 d ays a te r the cyclosp orin was starte d so the re are no visib le chang e s b ut the p atie nt had le ss p ruritus and could sle e p at nig ht. He r re sp onse to cyclosp orine ove r the e nsuing months was e xce lle nt. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

683

PART 14 DERMATO LO GY

684

CHAPTER 143

INTRO DUCTIO N AD is a chronic and relapsing in ammatory skin disorder characterized by itching and in amed skin that is triggered by the interplay o genetic, immunologic, and environmental actors. It can present as persistent AD that developed in childhood and has continued into adulthood, or as new adult-onset AD.

SYNO NYMS AD is also known as eczema and atopic eczema.

EPIDEMIO LO GY • AD is the most requent in ammatory skin disorder in the United States, a ecting 10% to 20% o children and 1% to 3% o adults. 1,2 • Ninety percent o cases begin by 5 years o age and markedly improve in 30% to 50% o patients by late childhood or early adolescence. 1,2 • Thirty percent to 40% o cases will persist into adulthood. 1,2 O these adult patients, 50% to 60% will develop persistent and recurrent disease. 2,3 2,4

• Adult-onset AD typically occurs a ter the third decade o li e. In a recent study, adult-onset AD accounted or 8.8% o all AD subtypes. 4 • Sixty percent o adults with AD will have children with AD. 1

FIGURE 143-2 An 18-ye ar-old woman with atop ic de rmatitis (AD) sup e rin e cte d b y he rp e s (e cze ma he rp e ticum). (Re p rod uce d with p e rmission from Buccolo LS. Severe rash afte r de rmatitis. J Fam Pract. 2004;53(8):613-615. Re p rod uce d with p e rmission from Frontline Me d ical Communications.)

DIAGNO SIS • History—Pruritus is the hallmark symptom o AD. It is re erred to as “the itch that rashes” as patients will o ten eel the need to scratch be ore a primary lesion appears. I it does not itch, it is not AD. • The atopic triad is AD, allergic rhinitis, and asthma. Persons with AD o ten have a personal or amily history o these other allergic

ETIO LO GY AND PATHO PHYSIO LO GY • Strong amilial tendency, especially i atopy is inherited rom the maternal side. • Associated with elevated T-helper (Th) 2 cytokine response, elevated serum immunoglobulin (Ig) E, hyperstimulatory Langerhans cells, de ective cell-mediated immunity, and loss-o - unction mutation in f laggrin, an epidermal barrier protein. • Current literature has divided AD into extrinsic (IgE-allergic) and intrinsic (non-IgE-allergic) subtypes. The extrinsic subtype is associated with the atopic march and accounts the majority o adult AD patients. The intrinsic subtype a ects only 5% to 15% o adult AD cases and is typif ed by normal IgE levels, less respiratory symptoms, and negative skin-prick tests. 5,6 • Exotoxins o Staphylococcus aureus act as superantigens and stimulate activation o T cells and macrophages, worsening AD without actually showing signs o superin ection. • Malassezia yeasts, which colonize adult AD skin in the head and neck region, may also trigger disease. 5 • Sensitivity to environmental allergens, especially dust mite, a ects the majority o adults with AD. 5 • Patients may have a primary T-cell de ect. This may be why they can get more severe skin in ections caused by herpes simplex virus (eczema herpeticum as seen in Figure 143-2) or bacteria (widespread impetigo). They are also at risk o a bad reaction to the smallpox vaccine with dissemination o the attenuated virus beyond the vaccination site. Eczema vaccinatum is a potentially deadly complication o smallpox vaccination (Figure 143-3).

FIGURE 143-3 Ecze ma vaccinatum in a woman with atop ic d e rmatitis (AD) who was g ive n the smallp ox vaccine . This e rup tion b e came this se ve re 8 d ays a te r he r vaccinatio n. (Re p rod uce d with p e rmission from CDC and Arthur E. Kaye .)

PART 14 DERMATO LO GY

ATO PIC DERMATITIS

conditions. In a recent study, respiratory symptoms in adult AD patients occurred in 71 out o 80 patients. 2 • Atopic persons have an exaggerated in ammatory response to actors that irritate the skin. The prevalence o allergic and irritant contact dermatitis mediated through delayed-type hypersensitivity reaction and nonimmune-mediated reaction, respectively, is increased in adults with AD. 6 • Physical examination—Primary lesions include vesicles, scale, papules, and plaques. • Secondary (or sequential) lesions include linear excoriations rom scratching or rubbing which may result in lichenif cation (thickened skin with accentuation o skin lines), f ssuring, and prurigo nodularis. Crust may indicate that a secondary in ection has occurred. Postin ammatory hyperpigmentation and ollicular hyperaccentuation (more prominent hyperkeratotic ollicles) (Figure 143-4) may also be identif ed. TYPICAL DISTRIBUTIO N • AD in adult can occur anywhere, but is most common on the exural olds (Figures 143-5 and 143-6), head-and-neck (Figures 143-7 and 143-8), wrists, hands (Figure 143-9) and ace (Figure 143-10). • Eczematous erythroderma with erythema and scaling covering all or nearly all o the body can occur and is more common in elderly AD patients. 5 • There is a higher requency o hand eczema in adult-onset AD. In one series, the prevalence o hand involvement in patients with active AD was 58.9%. In the same study, there was a signif cant trend toward an increasing prevalence o hand involvement with increasing age. 4,7 O THER FEATURES O R CO NDITIO NS ASSO CIATED WITH ATO PIC DERMATITIS • Keratosis pilaris (Figure 143-11). • Ichthyosis (Figure 143-12).

FIGURE 143-5 Atop ic d e rmatitis (AD) in the ante cub ital ossae and ore arms o this woman. She has had AD since child hood . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Dennie-Morgan lines (in raorbital old) (see Figure 143-10). • Hand or oot dermatitis (see Chapter 145, Hand Eczema). • Cheilitis (Figure 143-13) (see Chapter 29, Angular Cheilitis). • Susceptibility to cutaneous in ections (see Figures 143-2 and 143-3). • Xerosis (dry skin).

• Pityriasis alba (mostly in children). • Palmar or plantar hyperlinearity.

FIGURE 143-4 A b lack man with a are o his atop ic d e rmatitis (AD) showing ollicular hyp e racce ntuation on the arms. This p atte rn o AD is more common in p e rsons o color. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 143-6 A 20-ye ar-old young woman with se ve re chronic atop ic d e rmatitis (AD) showing liche nif cation and hyp e rp ig me ntation in the p op lite al ossa. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

685

686

PART 14 DERMATO LO GY

FIGURE 143-7 A young nurse with atop ic d e rmatitis (AD) mad e worse b y we aring the ste thoscop e around he r ne ck. (Re p rod uce d with p e rmission from Milg rom EC, Usatine RP, Tan RA, Sp e ctor SL. Practical Alle rg y. Philad e lp hia, PA: Else vie r; 2004.)

CHAPTER 143

FIGURE 143-10 A young woman with chronic atop ic d e rmatitis (AD) around he r e ye s and mouth. In ad d ition to the e ye lid involve me nt the p atie nt has De nny Morg an line s visib le on the lowe r e ye lid s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 143-8 Black woman with are o ato p ic d e rmatitis on the ne ck a te r e e ing hurricane Katrina. The ollicular hyp e racce ntuation is typ ical in p e rsons o color. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 143-9 Atop ic d e rmatitis on the wrists and hand s o a 58-ye ar-old man with a co-e xisting nicke l alle rg y. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 143-11 Ke ratosis p ilaris on the late ral up p e r arm. Note how the p ap ule s can vary in color rom p ink to b rown to white . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

ATO PIC DERMATITIS

FIGURE 143-12 Acq uire d ichthyosis on the le g o a 55-ye ar-old b lack man with atop ic d e rmatitis (AD). Note the f sh-scale ap p e arance along with the d ry skin. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Eye f ndings—Recurrent conjunctivitis, keratoconus (Figure 143-14), cataracts, orbital darkening.

A

• A horizontal nasal crease may be seen over the bridge o the nose in a patient with allergic rhinitis prone to per orming the allergic salute. In some patients this crease may become hyperpigmented (Figure 143-15). LABO RATO RY STUDIES Laboratory studies are rarely needed i the history and physical examination support the diagnosis. Occasionally, a potassium hydroxide (KOH) preparation or tinea or skin scraping or scabies may be needed to rule out primary or concomitant disease. Adult-onset AD that is not improving with therapy may need urther investigation with skin patch testing to rule out primary or concomitant allergic contact dermatitis. Radioallergosorbent test (RAST) or ood allergies, eosinophil counts, and serum IgE levels are not o proven benef t or diagnosis or management, however, IgE serum levels and eosinophil count correlate with disease severity and are potential strategies or targeted drug development. 2 B FIGURE 143-14 Ke ratoconus in a young woman with se ve re atop ic d e rmatitis (AD). She ad mits to rub b ing he r e ye s re q ue ntly. A. In ke ratoconus the corne a b ulg e s out in the mid d le like a cone . B. Two ye ars late r the ke ratoconus le d to corne al op acif cation. She now ne e d s a corne al transp lant. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIFFERENTIAL DIAGNO SIS • Dyshidrotic eczema—Dry in amed scaling skin on the hands and eet with tapioca-like vesicles, especially seen between the f ngers (see Chapter 145, Hand Eczema). • Seborrheic dermatitis—Greasy, scaly lesions on scalp, ace, and chest (see Chapter 149, Seborrheic Dermatitis). FIGURE 143-13 Atop ic d e rmatitis (AD) with ang ular che ilitis and p ostin ammatory hype rp igmentation on the lips rom rubb ing se condary to pruritus. The angular che ilitis occurre d during a are o the atopic de rmatitis on the arms and le gs. (Re produce d with p ermission from Richard P. Usatine , MD.)

• Psoriasis—Thickened plaques on extensor sur aces, scalp, and buttocks; pitted nails (see Chapter 150, Psoriasis). • Lichen simplex chronicus (sometimes called neurodermatitis)— Usually, a single patch in an area accessible to scratching such as the

687

688

PART 14 DERMATO LO GY

CHAPTER 143

contact allergy in a patient with existing AD. (see Chapter 144, Contact Dermatitis). • Scabies—Papules, burrows, f nger web involvement, positive skin scraping (see Chapter 141, Scabies). • Dermatophyte in ection—On the hands or eet, can look just like hand or oot dermatitis; a positive KOH preparation or hyphae can help make the diagnosis (see Chapter 138, Tinea Pedis).

MANAGEMENT

FIGURE 143-15 Hyp e rp ig me nte d horizontal nasal cre ase in a p atie nt with the atop ic triad who re p e ate d ly p e r orms the alle rg ic salute whe n he r nose is e e ling pruritic. (Re produce d with pe rmission from Richard P. Usatine, MD.)

ankle, wrist, and neck (Figure 143-16) (see Chapter 147, Psychocutaneous Disorders). • Contact dermatitis—Positive exposure history, rash in area o exposure; absence o amily history. Patch testing may be help ul in distinguishing rom contact dermatitis rom AD or rom diagnosing a new

• There is some evidence suggesting that controlling house dust mites reduces severity o symptoms in patients with the atopic triad. Bedding covers were ound to be the most e ective method to control dust mites and AD symptoms in this subgroup o AD patients. Un ortunately, dust mite interventions are not proven to be e ective or patients with AD that do not have the ull atopic triad. 1 SO R B • There is no evidence that dietary manipulation in adults reduces symptom severity and may cause iatrogenic malnourishment. SO R B • Patient education, avoidance o possible triggers (enzyme-rich detergents, wool clothing), and dry skin care should be optimized. • Dilute bleach baths (0.5 cup o 6% bleach in tub o bath water) lower the S. aureus burden on the skin, decreasing severity o AD in children. 8 SO R B While there are no studies using bleach baths in adults with AD, this treatment may be worth trying in those adults willing to give it a try. TO PICAL THERAPIES • Topical steroids and emollients have been proven to work or AD and are the mainstay o treatment. 1 SO R A • Vehicle selection and steroid strength are based on age, body location, and lesion morphology. The ointments are best or dry and cracked skin and are more potent. Creams are easier to apply and are better tolerated by some patients. • Use stronger steroids or thicker skin, severe outbreaks, or lesions that have not responded to weaker steroids. Avoid strong steroids on ace, genitals, and armpits (Figure 143-17). • To avoid adverse e ects, the highest-potency steroids (eg, clobetasol) should not be used or longer than 2 weeks on a daily basis. However, they can be used intermittently or recurring AD in a pulse-therapy mode (eg, apply every weekend, with the use o emollients, lowerpotency topical steroid or topical calcineurin inhibitor on weekdays). • Topical calcineurin inhibitors (immunomodulators, such as pimecrolimus and tacrolimus) reduce the rash severity and symptoms in children and adults. 1 SO R A These work by suppressing antigen-specif c T-cell activation and inhibiting in ammatory cytokine release. These are steroid-sparing medications that are help ul or eyelid eczema and in other areas when steroids may thin the skin (Figure 143-18). The FDA states that they should not be used as f rst-line agents because o a possible risk o causing cancer. The American Academy o Dermatology (AAD) has released a statement that the “data does not prove that the proper topical use o pimecrolimus and tacrolimus is dangerous.”

FIGURE 143-16 Atop ic d e rmatitis (AD) since child hood in a Hisp anic woman showing liche nif cation on the ace rom many ye ars o rub b ing the skin. The thicke ning o the skin has also a e cte d the e ye lid s and cause d p ostin ammatory hyp e rp ig me ntation. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Short-term adjunctive use o topical doxepin may aid in the reduction o pruritus. 1 SO R A • Topical and systemic antibiotics are used or AD that has become secondarily in ected with bacteria. The most common in ecting organism

PART 14 DERMATO LO GY

ATO PIC DERMATITIS

TABLE 143-1 Writte n Action Plan to Be Give n to Patie nts

No skin le sions or d ry skin

Pre ve ntion: Emollie nts, d ry skin care , rag rance - re e d e te rg e nt, no d rie r she e ts, once we e kly b le ach b ath

Mild are

Pre ve ntion p lus low-mid p ote ncy top ical ste roid and /or calcine urin inhib itors (e g , hyd rocortisone 2.5% or tacrolimus 0.1% to ace , axillae , g e nitals; d e sonid e 0.1% or triamcinolone 0.1% to b od y)

Mod e rate are

Pre ve ntion p lus mid -hig h p ote ncy top ical ste roid s and /or calcine urin inhib itor (e g , triamcinolone und e r we t p ajamas b id to clob e tasol or short course )

Se ve re are

Syste mic the rap y

Data rom Rance F, Bog unie wicz M, and Lau S,3 and rom Chisolm SS, Taylor SL, Balkrishnan R, e t al.9

FIGURE 143-17 Se ve re li e long atop ic d e rmatitis (AD) in a 31-ye ar-old A rican Ame rican woman. AD is p articularly se ve re on the ace and around the ne ck and has le d to p ostin ammatory hyp e rp ig me ntation. The e ye lid s and p e rioral re g ions are involve d with this woman who also has asthma and alle rg ic rhinitis (atop ic triad ). (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

is S. aureus. Weeping uid and crusting during an exacerbation should prompt consideration o antibiotic use1 (see Figure 143-1). SO R A

• The value o antihistamines in AD is controversial. I antihistamines are to be used, the sedating agents are most e ective and can be given at night. 1 SO R B • Cyclosporine or severe re ractory AD can be used in long-term maintenance therapy to treat and avoid relapse. 1 SO R A Cyclosporine is approved or 1 year o li etime therapy or skin diseases in the United States and 2 years in Europe (see Figure 143-1). • Ultraviolet (UV) phototherapy may also be used in severe re ractory AD with some success. 1 SO R A • Azathioprine, methotrexate, and mycophenolate mo etil are o possible benef t, but there is less evidence or their e ectiveness.1 SO R C

O RAL/ SYSTEMIC THERAPIES • For extensive ares, consider oral prednisone or an intramuscular (IM) shot o triamcinolone (40 mg in 1 mL o 40 mg/ mL suspension or adults). 1 SO R C

PATIENT EDUCATIO N Patients need to know that scratching their AD makes is worse. Behavior modif cation may involve cutting f ngernails short and occluding hands/ body with wraps, cotton gloves or clothing. Because o its chronicity and cyclic nature, AD patients may have poor adherence. In one recent study, overall adherence was only 32%. 9 A written action plan may improve compliance (Table 143-1).

FO LLO W-UP Regular ollow-up should be given to patients with chronic and di f cultto-control AD. Studies show hospitalization rates as high as 50% is adult AD patients who are uncontrolled. 2 Establishing a good regimen is crucial to good control and then visits may be adjusted to longer intervals between visits.

FIGURE 143-18 Atop ic d e rmatitis (AD) involving the e ye lid s in this 19-ye arold woman with re lative ly se ve re AD since in ancy. A top ical calcine urin inhib itor he lp e d to g e t the e ye lid e cze ma und e r control. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

689

PART 14 DERMATO LO GY

690

PATIENT RESO URCES

• American Academy o Dermatology—www.skincarephysicians .com/ eczemanet/ . • The National Eczema Association—www.nationaleczema .org/ . PRO VIDER RESO URCES

• Medscape. Atopic dermatitis—http:/ / emedicine.medscape. com/ article/ 1049085-overview.

REFERENCES

CHAPTER 143

3. Rance F, Boguniewicz M, Lau S. New visions or atopic eczema: an iPAC summary and uture trends. Pediatr Allergy Immunol. 2008;19(suppl 19):17-25. 4. Ingordo V, D’Andria G, D’Andria C. Adult-onset atopic dermatitis in a patch test population. Dermatology. 2003;206(3):197-203. 5. Katsarou A, Armenaka M. Atopic dermatitis in older patients: particular points. J Eur Acad DermatolVenereol. 2011 Jan;25(1):12-18. 6. Wüthrich B, Schmid-Grendelmeier P. The atopic eczema/ dermatitis syndrome. Epidemiology, natural course, and immunology o the IgEassociated (“extrinsic”) and the nonallergic (“intrinsic”) AEDS. J Investig Allergol Clin Immunol. 2003;13(1):1-5. 7. Simpson EL. Prevalence and morphology o hand eczema in patients with atopic dermatitis. Dermatitis. 2006;17:123-127.

1. Hanif n JM, Cooper KD, Ho VC, et al. Guidelines o care or atopic dermatitis. JAmAcad Dermatol. 2004;50:391-404.

8. Huang JT, Abrams M, Tlougan B, et al. Dilute bleach baths or Staphylococcus aureus colonization in atopic dermatitis to decrease disease severity. Pediatrics. 2009;123(5):e808-e814.

2. Or ali RL, Shimizu MM, Takaoka R, et al. Atopic dermatitis in adults: clinical and epidemiological considerations. Rev Assoc Med Bras. 2013 May-Jun;59(3):270-275.

9. Chisolm SS, Taylor SL, Balkrishnan R, et al. Written action plans: potential or improving outcomes in children with atopic dermatitis. JAmAcad Dermatol. 2008;59:677-683.

PART 14

CO NTACT DERMATITIS

DERMATO LO GY

144 CO NTACT DERMATITIS Richard P. Usatine , MD

PATIENT STO RY A 38-year-old woman twisted her right ankle and applied a Chinese medicine patch to relieve the pain. The ollowing day the patient developed a severe contact dermatitis (CD) with many small vesicles (< 5 mm) and bullae (>5 mm) (Figure 144-1). The erythema had a well-demarcated border and was traced by the doctor’s pen. Cold compresses and a highpotency topical steroid were prescribed. When the patient showed little improvement a 2-week course o oral prednisone was given starting with 60 mg daily and tapering down to 5 mg daily. The patient responded rapidly and the CD ully resolved. 1,2

FIGURE 144-2 O ccup ational irritant contact d e rmatitis in a woman whose hand s are e xp o se d to che micals while making cowb oy hats in Te xas. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

INTRO DUCTIO N CD is a common in ammatory skin condition characterized by erythematous and pruritic skin lesions resulting rom the contact o skin with a oreign substance. Irritant contact dermatitis (ICD) is caused by the nonimmune-modulated irritation o the skin by a substance, resulting in skin changes. Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity reaction in which a oreign substance comes into contact with the skin, and upon reexposure, skin changes occur. 3

EPIDEMIO LO GY • Some o the most common types o CD are secondary to exposures to poison ivy, nickel, and ragrances. 4 • Patch testing data indicate that the 5 most prevalent contact allergens out o more than 3700 known contact allergens are nickel (14.3% o patients tested), ragrance mix (14%), neomycin (11.6%), balsam o Peru (10.4%), and thimerosal (10.4%). 5 • Occupational skin diseases (chie y CD) rank second only to traumatic injuries as the most common type o occupational disease. Chemical irritants such as solvents and cutting uids account or most ICD cases. Sixty percent were ACD and 32% were ICD. Hands were primarily a ected in 64% o ACD and 80% o ICD4 (Figure 144-2).

ETIO LO GY AND PATHO PHYSIO LO GY • CD is a common in ammatory skin condition characterized by erythematous and pruritic skin lesions resulting rom the contact o skin with a oreign substance. • ICD is caused by the nonimmune-modulated irritation o the skin by a substance, resulting in a skin rash. • ACD is a delayed-type hypersensitivity reaction in which a oreign substance comes into contact with the skin, and is linked to skin protein orming an antigen complex that leads to sensitization. Upon reexposure o the epidermis to the antigen, the sensitized T cells initiate an in ammatory cascade, leading to the skin changes seen in ACD.

DIAGNO SIS HISTO RY Ask the patients about contact with known allergens (ie, nickel, ragrances, neomycin, and poison ivy/ oak). FIGURE 144-1 Se ve re acute alle rg ic contact d e rmatitis on the ankle of a woman afte r ap p lication of a Chine se top ical me d icine for a sp raine d ankle . (Re p rod uce d with p e rmission from Milg rom EC, Usatine RP, Tan RA, Sp e ctor SL. Practical Alle rg y. Philad e lp hia, PA: Else vie r, Inc; 2004.)

• Nickel exposure is o ten related to the wearing o rings, jewelry, and metal belt buckles (Figures 144-3 to 144-5). • Fragrances in the orms o deodorants and per umes (Figure 144-6).

691

692

PART 14

DERMATO LO GY

FIGURE 144-3 Alle rg ic contact d e rmatitis to nicke l in a che ap watch b and .

• Ask about occupational exposures, especially solvents. For example, chemicals used in hat making can cause ICD on the hands (see Figure 144-2). Allergic contact dermatitis to cement occurs in construction workers (Figure 144-7). • Neomycin applied as a triple antibiotic ointment by patients (Figures 144-8 and 144-9). • Poison ivy/ oak in outdoor settings. Especially ask when the distribution o the reaction is linear (Figures 144-10 and 144-11). • Tapes applied to skin a ter cuts or surgery are requent causes o CD (Figure 144-12). • I the CD is on the eet, ask about new shoes (Figures 144-13 and 144-14).

FIGURE 144-4 Alle rg ic contact d e rmatitis to the me tal in the b e llyb utton ring of a young woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Ch a pt e r 144

FIGURE 144-5 Alle rg ic contact d e rmatitis to the me tal in the b e lt b uckle causing e rythe ma, scaling , and hyp e rp ig me ntation. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

A detailed history o products used on the skin may reveal a suspected allergen. In Figure 144-15, this truck driver was using baby wipes to clean his skin during long drives. Patch testing ultimately revealed that he was allergic to one o the ingredients in those wipes. CLINICAL FEATURES All types o CD have erythema. Although it is not always possible to distinguish between ICD and ACD, here are some eatures that might help: • ICD ° Location—usually the hands

FIGURE 144-6 Alle rg ic contact d e rmatitis to the frag rance in a ne w d e od orant. (Re p rod uce d with p e rmission from Milg rom EC, Usatine RP, Tan RA, Sp e ctor SL. Practical Alle rg y. Philad e lp hia, PA: Else vie r, Inc; 2004.)

CO Nt a Ct De r Ma t It IS

FIGURE 144-7 Alle rg ic contact d e rmatitis to ce me nt in a construction worke r. Note how the re action is strong e st on the fore arms whe re the g re ate st e xp osure occurs. The p atie nt note s that whe n he we ars p rote ctive clothing ove r the arms he is ab le to work with ce me nt. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

PART 14

DERMATO LO GY

FIGURE 144-10 A line ar p atte rn of alle rg ic contact d e rmatitis from p oison ivy. (Re p rod uce d with p e rmission from Jack Re sne ck, Sr., MD.)

° Symptoms—burning, pruritus, pain ° Dry and f ssured skin (see Figure 144-2) ° Indistinct borders • ACD ° Location—usually exposed area o skin, o ten the hands ° Pruritus, the dominant symptom ° Vesicles and bulla (Figures 144-1 and 144-16) ° Distinct angles, lines, and borders (see Figures 144-8 to 144-12) Both ICD and ACD may be complicated by bacterial superin ection showing signs o exudate, weeping, and crusts.

FIGURE 144-8 Alle rg ic contact d e rmatitis to ne omycin ap p lie d to the le g of a young wo man. He r mom g ave he r trip le antib iotic ointme nt to p lace ove r a b ug b ite with a larg e nonstick p ad . The contact alle rg y follows the e xact size of the p ad and o nly o ccurs whe re the antib iotic was ap p lie d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 144-9 Alle rg ic contact d e rmatitis to a ne omycin containing top ical antib iotic on the b re asts. This woman ap p lie d this me d icine to tre at he r b re ast d iscomfort that b e g an whe n he r b re ast-fe e d ing b ab y d e ve lop e d thrush. (Re p rod uce d with p e rmission from Jack Re sne ck, Sr., MD.)

FIGURE 144-11 Multip le line s of ve sicle s from p oison oak on the arm. (Re p rod uce d with p e rmission from Milg rom EC, Usatine RP, Tan RA, Sp e ctor SL. Practical Alle rg y. Philad e lp hia, PA: Else vie r, Inc; 2004.)

693

694

PART 14

DERMATO LO GY

Ch a pt e r 144

FIGURE 144-12 Alle rg ic contact d e rmatitis to the tap e use d afte r an ab d ominal hyste re ctomy. (Re p ro d uce d with p e rmission fro m Milg rom EC, Usatine RP, Tan RA, Sp e ctor SL. Practical Alle rg y. Philad e lp hia, PA: Else vie r, Inc; 2004.)

Toxicodendron (Rhus) dermatitis (poison ivy, poison oak, and poison sumac) is caused by urushiol, which is ound in the saps o this plant amily. Clinically, a line o vesicles can occur rom brushing against one o the plants. Also, the linear pattern occurs rom scratching onesel and dragging the oleoresin across the skin with the ingernails (see Figures 144-10 and 144-11). Systemic CD is a rare orm o CD seen a ter the systemic administration o a substance, usually a drug, to which topical sensitization has previously occurred. 6

FIGURE 144-14 A 25-ye ar-old man with alle rg ic contact d e rmatitis to a che mical in his b oots. His b oots we re hig he r b ut he cut the m d own to try to alle viate the d iscomfort coming from the b oots hig he r on his le g . (Re p rod uce d with p e rmission from Milg rom EC, Usatine RP, Tan RA, Sp e ctor SL. Practical Alle rg y. Philad e lp hia, PA: Else vie r, Inc; 2004.)

• KOH preparation and/ or ungal culture i tinea is suspected. • Microscopy or scabies mites and eggs.

LABO RATO RY STUDIES The diagnosis is most o ten made by history and physical examination. Consider culture i there are signs o superin ection and there is a concern or methicillin-resistant Staphylococcus aureus (MRSA). The ollowing tests may be considered when the diagnosis is not clear.

FIGURE 144-13 Alle rg ic contact d e rmatitis to ne w shoe s. This is the typ ical d istrib ution found on the d orsum of the fe e t. Patch te sting re ve ale d that the p atie nt was alle rg ic to thiuram mix which is found in rub b e r use d to make shoe s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Latex allergy testing—This type o reaction is neither ICD (nonimmunologic) nor ACD. The latex allergy type o reaction is a type I, or immunoglobulin (Ig)E-mediated response to the latex allergen.

FIGURE 144-15 A 49-ye ar-old truck d rive r d e ve lop e d p ruritic e rythe matous e rup tion on his arms and trunk that p e rsiste d for 1 ye ar d e sp ite various tre atme nts. Patch te sting ultimate ly re ve ale d that he was alle rg ic to Cl+ Me – isothiazolinone . He we nt home and d iscove re d this was one of the ing re d ie nts in the b ab y wip e s he use d to cle an his skin d uring long d rive s. His alle rg ic contact d e rmatitis re solve d once he stop p e d using the wip e s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

CO Nt a Ct De r Ma t It IS

A

PART 14

DERMATO LO GY

FIGURE 144-17 The T.R.U.E. Te st is an e asy-to -use stand ard ize d p atch te st that is ap p lie d to the b ack using 3 tap e strip s to te st for 35 common alle rg e ns. Extra hyp oalle rg e nic tap e is ap p lie d to ke e p the strip s from p e e ling off for 2 d ays. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

° Critics o the T.R.U.E. Test state that it misses other important

B FIGURE 144-16 Se ve re acute alle rg ic contact d e rmatitis in a house p ainte r re ce ntly working with insulation. He re sp ond e d rap id ly to oral p re d nisone . Patch te sting afte r he cle are d d e monstrate d alle rg ic contact d e rmatitis to formald e hyd e found in b oth insulatio n and p aint. It was no t until the p atch te st was p ositive to formald e hyd e and the p atie nt re ad the list of sub stance s in which formald e hyd e occurs that he p ut tog e the r the insulation e xp osure and his skin rash. A. Ve sicle s on the fore arm. B. Erosions on the d orsum of the hand s whe re the re we re p re vious ve sicle s and b ullae . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

antigens. There are a number o dermatologists who create their own more extensive panels in their o f ce. I the suspected allergen is not in the T.R.U.E. Test, re er to a specialist who will customize the patch testing. Also, personal products, such as cosmetics and lotions, can be diluted or special patch testing. ° Once the patch test results are known, it is important to determine i the result is “relevant” to the patient’s dermatitis. One method or classi ying clinical relevance o a positive patch test reaction is (a) current relevance—the patient has been exposed to allergen during the current episode o dermatitis and improves when the exposure ceases; (b) past relevance—past episode o dermatitis rom exposure to allergen; (c) relevance not known—not sure i exposure is current or old; (d) cross-reaction—the positive test is a result o cross-reaction with another allergen; and (e) exposed—a history o exposure but not resulting in dermatitis rom that exposure, or no history o exposure but a def nite positive allergic patch test. 6 • Punch biopsy—When another underlying disorder is suspected that is best diagnosed with histology (eg, psoriasis).

DIFFERENTIAL DIAGNO SIS • Patch testing—Common antigens are placed on the skin o a patient. The T.R.U.E. Test comes in 3 tape strips that are easy to apply to the back (Figure 144-17). There is no preparation needed to test or the 35 common allergens embedded into these strips (Table 144-1 or a list o the 35 allergens). The strips are removed in 2 days and read at that time and again in 2 more days (Figure 144-18). The T.R.U.E. Test website provides detailed in ormation on how to per orm the testing and how to counsel patients about the meaning o their results. Any clinician with an interest in patch testing can easily per orm this service in the o f ce. ° A meta-analysis o the T.R.U.E. Test shows that nickel (14.7% o tested patients), thimerosal (5.0%), cobalt (4.8%), ragrance mix (3.4%), and balsam o Peru (3.0%) are the most prevalent allergens detected using this system. 5

• Atopic dermatitis is usually more widespread than CD. There is o ten a history o other atopic conditions, such as allergic rhinitis and asthma. There may be amily history o allergies. However, persons with atopic dermatitis are more prone to CD (see Chapter 143, Atopic Dermatitis). • Dyshidrotic eczema—Seen on the hands and eet with tapioca vesicles, erythema, and scale. Although this is not primarily caused by contact to allergens, various irritating substances can make it worse. It is also possible to an ACD on top o an existing case o dyshidrotic eczema. (see Chapter 145, Hand Eczema). • Immediate IgE contact reaction (eg, latex glove allergy)—Immediate erythema, itching, and possibly systemic reaction a ter contact with a known (or suspected) allergen.

695

PART 14

696

Ch a pt e r 144

DERMATO LO GY TABLE 144-1 Alle rg e ns in T.R.U.E. Te st (Patch Te st for Contact De rmatitis)

Pane l 1.2

Pane l 2.2

Pane l 3.2

1. Nicke l sulfate

13. p -te rt-Butylp he nol formald e hyd e re sin

25. Diazolid inyl ure a

2. Wool alcohols

14. Ep oxy re sin

26. Q uinoline mix

3. Ne omycin sulfate

15. Carb a mix

27. Tixocortol-21-p ivalate

4. Potassium d ichromate

16. Black rub b e r mix

28. Gold sod ium thiosulfate

5. Caine mix

17. Cl+ Me – isothiazolinone (MCI/MI)

29. Imid azolid inyl ure a

6. Frag rance mix

18. Q uate rnium-15

30. Bud e sonid e

7. Colop hony

19. Me thyld ib romo g lutaronitrile

31. Hyd rocortizone -17-b utyrate

8. Parab e n mix

20. p -Phe nyle ne d iamine

32. Me rcap tob e nzothiazole

9. Ne g ative control

21. Formald e hyd e

33. Bacitracin

10. Balsam of Pe ru

22. Me rcap to mix

34. Parthe nolid e

11. Ethyle ne d iamine d ihyd rochlorid e

23. Thime rosal

35. Disp e rse b lue 106

12. Cob alt d ichlorid e

24. Thiuram mix

36. 2-Bromo-2-nitrop rop ane 1,3-d iol (Bronop ol)

The re are 35 alle rg e ns and one ne g ative control at numb e r 9.

• Fungal in ections—A dermatophyte in ection that can closely resemble CD when it occurs on the hands and eet. Tinea pedis is usually seen between the toes, on the soles, or on the sides o the eet. CD o the eet is o ten on the dorsum o the oot and related to rubber or other chemicals in the shoes (see Figures 144-13 and 144-14; see Chapter 138, Tinea Pedis).

MANAGEMENT • Identi y and avoid the o ending agent(s). 4 SO R A ° Be aware that some patients are actually allergic to topical steroids. This un ortunate situation can be diagnosed with patch testing.

• Scabies on the hands can be mistaken or CD. Look or burrows and or the typical distribution o the scabies in estation to distinguish this rom CD (see Chapter 141, Scabies). • Allergies to the dyes used in tattoos can occur. Although this is not strictly a CD because the dye is injected below the skin, the allergic process is similar (Figure 144-19).

FIGURE 144-18 This p ositive p atch te st re sult for nicke l shows small ve sicle s on an e rythe matous b ase . The T.R.U.E. Te st re ad ing strip is he ld ag ainst the skin to id e ntify the p ositive antig e n. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 144-19 Man with alle rg y to re d d ye in tattoo . Eve rywhe re that the re d d ye was use d , the p atie nt d e ve lop e d p ain and swe lling . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14

CO Nt a Ct De r Ma t It IS

DERMATO LO GY

° In cases o nickel ACD, we recommend the patient cover the metal tab o their jeans with an iron-on patch or a ew coats o clear nail polish.

• Cool compresses can soothe the symptoms o acute cases o CD. 4 SO R C

• Calamine and colloidal oatmeal baths may help to dry and soothe acute, oozing lesions. 3,4 SO R C • Localized acute ACD lesions respond best with mid-potency to highpotency topical steroids such as 0.1% triamcinolone to 0.05% clobetasol, respectively. 4 SO R A • On areas o thinner skin (eg, exural sur aces, eyelids, ace, anogenital region) lower-potency steroids such as desonide ointment can minimize the risk o skin atrophy. 3,4 SO R B • There is insu f cient data to support the use o topical steroids or ICD, but because it is di f cult to distinguish clinically between ACD and ICD, these agents are requently tried. SO R C • I ACD involves extensive skin areas (> 20%), systemic steroid therapy is o ten required and o ers relie within 12 to 24 hours. The recommended dose is 0.5 to 1 mg/ kg daily or 5 to 7 days, and i the patient is com ortable at that time, the dose may be reduced by 50% or the next 5 to 7 days. The rate o reduction o steroid dosage depends on actors such as severity, duration o ACD, and how e ectively the allergen can be avoided. 4 SO R B • Oral steroids should be tapered over 2 weeks because rapid discontinuance o steroids can result in rebound dermatitis. Severe poison ivy/ oak is o ten treated with oral prednisone or 2 to 3 weeks. Avoid using a Medrol dose-pack, which has insu f cient dosing and duration. 4

FIGURE 144-20 Se ve re occup ational contact d e rmatitis to p e trole um p rod ucts in a man who works as a car me chanic. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Petrolatum applied twice a day is a great way to moisturize dry and cracked skin without exposing the patient to new irritants. I the CD is severe enough (Figure 144-20), the patient may need to change work to completely avoid the o ending irritant or antigen.

FO LLO W-UP

SO R B

• The e f cacy o topical immunomodulators (tacrolimus and pimecrolimus) in ACD or ICD has not been well established. 4 However, one randomized controlled trial (RCT) did demonstrate that tacrolimus ointment is more e ective than vehicle in treating chronically exposed, nickel-induced ACD. 7 SO R B • Although antihistamines are generally not e ective or pruritus associated with ACD, they are commonly used. Sedation rom more soporif c antihistamines may o er some degree o palliation (diphenhydramine, hydroxyzine). 4 SO R C

May need requent ollow-up i the o ending substance is not ound, the rash does not resolve, and i patch testing will be needed.

PATIENT EDUCATIO N Avoid the o ending agent and take the medications as prescribed to relieve symptoms.

• Bacterial superin ection should be treated with an appropriate antibiotic that will cover Streptococcus pyogenes and S. aureus. Treat or MRSA i suspected.

PATIENT RESO URCES

• Once the diagnosis o any CD is established, emollients and moisturizers may help soothe irritated skin. 4 SO R C

• The T.R.U.E. Test website has a wealth o in ormation on reading labels, common allergens and patch testing or patients—http:/ / www.truetest.com/ .

For ICD and occupational CD o the hands use the ollowing: • Wear protective gloves when working with known allergens or potentially irritating substances such as solvents, soaps, and detergents. 6,8 SO R A

• Use cotton liners under the gloves or both com ort and the absorption o sweat. Wearing cotton glove liners can prevent the development o an impaired skin barrier unction caused by prolonged wearing o occlusive gloves. 8 SO R B ° There is insu f cient evidence to promote6,8the use o barrier creams to protect against contact with irritants. SO R A can improve skin condition in ° A ter work, conditioning creams workers with damaged skin. 8 SO R A • Keep hands clean, dry, and well moisturized whenever possible.

• PubMed Health. Contact Dermatitis—http:/ / www.ncbi.nlm .nih.gov/ pubmedhealth/ PMH0001872/ .

PRO VIDER RESO URCES

• American Family Physician. Diagnosis and Management of Contact Dermatitis—http:/ / www.aafp.org/ afp/ 2010/ 0801/ p249.html. • The T.R.U.E. Test website has a wealth o in ormation on patch testing or healthcare pro essionals—http:/ / www.truetest.com/ . REFERENCES 1. Usatine RP. A red twisted ankle. West J Med. 1999;171:361-362. 2. Halstater B, Usatine RP. Contact dermatitis. In: Milgrom E, Usatine RP, Tan R, Spector S, eds. Practical Allergy. Philadelphia, PA: Elsevier; 2004.

697

698

PART 14

DERMATO LO GY

CHAPTER 144

3. Usatine RP, Riojas M. Diagnosis and management o contact dermatitis. Am Fam Physician. 2010;82:249-255.

6. Bourke J, Coulson I, English J. Guidelines or the management o contact dermatitis: an update. Br J Dermatol. 2009;160:946-954.

4. Beltrani VS, Bernstein IL, Cohen DE, Fonacier L. Contact dermatitis: a practice parameter. Ann Allergy Asthma Immunol. 2006;97:S1-S38.

7. Belsito D, Wilson DC, Warshaw E, et al. A prospective randomized clinical trial o 0.1% tacrolimus ointment in a model o chronic allergic contact dermatitis. JAmAcad Dermatol. 2006;55:40-46.

5. Krob HA, Fleischer AB Jr, D’Agostino R Jr, Haverstock CL, Feldman S. Prevalence and relevance o contact dermatitis allergens: a meta-analysis o 15 years o published T.R.U.E. test data. JAm Acad Dermatol. 2004;51:349-353.

8. Nicholson PJ, Llewellyn D, English JS. Evidence-based guidelines or the prevention, identif cation and management o occupational contact dermatitis and urticaria. Contact Dermatitis. 2010;63:177-186.

HAND ECZEMA

145 HAND ECZEMA Richard P. Usatine , MD

PATIENT STO RY An Asian-American physician presents with dry scaling on her hands. Frequent hand washing makes it worse and it sometimes cracks. She has allergic rhinitis and she had more widespread atopic dermatitis in her youth. This is a case o chronic atopic hand dermatitis (Figure 145-1). The treatment suggested was use o Cetaphil (or equivalent nonsoap cleanser) instead o soap and water. She was directed to soak her hands 3 to 5 minutes in warm water every night, apply triamcinolone 0.1% ointment, and cover with cotton gloves overnight. Her hands cleared 90% with this treatment and she was pleased with the results.

PART 14

DERMATO LO GY EPIDEMIO LO GY The prevalence o hand dermatitis is estimated at approximately 2% to 8.9% in the general population. 1

ETIO LO GY AND PATHO PHYSIO LO GY • There are many clinical variants o hand dermatitis and a number o di erent classif cation schemas. Here is one accepted classif cation scheme: 1. Contact (ie, allergic and irritant) (Figure 145-2) 2. Hyperkeratotic (ie, psoriasi orm) (Figure 145-3) 3. Frictional (Figure 145-4) 4. Nummular (Figure 145-5) 5. Atopic (Figure 145-6) 6. Pompholyx (ie, dyshidrosis) (Figures 145-7 and 145-8)

INTRO DUCTIO N Hand eczema re ers to a wide spectrum o in ammatory skin diseases o the hands, including atopic dermatitis, contact dermatitis, pompholyx, and dyshidrotic eczema.

7. Chronic vesicular hand dermatitis1 (Figure 145-9) • Another way o looking at hand dermatitis is to break it down into 3 categories2: 1. Endogenous—Atopic, psoriasis, pompholyx, dyshidrotic (we do not include psoriasis as a type o hand eczema in this chapter) 2. Exogenous—Allergic and irritant contact dermatitis

SYNO NYMS Hand eczema is also known as hand dermatitis, pompholyx, dyshidrotic eczema, and vesicular palmoplantar eczema. Although some people use pompholyx and dyshidrotic eczema synonymously, others reserve pompholyx or hand eczema with vesicles and bullae on the palms and dyshidrotic eczema or conditions with smaller vesicles between the f ngers and toes.

FIGURE 145-1 An Asian-Ame rican p hysician with chronic atop ic hand d e rmatitis. She has alle rg ic rhinitis and she had more wid e sp re ad atop ic d e rmatitis in he r youth. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

3. In ectious—Tinea, Candida, and/ or superimposed Staphylococcus aureus (Figure 145-10) • Most contact dermatitis o the hands is secondary to irritants such as soap, water, solvents, and other chemicals. • Allergic contact dermatitis (ACD) is a type IV, delayed-type, cellmediated, hypersensitivity reaction. • The 9 most requent allergens related to hand contact dermatitis were identif ed by patch testing rom 1994 to 2004. 3 These are quaternium-15 (16.5%), ormaldehyde (13%), nickel sul ate (12.2%), ragrance mix

FIGURE 145-2 Contact d e rmatitis to rag rance mix on the d orsum o the hand se cond ary to using the b ack o the hand to ap p ly p e r ume to ne ck. (Re p rod uce d with p e rmission from Usatine RP. Ne w rash on the rig ht hand and ne ck. J Fam Pract. 2003;52(11):863-865. Re p rod uce d with p e rmission from Frontline Me d ical Communicatio ns.)

699

700

PART 14

DERMATO LO GY

Ch a pt e r 145

FIGURE 145-3 Hyp e rke ratotic hand d e rmatitis in a b lack woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 145-6 Atop ic hand d e rmatitis on p alms in Asian Ame rican woman with long history o atop ic d e rmatitis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD. Pre viously p ub lishe d in Practical Alle rg y.)

FIGURE 145-4 Frictional hand e cze ma that is worse on the hand that is use d or the cane . The othe r sid e was a e cte d b y a stroke , so only one hand is usab le or amb ulating with a cane . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 145-7 Dyshid rotic e cze ma with acute outb re ak o tap ioca ve sicle s on the sid e s o the ng e rs. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 145-5 Nummular hand de rmatitis with tiny papule s, papulove sicle s, and “coin-shap e d ” e cze matous p laq ue s on the d istal ng e rs. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 145-8 Se ve re p omp holyx worse ning with top ical ste roid s. Patch te sting showe d she was alle rg ic to top ical ste roid s. He r hand s nally cle are d with oral cyclosp orine and avoid ance o all top ical and oral ste roid s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14

h a ND e CZe Ma

DERMATO LO GY DIAGNO SIS CLINICAL FEATURES1 Contact (ie, allergic and irritant) (see Figure 145-2) • Symptoms include burning, stinging, itching, and tenderness at the site o exposure to the irritant or allergen. 1 • Acute signs include papules, vesicles, bullae, and edema. • Weeping and crusting can occur with or without superin ection. • Chronic signs include plaques with f ssuring, hyperpigmentation, and/ or lichenif cation. • Irritant contact dermatitis may predispose to ACD. Hyperkeratotic (ie, psoriasi orm) (see Figure 145-3). • Symmetric hyperkeratotic plaques. • May be localized to the proximal or middle part o the palms.

FIGURE 145-9 Chronic ve sicular hand d e rmatitis g oing on or d e cad e s in this 51-ye ar-old Hisp anic woman. It is p articularly b ad in the hyp othe nar are a. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Pain ul f ssures are common. Frictional (see Figure 145-4) • Mechanical actors, o ten rom work, such as trauma, riction, pressure, and vibration, induce skin changes with erythema and scale. • “Wear-and-tear dermatitis.”1

(11.3%), thiuram mix (10.2%), balsam o Peru (9.6%), carba mix (7.8%), neomycin sul ate (7.7%), and bacitracin (7.4%). 3

• Can be caused by contact with paper and abrics. Nummular (see Figure 145-5)

• Rubber allergens were commonly associated with occupation. Onethird o patients with ACD had identif able relevant irritants. 3

• Nummular hand dermatitis (also called discoid hand dermatitis).

• Most common allergens are preservatives, metals, ragrances, topical antibiotics, or rubber additives. 3

• Dorsal hands and distal f ngers are o ten involved.

• Tiny papules, papulovesicles, or “coin-shaped” eczematous plaques. Atopic • Patients with childhood atopic dermatitis are predisposed to develop hand dermatitis as adults (see Figure 145-6). • There is no characteristic pattern and it can occur on any part o the hand. • Extension to or involvement o the wrist is common (Figure 145-11).

FIGURE 145-10 Contact hand d e rmatitis in a Chine se cook sup e rin e cte d with Cand id a. Se e the white scale b e twe e n the ng e rs. The Cand id a in the inte rd ig ital sp ace is also calle d e rosio inte rd ig italis b lasto myce tica and is se e n in p atie nts with d iab e te s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 145-11 Hand d e rmatitis with p romine nt wrist involve me nt in a 20-ye ar-old Hisp anic woman with mod e rate ly se ve re wid e sp re ad atop ic d e rmatitis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

701

702

PART 14

DERMATO LO GY

Ch a pt e r 145

Pompholyx (ie, dyshidrosis, dyshidrotic eczema) • Has recurrent crops o papules, vesicles, and bullae on the lateral aspects o the f ngers, as well as the palms and soles, on a background o nonerythematous skin (see Figures 145-7 and 145-8). • These are described as tapioca vesicles as they look like the small spheres in tapioca. The vesicles open and the skin then peels (mild desquamation). • There may be pruritus or pain. • Although some use the names pompholyx and dyshidrotic eczema interchangeably, others only use the name pompholyx to describe an explosive onset o large bullae, usually on the palms (see Figure 145-8) and dyshidrotic eczema to mainly describe chronic small tapioca vesicles on the sides o the f ngers (see Figure 145-7). • Both conditions may last 2 to 3 weeks and resolve, leaving normal skin, only to recur again at varying intervals. • Both conditions are idiopathic and closely related, i not identical. • Symptoms may be associated with exogenous actors (eg, nickel or hot weather) or endogenous actors (eg, atopy or stress). Chronic vesicular hand dermatitis (see Figure 145-9)

FIGURE 145-12 Patch te sting p ositive to 2 typ e s o top ical ste ro id s in a p atie nt with se ve re p omp holyx (se e Fig ure 145-8) and top ical ste roid alle rg ic contact d e rmatitis. Re ad ing o T.R.U.E. Te st. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Chronic vesicles that are mostly palmar and pruritic. • Di erentiated rom pompholyx by a more chronic course and the presence o vesicles with an erythematous base. • The soles o the eet may also be involved. • Poorly responsive to treatments. • In one series, 55% o patients with this type o hand dermatitis were ound to have positive patch test results. 4 TYPICAL DISTRIBUTIO N O course, hand dermatitis is on the hands, but both hands and eet can be involved in dyshidrotic eczema and chronic vesicular hand dermatitis. LABO RATO RY STUDIES Scraping and using microscopy with potassium hydroxide (KOH) (with or without a ungal stain) to look or dermatophytes is help ul (see Chapter 134, Fungal Overview). Patch testing can be crucial to the diagnosis and treatment o hand eczema. Patch testing is described in detail in the previous chapter (Chapter 144, Contact Dermatitis). The patient in Figure 145-8 had severe pompholyx worsening with topical steroids. Patch testing showed she was allergic to topical steroids (Figure 145-12). Her hands f nally cleared with oral cyclosporine and avoidance o all topical and oral steroids.

the hand. Palmoplantar psoriasis will involve the hands and eet (see Chapter 150, Psoriasis). • Knuckle pads are thickening o the skin over the knuckles. These can be accompanied by hyperpigmentation.

MANAGEMENT • Lifestyle modifying factors, as listed in Table 145-1, are essential. • Avoid irritants and “wet work” at home and at work as much as possible. SO R C • Wear protective gloves when working with known allergens or potentially irritating substances such as solvents, soaps, and detergents. 5,6 SO R A

DIFFERENTIAL DIAGNO SIS • Tinea manus is o ten ound as part o the 2- oot, 1-hand syndrome in which both eet have scaling tinea pedis and one hand has scale as well (Figure 145-13) (see Chapter 134, Fungal Overview and Chapter 138, Tinea Pedis). • Candida can be seen in between the f ngers with erythema and scale over the f ngers and hand (see Figure 145-10) (see Chapter 135, Candidiasis). • Psoriasis o ten involves the hand. It can present with plaques on the dorsum o hand and over the knuckles o the f ngers or on the palm o

FIGURE 145-13 Tine a manus in a p atie nt with 2- oot, 1-hand synd rome . The scrap ing showe d hyp hae und e r the microscop e with a KO H p re p aration. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14

h a ND e CZe Ma

DERMATO LO GY

TABLE 145-1 Samp le Patie nt Hand out on Li e style Manag e me nt o Hand De rmatitis

Hand washing and moisturizing • Use luke warm or cool wate r, and mild cle anse rs without p e r ume , coloring , or antib acte rial ag e nts, and with minimal p re se rvative s. In g e ne ral, b ar soap s te nd to have e we r p re se rvative s than liq uid soap s (Ce tap hil or Aq uanil liq uid cle anse rs or g e ne ric e q uivale nts are e xce p tions to this state me nt). • Pat hand s d ry, e sp e cially b e twe e n ng e rs. • Imme d iate ly ollowing p artial d rying o hand s (e g , within 3 minute s), ap p ly a g e ne rous amount o a he avy cre am or ointme nt (not lotion); p e trole um je lly, a 1-ing re d ie nt lub ricant, works we ll. • It is he lp ul to have containe rs o cre ams or ointme nts ne xt to e ve ry sink in your home (ne xt to the b e d , ne xt to the TV, in the car, and at multip le p lace s at work). • Moisturizing should b e re p e ate d as o te n as p ossib le throug hout the d ay, id e ally 15 time s p e r d ay. • Avoid using washcloths, rub b ing , scrub b ing , or ove ruse o soap or wate r. O cclusive the rap y at nig ht or inte nsive the rap y • Ap p ly a g e ne rous amount o your d octor’s re comme nd e d e mollie nt or p re scrib e d me d icine on your hand s. • The n p ut on cotton g love s and we ar ove rnig ht. Whe n p e r orming “we t work” • We ar cotton g love s und e r vinyl or othe r nonlate x g love s. • Try not to use hot wate r and d e cre ase e xp osure to wate r to le ss than 15 minute s at a time , i p ossib le . • Use running wate r rathe r than imme rsing hand s, i p ossib le . • Re move ring s b e ore we t or d ry work. We ar p rote ctive g love s in cold we athe r and or d usty work. For rictional e xp osure s, we ar tig ht- tting le athe r g love s (e g , rid ing or g ol ng g love s). Avoid d ire ct contact with the ollowing , i p ossib le : • Shamp oo • Pe e ling ruits and ve g e tab le s, e sp e cially citrus ruits • Polishe s o all kind s • Solve nts (e g , white sp irit, thinne rs, and turp e ntine ) • Hair lotions, cre ams, and d ye s • De te rg e nts and strong cle ansing ag e nts • Frag rance d che micals • “Unknown” che micals He avy-d uty vinyl g love s are b e tte r than rub b e r, nitrile , or othe r synthe tic g love s b e cause vinyl is le ss like ly to cause alle rgic re actions. Data rom Fig ure 9 in Warshaw E, Le e G, Storrs FJ. Hand d e rmatitis: a re vie w o clinical e ature s, the rap e utic op tions, and long -te rm outcome s. Am J Contact De rmat. 2003;14:126.

• Use cotton liners under the gloves or both com ort and the absorption o sweat. Wearing cotton glove liners can prevent the development o an impaired skin barrier unction caused by prolonged wearing o occlusive gloves. 5,6 SO R B There is insu f cient evidence to promote the use o barrier creams to protect against contact with irritants. 5,6 SO R A Applying conditioning creams a ter work can improve skin condition in workers with damaged skin on the hands. 6 SO R A • Avoid latex gloves because o a high risk o latex allergy among patients with hand dermatitis. SO R C • Frequent and liberal use o emollients can help restore normal skinbarrier unction. Simple, inexpensive, petrolatum-based emollients were ound to be equally as e ective as an emollient containing skinrelated lipids in a 2-month study o 30 patients with mild-to-moderate hand dermatitis. 7 SO R B

• For patients with very dry skin that is not irritated by water, it may help to soak hands 3 to 5 minutes in warm water at night, apply triamcinolone 0.1% ointment, and cover with cotton gloves overnight. The cotton gloves may be used repeatedly even though they will soak up some o the ointment. SO R C • Do not wash hands with soap. Use Cetaphil, a nonsoap cleanser. SO R C

See Table 145-2 or a summary o the recommended therapeutic agents or di erent types o hand dermatitis. TO PICAL AGENTS • Topical steroids are f rst-line agents or in ammatory hand dermatitis. Ointments are considered more e ective and contain a ewer preservatives and additives than creams. Some patients will pre er a cream vehicle, so that patient pre erence should be considered in prescribing

703

PART 14

704

Ch a pt e r 145

DERMATO LO GY TABLE 145-2 Re comme nd e d The rap ie s or Hand De rmatitis Variants

Hand De rmat it is Variant The rap e ut ic Ag e nt

Irrit ant Co nt act

Alle rg ic Co nt act

Hyp e rke rat o t ic

Po mp ho lyx Chro nic Nummular (Dyshid ro sis) Frict io nal Ve sicular

Corticoste roid s Top ical O ral

*

Cyclosp orine Me thotre xate Mycop he nolate mo e til Tacrolimus or p ime crolimus (top ical) Photothe rap y (UVB, p sorale n UVA, and Gre nz) Re tinoid s (top ical and /or oral) Calcip otrie ne (top ical) *

Acute f are s. Data rom Warshaw E, Le e G, Storrs FJ. Hand d e rmatitis: a re vie w o clinical e ature s, the rap e utic op tions, and long -te rm outco me s. Am J Contact De rmat. 2003;14:128.

topical steroids. It is better to have a patient use a cream than not use an ointment. • Start with 0.1% triamcinolone ointment bid as it is inexpensive and e ective. SO R C Cut back on use when possible to avoid skin atrophy, striae, and telangiectasias. • Topical calcineurin inhibitors, tacrolimus, and pimecrolimus, are e ective in the treatment o atopic and other allergic types o hand dermatitis. 8,9 SO R B Skin burning or an unpleasant sensation o warmth is reported by approximately 50% o patients using topical tacrolimus and 10% with pimecrolimus. 10

8 weeks the relative e ectiveness was 55%. 11 For patients with severe unctional problems this can be a great relie (Figures 145-8 and 145-14). Un ortunately, relapse rates are high a ter discontinuation o the cyclosporine. 10 SO R B • Mycophenolate mo etil and methotrexate have been reported to be benef cial in case reports. 10 SO R C • Alitretinoin (9-cis-retinoic acid) is an e ective treatment or severe chronic hand eczema. 12 SO R B Like all systemic retinoids it is

PHO TO THERAPY AND IO NIZING RADIATIO N • Psoralen and ultraviolet A (UVA) irradiation (PUVA) has been used to treat patients with all orms o hand dermatitis. 10 SO R C • Grenz rays (ionizing radiation with ultraso t X-rays or Bucky rays) usually require 200 to 400 rad (2 to 4 Grays or Gy) every 1 to 3 weeks or up to a total o 6 treatments, ollowed by a 6-month hiatus. 10 SO R C SYSTEMIC STERO IDS AND IMMUNO MO DULATO RS • Oral prednisone may be used to treat the most severe and recalcitrant case o hand dermatitis. Pulse dosing o 40 to 60 mg daily or 3 to 4 days may be valuable. 10 For atopic dermatitis o the hands, an injection o 40-mg triamcinolone acetonide is another option when topical meds are not ully working. SO R C • Cyclosporine is a potent immunomodulating agent used to treat severe and recalcitrant cases o atopic dermatitis and hand dermatitis. In a systematic review, cyclosporin consistently decreased the severity o atopic dermatitis. The decrease in disease severity was greater at 2 weeks with dosages greater than or equal to 4 mg/ kg. A ter 6 to

FIGURE 1 4 5 -1 4 Se ve re hand d e rmatitis no t re sp o nd ing to all o rms o to p ical the rap y. Patch te sting was ne g ative and the p atie nt was starte d o n cyclo sp o rine to cle ar the d e rmatitis so that she may re turn to wo rk. (Re p ro d uce d with p e rmissio n from Richard P. Usatine , MD.)

h a ND e CZe Ma

teratogenic and requires care ul monitoring. This medication is not yet available in the United States, but is being used in Canada and the United Kingdom.

PATIENT EDUCATIO N See Table 145-1.

FO LLO W-UP Patients with chronic hand dermatitis are o ten desperately looking or help and o ten appreciate requent ollow-up until the dermatitis is controlled. Patch testing requires 3 visits within a 1-week period. PATIENT RESO URCES

• DermNet—http:/ / www.dermnetnz.org/ dermatitis/ hand-dermatitis.html. PRO VIDER RESO URCES

• Medscape. Dyshidrotic eczema—http:/ / emedicine.medscape .com/ article/ 1122527. • Medscape. Vesicular Palmoplantar Eczema—http:/ / emedicine .medscape.com/ article/ 1124613.

REFERENCES 1. Warshaw E, Lee G, Storrs FJ. Hand dermatitis: a review of clinical eatures, therapeutic options, and long-term outcomes. Am J Contact Dermat. 2003;14:119-137. 2. Bolognia J. Dermatology. St. Louis, MO: Mosby; 2003.

PART 14

DERMATO LO GY 3. Warshaw EM, Ahmed RL, Belsito DV, et al; North American Contact Dermatitis Group. Contact dermatitis o the hands: cross-sectional analyses o North American Contact Dermatitis Group Data, 1994-2004. JAmAcad Dermatol. 2007;57(2):301-314. 4. Li LF, Wang J. Contact hypersensitivity in hand dermatitis. Contact Dermatitis. 2002;47:206-209. 5. Bourke J, Coulson I, English J. Guidelines for the management of contact dermatitis: an update. Br J Dermatol. 2009;160:946-954. 6. Nicholson PJ, Llewellyn D, English JS. Evidence-based guidelines or the prevention, identif cation and management o occupational contact dermatitis and urticaria. Contact Dermatitis. 2010;63: 177-186. 7. Kucharekova M, Van De Kerkho PC, Van Der Valk PG. A randomized comparison o an emollient containing skin-related lipids with a petrolatum-based emollient as adjunct in the treatment o chronic hand dermatitis. Contact Dermatitis. 2003;48:293-299. 8. Belsito DV, Fowler JF Jr, Marks JG Jr, et al; Multicenter Investigator Group. Pimecrolimus cream 1%: a potential new treatment or chronic hand dermatitis. Cutis. 2004;73(1):31-38. 9. Belsito D, Wilson DC, Warshaw E, et al. A prospective randomized clinical trial o 0.1% tacrolimus ointment in a model o chronic allergic contact dermatitis. JAmAcad Dermatol. 2006;55:40-46. 10. Warshaw EM. Therapeutic options or chronic hand dermatitis. Dermatol Ther. 2004;17:240-250. 11. Schmitt J, Schmitt N, Meurer M. Cyclosporin in the treatment of patients with atopic eczema—a systematic review and meta-analysis. J Eur Acad DermatolVenereol. 2007;21:606-619. 12. Ruzicka T, Lynde CW, Jemec GBE, et al. Ef cacy and safety of oral alitretinoin (9-cis retinoic acid) in patients with severe chronic hand eczema re ractory to topical corticosteroids: results o a randomized, double-blind, placebo-controlled, multicentre trial. Br J Dermatol. 2008;158:808-817.

705

PART 14 DERMATO LO GY

706

Ch Apt ER 146

146 NUMMULAR ECZEMA Yu Wah, MD Richard P. Usatine , MD

PATIENT STO RY A 27-year-old man presents with a new rash on his legs and abdomen or 1 month. He denies ever having a rash like this be ore. He states that the rash itches somewhat but that he can sleep at night. He denies exposure to anyone else with similar rash and he is otherwise in good health. The physician per orms a potassium hydroxide (KOH) preparation and does not nd any hyphae or ungal elements. The physician also notes that the lesions are coin shaped and makes the presumptive diagnosis o nummular eczema. To increase the level o certainty a punch biopsy is per ormed on one o the abdominal lesions. Clobetasol ointment 0.05% is prescribed to be applied twice daily with a 2-week ollow-up. In 2 weeks the patient returns and the lesions are over 90% gone. The physician explains to the patient that the biopsy con rmed the diagnosis o nummular eczema (NE) (Figure 146-1). The patient is directed to use the clobetasol until the lesions ully resolve.

A

INTRO DUCTIO N NE is a type o eczema characterized by circular or oval-shaped scaling plaques with well-de ned borders. The term nummular re ers to the shape o a coin (Latin or coin is nummus). The lesions are typically multiple and most commonly ound on the dorsa o the hands, arms, and legs. It o ten overlaps with other clinical types o eczema: atopic dermatitis, stasis dermatitis, and asteatotic eczema. 1,2

SYNO NYMS NE is also known as nummular dermatitis, discoid eczema, microbial eczema, and orbicular eczema.

EPIDEMIO LO GY • Prevalence is reported to range widely rom 0.1% to 9.1%. 1 • It is slightly more common in males than in emales.

1

• Males are also a ected at a later age (peak age >50 years) than emales (peak age 6 weeks’ duration) is determined in less than 20% o cases. 2 • Chronic urticaria is twice as common in women as in men. 3 • Chronic urticaria predominantly a ects adults. 3 • Up to 40% o patients with chronic urticaria o more than 6 months’ duration still have urticaria 10 years later. 3

ETIO LO GY AND PATHO PHYSIO LO GY • The pathophysiology o angioedema and urticaria can be immunoglobulin (Ig) E mediated, complement mediated, related to physical stimuli, autoantibody mediated, or idiopathic. • These mechanisms lead to mast cell degranulation resulting in the release o histamine. The histamine and other inf ammatory mediators produce the wheals, edema, and pruritus. • Urticaria is a dynamic process in which new wheals evolve as old ones resolve. These wheals result rom localized capillary vasodilation, ollowed by transudation o protein-rich f uid into the surrounding skin. The wheals resolve when the f uid is slowly reabsorbed. FIGURE 148-1 A 26-yea -old man with acute u tica ia due to t imethop imsul amethoxazole. (Reproduced with permission from Richard P. Usatine, MD.)

• Angioedema is an edematous area that involves transudation o f uid into the dermis and subcutaneous tissue (Figures 148-3 and 148-4).

URTICARIA AND ANGIO EDEMA

PART 14 DERMATO LO GY

FIGURE 148-5 De matog ap hism in a 21-ye a -old man with ch onic u tica ia. Note the e xag g e ate d t ip le e action. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.) FIGURE 148-3 Young b lack woman with ang ioe d e ma a te b e ing sta te d on an ang iote nsin-conve ting e nzyme inhib ito (ACEI) o e sse ntial hyp e te nsion. (Re p rod uce d with p e rmission from Ad rian Casillas, MD.)

The ollowing etiologic types exist: • Immunologic—IgE mediated, complement mediated. Occurs more o ten in patients with an atopic background. Antigens are most commonly oods or medications. The most common oods are milk, nuts, wheat, and shell sh. • Physical urticaria—Dermatographism, cold, cholinergic, solar, pressure, vibratory urticaria (Figures 148-5 and 148-6). • Urticaria caused by mast cell–releasing agents—Mastocytosis, urticaria pigmentosa • Urticaria associated with vascular/ connective tissue autoimmune disease (Figures 148-7 and 148-8). • Hereditary angioedema is a potentially li e-threatening disorder that is inherited in an autosomal dominant manner. In this disease, angioedema occurs without urticaria (Figure 148-9). FIGURE 148-6 Choline g ic u tica ia showing small whe als. The p atie nt would g e t this u tica ia a te e xe cising . (Re p rod uce d with p e rmission from Philip C. And e rson, MD.)

FIGURE 148-4 Se ve e ang ioe d e ma a ound the e ye s and mouth. (Re p rod uce d with p e rmission from Danie l Stulb e rg , MD.)

FIGURE 148-7 Ch onic u tica ia in a woman with syste mic lup us e ythe matosus. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

717

PART 14 DERMATO LO GY

718

Ch ApTER 148

FIGURE 148-8 Acute u tica ia in a woman with he umatoid a th itis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 148-10 Ch onic u tica ia with annula u tica ial p laq ue s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIAGNO SIS CLINICAL FEATURES • Symptoms include itching, burning, and stinging. • Wheals vary in size rom small, 2-mm papules o cholinergic urticaria (see Figure 148-6) to giant hives where a single wheal may cover a large portion o the trunk. • The wheal may be all red or white, or the border may be red with the remainder o the sur ace white. • Wheals may be annular (Figures 148-10 and 148-11).

A

B FIGURE 148-9 He e d ita y ang ioe d e ma. A. Se ve e e d e ma o the ace d u ing an e p isod e , le ad ing to g ote sq ue d isf g u e me nt. B. Ang ioe d e ma will sub sid e within hou s. The p atie nt had a p ositive amily histo y and had multip le simila e p isod e s includ ing colicky ab d ominal p ain. (Re p rod uce d with p e rmission from Fitzp at ick’s Colo Atlas and Synop sis o Clinical De matolog y. 5th e d . Ne w York, NY: McGraw-Hill; 2005.)

FIGURE 148-11 Giant u tica ia (u tica ia multi o me ). Althoug h this ap p e a s to have ta g e ts the e al ta g e t le sio ns o e ythe ma multi o me have a ce nt al le sion and have a scaling o b ullous comp one nt a e cting the e p id e mis. The histo y sug g e sts that this may have b e e n a se um sickne ss typ e e action. (Re p rod uce d with p e rmission from Milg rom EC, Usatine RP, Tan RA, Sp e ctor SL. P actical Alle g y. Philad e lp hia, PA: Else vie r; 2003; and Danie l Stulb e rg , MD.)

URTICARIA AND ANGIO EDEMA

PART 14 DERMATO LO GY • Urticaria can be ound anywhere on the body and is o ten on the trunk and extremities (see Figures 148-1 and 148-2). LABO RATO RY STUDIES Consider tests that might help reveal the cause o the urticaria and/ or angioedema. • Investigate or hereditary or acquired C1 esterase inhibitor de ciency when angioedema occurs repeatedly without urticaria (see Figure 148-9). The most use ul initial test is a C1INH (the inhibitor o C1 esterase) level. However, the type II orm has a normal level o C1INH but low unction. There ore unctional assays must be done i the level is normal but hereditary angioedema is still suspected. • Consider allergen skin testing and/ or in vitro tests when the history reveals that urticaria/ angioedema occurs a ter direct contact with a suspected allergen.

FIGURE 148-12 Positive Da ie sig n in which st oking the le sion o u tica ia p ig me ntosum e sults in e d e ma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Punch biopsy o the involved area may be used to diagnose urticarial vasculitis or mastocytosis.

DIFFERENTIAL DIAGNO SIS • I dermatographism is present, one can write on the skin and be able to see the resulting words or shapes (see Figure 148-5).

• Insect bites—A good history and physical examination should help to distinguish between insect bites and urticaria.

• I you suspect urticaria pigmentosa, stroke a lesion with the wooden end o a cotton-tipped applicator. This induces erythema o the plaque and the wheal is con ned to the stroke site. This is called Darier sign (Figure 148-12).

• Erythema multi orme-like urticaria can occur in response to an allergic/ immunologic reaction to medications, in ections, and neoplasms. The classic lesion o erythema multi orme is the target lesion in which there is disruption o the epithelium in the center. This disruption may be a vesicle, bulla, or erosion. Do not con use annular lesions or concentric rings with erythema multi orme i the epidermis is intact (see Figure 148-11 is not erythema multi orme) (see Chapter 175, Erythema Multi orme, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis).

TYPICAL DISTRIBUTIO N • Angioedema is seen more o ten on the ace and is especially ound around the mouth and eyes (see Figures 148-3 and 148-4). Sometimes angioedema can occur on the genitals or the trunk (Figure 148-13).

• Urticarial vasculitis typically has lesions that last longer than 24 hours. The lesions are ound more commonly on the lower extremities, and when they heal, they o ten leave hyperpigmented areas. Causes range rom a hypersensitivity vasculitis, such as Henoch-Schönlein purpura to underlying connective tissue disease (Figure 148-14). 2 • Mast cell releasability syndromes are syndromes in which there are too many mast cells in the skin or other organs o the body. These include cutaneous mastocytosis and urticaria pigmentosa (see Figures 148-7, 148-8, and 148-12). • Pruritic urticarial papules and plaques o pregnancy can be di erentiated rom urticaria in pregnancy because the eruption remains xed and increases in intensity until delivery (Figure 148-15). • Pemphigoid gestationis can have lesions that are urticarial. However, it also has bullae that distinguish it rom urticaria and o course the patient is pregnant or postpartum.

MANAGEMENT NO NPHARMACO LO GIC THERAPY • Avoid any causative agent, medication, stimulus, or antigen i ound (Figure 148-16). SO R B FIGURE 148-13 Ang ioe d e ma and u tica ia o the b ack. The thicke d e e p e whe als a e ang ioe d e ma. (Re p ro d uce d with p e rmission from Milg rom EC, Usatine RP, Tan RA, Sp e ctor SL. P actical Alle g y. Philad e lp hia, PA: Else vie r; 2003; and Danie l Stulb e rg , MD.)

• Angiotensin-converting enzyme inhibitors (ACEIs) are especially prone to causing angioedema so should be stopped as soon as possible when suspected to be causative o angioedema or urticaria (Figure 148-3). 1

719

720

PART 14 DERMATO LO GY

Ch ApTER 148

FIGURE 148-16 U tica ial d ug e up tion that occu e d whe n a 59-ye a -old woman was sta te d on Le ve mi insulin o he d iab e te s. The u tica ia cle a e d whe n she was switche d to an alte nate o m o insulin. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

SO R A

FIGURE 148-14 He noch-Schönle in p u p u a on the le g o a 20-ye a -old woman. This is a typ e o u tica ial vasculitis. (Re p rod uce d with p e rmission from Milg rom EC, Usatine RP, Tan RA, Sp e ctor SL. P actical Alle g y. Philad e lp hia, PA: Else vie r; 2003; and Richard P. Usatine , MD.)

FIGURE 148-15 P u itic u tica ial p ap ule s and p laq ue s o p e g nancy on the a m o a p e g nant woman. The whe als a e ind isting uishab le om othe typ e s o u tica ia. (Re p rod uce d with p e rmission from Milg rom EC, Usatine RP, Tan RA, Sp e ctor SL. P actical Alle g y. Philad e lp hia, PA: Else vie r; 2003; and Richard P. Usatine , MD.)

Even an angiotensin receptor blocker (ARB) can cause angioedema and should be suspected in a patient on this class o medication (Figure 148-17). • In chronic urticaria, patients may bene t rom avoidance o potential urticarial precipitants such as aspirin, nonsteroidal anti-inf ammatory drugs (NSAIDs) (Figure 148-18), opiates, and alcohol. 1 SO R B

FIGURE 148-17 Ang ioe d e ma se cond a y to an ang iote nsin e ce p to b locke g ive n o hyp e te nsion. The ang ioe d e ma e solve d and d id not e tu n once the p atie nt stop p e d the o e nd ing me d icatio n. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

URTICARIA AND ANGIO EDEMA

• Low-sedating antihistamines seem to be e ective in the treatment o acquired cold urticaria by signi cantly reducing the presence o wheals and pruritus a ter cold exposure. 11 SO R A CO RTICO STERO IDS • Oral corticosteroids should be restricted to short courses or severe acute urticaria or angioedema a ecting the mouth (eg, prednisone 60 mg/ d or 3-4 days in adults). 8,12 SO R B • Short tapering courses o oral steroids over 3 to 4 weeks may be necessary or urticarial vasculitis and severe delayed pressure urticaria. • Long-term oral corticosteroids should not be used in chronic urticaria. It is better to use oral cyclosporine i needed as it has a ar better riskto-bene t ratio compared with steroids. 1,8 FIGURE 148-18 U tica ia that occu e d within an hou a te a p atie nt was g ive n ib up o e n to t e at a hig h e ve . (Re p ro d uce d with p e rmission fro m Richard P. Usatine , MD.)

• A randomized controlled trial showed that clobetasol 0.05% in a oam ormulation was sa e and e ective in the short-term treatment o patients with delayed pressure urticaria. 13 SO R B IMMUNO MO DULATO RY AGENTS

• In ections may be a cause, an aggravating actor, or an unassociated bystander. 1 Look or sources o chronic in ections such as parasitic in ections, dental in ections, gastrointestinal (GI) in ections, respiratory in ections, and tinea pedis. Treat these, as it is possible, but unproven, that they can contribute to the chronic urticaria. SO R C • Stop all unnecessary nonprescription medications, supplements, and vitamins in chronic urticaria. SO R C • Avoidance o physical stimuli or the treatment o physical urticaria is desirable, but not always possible (observational studies only). 1 SO R B • Stress reduction techniques may help in chronic urticaria but this is unproven. SO R C ANTIHISTAMINES • Low-sedating, second-generation antihistamines should be prescribed as a rst-line treatment or chronic urticaria. 4-6 SO R A • Increasing the dose o cetirizine rom 10 mg to 20 mg daily produced a signi cant improvement in the severity o wheal and itching in urticaria re ractory to the standard doses o antihistamines. 7 SO R B • The British guidelines even suggest using antihistamines at up to quadruple the manu acturers’ recommended dosages be ore changing to an alternative therapy. They also recommend waiting up to 4 weeks to allow ull e ectiveness o the antihistamines be ore considering re erral to a specialist. 1 SO R C • All patients should be o ered the choice o at least 2 low-sedating H1 antagonists because responses and tolerance vary between individuals. 8 SO R A

• Addition o a sedating antihistamine at night may help patients sleep better, although they probably add little to existing H1 receptor blockade.8 • The addition o an H2 antagonist may give better control o urticaria than H1 antagonists alone, SO R B although a bene t is not always seen. 8 In one study, adding H2 blockers to H1 antagonists resulted in improvement o certain cutaneous outcomes or patients presenting with acute allergic syndromes to an emergency department. 9 SO R B • When initial antihistamines are not working, consider doxepin, an antidepressant and potent H1 antagonist. 10 SO R B Its use is limited by the side e ects o sedation and dry mouth. Start with 10-mg doxepin in the evening and titrate up as needed and tolerated.

• Immunosuppressive therapies or autoimmune urticaria should be restricted to patients with disabling disease who have not responded to optimal conventional treatments. 6 • A retrospective study o methotrexate in 8 patients with recalcitrant chronic urticaria indicated that methotrexate was both sa e and e ective, with a mean dose o 15-mg methotrexate per week. Seven o 8 patients achieved a complete response and 5 o 8 remained disease ree a ter methotrexate was stopped. 14 SO R B • Cyclosporine, plasmapheresis, anti-IgE (omalizumab), and intravenous immunoglobulin have been used in severe recalcitrant cases. 1 SO R C • Plasmapheresis is very costly and should be reserved or autoantibodypositive chronic spontaneous urticaria patients. 1 O THERS • Epinephrine is valuable in severe acute urticaria or angioedema, especially i there is a suspicion o airway compromise or anaphylaxis. • The evidence or leukotriene modi ers in the treatment o urticaria is poor. SO R C • Ecallantide is a new plasma kallikrein inhibitor or the subcutaneous treatment o acute attacks o hereditary angioedema. 15 SO R B • Anti-inf ammatory drugs, such as colchicine, dapsone, and sul asalazine, have been reported as help ul in uncontrolled trials or case series. 1

PATIENT EDUCATIO N In most cases, we are not able to nd the cause o urticaria. This is especially true or chronic urticaria. Fortunately, most chronic urticaria will subside over time and there are medicines to treat the condition until it runs its course. I one medication does not work keep your ollow-up visits to try other medications. Care ully observe or causative agents.

FO LLO W-UP Follow-up is especially needed when the urticaria or angioedema persist or recur.

721

PART 14 DERMATO LO GY

722

PATIENT RESO URCES

• eMedicineHealth.com is a consumer health site with in ormation and support groups—http:/ / www.emedicinehealth.com/ hives_and_angioedema/ article_em.htm. PRO VIDER RESO URCES

• Well-written guideline based on a joint initiative of a number of European dermatology, allergy, and immunology organizations— http:/ / onlinelibrary.wiley.com/ doi/ 10.1111/ j.1398 -9995.2009.02178.x/ full.

REFERENCES 1. Zuberbier T, Asero R, Bindslev-Jensen C, et al. EAACI/ GA(2) LEN/ EDF/ WAO guideline: management o urticaria. Allergy. 2009;64:1427-1443. 2. Baxi S, Dinakar C. Urticaria and angioedema. Immunol Allergy Clin North Am. 2005;25:353-367, vii. 3. Usatine RP. Urticaria and angioedema. In: Milgrom E, Usatine RP, Tan R, Spector S, eds. Practical Allergy. Philadelphia, PA: Elsevier; 2003:78-96. 4. Finn AF Jr, Kaplan AP, Fretwell R, et al. A double-blind, placebocontrolled trial o exo enadine HCl in the treatment o chronic idiopathic urticaria. JAllergy Clin Immunol. 1999;104:1071-1078. 5. Ortonne JP, Grob JJ, Auquier P, Drey us I. E cacy and sa ety o desloratadine in adults with chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, multicenter trial. Am J Clin Dermatol. 2007;8:37-42. 6. Ortonne JP. Chronic urticaria: a comparison o management guidelines. Expert Opin Pharmacother. 2011;12(17):2683-2693.

CHAPTEr 148

7. Okubo Y, Shigoka Y, Yamazaki M, Tsuboi R. Double dose o cetirizine hydrochloride is e ective or patients with urticaria resistant: a prospective, randomized, non-blinded, comparative clinical study and assessment o quality o li e. J DermatologTreat. 2013;24(2): 153-160. 8. Grattan C, Powell S, Humphreys F. Management and diagnostic guidelines or urticaria and angio-oedema. Br J Dermatol. 2001;144: 708-714. 9. Lin RY, Curry A, Pesola GR, et al. Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 and H2 antagonists. Ann Emerg Med. 2000;36:462-468. 10. Goldsobel AB, Rohr AS, Siegel SC, et al. E cacy o doxepin in the treatment o chronic idiopathic urticaria. JAllergy Clin Immunol. 1986;78:867-873. 11. Weinstein ME, Wol AH, Bielory L. E cacy and tolerability o second- and third-generation antihistamines in the treatment o acquired cold urticaria: a meta-analysis. Ann Allergy Asthma Immunol. 2010;104:518-522. 12. Pollack CV Jr, Romano TJ. Outpatient management o acute urticaria: the role o prednisone. Ann Emerg Med. 1995;26:547-551. 13. Vena GA, Cassano N, D’Argento V, Milani M. Clobetasol propionate 0.05% in a novel oam ormulation is sa e and e ective in the short-term treatment o patients with delayed pressure urticaria: a randomized, double-blind, placebo-controlled trial. Br J Dermatol. 2006;154:353-356. 14. Sagi L, Solomon M, Baum S, et al. Evidence or methotrexate as a use ul treatment or steroid-dependent chronic urticaria. Acta Derm Venereol. 2011;91:303-306. 15. Stolz LE, Horn PT. Ecallantide: a plasma kallikrein inhibitor or the treatment o acute attacks o hereditary angioedema. DrugsToday (Barc). 2010;46:547-555.

PART 14 DERMATO LO GY

SEBO RRHEIC DERMATITIS

SECTIO N 7

PAPULO SQ AMO US CO NDITIO NS

149 SEBO RRHEIC DERMATITIS Richard P. Usatine , MD Me re d ith Hancock, MD Yoon-Soo Cind y Bae -Harb oe , MD

PATIENT STO RY A 59-year-old man presents with a 3-month history o an itchy rash on his ace (Figure 149-1)). He states that he has had this rash intermittently or many years, but had recently worsened. He denies any major risk actors or HIV and does not have Parkinson disease. He has been under more stress lately and has noticed that this rash ares when under increased stress. Note the scale visible on the orehead and under the eyebrows and beard. There is also some mild erythema on the cheeks and around the nasolabial olds. The diagnosis o seborrheic dermatitis is made and treatment is begun with appropriate topical agents to treat the in ammation and the Malassezia. On the ollowing visit, the patient has complete clearance o his seborrheic dermatitis.

INTRO DUCTIO N A

Seborrheic dermatitis is a common, chronic, relapsing dermatitis a ecting sebum-rich areas o the body. In ants and adults, men and women may be a ected. Presentation may vary rom mild erythema to greasy scales, and rarely as erythroderma. Treatment is targeted to reduce in ammation and irritation as well as eliminate Malassezia ungus whose exact role is not completely understood.

SYNO NYMS Seborrheic dermatitis is also known as seborrhea, seborrheic eczema, and dandru .

EPIDEMIO LO GY • Seborrheic dermatitis is most commonly seen in male patients aged 20 to 50 years. The prevalence is approximately 3% to 5% in healthy young adults who are HIV negative. 1 More people may be a ected, but do not seek medical attention or mild cases. • The prevalence is higher in immunocompromised persons (eg, HIV positive/ AIDS); however, the vast majority o a ected persons have a normal immune system. • More common in persons with Parkinson disease. • In ants can have seborrhea o the scalp (cradle cap), ace, and diaper area.

B FIGURE 149-1 Se b orrhe ic d e rmatitis ollowing the ty ical d istrib ution on the ace o a 59-ye ar-old man. A. Note the romine nt scale and e rythe ma on his ore he ad , g lab e lla, and b e ard re g ion. B. Close -u o se b orrhe ic d e rmatitis showing the f aking scale and e rythe ma around the b e ard re g ion. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

723

PART 14 DERMATO LO GY

724

CHApTER 149

ETIO LO GY AND PATHO PHYSIO LO GY • Seborrheic dermatitis is a chronic, superf cial, localized in ammatory dermatitis that is ound in sebum-producing areas o the body. • The actual cause o seborrheic dermatitis is not well understood. It appears to be related to the interplay between host susceptibility, environmental actors, and local immune response to antigens. 2-4 • Patients with seborrheic dermatitis may be colonized with certain species o lipophilic yeast o the genus Malassezia (also called Pityrosporum). However, Malassezia is considered normal skin ora and una ected persons also may be colonized. • Recent evidence suggests that Malassezia may produce di erent irritants or metabolites on a ected skin. 4

RISK FACTO RS • Male gender. • Immunocompromise (HIV/ AIDS, Parkinson disease).

FIGURE 149-3 Se b orrhe ic d e rmatitis in a b lack man with hy o ig me ntation and e rythe ma re late d to the inf ammation. Note the romine nt involve me nt in the nasolab ial old s and the we ll-d e marcate d b ord e rs. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Stress. • Environmental actors (cold, dry weather). • Certain medications may cause seborrheic dermatitis to are. These medications include captopril, cimetidine, interleukin-2, isotretinoin, nicotine, and psoralens. 5-9

• Poorly-demarcated, erythematous plaques o greasy, yellow scale, in the characteristic seborrheic distribution (see description below). • Common precipitating actors are stress, immunosuppression, and cold weather. • Face, scalp, and ears may be very pruritic.

DIAGNO SIS The clinical diagnosis is made by history and physical examination. Figures 149-1 and 149-2 reveal erythema and scale across the eyebrows, cheeks, and under beard. Biopsy is not generally indicated unless ruling out other possibilities (see Di erential Diagnosis).

• May be the presenting sign o HIV seropositivity. • In dark-skinned individuals, the involved skin and scale may become hypopigmented (Figure 149-3) or hyperpigmented (Figure 149-4).

CLINICAL FEATURES • Chronic skin condition is characterized by remissions and exacerbations.

FIGURE 149-2 Se ve re se b orrhe ic d e rmatitis on the ace o a hos italize d man. The stre ss o his illne ss has worse ne d his othe rwise mild se b orrhe a. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 149-4 Se b orrhe a in a b lack woman with hy e r ig me ntation re late d to the inf ammation. No te the romine nt involve me nt in the nasolab ial old s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

SEBO RRHEIC DERMATITIS

PART 14 DERMATO LO GY

FIGURE 149-5 Se b orrhe ic d e rmatitis with e rythe ma and scale und e r the e ye b rows and in the g lab e lla re g ion on a young man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

TYPICAL DISTRIBUTIO N Occurs on scalp (ie, dandru ), eyebrows (Figures 149-5), nasolabial creases (see Figures 149-3), orehead (Figures 149-6), cheeks, around the nose, behind the ears (Figure 149-7), external auditory meatus, and under acial hair (Figure 149-8). Seborrhea can also occur over the sternum (Figures 149-9) and in the axillae, submammary olds, umbilicus, groin, and gluteal creases.

FIGURE 149-7 Se b orrhe ic d e rmatitis b e hind the e ar in a young woman. This is a g ood lace to look or e vid e nce o se b orrhe a. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

LABO RATO RY STUDIES

• Also consider testing or systemic lupus erythematosus (SLE) in setting o associated systemic symptoms or i treatment resistant.

• Test or HIV and/ or syphilis i patient has risk actors (Figures 149-10 and 149-11).

• Consider potassium hydroxide (KOH) test to rule out tinea. • Consider zinc level or alkaline phosphatase to rule out nutritional/ zinc def ciency.

DIFFERENTIAL DIAGNO SIS • Psoriasis—The scale o psoriasis tends to be thicker, on well-demarcated plaques distributed over extensor sur aces along with the scalp.

FIGURE 149-6 Se b orrhe ic d e rmatitis with e rythe ma and scale on the ore he ad and nose o an old e r man in the hos ital. (Re p rod uce d with p e rmission from Suraj Re d d y, MD.)

FIGURE 149-8 Seborrhea o the beard and mustache distribution with rominent e rythema. (Reproduce d with permission from Richard P. Usatine, MD.)

725

726

PART 14 DERMATO LO GY

CHApTER 149

FIGURE 149-11 Se b orrhe ic d e rmatitis on the ace o a man with AIDS. Note e rythe ma and scale on the ore he ad , nose , and che e ks. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Look or signs o nail involvement that may support the diagnosis o psoriasis (see Chapter 150, Psoriasis). FIGURE 149-9 Se b orrhe ic d e rmatitis on the che st and b e twe e n the b re asts o a wo man that also has se b orrhe a o the scal and ace . This is one o the more common locations to se e se b orrhe ic d e rmatitis on the trunk. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• SLE with butter y rash—Rash across nasal bridge in patient with associated systemic symptoms and abnormal blood tests (see Chapter 178, Lupus Erythematosus—Systemic and Cutaneous). • Rosacea—The erythema on the ace is o ten associated with papules, pustules, telangiectasia, and an absence o scales. May also present with chalazia or hordeola (see Chapter 115, Rosacea). • Tinea capitis—Scale and erythema commonly associated with hair loss. KOH and/ or culture can help make the distinction. This is rare in adults but may be seen in adolescents. • Secondary syphilis—Skin presentation may mimic seborrheic dermatitis. Examine patient or mucosal or palmar involvement. Laboratory testing or syphilis may be necessary i this is suspected (see Chapter 218, Syphilis). • Perioral dermatitis—Usually restricted around the mouth with minimal scale and f ne papules and pustules (see Chapter 115, Rosacea). • Tinea versicolor (trunk)—The scale o tinea versicolor is f ne and white and scales with scraping (see Chapter 139, Tinea Versicolor). • Allergic or irritant contact dermatitis—May present with a welldemarcated lesion with f ne white scale, secondarily impetiginized lesions may have associated yellow-colored crust, not scale (see Chapter 144, Contact Dermatitis). • Candidiasis—May be ound in intertriginous areas, but present bright red with satellite lesions (see Chapter 135, Mucocutaneous Candidiasis).

MANAGEMENT As seborrheic dermatitis is a recurrent, chronic condition, repeated and/ or maintenance therapy is o ten required. FIGURE 149-10 Se b orrhe ic d e rmatitis on the ace o a man with AIDS. Note the involve me nt o the ore he ad , che e ks, and chin causing hy o ig me ntation and scaling . (Re p ro d uce d with p e rmission fro m Yoon-Soo Cind y Bae -Harb oe , MD.)

• Mainstay o treatment is topical anti ungals and low-potency topical steroids. • For seborrheic dermatitis o the scalp, patients should wash their hair with anti ungal shampoos (containing selenium sulf de, ketoconazole, or

PART 14 DERMATO LO GY

SEBO RRHEIC DERMATITIS

ciclopirox) several times per week, each time leaving the lather on the a ected areas or several minutes until remission is attained. Patients may continue to use anti ungal shampoo as maintenance therapy. 3 • Shampoos containing ketoconazole, selenium sulf de, or zinc pyrithione (ZPT) are active against the Malassezia and are e ective in the treatment o moderate-to-severe dandru . 10,11 SO R A • Ketoconazole 2% shampoo was ound to be superior to zinc pyrithione 1% shampoo when used twice weekly. Ketoconazole led to a 73% improvement in the total dandru severity score compared with 67% or ZPT 1% at week 4. 11 SO R B • Ciclopirox 1% shampoo is e ective and sa e in the treatment o seborrheic dermatitis o the scalp. 12,13 SO R A It is by prescription only and is very expensive. • Ketoconazole 2% cream, gel, or emulsion is sa e and e ective or acial seborrheic dermatitis. 14-16 SO R B • Ciclopirox 1% cream is also sa e and e ective or acial seborrheic dermatitis and is equivalent to ketoconazole 2% cream. 14,17 SO R B • Oral terbinaf ne 250 mg daily or 4 weeks is e ective or moderate-tosevere seborrhea. 18,19 SO R A However, due to the potential or harmul side e ects o oral anti ungals and the limited study o their e f cacy, they are not f rst-line treatments. 3 Oral terbinaf ne may be considered in erythroderma caused by seborrhea. Topical corticosteroids are use ul in treating associated erythema and pruritis. 3 Long-term use may lead to skin atrophy3 and should be used with caution. • Lotion or solution is pre erable on hair-covered area or patient comort and usability. • Hydrocortisone 1% cream or lotion can be used bid to ace, scalp, or other a ected areas. 16,20 SO R B • Desonide 0.05% lotion is sa e and e ective or short-term treatment o seborrheic dermatitis o the ace. 21 SO R B It is a non uorinated low- to mid-potency steroid that is higher in potency than 1% hydrocortisone. • For moderate to severe seborrheic dermatitis on the scalp. • Fluocinonide 0.05% solution once daily is a ordable and benef cial. SO R C

• One small randomized controlled trial (RCT) using homeopathic medication consisting o potassium bromide, sodium bromide, nickel sulate, and sodium chloride or 10 weeks showed signif cant improvement over placebo. 27 SO R C

PATIENT EDUCATIO N For improved treatment results, encourage patients to wash the hair and scalp daily with an anti ungal shampoo. Some patients ear that washing their hair too o ten will cause a “dry” scalp and need to understand that the scaling and aking will improve rather than worsen with more requent hair washing.

FO LLO W-UP Patients with long-standing and severe seborrhea will appreciate a ollow-up visit in most cases. Milder cases can be ollowed as needed. PATIENT RESO URCES

• PubMed Health. Seborrheic Dermatitis—http:/ / www.ncbi.nlm .nih.gov/ pubmedhealth/ PMH0001959/ . PRO VIDER RESO URCES

• Medscape. Seborrheic Dermatitis—http:/ / emedicine.medscape .com/ article/ 1108312. REFERENCES 1. Usatine RP. A red rash on the ace. J Fam Pract. 2003;52:697-699. 2. Gaitanis G, Magiatis P, Hantschke M, Bassukas ID, Velegraki A. The Malassezia genus in skin and systemic diseases. Clin Microbiol Rev. 2012;25(1):106. 3. Naldi L, Rebora A. Seborrheic dermatitis. N Engl J Med. 2009;360(4): 387-396. 4. Hay RJ. Malassezia, dandru and seborrheic dermatitis: an overview. Br J Dermatol. 2011;165(suppl 2):2-8.

• Clobetasol 0.05% shampoo, solution, spray, or oam work well but are more costly. SO R C

5. Yamamoto T, Tsuboi R. Interleukin-2-induced seborrheic dermatitis-like eruption. J Eur Acad DermatolVenereol. 2008;22(2): 244-245.

O THER TREATMENTS

6. Sudan BJ, Brouillard C, Sterboul J, Sainte-Laudy J. Nicotine as a hapten in seborrheic dermatitis. Contact Dermatitis. 1984;11(3): 196-197.

• Pimecrolimus 1% cream is an e ective and well-tolerated treatment or acial seborrheic dermatitis. 20,22,23 SO R B In one study, there was more burning noted with the pimecrolimus than with the betamethasone 17-valerate 0.1% cream. 22 • Metronidazole gel—Two small studies have ound di erent results in the treatment o seborrheic dermatitis on the ace. One suggests it works better than the vehicle alone and the other ound no statistically signif cant di erence rom placebo. 24,25 SO R B CO MPLIMENTARY AND ALTERNATIVE THERAPY • Tea tree oil 5% shampoo showed a 41% improvement in the quadrant-area-severity score compared with 11% in the placebo. Statistically signif cant improvements were also observed in the total area o involvement score, the total severity score, and the itchiness and greasiness components o the patients’ sel -assessments. 26 SO R B

7. Kitamura K, Aihara M, Osawa J, Naito S, Ikezawa Z. Sul hydryl drug-induced eruption: a clinical and histological study. J Dermatol. 1990;17(1):44-51. 8. Tegner E. Seborrheic dermatitis o the ace induced by PUVA treatment. Acta DermVenereol. 1983;63(4):335-339. 9. Barzilai A, David M, Trau H, Hodak E. Seborrheic dermatitis-like eruption in patients taking isotretinoin therapy or acne: retrospective study o f ve patients. Am J Clin Dermatol. 2008;9(4):255-261. 10. Danby FW, Maddin WS, Margesson LJ, Rosenthal D. A randomized, double-blind, placebo-controlled trial o ketoconazole 2% shampoo versus selenium sulf de 2.5% shampoo in the treatment o moderate to severe dandru . JAm Acad Dermatol. 1993;29: 1008-1012.

727

728

PART 14 DERMATO LO GY 11. Pierard-Franchimont C. A multicenter randomized trial o ketoconazole 2% and zinc pyrithione 1% shampoos in severe dandru and seborrheic dermatitis. Skin Pharmacol Appl Skin Physiol. 2002;15(6): 434-441.

CHApTER 149

investigator-blinded, placebo-controlled trial. Br J Dermatol. 2001; 149(4):854-857.

12. Aly R. Ciclopirox gel or seborrheic dermatitis o the scalp. Int J Dermatol. 2003;42(suppl 1):19-22.

20. Firooz A, Solhpour A, Gorouhi F, et al. Pimecrolimus cream, 1%, vs hydrocortisone acetate cream, 1%, in the treatment o acial seborrheic dermatitis: a randomized, investigator-blind, clinical trial. Arch Dermatol. 2006;142:1066-1067.

13. Lebwohl M, Plott T. Sa ety and e f cacy o ciclopirox 1% shampoo or the treatment o seborrheic dermatitis o the scalp in the US population: results o a double-blind, vehicle-controlled trial. Int J Dermatol. 2004;43(suppl 1):17-20.

21. Freeman SH. E f cacy, cutaneous tolerance and cosmetic acceptability o desonide 0.05% lotion (Desowen) versus vehicle in the shortterm treatment o acial atopic or seborrheic dermatitis. Australas J Dermatol. 2002;43(3):186-189.

14. Chosidow O, Maurette C, Dupuy P. Randomized, open-labeled, non-in eriority study between ciclopiroxolamine 1% cream and ketoconazole 2% oaming gel in mild to moderate acial seborrheic dermatitis. Dermatology. 2003;206:233-240.

22. Rigopoulos D, Ioannides D, Kalogeromitros D, Gregoriou S, Katsambas A. Pimecrolimus cream 1% vs. betamethasone 17-valerate 0.1% cream in the treatment o seborrheic dermatitis. A randomized open-label clinical trial. Br J Dermatol. 2004;149:1071-1075.

15. Pierard GE, Pierard-Franchimont C, Van CJ, Rurangirwa A, Hoppenbrouwers ML, Schrooten P. Ketoconazole 2% emulsion in the treatment o seborrheic dermatitis. Int J Dermatol. 1991;30:806-809.

23. Warshaw EM, Wohlhuter RJ, Liu A, et al. Results o a randomized, double-blind, vehicle-controlled e f cacy trial o pimecrolimus cream 1% or the treatment o moderate to severe acial seborrheic dermatitis. JAmAcad Dermatol. 2007;57(2):257-264.

16. Katsambas A, Antoniou C, Frangouli E, Avgerinou G, Michailidis D, Stratigos J. A double-blind trial o treatment o seborrheic dermatitis with 2% ketoconazole cream compared with 1% hydrocortisone cream. Br J Dermatol. 1989;121:353-357. 17. Dupuy P, Maurette C, Amoric JC, Chosidow O. Randomized, placebo-controlled, double-blind study on clinical e f cacy o ciclopiroxolamine 1% cream in acial seborrheic dermatitis. Br J Dermatol. 2001;149:1033-1037. 18. Vena GA, Micali G, Santoianni P, Cassano N, Peruzzi E. Oral terbinaf ne in the treatment o multi-site seborrheic dermatitis: a multicenter, double-blind placebo-controlled study. Int J Immunopathol Pharmacol. 2005;18:745-753. 19. Scaparro E, Quadri G, Virno G, Orif ci C, Milani M. Evaluation o the e f cacy and tolerability o oral terbinaf ne (Daskil) in patients with seborrheic dermatitis. A multicentre, randomized,

24. Parsad D, Pandhi R, Negi KS, Kumar B. Topical metronidazole in seborrheic dermatitis—a double-blind study. Dermatology. 2001; 202:35-37. 25. Koca R. Is topical metronidazole e ective in seborrheic dermatitis? A double-blind study. Int J Dermatol. 2003;42(8):632-635. 26. Satchell AC, Saurajen A, Bell C, Barnetson RS. Treatment o dandru with 5% tea tree oil shampoo. JAmAcad Dermatol. 2002;47(6): 852-855. 27. Smith SA, Baker AE, Williams JH. E ective treatment o seborrheic dermatitis using a low dose, oral homeopathic medication consisting o potassium bromide, sodium bromide, nickel sul ate, and sodium chloride in a double-blind, placebo-controlled study. Altern Med Rev. 2002;7(1):59-67.

PART 14

PSO RIASIS

DERMATO LO GY

150 PSO RIASIS Richard P. Usatine , MD

PATIENT STO RY A 33-year-old woman presents with uncontrolled psoriasis or 20 years. In addition to the plaque psoriasis (Figure 150-1), she has inverse psoriasis (Figure 150-2). Topical ultrahigh-potency steroids and topical calcipotriol have not controlled her psoriasis. The options or phototherapy and systemic therapy were discussed. The patient chose to try narrowband ultraviolet B (UVB) treatment in addition to her topical therapy.

INTRO DUCTIO N Psoriasis is a chronic in ammatory papulosquamous and immune-mediated skin disorder. It is also associated with joint and cardiovascular comorbidities. Psoriasis can present in many di erent patterns rom the scalp to the eet and cause psychiatric distress and physical disabilities. It is crucial to be able to identi y psoriasis in all its myriad presentations so that patients receive the best possible treatments to improve their quality o li e and avoid comorbidities.

FIGURE 150-2 Inve rse p soriasis in the in ramammary old s o the p atie nt in Fig ure 150-1. This is not a Cand id a or tine a in e ction. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Sex—No gender pre erence. • Age—Psoriasis can begin at any age. In one population study o the age o onset o psoriasis 2 peaks were revealed, one occurring at the age o 16 years ( emale) or 22 years (males) and a second peak at the age o 60 years ( emale) or 57 years (males). 3

EPIDEMIO LO GY Psoriasis a ects approximately 2% o the world population. 1 The prevalence o psoriasis was 2.5% in white patients and was 1.3% in A rican American patients in one population study in the United States. 2

ETIO LO GY AND PATHO PHYSIO LO GY • Immune-mediated skin disease, where the T cell plays a pivotal role in the pathogenesis o the disease. • Langerhans cells (antigen-presenting cells in the skin) migrate rom the skin to regional lymph nodes, where they activate T cells that migrate to the skin and release cytokines. • Cytokines are responsible or epidermal and vascular hyperproli eration and proin ammatory e ects.

RISK FACTO RS • Family history • Obesity • Smoking and environmental smoke • Heavy alcohol use Table 150-1 lists the actors that trigger and exacerbate psoriasis. 4 The risk o psoriasis is higher in the ollowing occurrences5: • Family history o psoriasis (odds ratio [OR] = 33.96; 95% conf dence interval [CI] 14.14-81.57) • Change in work conditions (OR = 8.34; 95% CI = 1.86-37.43) • Divorce (OR = 5.69; 95% CI = 2.26-14.34) • Urban dwellers (OR = 3.61; 95% CI = 0.99-13.18) • Alcohol consumption (OR = 2.55; 95% CI = 1.26-5.17) FIGURE 150-1 Typ ical p laq ue p soriasis on the e lb ow and arm o a 33-ye arold woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Environmental tobacco smoke at home (OR = 2.29; 95% CI = 1.12-4.67)

729

PART 14

730

DERMATO LO GY

Ch a pt e r 150

TABLE 150-1 Factors That Trig g e r and Exace rb ate Psoriasis

• Stre ss • Physical trauma to the skin (Koe b ne r p he nome non) • Cold d ry we athe r • Sun e xp osure and hot we athe r • In e ctions (e g , stre p throat, HIV) • Me d ications (e g , ACE-inhib itors, antimalarials, β-b locke rs, lithium, NSAIDs)

DIAGNO SIS Psoriasis has many orms and locations. These 9 categories were used to describe psoriasis in a consensus statement o the American Academy o Dermatology (AAD)6: 1. Plaque (80%-90% o patients with psoriasis) (Figures 150-1 and 150-3)

FIGURE 150-4 Scalp p soriasis visib le at the hairline . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

2. Scalp psoriasis (Figure 150-4) 3. Guttate psoriasis (Figure 150-5) 4. Inverse psoriasis (Figures 150-2 and 150-6) 5. Palmar-plantar psoriasis (Figure 150-7), also known as palmoplantar psoriasis 6. Erythrodermic psoriasis (Figure 150-8) 7. Pustular psoriasis—localized and generalized (Figure 150-9) 8. Nail psoriasis (Figure 150-10) (see Chapter 193, Psoriatic Nails) 9. Psoriatic arthritis (Figure 150-11) Typical distribution in general occurs at elbows, knees, extremities, trunk, scalp, ace, ears, hands, eet, genitalia and intertriginous areas, and nails. Table 150-2 provides percentages or the most common locations o lesions in patients with psoriasis. Plaque psoriasis • White scale on an erythematous raised base with well-demarcated borders (see Figures 150-1 and 150-3).

A

B

FIGURE 150-3 We ll-d e marcate d p laq ue s o p laq ue p soriasis in a 44-ye arold man with se ve re p soriasis and p soriatic arthritis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 150-5 Guttate p soriasis may ollow a stre p p haryng itis in child re n and some time s in young ad ults. Howe ve r, small g uttate (wate r d rop ) p laq ue s may b e se e n in ad ults with p soriasis without any kno w p re ce d ing in e ctions. A. Guttate p soriasis on the arm o an ad ult. B. Guttate p soriasis on the trunk o an ob e se 46-ye ar-old woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

pSO r Ia SIS

PART 14

DERMATO LO GY

FIGURE 150-6 Inve rse p soriasis in the axilla o this mid d le -ag e d woman. The re is consid e rab le e rythe ma and ve ry little scale . Prior to this visit he r cond ition was misd iag nose d as ung al in orig in. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 150-8 Erythrod e rmic p soriasis cove ring most o the b o d y sur ace . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

A

FIGURE 150-9 Pustular psoriasis on the back that occurred when oral prednisone was stopped. (Reproduced with permission from Jack Resneck, Sr., MD.)

B FIGURE 150-7 A. Palmop lantar p soriasis with p ustulosis that starte d 3 months ag o on the hand s o a 62-ye ar-old woman. B. Note the e rythe ma, scale , b rown macule s (mahog any sp ots), and p ustule s that are typ ical o this cond ition. This is consid e re d to b e a localize d orm o p ustular p soriasis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 150-10 Nail p itting rom p soriasis. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

731

PART 14

732

Ch a pt e r 150

DERMATO LO GY

FIGURE 150-11 Psoriatic arthritis that has be come crippling to this 44-ye arold man. The shorte ning o the ng e rs ts the p soriatic arthritis mutilans sub typ e . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Silvery scale with hyperpigmentation may be seen in patients with darker skin (Figures 150-12 and 150-13). • Plaques can appear in di erent colors including hypopigmented (Figure 150-14) and silvery gray (Figure 150-15). A tricolored presentation occurs when the in ammation leads to leukoderma (Figure 150-16).

FIGURE 150-12 Plaq ue p soriasis with silve ry scale on a b lack man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• The thickness and extent o the scale is variable (see Figure 150-15). • Positive Auspitz sign in which the peeling o the scale produces pinpoint bleeding on the plaque below. • Typical distribution includes the elbows and knees and other extensor sur aces. The plaques can be ound rom head to toe including the penis (Figure 15-17). • Plaques tend to be symmetrically distributed. • Plaques can be annular with central clearing (Figure 150-18). • When plaques occur at a site of injury, it is known as the Koebner phenomenon (Figure 150-19).

TABLE 150-2 The Mo st Common Locations o Le sio ns in Patie nts With Psoriasis

Lo cat io n

% o Pso riasis Pat ie nt s

Scalp

80

Elb ows

78

Le g s

74

Kne e s

57

Arms

54

Trunk

53

Lowe r p art o the b od y

47

Base o the b ack

38

Palms and sole s

12

FIGURE 150-13 Psoriasis on the kne e o a Hisp anic man sho wing p ostinf ammatory hyp e rp ig me ntation. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14

pSO r Ia SIS

DERMATO LO GY

A

FIGURE 150-15 Thick p laq ue p soriasis cove ring the lowe r le g s o this ob e se man. Note the silve r g ray color to his p laq ue s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Inverse psoriasis • Found in the intertriginous areas o the axilla, groin, in ramammary olds, and intergluteal old (Figures 150-2, 150-6, and 150-22). It can also be seen below the pannus or within adipose olds in obese individuals. • The term inverse re ers to the act that the distribution is not on extensor sur aces but in areas o body olds. B

• Morphologically the lesions have little to no visible scale.

FIGURE 150-14 Plaq ue p soriasis can cause hyp o p ig me ntation. A. Hyp op ig me ntation in are as o active p laq ue s with p ostinf ammatory hyp e rp ig me ntation visib le on the up p e r b ack. B. Annular p soriatic p laq ue s that le ave hyp op ig me ntation whe n the y cle ar. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Scalp psoriasis • Plaque on the scalp may be seen at the hairline and around the ears (see Figure 150-4). • The thickness and extent o the plaques are variable as seen in plaque psoriasis. Guttate psoriasis • Small round plaques that resemble water drops (guttate means like a water drop) (Figure 150-20). • Classically described as occurring a ter strep pharyngitis or another bacterial in ection. This is one type o psoriasis that occurs in childhood. • Typical distribution includes the trunk and extremities but may include the ace and neck (Figure 150-21).

FIGURE 150-16 Plaq ue p soriasis that has cause d hyp op ig me ntation in a b and across the b ack. His orig inal skin color is b rown so that the b rown, white , and p ink colors p rod uce the ap p e arance o a Ne ap olitan ice cre am p atte rn. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

733

734

PART 14

DERMATO LO GY

FIGURE 150-17 Plaq ue p soriasis on the p e nis, cove ring the g lans and p art o the sha t. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

Ch a pt e r 150

FIGURE 150-20 Guttate p soriasis in a young man ollowing an e p isode o stre p p haryng itis. (Re produce d with p ermission from Richard P. Usatine , MD.)

• Color is generally pink to red but can be hyperpigmented in dark-skinned individuals. Palmar-plantar (palmoplantar) psoriasis • Psoriasis occurs on the plantar aspects o the hands and eet (palms and soles) (Figure 150-23). The psoriasis can also be seen on other parts o the hands and eet. • Patients with this type o psoriasis o ten experience severe oot and hand pain that can impair walking and other daily activities o living. Hand involvement can result in pain with many types o work. • Morphologically this can be plaque like, vesicular, or pustular (Figure 150-24). Brown spots may be present as macules or at papules. These are called mahogany spots and although they are not always present, they are characteristic o palmar-plantar psoriasis. Ex oliation o the skin can occur on the palms and soles. FIGURE 150-18 Plaq ue p soriasis with an annular con g uration. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 150-19 Line ar d istrib ution o p soriasis on the arm se cond ary to the Koe b ne r p he nome non. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Erythrodermic psoriasis • Erythrodermic psoriasis is widespread and erythematosus covering most o the skin (Figure 150-25).

FIGURE 150-21 Guttate p soriasis with d rop -like p ink p laq ue s on the trunk. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

pSO r Ia SIS

A

PART 14

DERMATO LO GY

FIGURE 150-23 Palmar-p lantar p soriasis that was b iop sy p rove n. Note the wid e sp re ad e rythe ma and scale that could b e mistake n or tine a p e d is and tine a manus. The p atie nt d oe s not have p ustule s or mahog any sp ots b ut those le sions are o te n not p re se nt in p almar-p lantar p soriasis. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

• In the generalized type, the skin initially becomes f ery red and tender and the patient experiences constitutional signs and symptoms such as headache, ever, chills, arthralgia, malaise, anorexia, and nausea (Figure 150-26). The desquamation that occurs in the generalized orm can impair the important unctions o the skin predisposing to dehydration and sepsis. This is a dermatologic emergency requiring hospitalization and IV uids, pre erably in a monitored bed with good nursing care. • Typical distribution: Flexural and anogenital (Figure 150-27). Less o ten, acial lesions occur. Pustules may occur on the tongue and subungually, resulting in dysphagia and nail shedding, respectively. • Time course: Within hours, clusters of nonfollicular, super cial 2- to 3-mm pustules may appear in a generalized pattern. These pustules coalesce within 1 day to orm lakes o pus that dry and desquamate in sheets, leaving behind a smooth erythematous sur ace on which new crops o pustules may appear. These episodes o pustulation may occur or days to weeks causing the patient severe discom ort and exhaustion. Upon remission o the pustular component, most systemic symptoms disappear; however, the patient may be in an erythrodermic state or may have residual lesions. 1 B FIGURE 150-22 Two me n with inve rse p soriasis in the ing uinal are a. A. Erythe ma and scaling in ing uinal old s with involve me nt on the p e nis. B. Inve rse p soriasis in the ing uinal are a only sp aring the p e nis. This was mistake n or tine a cruris or a long time . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Morphologically, it can have plaques and erythema or the erythroderma can appear with the desquamation o pustular psoriasis. • Widespread distribution can impair the important functions of the skin and this can be a dermatologic urgency requiring hospitalization and intravenous (IV) uids. Chills, ever, tachycardia, and orthostatic hypotension are all signs that the patient may need hospitalization. Pustular psoriasis • Pustular psoriasis comes in localized and generalized types. One example o the local type is pustular psoriasis on the eet (see Figure 150-24).

FIGURE 150-24 Palmar-plantar psoriasis with e xte nsive p ustule s and mahogany spots. (Re p roduced with pe rmission from UTHSCSA d ermatology.)

735

PART 14

736

DERMATO LO GY

Ch a pt e r 150

FIGURE 150-27 Localize d p ustular p soriasis in the g roin. (Re p rod uce d with p e rmission from Je ffre y Me ffe rt, MD.)

FIGURE 150-25 Erythrod e rmic p soriasis in a 45-ye ar-old man. No te the e xte nsive e x oliatio n o the skin alo ng with the d e e p e rythe ma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Nail psoriasis • Nail involvement in psoriasis can lead to pitting, onycholysis, subungual keratosis, splinter hemorrhages, oil spots, and nail loss (see Figure 150-10 and Chapter 193, Psoriatic Nails). Psoriatic arthritis • Asymmetric oligoarthritis typically involves the hands, eet, and knees. The arthritis can also be symmetric resembling rheumatoid arthritis. Distal interphalangeal joint (DIP) involvement is a classic f nding, but DIP predominance is present in the minority o cases. The f ngers may

FIGURE 150-26 Ge ne ralize d p ustular p soriasis in a 47-ye ar-old man with e ve r, e x oliation, and d e hyd ration. This is the twe ntie th time or this p atie nt in his li e . His sib ling s also g e t se ve re g e ne ralize d p ustular p soriasis. (Re p rod uce d with p e rmission from Me ng Lu, MD.)

FIGURE 150-28 Dactylitis with sausag e -shap e d ng e rs in this mid d le -ag e d woman with p laq ue p soriasis and p soriatic arthritis. Note the nail involve me nt along with d istal inte rp halang e al joint involve me nt. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 150-29 Rad iog rap h showing the p e ncil-in-cup d e ormity at the d istal inte rp halang e al joint o the se cond and third d ig its. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

PART 14

pSO r Ia SIS

DERMATO LO GY

be swollen like sausages which is called dactylitis (Figure 150-28). (see Chapter 100, Psoriatic Arthritis) • Hand involvement can be disabling (see Figure 150-11). X-rays should be ordered when a person with psoriasis has joint pains suggesting psoriatic arthritis. Typical f ndings are juxta-articular erosions and the pencil-cup de ormity (Figure 150-29). • There may be in ammation at the insertion o tendons onto bone (enthesopathy). This may occur at the Achilles tendon. • Patients with psoriatic arthritis need to be treated with systemic agents (methotrexate [MTX] or biologics) to prevent advancement o the disease. DISEASE SEVERITY • Moderate-to-severe disease is def ned by psoriasis o the palms, soles, head and neck, or genitalia, and in patients with more than 5% body sur ace area (BSA) involvement. A person’s palm is approximately 1% BSA and can be used to estimate BSA. • Another grading system or severity uses the ollowing numbers: ° Mild: Up to 3% BSA ° Moderate: 3% to 10% BSA ° Severe: Greater than 10% BSA • Patients with psoriatic arthritis may have limited skin disease but require more aggressive systemic therapies. • Note that palmoplantar psoriasis is considered moderate to severe even i the BSA involved is not above 3% or 5% (Figure 150-30).

A

LABO RATO RY STUDIES Laboratory studies are rarely needed. A punch biopsy or scoop shave is used or evaluating atypical cases. For pustular psoriasis, a 4-mm punch around an intact pustule is pre erred (Figure 132-31). IMAGING Plain f lms should be ordered when a person with psoriasis has joint pains suggesting psoriatic arthritis (see Figure 150-29). Early psoriatic arthritis o ten has no f ndings on plain f lms, but i history and physical

B FIGURE 150-31 Pustular p soriasis in a 41-ye ar-old woman. A 4-mm p unch b iop sy includ ing at le ast one p ustule he lp e d to con rm the clinical d iag nosis. The p atie nt was stab le or outp atie nt tre atme nt and was starte d on cyclosp orine and acitre tin tog e the r with the p lan to stop the cyclosp orine once the p ustule s have cle are d . A. Arm involve me nt. B. Close -up o p ustule s on the le g . (Re p rod uce d with p e rmission from Rob e rt T. Gilson, MD.)

examination suggest the diagnosis, one should not wait or irreversible visible joint damage to initiate therapy.

FIGURE 150-30 Palmop lantar p soriasis in a 31-ye ar-old man with e rythe ma, p ustule s, and lake s o p us. Note the typ ical b rown macule s that are calle d mahog any sp ots. Hig h-p ote ncy top ical ste roid s d id not he lp at all. It is p ain ul o r him to walk and syste mic the rap y has just b e e n starte d . This is a localize d orm o p ustular p soriasis. (Re p rod uce d with p e rmission from Je ff Me ffe rt, MD.)

DIFFERENTIAL DIAGNO SIS • Cutaneous T-cell lymphoma (CTCL) can have plaques that resemble psoriasis. In most cases o psoriasis, the distribution and nail changes will help to di erentiate between these diseases. Plaque-type CTCL

737

738

PART 14

DERMATO LO GY tends to be more central and truncal, whereas psoriasis o ten involves the extremities along with the trunk. I needed, a punch biopsy can help to di erentiate between these 2 conditions (see Chapter 174, Cutaneous T-cell Lymphoma). • Lichen planus is another papulosquamous disease. Its distribution is more on exor sur aces and around the wrists and ankles than the elbows and knees (see Chapter 152, Lichen Planus). • Lichen simplex chronicus is a hyperkeratotic plaque with lichenif cation. It usually presents with ewer plaques than psoriasis and is typically ound on the posterior neck, ankle, wrist, or lower leg. There is usually more lichenif cation than thick scale and it is always pruritic (see Chapter 147, Psychocutaneous Disorders). • Nummular eczema presents with coin-like plaques. These are most commonly ound on the legs and are usually not as thick as the plaques o psoriasis. Nummular eczema may also have vesicles and bullae. Psoriasis has a di erent distribution and o ten includes nail changes (see Chapter 143, Atopic Dermatitis). • Pityriasis rosea is a sel -limited process that has papulosquamous plaques. These plaques are less keratotic and have a collarette scale. Pityriasis rosea requently has a herald patch (see Chapter 151, Pityriasis Rosea).

Ch a pt e r 150

is an important actor in worsening their condition. Use preventive techniques as much as possible by avoiding known precipitants. Patient perception o their disease and expectations or therapy are as important as the evidence and recommendations that ollow. Some patients are willing to live with some skin changes rather than go on systemic treatment, whereas others want everything done with a goal o 100% clearance. Consequently, therapeutic choices are made in conjunction with patient’s values and their li e situation (economic and time issues surrounding treatment options). Choice of topical vehicles • An ointment has a petrolatum base and will penetrate thick scale best. • An emollient cream has some o the advantages o an ointment but is cosmetically more appealing to patients who f nd a basic ointment to be too greasy. • Some patients pre er cream to avoid the oily eel o ointment even though it is less e ective in general than an ointment. However, in many cases the most e ective vehicle is the one the patient will use. • Lotions and oams are good or hair-bearing areas when some moisturizing is desired. • Steroid solutions work well or psoriasis o the scalp.

• Seborrheic dermatitis o the scalp can closely resemble psoriasis o the scalp, especially when it is severe. Psoriasis generally has thicker plaques on the scalp and the plaques o ten cross the hairline. Seborrhea and psoriasis can both involve the ear. Both conditions respond to topical steroids (see Chapter 149, Seborrheic Dermatitis).

• New oam preparations have rapid absorption and are cosmetically appealing. These tend to be more expensive at this time.

• Syphilis is the great imitator and secondary syphilis can have a papulosquamous eruption similar to psoriasis. Secondary syphilis o ten involves the palms and soles and the rapid plasma reagin (RPR) will be positive (see Chapter 218, Syphilis).

• Research supports potent topical steroids as f rst-line therapy. 8 SO R A Clobetasol is an ultrahigh-potency steroid that is generic and comes in many vehicles or use on the body and scalp. A meta-analysis o the studies with clobetasol demonstrated 68% to 89% o patients had clear improvement or complete healing. 9 SO R A

• Tinea corporis or cruris can resemble inverse psoriasis in the intertriginous areas as both conditions tend to have erythema and thinner plaques without central clearing in these regions. Tinea corporis in non-intertriginous areas typically presents with annular plaques with central clearing. Psoriasis can do this as seen in Figure 150-18. Tinea corporis usually does not have as many plaques as psoriasis but a potassium hydroxide (KOH) preparation can be used to look for fungal elements to distinguish between these 2 conditions (see Chapter 136, Tinea Corporis). • Cutaneous candidiasis appears similar to inverse psoriasis when ound in intertriginous areas (see Chapter 135, Candidiasis). • Reactive arthritis (see Chapter 153, Reactive Arthritis) is a nonin ectious acute oligoarthritis that occurs in response to an in ection, most commonly in the gastrointestinal (GI) or urogenital tract. Patients present 1 to 4 weeks a ter the triggering in ection, with joint pain in asymmetric large joints, eye disease such as conjunctivitis, and skin changes including erythema nodosum, keratoderma blennorrhagicum, and circinate balanitis. Diagnosis is based on the clinical presentation plus evidence o associated in ection. 7 The skin lesions closely resemble psoriasis so the diagnosis depends on the constellation o the clinical involvement and the history.

MANAGEMENT Treat precipitating and underlying actors when these are known. Encourage smoking cessation to all who smoke (see Chapter 237, Tobacco Addiction). Avoid or minimize alcohol use (see Chapter 238, Alcoholism). Stress management techniques can be suggested in patients who admit that stress

Topical treatments • Table 150-3 summarizes the strength o recommendations or the treatment o psoriasis using topical therapies.

• There are 2 vitamin D analogs available or topical use: calcipotriene (Dovonex and generic) and calcitriol (Vectical). These vitamin D preparations are recommended as f rst-line therapy with or without topical corticosteroids or the treatment o childhood psoriasis. 10 SO R A They are also use ul or adults but most patients report that clobetasol is more e ective. • Comparable e f cacy has been shown or topical calcipotriene (vitamin D analog) and tazarotene (retinoid) with a slight increase in adverse e ects or tazarotene. 8 SO R A • Using topical steroids and calcipotriene or tazarotene is an e ective regimen. It has increased e f cacy and ewer side e ects. 8,9 SO R A However, in monotherapy studies o topical agents in psoriasis, steroids caused ewer adverse reactions compared to vitamin D analogs and tazarotene. 11 SO R A • One expensive topical preparation combines betamethasone and calcipotriene (Taclonex ointment) to be applied once daily. Another option is to prescribe generic clobetasol ointment and generic calcipotriene cream to be used simultaneously or in an alternating ashion. • Clobetasol in the morning and tazarotene in the evening is a good combination to reduce irritation and increase e f cacy. 9 SO R A • Two trials randomized potent steroid treatment responders to either an intermittent maintenance regime (3 applications each weekend) or to no maintenance. The results o more than 6 months indicate that patients receiving maintenance therapy were more than 3 times as likely to stay in remission. 12 SO R B

PART 14

pSO r Ia SIS

DERMATO LO GY

TABLE 150-3 Stre ng th o Re comme nd ations or the Tre atme nt o Psoriasis Using Top ical The rap ie s 1

Ag e nt

St re ng t h o Le ve l o Re co mme nd at io n Evid e nce

Class I corticoste roid s (hig he st p ote ncy)

A

I

Class II corticoste roid s

B

II

Classe s III/IV corticoste roid s (me d ium p ote ncy)

A

I

Classe s V/VI/VII corticoste roid s (lowe st p ote ncy)

A

I

Vitamin D analog s

A

I

Tazarote ne

A

I

Tacrolimus and p ime crolimus

B

II

Anthralin

C

III

Coal tar

B

II

Comb ination corticoste roid and salicylic acid

B

II

Phototherapy

Comb ination corticoste roid and vitamin D analog

A

I

• It is indicated in the presence o extensive and widespread disease (practically def ned as more lesions than can be easily counted) and psoriasis not responding to topical therapy.

Comb ination corticoste roid and tazarote ne

A

Comb ination tacrolimus and salicylic acid

B

I II

Data rom Me nte r A, Korman NJ, Elme ts CA, e t al; Ame rican Acad e my o De rmatolog y. Guid e line s o care or the manag e me nt o p soriasis and p soriatic arthritis. Se ction 3. Guid e line s o care or the manag e me nt and tre atme nt o p soriasis with top ical the rap ie s. J Am Acad De rmatol. 2009;60(4):643-659.

• Older treatments still in use include topical coal tar and topical anthralin. 9 Evidence does not support the use o coal tar alone or in combination at this time. 9 SO R A Topical anthralin is messy, not practical or long-term use and not supported by evidence. 1,5 SO R A • Topical calcineurin inhibitors previously approved or eczema are being studied or use in psoriasis. Tacrolimus ointment seems most e ective in treating psoriasis o the ace and intertriginous areas where the skin is thin. Clinical trials suggest that tacrolimus (0.1%) ointment twice a day produces a good response in a majority o patients with acial and intertriginous (inverse) psoriasis (see Figure 150-6). 13-15 SO R B

• Emollients and keratolytics are sa e and probably benef cial as adjunctive treatment. SO R C • Intralesional steroids may help small plaques resolve (Figure 150-32). Use triamcinolone acetonide 5 to 10 mg/ mL injected with a 27-gauge needle into the plaque. SO R C

FIGURE 150-32 Intrale sional inje ction o small p laq ue s ove r the kne e those we re re sistant to tre atme nt with hig h-p ote ncy top ical ste roid s. A 27-g aug e ne e d le was e mp loye d with 5 mg /mL triamcinolone . (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

• Narrowband UVB is more e ective than broadband UVB and approaches psoralen and UVA (PUVA) in e f cacy or the treatment o psoriasis in patients with skin types I to III (lighter skin). 16 SO R A • At present, there are no predictors o the type(s) o psoriasis most responsive to narrowband UVB. 16 • O patients with psoriasis, 63% to 80% will clear with a course o narrowband UVB with equivalent relapse rates compared with PUVA. 16 • Lack o requirement or psoralen and convenience suggests that narrowband UVB could be considered as the f rst-line phototherapy option with PUVA reserved or treatment ailures. 16 • MTX pretreatment (15 mg/ wk × 3) allowed physicians to clear psoriasis in ewer phototherapy sessions than when phototherapy was administered alone in one study. 17 SO R B • According to one consensus con erence, acitretin combined with UV therapy is sa e and e ective and limits treatment requency, duration, and cumulative doses o both agents. They state this combination is better tolerated, more convenient, less costly, and, perhaps, sa er during long-term treatment than phototherapy alone. 18 SO R C • Avoid use o cyclosporine with UV therapy because o an increased risk o skin cancer. 19 Systemic • When topical agents (and/ or phototherapy fail), systemic agents (including biologic agents) are the next step. Table 150-4 summarizes the systemic drugs used in treatment o psoriasis. • MTX and biologic agents are especially valuable in patients with psoriatic arthritis and may be started early in the course o treatment to prevent permanent joint damage. • Do not use systemic corticosteroid therapy or psoriasis. Pustular ares o disease may be provoked and these ares can be atal (see Figure 150-18).

739

PART 14

740

Ch a pt e r 150

DERMATO LO GY TABLE 150-4 Syste mic Drug s Use d in Tre atme nt o Psoriasis 31

Drug Name

Classif cat io n/ Me chanism o Act io n

Acitre tin

O ral re tinoid

First-line syste mic d rug or chronic p almop lantar or p ustular p soriasis in p atie nts o nonchild b e aring p ote ntial. Limite d b e ne t or p laq ue p soriasis.

Cyclosp orine

O ral calcine urin inhib itor

Fast-acting syste mic d rug that is o te n use d rst line or p ustular p soriasis or e rythrod e rmic p soriasis. For inte rmitte nt use in p e riod s up to 12 wk as a short-te rm ag e nt to control a f are o p soriasis.

Me thotre xate sod ium

Inhib itor o olate b iosynthe sis

May b e use d as a rst-line syste mic d rug or p laq ue p soriasis and p soriatic arthritis. Comp are d with cyclosp orine , has a more mod e st e e ct, b ut can b e use d continuously or ye ars or d e cad e s.

Ad alimumab

TNF inhib itor

May b e use d as rst-line syste mic tre atme nt o p laq ue p soriasis and p soriatic arthritis.

Co mme nt s

Has hig he r e cacy and lowe r rate o ad ve rse e e cts comp are d with me thotre xate . Etane rce p t

TNF inhib itor

Commonly use d as a rst-line syste mic d rug or chronic p laq ue p soriasis and p soriatic arthritis.

Inf iximab

TNF inhib itor

Intrave nous in usion with hig h rate s o e e ctive ne ss. Fast-acting d rug that is o te n use d as a se cond - or third -line b iolog ical or chronic p laq ue p soriasis.

Uste kinumab

Monoclonal antib od y that b ind s the share d p 40 p rote in sub unit o IL-12 and IL-23

Favorab le re sults whe n comp are d with e tane rce p t in te rms o e cacy and sa e ty. May b e use d as rst-line syste mic tre atme nt or chronic p laq ue p soriasis.

IL, inte rle ukin; TNF, tumor ne crosis actor.

• MTX and oral retinoids can cause birth de ects so appropriate counseling, contraception, and testing should accompany therapy with these agents. • MTX is given as a weekly dose o 7.5 to 25 mg/ wk depending on response and side e ects. 20 SO R A Tuberculosis (TB) screening with purif ed protein derivative (PPD) or QuantiFERON-TB Gold blood test should precede treatment (i positive results, then the TB needs treatment be ore starting this therapy). Pretreatment laboratories should include a complete blood count (CBC), di erential, liver unction tests (LFTs), a chemistry prof le, and hepatitides B and C serologies. A CBC and LFTs should be ollowed regularly. Patients should take olic acid 1 mg/ d to prevent some o the possible adverse e ects o MTX. For MTX, reliable contraceptive methods should be used during and or at least 3 months a ter therapy in both men and women. 5 • The starting dose o MTX is between 5 and 10 mg/ wk or the f rst week based on expert experience. 21 The dose is escalated with monitoring to obtain a therapeutic target dose o 15 to 25 mg/ wk. Oral dosing is pre erred but subcutaneous (SQ) dosing is an option in the event o poor GI tolerance (same dosing as oral). Type 2 diabetes and

obesity appear to be signif cant risk actors in f brosis. 21 A combination o f brotests and f broscans together with measurement o the type III serum procollagen aminopeptide are noninvasive methods to monitor or liver toxicity. 21 SO R C The question o whether or when to do a liver biopsy and/ or stop MTX is controversial. The National Psoriasis Foundation has published that liver “biopsies are now advocated a ter a cumulative dose o 3.5 g in low-risk patients and 1.5 g in high-risk patients.” The same recommendations are cited in the 2009 National Psoriasis Foundation Consensus Con erence on MTX and psoriasis. 22 SO R C

• Cyclosporine (oral) is a T-cell inhibitor and is very e ective in rapidly treating psoriasis. The recommended starting dose is 2.5 to 6 mg/ kg/ d (actual body weight) divided twice a day. 19 SO R C Serum creatinine and blood pressure should be monitored monthly. Also CBC, uric acid, potassium, lipids, LFTs, and magnesium should be monitored monthly. Cyclosporine can be used or long-term therapy in patients with severe psoriasis or up to 2 years li etime maximum based on European guidelines and 1 year maximum based on the US guidelines.9,19 SO R C Cyclosporine is pregnancy category C, with several studies indicating an increased risk o premature birth but no major mal ormations.19

PART 14

pSO r Ia SIS

DERMATO LO GY

TABLE 150-5 FDA-Ap p rove d Biolog ic Ag e nts or Tre ating Psoriasis

Bio lo g ic Ag e nt

Pro d uct Name

Me chanism o Act io n

Ro ut e o De live ry

Fre q ue ncy o Maint e nance Do sing

Ad alimumab

Humira

TNF inhib itor

SQ

Eve ry 2 wk

Etane rce p t

Enb re l

TNF inhib itor

SQ

O nce to twice we e kly

Inf iximab

Re micad e

TNF inhib itor

IV in usion

Eve ry 6-8 wk

Uste kinumab

Ste lara

Monoclonal antib od y that b ind s p 40 p rote in sub unit o IL-12 and IL-23

SQ

Eve ry 3 mo

IL, Inte rle ukin; IV, Intrave nous; TNF, tumor ne crosis actor.

• Oral retinoids: Acitretin is a potent systemic retinoid used or psoriasis. 23 SO R A Acitretin appears to provide better e f cacy in pustular psoriasis (including palmoplantar psoriasis) than in plaque-type psoriasis as a single-agent treatment (see Figure 150-31). 24 SO R A Low-dose acitretin therapy (25 mg/ d) seems to be better tolerated and associated with ewer abnormalities ound a ter laboratory testing and ewer adverse e ects than the 50 mg/ d dosage. 23 Acitretin is known to cause etal mal ormations just like isotretinoin so it is best to avoid use in women capable o pregnancy, especially as it may remain in the body or up to 3 years a ter stopping therapy. Biologic agents There are 4 biologic agents available and Food and Drug Administration (FDA) approved or treating psoriasis.25 See Tables 150-5 and 150-6 or in ormation about mechanism o action and the e ectiveness o these agents. • Be ore starting therapy, obtain a PPD or QuantiFERON-TB Gold blood test. These agents can reactivate dormant TB. Screening or TB should continue yearly during biologic therapy. 26 • The tumor necrosis actor (TNF) inhibitors (adalimumab, etanercept, and in iximab) share a common mechanism o action that leads to sa ety concerns. Sa ety concerns include serious in ections (eg, sepsis,

tuberculosis, and viral in ections), autoimmune conditions (lupus and demyelinating disorders), and lymphoma. 27 • Etanercept (subcutaneous): For adults the dose is 50 mg SQ twice weekly or 3 months then 50 mg weekly therea ter.9 SOR A This agent is especially valuable in patients with psoriatic arthritis as well as psoriasis.9 SOR A • Ustekinumab is a new biologic agent that is given SQ every 3 months. It targets interleukin (IL)-12 and IL-23 in the treatment o moderateto-severe psoriasis. The sa ety prof le o continued ustekinumab exposure through up to 3 years is avorable including the risk or either in ections or malignancies. 28,29 • While the biologic agents are all very expensive, insurance often pays and there are patient assistance programs or uninsured patients with limited resources. Methotrexate versus biologic agents20 • MTX is a very inexpensive medication with more than a 40-year track record, but with known potential or hepatotoxicity. It is very e ective, but requires monitoring o the LFTs and the blood count on a regular basis. • The biologic agents are engineered proteins with a potentially sa er prof le than MTX. However, they are very expensive and require

TABLE 150-6 Biolog ic Ag e nts as Tre atme nt o Plaq ue Psoriasis—Estimate d Prob ab ilitie s o Re sp onse Base d on Synthe sis o Evid e nce

PASI 50, me an (95% CrI)

PASI 75, me an (95% CrI)

PASI 90, me an (95% CrI)

Place b o

13% (12-14)

4% (3-4)

1% (0-1)

Etane rce p t 25 mg

65% (56-73)

39% (30-48)

15% (10-21)

Etane rce p t 50 mg

76% (71-81)

52% (45-59)

24% (19-30)

Ad alimumab

81% (74-87)

58% (49-68)

30% (23-39)

Uste kinumab 45 mg

88% (84-91)

69% (62-75)

40% (33-48)

Uste kinumab 90 mg

90% (87-93)

74% (68-80)

46% (39-54)

Inf iximab

93% (89-96)

80% (70-87)

54% (42-64)

CrI, cre d ib le inte rval; PASI, Psoriasis Are a and Se ve rity Ind e x is use d to e xp re ss the se ve rity o p soriasis. It comb ine s the se ve rity (e rythe ma, ind uration, and d e sq uamation) and p e rce ntag e o a e cte d are a (lowe r numb e r is b e tte r and the hig he st numb e r or worst d ise ase is 72); PASI 50 = 50% re d uction in PASI score —clinically me aning ul imp rove me nt; PASI 75 = 75% re d uction in PASI score —ve ry g ood imp rove me nt; PASI 90 = 90% re d uction in PASI score —e xce lle nt imp rove me nt. Data rom Re ich K, Burd e n AD, Eaton JN, Hawkins NS. E cacy o b iolog ics in the tre atme nt o mod e rate to se ve re p soriasis: a ne twork me ta-analysis o rand omize d controlle d trials. Br J De rmatol. 2012;166:179-188.

741

PART 14

742

DERMATO LO GY parenteral administration. Biologics have the advantage o requiring less monitoring with blood tests. The biologic agents are not side e ect ree and some o the potential side e ects, while rare, are quite dangerous, and include the risks o sepsis, malignancy, and demyelinating disease.

Ch a pt e r 150

PALMAR-PLANTAR PSO RIASIS For mild disease, start with topical treatments as in plaque psoriasis. For moderate-to-severe cases, systemic therapy such as oral acitretin, MTX, or one o the biologics may be needed. ERYTHRO DERMIC/ GENERALIZED PSO RIASIS

THERAPY BY TYPE O F PSO RIASIS PLAQ UE TYPE Mild-to-moderate plaque psoriasis: Clobetasol twice daily or 2 to 4 weeks. Then decrease use o clobetasol and consider adding a steroid-sparing topical agent such as a vitamin D topical product. Severe plaque orm psoriasis: One systematic review ound 665 studies dealing with the treatment o severe plaque psoriasis. 17 Photochemotherapy showed the highest average proportion o patients with clearance (70% [6947/ 9925]) and good response (83% [8238/ 9925]), ollowed by UVB (67.9% [620/ 913]) and cyclosporine (64% [1030/ 1609]) therapy. 30 SO R A Expert consensus in a meeting ollowing data analysis supported the ollowing sequence or the treatments: UVB, photochemotherapy, MTX, acitretin, and cyclosporine. 30 SO R C The Consensus guidelines or the management o plaque psoriasis published in 2012 is based on US National Psoriasis Foundation review and update o the Canadian Guidelines or the Management o Plaque Psoriasis. It includes newly approved agents such as ustekinumab and the excimer laser. The management o psoriasis in special populations is discussed. 31 In particular, current evidence does support the use o TNF antagonists or the treatment o psoriasis in patients with hepatitis C.31 Table 150-4 summarizes the systemic treatments or plaque type psoriasis. SCALP One head-to-head trial (no pun intended) in scalp psoriasis demonstrated no therapeutic di erence between a topical vitamin D derivative and a topical potent steroid. 12 Generic uocinonide solution daily to the scalp is e ective. Derma-smooth is another a ordable scalp product that combines a high-potency steroid with a peanut oil. Calcipotriene daily to scalp also helps but is more expensive. Mineral oil may be used to moisturize and remove scale. Shampoos with tar and/ or salicylic acid (T-Gel and T-Sal) can help to dissolve and wash away some o the scale. O course, systemic therapies or more severe psoriasis will help clear scalp psoriasis. GUTTATE PSO RIASIS Phototherapy works particularly well or guttate psoriasis. 6 SO R C Narrowband UVB therapy may produce clearing in less than 1 month. Topical therapies are a reasonable option when phototherapy is not available (see Figure 150-20). 6 SO R C Although both antibiotics and tonsillectomy have requently been advocated or patients with guttate psoriasis, there is no good evidence that either intervention is bene icial. 32

Treatment considerations include hospitalization or dehydration and close monitoring, cyclosporine, MTX, oral retinoids, phototherapy, or photochemotherapy. 6 SO R C Cyclosporine is very e ective in rapidly treating the most severe erythrodermic psoriasis (see Figure 150-25). The recommended starting dose is 2.5 to 6 mg/ kg/ d (actual body weight) divided twice a day. 19 PUSTULAR PSO RIASIS Options include oral retinoids such as isotretinoin or acitretin (depends on sex and age o the patient), MTX, cyclosporine, phototherapy, and hospitalization as needed. 6 SO R C Cyclosporine is very e ective in rapidly treating pustular psoriasis at 2.5 to 6 mg/ kg/ d (actual body weight) divided twice a day. 19 One strategy is to start cyclosporine and acitretin together and to stop the cyclosporine once the pustules have cleared (see Figure 150-31).

PRO GNO SIS Prognosis is dependent on the type o psoriasis with the palmar-plantar type being the most dif cult to treat. While erythrodermic and generalized pustular psoriasis are the most immediately dangerous types the response to treatment may vary rom excellent to disappointing. Widespread plaque psoriasis is challenging to treat but the prognosis is not easily predictable and patient adherence is a very important actor in the prognosis. Excellent control is always the goal and cure should not be expected (even guttate psoriasis in children can come back as plaque psoriasis later in li e).

FO LLO W-UP • Follow-up may need to be requent or various therapies including cytotoxic drugs, the biologics, and light therapy. • While there are many safety concerns with the biologic agents a recent integrated sa ety analysis o short- and long-term sa ety prof les o etanercept in patients with psoriasis concluded that rates o nonin ectious and in ectious adverse events were comparable between placebo and etanercept groups. 33 Also, there was no increase in overall malignancies with etanercept therapy compared with the psoriasis population. 33 • Well-controlled psoriasis on topical agents does not require frequent ollow-up.

INVERSE PSO RIASIS Mid- to high-potency topical steroids can be used or inverse psoriasis even though the disease occurs in skin olds (Figure 150-6). A number o studies have shown that tacrolimus works well to treat inverse psoriasis when applied twice daily. 13-15 SO R B Some patients did report a warm sensation or pruritus upon application so patients should be warned o this and told not to stop using the tacrolimus as this may improve over time. 13-15

PATIENT EDUCATIO N This is a chronic disease that cannot be cured. There are many methods to control psoriasis. Patients need to develop a relationship with a amily physician or dermatologist to control the psoriasis or maximum quality o li e. Table 150-7 lists discussion points.

pSO r Ia SIS

TABLE 150-7 Discussion Points or He alth Care Provid e r and Patie nt at Initial Visits

• • • • • • • •

He re d itary asp e cts Syste mic mani e stations Exace rb ating and ame liorating actors Past tre atme nt re sp onse s Rang e o the rap e utic op tions Chronic long -te rm d ise ase Psycholog ical issue s O p timism or tomorrow b ase d on rap id re se arch d e ve lop me nts • Sup p ort or se rvice s availab le rom the National Psoriasis Found ation PATIENT RESO URCES

• The National Psoriasis Foundation—http:/ / www.psoriasis .org/ . PRO VIDER RESO URCES

• Hsu S, Papp KA, Lebwohl MG, et al. Consensus guidelines for the management o plaque psoriasis. Arch Dermatol. 2012;148(1): 95-102—http:/ / archderm.ama-assn.org/ cgi/ content/ short/ 148/ 1/ 95.

PART 14

DERMATO LO GY 5. Jankovic S, Raznatovic M, Marinkovic J, et al. Risk actors or psoriasis: a case-control study. J Dermatol. 2009;36:328-334. 6. Callen JP, Krueger GG, Lebwohl M, et al. AAD consensus statement on psoriasis therapies. JAmAcad Dermatol. 2003;49:897-899. 7. van de Kerkhof PCM. Clinical features. In: van de Kerkhof PCM, ed. Textbook of Psoriasis. Oxford, UK: Blackwell Science; 2003:3-29. 8. Af f T, de Gannes G, Huang C, Zhou Y. Topical therapies or psoriasis: evidence-based review. Can Fam Physician. 2005;51:519-525. 9. Nast A, Kopp I, Augustin M, et al. German evidence-based guidelines or the treatment o Psoriasis vulgaris (short version). Arch Dermatol Res. 2007;299:111-138. 10. de Jager ME, de Jong EM, van de Kerkhof PC, Seyger MM. Ef cacy and sa ety o treatments or childhood psoriasis: a systematic literature review. JAmAcad Dermatol. 2010;62:1013-1030. 11. Bruner CR, Feldman SR, Ventrapragada M, Fleischer AB Jr. A systematic review o adverse e ects associated with topical treatments or psoriasis. Dermatol Online J. 2003;9:2. 12. Mason J, Mason AR, Cork MJ. Topical preparations or the treatment o psoriasis: a systematic review. Br J Dermatol. 2002;146: 351-364. 13. Brune A, Miller DW, Lin P, et al. Tacrolimus ointment is effective or psoriasis on the ace and intertriginous areas in pediatric patients. Pediatr Dermatol. 2007;24:76-80.

• Guidelines of Care for the Management of Psoriasis and Psoriatic Arthritis: 6 parts published in Journal of the American Academy of Dermatology rom 2008 to 2010.

14. Lebwohl M, Freeman AK, Chapman MS, et al. Tacrolimus ointment is e ective or acial and intertriginous psoriasis. JAm Acad Dermatol. 2004;51:723-730.

• National Guideline Clearinghouse. Guidelines of Care for the Management o Psoriasis and Psoriatic Arthritis. Section 3. Guidelines o Care or the Management and Treatment o Psoriasis with Topical Therapies—http:/ / www.guidelines.gov/ content.aspx?id =14572&search=psoriasis.

15. Martin EG, Sanchez RM, Herrera AE, Umbert MP. Topical tacrolimus or the treatment o psoriasis on the ace, genitalia, intertriginous areas and corporal plaques. J Drugs Dermatol. 2006;5:334-336.

• The National Psoriasis Foundation (NPF). This includes a pocket guide that can be downloaded as a PDF. This excellent pocket guide includes treatment algorithms or specif c patient types, combination therapies, and transitional strategies or switching meds. By joining the NPF you can get this printed guide or your pocket— http:/ / www.psoriasis.org/ health-care-providers/ treating-psoriasis. • Medscape. Psoriasis—http:/ / emedicine.medscape.com/ article/ 1943419. REFERENCES 1. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management o psoriasis and psoriatic arthritis. Section 3. Guidelines o care or the management and treatment o psoriasis with topical therapies. JAmAcad Dermatol. 2009;60:643-659. 2. Gel and JM, Stern RS, Nijsten T, et al. The prevalence o psoriasis in A rican Americans: results rom a population-based study. JAmAcad Dermatol. 2005;52:23-26. 3. Henseler T, Christophers E. Psoriasis o early and late onset: characterization o two types o psoriasis vulgaris. JAmAcad Dermatol. 1985; 13:450-456. 4. Menter A, Weinstein GD. An overview of psoriasis. In: Koo YM, Lebwohl MD, Lee CS, eds. Therapy of Moderate-to-Severe Psoriasis. London, UK: Informa Healthcare; 2008:1-26.

16. Ibbotson SH, Bilsland D, Cox NH, et al. An update and guidance on narrowband ultraviolet B phototherapy: a British Photodermatology Group Workshop Report. Br J Dermatol. 2004;151:283-297. 17. Asawanonda P, Nateetongrungsak Y. Methotrexate plus narrowband UVB phototherapy versus narrowband UVB phototherapy alone in the treatment o plaque-type psoriasis: a randomized, placebocontrolled study. JAmAcad Dermatol. 2006;54:1013-1018. 18. Lebwohl M, Drake L, Menter A, et al. Consensus con erence: acitretin in combination with UVB or PUVA in the treatment o psoriasis. JAmAcad Dermatol. 2001;45:544-553. 19. Rosmarin DM, Lebwohl M, Elewski BE, Gottlieb AB. Cyclosporine and psoriasis: 2008 National Psoriasis Foundation Consensus Con erence. JAmAcad Dermatol. 2010;62:838-853. 20. Saporito FC, Menter MA. Methotrexate and psoriasis in the era o new biologic agents. JAmAcad Dermatol. 2004;50:301-309. 21. Montaudie H, Sbidian E, Paul C, et al. Methotrexate in psoriasis: a systematic review o treatment modalities, incidence, risk actors and monitoring o liver toxicity. J Eur Acad DermatolVenereol. 2011;25(suppl 2):12-18. 22. Kalb RE, Strober B, Weinstein G, Lebwohl M. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Con erence. JAmAcad Dermatol. 2009;60:824-837. 23. Pearce DJ, Klinger S, Ziel KK, et al. Low-dose acitretin is associated with ewer adverse events than high-dose acitretin in the treatment o psoriasis. Arch Dermatol. 2006;142:1000-1004.

743

744

PART 14

DERMATO LO GY 24. Sbidian E, Maza A, Montaudie H, et al. E f cacy and sa ety o oral retinoids in di erent psoriasis subtypes: a systematic literature review. J Eur Acad DermatolVenereol. 2011;25(suppl 2):28-33. 25. Reich K, Burden AD, Eaton JN, Hawkins NS. Ef cacy of biologics in the treatment o moderate to severe psoriasis: a network meta-analysis o randomized controlled trials. Br J Dermatol. 2012;166:179-188. 26. Sivamani RK, Goodarzi H, Garcia MS, et al. Biologic therapies in the treatment o psoriasis: a comprehensive evidence-based basic science and clinical review and a practical guide to tuberculosis monitoring. Clin Rev Allergy Immunol. 2013;44(2):121-140. 27. Gottlieb A, Korman NJ, Gordon KB, et al. Guidelines of care for the management o psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines o care or treatment with an emphasis on the biologics. JAmAcad Dermatol. 2008;58:851-864. 28. Gordon KB, Papp KA, Langley RG, et al. Long-term safety experience o ustekinumab in patients with moderate to severe psoriasis (part II o II): results rom analyses o in ections and malignancy rom

CHAPTER 150

pooled phase II and III clinical trials. JAmAcad Dermatol. 2012;66: 742-751. 29. Lebwohl M, Leonardi C, Gri f ths CE, et al. Long-term sa ety experience o ustekinumab in patients with moderate-to-severe psoriasis (part I o II): results rom analyses o general sa ety parameters rom pooled phase 2 and 3 clinical trials. JAmAcad Dermatol. 2012;66:731-741. 30. Spuls PI, Bossuyt PM, van Everdingen JJ, et al. The development o practice guidelines or the treatment o severe plaque orm psoriasis. Arch Dermatol. 1998;134:1591-1596. 31. Hsu S, Papp KA, Lebwohl MG, et al. Consensus guidelines for the management o plaque psoriasis. Arch Dermatol. 2012;148:95-102. 32. Owen CM, Chalmers RJ, O’Sullivan T, Gri f ths CE. A systematic review o antistreptococcal interventions or guttate and chronic plaque psoriasis. Br J Dermatol. 2001;145:886-890. 33. Pariser DM, Leonardi CL, Gordon K, et al. Integrated safety analysis: Short- and long-term sa ety prof les o etanercept in patients with psoriasis. JAmAcad Dermatol. 2012;67(2):245-256.

PITYRIASIS RO SEA

PART 14 DERMATO LO GY

151 PITYRIASIS RO SEA David He nd e rson, MD Richard P. Usatine , MD

PATIENT STO RY A young woman comes to the o ice because o a rash that appeared 3 weeks ago or no apparent reason (Figures 151-1 to 151-3). She was eeling well and the rash is only occasionally pruritic. With and without mom in the room, the young woman denied sexual activity. The diagnosis o pityriasis rosea was made by the clinical appearance even though there was no obvious herald patch. The collarette scale was visible and the distribution was consistent with pityriasis rosea. The young woman was reassured that this would resolve spontaneously. At a subsequent visit the skin was ound to be completely clear with no scarring.

FIGURE 151-1 Pityriasis rose a in a young woman. Le sions are o te n conce ntrate d in the lowe r ab d o minal are a. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

INTRO DUCTIO N Pityriasis rosea is a common, sel -limited, papulosquamous skin condition originally described in the 19th century. It is seen in children and adults. Despite the long history, its etiology remains elusive. A number o in ectious etiologies have been proposed, but at present, supporting evidence is inconclusive. Pityriasis rosea has unique eatures including a herald patch in many cases and collarette scale that are use ul in distinguishing it rom other papulosquamous eruptions.

EPIDEMIO LO GY • Pityriasis rosea is a papulosquamous eruption o unknown etiology. 1,2 • It occurs throughout the li e cycle. It is most commonly seen between the ages o 10 and 35 years. 3 • The peak incidence is between 20 and 29 years o age.

1

• The gender distribution is essentially equal. 1

FIGURE 151-2 Scaling le sions se e n on the b uttocks o the same young wo man in Fig ure 151-1. No te ho w so me o the le sio ns are annular. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

• The rash is most prevalent in winter months. 4

ETIO LO GY AND PATHO PHYSIO LO GY • The cause o pityriasis rosea is unknown, although numerous causes have been proposed. • It has long been suspected that it may have a viral etiology because a viral-like prodrome o ten occurs prior to the onset o the rash. Human herpesviruses 6 and 7 have been proposed as causes, but numerous studies have ailed to demonstrate conclusive supportive evidence. 1,2 • Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila have been proposed as potential etiologic agents, but studies have not demonstrated any signi cant rise in antibody levels against any o these pathogens in patients with pityriasis rosea. 1 • Pityriasis rosea has also been associated with negative pregnancy outcomes, particularly premature birth. The risk seems to be greatest when the condition occurs in the rst 15 weeks o gestation. 2

FIGURE 151-3 Close -up o le sion showing collare tte scale . Note how the le sions can b e annular with some ce ntral cle aring . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

745

PART 14 DERMATO LO GY

746

Ch APTER 151

• Pityriasis rosea may rarely occur as the result o a drug reaction. Documented drug reactions that have produced a pityriasis rosea-like eruption include barbiturates, captopril, clonidine, inter eron, bismuth, gold, and the hepatitis B vaccine. 1,2

DIAGNO SIS CLINICAL FEATURES • In approximately 20% to 50% o cases, the rash o pityriasis rosea is preceded by a viral-like illness consisting o upper respiratory or gastrointestinal (GI) symptoms. • This is ollowed by the appearance o a herald patch in 17% o cases (Figures 151-4 to 151-6). 4 • The herald patch is a solitary, oval, f esh-colored to salmon-colored lesion with scaling at the border. It o ten occurs on the trunk, and is generally 2 to 10 cm in diameter (see Figures 151-4 and 151-5). • One to 2 weeks a ter the appearance o the herald patch, other papulosquamous lesions appear on the trunk and sometimes on the extremities. • These lesions vary rom oval macules to slightly raised plaques, 0.5 to 2 cm in size. They are salmon colored (or hyperpigmented in individuals with dark skin), and typically have a collarette o scaling at the border (see Figure 151-3). It is common or some o the lesions to appear annular with central clearing. • In many cases, the herald patch has resolved by the time the rest o the exanthem erupts which can make the diagnosis more di cult.

FIGURE 151-5 Pityriasis rose a with an ob vious-he rald p atch in a woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• The lesions ollow the cleavage, or Langer lines, and may create the typical f r or Christmas tree pattern over the back (Figures 151-7 and 151-8). Do not expect to always see a Christmas tree pattern. • Over the chest, the lesions create a V-shaped pattern, and run transversely over the abdomen (Figure 151-9). • An inverse orm has been described, characterized by more intense involvement o the extremities and relative sparing o the trunk (Figures 151-10 to 151-12).

• There are no systemic symptoms.

LABO RATO RY STUDIES

• Itching occurs in approximately 25% o patients.

Pityriasis rosea is a clinical diagnosis. There are no laboratory tests that aid in the diagnosis. Biopsy o lesions typically reveals only nonspeci c inf ammatory changes. Because secondary syphilis is also a papulosquamous eruption and can be di cult to distinguish rom pityriasis rosea on clinical grounds, taking a sexual history is important when a diagnosis o pityriasis rosea is being considered. In patients with a history o sexually transmitted diseases, or sexual practices that place them at risk, a blood test or syphilis should be considered (see Figures 151-9 and 151-10) (see Chapter 218, Syphilis).

• The exanthem resolves in 8 weeks in 80% o patients. 1 However, it can last up to 3 to 5 months. 3 TYPICAL DISTRIBUTIO N • The rash is bilaterally symmetrical, generally most dense on the trunk, but also involves the upper and lower extremities.

FIGURE 151-4 Pityriasis rose a in a 25-ye ar-old Hisp anic man. Arrow p oints to he rald p atch. (Re p rod uce d with p e rmission from Scott Young q uist, MD. Pre viously p ub lishe d in Young q uist S, Usatine R. It’s b e g inning to look a lot like Christmas. We st J Me d . 2001;175(4):227-228.)

FIGURE 151-6 Pityriasis rose a in a te e nag e b oy with the he rald p atch on the ne ck ne ar the hairline . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PITYRIASIS RO SEA

PART 14 DERMATO LO GY

FIGURE 151-7 Pityriasis rose a in a te e nag e b oy. The scaling le sions ollow skin line s and re se mb le a Christmas tre e . (Re p rod uce d with p e rmission from E.J. Maye aux, Jr., MD.)

FIGURE 151-9 Pityriasis rose a on the che st and ab d ome n o a young woman. Blood te st or syp hilis was ne g ative . (Re p rod uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

FIGURE 151-8 Pityriasis rose a in 31-ye ar-old man with hyp op ig me nte d scaling le sions that re se mb le a Christmas tre e on the b ack. The le sions b e g an 3 we e ks b e ore the p atie nt p re se nte d or e valuation. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 151-10 Pityriasis rosea in a 40-ye ar-old man with an inve rse patte rn. Note how the re is a hig he r d e nsity o le sions on the le g s. Rap id p lasma re ag in (RPR) was ne g ative and the d iag nosis was conf rme d with a p unch b iop sy. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

747

748

PART 14 DERMATO LO GY

Ch APTER 151

DIFFERENTIAL DIAGNO SIS • Tinea corporis is usually more localized than pityriasis rosea. However, the annular patterns, scale, and central clearing o some lesions in pityriasis rosea can mislead the clinician to misdiagnose tinea corporis. Tinea corporis tends to have ewer annular lesions and may have concentric circles rather than a single ring. Microscopy with potassium hydroxide (KOH) usually demonstrates branching hyphae (see Chapter 136, Tinea Corporis). • Tinea versicolor has a distribution similar to pityriasis rosea, but is not associated with a herald patch. The pattern o scaling noted is generally more di use and not annular. Microscopy with KOH demonstrates the spaghetti-and-meatball pattern typical o Pityrosporum (see Chapter 139, Tinea Versicolor). • Secondary syphilis is also a papulosquamous eruption. Lesions are o ten ound on the palms and soles, which is not the case in pityriasis rosea; however, because the 2 conditions cannot always be accurately distinguished on clinical grounds, a blood test or syphilis is indicated i there is a signi icant doubt in the diagnosis (see Chapter 218, Syphilis). • Nummular eczema has coin-like areas o scale that can resemble pityriasis rosea. The scale is not collarette and nummular eczema has a predilection or the legs, an area that is less o ten involved with pityriasis rosea (see Chapter 143, Atopic Dermatitis). FIGURE 151-11 Pityriasis rose a on the arms with p ro mine nt e rythe matous le sions. (Re p ro d uce d with p e rmission fro m the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

• Guttate psoriasis generally presents as oval to round, scaly macules on the trunk, and so can be con used with pityriasis rosea. However, the scaling is generally thicker and more adherent than in pityriasis rosea (see Chapter 150, Psoriasis).

MANAGEMENT • Pityriasis rosea o ten requires no treatment at all other than reassurance. • Topical steroids and oral diphenhydramine may be used to relieve itching when there is pruritus involved. SO R • One study ound oral erythromycin to be e ective in treating patients with pityriasis rosea, 5 although a subsequent study did not nd erythromycin to be better than placebo. 6 SO R B • Azithromycin did not cure pityriasis rosea in a study o children with this condition. 7 • A Cochrane systematic review ound inadequate evidence or e cacy or most treatments or pityriasis rosea. 8 Based on one small randomized controlled trial (RCT), the review authors noted that oral erythromycin may be e ective in treating the rash and decreasing the itch. 5,8 The authors stated that this result should be treated with caution as it comes rom only one small RCT. 5,8 SO R B

PATIENT EDUCATIO N

FIGURE 151-12 Pityriasis rose a in an inve rse p atte rn with le sions on the arms and le g s and sp aring o the trunk. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

Patients are o ten concerned about the duration o the rash and whether they are contagious. They should be reassured that pityriasis rosea is sel limited and not truly contagious. Although there have been reported clusters o pityriasis rosea in settings where people are living in close quarters (eg, dormitories), it is not considered to be contagious. It has a reported recurrence rate o only 2%. 5

PART 14 DERMATO LO GY

PITYRIASIS RO SEA

FO LLO W-UP Patients should be instructed to ollow-up i the rash persists or longer than 3 months as reevaluation and consideration o an alternate diagnosis may be prudent. PATIENT RESO URCES

• Mayo Clinic. Pityriasis Rosea—http:/ / www.mayoclinic.com/ health/ pityriasis-rosea/ DS00720. • WebMD. Pityriasis Rosea: Topic Overview—http:/ / www.webmd .com/ skin-problems-and-treatments/ tc/ pityriasis-rosea-topic-overview.

REFERENCES 1. Stulberg DH, Wol rey J. Pityriasis rosea. Am Fam Physician. 2004;69: 87-92, 94. 2. Browning JC. An update on pityriasis rosea and other similar childhood exanthems. Curr Opin Pediatr. 2009;21(4):481-485. 3. Youngquist S, Usatine R. It’s beginning to look a lot like Christmas. West J Med. 2001;175(4):227-228. 4. Habi TP. Clinical Dermatology. 5th ed. St Louis, MO: Mosby; 2009:316-319. 5. Sharma PK, Yadav TP, Gautam RK, et al. Erythromycin in pityriasis rosea: a double-blind, placebo-controlled clinical trial. J Am Acad Dermatol. 2000;42(2 pt 1):241-244.

PRO VIDER RESO URCES

6. Rasi A, Tajziehchi L, Savabi-Nasab S. Oral erythromycin is ine ective in the treatment o pityriasis rosea. J Drugs Dermatol. 2008;7(1):35-38.

• Medscape. Pityriasis Rosea in Emergency Medicine—http:/ / emedicine.medscape.com/ article/ 762725.

7. Amer H, Fischer H. Azithromycin does not cure pityriasis rosea. Pediatrics. 2006;117(4):1702-1705.

• American Academy of Dermatology. Pityriasis Rosea—http:/ / www.aad.org/ skin-conditions/ dermatology-a-to-z/ pityriasis-rosea.

8. Chuh AA, Do tas BL, Comisel GG, et al. Interventions or pityriasis rosea. Cochrane Database Syst Rev. 2007;(2):CD005068.

749

PART 14 DERMATO LO GY

750

CHAPt Er 152

152 LICHEN PLANUS Rob e rt Kraft, MD Richard P. Usatine , MD

PATIENT STO RY A 38-year-old Hispanic woman presents with a rash on her orearms, wrists, ankle, and back (Figures 152-1 to 152-3). She states the rash is mildly itchy and she does not like the way it looks. She would like some medication to make this better. Lichen planus (LP) was diagnosed and clobetasol was prescribed to keep the LP under better control.

INTRO DUCTIO N LP is a sel -limited, recurrent, or chronic autoimmune disease a ecting the skin, oral mucosa, and genitalia. LP is generally diagnosed clinically with lesions classically described using the 6 Ps (planar, purple, polygonal, pruritic, papules, and plaques).

FIGURE 152-2 Ankle o the woman in Fig ure 152-1 with typ ical liche n planus e up tion. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

EPIDEMIO LO GY • LP is an in ammatory dermatosis o skin or mucous membranes that occurs in approximately 1% o all new patients seen at health care clinics. 1 • Although most cases occur between ages 30 and 60 years, LP can occur at any age. 1,2 • There may be a slight emale predominance. 2-4

ETIO LO GY AND PATHO PHYSIO LO GY A

• Usually idiopathic, thought to be a cell-mediated immune response to an unknown antigen. 2,3,5 • Possible human leukocyte antigen (HLA)-associated genetic predisposition. 2 • Lichenoid-type reactions may be associated with medications (eg, angiotensin-converting enzyme inhibitors [ACEIs], thiazide-type diuretics, tetracycline, chloroquine), metals (eg, gold, mercury), or in ections (eg, secondary syphilis). 2,5 • Associated with liver disease, especially related to hepatitis C virus. 2,5,6 • LP may be ound with other diseases o altered immunity (eg, ulcerative colitis, alopecia areata, myasthenia gravis). 1 • Malignant trans ormation has been reported in ulcerative oral lesions in men. 1

RISK FACTO RS B

• Possible HLA-associated genetic predisposition

FIGURE 152-1 A. A 38-ye a -old Hisp anic woman with liche n p lanus on he w ist. B. Close -up o w ist showing line a ity o the le sions on the f e xo su ace . Le sions may b e p ink athe than p u p le . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Hepatitis C virus in ection, although causal relationship is not established6 • Certain drugs (see “Etiology and Pathophysiology” above)

LICHEN PLANUS

PART 14 DERMATO LO GY

FIGURE 152-4 Hyp e t op hic liche n p lanus on the oot o a man. Pu p le p olyg onal p ap ule s and p laq ue s a e visib le . (Re p ro d uce d with p e rmission from M. Crave n, MD.)

• An initial lesion is usually located on the exor sur ace o the limbs, such as the wrists, ollowed by a generalized eruption with maximal spreading within 2 to 16 weeks. 1 • Lesions may demonstrate the Koebner phenomenon (linear distribution) rom scratching (see Figure 152-1). A

• Lesions are more o ten hyperpigmented rather than purple or pink in dark-skinned persons, and skin may remain hyperpigmented a ter lesions resolve (Figures 152-5 and 152-6). • Skin variants ° Hypertrophic—Typical papules develop into thicker reddish-brown to purple plaques (see Figures 152-4 and 152-6) most commonly on the oot and shins. Seen more o ten in black men with hyperpigmented and hypertrophic lesions (see Figure 152-6). ° Follicular—Pinpoint hyperkeratotic projections o ten on scalp, may lead to cicatricial alopecia. ° Vesicular—Vesicles or bullae occur alongside the more typical LP lesions (Figure 152-7).

B FIGURE 152-3 A. Liche n p lanus on the b ack o the woman in Fig ure 152-1. B. Close -up o le sions on the b ack showing Wickham st iae c ossing the f at p ap ule s o liche n p lanus. The se line s a e white and e ticula like a ne t. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIAGNO SIS CLINICAL FEATURES • Classically, the 6 Ps o LP are planar, purple, polygonal, pruritic, papules, and plaques (Figures 152-1 to 152-4). 2,5 • These well-demarcated at-topped violaceous lesions are o ten covered by lacy, reticular white lines (called Wickham striae or Wickham lines) (see Figure 152-3B).

FIGURE 152-5 Hyp e p ig me nte d liche n p lanus on the b ack p ove n b y p unch b iop sy. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

751

752

PART 14 DERMATO LO GY

CHAPt Er 152

FIGURE 152-8 Actinic liche n p lanus on the ace . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 152-6 Hyp e t op hic liche n p lanus on the le g o a b lack man. Note the hyp e p ig me ntation that is common whe n liche n p lanus occu s in a p e son with d a k skin. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

° Actinic—Typical lesions in sun-exposed areas, such as the ace, back o hands and arms (Figures and 152-8 and 152-9). ° Atrophic—The lesions are atrophic rather than standard plaques (Figure 152-10). ° Ulcerative—Ulcers develop within typical lesions or start as waxy semitranslucent plaques on palms and soles; may require skin gra ting. • Mucous membrane variants ° May be reticular (net-like; Figure 152-11), atrophic, erosive (Figures 152-12 and 152-13), or bullous. It is almost always bilateral. or have a burning sensation; pain ° Oral lesions may be asymptomatic occurs with ulceration. 1,4,6 7,8 ° Oral LP is o ten associated with extraoral LP.

• Genitalia variants ° Reticular, annular (Figure 152-14), papular (Figure 152-15), or erosive lesions on penis, scrotum, labia, or vagina. with dyspareunia, a ° Vulvar/ vaginal lesions may be associated burning sensation, and/ or pruritus. 1,7 1,7 Vulvar and urethral stenosis can also be present. ° • Hair and nail variants, the latter presents in 10% o patients. 1 ° Violaceous, scaly, pruritic papules on the scalp can progress to scarring alopecia. Lichen planopilaris (LP o the scalp) can cause widespread hair loss (see Chapter 187, Scarring Alopecia). 9 ° Nail plate thinning results in longitudinal grooving and ridging; rarely destruction o nail old and nail bed with splintering (Figure 152-16). ° Hyperpigmentation, subungual hyperkeratosis,1 onycholysis, and longitudinal melanonychia can result rom LP. TYPICAL DISTRIBUTIO N LP occurs on the wrists (Figure 152-17), ankles, lower back, eyelids, shins, scalp, penis, and mouth (ie, buccal mucosa, lateral tongue, and gingiva). 2,5 LABO RATO RY STUDIES Wickham striae can be accentuated by a drop o oil on the skin plaque and magnif cation. 5 Not all LP has visible Wickham striae. This study is rarely needed. I the diagnosis is uncertain, a punch biopsy should be per ormed. BIO PSY • A punch biopsy is a valuable method to make as initial diagnosis i the clinical picture is not certain. A biopsy is rarely needed to evaluate or malignant trans ormation. 5,10 • Mainly lymphocytic immunoin ammatory inf ltrate with hyperkeratosis, increased granular layer, and lique action o basal cell layer. 2,5 • Linear f brin and f brinogen deposits along basement membrane. 2,5

FIGURE 152-7 Bullous liche n p lanus on the b utto cks. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Direct immuno uorescence on biopsy specimen reveals globular deposits o immunoglobulin (Ig) G, IgM, IgA, and complement at dermal–epidermal junction. 5

LICHEN PLANUS

PART 14 DERMATO LO GY

FIGURE 152-10 At op hic liche n p lanus (b iop sy p ove n) on the o e a m sho wing multip le co lo s within the at o p hic le sio ns. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

A

FIGURE 152-11 Asymp tomatic white ke atotic st iae o liche n p lanus on le t b uccal mucosa o a 56-ye a -old woman. The p atie nt had simila involve me nt o the ig ht b uccal mucosa and g ing ivae . Liche n p lanus in the mouth is b ilate al. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

B FIGURE 152-9 Actinic liche n p lanus in a b lack man e late d to sun e xp osu e and p ove n b y b io p sy. A. Hyp e p ig me nte d f at p laq ue s on the ace and ne ck and B. on the d o sum o the hand s. (Re p ro d uce d with p e rmission fro m Richard P. Usatine , MD.)

DIFFERENTIAL DIAGNO SIS Skin lesions that may be con used with LP are as below: • Eczematous dermatitis—“The itch that rashes” includes dry skin, itching, o ten excoriations and lichenif cation o skin with predilection or exor sur aces (see Chapter 143, Atopic Dermatitis). • Psoriasis has more prominent silvery scale and is generally located on extensor sur aces. 5 A punch biopsy can be used to distinguish between these 2 when the clinical picture is not clear (see Chapter 150, Psoriasis).

FIGURE 152-12 E o sive liche n p lanus, late al su ace o the tong ue . This 52-ye a -old woman e xp e ie nce s tong ue d iscom o t while e ating acid ic o sp icy ood s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

753

754

PART 14 DERMATO LO GY

FIGURE 152-13 Liche n p lanus in the mouth with e osions. The lip s, tong ue , and p alate a e all involve d . (Re p rod uce d with p e rmission from Eric Kraus, MD.)

• Stasis dermatitis—Lower-extremity eczematous dermatitis with in ammatory papules and o ten ulceration, in the setting o chronic venous insu f ciency with dependent edema (see Chapter 51, Venous Stasis). • Pityriasis rosea—Herald patch and subsequent pink papules and plaques with long axes along skin lines (Christmas tree pattern) (see Chapter 151, Pityriasis Rosea).

CHAPt Er 152

FIGURE 152-15 Liche n p lanus on the p e nis that is mo e simila to the p atte n se e n on othe p a ts o the b od y. This is an e xamp le o p lana , p u p le , p olyg onal p ap ule s on the p e nis. (Re p rod uce d with p e rmission fro m John Gonzale z, MD.)

• Bowen disease—Sharply-demarcated pink, red, brown, or black scaling or hyperkeratotic macule, papule, or plaque, usually mistaken or eczema or psoriasis, associated with ultraviolet radiation, human papilloma virus (HPV), chemicals, and chronic heat exposure. Biopsy is

• Chronic cutaneous lupus erythematosus—Bright-red sharply-demarcated papules with adherent scale. Tend to regress centrally and can be light induced. Generally located on ace, scalp, orearms, and hands. Biopsy may be necessary to di erentiate (see Chapter 178, Lupus: Systemic and Cutaneous). 5

FIGURE 152-14 Liche n p lanus on the p e nis showing a lacy white p atte n. (Re p rod uce d with p e rmission from Dan Stulb e rg , MD.)

FIGURE 152-16 Hyp e t op hic liche n p lanus cove ing the d o sum o b oth e e t with nail sp linte ing . No te the p u p le colo and Wickham line s. (Re p ro d uce d with p e rmission from Eric Kraus, MD.)

PART 14 DERMATO LO GY

LICHEN PLANUS

• Localized/ topical treatment. 11-13 SO R B Mid- to highTopical corticosteroids twice a day. ° potency steroids are usually needed. Clobetasol cream or ointment may be used on the skin and clobetasol ointment or gel may be used in the mouth. 14,15 Topical aloe vera gel has demonstrated e f cacy against oral LP. ° SO R B

° Intralesional triamcinolone (3-5 mg/ mL) or hypertrophic or mucous membrane lesions, may repeat every 3 to 4 weeks. 2,5,10,11 SO R B ° Tacrolimus, pimecrolimus, retinoids, or cyclosporine in mouthwash or adhesive base or oral disease unresponsive to topical corticosteroids. 3,4,10,12,16-19 SO R B ° Topical corticosteroids, tacrolimus and aloe vera gel have demonstrated e f cacy or vulvar LP. 20,21 SO R B

FIGURE 152-17 Thick hyp e t op hic papule s and p laque s on the w ist o the man in Fig ure 152-16. (Re p rod uce d with p e rmission from Eric Kraus, MD.)

needed to make the diagnosis (see Chapter 164, Actinic Keratosis and Bowen Disease). • Lichen simplex chronicus—Localized con uence o lichenif cation rom excoriation; patients have a strong urge to scratch their skin (see Chapter 147, Psychocutaneous Disorders). • Prurigo nodularis—Nodular orm o lichen simplex chronicus, brownto-red hard, domed nodules rom scratching and picking o intense pruritus. LP is not usually so pruritic (see Chapter 147, Psychocutaneous Disorders). Other mucous membrane lesions that may appear similar are as below5: • Leukoplakia—White adherent patch or plaque to oral mucosa. Less net-like pattern. Biopsy warranted because o the risk o malignancy (see Chapter 38, Leukoplakia). • Thrush—Removable whitish plaques over an erythematous mucosal sur ace caused by Candida in ection, conf rmed by potassium hydroxide (KOH) preparation (see Chapter 135, Candidiasis). • Bite trauma in the mouth—May result in white areas o the lip or buccal mucosa; Persons may have a white bite line where the upper and lower molars occlude and this can be con used with oral LP. I in doubt, a biopsy may be needed. Genital lesions that may be di erentiated rom LP are as below5: • Psoriasis on the penis can look like LP on the penis. A shave biopsy can be used to di erentiate between these 2 diagnoses (see Chapter 150, Psoriasis). • Syphilis—Primary in ection mani ests as painless shallow ulcer (chancre) at site o inoculation, i untreated secondary syphilis presents with macular and then papular, pustular, or acnei orm eruption on trunk, neck, palms, and soles, condyloma lata (so t, moist, at-topped pinkto-tan papules) in the anogenital region (see Chapter 218, Syphilis).

MANAGEMENT LP may persist or months to years. Hypertrophic LP and oral LP can last or decades. 2 Any type o LP can recur. Antihistamines can be used or symptomatic pruritus. 5 SO R Symptomatic and severe cases can be treated as ollows:

• Systemic treatment can be considered or resistant, widespread, or severe cases. ° Oral steroids may be used starting with a 3-week tapered course o oral prednisone (60 mg/ d starting dose). 2,10,11,22,23 SO R B ° Systemic retinoids (eg, acitretin 25 mg/ d). Monitor serum creatinine, liver unction tests (LFTs), asting lipids. 3,10,23 SO R B Contraindicated in women o childbearing potential. ° Cyclosporine (5 mg/ kg per day). Monitor complete blood count, serum creatinine, LFTs, and blood pressure. 2 SO R B ° Azathioprine may be used as a steroid-sparing agent (50 mg PO daily to start and titrate to 100-250 mg PO daily). Monitor complete blood count and LFTs. 5,10 SO R ° Psoralen UVA (PUVA) phototherapy may be e ective but can cause phototoxic reactions and has long-term risks, including the development o squamous cell carcinoma. 24 SO R ° Carbon dioxide laser and low-level laser therapy have reports o treatment success against oral LP. 25,26 SO R

PRO GNO SIS • Generally sel -limiting and spontaneous resolution may occur in 12 to 18 months. • Recurrences are common. • Mucosal LP is generally more persistent than cutaneous orms. • Malignant trans ormation o LP is rare.

FO LLO W-UP • Follow-up depends on severity and treatment course. • Oral and vaginal disease may be most challenging to treat. • Follow oral or vaginal lesions or possible malignant trans ormation. Because o low risk o trans ormation even with oral LP (best estimate 0.2% per year), routine screening and biopsy are not recommended. 10 Biopsy is recommended i suspecting malignancy; lesion becomes larger, ulcerated, nodular, or lose reticular pattern.

PATIENT EDUCATIO N • Patients should understand that LP is o ten sel -limiting and may resolve in 12 to 18 months. • There is a signif cant chance o recurrence.

755

PART 14 DERMATO LO GY

756

PATIENT RESO URCES

• Online support group for LP—http:/ / www.mdjunction .com/ lichen-planus. • Online support group for oral LP—http:/ / bcdwp.web .tamhsc.edu/ iolpdallas/ . PRO VIDER RESO URCES

• Usatine RP, Tinitigan M. Diagnosis and treatment of LP. Am Fam Physician. 2011;84(1):53-60. Available online—http:/ / www .aafp.org/ afp/ 2011/ 0701/ p53.html# afp20110701p53-b14.

REFERENCES

CHAPTEr 152

12. Corrocher G, Di Lorenzo G, Martinelli N, et al. Comparative e ect o tacrolimus 0.1% ointment and clobetasol 0.05% ointment in patients with oral lichen planus. J Clin Periodontol. 2008;35(3): 244-249. 13. Carbone M, Arduino PG, Carrozzo M, et al. Topical clobetasol in the treatment o atrophic-erosive oral lichen planus: a randomized controlled trial to compare two preparations with di erent concentrations. J Oral Pathol Med. 2009;38(2):227-233. 14. Choonhakarn C, Busaracome P, Sripanidkulchai B, Sarakam P. The e f cacy o aloe vera gel in the treatment o oral lichen planus: a randomized controlled trial. Br J Dermatol. 2008;158(3):573-577. 15. Salazar SN. E f cacy o topical Aloe vera in patients with oral lichen planus: a randomized double-blind study. J Oral Pathol Med. 2010;39(10):735-740.

2. Wol K, Johnson RA. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 6th ed. New York, NY: McGraw-Hill; 2009;128-133.

16. Conrotto D, Carbone M, Carrozzo M, et al. Ciclosporine vs. clobetasol in the topical management o atrophic and erosive oral lichen planus: a double-blind, randomized controlled trial. Br J Dermatol. 2006;152(1):139-145.

3. Zakrzewska JM, Chan ES-Y, Thornhill MH. A systematic review o placebo-controlled randomized clinical trials o treatments used in oral lichen planus. Br J Dermatol. 2005;153:336-341.

17. Swi t JC, Rees TD, Plemons JM, et al. The e ectiveness o 1% pimecrolimus cream in the treatment o oral erosive lichen planus. J Periodontol. 2005;76(4):627-635.

4. Laeijendecker R, Tank B, Dekker SK, Neumann HA. A comparison o treatment o oral lichen planus with topical tacrolimus and triamcinolone acetonide ointment. Acta DermVenereol. 2006;86(3): 227-229.

18. Volz T, Caroli U, Ludtke H, et al. Pimecrolimus cream 1% in erosive oral lichen planus—a prospective randomized double-blind vehicle-controlled study. Br J Dermatol. 2008;159(4):936-941.

1. Chuang T-Y, Stitle L. http:/ / emedicine.medscape.com/ article/ 1123213-overview. Accessed September 20, 2011.

5. Habi TP. Clinical Dermatology:A Color Guide to Diagnosis andTherapy. 5th ed. Philadelphia, PA: Mosby; 2010.

19. Thongprasom K, Carrozzo M, Furness S, Lodi G. Interventions or treating oral lichen planus. Cochrane Database Syst Rev. 2011 Jul 6;(7):CD001168.

6. Shengyuan L, Songpo Y, Wen W, et al. Hepatitis C virus and lichen planus: a reciprocal association determined by a meta-analysis. Arch Dermatol. 2009;145(9):1040-1047.

20. Rajar UD, Majeed R, Parveen N, et al. E f cacy o aloe vera gel in the treatment o vulval lichen planus. J Coll Physicians Surg Pak. 2008;18(10):612-614.

7. Di Fede O, Belf ore P, Cabibi D, et al. Unexpectedly high requency o genital involvement in women with clinical and histological eatures o oral lichen planus. Acta DermVenereol. 2006;86(5):433-438.

21. McPherson T, Cooper S. Vulval lichen sclerosis and lichen planus. Dermatol Ther. 2010;23(5):523-532.

8. Imail SB, Kumar SK, Zain RB. Oral lichen planus and lichenoid reactions: etiopathogenesis, diagnosis, management and malignant trans ormation. J Oral Sci. 2007;49(2):89-106. 9. Cevacso NC, Berg eld WF, Remzi BK, de Knott HR. A case-series o 29 patients with lichen planopilaris: the Cleveland Clinic Foundation experience on evaluation, diagnosis, and treatment. JAmAcad Dermatol. 2007;57(1):47-53. 10. Lodi G, Scully C, Carrozzo M, et al. Current controversies in oral lichen planus: report o an international consensus meeting, part 2. Clinical management and malignant trans ormation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100:164-178. 11. Cribier B, Frances C, Chosidow O. Treatment o lichen planus. An evidence-based medicine analysis o e f cacy. Arch Dermatol. 1998;134(12):1521-1530.

22. Thongprasom K, Dhanuthai K. Steroids in the treatment o lichen planus: a review. J Oral Sci. 2008;50(4):377-385. 23. Asch S, Goldenberg G. Systemic treatment o cutaneous lichen planus: an update. Cutis. 2011;87(3):129-134. 24. Wackernagel A, Legat FJ, Ho er A, et al. Psoralen plus UVA vs. UVB-311 nm or the treatment o lichen planus. Photodermatol Photoimmunol Photomed. 2007;23(1):15-19. 25. van der Hem PS, Egges M, van der Wal JE, Roodenburg JL. CO2 laser evaporation o oral lichen planus. Int J Oral Maxillofac Surg. 2008;37(7):630-633. 26. Ca aro A, Albanese G, Arduino PG, et al. E ect o low-level laser irradiation on unresponsive oral lichen planus: early preliminary results in 13 patients. Photomed Laser Surg. 2010;28(suppl 2): S99-S103.

PART 14 DERMATO LO GY

REACTIVE ARTHRITIS

153 REACTIVE ARTHRITIS He id i Chumle y, MD Ang e la She d d , MD Suraj Re d d y, MD Richard P. Usatine , MD

PATIENT STO RY A 29-year-old man presented with concerns about an extensive rash that had developed over the previous month. The rash was reported to involve the scalp, abdomen, penis, hands, and eet (Figures 153-1 to 153-5). He also complained o severe joint pain, involving the back, knees, and eet. He denied ocular, gastrointestinal (GI), or genitourinary (GU) complaints, but was prescribed a course o antibiotics last month when his partner was diagnosed with Chlamydia. The patient’s young age, rapid onset o symptoms, dermatologic ndings, and arthritis were suggestive o reactive arthritis. The patient’s joint pain was treated with nonsteroidal anti-inf ammatory drugs (NSAIDs) and skin lesions were treated with topical corticosteroids. No antibiotics were prescribed because no current in ectious agent was identi ed. In conjunction with a dermatologist, acitretin 25 mg daily was started to treat his psoriasi orm lesions.

INTRO DUCTIO N Reactive arthritis is a nonin ectious acute oligoarthritis that occurs in response to an in ection, most commonly in the GI or urogenital tract. Patients present 1 to 4 weeks a ter the triggering in ection, with joint pain in asymmetric large joints; eye disease, such as conjunctivitis; and skin changes including erythema nodosum, keratoderma blennorrhagicum, and circinate balanitis. Diagnosis is based on the clinical presentation plus

FIGURE 153-1 Re active arthritis in a young man showing annular scalp le sions (circinate p laq ue s). (Re p ro d uce d with p e rmission fro m She d d AD, Re d d y SG, Me ffe rt JJ, Kraus EW. Acute onse t of rash and olig oarthritis. J Fam Pract. 2007;56(10):811-814. Re p rod uce d with p e rmission from Frontline Me d ical Co mmunications.)

FIGURE 153-2 Ke ratod e rma b le nnorrhag icum with hyp e rke ratotic p ap ule s, p laq ue s, and p ustule s that have coale sce d to orm circular b ord e rs. (Re p rod uce d with p e rmission from She d d AD, Re d d y SG, Me ffe rt JJ, Kraus EW. Acute onse t of rash and olig oarthritis. J Fam Pract. 2007;56(10):811-814. Re p rod uce d with p e rmission from Frontline Me d ical Communications.)

evidence o associated in ection. Treatment includes anti-inf ammatory medications and treatment o triggering in ection.

SYNO NYMS Reiter syndrome is no longer the pre erred name as Dr. Reiter was a Nazi physician who per ormed unethical experimentation on human subjects.

FIGURE 153-3 Erythe ma and scale se e n o n the toe s o the p atie nt in Fig ure 153-1. No te the nail involve me nt with sub ung ual ke ratosis and onycholysis. The ourth toe is re d and swo lle n; this is calle d d actylitis. (Re p ro d uce d with p e rmission from She d d AD, Re d d y SG, Me ffe rt JJ, Kraus EW. Acute onse t of rash and olig oarthritis. J Fam Pract. 2007;56(10):811-814. Re p rod uce d with p e rmission from Frontline Me d ical Communications.)

757

758

PART 14 DERMATO LO GY

CHApTER 153

RISK FACTO RS • In ection with a triggering agent. • Presence o human leukocyte antigen (HLA)-B27 is associated with an increased risk o chronic disease and a more severe arthritis. • HLA-B27 has been ound in a high percentage o patients with severe disease, but there is no increase in HLA-B27 prevalence in population studies.

DIAGNO SIS De nite reactive arthritis: Two major criteria and one minor criterion Probable reactive arthritis: one major criterion and one minor criterion FIGURE 153-4 The p atie nt in Fig ure 153-1 with p soriasi orm le sion on the corona and g lans. The p atie nt also has e rythe ma in the ing uinal are a that re se mb le s inve rse p soriasis. This p articular case d oe s not e xe mp li y classic b alanitis circinata, which is characte rize d b y annular or arcuate thin scaly p laq ue s, as op p ose d to the nonsp e ci c scaly p laq ue s ound on this p atie nt. (Re p rod uce d with p e rmission from Suraj Re d d y, MD.)

Major criteria • Arthritis with 2 o 3 eatures: asymmetric, mono- or oligoarthritis, lower limbs predominately a ected • Preceding enteritis or urethritis Minor criteria

EPIDEMIO LO GY

• Evidence o triggering in ection • Evidence o synovial in ection

• Incidence is 0.6 to 27 per 100,000 people. 1 • Most common in young adults ages 30 to 40 years, rare in children. 1 • Reactive arthritis a ter a GU in ection is more common in young men; reactive arthritis a ter a GI in ection is equally common in men and women.1

ETIO LO GY AND PATHO PHYSIO LO GY

CLINICAL FEATURES • The classic triad consists o urethritis, conjunctivitis (Figure 153-6), and arthritis; however, ew patients present with the classic triad. • Tendinitis, bursitis or enthesitis, or low back pain may be present.

• Follows a GI (Yersinia, Salmonella, Shigella, Campylobacter, or rarely Escherichia coli or Clostridium di f cile) or GU (Chlamydia trachomatis, Ureaplasma urealyticum) in ection, less commonly ollows a respiratory in ection with Chlamydia pneumonia. • Mechanism by which the triggering agent leads to development o arthritis is not ully understood.

FIGURE 153-5 Psoriatic-ap p e aring p laq ue on the le g in the same p atie nt o Fig ure 153-1 with re active arthritis. (Re p rod uce d with p e rmission from She d d AD, Re d d y SG, Me ffe rt J J , Kraus EW. Acute o nse t o f rash and olig o arthritis. J Fam Pract. 2007;56(10):811-814. Re p rod uce d with p e rmission from Frontline Me d ical Communicatio ns.)

FIGURE 153-6 Re active arthritis with conjunctivitis as a re sult o chlamyd ial p e lvic inf ammatory d ise ase in a 42-ye ar-old woman. She p re se nte d with e ve r, chills, and g e ne ralize d p ain in he r jo ints, ab d ome n, and p e lvis. (Re p ro d uce d with p e rmissio n from J o se p h Mazzio tta, MD, and from Mazzio tta JM, Ahme d N. Conjunctivitis and ce rvicitis. J Fam Pract. 2004;53(2):121-123. Re p rod uce d with p e rmission from Frontline Me d ical Communications.)

REACTIVE ARTHRITIS

FIGURE 153-7 Ke ratod e rma b le nnorrhag icum on the sole s o the oot o a man with re active arthritis. (Re p rod uce d with p e rmission from Ricard o Zunig a-Monte s, MD.)

• Skin ndings (psoriasi orm) typically involve the palms, soles (keratoderma blennorrhagicum) (Figures 153-2 and 153-7), and the glans penis (balanitis circinata). Nail dystrophy, thickening, and destruction may occur (Figures 153-3 and 153-8). Many other body sur aces may be a ected including the scalp (see Figure 153-1), intertriginous areas (see Figure 153-4), and the oral mucosa (Figure 153-9). Erosive lesions on the tongue and hard palate may be seen. • Rarely, carditis and atrioventricular conduction disturbances are present.

PART 14 DERMATO LO GY

FIGURE 153-9 O ral mucosal inf ammation with re active arthritis se cond ary to chlamyd ial p e lvic inf ammatory d ise ase . The ce rvix was also inf ame d on e xamination. (Re p rod uce d with p e rmission from Jose p h Mazziotta, and from Mazziotta JM, Ahme d N. Conjunctivitis and ce rvicitis. J Fam Pract. 2004;53(2):121-123. Re p rod uce d with p e rmission from Frontline Me d ical Communications.)

LABO RATO RY TESTING • No speci c laboratory test is used to con rm reactive arthritis. • Erythrocyte sedimentation rate (ESR) and C-reactive protein are usually elevated. • Urethral/ cervical swab or urine test or C. trachomatis when a GU in ection precedes the onset o symptoms. • Stool culture may detect an enteric pathogen when GI in ection precedes the onset o symptoms. • Salmonella, Yersinia, and Campylobacter antibodies can be detected in the serum a ter microbes are no longer detectable in the stool. • Skin biopsy i per ormed resembles that o psoriasis with acanthosis o the epidermis, a neutrophilic perivascular in ltrate, and spongi orm pustules.

DIFFERENTIAL DIAGNO SIS • Spondyloarthropathies and reactive arthropathies may present with acute joint pain but o ten lack the skin ndings seen with reactive arthritis (see Chapter 101, Ankylosing Spondylitis). • Psoriatic arthritis may be easily con used especially in immunocompromised patients. Lack o constitutional symptoms and a more chronic course help di erentiate rom reactive arthritis. • Gonococcal arthritis is characterized by migratory polyarthralgia that settles in one or more joints. O ten erythematous macules or hemorrhagic papules on acral sites help distinguish rom reactive arthritis. FIGURE 153-8 Nail d ystrop hy, thicke ning , and nail d e struction in a man with re active arthritis. (Re p rod uce d with p e rmission from Ricard o Zunig aMonte s, MD.)

• Rheumatoid arthritis o ten presents with a progressive, symmetric polyarthritis o the small joints o the hands and wrists. Females are a ected more o ten than males (see Chapter 99, Rheumatoid Arthritis).

759

PART 14 DERMATO LO GY

760

MANAGEMENT • Treat patients with acute C. trachomatis with 1 g azithromycin single dose or 100 mg doxycycline twice a day or 7 days. 1,2 SO R Treat partners when possible. 1 • The current recommendation no longer calls or long-term antibiotics as studies do not support this previous treatment. 3,4 SO R B

CHAPTER 153

FO LLO W-UP Follow patients closely at the time o diagnosis to ensure response to therapy and timely re erral or nonresponders. PATIENT RESO URCES

• GI-triggering in ections are typically sel -limiting and do not require antibiotics.

• FamilyDoctor.org. Reactive Arthritis—http:/ / familydoctor .org/ familydoctor/ en/ diseases-conditions/ reactive-arthritis.html.

• Treat inf ammation with NSAIDs. 2 SO R B

PRO VIDER RESO URCES

• Consider glucocorticoid joint injections in patients with severe joint pain.

• Medscape. Reactive Arthritis—http:/ / emedicine.medscape .com/ article/ 331347.

• For re ractory arthritic disease, immunosuppressive agents, such as sul asalazine at 2000 mg/ d, have demonstrated some bene it. 5 SO R B

PATIENT EDUCATIO N

• Treat mucosal and skin lesions with topical corticosteroids. • Psoriasi orm skin lesions may be treated with some o the same medications used to treat psoriasis (including acitretin). SO R C • Systemic steroids are indicated or patients with systemic symptoms ( ever) or in those who develop carditis. • Current evidence demonstrates that chronic antimicrobial therapy is not recommended. 3,4 REFERRAL • Re er patients with severe or nonresponsive joint pain to a rheumatologist. • Re er patients who develop cardiac mani estations to a cardiologist.

PRO GNO SIS • Arthritic symptoms typically resolve in 3 to 5 months. 1 Persistent symptoms that last longer than 6 months are associated with the development o chronic symptoms. • Sixteen percent to 68% o patients developed chronic symptoms across several studies. Type o triggering in ection and presence o HLA-B27 a ect prognosis.

There is no curative treatment. Symptoms may resolve permanently, relapse, or persist. Medications and physical or occupational therapy can help relieve pain and preserve unction. Seek medical care or extraarticular symptoms, especially those involving the eye. REFERENCES 1. Hannu T. Reactive arthritis. Best Pract Res Clin Rheumatol. 2011;25(3):347-357. 2. Colmegna I, Cuchacovich R, Espinoza LR. HLA-B27-associated reactive arthritis: pathogenetic and clinical considerations. Clin Microbiol Rev. 2004;17(2):348-369. 3. Kvien TK, Gaston JS, Bardin I, et al. Three months treatment o reactive arthritis with azithromycin: a EULAR double blind, placebo controlled study. Ann Rheum Dis. 2004;63(9):1113-1119. 4. Putschky N, Pott HG, Kuipers JG, et al. Comparing 10-day and 4-month doxycycline courses or treatment o Chlamydia trachomatis– reactive arthritis: a prospective, double-blind trial. Ann Rheum Dis. 2006;65(11):1521-1524. 5. Clegg DO, Reda DJ, Weisman MH, et al. Comparison o sul asalazine and placebo in the treatment o reactive arthritis (Reiter’s syndrome). A Department o Veterans A airs Cooperative Study. Arthritis Rheum. 1996;39(12):2021-2027.

PART 14 DERMATO LO GY

ERYTHRO DERMA

154 ERYTHRO DERMA David He nd e rson, MD Richard P. Usatine , MD

PATIENT STO RY A 34-year-old man presented with red skin rom his neck to his eet or the last month (Figure 154-1). He was having a lot o itching and his skin was shedding so that wherever he would sit, there would be a pile o skin that would remain. He denied ever and chills. He admitted to smoking and drinking heavily. The patient’s vital signs were stable with normal blood pressure and he pre erred not to be hospitalized. He had some nail pitting but no personal or amily history o psoriasis. The presumed diagnosis was erythrodermic psoriasis but a punch biopsy was done to con rm this. A complete blood count (CBC) and chemistry panel were ordered in anticipation o the patient needing systemic medications. A puri ed protein derivative (PPD) was also placed. The patient was started on total body 0.1% triamcinolone under wet wrap overnight and given a ollow-up appointment or the next day. The patient was also counseled to quit smoking and drinking. The ollowing day his laboratory results showed mild elevation in his liver unction tests (LFTs) only. The ollowing day his PPD was negative and he was already eeling a bit better rom the topical triamcinolone. Cyclosporine was started and the patient improved rapidly.

INTRO DUCTIO N Erythroderma is an uncommon condition that a ects all age groups. It is characterized by a generalized erythematous rash with associated scaling.

It is generally a mani estation o another underlying dermatosis or systemic disorder. It is associated with a range o morbidity, and can have li e-threatening metabolic and cardiovascular complications. Therapy is usually ocused on treating the underlying disease, as well as addressing the systemic complications.

SYNO NYMS Erythroderma is also known as ex oliative dermatitis.

EPIDEMIO LO GY Erythroderma or ex oliative dermatitis is an uncommon condition that is generally a mani estation o underlying systemic or cutaneous disorders. • It a ects all age groups, rom in ants to elderly people. • In adults, the average age o onset is 41 to 61 years, with a male-toemale ratio o 2:1 to 4:1. 1 • It accounts or approximately 1% o all dermatologic hospital admissions. 2 • It can be a very serious condition resulting in metabolic, in ectious, cardiorespiratory, and thermoregulatory complications. 3

ETIO LO GY AND PATHO PHYSIO LO GY In almost 50% o cases, erythroderma occurs in the setting o a preexisting dermatosis; however, it may also occur secondary to underlying systemic disease, malignancy, and drug reactions. It is classi ed as idiopathic in 9% to 47% o cases. 3 • The pathophysiology is not ully understood, but it is related to the pathophysiology o the underlying disease. However, the actors that promote the development o erythroderma are not well de ned. • The rapid maturation and migration o cells through the epidermal layer results in excessive scaling. The rapid turnover o the epidermis also results in f uid, electrolyte, and protein losses that may have severe metabolic consequences, including heart ailure and acute respiratory distress syndrome. 4 • The underlying pathogenesis may be an interaction o immunologic modulators, including interleukins 1, 2, and 8, as well as tumor necrosis actor. 2 Table 154-1 presents the conditions most commonly associated with erythroderma. Dermatologic conditions commonly associated with erythroderma include the ollowing1-5: • Psoriasis, especially generalized pustular psoriasis with ex oliation (Figures 154-1 to 154-3) • Atopic dermatitis (Figure 154-4)2,3 • Contact dermatitis (Figure 154-5) • Seborrhea (see Figure 154-5) • Pityriasis rubra pilaris • Bullous pemphigoid4

FIGURE 154-1 Erythrod e rmic p soriasis in a 34-ye ar-old man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Impetigo herpeti ormis4 • Photosensitivity reaction4

761

PART 14 DERMATO LO GY

762

CHApTER 154

TABLE 154-1 Cond itions Most Commonly Associate d With Erythrod e rma

De rmat o se s

Infe ct io ns

Syst e mic/ Cance r

Pe d iat ric

Drug s

Psoriasis (Fig ure s 154-1, 154-2, 154-3, and 154-8)

HIV

Sarcoid osis

O me nn synd rome

Pe nicillins

Atop ic d e rmatitis (Fig ure 154-4)

Norwe g ian scab ie s

Thyrotoxicosis

Kwashiorkor

Sul onamid e s

Contact d e rmatitis (Fig ure 154-5)

He p atitis

Gra t-ve rsus-host re action

Cystic f b rosis

Te tracycline d e rivative s

Se b orrhe a (Fig ure 154-5)

Murine typ hus (Fig ure 154-6)

De rmatomyositis

Amino acid d isord e rs

Sul onylure as

Pityriasis rub ra p ilaris

Human he rp e svirus 6

Lung cance r

Immunod e f cie ncy

Calcium channe l b locke rs

Photose nsitivity re action

Toxic shock synd rome

Colon cance r

Cap top ril

Bullous p e mp hig oid

Stap hylococcal scald e d skin synd rome

Prostate cance r

Thiazid e s

Imp e tig o he rp e ti ormis

Histop lasmosis Tub e rculosis

Bre ast cance r B- and T-ce ll lymp homa (Fig ure 154-7) Le uke mia

NSAIDs Barb iturate s Vancomycin Lithium Antivirals Antimalarials

Erythroderma may also occur secondary to a number o in ectious diseases, including the ollowing: • HIV • Tuberculosis • Norwegian scabies • Hepatitis • Murine typhus (Figure 154-6) • Human herpesvirus 64

• Toxic shock syndrome4 • Staphylococcal scalded skin syndrome4 • Histoplasmosis3 Systemic diseases associated with erythroderma include the ollowing: • • • •

Sarcoidosis Thyrotoxicosis Gra t-versus-host reaction Dermatomyositis3,4

The exact incidence o erythroderma in association with underlying malignancy is not known but reticuloendothelial neoplasms are the most common, most notably T-cell lymphomas. 1,2 It may precede or ollow the diagnosis o cutaneous T-cell lymphoma, and chronic idiopathic erythroderma carries a high risk o development o cutaneous T-cell lymphoma over time (Figure 154-7). 5 In addition colon, lung, prostate, and thyroid malignancies account or 1% o cases o erythroderma. 2 Speci cally in children, it may be associated with the ollowing: • Kwashiorkor • Cystic brosis • Amino acid disorders1-5

FIGURE 154-2 Erythrod e rmic p soriasis with she e ts o e x oliation causing d e hyd ration and li e -thre ate ning illne ss. This is se cond ary to g e ne ralize d p ustular p soriasis. (Re p rod uce d with p e rmission from Jack Re sne ck, Sr., MD.)

Drug reactions are a common cause o erythroderma. The list o drugs associated with erythroderma is extensive and includes both systemic and topical medications, many o which are very commonly used, including a number o herbal, homeopathic, and ayurvedic medications. 5 The list o medications includes the ollowing: • Penicillins • Sul onamides

PART 14 DERMATO LO GY

ERYTHRO DERMA

A

FIGURE 154-4 Erythrod e rma atop ic d e rmatitis in a 55-ye ar-old woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Tetracycline derivatives • Sul onylureas • Calcium channel blockers • Captopril • Thiazides • Nonsteroidal anti-inf ammatory drugs (NSAIDs) • Barbiturates • Lithium2,3,5 In children, an association with topical boric acid has been identi ed. 5 The cause o erythroderma may not always be identi ed (Figure 154-8).

DIAGNO SIS CLINICAL FEATURES • The clinical presentation o erythroderma may be variable depending on the underlying cause. In association with drug reactions, the onset tends to be more abrupt and the resolution more rapid.

B FIGURE 154-3 A. Ge ne ralize d p ustular p soriasis causing a li e -thre ate ning case o e rythrod e rma in a 67-ye ar-old woman. This all starte d 3 we e ks b e ore p re se ntation and she had no p re vious history o p soriasis. Patie nt was hosp italize d and tre ate d with top ical ste roid s and oral acitre tin with g ood re sults. B. Close -up o p oste rior thig h showing p ustule s on an e rythe matous p laq ue in a ne w case o e rythrod e rma rom g e ne ralize d p ustular p soriasis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Cutaneous mani estations begin with pruritic, erythematous patches that spread and coalesce into areas o erythema that cover the body. Scaling eventually develops. Large scales are seen more o ten in acute settings and in chronic erythroderma smaller scales predominate. • Although the red color o erythroderma is very evident in light skin, erythroderma may be only light pink to brown in darker-skinned individuals (Figure 154-9). • Scalp involvement is very common with alopecia occurring in 25% o patients. 2 • Systemic mani estations associated with compromise o the protective cutaneous barrier and loss o vasoconstriction o vessels in the dermis that occurs in erythroderma include loss o f uid and electrolytes.

763

PART 14 DERMATO LO GY

764

CHApTER 154

FIGURE 154-6 Murine typ hus causing e rythe ma and e x oliation in a e b rile syste mically ill man in southe rn Te xas. (Re p rod uce d with p e rmission from Ang e la Pe ng , MD.)

A

TYPICAL DISTRIBUTIO N The distribution is variable, but there is usually sparing o mucous membranes, the palms, and the soles o the eet. Sparing o the nose and nasolabial region has also been reported. 2 LABO RATO RY STUDIES Skin biopsy is use ul, but o ten nondiagnostic. Because 50% o individual biopsies ail to reveal a speci c diagnosis, multiple biopsies are recommended when evaluating patients or erythroderma. In addition to conventional histopathologic evaluation, direct immunof uorescence may

B FIGURE 154-5 A. Erythrode rma cause d by seborrheic dermatitis and contact dermatitis. The biopsy showed change s consistent with seborrheic d ermatitis but the history sugg ested that the erythroderma was worsened b y contact with products used in auto maintenance. B. A ter the erythrode rma cleared, the arms and hand s would worsen every time the patient went back to working on cars. (Reproduced with pe rmission from Richard P. Usatine , MD.)

• Protein losses can be as high as 25% to 30% in psoriatic erythroderma, resulting in hypoalbuminemia and edema. 3 Increased per usion to denuded inf amed skin may result in thermoregulatory disturbances and high output cardiac ailure. In addition, there is an increased risk o staphylococcal in ection and sepsis. 2,3 Any o these complications can be li e threatening.

FIGURE 154-7 Erythe ma se cond ary to ne w-o nse t mycosis ung oid e s. (Re p rod uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

PART 14 DERMATO LO GY

ERYTHRO DERMA

A

FIGURE 154-8 Erythrod e rmic p soriasis in a b lack man showing visib le scaling b ut le ss ob vious e rythe ma se cond ary to the d arke r skin color. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

be help ul in immunobullous disease (eg, pemphigus). T-cell receptor gene rearrangement studies may aid in the diagnosis o lymphoproli erative disorders. 3 Laboratory tests are o ten nonspeci c; however, common ndings include the ollowing: • Leukocytosis • Lymphocytosis • Mild anemia • Eosinophilia • Elevated sedimentation rate • Polyclonal gammopathy • Elevated immunoglobulin (Ig) E levels • Hypoalbuminemia • Elevated serum creatinine • Elevated uric acid levels1-5 HIV testing should be considered in those with risk actors. 5 In children a sweat test, zinc, amino acid, and lipid levels should be considered. 5

DIFFERENTIAL DIAGNO SIS Erythroderma is the dermatologic mani estation o a number o underlying disease processes, including in ectious diseases, lymphoproli erative disorders, malignancies, dermatoses, acquired and inborn metabolic disorders, and drug reactions. The key to proper diagnosis and treatment is contingent on identi cation o the underlying cause. 1-5 (For a list o underlying conditions, see “Etiology and Pathophysiology” earlier.)

B FIGURE 154-9 A. Comp le te e rythrod e rma o unknown e tiolog y with e xtre me re d d e ning o the skin and e x oliation. B. The b ack o the same p atie nt with a close r vie w o the e x oliation. (Re p rod uce d with p e rmission from Gwe n De nton, MD.)

MANAGEMENT Hospitalization and urgent dermatologic re erral should be considered or patients presenting with erythroderma acutely as the metabolic, in ectious, thermoregulatory, and cardiovascular complications can be li e threatening (see Figures 154-1 to 154-9). 2,5 Therapeutic interventions include the ollowing: • Topical skin care measures such as emollients, oatmeal baths, and wet dressings. 1-5 SO R • Mid-potency topical steroid ointments such as 0.1% triamcinolone applied to all the a ected areas. 1-5 SO R Using the wet wrap

765

PART 14 DERMATO LO GY

766

technique (see Chapter 143, Atopic Dermatitis) can help promote quicker absorption and aster onset o action. SO R • High-potency topical steroids and topical immunomodulators should be avoided owing to risk o increased cutaneous absorption. 3 SO R

CHAPTER 154

risk o recurrence. Relapses occur in 15% o patients with psoriatic erythroderma. Fi ty percent o patients with idiopathic erythroderma experience partial remission, and one-third complete remission. 3

• Systemic steroids are use ul in drug reactions and eczema, but should be avoided in psoriasis. 2,3,5 SO R

PATIENT RESO URCES

• Consider methotrexate, cyclosporine, or cases secondary to psoriasis. Inf iximab has also been used (see Figures 154-3 to 154-5). 2,4 SO R Cyclosporine acts most rapidly in cases caused by psoriasis or atopic dermatitis. SO R

PRO VIDER RESO URCES

• Immunosuppressive agents (methotrexate, azathioprine, inf iximab). 2-4 SO R

• Discontinuation o all nonessential medications. 2,3 SO R • Antibiotic therapy when in ection is suspected. 2,3 SO R • Close monitoring o f uid, electrolyte, and nutritional status and replacement o de cits. 1-5 SO R

PATIENT EDUCATIO N Patients should be advised that erythroderma can be li e threatening because o the in ectious, thermoregulatory, metabolic, and cardiovascular complications. This is important when it might be necessary to hospitalize a patient who does not appreciate the seriousness o the condition. They should also be advised that with certain underlying etiologies, the condition may recur. This is particularly true o idiopathic erythroderma (see Figure 154-8).

FO LLO W-UP The prognosis in erythroderma is very much dependent on the underlying cause. Most deaths occur in malignancy-associated erythroderma. Drug-induced erythroderma carries the best prognosis and the lowest

• Health-Disease—a family medical guide—http:/ / www .health-disease.org/ skin-disorders/ erythroderma.htm. • Medscape. Erythroderma (Generalized Exfoliative Dermatitis)— http:/ / emedicine.medscape.com/ article/ 1106906. • DermNet NZ. Erythroderma—http:/ / www.dermnetnz.org/ reactions/ erythroderma.html. • DermIS. Congenital Ichthyosiform and Psoriatic Erythroderma— http:/ / www.dermis.net/ dermisroot/ en/ list/ erythroderma/ search.htm.

REFERENCES 1. Rothe MJ, Bialy TL, Grant-Kels JM. Erythroderma. Dermatol Clin. 2000;18:405-415. 2. Karakayli G, Beckham G, Orengo I, Rosen T. Ex oliative dermatitis. Am Fam Physician. 1990;59(3):625-630. 3. Rothe JH, Bernstein ML, Grant-Kels JM. Li e-threatening erythroderma: diagnosing and treating the “red man”. Clin Dermatol. 2005;23(2):206-217. 4. Grant-Kels JM, Bernstein ML, Rothe MJ. Ex oliative dermatitis. In: Wol K, Goldsmith LA, Katz SI, Gilchrest B, Paller AS, Le ell DJ, eds. Fitzpatrick’s Dermatology in General Medicine. 7th ed. http:/ / www. accessmedicine.com/ content.aspx?aID= 2984502# 2984502. 5. Sehgal VN, Srivastava G. Erythroderma/ generalized ex oliative dermatitis in pediatric practice: an overview. Int J Dermatol. 2006;45:831-839.

PART 14 DERMATO LO GY

SKIN TAG

SECTIO N 8

BENIGN NEO PLASMS

155 SKIN TAG Mind y A. Smith, MD, MS

PATIENT STO RY A 55-year-old man requests removal o multiple skin tags around his neck. He is overweight and has diabetes and acanthosis nigricans. Although some o his skin tags occasionally get caught on his clothing, he just does not like the way they look. The patient chose to have many o them removed by the snip excision method.

INTRO DUCTIO N Skin tags (acrochordons) are esh-colored, pedunculated lesions that tend to occur in areas o skin olds especially around the neck and in the axillae.

FIGURE 155-1 Many skin tags and acanthosis nigricans on the ne ck o a man with d iab e te s. (Re produce d with pe rmission from Richard P. Usatine , MD.)

SYNO NYMS It is also re erred to as f broepithelial polyps.

EPIDEMIO LO GY • In an unselected population study, skin tags were ound in 46% o patients, particularly in patients who were obese. 1 • Skin tags increase in requency through the f th decade o li e so that as many as 59% o individuals have them by the time they are 70 years old; however, the increase slows a ter age 50 years. 1

ETIO LO GY AND PATHO PHYSIO LO GY • Three types o skin tags are described as below1: ° Small, urrowed papules o approximately 1 to 2 mm in width and height, located mostly on the neck and the axillae (Figure 155-1). ° Single or multiple f li orm lesions o approximately 2 mm in width and 5 mm in length occurring elsewhere on the body (Figure 155-2). ° Large, pedunculated tumor or nevoid, bag-like, so t f bromas occur on the lower part o the trunk (Figure 155-3). • Etiology is unknown, but it is theorized that skin tags occur in localized areas with a paucity o elastic tissue resulting in sessile or atrophic lesions. In addition, hormone imbalances appear to acilitate their development (eg, high levels o estrogen and progesterone seen during pregnancy) and other actors including epidermal growth actor, tissue growth actor-α , and in ection (eg, human papillomavirus) have been implicated as co actors.

FIGURE 155-2 Fili orm p e d unculate d skin tag s on the e ye lid s. The se we re re move d with a rad io re q ue ncy lo op a te r local ane sthe sia with lid ocaine and e p ine p hrine to minimize b le e d ing . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 155-3 Larg e p e d unculate d b ag -like so t f b roma on the trunk. This is a larg e acrochord on or f b roe p ithe liomatous p olyp . Local ane sthe tic was g ive n p rior to e xcision. (Re p ro d uce d with p e rmission fro m Richard P. Usatine , MD.)

767

PART 14 DERMATO LO GY

768

Ch ApTe r 155

• Acrochordons also appear to be associated with impaired carbohydrate metabolism and diabetes mellitus (see Figure 155-1). 2 • Pedunculated lesions may become twisted, in arcted, and all o spontaneously. • Very rarely neoplasms are ound at the base o skin tags. In a study o consecutive cutaneous pathology reports, 5 o 1335 clinically diagnosed f broepithelial polyp specimens were malignant (ie, 4 were basal cell carcinomas and 1 was squamous cell carcinoma in situ). 3 There is selection bias in this study because most skin tags are not sent to the pathologist.

DIAGNO SIS CLINICAL FEATURES • Small, so t, usually pedunculated lesions. • Skin colored or hyperpigmented. • Most vary in size rom 2 to 5 mm, but larger ones may be seen.

FIGURE 155-4 Multip le so t ne urof b romas o n the ne ck o a p atie nt with ne urof b romato sis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Usually asymptomatic, but can be pruritic or become pain ul and in amed by catching on clothing or jewelry.

MANAGEMENT

TYPICAL DISTRIBUTIO N Most typically seen on the neck and in the axillae (see Figure 155-1), but any skin old may be a ected. They are also seen on the trunk (see Figure 155-3), the abdomen, and the back. ANCILLARY TESTING Dermatoscopy may be a use ul diagnostic tool to analyze acrochordonlike lesions in people with basal cell syndromes to acilitate early diagnosis and treatment. 4 BIO PSY Not usually indicated unless the diagnosis is not clear. Typical skin tags do not need to be sent to pathology upon removal. Skin tags, on histology, are characterized by acanthotic, attened, or rond-like epithelium. A papillary-like dermis is composed o loosely arranged collagen f bers and dilated capillaries and lymphatic vessels.

Skin tags may be removed or cosmetic reasons or because o irritation in a number o ways: • Small lesions may be snipped with a sharp iris scissor with or without anesthesia (Figure 155-5). • Larger skin tags and f bromas may be removed with shave excision a ter injecting with lidocaine and epinephrine. • I there is any bleeding, aluminum chloride on a cotton-tipped applicator is applied or hemostasis. • Electrodesiccation with or without anesthesia works or very tiny skin tags, too small to grab with the orceps. • Skin tags on the eyelids may be removed with a radio requency loop a ter local anesthesia with lidocaine and epinephrine to minimize bleeding.

DIFFERENTIAL DIAGNO SIS Lesions that can be con used with skin tags include the ollowing: • Warts—Cutaneous neoplasm caused by papilloma virus. Sessile, dome-shaped lesions approximately 1 cm in diameter are seen with hyperkeratotic sur ace. Paring usually demonstrates a central core o keratinized debris and punctate bleeding points. • Neurof bromas—Benign Schwann cell tumors, cutaneous tumors tend to orm multiple, so t pedunculated masses (Figure 155-4). • Epidermal hyperplasia in melanocytic nevi (also called keratotic melanocytic nevus [KMN])—Although most common moles are round, tan to brown, less than 6 mm, and at to slightly elevated, some nevi have overlying hyperplastic epidermis resembling skin tags. In a study o melanocytic nevi submitted or pathology over an 8-month period, 6% were KMN, most o ten located on the trunk (76%). 5 Dermal nevi can be pedunculated but they are usually larger than skin tags and may appear warty above the stalk. • Basal cell carcinomas in certain syndromes.

4,6

FIGURE 155-5 Snip e xcision o skin tag with iris scissors and no ane sthe sia. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

SKIN TAG

PATIENT RESO URCES

• MedlinePlus. Cutaneous skin tag— http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000848.htm. PRO VIDER RESO URCES

• For quick cryosurgery of skin tags, the Cryo Tweezer can be ordered rom—http:/ / www.brymill.com/ . For detailed in ormation on the treatment o skin tags see: • Usatine R, Pfenninger J, Stulberg D, and Small R. Dermatologic and Cosmetic Procedures in O f ce Practice. Elsevier, Inc., Philadelphia. 2012. • Usatine R, Stulberg D, Colver G. Cutaneous Cryosurgery. 4th Edition. Taylor and Francis, London, 2014. Both are available electronically through www.usatinemedia.com.

FIGURE 155-6 Cryothe rap y using Cryo Twe e ze rs to g rasp the skin tag without re e zing the skin around it. This is e sp e cially he lp ul on the e ye lid s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Cryotherapy can be applied directly to the skin tag with a Cryogun or a cotton-tipped applicator. One pre erred method involves dipping orceps into liquid nitrogen and then grasping the skin tag until it turns white. This allows you to grasp the skin tag without reezing the skin around it. This is especially help ul on the eyelids. A special cryo orceps is made by Brymill, Inc. that has more metal at the end to hold the cold longer (Figure 155-6). This is a very e f cient way to treat multiple skin tags quickly. • An adhesive patch that applies pressure to the base o a skin tag was ound e ective in 65% o skin tags in one case series. 7 • Most insurance companies will not pay or the cosmetic removal o skin tags. • To avoid large health care costs, only send suspicious looking skin tags to the pathologist.

FO LLO W-UP Follow-up is not usually necessary.

PATIENT EDUCATIO N Advise patients that these are benign growths that can be removed i irritation occurs or or cosmetic purposes. Patients who are overweight should be encouraged to lose weight or their general health and to avoid new skin tags.

REFERENCES 1. Banik R, Lubach D. Skin tags: localization and requencies according to sex and age. Dermatologica. 1987;174(4):180-183. 2. Demir S, Demir Y. Acrochordon and impaired carbohydrate metabolism. Acta Diabetol. 2002;39(2):57-59. 3. Eads TJ, Chuang TY, Fabre VC, et al. The utility o submitting f broepithelial polyps or histological examination. Arch Dermatol. 1996;132(12):1459-1462. 4. Feito-Rodríguez M, Sendagorta-Cudós E, Moratinos-Martínez M, et al. Dermatoscopic characteristics o acrochordon-like basal cell carcinomas in Gorlin-Goltz syndrome. JAmAcad Dermatol. 2009;60(5):857-861. 5. Horenstein MG, Prieto VG, Burchette JL Jr, Shea CR. Keratotic melanocytic nevus: a clinicopathologic and immunohistochemical study. J Cutan Pathol. 2000;27(7):344-350. 6. Lortscher DN, Sengelmann RD, Allen SB. Acrochordon-like basal cell carcinomas in patients with basal cell nevus syndrome. Dermatol Online J. 2007;13(2):21. 7. Fredriksson CH, Ilias M, Anderson CD. New mechanical device or e ective removal o skin tags in routine health care. Dermatol Online J. 2009;15(2):9.

769

770

PART 14 DERMATO LO GY

Ch a pt e r 156

156 SEBO RRHEIC KERATO SIS Mind y Smith, MD, MS Richard P. Usatine , MD

PATIENT STO RY An elderly woman noted a growth o a lesion on her chest (Figure 156-1). She was a raid that it might be melanoma. Her amily physician recognized the typical eatures o a seborrheic keratosis (SK) (stuck-on with visible horn cysts) and attempted to reassure her. Dermoscopy was per ormed and the eatures were so typical o SK; the physician was able to convince the patient not to have a biopsy (Figure 156-2). The black comedonallike openings and white milia-like cysts are typical o SK and can be seen with the naked eye and magni ed with a dermatoscope.

INTRO DUCTIO N SK is a benign skin tumor and a orm o localized hyperpigmentation as a result o epidermal alteration; it develops rom the proli eration o epidermal cells, although the cause is unknown.

FIGURE 156-2 De rmosco y of the se b orrhe ic ke ratosis in Fig ure 156-1 showing come d o-like o e ning s (b lack, like b lackhe ad s) and milia-like cysts (white , like milia). (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• In an Australian study per ormed in 2 general practices, 23.5% (40 out o 170) o individuals between ages 15 and 30 years had at least 1 SK; prevalence and size increased with age. 2 • Approximately hal o cases o multiple SKs occur within amilies, with an autosomal dominant mode o inheritance. 3

EPIDEMIO LO GY • It is the most common benign tumor in older individuals; requency increases with age. • In an older study o individuals older than age 64 years in North Carolina, 88% had at least one SK. Ten or more SKs were ound in 61% o the black men and women, 38% o the white women, and 54% o the white men in the study. 1

ETIO LO GY AND PATHO PHYSIO LO GY • In pigmented SKs, the proli erating keratinocytes secrete melanocytestimulating cytokines triggering activation o neighboring melanocytes. 3 • A high requency o mutations have been ound in certain types o SKs in the gene encoding the tyrosine kinase receptor broblast growth actor receptor 3 (FGFR3). 3 One study ound that FGFR3 and transcription actor orkhead box N1 (FOXN1) were highly expressed in SKs but close to undetectable in squamous cell skin cancer. 4 This may represent a positive regulatory loop between FGFR3 and FOXN1 that underlies a benign versus malignant skin tumor phenotype. • Reticulated SKs, usually ound on sun-exposed skin, may develop rom solar lentigines. 3 • Multiple eruptive seborrheic keratoses (the sign o Leser-Trélat) can be associated with internal malignancy (most o ten adenocarcinoma o the gastrointestinal [GI] tract) (Figure 156-3), 5 although this association has been questioned. 6 • An eruption o seborrheic keratoses may develop a ter an inf ammatory dermatosis such as severe sunburn or eczema. 3 There is also a report o exacerbation o SK by topical f uorouracil. 7

DIAGNO SIS SKs have a variety o appearances. CLINICAL FEATURES FIGURE 156-1 Se borrhe ic ke ratosis with associate d horn cysts. (Re produce d with p e rmission from Richard P. Usatine , MD.)

• Typically oval or round brown plaques with adherent greasy scale (Figure 156-4). • Color ranges rom black to tan (Figures 156-4 to 156-6).

Se BO r r h e IC Ke r a t O SIS

A

PART 14 DERMATO LO GY

FIGURE 156-4 Round e le vate d se b orrhe ic ke ratosis with ve ry visib le horn cysts. Horn cysts consist of ke ratin. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Lesions may be large (up to 35 × 15 cm), pigmented, and have irregular borders (see Figure 156-5). • Lesions can also be f at (Figure 156-7). • Many lesions show keratotic plugging o the sur ace (see Figures 156-1 and 156-2). • May have sur ace cracks and associated horn cysts (keratin- lled cystic structures). The dermoscopy terms or the horn cysts are comedo-like

B FIGURE 156-3 Multi le e ru tive se b orrhe ic ke ratose s as se e n in the sig n of Le se r-Tré lat. A. This 90-ye ar-old woman re se nte d with ascite s and a le thora of se b orrhe ic ke ratose s and was found to have me tastatic Me rke l ce ll carcinoma. B. This 49-ye ar-old man had many se b orrhe ic ke ratose s b ut no known cance r. While the sig n of Le se r-Tré lat is a arane o lastic synd rome most e o le with e xte nsive se b orrhe ic ke ratose s d o not have cance r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Most o ten have a velvety to nely verrucous sur ace and appear to be “stuck-on.” • Some are so verrucous that they can appear to be warty (see Figure 156-6).

FIGURE 156-5 Se borrhe ic ke ratosis that is lightly igme nte d, waxy, and a e ars stuck-on. (Re produce d with pe rmission from Richard P. Usatine , MD.)

771

772

PART 14 DERMATO LO GY

Ch a pt e r 156

FIGURE 156-6 Se b orrhe ic ke ratosis with ve rrucous a e arance on the fore he ad . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

openings and milia-like cysts (see Figures 156-1 and 156-2; see Appendix C, Dermoscopy). • Occasionally, lesions become irritated and can itch, grow, and bleed; secondary in ection may occur. • Variants o SK include the ollowing: ° Dermatosis papulosa nigra—Consists o multiple brown-black dome-shaped, smooth papules ound on the ace in young and middle-aged persons o color, predominantly A rican Americans (Figures 156-8 and 156-9). ° Stucco keratosis—Consists o large numbers o super cial gray-tolight brown f at keratotic lesions usually on the tops o the eet, the ankles, and the back o the hands and orearms (Figure 156-10).

FIGURE 156-7 Se b orrhe ic ke ratosis (SK) with irre g ular b ord e rs and variatio n in color that sug g e st a ossib le me lanoma. De rmosco y in traine d hand s can cle arly d e te rmine that this is a b e nig n SK without a b io sy. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 156-8 De rmatosis a ulosa nig ra with multi le se b orrhe ic ke ratose s on the face of a Ce ntral Ame rican woman. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

TYPICAL DISTRIBUTIO N • It is ound on trunk, ace, back, abdomen, extremities; not present on the palms and soles or on mucous membranes. May be present on the areola and breasts (Figures 156-11 and 156-12). • Dermatosis papulosa nigra is ound on the ace, especially the upper cheeks and lateral orbital areas (see Figures 156-8 and 156-9). IMAGING No imaging studies are needed unless there is a sudden appearance o multiple seborrheic keratoses as in the sign o Lesser-Trélat (see Figure 156-3). These are associated with adenocarcinoma o the GI tract, lymphoma, Sézary syndrome, and acute leukemia. 3,8

FIGURE 156-9 De rmatosis a ulosa nig ra on the che e ks and in the hairline . The atie nt was tre ate d e ffe ctive ly with cryothe ra y and had a g re at cosme tic re sult. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

Se BO r r h e IC Ke r a t O SIS

FIGURE 156-10 Stucco ke ratosis on the foot of an elderly man. (Re produced with p e rmission from Richard P. Usatine , MD.)

FIGURE 156-13 Me lanoma in situ on the late ral face of a 48-ye ar-old man. This re se mb le s a se b o rrhe ic ke ratosis b ut this larg e le sion also has all the ABCDEs (Color variation, Diame te r > 6 mm, Evolving ) of me lanoma and ne e d e d to b e b io sie d . (Re p ro d uce d with p e rmissio n from Richard P. Usatine , MD.)

BIO PSY Should be per ormed i there is a suspicion o melanoma (Figures 156-7 and 156-13). Some melanomas resemble SKs and a biopsy is needed to avoid missing the diagnosis o melanoma. Do not reeze or curette a suspicious SK; these need surgical intervention to send tissue to the pathologist.

DIFFERENTIAL DIAGNO SIS

FIGURE 156-11 Multi le se borrhe ic keratose s on the are ola of a 46-ye ar-old woman. Cryothe ra y cle are d the se b orrhe ic ke ratose s e asily. (Re produce d with p e rmission from Richard P. Usatine , MD.)

• Melanoma—When keratin plugs are visible in the sur ace o the SK, this helps to distinguish it rom a melanoma. Figure 156-7 is a SK that has the ABCDE eatures (asymmetry, border irregular, color variation, diameter >6 mm, evolving) o melanoma (see Chapter 170, Melanoma). A biopsy was per ormed and the lesion was proven to be benign. In Figure 156-13, a possible SK turned out to be a melanoma in situ. • Solar lentigo—Flat, uni ormly medium or dark brown lesion with sharp borders (see Chapter 166, Lentigo Maligna). These are f at and seen in sun-exposed areas, typically on the ace or back o the hands. Also called liver spots, these hyperpigmented areas are not palpable, whereas SK is a palpable plaque even when it is thin (see Figure 156-7). • Wart—Cutaneous neoplasm caused by papilloma virus (see Chapter 130, Common Warts). Sessile, dome-shaped lesions approximately 1 cm in diameter with hyperkeratotic sur ace. Paring usually demonstrates central core o keratinized debris and punctate bleeding points. • Pigmented actinic keratosis (AK)—Although most AKs are nonpigmented and do not look like a SK, occasionally a biopsy o an unknown pigmented plaque will be a pigmented AK secondary to sun damage (see Chapter 164, Actinic Keratosis and Bowen Disease). • An inf amed SK may be con used with a malignant melanoma or a squamous cell carcinoma and should be biopsied to determine the diagnosis.

FIGURE 156-12 Waxy se b orrhe ic ke ratose s on the b re asts of this 70-ye arold woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Even a basal cell carcinoma (BCC) can have eatures that suggest a SK (Figure 156-14) (see Chapter 168, Basal Cell Carcinoma).

773

PART 14 DERMATO LO GY

774

CHApTER 156

• Unless the SK is suspicious or cancer or inf amed, removal is or cosmetic purposes only and is o ten not covered by insurance. • Although SKs may resolve on occasion, spontaneous resolution does not ordinarily occur.

PATIENT RESO URCES

• MedkinePlus. Seborrheic keratosis— http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000884.htm. PRO VIDER RESO URCES

• Medscape. Seborrheic Keratosis— http:/ / emedicine.medscape .com/ article/ 1059477. For detailed in ormation on the treatment o SKs see: • Usatine R, Pfenninger J, Stulberg D, and Small R. Dermatologic and Cosmetic Procedures in O f ce Practice. Elsevier, Inc., Philadelphia. 2012 • Usatine R, Stulberg D, and Colver G. Cutaneous Cryosurgery. 4th Edition. Taylor and Francis, London, 2014 FIGURE 156-14 Basal ce ll carcinoma with surface cracks and a stuck-on a e arance re se mb ling an se b orrhe ic ke ratosis. The shave b io sy d e monstrate d the d iag nosis of b asal ce ll carcinoma. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

MANAGEMENT • Cryosurgery with liquid nitrogen, with a 1-mm halo, is a quick and easy treatment. The risks include pigmentary changes, incomplete resolution, and scarring. Hypopigmentation is the most common complication o this treatment, especially in dark-skinned individuals. • Removal o benign lesions by curettage assures complete removal without taking the normal tissue below. • Light electro ulguration can make the curettage so easy that it can be accomplished with a wet gauze pad. • I the diagnosis is uncertain but there are no eatures suggesting a melanoma, SK may be removed by shave biopsy and the tissue sent to pathology. • I melanoma or other skin cancers are suspected, per orm a ullthickness biopsy by punch or elliptical excision and send to pathology.

FO LLO W-UP Some experts suggest ollow-up or patients with multiple SKs because malignant tumors can develop elsewhere on the body and rarely within a SK. 3,8 SO R C

PATIENT EDUCATIO N • Reassure patients that SKs are benign lesions that do not become cancer. Although SKs may grow larger and thicker with time, this is not dangerous.

Both are available electronically through www.usatinemedia.com.

REFERENCES 1. Tindall JP, Smith JG. Skin lesions of the aged and their association with internal changes. JAMA. 1963;186:1039-1042. 2. Gill D, Dorevitch A, Marks R. The prevalence o seborrheic keratoses in people aged 15 to 30 years. Arch Dermatol. 2000;136:759-762. 3. Balin AK. Seborrheic Keratosis. http:/ / emedicine.medscape.com/ article/ 1059477-overview# a0104. Accessed May 29, 2011. 4. Mandinova A, Kolev V, Neel V, et al. A positive FGFR3/ FOXN1 eedback loop underlies benign skin keratosis versus squamous cell carcinoma ormation in humans. J Clin Invest. 2009;119(10): 3127-3137. 5. Ponti G, Luppi G, Losi L. Leser-Trélat syndrome in patients a ected by six multiple metachronous primitive cancers. J Hematol Oncol. 2010;3:2. 6. Lindelo B, Sigurgeirsson B, Melander S. Seborrheic keratoses and cancer. JAmAcad Dermatol. 1992;26(6):947-950. 7. Brodell EE, Smith E, Brodell RT. Exacerbation o seborrheic dermatitis by topical f uorouracil. Arch Dermatol. 2011;147(2):245-246. 8. Cascajo CD, Reichel M, Sanchez JL. Malignant neoplasms associated with seborrheic keratoses. An analysis o 54 cases. Am J Dermatopathol. 1996;18(3):278-282.

PART 14 DERMATO LO GY

SEBACEO US HYPERPLASIA

157 SEBACEO US HYPERPLASIA Mind y Smith, MD, MS

PATIENT STO RY A 65-year-old man noted a new growth on his ace or 1 year (Figure 157-1). On close examination, the growth was pearly with a ew telangiectasias. The doughnut shape and presence o sebaceous hyperplasia scattered on other areas o the ace were reassuring that this may be nothing but benign sebaceous hyperplasia (SH). To reassure the patient and to remove the lesion a shave biopsy was per ormed to rule out basal cell carcinoma (BCC). The patient was relieved when the pathology result was in act sebaceous hyperplasia. Additionally, he was pleased with the cosmetic result.

INTRO DUCTIO N SH is a common, benign condition o sebaceous glands consisting o multiple asymptomatic small yellow papules with a central depression. The sebaceous lobules o SH are greater in number and higher in the dermis than normal sebaceous glands and only one gland appears enlarged. 1 Consequently, the term hyperplasia appears to be a misnomer, and SH is more accurately classi ed as a hamartoma (disorganized overgrowth o tissue normally ound at that site). 1

EPIDEMIO LO GY

• The cells that orm the sebaceous gland, sebocytes, accumulate lipid material as they migrate rom the basal layer o the gland to the central duct where they release the lipid content as sebum. In younger individuals, turnover o sebocytes occurs approximately every month. • With aging, turnover o sebocytes slows; this results in crowding o primitive sebocytes within the sebaceous gland, causing a benign hamartomatous enlargement called SH. 1 • Genetic actors include overexpression o the aging-associated gene Smad7 and parathormone-related protein. 4 • There is no known potential or malignant trans ormation, but SH may be associated with nonmelanoma skin cancer in patients ollowing organ transplantation.

RISK FACTO RS • Older age • Associated with Muir-Torre syndrome (concurrent or sequential development o a sebaceous neoplasm and an internal malignancy or multiple keratoacanthomas, an internal malignancy, and a amily history o Muir-Torre syndrome) • Immunosuppression • Ultraviolet radiation4

DIAGNO SIS CLINICAL FEATURES • Lesions appear as yellowish, so t, small papules ranging in size rom 2 to 9 mm (Figures 157-1 to 157-3). 1 • Sur ace varies rom smooth to slightly verrucous.

• SH occurs in approximately 1% to 26% o the adult population; the latter number is rom a population study o hospitalized patients with a mean age o 82 years. 1 • The prevalence o SH is increased in those with immunosuppression by 10- old to 30- old1; or example, 10% to 16% o patients receiving long-term immunosuppression with cyclosporine in one study had SH. 2

• Lesions can be single or multiple. • Increasing number o lesions with aging; higher requencies a ter 40 to 50 years o age. 1 • In unctional amilial SH, lesions may appear thick and plaque like, with pores that resemble an orange peel; the skin in these patients is quite oily.1

• SH has been reported overlying other skin lesions including neuro bromas, melanocytic nevi, verruca vulgaris, and skin tags. 1 • Rare orms o SH include giant linear (up to 5 cm in diameter) and unctional amilial (also called premature or di use SH)3; the latter occurring typically around puberty as thick plaque-like lesions with pores resembling an orange peel. 1

ETIO LO GY AND PATHO PHYSIO LO GY • Sebaceous glands, a component o the pilosebaceous unit, are ound throughout the skin, everywhere that hair is ound. The greatest number is ound on the ace, chest, back, and the upper outer arms. • The glands are composed o acini attached to a common excretory duct. In some areas, these ducts open directly to the epithelial sur ace, including the lips and buccal mucosa (ie, Fordyce spots), glans penis or clitoris (ie, Tyson glands), emale areolae (ie, Montgomery glands), and eyelids (ie, meibomian glands). 1 • Sebaceous glands are highly androgen sensitive and become increasingly active at puberty and reach their maximum by the third decade o li e.

FIGURE 157-1 Larg e sing le le sion o se b ace ous hyp e rp lasia that was re move d b y shave b iop sy to con rm that it was not a b asal ce ll carcinoma. Doug hnut shap e is visib le . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

775

PART 14 DERMATO LO GY

776

FIGURE 157-2 Multip le le sio ns o se b ace ous hyp e rp lasia on the che e k and chin. Simultane ous ap p e arance o multip le le sions make s the m le ss like ly to b e b asal ce ll carcino ma. (Re p ro d uce d with p e rmissio n fro m Richard P. Usatine , MD.)

• Lesions may become red and irritated and bleed a ter scratching, shaving, or other trauma and may be associated with telangiectasias. • Central umbilication (doughnut shape) rom which a small amount o sebum can sometimes be expressed (see Figures 157-1 to 157-3). TYPICAL DISTRIBUTIO N Most commonly located on the ace, particularly the nose, cheeks, and orehead. May also be ound on the chest, areola, mouth, and, rarely, the vulva. 1,5 IMAGING Dermoscopy may aid in distinguishing between nodular BCC and SH; a vascular pattern with orderly winding, scarcely branching vessels extending toward the center o the lesion is speci c or hyperplastic sebaceous glands. 6

FIGURE 157-3 Larg e se b ace ous hyp e rp lasia on the ore he ad with te lang ie ctasias. Doug hnut shap e is visib le . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Ch a pt e r 157

FIGURE 157-4 Basal ce ll carcinoma on the ore he ad that could b e mistake n or se b ace ous hyp e rp lasia. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

BIO PSY Not usually necessary unless concerned about BCC.

DIFFERENTIAL DIAGNO SIS • Nodular BCC—These lesions can appear as waxy papules with a central depression that may ulcerate, most commonly located on the head, neck, and upper back. They may have a pearly appearance, sur ace telangiectases, and bleed easily (Figures 157-4 and 157-5). • Fibrous papule o the ace is a benign, rm, papule o 1 to 5 mm that is usually dome shaped and indurated with a shiny, skin-colored appearance. Most lesions are located on the nose and, less commonly, on the cheeks, chin, neck, and, rarely, the lip or orehead.

FIGURE 157-5 Close -up o same b asal ce ll carcinoma on the ore he ad in Figure 157-4 that shows irregular distribution o telangiectasias and lack o the doughnut shape. (Reproduced with permission from Richard P. Usatine, MD.)

PART 14 DERMATO LO GY

Se Ba Ce O US h Ype r pLa SIa

FIGURE 157-6 Syring omas and milia on the lowe r e ye lid o a 23-ye ar-old man. The milia are the white round e p id e rmal cysts and the syring omas are f e sh co lo re d and larg e r. (Re p ro d uce d with p e rmissio n from Richard P. Usatine , MD.)

• Milia are common, benign, keratin- lled cysts (histologically identical to epidermoid cysts) that occur in persons o all ages. They are 1 to 2 mm, super cial, uni orm, pearly-white to yellowish, domed lesions usually occurring on the ace (Figure 157-6). • Molluscum contagiosum are rm, smooth, usually 2- to 6-mm umbilicated papules that may be present in groups or widely disseminated on the skin and mucosal sur aces. The lesions can be f esh colored, white, translucent, or even yellow in color. Lesions generally are sel -limited but can persist or several years (see Chapter 129, Molluscum Contagiosum). • Syringoma is a benign adnexal neoplasm ormed by well-di erentiated ductal elements. They are 1- to 3-mm skin-colored or yellowish dermal papules with a rounded or f at top arranged in clusters, and symmetrically distributed primarily on the upper parts o the cheeks and lower eyelids (see Figure 157-6). • Xanthomas are deposits o lipid in the skin or subcutaneous tissue that mani est clinically as yellowish papules, nodules, or tumors. They are usually a consequence o primary or secondary hyperlipidemia and occur in patients older than age 50 years. The lesions are so t, velvety, yellow, f at, polygonal papules that are asymptomatic and usually bilateral and symmetric (see Chapter 223, Hyperlipidemia).

MANAGEMENT SH does not require treatment but can be removed or cosmetic purposes or i it becomes irritated. Evidence supporting treatment comes primarily rom case series. • Options or removal include cryotherapy, electrodesiccation, topical chemical treatments (eg, with bichloracetic acid or trichloroacetic acid), oral isotretinoin (10-40 mg a day or 2-6 weeks), laser treatment (eg, with argon, carbon dioxide, or pulsed-dye laser), photodynamic therapy (ie, combined use o 5-aminolevulinic acid and visible light), 7 shave excision, and punch excision. 1 Complications o these therapies include atrophic scarring and changes in pigmentation. • I there is any suspicion that what appears to be sebaceous hyperplasia may be a basal cell carcinoma, per orm a shave biopsy as treatment (Figure 157-7).

FIGURE 157-7 Sing le , larg e , e le vate d le sion o se b ace ous hyp e rp lasia on the nose o a 51-ye ar-old man with rosace a. A shave b iop sy rule d out b asal ce ll carcinoma and g ave the d e nitive d iag nosis o se b ace ous hyp e rp lasia. The co sme tic re sult was e xce lle nt. (Re p ro d uce d with p e rmissio n from Richard P. Usatine , MD.)

FO LLO W-UP No ollow-up is needed. PATIENT RESO URCES

• Skinsight.com. Sebaceous Hyperplasia—http:/ / www.skinsight .com/ adult/ sebaceousHyperplasia.htm. PRO VIDER RESO URCES

• Medscape. Sebaceous Hyperplasia—http:/ / emedicine .medscape.com/ article/ 1059368-overview.

REFERENCES 1. Eisen DB, Michael DJ. Sebaceous lesions and their associated syndromes: part 1. JAmAcad Dermatol. 2009;61:549-560. 2. Boschnakow A, May T, Assa C, et al. Ciclosporin A-induced sebaceous gland hyperplasia. Br J Dermatol. 2003;149(1):198-200. 3. Oh ST, Kwon HJ. Premature sebaceous hyperplasia in a neonate. Pediatr Dermatol. 2007;24:443-445. 4. Zouboulis CC, Boschnakow A. Chronological ageing and photoageing o the human sebaceous gland. Clin Exp Dermatol. 2001;26(7):600-607. 5. Al-Daraji WI, Wagner B, Ali RBM, McDonagh AJG. Sebaceous hyperplasia o the vulva: a clinicopathological case report with a review o the literature. J Clin Pathol. 2007;60(7):835-837. 6. Zaballos P, Ara M, Puig S, Malvehy J. Dermoscopy o sebaceous hyperplasia. Arch Dermatol. 2005;141:808. 7. Gold MH, Bradshaw WL, Boring MM, et al. Treatment o sebaceous hyperplasia by photodynamic therapy with 5-aminolevulinic acid and a blue light source or intense pulsed light source. J Drugs Dermatol. 2004;3(suppl 6):S6-S9.

777

PART 14 DERMATO LO GY

778

158 DERMATO FIBRO MA Mind y A. Smith, MD, MS Richard P. Usatine , MD

Ch a pt e r 158

• Approximately 20% occur in patients younger than age 17 years. 1 In 1 case series, 80% occurred in people between the ages o 20 and 49 years. 2

ETIO LO GY AND PATHO PHYSIO LO GY PATIENT STO RY A 25-year-old woman reports a rm nodule on her leg that gets in the way o shaving her leg (Figure 158-1). Upon questioning, the nodule may have started there a ter she cut her leg shaving 1 year ago. She is worried it could be a cancer and wants it removed. Close observation showed a brown halo and a rm nodule that dimpled down when pinched. A diagnosis o a dermato broma (DF) was made and the choices or treatment were discussed.

• Uncertain etiology—Nodule may represent a brous reaction triggered by trauma, a viral in ection, or insect bite; however, DFs show clonal proli erative growth seen in both neoplastic and inf ammatory conditions. 3 • Multiple DFs (ie, > 15 lesions) have been reported associated with systemic lupus erythematosus, HIV in ection, Down syndrome, Graves disease, or leukemia, and may represent a worsening o immune unction. 1 A case o amilial eruptive DFs has also been reported associated with atopic dermatitis. 4

INTRO DUCTIO N DF is a benign brohistiocytic tumor, usually ound in the mid dermis, composed o a mixture o broblastic and histiocytic cells. These scar-like nodules are most commonly ound on the legs and arms o adults.

SYNO NYMS DF is also called as benign brous histiocytoma.

EPIDEMIO LO GY • Occurs more o ten in women (male-to- emale ratio is 1:4). 1

DIAGNO SIS CLINICAL FEATURES • Firm-to-hard nodule; skin is reely movable over the nodule except or the area o dimpling. • Color o the overlying skin ranges rom f esh to gray, pink, red, blue, brown, or black (Figures 158-2 and 158-3), or a combination o hues (Figure 158-4). • Dimples downward when compressed laterally because o tethering o the overlying epidermis to the underlying nodule (see Figure 158-3). • Usually asymptomatic but may be tender or pruritic.

• Found in patients o all races.

FIGURE 158-1 De rmatof b roma on the le g o a 25-ye ar-old woman that may have b e g un a te r she cut he r le g shaving 1 ye ar ag o. Note the b rown halo , p ink hue , and raise d ce nte r. (Re p ro d uce d with p e rmissio n fro m Richard P. Usatine , MD.)

FIGURE 158-2 De rmatof b roma on the thig h o b lack woman. Note the d arke r b rown halo around the lig hte r ce nte r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

De r Ma t O FIBr O Ma

IMAGING Dermoscopy is a use ul adjunctive diagnostic technique or DF (Figure 158-5). Although the most common nding is a peripheral pigment network with a central white area (34.7% o cases), 10 dermoscopic patterns have been identi ed; in a large case series, pigment network was observed in 71.8% (3% atypical pigment network)7 (see Appendix C, Dermoscopy). TYPICAL DISTRIBUTIO N May be ound anywhere, but usually on the legs and arms, especially the lower legs. In one case series, 70% were on the lower extremities. 2 BIO PSY • A punch biopsy can be both diagnostic and therapeutic. DFs have been reported with overlying basal cell carcinoma and associated melanoma. 8,9 • Histologically, DFs can be brocollagenous (40.1%), histiocytic (13.1%), cellular (11.5%), aneurysmal (7.4%), angiomatous (6.5%), sclerotic (6.5%), monster (4.9%), palisading (1.6%), keloidal (0.8%), or mixed type (7.3%).2 Also reported are ossi ying DFs10 and a signet-ring cell DF.11 • Electron microscopy and immunohistochemistry may be needed to di erentiate atypical or pigmented DFs rom other lesions. 7 FIGURE 158-3 Pinch te st showing a d e e p d imp ling o this d e rmatof b roma on the b uttocks. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIFFERENTIAL DIAGNO SIS • Size ranges rom 0.3 to 10 mm; usually less than 6 mm. Rarely, DFs grow to larger than 5 cm. 5 • May have a hyperpigmented halo and a scaling sur ace (Figure 158-4). • DFs can rarely be located entirely within subcutaneous tissue. 6

DFs may be con used with the ollowing malignant tumors; diagnosis based on histology and excision should be undertaken or enlarging or ulcerating tumors. • Dermato brosarcoma protuberans—A low-grade malignant brotic tumor o the skin and subcutaneous tissues (Figure 158-6). A punch biopsy will provide adequate tissue to make the diagnosis. • Pseudosarcomatous DF—A rare connective tissue tumor arising on the trunk and limbs in young adults. • Malignant brous histiocytoma—A common so t tissue sarcoma occurs in the extremities. Presentation as a primary cutaneous lesion is rare and more o ten presents as a metastasis rom another location such as the breast. Many benign lesions have a similar appearance, including the ollowing: • Pigmented seborrheic keratosis—May be macular and o ten larger than DF. Distinguished by sur ace cracks, verrucous eatures, stuck-on appearance, and adherent greasy scale (see Chapter 156, Seborrheic Keratosis). • Epidermal inclusion cyst—Sharply circumscribed, skin-colored nodule o ten with a central punctum. Most common on ace, neck, or trunk. Composed o strati ed epithelium surrounding a mass o keratinized material that has a oul odor when it drains. • Hypertrophic scar—Occurs within previous wounds or lacerations. • Neuro broma—Benign Schwann cell tumors; single lesions are seen in normal individuals. Cutaneous tumors tend to orm multiple, so t, pedunculated masses, whereas subcutaneous nodules are skin-colored so t nodules attached to peripheral nerves. The latter shows similar invagination as DF (see Chapter 235, Neuro bromatosis).

MANAGEMENT FIGURE 158-4 De rmatof b roma on the b ack. Note the b rown halo around the lig hte r ce ntral nod ule . (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

• No treatment is necessary unless the diagnosis is questioned or symptoms warrant.

779

PART 14 DERMATO LO GY

780

Ch a pt e r 158

A

B

C

FIGURE 1 58-5 A. De rmatof b roma o n the le g that has a p ink ce nte r and a lig ht b rown halo. B. Close -up o the d e rmatof b roma showing the p ink ce nte r and b rown halo. C. De rmoscop ic vie w o the d e rmatof b roma showing the typ ical p atte rn with a rad ially stre aking b rown halo and a p ink ce nte r with white ste llate scar. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

De r Ma t O FIBr O Ma

PATIENT RESO URCES

• American Osteopathic College of Dermatology. Dermatof broma— http:/ / www.aocd.org/ skin/ dermatologic_diseases/ dermatof broma.html. • Skinsight. Dermatof broma—http:/ / www.skinsight.com/ adult/ dermatof broma.htm. PRO VIDER RESO URCES

• Medscape. Dermatof broma—http:/ / emedicine.medscape .com/ article/ 1056742. REFERENCES

FIGURE 158-6 Larg e d e rmatof b rosarcoma p rotub e rans g rowing on the thig h o this 55-ye ar-old man. The f rst p unch b iop sy was re ad as a b e nig n d e rmatof b roma. Continue d g rowth p romp te d a se cond b iop sy that d e te cte d the malig nancy. The f rst e xcision d id not achie ve cle ar marg ins so the f nal tre atme nt consiste d o Mohs surg e ry. Note the shiny sur ace and multilo b ular lo o k that can b e characte ristic o a d e rmato f b ro sarco ma p ro tub e rans. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Punch excision or shave excision may be used or small lesions; with the latter technique, the healed area may remain hard as a result o remaining brous tissue. • Larger lesions may require an elliptical ( usi orm) excision, down to the subcutaneous at. • One author noted that DFs occurring on the ace o ten have involvement o deeper structures and an increased rate o local recurrences and there ore recommend excision with wider margins in comparison with DFs occurring on the extremities. 12 • Cryotherapy has also been used, but the cure rate is low and lesions may recur. • Several case reports ound success in treating multiple DFs with carbon dioxide laser13 or isotretinoin. 14

PRO GNO SIS • Although DFs are usually unchanging and persist inde nitely, there are reports o spontaneous regression. 15 • Following excision, DFs have a low recurrence rate o less than 2%, with higher recurrence believed to occur in cellular, aneurysmal, and atypical types. 7,10 • A higher rate o recurrence has been noted in the subcutaneous and deep types, and in lesions located on the ace, in which a recurrence rate o 15% to 19% has been reported. 16,17

PATIENT EDUCATIO N DFs are best le t alone i they are relatively asymptomatic and stable.

1. Pierson JC. Dermatof broma. http:/ / emedicine.medscape.com/ article/ 1056742-overview# a0104. Accessed July 2011. 2. Han TY, Chang HS, Lee JH, et al. A clinical and histopathological study o 122 cases o dermato broma (benign brous histiocytoma). Ann Dermatol. 2011;23(2):185-192. 3. Chen TC, Kuo T, Chan HL. Dermato broma is a clonal proli erative disease. J Cutan Pathol. 2000;27:36-39. 4. Yazici AC, Baz K, Ikizoglu G, et al. Familial eruptive dermato bromas in atopic dermatitis. J Eur Acad DermatolVenereol. 2006;20(1):90-92. 5. Lang KJ, Lidder S, Ho er M, et al. Rapidly evolving giant dermato broma. Case Report Med. 2010;2010:620910. 6. Jung KD, Lee DY, Lee JH, et al. Subcutaneous dermato broma. Ann Dermatol. 2011;23(2):254-257. 7. Zaballos P, Puig S, Llambrich A, Malvehy J. Dermoscopy o dermato bromas: a prospective morphological study o 412 cases. Arch Dermatol. 2008;144(1):75-83. 8. Rosmaninho A, Farrajota P, Peixoto C, et al. Basal cell carcinoma overlying a dermato broma: a revisited controversy. Eur J Dermatol. 2011;21(1):137-138. 9. Kovach BT, Boyd AS. Melanoma associated with dermato broma. J Cutan Pathol. 2007;34(5):420-492. 10. Papalas JA, Balmer NN, Wallace C, Sangüeza OP. Ossi ying dermato broma with osteoclast-like giant cells: report o a case and literature review. Am J Dermatopathol. 2009;31(4):379-833. 11. Garrido-Ruiz MC, Carrillo R, Enguita AB, Peralto JL. Signet-ring cell dermato broma. Am J Dermatopathol. 2009;31(1):84-87. 12. Mentzel T, Kutzner H, Rutten A, Hugel H. Benign brous histiocytoma (dermato broma) o the ace: clinicopathologic and immunohistochemical study o 34 cases associated with an aggressive clinical course. Am J Dermatopathol. 2001;23(5):419-426. 13. Sardana K, Garg VK. Multiple dermato bromas on ace treated with carbon dioxide laser: the importance o laser parameters. Indian J DermatolVenereol Leprol. 2008;74(2):170. 14. Kwinter J, DeKoven J. Generalized eruptive histiocytoma treated with isotretinoin. J Cutan Med Surg. 2009;4(4):490-491. 15. Niemi KM. The benign brohistiocytic tumours o the skin. Acta DermVenereol Suppl (Stockh). 1970;50(63):(suppl 63):1-66. 16. Fletcher CD. Benign brous histiocytoma o subcutaneous and deep so t tissue: a clinicopathologic analysis o 21 cases. Am J Surg Pathol. 1990;14:801-809. 17. Mentzel T, Kutzner H, Rütten A, Hügel H. Benign brous histiocytoma (dermato broma) o the ace: clinicopathologic and immunohistochemical study o 34 cases associated with an aggressive clinical course. Am J Dermatopathol. 2001;23:419-426.

781

PART 14 DERMATO LO GY

782

159 PYO GENIC GRANULO MA Mind y A. Smith, MD, MS Richard P. Usatine , MD

Ch a pt e r 159

ETIO LO GY AND PATHO PHYSIO LO GY • Etiology is unknown but may be the result o trauma, in ection, or preceding dermatoses. • Consists o dense proli eration o capillaries and f broblastic stroma that is inf ltrated with polymorphonuclear leukocytes.

PATIENT STO RY A 20-year-old woman presents to the o f ce with a new growth on her lip (Figure 159-1). She stated that the growth on her lip bled very easily but was not pain ul. She was diagnosed with a pyogenic granuloma (PG) and pre erred to wait until her pregnancy was over to have it removed. The lesion did not regress spontaneously a ter pregnancy and was surgically excised.

INTRO DUCTIO N PG is the name or a common, benign, acquired, vascular neoplasm o the skin and mucous membranes.

SYNO NYMS The term lobular capillary hemangioma has been suggested because PG is neither pyogenic (purulent bacterial in ection) nor a granuloma. 1

• Multiple PGs have been reported at burn sites and ollowing use o oral contraceptives, protease inhibitors, and topical application o tretinoin or acne. 2 • PGs are known to regress ollowing pregnancy. Vascular endothelial growth actor (VEGF) was ound in one study to be high in the granulomas during pregnancy, was almost undetectable a ter parturition, and was associated with apoptosis o endothelial cells and regression o granuloma.3

RISK FACTO RS • Trauma (up to 50%) or chronic irritation. 1 • Multiple lesions can ollow manipulation o a primary lesion. 4 • Pregnancy or use o oral contraceptives or oral PGs; postulated caused by imbalance between angiogenesis enhancers and inhibitors. 1 • In ection with Bartonella.1

DIAGNO SIS EPIDEMIO LO GY • Most o ten seen in children and young adults (0.5% o children’s skin lesions); 42% o cases occur by 5 years o age and approximately 1% are present at birth. 1

CLINICAL FEATURES • Usually solitary, erythematous, dome-shaped papule or nodule that bleeds easily (Figures 159-1 to 159-6); rarely causes anemia. Satellite lesions may rarely occur.

• Oral lesions occur most o ten in the second and third decade, more commonly in women ( emale-to-male ratio is 2:1). 1 • Also common during pregnancy. • PG has also been reported in the gastrointestinal (GI) tract, the larynx, and on the nasal mucosa, conjunctiva, and cornea.

FIGURE 159-1 Pyog e nic g ranuloma on the lowe r lip arising d uring p re g nancy. (Re p rod uce d with p e rmission from Usatine RP, Moy RL, Tob inick EL, Sie g e l DM. Skin Surg e ry: A Practical Guid e . St. Louis, MO : Mosb y; 1998.)

FIGURE 159-2 Pyo g e nic g ranulo ma o n the nose in a young ad ult. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

pYO Ge NIC Gr a NULO Ma

FIGURE 159-3 Larg e p yog e nic g ranuloma on the hand o a 33-ye ar-old man p re se nt or 3 months. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 159-6 Pyog e nic g ranuloma on the le g or 6 months b e ore the p atie nt p re se nte d or tre atme nt. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Prone to ulceration, erosion, and crusting. • Size ranges rom a ew millimeters to several centimeters (average size is 6.5 mm). 1 • Rapid growth over a period o weeks to maximum size. • Variants include cutaneous, oral mucosal (granuloma gravidarum), satellite, subcutaneous, intravenous, and congenital types. 1 TYPICAL DISTRIBUTIO N • Cutaneous PG most o ten ound on the head and neck (62.5%) specif cally the gingiva, lips as in Figure 159-1, nose (see Figure 159-2), ace, trunk (20%), and extremities (18%) (see Figures 159-3 to 159-6). 1 FIGURE 159-4 Larg e p yog e nic g ranuloma on the f ng e r o a 22-ye ar-old man p re se nt or 4 months. He was se nt out o multip le clinical se tting s untre ate d until we e xcise d this. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Pregnancy PG occurs most commonly along the maxillary intraoral mucosal sur ace. IMAGING Reddish homogeneous area surrounded by a white collarette is the most requent dermoscopic pattern in PGs (85%). 5 In more advanced lesions, white lines that intersect the central areas may be seen that are likely f brous septa. BIO PSY • Early lesions resemble granulation tissue (numerous capillaries and venules with endothelial cells arrayed radially toward the skin sur ace; stroma is edematous). 1 • The mature PG exhibits a f bromyxoid stroma separating the lesion into lobules. Proli eration o capillaries is present, with prominent endothelial cells. The epidermis exhibits inward growth at the lesion base. 1 • A regressing PG has extensive f brosis.

DIFFERENTIAL DIAGNO SIS FIGURE 159-5 Small p yog e nic g ranuloma on the f ng e r or 2 months. It starte d with a small injury to the f ng e r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PG may be con used with a number o cutaneous malignancies, including atypical f broxanthoma, basal cell carcinoma, Kaposi sarcoma, metastatic cutaneous lesions, squamous cell carcinoma, and amelanotic melanoma

783

784

PART 14 DERMATO LO GY

Ch a pt e r 159

FIGURE 159-9 Vascular g rowth on the nose o a p re g nant woman that ap p e ars to b e a p yog e nic g ranuloma. Biop sy re ve ale d a b e nig n cle ar ce ll variant o a f b rous p ap ule . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 159-7 Ame lanotic me lanoma on the nose that could b e con use d with a p yog e nic g ranuloma. Always se nd what you susp e ct to b e a PG to the p atholog ist. (Re p rod uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

(Figure 212-8). Nodules a ect all age groups and may reach 10 cm in size. This in ection is more likely to occur in persons with AIDS. Weight loss and lymphadenopathy may occur.

MANAGEMENT (Figure 159-7). It is especially important to send the excised lesion that appears to be a PG or pathology to make sure that a malignancy is not missed. Benign tumors that may be con used with PG include the ollowing:

Removal o the lesion is indicated to alleviate any bleeding or discom ort, or cosmetic reasons, or when the diagnosis is uncertain.

• Cherry hemangioma—Small, bright-red, dome-shaped papules that represent benign proli eration o capillaries (Figure 159-8).

NO NPHARMACO LO GIC

• Fibrous papule o the nose is a benign tumor o the nose. Most are skin colored and not con used with PG. A benign clear cell variant o a f brous papule can closely resemble a PG as seen in Figure 159-9. • Bacillary angiomatosis—A systemic in ectious disease caused by 2 Bartonella species. Globular angiomatous papules appear like PG

Untreated PGs eventually atrophy, become f bromatous, and slowly regress, especially i the causative agent is removed. MEDICATIO NS A case o success ul treatment o a recurrent PG was reported using a 14-week course o twice-weekly imiquimod 5% topical application. 6 SO R C

PRO CEDURES A number o procedures have been used or elimination o PGs; data are limited to case series reports. 7 • Simple surgical excision has a low recurrence rate (< 4%) but is associated with scarring (55%). 7 SO R C • Removal can be accomplished with shave excision and electrodesiccation; the latter reduces recurrence (approximately 10%) and scarring appears less than with either simple excision (31%) or cauterization alone (43.5%). 1,7 PGs bleed extensively when manipulated or cut. It is important to use lidocaine with epinephrine, wait 10 minutes or the epinephrine to work, and have an electrosurgery device to control bleeding. Cut the PG o with a blade and send to pathology. Curetting the base will also help stop the bleeding and prevent recurrence. The base is curetted and electrodesiccated until the bleeding stops. SO R C FIGURE 159-8 He mang ioma on the lip o a 67-ye ar-old man. By ap p e arance alone this is hard to d i e re ntiate rom a p yog e nic g ranuloma (lob ular cap illary he mangioma). This did not ble e d e xte nsively at time o e xcision and the patholog y re sult conf rme d that this was a he mangioma. (Re produce d with p e rmission from Richard P. Usatine , MD.)

• Both cryosurgery and laser surgery o ten require more than one treatment and rates o scarring may be high (12%-42% and 44%, respectively). 1,7 SO R C

• In one case series, sclerotherapy was reported to leave no scarring or recurrence. 7 SO R C

PART 14 DERMATO LO GY

pYO Ge NIC Gr a NULO Ma

PRO GNO SIS • PG develops over weeks and growth typically stabilizes over several months. 1 Eventually, it shrinks to become a f brotic “angioma.” Some nodules spontaneously in arct and involute. • Congenital PG is an uncommon disseminated variant that presents with multiple lesions, is similar in appearance to the cutaneous orm, and is present at birth. The condition appears to ollow a benign course, with spontaneous resolution over 6 to 12 months. 1

PRO VIDER RESO URCES

• Medscape. Pediatric Pyogenic Granuloma—http:/ / emedicine .medscape.com/ article/ 910112. • Medscape. Oral Pyogenic Granuloma—http:/ / emedicine .medscape.com/ article/ 1077040. • Usatine R, P enninger J, Stulberg D, Small R. Dermatologic and Cosmetic Procedures in O f ce Practice. Philadelphia, PA: Elsevier; 2012. The book has many photographs and descriptions that provide details o how to surgically treat PGs. It is also available as an electronic application, with video included, at www.usatinemedia.com.

PATIENT EDUCATIO N • Explain to patients that lesions may resolve spontaneously and that multiple success ul treatments are available (note that most patients will be grate ul to have treatment that day as the lesion tends to be a great nuisance by bleeding easily and having an undesirable appearance). • Once treated, i the lesion begins to recur, patients should ollow up quickly be ore the lesion gets larger and harder to treat.

FO LLO W-UP Follow-up in 2 weeks to receive the result o the pathology and to check wound healing. PATIENT RESO URCES

• MedlinePlus. Medical Encyclopedia—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 001464.htm. • PubMed Health. Pyogenic granuloma—http:/ / www.ncbi.nlm .nih.gov/ pubmedhealth/ PMH0002435/ .

REFERENCES 1. Lin RL, Janniger CK. Pyogenic granuloma. Cutis. 2004;74(4): 229-233. 2. Teknetzis A, Tonannides D, Vakali G, et al. Pyogenic granulomas ollowing topical application o tretinoin. J Eur Acad DermatolVenereol. 2004;18(3):337-339. 3. Yuan K, Lin MT. The roles o vascular endothelial growth actor and angiopoietin-2 in the regression o pregnancy pyogenic granuloma. Oral Dis. 2004;10(3):179-185. 4. Blickensta RD, Roenigk RK, Peters MS, et al. Recurrent pyogenic granuloma with satellitosis. JAmAcad Dermatol. 1989;21:1241-1244. 5. Zaballos P, Llambrich A, Cuellar F, et al. Dermoscopic f ndings in pyogenic granuloma. Br J Dermatol. 2006;154(6):1108-1111. 6. Goldenberg G, Krowchuk DP, Jorizzo JL. Success ul treatment o a therapy-resistant pyogenic granuloma with topical imiquimod 5% cream. J DermatologTreat. 2006;17(2):121-123. 7. Gilmore A, Kelsberg G, Sa ranek S. Clinical inquiries. What’s the best treatment or pyogenic granuloma? J Fam Pract. 2010;59(1):40-42.

785

PART 14 DERMATO LO GY

786

SECTIO N 9

Ch a pt e r 160

NEVI

160 BENIGN NEVI Mind y A. Smith, MD, MS Richard P. Usatine , MD

PATIENT STO RY A young woman comes to the o ce because her husband has noted that the moles on her back are changing (Figure 160-1). A ew have white halos around the brown pigmentation and some have lost their pigment completely, with a light area remaining. She has no symptoms but wants to make sure these are not skin cancers. Halo nevi are an uncommon variation o common nevi. These appear benign and the patient is reassured.

INTRO DUCTIO N Most nevi are benign tumors caused by the aggregation o melanocytic cells in the skin. However, nevi can occur on the conjunctiva, sclera, and other structures o the eye. There are also nonmelanocytic nevi that are produced by other cells as seen in Becker nevi and comedonal nevi. Although most nevi are acquired, many nevi are present at birth.

SYNO NYMS Benign nevi are also called as moles.

EPIDEMIO LO GY • Acquired nevi are common lesions, orming during early childhood; ew adults have none. • Prevalence appears to be lower in dark-skinned individuals. • Present in 1% o neonates increasing through childhood and peaking at puberty; new ones may continue to appear in adulthood. In a population study o children (N = 180, ages 1-15 years) in Barcelona, the mean number o nevi was 17.5. 1 • Adults typically have 10 to 40 nevi scattered over the body. In a population study in Germany, 60.3% o 2823 adults (mean age 49 years; 50% women) exhibited 11 to 50 common nevi and 5.2% had at least 1 atypical nevus. 2 • The peak incidence o melanocytic nevi (MN) is in the ourth to th decades o li e; the incidence decreases with each successive decade. 3

A

ETIO LO GY AND PATHO PHYSIO LO GY • Benign tumors composed o nevus cells derived rom melanocytes, pigment-producing cells that colonize the epidermis. • MN represent proli erations o melanocytes those are in contact with each other, orming small collections o cells known as nests. Genetic mutations present in common nevi as well as in melanomas include BRAF, NRAS, and c-kit. 4 • Sun (UV) exposure, skin-blistering events (eg, sunburn), and genetics play a role in the ormation o new nevi. 3 • Nevi commonly darken and/ or enlarge during pregnancy. Melanocytes have receptors or estrogens and androgens and melanogenesis is responsive to these hormones. 3

B FIGURE 160-1 A. Multi l h lo n vi on th b ck. B. Clos -u o h lo n vus in t nsitio n. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Three broad categories o MN are based on location o nevus cells2 are as below: ° Junctional nevi—Composed o nevus cells located in the dermalepidermal junction; may change into compound nevi a ter childhood (except when located on the palms, soles, or genitalia) (Figure 160-2). ° Compound nevi—A nevus in which a portion o nevus cells have migrated into the dermis (Figure 160-3).

Be NIGN Ne VI

FIGURE 160-2 Two b nig n junction l n vi on th m o 19-y -old wom n. Not how th s f t m cul s. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

° Dermal nevi—Composed o nevus cells located within the dermis (usually ound only in adults). These are usually raised and have little to no visible hyperpigmentation (Figures 160-4 and 160-5). • Special categories o nevi are as below: ° Halo nevus—Compound or dermal nevus that develops a symmetric, sharply demarcated, depigmented border (see Figure 160-1). Most commonly occurs on the trunk and develops during adolescence. Repigmentation may occur. ° Blue nevus—A dermal nevus that contains large amounts o pigment so that the brown pigment absorbs the longer wavelengths o light and scatters blue light (Tyndall e ect) (Figure 160-6). Blue nevi are not always blue and color varies rom tan to blue, black, and gray. Types o blue nevi include amelanotic, desmoplastic, atypical, and malignant variants; genetic mutations seen in blue nevi are o ten di erent than those seen in common nevi and include the Ga q class o G-protein α subunits, Gnaq, and Gna11 proteins. 4 The nodules are rm because o associated stromal sclerosis. Usually appears in childhood on the extremities, dorsum o the hands, and ace. A rare variant, the cellular blue nevus is large (> 1 cm), requently located on the buttocks, and may undergo malignant degeneration. ° Nevus spilus—Hairless, oval, or irregularly shaped brown lesion with darker brown to black dots containing nevus cells (Figure 160-7). May appear at any age or be present at birth; unrelated to sun exposure.

FIGURE 160-3 B nig n com o und n vus o v n b y b io sy on th b ck o 35-y -old wom n. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

FIGURE 160-4 D m l n vus (int d m l m l nocytic n vus)—d om sh d with som sc tt d ig m nt tion. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

° Spitz nevus ( ormerly called benign juvenile melanoma because o its clinical and histologic similarity to melanoma)—Hairless, red, or reddish brown dome-shaped papules generally appearing suddenly in children, sometimes ollowing trauma (Figures 160-8 and 160-9). The pink color is caused by increased vascularity. Most importantly, these should be ully excised with clear margins. ° Nevus o Ota—Dark brown nevus that occurs most commonly around the eye and can involve the sclera (Figure 160-10). • Both acquired and congenital MN hold some risk or the development o melanoma; the number o MN, especially more than 100, is an important independent risk actor or cutaneous melanoma. 5 NO NMELANO CYTIC NEVI • Becker nevus—A brown patch o ten with hair located on the shoulder, back or submammary area, most o ten in adolescent men (Figures 160-11 and 160-12). The lesion may enlarge to cover an

FIGURE 160-5 D m l n vus d uncul t d with sm ll t l ng i ct si s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

787

788

PART 14 DERMATO LO GY

Ch a pt e r 160

A

FIGURE 160-6 Blu n vus on th l t ch k th t could s mb l m l nom with its d k colo . In this c s it w s ully xcis d with 5-mm unch with g ood cosm tic sult. Blu n vi b nig n nd d o not n d to b xcis d unl ss th sus icious ch ng s. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

B FIGURE 160-9 A. Int d m l n vus with s itzoid tu s on th mo this m n. It w s ully xcis d . B. D mosco y o this n vus shows som i h l ctiv g owth with st ming nd c yst llin st uctu s (whit ). Th d mo sco y w s co nc ning o S itz n vus o m l no m . (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.) FIGURE 160-7 N vus s ilus on th l g o young wom n om b i th. It s b nig n nd n d s no int v ntion. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 160-8 S itz n vus th t g w ov th st y on th nos o this 18-y -old wom n. It w s ully xcis d with no com lic tions. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 160-10 N vus o O t on th c o this young wom n sinc child hood . It involv d b oth y s nd th skin ound b oth y s. Th scl ig m nt tion looks b lu . (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

ly l

Be NIGN Ne VI

FIGURE 160-11 B ck n vus th t d v lo d d u ing d ol sc nc in this young m n. H i is q u ntly s n on this ty o nonm l nocytic n vus. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

entire shoulder or upper arm. Although it is called a nevus, it does not actually have nevus cells and has no malignant potential. It is a type o hamartoma, an abnormal mixture o cells and tissues normally ound in the area o the body where the growth occurs. • Nevus depigmentosus is usually present at birth or starts in early childhood. There is a decrease number o melanosomes within a normal number o melanocytes. It typically has a serrated or jagged edge (Figure 160-13).

PART 14 DERMATO LO GY

FIGURE 160-13 N vus d ig m ntosus on th h nd o this m n sinc b i th. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Epidermal nevi are congenital hamartomas o ectodermal origin classied on the basis o their main component: sebaceous, apocrine, eccrine, ollicular, or keratinocytic. See Chapter 161, Congenital Nevi or a ull discussion o this type o nevus. Note nevus comedonicus and epidermal nevi tend to ollow Blaschko lines, which come rom embryologic development.

• Nevus anemicus—A congenital hypopigmented macule or patch that is stable in relative size and distribution. It occurs as a result o localized hypersensitivity to catecholamines and not a decrease in melanocytes. On diascopy (pressure with a glass slide) the skin is indistinguishable rom the surrounding skin (Figure 160-14). • Nevus comedonicus (comedonal nevus) is a rare congenital hamartoma characterized by an aggregation o comedones in one region o the skin (Figure 160-15).

FIGURE 160-12 B ck n vus on th b ck o His nic t n g o 2 y s. Whil this n vus d id not h v h i , it d id h v inc s d cn within th — noth tu o th B ck n vus. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 160-14 N vus n micus on th ost io n ck. Th loc liz d hy s nsitivity to c t chol min s c us s th to st y lig ht th n th su ound ing skin. (Re p rod uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

789

PART 14 DERMATO LO GY

790

Ch a pt e r 160

• In an Australian study o white children, MN o all sizes were highest on the outer orearms, ollowed by the outer upper arms, neck, and ace. 8 Boys had higher densities o MN o all sizes on the neck than girls, and girls had higher densities o MN o 2 mm or greater on the lower legs and thighs than boys. Habitually sun-exposed body sites had higher densities o small MN and highest prevalence o larger MN. IMAGING • Dermoscopy can be a use ul technique or diagnosing benign nevi. For MN, dermoscopic diagnosis relies on color; pattern (ie, globular, reticular, starburst, and homogeneous blue pattern); pigment distribution (ie, multi ocal, central, eccentric, and uni orm); and special sites (eg, ace, acral areas, nail, and mucosa), in conjunction with patient actors (eg, history, pregnancy) (see Figure 160-9)9 (see Appendix C, Dermoscopy). FIGURE 160-15 N vus com d onicus on th n ck o this wom n sinc b i th. This is cong nit l h m tom with o n com d on s. It is not cn . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

RISK FACTO RS • In the Barcelona study o children, male gender, past history o sunburns, acial reckling, and amily history o breast cancer were independent risk actors or having a higher number o nevi. 1 • In one study among very light-skinned (and not darker-skinned) children without red hair, children who develop tans have greater numbers o nevi. 6 • Neonatal blue-light phototherapy is not related to nevus count. 7

DIAGNO SIS CLINICAL FEATURES Most benign MN are tan to brown, usually less than 6 mm, with round shape and sharp borders. • Junctional nevi—Macular or slightly elevated mole o uni orm brown to black pigmentation, smooth sur ace, and a round or oval border (see Figure 160-2). Most are hairless and vary rom 1 to 6 mm. • Compound nevi—Slightly elevated, symmetric, uni ormly f esh colored or brown with a round or oval border, o ten becoming more elevated with age (see Figure 160-3). Hair may be present and a white halo may orm. • Dermal nevi (same as intradermal nevi)—Skin color or brown color that may ade with age; dome-shaped nevus is most common, but shapes vary, including polypoid, warty, and pedunculated. O ten ound on the ace and may have telangiectasias (see Figures 160-4 and 160-5). Size ranges rom 1 to 10 mm. TYPICAL DISTRIBUTIO N

• In the Barcelona study, the most requent dominant dermoscopic pattern was the globular type with the homogeneous pattern predominating in the youngest children and the reticular pattern predominating in adolescents.1 BIO PSY Biopsy is necessary i you suspect melanoma or a Spitz nevus. A biopsy that cuts below the pigmented area is pre erred i there is a reasonable suspicion or melanoma. This can be done with a scoop shave, a punch that gets the whole lesion, or an elliptical excision. I the patient wants a raised benign-appearing nevus excised or cosmetic reasons, a shave excision may be adequate. Send all lesions (except skin tags) to the pathologist or examination, even when they appear benign, to avoid missing a melanoma.

DIFFERENTIAL DIAGNO SIS Benign nevi may develop atypia or become melanoma. This should be suspected i a lesion has atypical eatures including asymmetry, border irregularity, color variability, diameter greater than 6 mm, and evolving (called the ABCDE approach [asymmetry, border irregularity, color irregularity, diameter > 6 mm, evolution]). Any lesion that becomes symptomatic (eg, itchy, pain ul, irritated, or bleeding), or develops a loss or increase in pigmentation, should be evaluated and biopsied i needed. Dermoscopy can be used to increase one’s accuracy in distinguishing between benign and malignant lesions (see Appendix C, Dermoscopy). • Melanomas are skin cancers that may develop rom a preexisting nevus. The most important skill to develop is how to distinguish a benign nevus rom a nevus that might be malignant melanoma. Because clinical appearance can be misleading, a biopsy is necessary when there is a reasonable suspicion or cancer (see Chapter 170, Melanoma). • Dysplastic or atypical nevi are variants that are relatively f at, thinly papular, and relatively broad. O ten, the lesions exhibit target-like or ried egg-like morphology, with a central papular zone and a macular surrounding area with di ering pigmentation (see Chapter 163, Dysplastic Nevus).

• Most o ten ound above the waist on sun-exposed areas but may appear anywhere on the cutaneous sur ace; less commonly ound on the scalp, breasts, or buttocks.

• Seborrheic keratoses are benign growths that appear more with increasing age and are o ten hyperpigmented as seen with many nevi. These are more super cial and stuck-on in their appearance (see Chapter 156, Seborrheic Keratosis).

• Among the children in the Barcelona study, 61.1% had nevi on the ace and neck, 17.2% on the buttocks, and 11.7% on the scalp; approximately one-third had congenital nevi (see Chapter 161, Congenital Nevi).1

• Labial melanotic macules are benign dark macules on the lip that are not nevi and not melanomas (Figure 160-16). They can be removed or cosmetic purposes.

PART 14 DERMATO LO GY

Be NIGN Ne VI

new nevi on the trunk than did children in the control group at 3-year ollow-up. 10

PRO GNO SIS • Degeneration o common nevi into melanoma is very rare. • Patients with multiple or large MN appear to have an increased risk o melanoma. 3 • Nevi may recur or persist ollowing removal; in one study, dysplastic MN were the most likely to persist. 11 In another study, o 61 benign nevi biopsy sites reexamined, 2 (3.3%) recurred. 12

FO LLO W-UP Patients with multiple or sizable MN should be ollowed by an experienced clinician because they appear to have an increased li etime risk o melanoma, with the risk increasing in rough proportion to the size and/ or number o lesions. 3

PATIENT EDUCATIO N FIGURE 160-16 L b i l m l notic m cul . Th s b nig n b ut n vi. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

not

• Patients should be encouraged to use sunscreen to prevent skin cancer as well as to reduce the development o new nevi. • Patients with multiple or sizable MN should be taught to look or and report asymmetry, border irregularity, new symptoms, and color and size changes.

MANAGEMENT Nevi are generally only removed or cosmetic reasons or because o concern over changes in the lesion suggestive o dysplasia or melanoma. • A ull excisional biopsy with a sutured closure is usually the best means to diagnose a lesion i concern exists regarding the possibility o melanoma. I the lesion is ound to be benign, no urther treatment is usually required. • Punch excision can be used to excise smaller lesions. • Scoop shave—Un ortunately, i a punch biopsy is used to sample a larger lesion it may miss a melanoma in another part o the lesion. A broad scoop shave is better than a punch biopsy when a ull elliptical excision is not possible or desirable (eg, a large f at pigmented lesion on the ace). • Nevi removed or cosmesis are o ten removed by shave excision.

3

I a Spitz nevus is suspected, either biopsy it now or schedule the patient or a ull excision. The histopathology is too close to a melanoma to just watch it. • Becker nevi and comedonal nevi do not become melanoma because they lack melanocytes. There ore, there is no reason to excise them. Generally, these are large and the risks o excision or cosmetic reasons outweigh the bene ts.

PREVENTIO N Sun protection to limit sunburn may help reduce the appearance o nevi. In a trial o 209 white children, children randomized to the sunscreen group, especially those with reckles, had signi cantly ewer

PATIENT RESO URCES

• VisualDxHealth—http:/ / www.visualdxhealth.com/ adult/ nevus.htm. • MedlinePlus. Moles—http:/ / www.nlm.nih.gov/ medlineplus/ moles.html. • American Osteopathic College o Dermatology—http:/ / www .aocd.org/ skin/ dermatologic_diseases/ moles.html. PRO VIDER RESO URCES

• Medscape. Melanocytic Nevi—http:/ / emedicine.medscape .com/ article/ 1058445-overview.

REFERENCES 1. Aguilera P, Puig S, Guilabert A, et al. Prevalence study o nevi in children rom Barcelona. Dermoscopy, constitutional and environmental actors. Dermatology. 2009;18(3):203-214. 2. Scha er T, Merkl J, Klemm E, et al. The epidemiology o nevi and signs o skin aging in the adult general population: results o the KORA-Survey 2000. J Invest Dermatol. 2006;126(7):1490-1496. 3. McCalmont T. Melanocytic Nevi. http:/ / emedicine.medscape.com/ article/ 1058445-overview# a0199. Accessed October 2011. 4. Zembowicz A, Phadke PA. Blue nevi and variants: an update. Arch Pathol Lab Med. 2011;135(3):327-336.

791

792

PART 14 DERMATO LO GY 5. Gandini S, Sera F, Cattaruzza MS, et al. Meta-analysis o risk actors or cutaneous melanoma: I. Common and atypical nevi. Eur J Cancer. 2005;41(1):28-44. 6. Aalborg J, Morelli JG, Mokrohisky ST, et al. Tanning and increased nevus development in very-light-skinned children without red hair. Arch Dermatol. 2009;145(9):989-996. 7. Mahé E, Beauchet A, Aegerter P, Saiag P. Neonatal blue-light phototherapy does not increase nevus count in 9-year-old children. Pediatrics. 2009;123(5):e896-e900. 8. Harrison SL, Buettner PG, MacLennan R. Body-site distribution o MN in young Australian children. Arch Dermatol. 1999;135(1):47-52. 9. Zalaudek I, Docimo G, Argenziano G. Using dermoscopic criteria and patient-related actors or the management o pigmented melanocytic nevi. Arch Dermatol. 2009;145(7):816-826.

CHa pTe r 160

10. Lee TK, Rivers JK, Gallagher RP. Site-speci c protective e ect o broad-spectrum sunscreen on nevus development among white schoolchildren in a randomized trial. JAmAcad Dermatol. 2005;52(5):786-792. 11. Sommer LL, Barcia SM, Clarke LE, Helm KF. Persistent melanocytic nevi: a review and analysis o 205 cases. J Cutan Pathol. 2011;38(6):503-507. 12. Goodson AG, Florell SR, Boucher KM, Grossman D. Low rates o clinical recurrence a ter biopsy o benign to moderately dysplastic melanocytic nevi. JAm Acad Dermatol. 2010;62(4):591-596.

CO NGENITAL NEVI

PART 14

DERMATO LO GY

161 CO NGENITAL NEVI Mind y A. Smith, MD, MS Richard P. Usatine , MD

PATIENT STO RY A 24-year-old woman presents with concerns about a mole on her breast (Figure 161-1). This mole has been present all of her life but her boyfriend wanted her to see her doctor about it. It had slowly increased in size throughout childhood but has not changed for years. Her primary care physician tells her that it is a congenital nevus that has no clinical features that suggest malignancy. No biopsy or excision is needed.

INTRO DUCTIO N Congenital melanocytic nevi are benign pigmented lesions that have a wide variation in presentation and are composed of melanocytes, the pigment-forming cells in the skin.

SYNO NYMS • It is also called as garment nevus, bathing trunk nevus, giant hairy nevus, giant pigmented nevus, pigmented hairy nevus, nevus pigmentosus, nevus pigmentosus et pilosus, and Tierfell nevus. 1 • Tardive congenital nevus refers to a nevus with similar features to congenital nevi, but appears at age 1 to 2 years.

EPIDEMIO LO GY • Congenital melanocytic nevi develop in 1% to 6% of newborns and are present at birth or develop during the rst year of life. 1

FIGURE 161-1 Cong e nital ne vus on the b re ast of a 24-ye ar-old woman. It is ve rrucous, b ut e ntire ly b e nig n. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 161-2 Me lano ma arising in an acq uire d ne vus showing fe ature s of ce ntral re g re ssion and a ne w e le vate d nod ule . The se are the same fe ature s that make a cong e nital ne vus susp icious for me lanoma. (Re p ro d uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

• In an Italian prevalence study of more than 3000 children ages 12 to 17 years, congenital melanocytic nevi or congenital nevus-like nevi were found in 17.5%; most (92%) were small (< 1.5 cm). 2 • Congenital nevi are also seen in neurocutaneous melanosis, a rare syndrome characterized by the presence of congenital melanocytic nevi and melanotic neoplasms of the central nervous system. • The development of melanoma within congenital nevi (Figure 161-2) is believed to occur at a higher rate than in normal skin. Estimates range from 4% to 10%, with smaller lesions having lowest risk. 1 ° In a systematic review, 46 of 651 patients with congenital melanocytic nevi (0.7%), who were followed for 3.4 to 23.7 years, developed melanomas, representing a 465-fold increased relative risk of developing melanoma during childhood and adolescence. 3 The mean age at diagnosis of melanoma was 15.5 years (median 7 years). ° Patients with giant congenital melanocytic nevi appear to be at highest risk where subsequent melanoma has been reported in 5% to 7% by age 60 years. 4 In one study, 70% of patients with a large congenital melanocytic nevi diagnosed with melanoma were diagnosed within the rst 10 years of life. 5 ° In a prospective study of 230 medium-sized congenital nevi (1.5-19.9 cm) in 227 patients from 1955 to 1996, no melanomas occurred. The average follow-up period being 6.7 years to an average age of 25.5 years. 6 ° Other risk factors for melanoma include personal or family history of melanoma or other skin cancer, presence of multiple nevi, red hair, blue eyes, freckling, and history of radiation (see Chapter 170, Melanoma). 1

793

PART 14

794

DERMATO LO GY

Ch a pt e r 161

ETIO LO GY AND PATHO PHYSIO LO GY • The etiology of congenital nevi is unknown. • Congenital nevi result from a proliferation of benign melanocytes in the dermis, epidermis, or both. Melanocytes of the skin originate in the neuroectoderm and migrate vertically to the skin and other locations such as the central nervous system (CNS) and eye. 1 Defects in migration or maturation are hypothesized as causal.

DIAGNO SIS Diagnosis is usually made based on clinical features and the history of the nevus being present at birth or develop during the rst year of life. CLINICAL FEATURES1 • Variable mixtures of color including pink-red (primarily at birth), tan, brown, black, or multiple shades are seen within a single lesion (Figures 161-3 and 161-4); color usually remains constant over time but the nevus will grow as the person grows. Congenital nevi that are speckled or spotted are called spilus nevi (Figures 161-5 and 161-6). • Shapes are also highly variable, including oval, round, linear, and random; lesions have irregular but well-demarcated borders (Figures 161-7 and 161-8). The pigment may fade off into surrounding skin. • Nevi may become raised over time (Figures 161-8 and 161-9) and the skin surface ranges from smooth to pebbly to hyperkeratotic (eczema-like appearance). • Macular portion usually found at edges. • Frequently exhibit hypertrichosis (Figures 161-9 and 161-10). • Heavily pigmented large congenital melanocytic nevi over a limb may be associated with underdevelopment of the limb. 1 • Lesions are classi ed by size in adulthood as the following1: ° Small (< 1.5 cm) ° Medium (1.5-19 cm) (see Figures 163-5 and 163-9) ° Large (> 20 cm) (Figures 161-10 and 161-11)

FIGURE 161-3 Pink cong e nital ne vus on the che st of a fair-skinne d woman. It is some what hyp e rke ratotic as may b e se e n in a se b orrhe ic ke ratosis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 161-4 Darkly p ig me nte d b e nig n cong e nital ne vus b e twe e n the b re asts of a Hisp anic woman. Note the hyp e rtrichosis and multip le colors. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Giant nevi are often surrounded by several smaller satellite nevi (see Figure 161-10). IMAGING • Dermoscopy ndings depend on the age and location. 7 The majority of reticular lesions are located on the limbs and the variegated pattern was the most speci c for congenital nevi. • Magnetic resonance imaging (MRI) of the central nervous system can be a useful diagnostic tool in patients suspected of having neurocutaneous melanosis; one author recommended a screening MRI for patients with giant congenital melanocytic nevi. 8

FIGURE 161-5 Cong e nital sp e ckle d ne vus on the e xte nsor surface of the arm. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

CO NGe NIt a L Ne VI

PART 14

DERMATO LO GY

FIGURE 161-6 A sp e ckle d cong e nital ne vus (ne vus sp ilus) on the b ack of a young woman. The re are are as in which the color is the same as the surround ing skin. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

TYPICAL DISTRIBUTIO N Congenital nevi can be found anywhere on the body. BIO PSY Although there are many histologic subtypes, distinguishing histologic features of congenital nevi include the following1: • Involvement by nevus cells of deep dermal appendages and neurovascular structures (eg, hair follicles, sebaceous glands, arrector pili muscles, and within walls of blood vessels) • In ltration of nevus cells between collagen bundles

DIFFERENTIAL DIAGNO SIS • Becker nevus—A brown macule, patch of hair, or both on the shoulder, back, or submammary area that develops in adolescence.

FIGURE 161-7 Me d ium-size d cong e nital ne vus ne ar the waistline with an irre g ular shap e and b ord e r. While this man was co nce rne d that it was g rowing the re we re no are as susp icious for me lanoma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 161-8 Cong e nital comp ound me lanocytic ne vus that was raise d and ve rrucous. The p atie nt re q ue ste d re moval and the re we re no sig ns of malig nancy. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

The border is irregular and the lesion may enlarge to cover an entire shoulder or upper arm. It is a type of hamartoma and is not a melanocytic nevus (see Chapter 160, Benign Nevi). • Café-au-lait spots—Coffee-and-milk-colored patch that can be present at birth or develop during early childhood. Although a number of large café-au-lait spots are associated with neuro bromatosis, a few of them can occur in completely unaffected individuals. These light-brown patches have increased melanin but are not nevi (see Chapter 235, Neuro bromatosis).

FIGURE 161-9 Cong e nital ne vus with some hyp e rtrichosis and a ce ntrally raise d are a. This was a b e nig n me lanocytic ne vus on the che st of a young woman. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

795

796

PART 14

DERMATO LO GY

FIGURE 161-10 Larg e b athing trunk ne vus on the b ack of a b oy since b irth. Note the hyp e rtrichosis and the sate llite le sions. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Ch a pt e r 161

FIGURE 161-12 This cong e nital ne vus was e llip tically e xcise d from the le g of a young wo man at he r re q ue st. The p atholog y sho we d a comp ound co ng e nital me lanocytic ne vus. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

MANAGEMENT The management of congenital nevi depends on size and location of the lesion (dif culty in monitoring), associated symptoms, age of the patient, the effect on cosmesis, and the potential for malignant transformation. • For small- and medium-sized congenital melanocytic nevi, the risk of malignant transformation is small and prophylactic removal is not recommended. For cosmesis, treatments include surgical excision (Figure 161-12) or laser treatment. • Larger congenital nevi can be surgically removed but may require tissue expanders, tissue grafts, and tissue aps to close large defects. Excisions can also be staged in multiple steps. Because the melanocytes

may extend deep into underlying tissues (including muscle, bone, and central nervous system), removing the cutaneous component may not eliminate the risk of malignancy. ° There is also concern that surgical9intervention may adversely affect congenital melanocytic nevi cells. • Laser treatment of the lesions has been performed with a number of different types of lasers. 10 Because of the lack of penetrance to deeper tissue levels, long-term recurrence or malignant transformation is also an issue with these techniques. • Careful lifelong follow-up with photographs is an acceptable approach, especially now with the affordability of digital cameras. • Garment or bathing trunk nevi (see Figure 161-4) that develop in bathing trunk ° Approximately half of the melanomas nevi do so before age 5 years. 11 These melanomas can be missed by observation because they can have nonepidermal origins. ° Surgical excision is recommended by some experts to prevent melanoma. 11 SO R . • Changes to watch for that call for a biopsy include the following: ° Partial regression (depressed white areas) (see Figure 161-2) ° In ammation. ° Rapid growth or color change. ° Development of a rm nodule (see Figure 161-2). ° A halo of hypopigmentation may form around any nevus including a congenital nevus (Figure 161-13). This in itself does not signify malignant transformation unless there are other suspicious features.

PATIENT EDUCATIO N • All patients should be told about the importance of protection from ultraviolet (UV) light exposure. This is especially important in people with giant congenital nevi, because they are at a signi cantly increased risk of melanoma. FIGURE 161-11 Larg e cong e nital sp e ckle d ne vus that ap p e ars on one sid e of the trunk of this old e r woman. (Re p ro d uce d with p e rmission fro m Richard P. Usatine , MD.)

• Patients should be taught to look for signs of melanoma (ABCDE) (asymmetry, border irregularity, color irregularity, diameter > 6 mm, evolution).

PART 14

CO NGe NIt a L Ne VI

DERMATO LO GY REFERENCES 1. Lyon VB. Congenital melanocytic nevi. Pediatr Clin North Am. 2010;57:1155-1176. 2. Gallus S, Naldi L; Oncology Study Group of the Italian Group for Epidemiologic Research in Dermatology. Distribution of congenital melanocytic naevi and congenital naevus-like naevi in a survey of 3406 Italian schoolchildren. Br J Dermatol. 2008;159(2):433-438. 3. Krengel S, Hauschild A, Schafer T. Melanoma risk in congenital melanocytic naevi: a systematic review. Br J Dermatol. 2006;155(1):1-8. 4. Bett BJ. Large or multiple congenital melanocytic nevi: occurrence of cutaneous melanoma in 1008 persons. JAmAcad Dermatol. 2005;52(5):793-797.

FIGURE 161-13 This me d ium-size d cong e nital me lanocytic ne vus on the trunk b e g an to lose some of its color and d e ve lop e d a white halo surround ing the p ig me nte d ce nte r. The re we re no susp icious are as for malig nancy e ve n thoug h the re was e volution of this me lanocytic le sion. A b iop sy Biop sy p e rforme d to re assure the p atie nt, was b e nig n. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FO LLO W-UP • Patients with giant congenital nevi or multiple congenital nevi may bene t from consultation with a neurologist because of the risk of neurocutaneous melanosis and its neurologic manifestations or obstructive hydrocephalus. • Bathing trunk nevi can also be associated with spina bi da, meningocele, and neuro bromatosis. 11 • Because patients with all forms of congenital nevi, especially giant congenital melanocytic nevi, have an increased risk of developing melanoma, patients should consider baseline photography and regular follow-up with an experienced clinician for these patients. PATIENT RESO URCES

• PubMed Health. Birthmarks-Pigmented—http:/ / www.ncbi.nlm .nih.gov/ pubmedhealth/ PMH0001831/ . • Medline Plus. Giant congenital nevi—http:/ / www.nlm.nih .gov/ medlineplus/ ency/ article/ 001453.htm. • Nevus support group—http:/ / www.nevus.org. PRO VIDER RESO URCES

• Medscape. Congenital Nevi—http:/ / emedicine.medscape .com/ article/ 1118659.

5. Marghoob AA, Agero AL, Benvenuto-Andrade C, et al. Large congenital melanocytic nevi, risk of cutaneous melanoma, and prophylactic surgery. JAmAcad Dermatol. 2006;54(5):868-870. 6. Sahin S, Levin L, Kopf AW, et al. Risk of melanoma in mediumsized congenital melanocytic nevi: a follow-up study. JAmAcad Dermatol. 1998;39:428-433. 7. Seidenari S, Pellacani G, Martella A, et al. Instrument-, age- and site-dependent variations of dermoscopic patterns of congenital melanocytic naevi: a multicentre study. Br J Dermatol. 2006;155(1):56-61. 8. Arneia JS, Gosain AK. Giant congenital melanocytic nevi. Plast Reconstr Surg. 2009;124(suppl 1):e1-e13. 9. Kinsler V, Bulstrode N. The role of surgery in the management of congenital melanocytic naevi in children: a perspective from Great Ormond Street Hospital. J Plast Reconstr Aesthet Surg. 2009;62(5): 595-601. 10. Ferguson RE Jr, Vasconez HC. Laser treatment of congenital nevi. J Craniofac Surg. 2005;16(5):908-914. 11. Habif T. Clinical Dermatology:A Color Guide to Diagnosis andTherapy. 4th ed. St. Louis, MO: Mosby; 2003.

797

798

PART 14

DERMATO LO GY

Ch a pt e r 162

162 EPIDERMAL NEVUS AND NEVUS SEBACEO US Mind y A. Smith, MD, MS Richard P. Usatine , MD

PATIENT STO RY The young man is in the of ce for a college physical examination and asks about the brown bumps under his chin. He states that this has been there as long as he can remember but no one has given him a diagnosis. (Figure 162-1). The man reports no symptoms and is not worried about the appearance. He is otherwise healthy with no neurologic symptoms. You inform him that this is an epidermal nevus and there is no need to excise it at this time. He may choose to have this removed by a plastic surgeon in the future purely for cosmetic purposes.

INTRO DUCTIO N • Epidermal nevi (EN) are congenital hamartomas of ectodermal origin classi ed on the basis of their main component: sebaceous, apocrine, eccrine, follicular, or keratinocytic. • Nevus sebaceous (NS) is a hamartoma of the epidermis, hair follicles, and sebaceous and apocrine glands. A hamartoma is the disordered overgrowth of benign tissue in its area of origin.

FIGURE 162-2 Ne vus se b ace ous on the scalp o a Hisp anic woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

SYNO NYMS • EN syndrome is also called Solomon syndrome and is a neurocutaneous disorder characterized by EN and an assortment of neurologic and visceral manifestations. • NS is also called sebaceous nevus and nevus sebaceus of Jadassohn (Figure 162-2). • An in ammatory linear verrucous epidermal nevus (ILVEN) (Figure 162-3) can be part of an epidermal nevus syndrome but some affected persons only have the cutaneous EN.

EPIDEMIO LO GY • EN are uncommon (approximately 1%-3% of newborns and children), sporadic, and usually present at birth. • EN are associated with disorders of the eye, nervous, and musculoskeletal systems in 10% to 30% of patients; in one study, 7.9% of patients

FIGURE 162-1 Line ar e p id e rmal ne vus on the ne ck o a young man that ap p e are d in e arly child hood . The p atie nt had no ne urolog ic, musculoske le tal, or vision p rob le ms. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 162-3 In ammatory line ar ve rrucous e p id e rmal ne vus (ILVEN) on the trunk o an ad ult man. Top ical ste roid s we re not he lp ul in d iminishing his p ruritus. (Re p rod uce d with p e rmission from Rob e rt T. Gilson, MD.)

PART 14

e pIDe r Ma L Ne VUS a ND Ne VUS Se Ba Ce O US

DERMATO LO GY

with EN had 1 of the 9 syndromes—an estimated 1 per 11,928 pediatric patients. 1 • In another review of 131 cases of EN, most (60%) had nonin ammatory EN, one-third had NS, and 6% had ILVEN. 2 • NS is usually present at birth or noted in early childhood. 3 Most cases are sporadic but familial cases have been reported. 2 • Linear NS is estimated to occur in 1 per 1000 live births. 4 • Linear NS syndrome includes a range of abnormalities, including the central nervous system (CNS); patients with CNS involvement typically have cognitive impairment and seizures3; other organ systems, including the cardiovascular, skeletal, ophthalmologic, and urogenital systems, may be involved.

ETIO LO GY AND PATHO PHYSIO LO GY • EN histologically display hyperkeratosis and papillomatosis, similar microscopically to seborrheic keratosis (see Chapter 156, Seborrheic Keratosis). 2 Also similar to seborrheic keratosis, some EN of keratinocyte differentiation (approximately one-third) have been found to have a mutation in the broblast growth factor receptor 3 (FGFR3) gene. • Nine EN syndromes have been reported and are described in the referenced article. 5 • EN frequently have a linear pattern that follows Blaschko lines (see Figures 162-1 and 162-3), which are believed to represent epidermal migration during embryogenesis. • As in the case above, EN tend to become thicker, verrucous, and hyperpigmented at puberty. 2 • Similarly, NS demonstrates stages of evolution paralleling the histologic differentiation of normal sebaceous gland. Lesions evolve from smooth to slightly papillated, waxy, hairless thickening in infants and young children to verrucous irregular lesions with a surface covered with numerous closely aggregated yellow-to-brown papules (Figure 162-4).6 ° Development of secondary appendageal tumors (Figures 162-5 and 162-6) occurs in 20% to 30% of patients, most are benign (most commonly basal cell epithelioma or trichoblastoma), but single (most commonly basal cell carcinoma) or multiple malignant tumors

FIGURE 162-4 Nevus sebaceous on the scalp o a young woman that is ve rrucous and brown. (Reproduced with permission from Richard P. Usatine, MD.)

FIGURE 162-5 Ne vus se b ace ous on the scalp o a young woman. The p atie nt re p orte d a ne w are a o e le vation and b le e d ing . A b iop sy showe d no malig nant trans o rmation. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

of both epidermal and adnexal origins may be seen and metastases have been reported. 2 • NS was shown to have a high prevalence of human papillomavirus (HPV) DNA and authors postulate that HPV infection of fetal epidermal stem cells could play a role in the pathogenesis. 7 MAKING THE DIAGNO SIS Clinical features of EN • EN are linear, round, or oblong; well-circumscribed; elevated; and at topped (see Figure 162-1). • Color is yellow-tan to dark brown. • Surface is uniform velvety or warty. • ILVEN, a less common type of EN, is pruritic and erythematous (see Figure 162-3).

FIGURE 162-6 Ne vus se b ace ous with a b e nig n tumor id e ntif e d as a syring ocystad e noma p ap illi e rum b y shave b iop sy. Patie nt was re e rre d or ull re moval o the ne vus se b ace ous. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

799

PART 14

800

DERMATO LO GY

Ch a pt e r 162

Clinical features of NS • NS has an oval-to-linear shape ranging from 0.5 × 1 to 7 × 9 cm. • NS is usually a solitary, smooth, waxy, hairless thickening noted on the scalp at birth or in early childhood (see Figures 162-2 and 162-4). TYPICAL DISTRIBUTIO N • EN occur most commonly on the head and neck followed by the trunk and proximal extremities; only 13% have widespread lesions. Lesions may spread beyond their original distribution with age. • NS are commonly found on the scalp followed by forehead and retroauricular region (see Figures 162-2 and 162-6) and rarely involves the neck, trunk, or other areas. BIO PSY Biopsy is the most de nitive method for diagnosing these nevi. A biopsy is not needed if the clinical picture is clear and no operative intervention is planned. A shave biopsy should provide adequate tissue for diagnosis because the pathology is epidermal and in the upper dermis. • Histologic features of epidermolytic hyperkeratosis within an EN are associated with mutations in the keratin gene that may be transmitted to offspring; widespread cutaneous involvement may be seen. 2

DIFFERENTIAL DIAGNO SIS • Linear lichen planus (Figure 162-7)—Discrete, pruritic, violaceous papules are arranged in a linear fashion, usually extending along an entire limb (see Chapter 152, Lichen Planus). • Syringoma (Figure 162-8)—Benign adnexal tumor derived from sweat gland ducts. Autosomal dominant transmission, soft, small, skincolored to brown papules develop during childhood and adolescence, especially around the eyes, but may be found on the face, neck, and trunk.

FIGURE 162-8 Syring oma on the lowe r e ye lid . (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

children but does occur in adults. While it is most often seen on an extremity, it can appear on the trunk. It can resemble a linear EN but lichen striatus will usually regress within 1 year.

MANAGEMENT MEDICATIO NS There are no proven topical methods for treatment of these lesions. Topical retinoids may improve lesion appearance but recurrence is common. 2

• Lichen striatus—Discrete pink, tan, or skin-colored asymptomatic papules in a linear band that appear suddenly (Figure 162-9). The papules may be smooth, scaly, or at topped. It is mostly seen in

FIGURE 162-7 Liche n p lanus on the e xor asp e ct o the ore arm in a line ar p atte rn re se mb ling a line ar e p id e rmal ne vus. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 162-9 Liche n striatus ne ar the axilla o a middle -age d woman. This re semble s a line ar e pide rmal ne vus and the biopsy prove d it to be liche n striatus in an adult. (Re prod uce d with pe rmission from Richard P. Usatine , MD.)

PART 14

e pIDe r Ma L Ne VUS a ND Ne VUS Se Ba Ce O US

PRO CEDURES

DERMATO LO GY REFERENCES

• Destructive modalities for EN, such as electrodessication and cryotherapy, may temporarily improve the appearance of the lesion, but recurrence is frequent. 2

1. Vidaurri-de la Cruz H, Tamayo-Sanchez L, Duran-McKinster C, et al. Epidermal nevus syndromes: clinical ndings in 35 patients. Pediatr Dermatol. 2004;21(4):432-439.

• Carbon dioxide laser is an alternative option for EN; however, scarring and pigment changes are potential permanent complications, especially in patients with darker skin types. 8 This treatment does not completely remove NS and there is recurrence risk. 2

2. Rogers M, McCrossin I, Commens C. Epidermal nevi and the epidermal nevus syndrome. A review of 131 cases. JAmAcad Dermatol. 1989;20(3):476-488.

• Surgical excision is an option that may be complicated by scarring. • Because of the potential for malignant transformation particularly following puberty, some authors recommend early complete plastic surgical excision for NS; SO R reconstructive surgery may be needed. • Excision of large lesions may require reconstructive surgery with a rotation ap to close. 9

PRO GNO SIS • There are reports of spontaneous improvement in patients with widespread involvement of EN. • Malignant potential is low in EN. 2 • Malignant potential in NS is uncertain. Reports range from 0% to 2.7%.2 ° Early reports suggested a high rate of developing basal cell carcinomas, whereas more recent studies identi ed trichoblastoma and syringocystadenoma papilliferum in NS, usually in adulthood. 2 10 ° Squamous cell carcinoma has also been described in NS.

FO LLO W-UP Patients with NS should be examined for other associated findings. Consider a consultation with a neurologist and/ or ophthalmologist. • In a study of 196 subjects with NS examined for clinical neurologic abnormalities, only 7% had abnormalities. 11 Abnormal examinations were more frequent in individuals with extensive nevi (21% vs 5%) and a centrofacial location (21% vs 2%). The patients depicted in this chapter had no neurologic abnormalities. PATIENT RESO URCES

• Nevus Outreach. Other Kinds of Nevi—http:/ / www.nevus.org/ other-kinds-of-nevi_id559.html. • Genetics Home Reference. Epidermal Nevus—http:/ / ghr.nlm .nih.gov/ condition/ epidermal-nevus. PRO VIDER RESO URCES

• Medscape. Nevus Sebaceous—http:/ / emedicine.medscape .com/ article/ 1058733-overview. • Medscape. Epidermal Nevus Syndrome—http:/ / emedicine .medscape.com/ article/ 1117506-overview.

3. Brandling-Bennett HA, Morel KD. Epidermal nevi. Pediatr Clin North Am. 2010;57:1177-1198. 4. Menascu S, Donner EJ. Linear nevus sebaceous syndrome: case reports and review of the literature. Pediatr Neurol. 2008;38(3):207-210. 5. Happle R. The group of epidermal nevous syndromes. Part I. Well-de ned phenotypes. JAm Acad Dermatol. 2010;63:1-22. 6. Hammadi AA. Nevus Sebaceous. Last updated June 9, 2010. http:/ / emedicine.medscape.com/ article/ 1058733-overview. Accessed August 2013. 7. Carlson JA, Cribier B, Nuovo G, et al. Epidermodysplasia verruciformis-associated and genital-mucosal high-risk human papillomavirus DNA are prevalent in nevus sebaceus of Jadassohn. JAmAcad Dermatol. 2008;59(2):279-294. 8. Boyce S, Alster TS. CO2 laser treatment of epidermal nevi: longterm success. Dermatol Surg. 2002;28(7):611-614. 9. Davison SP, Khachemoune A, Yu D, Kauffman LC. Nevus sebaceus of Jadassohn revisited with reconstruction options. Int J Dermatol. 2005;44(2):145-150. 10. Aguayo R, Pallarés J, Casanova JM, et al. Squamous cell carcinoma developing in Jadassohn’s sebaceous nevus: case report and review of the literature. Dermatol Surg. 2010;36(11):1763-1768. 11. Davies D, Rogers M. Review of neurological manifestations in 196 patients with sebaceous naevi. Australas J Dermatol. 2002;43(1):20-23.

801

802

PART 14

DERMATO LO GY

Ch a pt e r 163

163 DYSPLASTIC NEVUS Mind y A. Smith, MD, MS Richard P. Usatine , MD

PATIENT STO RY A 44-year-old man presents with concern over a mole on his back that his wi e says is growing larger and more variable in color. The edges are irregular and the color almost appears to be “leaking” into the surrounding skin. He reports no symptoms related to this lesion. On physical examination, the nevus is 9 mm in diameter with asymmetry and variations in color and an irregular border (Figure 163-1). A ull-body skin examination did not demonstrate any other suspicious lesions. Dermoscopy showed an irregular network with multiple asymmetrically placed dots o the network (Figure 163-2). A scoop saucerization was per ormed with a DermaBlade taking 2-mm margins o clinically normal skin (Figure 163-3). Although this could have been an early thin melanoma, the pathology showed a completely excised compound dysplastic nevus with no signs o malignancy. No urther treatment was needed except yearly skin examinations to monitor or melanoma.

INTRO DUCTIO N Dysplastic nevi (DN)/ atypical moles are acquired melanocytic lesions o the skin whose clinical and histologic de nitions are controversial and still evolving. These lesions have some small potential or malignant trans ormation and patients with multiple DN have an increased risk or melanoma. 1 The presence o multiple DN is a marker or increased melanoma risk just as red hair is, and, analogously, cutting o the red hair or cutting out all the DN does not change that risk o melanoma. The problem with DN is that any one lesion that is suspicious or melanoma must be biopsied to avoid missing melanoma, not to prevent melanoma rom occurring in that nevus in the uture.

FIGURE 163-1 G owing 9-mm com ound d ys lastic n vus on th b ack o a 44-y a -old man. Th is asymm t y and va iations in colo and an i g ula b o d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 163-2 D mosco y o this com ound d ys lastic n vus shows an i g ula n two k with multi l asymm t ically lac d d ots o th n two k. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

SYNO NYMS Dysplastic nevus is also called as atypical nevus, atypical mole, Clark nevus, nevus with architectural disorder, and melanocytic atypia. 1

EPIDEMIO LO GY • Two percent to 9% o the population has atypical moles (AMs). 2,3 In a Swedish case control study, 56% o cases (121 patients with melanoma) and 19% o 310 control subjects had nevi ul lling the clinical criteria or DN. 4 Among patients with melanoma, the rate o DN ranges rom 34% to 59%. 3 • Individuals with air skin types are at higher risk o DN. 3 • The sudden eruption o benign and atypical melanocytic nevi has been reported and is associated with blistering skin conditions and a number

FIGURE 163-3 A scoo sauc ization was o m d with a D maBlad taking 2-mm ma g ins o clinically no mal skin. Althoug h this could hav b n an a ly thin m lano ma, th atholog y show d a com l t ly xcis d com ound d ys lastic n vus with no sig ns o malig nancy. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DYSpLa St IC Ne VUS

PART 14

DERMATO LO GY

o disease states, including immunosuppression. Subsets o patients with immunosuppression have increased numbers o nevi on the palms and soles. 5 • The National Institute o Health Consensus Con erence on the diagnosis and treatment o early melanoma de ned a syndrome o amilial atypical mole and melanoma (FAMM). The criteria o FAMM syndrome are as below6: ° The occurrence o malignant melanoma in one or more rst- or second-degree relatives. ° The presence o numerous (o ten >50) melanocytic nevi, some o which are clinically atypical. ° Many o the associated nevi show certain histologic eatures (see later under Biopsy).

ETIO LO GY AND PATHO PHYSIO LO GY • Most DN are compound nevi (see Figure 163-1) possessing a junctional and intradermal component (see Chapter 160, Benign Nevi).1 The junctional component is highly cellular and consists o an irregular distribution o melanocytes arranged in nests and lentiginous patterns along the dermalepidermal junction. The dermal component, located at the center, consists o nests and strands o melanocytes with distinct sclerotic changes.1 • DN exhibit a host response consisting o irregular rete ridge elongation, subepidermal sclerosis, proli eration o dermal capillaries, and a perivascular, lymphohistiocytic inf ammatory in ltrate. 1 • Individuals with DN may have de cient DNA repair, and DN lesions are associated with overexpression o pheomelanin (pigment produced by melanocytes), which may lead to increased oxidative DNA damage and tumor progression. 7

DIAGNO SIS

FIGURE 163-5 Dys lastic n vus on th ch st o a 30-y a -old man. A shav bio sy succ ss ully mov d th whol l sion and conf m d that it was not m lanoma. Althoug h it was l ss than 6 mm, it had i g ula b o d s and va iation o colo . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Irregular, notched borders; pigment may ade o into surrounding skin (see Figure 163-5). • Flat or slightly raised (Figures 163-4 to 163-6) with the macular portion at edge, not verrucous or pendulous. • Lesions requently surrounded by a reddish hue rom reactive hyperemia making them appear target-like. • Usually larger than 6 mm; may be larger than 10 mm (see Figures 163-1 and 163-4). • Patients with FAMM syndrome may have more than 100 lesions, ar greater than the average number o common moles ($400

diclo enac 3% gel was as e ective as 5-FU cream or AK o the ace and scalp and diclo enac produced ewer signs o in ammation. 8 • Imiquimod 5% cream has been demonstrated to be e ective over a 16-week course o treatment, but studies have only measured 8 weeks o ollow-up. 5 SO R By weight, it is 19 times the cost o 5-FU. They have similar side e ects. 5 • One meta-analysis comparing imiquimod to 5-FU showed average complete clearance o AKs or each drug was 5-FU, 52 ± 18% and imiquimod, 70 ± 12%. 9 • Imiquimod applied topically or 12 to 16 weeks produced complete clearance o AKs in 50% o patients compared to 5% with vehicle (number needed to treat [NNT] = 2.2). Adverse events included erythema (27%), scabbing or crusting (21%), aking (9%), and erosions (6%) (number needed to harm [NNH] = 3.2-5.9). 10 • Because o its immunostimulatory properties, imiquimod cream must be used with caution in transplant patients on immunosuppression therapy. 1 SO R • Topical tretinoin has some e f cacy on the ace, with partial clearance o AKs, but may need to be used or up to a year at a time to optimize benef t. 5 SO R

A

• Cryosurgery was e ective or up to 75% o lesions in trials comparing it with photodynamic therapy. It may be particularly superior or thicker lesions, but may leave scars. 5 SO R • Photodynamic therapy (PDT) was e ective in up to 91% o AKs in trials comparing it with cryotherapy, with consistently good cosmetic results. It may be particularly good or superf cial and con uent AKs, but is likely to be more expensive than most other therapies. It is o particular value where AKs are numerous or when located at sites o poor healing, such as the lower leg. 5 SO R • Other less accessible and expensive methods include lasers, dermabrasion, and chemical peels. • Ingenol mebutate (Picato)—A short 2 to 3 days o treatment with daily topical ingenol mebutate rom the sap o Euphorbia peplus plant, showed promising e f cacy with a avorable sa ety prof le in several randomized controlled trials (RCTs). One multicenter RCT showed 34.1% to 42.2% complete clearance o AKs with ingenol mebutate gel 0.05% or trunk and extremities, and 0.015% or ace. 11 Another RCT with 0.05% gel showed a complete clearance o 71% o treated lesions. 12 Ingenol mebutate appears to have a dual mechanism o action by rapid lesion necrosis and subsequent immune-mediated cellular cytotoxicity, providing e f cacy with short treatment period. 13

B

FIGURE 164-10 A. Actinic ke ratose s re d d e ne d and cruste d b y the ap p lication o 5-f uorouracil top ically twice d aily. B. Face he ale d months a te r the co urse o 5-f uorouracil was co mp le te d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

ACTINIC KERATO SIS AND BO WEN DISEASE

811

TABLE 164-2 Summary o the Main Tre atme nt O p tions or Bowe n Dise ase 14

Le sio n Charact e rist ics

To p ical To p ical 5-FU Imiq uimo d * Cryo t he rap y Cure t t ag e Excisio n

PDT

Rad io t he rap y Lase r †

Small, sing le / e w, g ood he aling site ‡

4

3

2

1

3

3

5

4

Larg e , sing le , g ood he aling site ‡ Multip le , g ood he aling site ‡ Small, sing le / e w, p oor he aling site ‡ Larg e , sing le , p oor he aling site ‡ Facial Dig ital Pe rianal

3

3

3

5

5

2

4

7

3

4

2

3

5

3

4

4

2

3

3

2

2

1-2

5

7

3

2-3

5

4

5

1

6

7

4 3 6

7 7 6

2 3 6

2 5 6

4§ 2§ 1¶

3 3 7

4 3 2 to 3

7 3 6

3

3

3

5

4§

3

2 to 3

3

Pe nile

5-FU, 5-f uorouracil; PDT, p hotod ynamic the rap y; 1, p rob ab ly tre atme nt o choice ; 2, g e ne rally g ood choice ; 3, g e ne rally air choice ; 4, re asonab le b ut not usually re q uire d ; 5, g e ne rally p oor choice ; 6, p rob ab ly should not b e use d ; 7, insu cie nt e vid e nce availab le . The sug g e ste d scoring o the tre atme nts liste d take s into account the e vid e nce or b e ne t, e ase o ap p lication or time re q uire d or the p roce d ure , wound he aling , cosme tic re sult, and curre nt availab ility/costs o the me thod or acilitie s re q uire d . Evid e nce or inte rve ntions b ase d on sing le stud ie s or p ure ly ane cd otal case s is not includ e d . *Doe s not have a p rod uct lice nse or Bowe n d ise ase . † De p e nd s on site . ‡ Re e rs to the clinician’s p e rce ive d p ote ntial or g ood or p oor he aling at the a e cte d site . § Consid e r microg rap hic surg e ry or tissue sp aring or i p oorly d e ne d /re curre nt. ¶ Wid e e xcision re comme nd e d .

BO WEN DISEASE • Table 164-2 compares and summarizes the main treatment options. • The risk o progression to invasive cancer is approximately 3%. This risk is greater in genital BD, and particularly in perianal BD. A high risk o recurrence, including late recurrence, is a particular eature o perianal BD and prolonged ollow-up is recommended or this variant.14 SOR • There is reasonable evidence to support use o 5-FU. 14 SO R It is more practical than surgery or large lesions, especially at potentially poor healing sites, and has been used or “control” rather than cure in some patients with multiple lesions. 8 • Topical imiquimod may be used o -label or BD or larger lesions or di f cult or poor healing sites. 14 SO R However, it is costly and the optimum regimen has yet to be determined. 14 • One prospective study suggests a superiority o curettage and electrodesiccation over cryotherapy in treating BD, especially or lesions on the lower leg. 10 SO R Curettage was associated with a signif cantly shorter healing time, less pain, ewer complications, and a lower recurrence rate when compared with cryotherapy. 15 Curettage and electrodesication is also a good option or Bowen disease o the trunk or arms (Figure 164-11).

PREVENTIO N • Protection rom UV exposure by limiting outdoor activities, and using sunscreens and protective gears (hat, umbrella, long sleeve garments, etc). • Avoid artif cial tanning beds and tobacco.

PRO GNO SIS Prognosis o treated AK and BD is excellent.

FO LLO W-UP Patients need skin examinations every 6 to 12 months to identi y new precancers and cancers. SO R More requent examinations may be needed or those who have continued exposure to o ending agents (eg, organ transplant recipients on immunosuppressant therapy), and those with history o recurrent skin malignancies.

PATIENT EDUCATIO N Patients must understand that they acquired these conditions through cumulative sun damage, and they need to avoid urther sun damage to minimize the likelihood o additional precancers and cancers. The sun damage is o ten rom childhood and early adulthood, so the lesions are likely to orm even with uture sun protection. Sel -skin examination is recommended. All topical treatments or AKs and BD will make the lesions look worse be ore they get better (see Figure 164-10). The 5-FU treatments are o ten given with topical corticosteroid preparations to use a ter the treatment is over so as to minimize the symptoms o the in ammation.

PART 14 DERMATO LO GY

812

A

CHAPTER 164

B

FIGURE 164-11 A. Cure ttag e o Bowe n d ise ase on the arm. Each cycle b e g ins with cure ttag e and e nd s with e le ctrod e siccation. B. Ele ctrod e siccation o Bowe n d ise ase on the same arm. Thre e cycle s we re p e r orme d to comp le te the p roce d ure . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PATIENT RESO URCES

• Skin Cancer Foundation has an excellent website with photos and patient in ormation—http:/ / www.skincancer.org/ ak/ index.php. PRO VIDER RESO URCES

• Cox NH, Eedy DJ, Morton CA. Guidelines for management of Bowen’s disease: 2006 update. Br J Dermatol 2007;156(1):11-21. For detailed in ormation on the treatment o AKs and Bowen disease see: • Usatine R, Pfenninger J, Stulberg D, Small R. Dermatologic and Cosmetic Procedures in O f ce Practice. Elsevier, Inc., Philadelphia. 2012. • Usatine R, Stulberg D, Colver G. Cutaneous Cryosurgery. 4th Edition. Taylor and Francis, London, 2014. Both are available electronically through www.usatinemedia.com.

REFERENCES 1. Bonerandi JJ, Beauvillain C, Caquant L, et al. Guidelines for the diagnosis and treatment o cutaneous squamous cell carcinoma and precursor lesions. J Eur Acad DermatolVenereol. 2011;25(suppl 5):1-51. 2. Leffell DJ. The scienti c basis of skin cancer. JAmAcad Dermatol. 2000;42(1 pt 2):18-22. 3. Anwar J, Wrone DA, Kimyai-Asadi A, Alam M. The development of actinic keratosis into invasive squamous cell carcinoma: evidence and evolving classif cation schemes. Clin Dermatol. 2004;22(3):189-196. 4. Criscione VD, Weinstock MA, Naylor MF, et al. Actinic keratoses: natural history and risk o malignant trans ormation in the Veterans A airs Topical Tretinoin Chemoprevention Trial. Cancer. 2009;115(11):2523-2530. 5. de Berker D, McGregor JM, Hughes BR. Guidelines for the management o actinic keratoses. Br J Dermatol. 2007;156(2):222-230.

6. Zouboulis CC, Röhrs H. [Cryosurgical treatment o actinic keratoses and evidence-based review]. Hautarzt. 2005;56(4):353-358. 7. Thai K-E, Fergin P, Freeman M, et al. A prospective study o the use o cryosurgery or the treatment o actinic keratoses. Int J Dermatol. 2004;43(9):687-692. 8. Smith SR, Morhenn VB, Piacquadio DJ. Bilateral comparison of the e f cacy and tolerability o 3% diclo enac sodium gel and 5% 5- uorouracil cream in the treatment o actinic keratoses o the ace and scalp. J Drugs Dermatol. 2006;5(2):156-159. 9. Gupta AK, Davey V, Mcphail H. Evaluation of the effectiveness of imiquimod and 5- uorouracil or the treatment o actinic keratosis: critical review and meta-analysis o e f cacy studies. J Cutan Med Surg. 2005;9(5):209-214. 10. Hadley G, Derry S, Moore RA. Imiquimod for actinic keratosis: systematic review and meta-analysis. J Invest Dermatol. 2006;126(6): 1251-1255. 11. Lebwohl M, Swanson N, Anderson LL, et al. Ingenol mebutate gel or actinic keratosis. N Engl J Med. 2012;366(11):1010-1019. 12. Siller G, Gebauer K, Welburn P, Katsamas J, Ogbourne SM. PEP005 (ingenol mebutate) gel, a novel agent or the treatment o actinic keratosis: results o a randomized, double-blind, vehicle-controlled, multicentre, phase IIa study. Australas J Dermatol. 2009;50(1):16-22. 13. Rosen RH, Gupta AK, Tyring SK. Dual mechanism of action of ingenol mebutate gel or topical treatment o actinic keratoses: rapid lesion necrosis ollowed by lesion-specif c immune response. JAm Acad Dermatol. 2012;66(3):486-493. 14. Cox NH, Eedy DJ, Morton CA. Guidelines for management of Bowen’s disease: 2006 update. Br J Dermatol. 2007;156(1):11-21. 15. Ahmed I, Berth-Jones J, Charles-Holmes S, O’Callaghan CJ, Ilchyshyn A. Comparison o cryotherapy with curettage in the treatment o Bowen’s disease: a prospective study. Br J Dermatol. 2000;143(4):759-766.

PART 14

KERATO ACANTHO MA

DERMATO LO GY

165 KERATO ACANTHO MA Alfonso Guzman, MD Richard P. Usatine , MD

PATIENT STO RY A 71-year-old woman presented with a rapidly growing lesion on her face over the past 4 months (Figure 165-1). The lesion had features of a basal cell carcinoma with a pearly border and telangiectasias (Figure 165-2). Also the central crater with keratin gave it the appearance of a keratoacanthoma (KA). A shave biopsy was performed and the pathology showed squamous cell carcinoma (SCC)–KA type. A full elliptical excision with 4-mm margins was then performed.

INTRO DUCTIO N The KA is a unique epidermal tumor characterized by rapid, abundant growth and a spontaneous resolution, with the classic presentation in middle-aged, light-skinned individuals in hair-bearing, sun-exposed areas. In the late 1940s, Freudenthal of Wroclaw coined the term keratoacanthoma, owing to the considerable acanthosis observed in the tumor. Controversies have arisen since the 1950s about the real nature of the tumor; some KAs may metastasize, and there is debate over the relationship to SCC.1,2 Many dermatopathologists now classify this tumor as a subtype of SCC.

FIGURE 165-2 Close -up of the ke ratoacanthoma with te lang ie ctasias and a ce ntral ke ratin core on the face of the woman in Fig ure 165-1. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Molluscum pseudocarcinomatosum • Cutaneous sebaceous neoplasm

SYNO NYMS 1

• Keratocarcinoma

• Molluscum sebaceum

• Self-healing squamous epithelioma • Intracutaneous cornifying epithelioma • Idiopathic cutaneous pseudoepitheliomatous hyperplasia • Verrugoma

EPIDEMIO LO GY • KA develops as a solitary nodule in sun-exposed areas. • Seen more commonly later in life with a predilection for males. 1 • Develops rapidly within 6 to 8 weeks. • May spontaneously regress after 3 to 6 months or may continue to grow and rarely metastasize. 3

ETIO LO GY AND PATHO PHYSIO LO GY • KAs share features such as in ltration and cytologic atypia with SCCs. • KAs have been reported to metastasize. • KA is considered to be a variant of SCC, called SCC-KA type. • Histologic criteria are not sensitive enough to discriminate reliably between KA and SCC. 4

RISK FACTO RS FIGURE 165-1 Pe arly ke ratoacanthoma with te lang ie ctasias and a ce ntral ke ratin core on the face of a 71-ye ar-old woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Age 40 to 60 • Occurs on sun-exposed areas of skin

813

PART 14

814

DERMATO LO GY

Ch a pt e r 165

• Light complexion • Male gender

DIAGNO SIS CLINICAL FEATURES Solitary nodule is seen in sun-exposed areas. Often have a central keratin plug that resembles a volcano (Figures 165-1 to 165-5). KAs may grow rapidly (Figure 165-6). Rare cases of multiple eruptive KAs have been reported. 1 TYPICAL DISTRIBUTIO N KAs occur on face, arms, hands, and trunk (see Figures 165-3 and 165-5). KAs can be found anywhere on the head and neck, including the ears (Figures 165-6 and 165-7). LABO RATO RY STUDIES Biopsy is the only reliable method to make the diagnosis. KAs are welldifferentiated squamoproliferative skin lesions.

DIFFERENTIAL DIAGNO SIS • Actinic keratoses are precancerous lesions found on sun-exposed areas that may progress to SCC. Because these lesions are generally at they are rarely confused with KAs (see Chapter 164, Actinic Keratosis and Bowen Disease). • Cutaneous horn is a raised, keratinaceous lesion that can arise in actinic keratoses and in all types of nonmelanoma skin cancers. It generally does not have pearly raised skin around the keratin horn and therefore does not have the crater appearance of a KA (see Chapter 167, Cutaneous Horn).

FIGURE 165-5 Ke ratoacanthoma on the che st of a 70-ye ar-old man with ce ntral ke ratin core that re se mb le s a volcano. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• SCCs of the skin have many forms and KA is considered to be one type of SCC (see Chapter 169, Squamous Cell Carcinoma).

MANAGEMENT • A shave biopsy may be used for diagnosis but is not an adequate nal treatment. Options for de nitive treatment should be discussed with patient. • Although some KAs may regress spontaneously, there is no way to distinguish between these and the ones that are variants of SCC, which may go on to metastasize. Therefore, the standard of care is to remove or destroy the remaining tumor. SO R

FIGURE 165-3 Ke ratoacanthoma on the che st of a 53-ye ar-old man with ce ntral scaling . (Re p ro d uce d with p e rmission fro m Richard P. Usatine , MD.)

FIGURE 165-4 Sq uamous ce ll carcinoma of the ke ratoacanthoma typ e on the arm of a 61-ye ar-old man with ce ntral scaling . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14

Ke r a t O a Ca Nt h O Ma

A

DERMATO LO GY

B

FIGURE 165-6 Two SCCs in a 65-ye ar-old man. A. The SCC ove r the te mp le was a ke ratoacanthoma typ e , whe re as the SCC on the ne ck was a we ll-d iffe re ntiate d SCC. B. Rap id g rowth occurre d in b oth tumors ove r the 6-we e k p e riod that the p atie nt waite d to have he ad and ne ck surg e ry. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Elliptically excise a KA with margins of 3 to 5 mm as you would do in a SCC. 4 SO R

• Mohs surgery may be indicated for large or recurrent KAs or KAs located in anatomic areas with cosmetic or functional considerations.4 SOR

• Smaller, less-aggressive KAs diagnosed with shave biopsy may be destroyed with curettage and desiccation or cryotherapy with 3- to 5-mm margins. SO R

• Multiple eruptive KAs have been treated with oral retinoids, methotrexate, and cyclophosphamide. 1 SO R

PRO GNO SIS When compared to other skin cancers, prognosis is good. Excision is typically curative. 5

FO LLO W-UP Patients should perform their own skin examinations and have yearly clinical skin examinations to examine for recurrence and the development of new skin cancers.

PATIENT EDUCATIO N KA is similar to other nonmelanoma skin cancers in that it occurs on sunexposed areas and patients who have one are at increased risk of developing new skin cancers. Therefore, sun avoidance and sun protection should be emphasized. PATIENT RESO URCES FIGURE 165-7 Ke ratoacanthoma on the e ar. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

• Skinsight. Keratoacanthoma—http:/ / www.skinsight.com/ adult/ KA.htm.

815

816

PART 14

DERMATO LO GY

CHAPTER 165

PRO VIDER RESO URCES

REFERENCES

• Medscape. Keratoacanthoma—http:/ / emedicine.medscape .com/ article/ 1100471.

1. Karaa A, Khachemoune A. Keratoacanthoma: a tumor in search of a classi cation. Int J Dermatol. 2007;46(7):671-678.

For detailed information on the treatment of KAs see:

2. Ko CJ. Keratoacanthoma: facts and controversies. Clin Dermatol. 2010;28(3):254-261.

• Usatine R, Pfenninger J, Stulberg D, Small R. Dermatologic and Cosmetic Procedures in O f ce Practice. Elsevier, Inc., Philadelphia. 2012. • Usatine R, Stulberg D, Colver G. Cutaneous Cryosurgery. 4th Edition. Taylor and Francis, London, 2014. Both are available electronically through www.usatinemedia.com.

3. Clausen OP, Aass HC, Beigi M, et al. Are keratoacanthomas variants of squamous cell carcinomas? A comparison of chromosomal aberrations by comparative genomic hybridization. J Invest Dermatol. 2006;126(10):2308-2315. 4. Chuang TY. Keratoacanthoma. Updated July 2005. http:/ / www .emedicine.com/ derm/ topic206.htm. Accessed on May 28, 2006. 5. Beham A, Regauer S, Soyer HP, Beham-Schmid C. Keratoacanthoma: a clinically distinct variant of well differentiated squamous cell carcinoma. Adv Anat Pathol. 1998;5(5):269-280.

LENTIGO MALIGNA

PART 14 DERMATO LO GY

166 LENTIGO MALIGNA

• Generally, patients with LM are older than age 40 years, with a peak incidence between the ages o 65 and 80 years. 2

E.J. Maye aux Jr, MD Richard P. Usatine , MD

• Persons with LM melanoma (LMM) tend to be older, air-skinned persons with markers o actinic skin damage and prior skin cancers, and the incidence is increasing. 3

PATIENT STO RY A 65-year-old woman noted that a brown spot on her ace was growing larger and darker (Figure 166-1). A broad shave biopsy showed lentigo maligna (LM) (melanoma in situ). The patient was re erred or Mohs surgery or de nitive treatment.

INTRO DUCTIO N

• The lesions occur more commonly on the driver’s side o the head and neck in men in Australia. 4

ETIO LO GY AND PATHO PHYSIO LO GY • LM is a subtype o melanoma in situ, a preinvasive lesion con ned to the epidermis (Figures 166-1 to 166-3). • It is caused by cumulative sun exposure and, there ore, seen later in li e. • LMM occurs when the lesion extends into the dermis (Figure 166-4).

LM begins as a tan-brown macule melanoma usually in sun-damaged areas o the skin in older individuals. It is a subtype o melanoma in situ.

SYNO NYMS LM is also known as Hutchinson melanotic reckle.

EPIDEMIO LO GY • The incidence o LM is directly related to sun exposure. In the United States, the incidence is greatest in Hawaii, intermediate in the central and southern states, and lowest in the northern states. 1

FIGURE 166-1 Le ntig o malig na (me lanoma in situ) on the ace . (Re p rod uce d with p e rmission from Usatine RP, Moy RL, Tob inick EL, Sie g e l DM. Skin Su g e y: A P actical Guid e . St. Louis, MO : Mosb y; 1998.)

• LM can be present or long periods (5-15 years) be ore invasion occurs, although rapid progression within months has been described. 5 • The risk or progression to LMM appears to be proportional to the size o the lesion o LM. 5

RISK FACTO RS • Ultraviolet (UV) radiation exposure: Risk increases with increased hours o exposure to sunlight, with the amount o actinic damage, and with a history o nonmelanoma skin cancer.

FIGURE 166-2 LM on the ace , p e se nting as a sing le la g e e volving p ig me nte d le sion with chang ing co lo . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

817

PART 14 DERMATO LO GY

818

Ch a pt e r 166

DIAGNO SIS CLINICAL FEATURES • Large pigmented patch with multiple colors, including brown, black, pink, and white (signi ying regression) (see Figures 166-1 to 166-3). • May have ill-de ned borders and microscopic extension that can determine the clinical borders and complete removal o the lesion di cult. • One retrospective study revealed the 4 most important eatures o LM: asymmetric pigmented ollicular openings, dark rhomboidal structures, slate-gray globules, and slate-gray dots with a sensitivity o 89% and a speci city o 96% (see Appendix C, Dermoscopy). 6 TYPICAL DISTRIBUTIO N LM occurs on ace, head, and neck. There is a predilection or the nose and cheek (see Figures 166-1 and 166-2). BIO PSY

FIGURE 166-3 LM on the e a (me lanoma in situ). (Re p rod uce d with p e rmission from Usatine RP, Moy RL, Tob inick EL, Sie g e l DM. Skin Su g e y: A P actical Guid e . St. Louis, MO : Mosb y; 1998.)

• Increased number o melanocytic nevi, including large or giant congenital nevi. • Fair skin. • History o severe sunburns. • Porphyria cutanea tarda. • Tyrosine-positive oculocutaneous albinism. • Xeroderma pigmentosum. • Occupational risk with sun exposure.

• Complete excisional biopsy is rarely practical because these lesions are requently large and are on the ace (see Figure 166-1). There is debate in the literature between doing broad shave biopsy, multiple punch biopsy, and incisional biopsy. 7 The goal is to avoid sampling error and misdiagnosing a LM or LMM as a benign lesion. • A lesion suspicious or LM or LMM can be biopsied using a broad scoop shave biopsy approach with a DermaBlade or sharp razor blade (see Figure 166-4). 7 The goal is to sample the dermal–epidermal junction and still produce a good cosmetic result (especially i the lesion turns out to be benign). • One option is multiple smaller biopsy samples o each morphologically distinct region o the lesion. 7 • I an area suspicious or invasion is noted, or i there is an area o induration suspicious or associated desmoplastic melanoma, a deeper incisional biopsy o this area should be per ormed. 7 • I sampling is incomplete, the presence o a solar lentigo, pigmented actinic keratosis, or reticulated seborrheic keratosis (SK) could mislead the pathologist and clinician to the wrong conclusion that the incisional specimen is representative o the whole, and that no LM is present. 7 • In a study o LM, contiguous pigmented lesions were present in 48% o the specimens obtained by broad shave biopsy or Mohs surgery. The most common lesion was a benign solar lentigo (30%), ollowed by pigmented actinic keratosis (24%). 7 This should be kept in mind when interpreting biopsy results to avoid alse negatives.

DIFFERENTIAL DIAGNO SIS

FIGURE 166-4 LMM on the che e k. This le sion is invasive and no long e me lanoma in situ. A p a tial b oad scoop shave b iop sy is a g ood way to make this d iag nosis, as a ull-d e p th comp le te e xcisional b iop sy would b e p ohib itive ly la g e and a p unch b iop sy mig ht miss the d iag nosis. (Re p rod uce d with p e rmission from the Skin Cance r Found ation. For more information www.skincance r.org .)

• Solar lentigo—These hyperpigmented patches are very common on the aces and the dorsum o the hands o persons with signi cant sun exposure and the incidence increases with age. A possible solar lentigo is more suspicious or LM or LMM when it is larger, more asymmetric, has irregular borders, and has more variation in colors. Pigmented lesions with these characteristics should be biopsied to determine the correct diagnosis. Many air-skinned individuals have a number o solar lentigines making this a challenge. The use o dermoscopy and judicious biopsies is necessary to avoid missing LM and LMM (Figures 166-5 and 166-6). • SKs are ubiquitous benign growths that occur more requently with age. An early SK can be f at and easily resemble a solar lentigo or LM.

PART 14 DERMATO LO GY

Le Nt IGO Ma LIGNa

• LMM is the eared outcome o missing an LM and not treating it properly. Any suspicious lesion requires biopsy. Do not be a raid to do a quick and easy shave biopsy rather than a ull-thickness excision. I it turns out to be a LM or LMM, you can re er or de nitive treatment and your biopsy technique does not change the prognosis; early diagnosis does. LMM accounts or 4% to 15% o cutaneous melanoma (see Figure 166-4) (see Chapter 170, Melanoma).

MANAGEMENT Therapy is directed toward preventing progression to invasive LMM. NO NSURGICAL • Nonsurgical therapy or primary cutaneous melanomas should only be considered when surgical excision is not possible. • Alternatives to surgery include topical imiquimod, cryosurgery, and observation. E cacy o nonsurgical therapies or LM has not been ully established. 8 SO R C MEDICATIO NS FIGURE 166-5 Sola le ntig o on the ace o a mid d le -ag e d Hisp anic woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

The SKs on the back are less likely to be con used or LM, but a large f at SK on the ace can easily be mistaken or a LM. More importantly, avoid missing a LM because it is assumed to be a f at early SK. When in doubt, biopsy the lesion with a quick and easy shave biopsy. Do not reeze a possible SK unless you are sure that it is truly benign (see Chapter 156, Seborrheic Keratosis).

Topical imiquimod 5% cream has been described in multiple studies to be e ective in treating LM, especially in patients who are not surgical candidates. It is an immune response modi er that is indicated or the treatment o actinic keratosis and super cial basal cell carcinomas. Studies are limited by highly variable treatment regimens and lack o longterm ollow-up. 8-10 SO R B SURGICAL • For melanoma in situ, wide excision with 0.5- to 1.0-cm margins is recommended. For LM histologic subtype may require larger than 0.5-cm margins to achieve histologically negative margins, because o characteristically broad subclinical extension. 8,10 SO R • Standard therapy is margin-controlled surgical excision with Mohs surgery or rush permanent sections. 10,11 SO R B • The perimeter technique is a method o margin-controlled excision o LM with rush permanent sections. The main advantage is that all margins are examined with permanent sections. The main drawback is that multiple operative sessions are required to complete the procedure. 12 • Recommended margins or standard excision o melanoma in situ are 0.5 cm. This margin is o ten inadequate or LM because o the subclinical extension that can occur. 10 The average margin required to clear LM in 90% to 95% o cases in one study was greater than 0.5 cm. 11 Consequently, margin-controlled excision o LM is recommended.11 SO R B • Cryosurgery may be used in patients who are not good surgical candidates. In a study o 18 such patients with LM, the lesions resolved clinically in all cases, with no recurrence or metastasis detected during a mean ollow-up o 75.5 months.13 SOR C These patients were treated with 2 reeze–thaw cycles o liquid nitrogen under local anesthesia in a single sitting.

PREVENTIO N FIGURE 166-6 De moscop y o the sola le ntig o in Fig u e 166-5. The mo th-e ate n ap p e a ing e d g e s a e typ ical o a sola le ntig o. The e a e no susp icious p atte ns and a shave b iop sy conf me d that it was b e nig n. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Because LMM is related to a li etime o exposure to UV radiation, patients should limit sun exposure, especially between 10 a m and 4 pm. When in the sun, make sure to wear sunscreen with a high sun-protection actor (SPF) that blocks both UVA and UVB. It’s also a good idea to

819

PART 14 DERMATO LO GY

820

protect skin by wearing a broad-brim hat and clothing that covers your arms and legs.

PRO GNO SIS There is a 5% estimated li etime risk o developing LMM in patients diagnosed with LM at age 45 years. 5

FO LLO W-UP • The National Comprehensive Cancer Network recommends that patients have regular clinical skin examinations at least yearly by their amily physician or a dermatologist. 14 • Regional lymph nodes should also be examined.

PATIENT EDUCATIO N Patients diagnosed with LM need to minimize sun exposure and do regular sel -skin examinations. PATIENT RESO URCES

• Medline Plus. Melanoma—http:/ / www.nlm.nih.gov/ medlineplus/ melanoma.html. PRO VIDER RESO URCES

• The Skin Cancer Foundation. Melanoma—1-800-SKIN-490 or http:/ / www.skincancer.org. • National Cancer Institute. Melanoma—http:/ / www.cancer.gov/ cancertopics/ types/ melanoma. • Dermoscopy.org: A website on dermoscopy to learn how to improve early diagnosis o melanoma—http:/ / www .dermoscopy.org/ . REFERENCES 1. Clark WH Jr, Mihm MC Jr. Lentigo maligna and lentigo-maligna melanoma. Am J Pathol. 1969;55(1):39-67. 2. Cohen LM. Lentigo maligna and lentigo maligna melanoma. JAm Acad Dermatol. 1995;33(6):923-936.

CHAPTEr 166

3. Swetter SM, Boldrick JC, Jung SY, et al. Increasing incidence o lentigo maligna melanoma subtypes: northern Cali ornia and national trends 1990-2000. J Invest Dermatol. 2005;125(4):685-691. 4. Jel s PL, Giles G, Shugg D, et al. Cutaneous malignant melanoma in Australia, 1989. Med JAust. 1994;161(3):182-187. 5. Weinstock MA, Sober AJ. The risk o progression o lentigo maligna to lentigo maligna melanoma. Br J Dermatol. 1987;116 (3):303-310. 6. Schi ner R, Schi ner-Rohe J, Vogt T, et al. Improvement o early recognition o lentigo maligna using dermatoscopy. JAmAcad Dermatol. 2000;42(1 pt 1):25-32. 7. Dalton SR, Gardner TL, Libow LF, Elston DM. Contiguous lesions in lentigo maligna. JAmAcad Dermatol. 2005;52:859-862. 8. Bichakjian CK, Halpern AC, Johnson TM, et al. Guidelines o care or the management o primary cutaneous melanoma. J Am Acad Dermatol. 2011;65(5):1032-1047. 9. Buettiker UV, Yawalkar NY, Braathen LR, Hunger RE. Imiquimod treatment o lentigo maligna: an open-label study o 34 primary lesions in 32 patients. Arch Dermatol. 2008;144(7):943-945. 10. Erickson C, Miller SJ. Treatment options in melanoma in situ: topical and radiation therapy, excision and Mohs surgery. Int J Dermatol. 2010;49(5):482-491. 11. Huang CC. New approaches to surgery o lentigo maligna. Skin Therapy Lett. 2004;9(5):7-11. 12. Mahoney MH, Joseph M, Temple CL. The perimeter technique or lentigo maligna: an alternative to Mohs micrographic surgery. J Surg Oncol. 2005;91(2):120-125. 13. de Moraes AM, Pavarin LB, Herreros F, et al. Cryosurgical treatment o lentigo maligna. J Dtsch Dermatol Ges. 2007;5(6):477-480. 14. The National Comprehensive Cancer Network. National Clinical Guidelines in Oncology: Melanoma, 2009. http:/ / www.mmmp.org/ mmmpFile/ image/ conv%20ther/ NCCN%20guidelines_Melanoma. pd . Accessed April 20, 2012.

CUTANEO US HO RN

PART 14 DERMATO LO GY

167 CUTANEO US HO RN Mind y A. Smith, MD, MS

PATIENT STO RY A 74-year-old man asks about a lesion on the back o his right ear (Figure 167-1). It has been present or approximately 5 years. Although the lesion does not bother him, his wi e is concerned because it has been slowly growing. Shave biopsy revealed that the horn was rom a basal cell carcinoma. The patient was re erred or Mohs surgery to excise the remainder o the cancer.

SYNO NYM Cutaneous horn is also known as cornu cutaneum.

INTRO DUCTIO N Cutaneous horn is a morphologic (not pathologic) designation or a hyperkeratotic protuberant mass rising above the skin, resembling the horn o an animal.

EPIDEMIO LO GY Relatively rare lesion, most o ten occurring on sun-exposed areas o the skin in elderly men; a recent Brazilian case series, however, ound a higher prevalence in women. 1

FIGURE 167-2 Cutane ous horn in a sq uamous ce ll carcinoma in situ just late ral to the e ye . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

ETIO LO GY AND PATHO PHYSIO LO GY • Results rom unusual cohesiveness o keratinized material rom the super cial layers o the skin or deeply embedded in the cutis. Etiology is unknown but may be related to skin damage rom sun exposure or trauma; in ectious causes have also been reported including molluscum contagiosum and leishmaniasis. 2 • Consists o marked retention o stratum corneum. • May be benign, premalignant, or malignant (Figures 167-1 to 167-3) at the base; in 2 large series, 58.6% and 38.9% had malignant or premalignant base pathology. 1,3 • A history o other malignant or premalignant lesions, tenderness at the base, large size, older age, and location on the penis increase the risk o underlying malignancy. 2-4

FIGURE 167-1 Cutane ous horn on p oste rior rig ht p inna arising in a b asal ce ll carcinoma. (Re p rod uce d with p e rmission from Usatine RP, Moy RL, To b inick EL, Sie g e l DM. Skin Surg e ry: A Practical Guid e . St. Louis, MO : Mosb y; 1998.)

FIGURE 167-3 Cutane ous horn on the arm o a 65-ye ar-old woman, which g re w rap id ly ove r 6 months. Biop sy re ve ale d a sq uamous ce ll carcinoma o the ke ratoacanthoma typ e . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

821

PART 14 DERMATO LO GY

822

Ch a pt e r 167

A

FIGURE 167-5 Cutane ous horn on the b ack o a 73-ye ar-old woman within an e nd op hytic wart. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

RISK FACTO RS • Advanced age (> 70 years) • Sun/ radiation exposure

B FIGURE 167-4 A. Cutane o us horn o n the hand o a 33-ye ar-old man o r 8 ye ars. He clip p e d it with nail clip p e rs many time s b ut it always g re w b ack. A shave e xcision succe ss ully re move d it and the p atholog y showe d a viral wart at the b ase . B. Clo se -up o the cutane o us ho rn. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

• Associated with many types o skin lesions (at the base) that can retain keratin and produce horns including actinic keratosis, warts (Figures 167-4 and 167-5), seborrheic keratosis (Figures 167-6 and 167-7), keratoacanthoma (see Figure 167-3), sebaceous gland, and basal or squamous cell carcinoma (see Figures 167-1 to 167-3). In the more recent case series, actinic keratosis was ound in 83.8% o the premalignant cases and squamous cell carcinoma was ound in 93.75% o the malignant cases. 1 • Rare cases have been described in association with metastatic renal cell carcinoma, lymphoma, dermato broma, pyogenic granuloma (Figure 167-8), and, recently, Kaposi sarcoma. 5

FIGURE 167-6 Larg e cutane ous horn on the ace o an 88-ye ar-old woman. A te r shave re moval the p atholog y showe d se b orrhe ic ke ratosis with chronic inf ammation and cutane ous horn ormation. (Re p rod uce d with p e rmission from Scott Be rg e aux, MD.)

PART 14 DERMATO LO GY

CUt a Ne O US h O r N

• Size may vary rom a ew millimeters to several centimeters; gigantic cutaneous horns (17-25 cm length and up to 2.5 cm width) have been reported, and in one series o 4 cases, all were benign. 6 • Because o their height, cutaneous horns may be traumatized causing bleeding or pain. TYPICAL DISTRIBUTIO N May occur on any area o the body; approximately 30% are ound on the ace (see Figures 167-2, 167-6, and 167-7) and scalp and another 30% on the upper limbs. 1 BIO PSY The horn itsel consists o concentric layers o corni ed epithelial cells (hyperkeratosis). The base may display eatures o the associated pathologic etiology.

DIFFERENTIAL DIAGNO SIS

FIGURE 167-7 Anothe r vie w o this amazing cutane ous horn. The p atie nt had the le sio n since he r e arly 30s and attrib ute d it to hot g re ase p op p ing on he r ace . She had shown it to othe r p hysicians who d e cline d to re move it. Patie nt state d it “mad e he r e e l 16 ag ain” to have it re move d . (Re p rod uce d with p e rmission from Scott Be rg e aux, MD.)

Common warts are well-demarcated, rough, hard papules with an irregular papillary sur ace. Although they may orm cylindrical projections, these o ten use to orm a sur ace mosaic pattern; paring the surace exposes punctate hemorrhagic capillaries (see Chapter 130, Common Warts).

MANAGEMENT DIAGNO SIS CLINICAL FEATURES • Horn-like protuberance. • Lesions are usually rm; have been described as f at, keratotic, nodular, pedunculated, and ulcerated. 3

• Shave excision, ensuring that the base o the epithelium is obtained or histologic examination, and send to pathology; i benign, may reeze remainder o the lesion. • Excisional biopsy may also be per ormed, with wider margins (tumorree margin o at least 3 mm) i suspected malignancy.

FO LLO W-UP • Routine ollow-up is not needed provided complete removal is accomplished or malignant and premalignant lesions; in one case series o 48 eyelid cutaneous horns, there was no recurrence over a mean o 21 months. 7 • Patients with any skin cancer should be seen yearly or skin examinations because one cancer puts them at higher risk or all skin cancers. SO R C

PATIENT AND PRO VIDER RESO URCES

• Medscape. Cutaneous Horn—http:/ / emedicine.medscape .com/ article/ 1056568. • Skinsight. Cutaneous Horn—http:/ / www.skinsight.com/ adult/ cutaneousHorn.htm REFERENCES 1. Mantese SA, Diogo PM, Rocha A, et al. Cutaneous horn: a retrospective histopathological study o 222 cases. An Bras Dermatol. 2010;85(2):157-163. FIGURE 167-8 Cutane ous horn arising in a p yog e nic g ranuloma. (Re p rod uce d with p e rmission from Suraj Re d d y, MD.)

2. Vera-Donoso CD, Lujan S, Gomez L, et al. Cutaneous horn in glans penis: a new clinical case. Scand J Urol Nephrol. 2009;43(1):92-93.

823

824

PART 14 DERMATO LO GY 3. Yu RC, Pryce DW, Mac arlane AW, Stewart TW. A histopathological study o 643 cutaneous horns. Br J Dermatol. 1991;124:499-452. 4. Solivan GA, Smith KJ, James WD. Cutaneous horn o the penis: its association with squamous cell carcinoma and HPV-16 in ection. JAm Acad Dermatol. 1990;23(5 pt 2):969-972. 5. Onak Kandemir N, Gun BD, Barut F, et al. Cutaneous horn-related Kaposi’s Sarcoma: a case report. Case Report Med. 2010;2010. pii: 825949.

CHAPTER 167

6. Michal M, Bisceglia M, Di Mattia A, et al. Gigantic cutaneous horns o the scalp: lesions with a gross similarity to the horns o animals: a report o our cases. Am J Surg Pathol. 2002;26:789-794. 7. Mencia-Gutiérrez E, Gutiérrez-Diaz E, Redondo-Marcos I, et al. Cutaneous horns o the eyelid: clinicopathological study o 48 cases. J Cutan Pathol. 2004;31:539-543.

BASAL CELL CARCINO MA

SECTIO N 11

PART 14 DERMATO LO GY

SKIN CANCER

168 BASAL CELL CARCINO MA Jonathan B. Karne s, MD Richard P. Usatine , MD

PATIENT STO RY A 52-year-old woman presented to the o ce with a “mole” that had been increasing in size over the last year (Figure 168-1). This “mole” had been on her ace or at least 5 years. The di erential diagnosis o this lesion was a nodular basal cell carcinoma (BCC) versus an intradermal nevus. A shave biopsy con rmed it was a nodular BCC and the lesion was excised with an elliptical excision.

INTRO DUCTIO N BCC is the most common cancer in humans. Usually ound on the head and neck, it is generally slow growing and almost never kills or metastasizes when treated in a timely ashion. However, the treatment necessary to eliminate it is o ten surgical and may cause scarring and changes in appearance and/ or unction.

EPIDEMIO LO GY • BCC is the most common skin cancer but the exact incidence is not known. 1 • Incidence o these cancers increases with age, related to cumulative sun exposure.

FIGURE 168-2 Nod ular b asal ce ll carcinoma (BCC) on the nasal ala o an 82-ye ar-old woman. The nose is a ve ry common location or a BCC. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Other clinical variants including pigmented, polypoid, giant, keloidal, linear, and broepithelioma o Pinkus have been recognized, but are less common to very rare. 2

ETIO LO GY AND PATHO PHYSIO LO GY • BCCs spread locally and very rarely metastasize. • Basal cell nevus syndrome, also known as Gorlin syndrome, is a rare autosomal dominant condition in which a ected individuals have multiple BCCs that may clinically mimic nevi (Figure 168-9).

• Nodular BCCs—Most common type (70%) (Figures 168-1 to 168-4). • Super cial BCCs—Next most common type (Figures 168-5 and 168-6). • Sclerosing (or morphea orm) BCCs—The least common type (Figures 168-7 and 168-8).

FIGURE 168-1 Pe arly nod ular b asal ce ll carcinoma (BCC) on the ace o a 52-ye ar-old woman p re se nt or 5 ye ars. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 168-3 Nod ular b asal ce ll carcinoma (BCC) on the lowe r e ye lid . Patie nt re e rre d or Mohs surg e ry. The d i e re ntial d iag nosis is a hid rocystoma. This BCC is a rm nod ule and a hid rocystoma is f uid - lle d and so te r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

825

PART 14 DERMATO LO GY

826

FIGURE 168-4 Larg e nod ular b asal ce ll carcinoma with an annular ap p e arance on the ace o a home le ss woman. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

RISK FACTO RS

Ch a pt e r 168

FIGURE 168-6 Sup e r cial b asal ce ll carcinoma on the arm o a air-skinne d we ld e r mimicking nummular e cze ma. (Re p rod uce d with p e rmission from Jonathan B. Karne s, MD.)

• Latitude • Immunosuppression

• Advanced age

• Genetic predisposition

• Cumulative sun exposure

• Family history

• Radiation exposure

• Skin type3

FIGURE 168-5 Sup e r cial b asal ce ll carcinoma on the b ack o a 45-ye ar-old man who e njo ys running in the Cali o rnia sun witho ut his shirt. Note the d i use scaling , thre ad y b o rd e r (slig htly raise d and p e arly), and sp o tty hyperpigmentation. (Reproduced with permission from Richard P. Usatine, MD.)

FIGURE 168-7 Scle rosing b asal ce ll carcinoma on the ore he ad o a man re se mb ling a scar. Note the white color with shiny atrop hic skin. (Re p rod uce d with p e rmission from the Skin Cance r Found ation. For more information www.skincance r.org .)

PART 14 DERMATO LO GY

Ba Sa L Ce LL Ca r CINO Ma

FIGURE 168-10 Larg e p ig me nte d nod ular b asal ce ll carcinoma on the ace with ulce ration mimicking me lanoma. (Re p rod uce d with p e rmission from Jonathan B. Karne s, MD.)

• May be moderately to deeply pigmented (Figures 168-10 to 168-12) • May ulcerate (Figures 168-13 to 168-16) and can leave a bloody crust FIGURE 168-8 Ad vance d scle rosing b asal ce ll carcinoma on the che e k o a man, causing e ctrop ion (the e ye lid is b e ing pulle d d own b y the scle rotic skin chang e s). (Re p roduce d with pe rmission from Usatine RP, Moy RL, Tob inick EL, Sie g e l DM. Skin Surge ry: A Practical Guid e . St. Louis, MO : Mosb y; 1998.)

DIAGNO SIS CLINICAL FEATURES Common clinical eatures o the 3 most common morphologic types are listed below. Nod ular BCC • Raised pearly white, smooth translucent sur ace with telangiectasias • Smooth sur ace with loss o the normal pore pattern (see Figures 168-1 to 168-4)

FIGURE 168-9 Basal ce ll ne vus synd rome with o ve r 30 small ne void b asal ce ll carcinomas on the ace o a 29-ye ar-old man. This is a rare autosomal d ominant cond ition. Note the scars rom the tre atme nt o p re vious BCCs and the hyp e rte lorism that is p art o the synd ro me . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

Sup e rf cial BCC • Red or pink patches to plaques o ten with mild scale and a thready border (slightly raised and pearly) (see Figure 168-5) • Found more commonly on the trunk and upper extremities than the ace Scle rosing (morp he a orm) • Ivory or colorless, f at or atrophic, indurated, may resemble scars, are easily overlooked (see Figures 168-7 and 168-8) • Called morphea orm because o their resemblance to localized scleroderma (morphea) • The border is not well demarcated and the tumor can spread ar beyond what is clinically visible (Figure 168-17) • These BCCs are the most dangerous and have the worst prognosis

FIGURE 168-11 Darkly p ig me nte d larg e b asal ce ll carcinoma with raise d b ord e rs and some ulce ration in a 53-ye ar-old Hisp anic man. A b iop sy was p e r orme d to rule out me lanoma b e ore this was e xcise d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

827

PART 14 DERMATO LO GY

828

Ch a pt e r 168

FIGURE 168-12 Darkly p ig me nte d b asal ce ll carcinoma with p e arly b ord e rs and some ulce ration in a 73-ye ar-old Hisp anic woman. A b iop sy was p e r orme d to rule out me lano ma b e ore this was e xcise d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 168-14 Basal ce ll carcinoma in the nasal alar g roove . The re is a hig h risk o re curre nce at this site so Mohs surg e ry is ind icate d or re moval. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

TYPICAL DISTRIBUTIO N

• Arborizing “tree-like” telangiectasia

Ninety percent appear on ace, ears, and head, with some ound on the trunk and upper extremities (especially the super cial type). 1 Recently lesions on the ears have been associated with a more aggressive behavior (Figure 168-18). 4

• Ulceration

DERMO SCO PY Dermoscopic characteristics o BCCs (Figures 168-19 and 168-20) include the ollowing: • Large blue-gray ovoid nests • Multiple blue-gray globules • Lea -like areas, also called clods, that look like maple leaves

• Shiny white areas/ stellate streaks (see Appendix C, Dermoscopy or urther in ormation) BIO PSY • A shave biopsy is adequate to diagnose a nodular BCC or a thick supercial BCC. • A scoop shave or punch biopsy is pre erred or a sclerosing BCC or a very f at super cial BCC. • In many instances, excision at the time o de nitive treatment reveals a di erent morphologic type in deeper tissue. 5

• Spoke-wheel areas

FIGURE 168-13 Ulce rate d b asal ce ll carcinoma on the scalp o a 35-ye arold woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 168-15 Larg e ad vance d b asal ce ll carcinoma with ulce rations and b lood y crusting in ltrating the up p e r lip . The p atie nt was re e rre d or Mohs surg e ry. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

Ba Sa L Ce LL Ca r CINO Ma

A

B

FIGURE 168-16 A. Ve ry larg e ulce rating b asal ce ll carcinoma on the ne ck o a 65-ye ar-old white man, which has b e e n g rowing the re or 6 ye ars. It was e xcise d in the op e rating room with a larg e f ap ro m his che st use d to close the b ig d e e ct. B. The same man showing re curre nce within the scar a e w ye ars late r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

DIFFERENTIAL DIAGNO SIS Nod ular BCC • Intradermal (dermal) nevi may look very similar to nodular BCCs with telangiectasias and smooth pearly borders (Figure 168-21). A history o stable size and lack o ulceration may be help ul in distinguishing them rom a nodular BCC. A simple shave biopsy is diagnostic and produces a good cosmetic result. Excisional biopsy is usually unnecessary and can be de orming. It is remarkable how similar Figure 168-21 appears to Figure 168-1 (both biopsies proven to be as labeled) (see Chapter 160, Benign Nevi). • Sebaceous hyperplasia is a benign adnexal tumor common on the ace in older adults and usually occurs with more than one lesion present (Figure 168-22). This benign overgrowth o the sebaceous glands produces small waxy yellow-to-pink papules with telangiectasias. Dermoscopy may show vessels that radiate out rom the center like spokes on a wheel (see Chapter 157, Sebaceous Hyperplasia). • Fibrous papule o the ace is a benign condition with small papules that can be rm and pearly. • Trichoepithelioma/ trichoblastoma/ trichilemmoma are benign tumors on the ace that can appear around the nose. They may be pearly but usually do not have telangiectasias. These are best diagnosed with a shave biopsy, but trichoepitheliomas can even mimic a BCC on histology. • Keratoacanthoma is a type o squamous cell carcinoma that is raised, nodular, and may be pearly with telangiectasias. A central keratin- lled crater may help to distinguish this rom a BCC (see Chapter 165, Keratoacanthoma).

Sup e rf cial BCC • Actinic keratoses are precancers that are f at, pink, and scaly. They lack the pearly and thready border o the super cial BCC (see Chapter 164, Actinic Keratosis and Bowen Disease). • Bowen disease is a squamous cell carcinoma in situ that appears like a larger thicker actinic keratosis with more distinct well-demarcated borders. It also lacks the pearly and thready border o the super cial BCC (see Chapter 164, Actinic Keratosis and Bowen Disease). • Nummular eczema can usually be distinguished by its multiple coinlike shapes, transient nature, and rapid response to topical steroids. These lesions are extremely pruritic and most patients will have other signs and symptoms o atopic disease (see Chapter 143, Atopic Dermatitis). • Discoid lupus erythematosus is a cutaneous mani estation o autoimmune disease and o ten presents with skin color change, scaling, and hair ollicle destruction. These have characteristic predilection or the ears, scalp, and ace, but may be ound on the trunk and extremities (see Chapter 178, Lupus). • Benign lichenoid keratosis is a variably scaly, f at, or slightly raised benign reactive neoplasm on sun-damaged skin. It is o ten on the trunk or extremities and can have blue-gray globules on dermoscopy and some pearly color. Scle rosing (morp he a orm) BCC Scars may look like a sclerosing BCC. Ask about previous surgeries or trauma to the area. I the so-called scar is f at, shiny, and enlarging, a biopsy still may be needed to rule out a sclerosing BCC.

829

PART 14 DERMATO LO GY

830

A

Ch a pt e r 168

B

C FIGURE 168-17 A. Scle rosing b asal ce ll carcinoma in an e ld e rly man. The size o the b asal ce ll carcinoma d id not ap p e ar larg e b y clinical e xamination. B. Mohs surg e ry o the same scle rosing b asal ce ll carcinoma. This took 4 e xcisions to g e t cle an marg ins. Usual 4- to 5-mm marg ins with an e llip tical e xcision would not have re move d the ull tumor. C. Re p air d one close the larg e d e e ct. The cure rate should b e close to 99%. (Re p rod uce d with p e rmission from Ryan O ’Q uinn, MD.)

MANAGEMENT • Mohs micrographic surgery (3 studies, N = 2660) is the gold standard but is not needed or all BCCs. Recurrence rate is 0.8% to 1.1% (see Figure 168-17B). Mohs micrographic surgery (pioneered by Dr. Frederick Mohs) entails surgical removal o tumors with immediate histologic processing in sequential horizontal layers preserving a continuous peripheral margin that is mapped to the clinical lesion. Concentric surgical margins are taken until all margins are clear

(see Figure 168-17). This is the treatment o choice or BCCs with poorly de ned clinical margins or in areas o signi cant cosmetic or unctional importance such as the ace. 6 SO R • Surgical excision (3 studies, N = 1303): Recurrence rate was 2% to 8%. Mean cumulative 5-year rate1 (all 3 studies) was 5.3%. Recommended margins are 4 to 5 mm. SO R • Cryosurgery (4 studies, N = 796): Recurrence rate was 3% to 4.3%. Cumulative 5-year rate (3 studies) ranged rom 0% to 16.5%. 6 SO R Recommended reeze times are 30 to 60 seconds with a 5-mm halo.

PART 14 DERMATO LO GY

Ba Sa L Ce LL Ca r CINO Ma

FIGURE 168-18 Ulce rate d nod ular b asal ce ll carcinoma o the e ar in a 67-ye ar-old man. This is an ag re ssive tumor and should b e re e rre d or Mohs surg e ry. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

A

B A

FIGURE 168-20 De rmoscop y o 2 d i e re nt b asal ce ll carcinomas. Characte ristic nd ing s o b asal ce ll carcinomas includ e arb orize d ve sse ls, b lue -g ray ovoid ne sts, sp oke whe e l structure s, and le a -like structure s. A. (Re p rod uce d with p e rmission rom Ash aq Marg hoob , MD.) B. Note the le a -like structure s on the p e rip he ry o this BCC. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

B FIGURE 168-19 A. Larg e nod ular b asal ce ll carcinoma on the che e k o a 52-ye ar-old man. The re is a loss o normal p ore p atte rn, p e arly ap p e arance , te lang ie ctasias, and some are as o d ark p ig me ntation. B. De rmoscop y o the no d ular b asal ce ll carcino ma. The re are visib le arb o rizing “tre e -like ” te lang ie ctasias, ulce rations, shiny white are as, and g ray-b lue g lob ule s all consiste nt with a b asal ce ll carcinoma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 168-21 Pe arly d ome -shap e d intrad e rmal ne vus ne ar the nose with te lang ie ctasias close ly re se mb ling a b asal ce ll carcinoma. A shave b iop sy p rove d that this was an intrad e rmal ne vus. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

831

832

PART 14 DERMATO LO GY

FIGURE 168-22 Exte nsive se b ace ous hyp e rp lasia on the che e k o a 52-ye ar-old woman. The larg e st one has visib le te lang ie ctasias and could b e mistake n or a b asal ce ll carcinoma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

This can be divided up into two 30-second reezes with a thaw in between. For such long reeze times, most patients will pre er a local anesthetic (Figure 168-23). SO R C • Curettage and desiccation (6 studies, n = 4212): Recurrence rate ranged rom 4.3% to 18.1%; cumulative 5-year rate ranged rom 5.7% to 18.8%. Three cycles o curettage and desiccation can produce higher cure rates than 1 cycle (Figure 168-24). 6 SO R

Ch a pt e r 168

FIGURE 168-24 Cure ttag e and e le ctrod e ssication o a sup e r cial b asal ce ll carcinoma on the e xtre mity is a rap id and e e ctive tre atme nt. The ab normal tumor tissue is so te r than the surround ing normal skin and scoop s out e asily. (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

• Imiquimod is Food and Drug Administration (FDA) approved or the treatment o super cial BCCs less than 2 cm in diameter. 7 SO R B Con rm diagnosis with biopsy and use when surgical methods are contraindicated. A recent study combining cryotherapy with imiquimod improved decreased the recurrence rate. 8 • Vismodegib is an FDA-approved targeted chemotherapy or the treatment o metastatic or nonresectable BCCs that cannot be treated with radiation. It targets the smoothened pathway, which is damaged in basal cell nevus syndrome and altered in most BCCs. 9 SO R B

PREVENTIO N AND SCREENING • All skin cancer prevention starts with sun protection. • Un ortunately there is no proo that sunscreen use prevents BCC. 10 • Sun protection should include sun avoidance, especially during peak hours o ultraviolet (UV) transmission, and protective clothing. • US Preventive Services Task Force has not ound su cient evidence to recommend regular screening or any skin cancer in the general population. 11 • Most experts believe that persons at high risk or BCC (including previous personal history o BCC, high-risk amily history, and high-risk skin types with signi cant sun exposure) should be screened regularly or skin cancer by a physician trained in such screening. • Evidence or the value o sel -screening is lacking but persons at high risk or skin cancer should also be encouraged to observe their own skin and to come in or evaluation i they see any suspicious changes or growths.

PRO GNO SIS FIGURE 168-23 Cryosurg e ry was a avore d tre atme nt mod ality in a 94-ye ar-old e male p atie nt with Alzhe ime r d e me ntia with a b asal ce ll carcinoma on the che e k. The amily ap p re ciate d how e asy this was to comp le te and ho w we ll it he ale d . (Re p ro d uce d with p e rmissio n fro m Richard P. Usatine , MD.)

The prognosis or BCC is generally excellent with high cure rates with surgery and destructive modalities. Large lesions on the ace or lesions that have spread to sites deep to the skin have a poorer prognosis.

Ba Sa L Ce LL Ca r CINO Ma

FO LLO W-UP Patients should be seen at least yearly a ter the diagnosis and treatment o a BCC. The 3-year risk o BCC recurrence a ter having a single BCC is 44%.12

PATIENT EDUCATIO N Patients should practice skin cancer prevention by sun-protective behaviors such as avoiding peak sun, covering up, and using sunscreen. PATIENT RESO URCES

• The Skin Cancer Foundation—http:/ / www.skincancer.org/ skin-cancer-information/ basal-cell-carcinoma • MedlinePlus. Basal cell carcinoma—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000824.htm • PubMed Health. Basal cell carcinoma—http:/ / www.ncbi.nlm .nih.gov/ pubmedhealth/ PMH0001827/ PRO VIDER RESO URCES

• Medscape. Basal cell carcinoma—http:/ / emedicine.medscape .com/ article/ 276624-overview Chapters and videos on diagnosing and surgically managing melanoma can be ound in the ollowing book/ DVD or electronic application: • Usatine R, Pfenninger J, Stulberg D, Small R. Dermatologic and Cosmetic Procedures in O f ce Practice. Philadelphia, PA: Elsevier, Inc.; 2012. In ormation about smartphone and tablet apps o this resource can be viewed at http:/ / www.usatinemedia.com.

REFERENCES 1. Ormerod A, Rajpara S, Craig F. Basal cell carcinoma. Clin Evid (Online). 2010;2010:1719. 2. Jackson SM, Nesbitt LT. Di erential Diagnosis or the Dermatologist. Berlin, Germany: Springer; 2008:1360.

PART 14 DERMATO LO GY 3. Madan V, Hoban P, Strange RC, et al. Genetics and risk actors or basal cell carcinoma. Br J Dermatol. 2006;154(suppl 1):5-7. 4. Jarell AD, Mully TW. Basal cell carcinoma on the ear is more likely to be o an aggressive phenotype in both men and women. JAmAcad Dermatol. 2012;66(5):780-784. 5. Welsch MJ, Troiani BM, Hale L, et al. Basal cell carcinoma characteristics as predictors o depth o invasion. JAmAcad Dermatol. 2012;67(1):47-53. 6. Thissen MR, Neumann MH, Schouten LJ. A systematic review o treatment modalities or primary basal cell carcinomas. Arch Dermatol. 1999;135(10):1177-1183. 7. Geisse J, Caro I, Lindholm J, et al. Imiquimod 5% cream or the treatment o super cial basal cell carcinoma: results rom two phase III, randomized, vehicle-controlled studies. JAmAcad Dermatol. 2004;50(5):722-733. 8. MacFarlane DF, Tal El AK. Cryoimmunotherapy: super cial basal cell cancer and squamous cell carcinoma in situ treated with liquid nitrogen ollowed by imiquimod. Arch Dermatol. 2011;147(11): 1326-1327. 9. Ho Von DD, LoRusso PM, Rudin CM, et al. Inhibition o the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. 2009;361(12):1164-1172. 10. van der Pols JC, Williams GM, Pandeya N, et al. Prolonged prevention o squamous cell carcinoma o the skin by regular sunscreen use. Cancer Epidemiol Biomarkers Prev. 2006;15(12):2546-2548. 11. Wol T, Tai E, Miller T. Screening or Skin Cancer:An Update o the Evidence or the U.S. Preventive ServicesTask Force [Internet]. Rockville (MD): Agency or Healthcare Research and Quality (US); 2009 Feb. http:/ / www.ncbi.nlm.nih.gov/ books/ NBK34051/ 12. Marcil I, Stern RS. Risk o developing a subsequent nonmelanoma skin cancer in patients with a history o nonmelanoma skin cancer: a critical review o the literature and meta-analysis. Arch Dermatol. 2000;136(12):1524-1530.

833

834

PART 14 DERMATO LO GY

Ch a pt e r 169

169 SQ UAMO US CELL CARCINO MA Jonathan B. Karne s, MD Richard P. Usatine , MD

PATIENT STO RY A 66-year-old armer presents with new growths on his scalp (Figure 169-1). The patient admits to lots o sun exposure and has already had one squamous cell carcinoma (SCC) excised rom the scalp 5 years ago. On close inspection there are many suspicious areas or SCC (see Figure 169-1). Figure 169-2 demonstrates a shave biopsy o a SCC on a scalp using a DermaBlade. The pathology demonstrated that 2 o 3 biopsy sites were positive or SCC (E and G were SCC and F was read as actinic keratoses). The patient was re erred or Mohs surgery. The Mohs surgeon recommended eld treatment with 5-f uoruracil or 4 weeks be ore surgery to minimize the amount o cutting that would be needed to clear the SCC rom this di usely sun-damaged scalp.

INTRO DUCTIO N Cutaneous SCC is the second most common cancer in humans and arises most o ten as a result o cumulative sun damage. Although the mortality is declining, incidence is increasing in all populations making this cancer a common and signi cant burden on patients.

FIGURE 169-2 Shave b iop sy o a sq uamous ce ll carcinoma on the scalp . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• The incidence is increasing in all age groups and populations at a rate o 3% to 10%. 2 • In the United States, approximately 2500 people die rom SCC every year. 3 • SCC is the second most common skin cancer and accounts or up to 25% o nonmelanoma skin cancers. 4 • More than 250,000 new cases o invasive SCC are diagnosed annually in the United States. 4

PATHO PHYSIO LO GY EPIDEMIO LO GY • Mortality rom SCC has been observed as 0.29 per 100,000 population. 1 • Metastasis rom SCC occurs in 2% to 9.9% o cases. 2

SCC is a malignant tumor o keratinocytes. Most SCCs arise rom precursor lesions called actinic keratoses. SCCs usually spread by local extension but are capable o regional lymph node metastasis and distant metastasis. Human papillomavirus (HPV)-related lesions may be ound on the penis, labia, and perianal mucosa, or in the periungual region or elsewhere associated with immunosuppression. 5 SCCs that metastasize most o ten start on mucosal sur aces and sites o chronic inf ammation.

RISK FACTO RS • Long-term cumulative ultraviolet (UV) exposure is the greatest risk actor. • Childhood sunburns. • Occupational exposure. • Other UV exposure including psoralens plus ultraviolet A (PUVA) therapy and tanning beds. • Smoking. • HPV exposure. • Exposure to ionizing radiation. FIGURE 169-1 Multip le sq uamous ce ll carcino mas on the scalp o a arme r with a lot o sun e xp osure . The p atholog y d e monstrate d that 2 o 3 b iop sy site s we re p ositive or sq uamous ce ll carcinoma (E and G we re sq uamous ce ll carcinomas and F was re ad as actinic ke ratosis). (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Arsenic exposure. • Fair skin. • Age older than 60 years.

PART 14 DERMATO LO GY

SQ Ua MO US Ce LL Ca r CINO Ma

• Male gender. • Living at lower latitude and higher altitude. • Nonhealing ulcers. • Chronic or severe immunosuppression, including posttransplant immunosuppression, HIV, and long-term steroid use. • Genetic syndromes, including Muir Torre, xeroderma pigmentosum, dystrophic epidermolysis bullosa, epidermodysplasia verruci ormis, and oculocutaneous albinism. 4

DIAGNO SIS The only sure method o making the diagnosis is a biopsy, biopsy suspicious lesions (thickened, tender, indurated, ulcerated, or crusting) especially in sun-exposed areas. CLINICAL FEATURES SCC o ten presents as areas o persistent ulceration, crusting, hyperkeratosis, and erythema, especially on sun-damaged skin. Less common types o SCC are as below: • Marjolin ulcer—SCC o the extremities ound in chronic skin ulcers or burn scars. This is a more common risk in darker pigmented individuals (Figure 169-3). • Erythroplasia o Queyrat—SCC in situ on the penis or vulva related to HPV in ection (Figure 169-4). This can progress to invasive SCC o the penis (Figure 169-5). TYPICAL DISTRIBUTIO N

FIGURE 169-4 Erythrop lasia o Q ue yrat (sq uamous ce ll carcinoma in situ) und e r the ore skin o an uncircumcise d man. This is re late d to human p ap illomavirus in e ction as is ce rvical cance r. (Re p rod uce d with p e rmission from John Pfe nning e r, MD.)

• Fingers (Figure 169-15) • Mucus membranes (Figure 169-16) (see Chapter 39, Oropharyngeal Cancer)

SCC is ound in all sun-exposed areas and on mucus membranes. The most common sites are as ollows:

BIO PSY

• Face (Figures 169-6 and 169-7)

• Punch biopsy or incisional biopsy is an alternative or lesions that are pigmented or appear to be deeper.

• Lower lip (Figures 169-8 and 169-9)

• Deep shave biopsy is adequate to make the diagnosis o most SCCs.

• Ears (Figure 169-10) • Scalp (Figures 169-1 and 169-11) • Extremities—arm—(Figures 169-12 and 169-13) • Hands (Figure 169-14)

FIGURE 169-3 Marjolin ulce r (sq uamous ce ll carcinoma) arising in a b urn that occurre d ye ars b e ore on the ace . (Re p rod uce d with p e rmission from Richard P Usatine , MD.)

FIGURE 169-5 Sq uamous ce ll carcinoma o the g lans p e nis. (Re p rod uce d with p e rmission from Je ff Me ffe rt, MD.)

835

PART 14 DERMATO LO GY

836

A

Ch a pt e r 169

A

B FIGURE 169-6 A. Sq uamous ce ll carcinoma on the nose o an 88-ye ar-old woman. B. Sub tle small sq uamous ce ll carcinoma on the nasal alae . Note that any crusting le sio n o n the ace may b e a sq uamo us ce ll carcino ma no matte r ho w small it is. (Re p ro d uce d with p e rmissio n fro m Richard P. Usatine , MD.)

B

FACTO RS AFFECTING METASTATIC PO TENTIAL O F CUTANEO US SQ UAMO US CELL CARCINO MA The ollowing actors are taken rom “Multipro essional guidelines or the management o the patient with primary cutaneous squamous cell carcinoma.”6 SITE Tumor location inf uences prognosis: Sites are listed in order o increasing metastatic potential. 2

FIGURE 169-7 A. Larg e cystic-ap p e aring sq uamous ce ll carcinoma on the ace . Altho ug h this could have b e e n a b asal ce ll carcinoma, it d e f nite ly re q uire d a b iop sy and e xcision. B. Small sub tle invasive sq uamous ce ll carcinoma on the ace that could have b e e n ove rlooke d o r tre ate d as an actinic ke ratosis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

SQ Ua MO US Ce LL Ca r CINO Ma

PART 14 DERMATO LO GY

FIGURE 169-8 Sq uamous ce ll carcinoma on the lowe r lip g rowing rap id ly in a p atie nt that was taking an immunosup p re ssive me d ication a te r a re nal transp lant. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 169-11 Sq uamous ce ll carcinoma on the shave n scalp o a 35-ye ar-old man, which was orme rly mistake n or a wart. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 169-9 Sq uamous ce ll carcinoma showing ulce ration on the lowe r lip o a man that was a smoke r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 169-12 Larg e sq uamous ce ll carcinoma on the le g o a home le ss man. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 169-10 Sq uamous ce ll carcino ma arising in an actinic ke rato sis on the he lix o a 33-ye ar-old woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 169-13 Thre e Larg e ulce rating sq uamous ce ll carcinoma on arm. (Re p rod uce d with p e rmission from Jonathan B. Karne s, MD.)

837

PART 14 DERMATO LO GY

838

Ch a pt e r 169

likely to recur and metastasize (metastatic rate 45.7%) compared with thinner tumors. Recurrence and metastases are less likely in tumors conned to the upper hal o the dermis and less than 4 mm in depth (metastatic rate 6.7%). HISTOLOGIC DIFFERENTIATION Poorly di erentiated tumors have a poorer prognosis, with more than double the local recurrence rate and triple the metastatic rate o better di erentiated SCC. Tumors with perineural involvement are more likely to recur and to metastasize. HOST IMMUNOSUPPRESSION Tumors arising in patients who are immunosuppressed have a poorer prognosis. Host cellular immune response may be important both in determining the local invasiveness o SCC and the host’s response to metastases. Figures 169-16, 169-17, and 169-18 are SCCs in patients who are HIV positive. FIGURE 169-14 Sq uamous ce ll carcinoma in situ on the the nar e mine nce o the hand . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

1. SCC arising at sun-exposed sites excluding lip and ear 2. SCC o the lip (see Figures 169-8 and 169-9)

PREVIOUS TREATMENT AND TREATMENT MODALITY The risk o local recurrence depends on the treatment modality. Locally recurrent disease itsel is a risk actor or metastatic disease. Local recurrence rates are considerably less with Mohs micrographic surgery than with any other treatment modality.

3. SCC o the ear (see Figure 169-10) 4. Tumors arising in non–sun-exposed sites (eg, perineum, sacrum, sole o oot) (see Figures 169-4, 169-5, and 169-16) 5. SCC arising in areas o radiation or thermal injury, chronic draining sinuses, chronic ulcers, chronic inf ammation, or Bowen disease, such as the SCC arising in a burn site (see Figure 169-3) SIZE: DIAMETER Tumors larger than 2 cm in diameter are twice as likely to recur locally (15.2% vs 7.4%), and 3 times as likely to metastasize (30.3% vs 9.1%) as smaller tumors (Figure 169-17). SIZE: DEPTH Tumors greater than 4 mm in depth (excluding sur ace layers o keratin) or extending down to the subcutaneous tissue (Clark level V) are more

A

DIFFERENTIAL DIAGNO SIS • Actinic keratoses are precancers on sun-exposed areas, which can progress to SCC (see Chapter 164, Actinic Keratosis and Bowen Disease). • Bowen disease is SCC in situ be ore it invades the basement membrane (see Chapter 164, Actinic Keratosis and Bowen Disease). • Keratoacanthoma is a subtype o SCC that may resolve spontaneously, but is generally treated as a low-risk SCC. Figure 169-19 shows an invasive SCC resembling a lower-risk keratoacanthoma subtype (see Chapter 165, Keratoacanthoma). • Basal cell carcinoma (BCC) cannot always be distinguished rom SCC by clinical appearance alone. Figure 169-17 could be a BCC by appearance but was proven to be SCC by biopsy (see Chapter 168, Basal Cell Carcinoma).

B

FIGURE 169-15 Two d i e re nt-ap p e aring case s o sq uamous ce ll carcinoma on the f ng e r. A. It took 2 shave b iop sie s to e stab lish the corre ct d iag nosis in this case . B. Sq uamous ce ll carcinoma in situ with human p ap illomavirus chang e s and p ig me nt incontine nce in a 35-ye ar-old woman. The irre g ular hyp e rp ig me nte d le sion on the p roximal nail old was orig inally susp icious or me lanoma. (Re p ro d uce d with p e rmission fro m Richard P. Usatine , MD.)

SQ Ua MO US Ce LL Ca r CINO Ma

FIGURE 169-16 Pe rianal invasive sq uamous ce ll carcinoma in a HIV-p ositive man who had e ng ag e d in anal inte rcourse and was in e cte d with human p ap illomavirus. The ulce rations we re susp icious or invasive sq uamous ce ll carcinoma and not typ ical o cond yloma acuminata. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Merkel cell carcinoma (neuroendocrine carcinoma o the skin) is a rare aggressive malignancy. It is most commonly seen on the ace o white elderly persons. It can resemble a SCC and the diagnosis is made on biopsy (Figure 169-20). • Nummular eczema can usually be distinguished by the multiple coinlike shapes, transient nature, and pruritus (see Chapter 143, Atopic Dermatitis).

PART 14 DERMATO LO GY

FIGURE 169-18 Sq uamous ce ll carcinoma invad ing the inte rnal nasal structure s in a HIV-p ositive man who was a raid o having a b iop sy d one e arlie r. Patie nt re e rre d to e ar, nose , and throat sp e cialist. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

MANAGEMENT The ollowing recommendations are derived rom the “Multipro essional guidelines or the management o the patient with primary cutaneous SCC.” See Table 169-1 or a summary o treatment options. Surgical resection or de nitive treatment should include margins as given below: • 4-mm margin—Should be adequate or well-de ned, low-risk tumors less than 2 cm in diameter, such margins are expected to remove the primary tumor mass completely in 95% o cases. 5 SO R • 6-mm margin—Recommended or larger tumors, high-risk tumors, tumors extending into the subcutaneous tissue, and those in high-risk locations (ear, lip, scalp, eyelids, nose). 5

FIGURE 169-17 Larg e sq uamous ce ll carcinoma on the arm o a HIV-p ositive 51-ye ar-old man. It g re w to this size in 1 ye ar and took 2 b iop sie s to g e t a d e f nitive d iag nosis. Di e re ntial d iag nosis includ e s mycosis ung oid e s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 169-19 Sq uamous ce ll carcinoma on the should e r o a HIV-p ositive man. Note that the p e arly b ord e rs and te lang ie ctasias re se mb le a b asal ce ll carcinoma and the ce ntral crate r sug g e sts that this could b e a ke ratoacanthoma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

839

PART 14 DERMATO LO GY

840

Ch a pt e r 169

The experienced clinician undertaking EDC can detect tumor tissue by its so t consistency, which may be o bene t in identi ying invisible tumor extension and ensuring adequate treatment. Electrodesiccation is applied to the curetted wound and the curettage-cautery cycle then repeated twice. SO R C CRYO SURGERY

FIGURE 169-20 Me rke l ce ll carcinoma on the lowe r lip o an e ld e rly woman. This is an ag g re ssive cance r with a hig h mortality rate . (Re p rod uce d with p e rmission from Je ff Me ffe rt, MD.)

MO HS MICRO GRAPHIC SURGERY Frederick Mohs pioneered a technique or excising cutaneous tumors with immediate analysis o a continuous margin mapped to the clinical site. Mohs surgery o ers superior cure rates compared with standard excision or destructive techniques, spares uninvolved tissue, and allows or reconstruction at the time o excision. Mohs surgery may be considered or any continuous tumor, but is speci cally indicated or lesions larger than 2 cm, lesions with ill-de ned clinical borders, lesions with aggressive histologic subtypes, recurrent lesions, and lesions on or near the eye, nose, ear, mouth, hair-bearing scalp, or chronic ulcers. Patients with chronic immunosuppression or genetic tumor syndromes may also bene t rom Mohs surgery compared to standard excision. 4

Good short-term cure rates have been reported or small, histologically con rmed SCC treated by cryosurgery in experienced hands. Prior biopsy is necessary to establish the diagnosis histologically. There is great variability in the use o liquid nitrogen or cryotherapy. Start by drawing a 4- to 6-mm margin around the SCC and then use a total reeze time o 60 seconds. This can be divided up into two 30-second reezes with a thaw in between. Most patients pre er local anesthetic because these long reeze times are quite pain ul. SO R C Cryosurgery and curettage and electrodesiccation are not appropriate or locally recurrent disease. RADIO THERAPY Radiation therapy alone o ers short- and long-term cure rates or SCC that is comparable with other treatments. It is recommended or lesions arising on the lip, nasal vestibule (and sometimes the outside o the nose), and ear. Certain very advanced tumors, where surgical morbidity would be unacceptably high, may also be best treated by radiotherapy. SO R C ELECTIVE PRO PHYLACTIC LYMPH NO DE DISSECTIO N Elective prophylactic lymph node dissection has been proposed or SCC on the lip that is greater than 6 mm in depth and or cutaneous SCC that is greater than 8 mm in depth, but evidence or this is weak. SO R C

PREVENTIO N AND SCREENING

CURETTAGE AND ELECTRO DESICCATIO N Excellent cure rates have been reported in several series, and experience suggests that small (< 1 cm), well-di erentiated, primary, slow-growing tumors arising on sun-exposed sites can be removed by experienced physicians with electrodessication and curettage (EDC). 5

• All skin cancer prevention starts with sun protection. • There is good evidence rom multiple randomized controlled trials (RCTs) that daily sunscreen use decreases the risk o developing

TABLE 169-1 Summary o Tre atme nt O p tions or Primary Cutane ous Sq uamous Ce ll Carcinoma

Tre at me nt

Ind icat io ns

Co nt raind icat io ns

No t e s

Surg ical e xcision

All re se ctab le tumors

Whe re surg ical morb id ity is like ly to b e unre asonab ly hig h

Ge ne rally tre atme nt o choice or SCC Hig h-risk tumors ne e d wid e marg ins or histolog ic marg in control

Mohs microg rap hic Hig h-risk tumors, re curre nt surg e ry/e xcision with tumors histolog ic control

Whe re surg ical morb id ity is like ly to b e unre asonab ly hig h

Rad iothe rap y

Nonre se ctab le tumors

Whe re marg ins are ill d e f ne d

Cure ttag e and caute ry

Small, we ll-d e f ne d , low-risk tumors

Hig h-risk tumors

Cure ttag e may b e he lp ul p rior to surg ical e xcision

Cryothe rap y

Small, we ll-d e f ne d , low-risk tumors

Hig h-risk tumors, re curre nt tumors

O nly suitab le or e xp e rie nce d p ractitione rs

Tre atme nt o choice or hig h-risk tumors

Data rom Motle y R, Ke rse y P, Lawre nce C. Multip ro e ssional g uid e line s or the manag e me nt o the p atie nt with p rimary cutane ous sq uamous ce ll carcinoma. BrJ Plast Surg . 2003;56:85-91.

PART 14 DERMATO LO GY

SQ Ua MO US Ce LL Ca r CINO Ma

sun-related SCCs. 7,8 SO R In the longest RCT, sunscreen was applied regularly to the head, neck, hands, and orearms or 4.5 years with a decrease in SCC during the study period. 7 A ter cessation o the trial, the participants were ollowed or another 8 years and SCC tumor rates were signi cantly decreased, by almost 40%, during the entire ollow-up period.8 • Sun protection should include sun avoidance, especially during peak hours o UV transmission, protective clothing, and sunscreen use. • Indoor tanning is not sa e and should be avoided. • US Preventive Services Task Force has not ound su cient evidence to recommend regular screening or any skin cancer in the general population. 9 • Most experts believe that persons at high risk or SCC (including previous personal history o any skin cancer, high-risk amily history and high-risk skin types with signi cant sun exposure, on immunosuppression a ter an organ transplant) should be screened regularly or skin cancer by a physician trained in such screening. • Evidence or the value o sel -screening is lacking but persons at high risk or skin cancer should also be encouraged to observe their own skin and to come in or evaluation i they see any suspicious changes or growths.

PRO GNO SIS Prognosis is excellent or small, thin lesions less than 2-mm thick that are removed with clear margins in immunocompetent patients. In these patients, the risk o metastasis is near zero. The risk o metastasis increases markedly with thicker lesions and lesions with thicknesses greater than 6 mm metastasize to the regional nodes 16% o the time. 10

FO LLO W-UP Patients should be seen at least yearly or skin examinations a ter the diagnosis and treatment o a SCC. The 3-year risk o recurrence o a new SCC a ter having a single SCC is 18%. 11

PATIENT EDUCATIO N It includes use o a hat and sunscreen on a regular basis with requent ollow-up or early recognition o new skin cancers. PATIENT RESO URCES

• The Skin Cancer Foundation. Squamous Cell Carcinoma—http:/ / www.skincancer.org/ skin-cancer-information/ squamous-cell-carcinoma. • PubMed Health. Squamous Cell Carcinoma—http:/ / www.ncbi .nlm.nih.gov/ pubmedhealth/ PMH0001832/ . • Skinsight. Squamous Cell Carcinoma—http:/ / www.skinsight .com/ adult/ squamousCellCarcinomaSCC.htm. • MedlinePlus. Squamous Cell Carcinoma—http:/ / www.nlm.nih .gov/ medlineplus/ ency/ article/ 000829.htm.

PRO VIDER RESO URCES

• Medscape. Head and Neck Cutaneous Squamous Cell Carcinoma— http:/ / emedicine.medscape.com/ article/ 1965430overview. • Skinsight. INFORMED: Melanoma and Skin Cancer Early Detection— http:/ / www.skinsight.com/ info/ for_professionals/ skin-cancer-detection-informed/ skin-cancer-education. • Chapters and videos on diagnosing and surgically managing SCC can be ound in the ollowing book/ DVD or electronic app: Usatine R, P enninger J, Stulberg D, Small R. Dermatologic and Cosmetic Procedures in O f ce Practice. Philadelphia, PA: Elsevier; 2012. ° In ormation about smartphone and tablet apps o this resource can be viewed at www.usatinemedia.com.

REFERENCES 1. Lewis KG, Weinstock MA. Nonmelanoma skin cancer mortality (1988-2000): the Rhode Island ollow-back study. Arch Dermatol. 2004;140(7):837-842. 2. Weinberg AS, Ogle CA, Shim EK. Metastatic cutaneous squamous cell carcinoma: an update. Dermatol Surg. 2007;33(8):885-899. 3. American Cancer Society. Cancer Facts &Figures 2010. http:/ / www .cancer.org/ research/ cancer acts gures/ cancer acts gures/ canceracts-and- gures-2010. Accessed June 1, 2012. 4. Bolognia JL, Jorizzo JL, Scha er JV. Dermatology. 3rd ed. Philadelphia, PA: Saunders; 2012:2776. 5. Berg D, Otley CC. Skin cancer in organ transplant recipients: epidemiology, pathogenesis, and management. JAmAcad Dermatol. 2002;47(1):1-17; quiz 18-20. 6. Motley R, Kersey P, Lawrence C. British Association o Dermatologists, British Association o Plastic Surgeons. Multipro essional guidelines or the management o the patient with primary cutaneous squamous cell carcinoma. Br J Plast Surg. 2003;56(2):85-91. 7. Green A, Williams G, Neale R, et al. Daily sunscreen application and betacarotene supplementation in prevention o basal-cell and squamous-cell carcinomas o the skin: a randomised controlled trial. Lancet. 1999;354:723-729. Erratum: Lancet. 1999;354:1038. 8. van der Pols JC, Williams GM, Pandeya N, Logan V, Green AC. Prolonged prevention o squamous cell carcinoma o the skin by regular sunscreen use. Cancer Epidemiol Biomarkers Prev. 2006;15(12): 2546-2548. 9. Wol T, Tai E, Miller T. Screening or Skin Cancer:An Update o the Evidence or the U.S. Preventive ServicesTask Force. Rockville, MD: Agency or Healthcare Research and Quality; 2009. http:/ / www .ncbi.nlm.nih.gov/ books/ NBK34051/ . 10. Brantsch KD, Meisner C, Schön sch B, et al. Analysis o risk actors determining prognosis o cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol. 2008;9(8):713-720. 11. Marcil I, Stern RS. Risk o developing a subsequent nonmelanoma skin cancer in patients with a history o nonmelanoma skin cancer: a critical review o the literature and metaanalysis. Arch Dermatol. 2000;136(12):1524-1530.

841

842

PART 14 DERMATO LO GY

Ch a pt e r 170

170 MELANO MA Jonathan B. Karne s, MD Richard P. Usatine , MD

PATIENT STO RIES A 40-year-old woman noticed a new dark spot on her neck (Figure 170-1). On examination the spot was 8 mm in its longest diameter, was asymmetrical with irregular borders, and had variation in color. A scoop shave biopsy demonstrated melanoma in situ. The spot was excised with 0.5-cm margins and no residual tumor was ound in the excised ellipse. She has a near 100% chance o complete cure. The wi e o a 73-year-old man noticed that a “mole” on his back was enlarging and bleeding. (Figure 170-2). It had been there or years. Even though a year earlier a doctor had told him not to worry about it, his wi e sent him to have it rechecked. Figure 170-2B shows a close-up o the pigmented lesion showing ulceration and bleeding. An elliptical excision was per ormed and the tissue appeared to be a nodular melanoma with dark pigment into the subcutaneous at (Figure 170-2C). Histology revealed a nodular melanoma with a Breslow depth o 22 mm. The patient was re erred to surgical and medical oncology. He underwent wide excision with 2-cm margins and a sentinel lymph node biopsy. The sentinel node was positive and urther nodal dissection showed a total o another 4 axillary lymph nodes positive (1 on right and 3 on le t). The lymph nodes on the le t were black and enlarged. No distant metastases were ound. Because more than 2 regional nodes were macroscopically positive, he was stage IIIC. He received radiation treatment to the original site and both axillae. Despite advances in targeted chemotherapy and immunotherapy, his prognosis was poor.

INTRO DUCTIO N

A

B

Melanoma is the third most common skin cancer and the most deadly. The incidence o melanoma and the mortality rom it are rising. Most lesions are ound by clinicians on routine examination. When discovered early,

C

FIGURE 170-1 Me lanoma in situ on the ne ck o a 40-ye ar-old woman. Note the ce ntral re g re ssion. (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

FIGURE 170-2 A. A 73-ye ar-old man p re se nts with b le e d ing “mole ” on his b ack. Ellip tical e xcision d e monstrate s this to b e a nod ular me lanoma o 22-mm d e p th. B. Close -up o the nod ular me lanoma showing it to b e thick with ulce rations and b le e d ing . C. Nod ular me lanoma a te r initial re se ction sho wing d ark p ig me nt into the sub cutane o us at. The Bre slo w d e p th is 22 mm with Clark le ve l V. (Re p ro d uce d with p e rmissio n fro m Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

Me La NO Ma

surgical treatment is almost always curative. However, deeper lesions are prone to metastasize and have a much poorer prognosis. New therapies directed at the known gene changes in melanoma are beginning to show some promise, but widespread bene ts o this research are still ar o .

DIAGNO SIS CLINICAL FEATURES Remember the ABCDE guidelines or diagnosing melanoma (Figure 170-3).4

EPIDEMIO LO GY • In 2012, an estimated 76,250 individuals will be diagnosed with melanoma o the skin and 9180 individuals will die rom metastatic disease—or about 1 every hour. 1 • Melanoma incidence has increased in every age group and in every thickness over the course o 1992 to 2006 among non-Hispanic whites, with death rates increasing in those older than age 65 years. 2 • Incidence continues to increase worldwide at approximately 4% to 8% per year. 3 • In the United States, the death rate or melanoma is decreasing among persons younger than age 65 years. 2 • Deaths rom thin melanomas account or more than 30% o total deaths. • The li etime risk o developing melanoma is 1 in 55 or men and 1 in 36 or women. 1

RISK FACTO RS Risk actors can be broadly thought o as genetic risks, environmental risks, and phenotypic risks arising rom a combination o genetic and environmental risks. For example, a air-skinned child (genetic risk) who gets a sunburn (environmental) is much more likely to develop reckles (phenotypic) and melanoma. ENVIRO NMENTAL RISKS

A = Asymmetry. Most early melanomas are asymmetrical: A line through the middle will not create matching halves. Benign nevi are usually round and symmetrical. B = Border. The borders o early melanomas are o ten uneven and may have scalloped or notched edges. Benign nevi have smoother, more even borders. C = Color variation. Benign nevi are usually a single shade o brown. Melanomas are o ten in varied shades o brown, tan, or black, but may also exhibit red, white, or blue. D = Diameter greater than or equal to 6 mm. Early melanomas tend to grow larger than most nevi. (Note: Congenital nevi are o ten large.) E = Evolving. Any evolving or enlarging nevus should make you suspect melanoma. Evolving could be in size, shape, symptoms (itching, tenderness), sur ace (especially bleeding), and shades o color. • A prospective controlled study compared 460 cases o melanoma with 680 cases o benign pigmented tumors and ound signi cant di erences or all individual ABCDE criteria (p < 0.001) between melanomas and benign nevi. 4 • Sensitivity o each criterion: A 57%, B 57%, C 65%, D 90%, E 84%; speci city o each criterion: A 72%, B 71%, C 59%, D 63%, E 90%. 4 • Sensitivity o ABCDE criteria varies depending on the number o criteria needed: Using 2 criteria it was 89.3%, with 3 criteria, it was 65.5%. Speci city was 65.3% using 2 criteria and 81% using 3. 4 • The number o criteria present was di erent between benign nevi (1.24 ± 1.26) and melanomas (3.53 ± 1.53; p intravenous), 11 immune activation o the individual, and immunogenetic predisposition; they are also more requent in women. 2 Multiple drug therapy may also increase risk.11 • Patients with the ollowing HLAs are at higher risk or cutaneous drug reactions: HLA-B*1502 (con ers a very high risk o carbamazepineinduced and other antiepileptic drug-induced SJS among people o

• Hypersensitivity to NSAIDs is a nonimmunologic reaction that can be immediate (within hours a ter exposure) or delayed (more than 24 hours a ter administration). 1 • WISN develops during the hypercoagulable state, as a result o a more rapid all in concentration o protein C compared to the other vitamin K–dependent procoagulant actors. Thrombophilic abnormalities such as amilial or acquired de iciency o protein C or S and antiphospholipid antibodies have been implicated in WISN (see Figure 201-6). • SJS/ TEN is most commonly associated with penicillins and sul onamide antibiotics but can also occur with anticonvulsants, NSAIDs, allopurinol, and corticosteroids. It is hypothesized that a speci c human leukocyte antigen (HLA)-B molecule may present the drug or its metabolites to naïve CD8 cells resulting in clonal expansion o CD8 cytotoxic lymphocytes and induction o cytotoxic e ector responses, resulting in apoptosis o keratinocytes. 10 This pathway is not likely to be speci c to SJS.

FIGURE 201-14 Re curre nt e rythe ma multi orme se cond ary to re p e ate d b outs o he rp e s simp le x in this 43-ye ar-old woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

1027

1028

PART 14 DERMATO LO GY

Ch a pt e r 201

DIAGNO SIS CLINICAL FEATURES AND TYPICAL DISTRIBUTIO N (THE MO ST CO MMO N AND IMPO RTANT DRUG ERUPTIO NS) • Maculopapular— These eruptions, red macules with papules, can occur any time a ter drug therapy is initiated (o ten 7-10 days) and last 1 to 2 weeks. The reaction usually starts on the upper trunk or head and neck then spreads symmetrically downward to limbs. The eruptions may become conf uent in a symmetric, generalized distribution that spares the ace (see Figures 201-1 and 201-2). Mild desquamation is normal as the exanthematous eruption resolves.

FIGURE 201-15 Erythe ma multi o rme showing targ e t le sions on the p alms. (Re p rod uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

southeastern Asian ethnicity); HLA-B*5801 (higher risk o allopurinolinduced severe cutaneous reactions); HLA-B*5701 (higher risk o abacavir [an antiretroviral drug] hypersensitivity reactions); HLA-B*3501, HLA-B*3505, HLA-B*1402, and HLA-Cw8 (nevirapine [an antiretroviral drug] sensitivity with rash; the latter 2 ound in a Sardinian population); HLA-DRB1*0101 (nevirapine hypersensitivity rash with hepatitis). 2,6 • Prior drug reaction may result in a aster recurrence on reexposure. 11 • Concomitant illness, especially viral in ections and autoimmune disorders. 11

• Urticaria and angioedema—Urticaria reactions present as circumscribed areas o blanching-raised erythema and edema o the super cial dermis (see Figure 201-3). They may occur on any skin area and are usually transient, migratory, and pruritic. Angioedema represents a deeper reaction, with swelling usually around the lips and eyes (see Chapter 148, Urticaria and Angioedema). • Hyperpigmentation— Drug-induced hyperpigmentation presents in many ways. Amiodarone causes a dusky red coloration that turns blue-gray with time in photo-exposed areas. Minocycline can cause a blue-gray color in acne lesions, on the gingiva and on the teeth. Phenytoin (Dilantin) and other hydantoins may cause melasma-like brown pigmentation on the ace. Bleomycin can cause a streaking hyperpigmentation on the trunk and extremities. Adriamycin, as evident in the case above, can cause hyperpigmentation o the ace and nails (see Figure 201-5). • NSAIDs—The cutaneous reactions to NSAID-associated drug hypersensitivity are urticaria, angioedema, or anaphylaxis. 1 These reactions can be caused by a single NSAID or multiple NSAIDs. There is also an NSAID-exacerbated urticaria and angioedema that occurs in patients with chronic idiopathic urticaria. • Warfarin-induced skin necrosis (WISN)— It presents with sudden onset o pain ul localized skin lesion that is initially erythematous and/ or hemorrhagic that becomes bullous, culminating in gangrenous necrosis (see Figure 201-6). It develops more o ten in obese women in their 50s in areas with high subcutaneous at content such as breasts, thighs, and buttocks. This is di erent rom a war arin bleed secondary to too much anticoagulation (see Figure 201-14). • Fixed drug eruption (FDE)—Presents with single or multiple sharply demarcated circular, violaceous, or hyperpigmented plaques that may include a central blister (Figures 201-8 to 201-13 and 201-17). The lesion(s) appear a ter drug exposure and reappear exactly at the same site each time the drug is taken. The site resolves, leaving an area o macular hyperpigmentation (see Figure 201-8). Lesions can occur anywhere including the hands and eet, but are commonly ound on the penis (see Figures 201-10 and 201-11). The eruption presents 30 minutes to 8 hours a ter drug administration. Bullous xed drug eruptions occur when the lesion blisters and erodes, ollowed by desquamation and crusting (see Figures 201-7, 201-11, and 201-17).

FIGURE 201-16 Ste ve ns-Johnson synd rome se cond ary to a sul a antib iotic. (Re p rod uce d with p e rmission from Eric Kraus, MD.)

• EM— It presents with typical target or raised edematous papules distributed acrally. Most importantly, there should be some type o epidermal disruption with bullae or erosions within the target lesions (see Figures 201-14 and 201-15). Severe EM becomes and more widespread epidermal detachment may occur involving less than 10% o total body sur ace area (see Chapter 175, Erythema Multi orme, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis).

PART 14 DERMATO LO GY

CUt a Ne O US Dr UG r e a Ct IO NS

TABLE 201-1 Alle rg ic Cutane ous Re actions to Drug s Re ce ive d b y at Le ast 1000 Patie nts

Drug

Re act io ns, No .

Re cip ie nt s, No .

Rat e ,%

95% Co nf d e nce Int e rval

Fluoroq uinolone s

16

1015

1.6

0.8 to 2.3

Amoxicillin

40

3233

1.2

0.9 to 1.6

Aug me ntin

12

1000

1.2

0.5 to 1.9

Pe nicillins

63

5914

1.1

0.8 to 1.3

Nitro urantoin

7

1085

0.6

0.2 to 1.1

Te tracycline

23

4981

0.5

0.3 to 0.7

Macrolid e s

5

1435

0.3

0 to 0.7

Data rom van d e r Lind e n PD, van d e r Le i J, Vlug AE, Stricke r BH. Skin re actions to antib acte rial ag e nts in g e ne ral p ractice . J Clin Ep id e miol. 1998;(51):703-708. © Else vie r.

TABLE 201-2 Fre q ue ncy o Various Classe s o Drug s Associate d With an Erup tion (in Case s With < 4 Susp e cte d Drug s)

Class o Drug

No . o Case s (N = 82)

Antib iotic

37

Antie p ile p tic

12

Phe nytoin

9

Antiarrhythmic

6

Calcium ion inhib itors

3

Anticoag ulant

5

Enoxap arin

2

Clop id og re l

2

War arin

1

Anti ung al

4

Antig out

4

Proton p ump inhib itors

4

ACE* inhib itors

3

Contrast

3

Diure tics

3

Anti-inf ammatory

2

Antire troviral (HIV)

2

Antiviral

2

β-Blocke rs

2

Che mothe rap e utic

2

O the r

11

• SJS—It presents with erythematous or pruritic macules, widespread blisters on the trunk and ace, and erosions o one or more mucous membranes (see Figure 201-16). Atypical target lesions or widespread erythema, particularly in the upper chest and back, are potential early signs o both SJS and TEN. 11 Burning or pain ul skin can be a sign o increased severity. Epidermal detachment occurs and involves less than 30% o total body sur ace area. • TEN—It is on the most severe side o the SJS spectrum. EM is diagnosed when less than 10% o the body sur ace area is involved, SJS/ TEN when 10% to 30% is involved, and toxic epidermal necrolysis when more than 30% is involved. • Drug reaction with eosinophilia and systemic symptoms (DRESS) or druginduced hypersensitivity syndrome (DIHS)—In ltrated, palpable lesions are potential heralds o this disorder.11 Central acial edema and erythema (Figure 201-18) and a maculopapular rash are seen along with high ever, generalized lymphadenopathy, and arthralgias. Drug reaction with eosinophilia and systemic symptoms can also cause an erythroderma (Figure 201-19). Latency between starting a drug and rst signs o drug reaction with eosinophilia and systemic symptoms can be up to 12 weeks. 11

*

ACE, Ang iote nsin-conve rting e nzyme . Data rom Ge rson D, Srig ane shan V, Ale xis JB. Cutane ous d rug e rup tions: a 5-ye ar e xp e rie nce . J Am Acad De rmatol. 2008 De c;59(6):995-999.

FIGURE 201-17 Bullous xe d d rug e rup tion with a d usky color and an annular p ink b ord e r on the ankle . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

1029

1030

PART 14 DERMATO LO GY

Ch a pt e r 201

FIGURE 201-20 Acute generalized exanthematous pustulosis caused by a drug eruption. The clusters o small pustules with erythematous skin are seen on the buttocks. In this case the pustules and erythema covered major portions o the back and buttocks. (Reproduced with permission from Robert T. Gilson, MD.)

FIGURE 201-18 Drug re action with e osinop hilia and syste mic symp toms on the ace with acial swe lling and e rythe ma. This 40-ye ar-o ld woman d e ve lop e d d rug re action with e osinop hilia and syste mic symp toms as a re action to a ne w Dilantin p re scrip tion. (Re p rod uce d with p e rmission from Rob e rt T. Gilson, MD.)

• Drugs most commonly known to cause SJS and TEN are sul onamide antibiotics, allopurinol, nonsteroidal antiinf ammatory agents, amine antiepileptic drugs (phenytoin and carbamazepine), and lamotrigine (see Chapter 175, Erythema Multi orme, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis). 12 Fi ty percent o SJS/ TEN cases have no identi able cause. LESS CO MMO N DRUG REACTIO NS • Acute generalized exanthematous pustulosis (AGEP)—It is a type o drug eruption that results in clusters o small pustules along with erythematous skin (Figure 201-20). The patients are o ten ebrile and the pustules are primarily non ollicular and sterile. • Systemic drug-related intertriginous and f exural exanthema (SDRIFE)—It is a type o drug eruption that causes erythema around the buttocks and genitalia along with intertriginous and f exural areas. I the pattern o erythema creates red buttocks then it may also be called the baboon syndrome (Figure 201-21).

FIGURE 201-19 Drug re action with e osinop hilia and syste mic symp toms synd rome (d rug re action, e osinop hilia, syste mic symp toms). Erythrod e rma has p e rsiste d b ut the p atie nt is e e ling b e tte r a te r tre atme nt and d ischarg e rom the hosp ital. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 201-21 Syste mic d rug -re late d inte rtrig inous and f e xural e xanthe ma. Be cause the p atte rn o e rythe ma cre ate s re d b uttocks it may also b e calle d the b ab oon synd rome . (Re p rod uce d with p e rmission from Rob e rt T. Gilson, MD.)

CUt a Ne O US Dr UG r e a Ct IO NS

PART 14 DERMATO LO GY

LABO RATO RY STUDIES The diagnosis o drug eruptions is usually made based on history and physical examination. • An FDE may be diagnosed by “provoking” the appearance o the lesion with an oral rechallenge with the suspected drug; however, this can be dangerous in bullous cases. • Severe reactions may need a complete blood count (CBC) with di erential and comprehensive serum chemistry panel to look or systemic involvement and check hydration status. • In more challenging cases, a skin biopsy may be help ul to con rm the diagnosis. • Intradermal skin testing may be hazardous to patients, and patch tests are not use ul. • Skin biopsies are usually not required or diagnosis o WISN, but may aid in the diagnosis. • Testing or thrombophilia (high platelet count) may also be done in WISN. • Laboratory tests in patients with DRESS/ DIHS may show atypical lymphocytes, eosinophilia, lymphocytopenia, and thrombocytopenia; liver abnormalities are o ten seen.

DIFFERENTIAL DIAGNO SIS • Viral exanthems look just like generalized maculopapular drug eruptions. Sometimes when a patient is given an antibiotic or an upper respiratory in ection, the rash that ensues may be the viral exanthem rather than a drug eruption. The best way to avoid this con usion is only to use antibiotics when the evidence or bacterial in ection is su cient to justi y the risks o a drug reaction. (See Section 3: Viral [Chapters 125-133] or more in ormation on viral exanthems.) • Urticarial reactions present as transient migratory circumscribed areas o blanching-raised erythema and edema o the super cial dermis. Patients experience itching. Identi ying urticaria is easy compared with nding the precipitating actors. I there is a temporal association with starting a new drug, it is best to stop the drug (in most cases) and see i the urticaria resolves. (See Chapter 148, Urticaria and Angioedema.) • EM presents with sudden onset o rapidly progressive, symmetrical, and cutaneus lesions with centripetal spread. The patient may have a burning sensation in a ected areas but usually has no pruritus. EM is most o ten caused by a reaction to an in ection such as herpes simplex virus (HSV) or mycoplasma, but may be caused by a drug reaction. Care ul history and physical examination can help di erentiate between the possible causes (see Chapter 175, Erythema Multi orme, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis). • SJS and TEN present with generalized cutaneous lesion with blisters, ever, malaise, arthralgias, headache, sore throat, nausea, vomiting, and diarrhea. The patient may also have di culty in eating, drinking, or opening his or her mouth secondary to erosion o oral mucous membranes (see Figure 201-16). Not all SJS or TEN is secondary to drug exposure, but it is the job o the clinician to investigate this cause and stop any suspicious medications. SJS and TEN can be li e threatening (see Chapter 175, Erythema Multi orme, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis). • DRESS/ DIHS can be distinguished by involvement o organs other than skin including liver (hepatitis in 50%-70%), kidney (nephritis in 10%), and, more rarely, pneumonitis, colitis, myocarditis, parotitis, meningitis, encephalitis, and pancreatitis; the pattern o organ

FIGURE 201-22 Larg e b le e d in the arm se cond ary to ove rcoag ulation with Coumad in. The larg e he matoma was surg ically e vacuate d to p re ve nt ne urovascular comp romise to the arm. (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

involvement appears to depend on the drug trigger. 7,13 Some o the sequelae rom DRESS/ DHIS are strongly related to herpes virus reactivation. 7 A recurrence o symptoms at the third week is common. Diagnostic criteria have been proposed to include all o the ollowing: maculopapular rash developing more than 3 weeks a ter drug exposure, prolonged clinical symptoms a ter drug discontinuation, ever (> 38°C [100.4°F]), liver abnormalities or other organ involvement, leukocyte abnormalities (atypical lymphocytosis, leukocytosis, eosinophilia), lymphadenopathy, and human herpesvirus-6 reactivation. 13 • Pityriasis rosea (PR) is a mysterious eruption o unknown etiology that could easily mimic a maculopapular drug eruption. Look and ask or the herald patch to help make the diagnosis o PR. In PR, look or the collarette scale and observe whether the eruption ollows the skin lines (causing a Christmas tree pattern on the back). These eatures should help positively identi y PR because there are no laboratory tests that are speci c to PR or most drug eruptions (see Chapter 151, Pityriasis Rosea). • Syphilis is the great imitator. Any generalized rash without a known etiology may be caused by secondary syphilis. A rapid plasma reagin (RPR) will always be positive in secondary syphilis and is easy to run (see Chapter 218, Syphilis). • Bullous pemphigoid and pemphigus vulgaris can resemble a bullous drug eruption. Biopsies are the best way to diagnose these bullous diseases. Their clinical pictures are described in detail in Chapter 182, Bullous Pemphigoid, and Chapter 183, Pemphigus. • Hematoma is a much more common complication o war arin therapy and must be distinguished rom WISN early to decrease permanent tissue damage; a high index o suspicion is needed and a very elevated international normalized ratio (INR) will con rm that bleeding is a result o overcoagulation (Figure 201-22).

MANAGEMENT NO NPHARMACO LO GIC • Discontinue the o ending medication or all types o drug reactions whenever possible. Older patients with drug eruptions may be on multiple medications and may be very ill; however, e orts should be made to discontinue all nonessential medications. 5 SO R C

1031

PART 14 DERMATO LO GY

1032

• Patients with maculopapular reactions may continue to be treated with the o ending agent i it is essential or treating a serious underlying condition. 5

Ch a pt e r 201

PREVENTIO N

• Maculopapular drug eruptions are not a precursor to severe reactions such as TEN. 5

• In the uture, prevention may occur through screening or HLA associations and drug avoidance. 1

• Hyperpigmentation—Stop the drug i possible. In the case o Adriamycin-induced skin hyperpigmentation, the Adriamycin may be continued i it is the best chemotherapy or a li e-threatening malignancy (see Figure 201-5).

• Screening or HLA-B*1502 is advised by the US FDA and Health Canada or patients o southeastern Asian ethnicity be ore carbamazepine therapy. 1

• Local wound care, debridement, and skin gra ting may need to be per ormed to repair resultant dis gurement rom necrosis. 14,15 MEDICATIO NS • Maculopapular- and urticarial/ angioedema-type drug reactions are treated with antihistamines. I the angioedema is causing airway compromise, epinephrine (10 µg/ kg intramuscular) and other treatments will be necessary. 5,13 SO R C Usually an H1-blocker is started. In some cases o urticaria/ angioedema, an H2-blocker is added on or broader antihistamine e ects (see Chapter 148, Urticaria and Angioedema). • Diphenhydramine (Benadryl)—Adult dosing is 25 to 50 mg orally every 4 to 6 hours (nonprescription). • Hydroxyzine (Atarax)—Adults receive 25 mg orally every 6 hours. Pediatric dose 0.5 to 1.0 mg/ kg per day orally 4 times daily. 5 • Loratadine (Claritin)—10 to 20 mg orally 1 time daily5 (nonprescription). • Any H2-blocker can be used by prescription or nonprescription. • Topical steroids such as triamcinolone or desonide may be used or symptomatic relie o pruritus. 5 SO R C • Oral steroids have been used, but little bene t has been shown. 5 13 SOR C These are used in DRESS/ DHIS. • FDEs are treated by discontinuing the drug and applying topical corticosteroids to the a ected area. 4 SO R C REFERRAL O R HO SPITALIZATIO N Patients with WISN, SJS, TEN, and DRESS/ DIHS are usually hospitalized. • WISN treatment is generally supportive, including discontinuing the war arin, admission to the hospital, and administration o vitamin K and resh rozen plasma. 14,15 • Many clinicians recommend resuming heparin therapy i needed or the patient’s underlying pathology that prompted the use o initial anticoagulation therapy. 14,15 • SJS, TEN, DRESS/ DIHS—Start with early diagnosis, rapid discontinuing o o ending agent, intravenous f uid replacement, and placement in an intensive care unit (ICU) or burn unit (see Chapter 175, Erythema Multi orme, Steven-Johnson Syndrome, and Toxic Epidermal Necrolysis). 4,5 Liver transplant has been used in patients with DRESS. 13 • Most experts and studies now agree that systemic corticosteroids should not be used. 4 SO R B • Nutritional support, care ul wound care, temperature control, and anticoagulation are recommended. 4 SO R C • Daily skin samples should be sent or bacterial Gram stain and culture to monitor or developing in ection. 4 SO R C

• Avoid reexposure to the drug.

PRO GNO SIS • Most cutaneous drug reactions resolve with discontinuation o the causative agent. • Mortality, however, is high at 10% or SJS and DRESS/ DHIS and 30% to 50% or TEN. 5,16 In a case series o patients with possible or probably DRESS, case atality rate was 5% (9/ 172). 6 • Some studies show the occurrence o autoimmune diseases, including type 1 diabetes mellitus, autoimmune thyroid disease, sclerodermoid gra t-versus-host disease (GVHD)-like lesions, and lupus erythematosus months to years a ter resolution o DIHS/ DRESS. 7 Because o the long symptom- ree interval in some patients, this relationship is questioned.

FO LLO W-UP • Follow-up is most important when the case is severe or the diagnosis is uncertain. Clear-cut mild drug reactions may not need scheduled ollow-up. • Continued surveillance or autoimmune disorders may be warranted in patients ollowing DRESS/ DHIS.

PATIENT EDUCATIO N • Most patients with drug eruptions recover ully without any complications. The patient should be warned that even a ter the responsible medication is stopped the eruptions may clear slowly or even worsen at rst; the patient should be advised that the reaction may not resolve or 1 to 2 weeks. • The patient should also be counseled that mild desquamation is normal as the exanthematous eruption resolves. Con rming the diagnosis o an FDE, especially lesions presenting on the glans, with a drug challenge may allay the patient anxiety about the venereal origin o the disease. • The amily should be counseled as to the genetic predisposition o some drug-induced eruptions. • The patient should be advised to enroll in a medic alert program and to wear a bracelet detailing the allergy. PATIENT RESO URCES

• MedlinePlus. Drug Allergies—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000819.htm. • Mayo Clinic. Stevens-Johnson Syndrome—http:/ / www. mayoclinic.com/ print/ stevens-johnson-syndrome/ DS00940/ DSECTION=all&METHOD=print.

CUt a Ne O US Dr UG r e a Ct IO NS

PRO VIDER RESO URCES

• Patient.co.uk. Drug Eruptions—http:/ / www.patient.co.uk/ doctor/ Drug-Eruptions.htm. • DermNet NZ. Drug Eruptions—http:/ / dermnetnz.org/ reactions/ drug-eruptions.html. • Medscape. Drug Eruptions—http:/ / emedicine.medscape. com/ article/ 1049474-overview. I the skin eruption is rare, serious, or unexpected, the drug reaction should be reported to the manu acturer and FDA.

REFERENCES 1. Sánchez-Borges M. NSAID hypersensitivity (respiratory, cutaneous, and generalized anaphylactic symptoms). Med Clin North Am. 2010;94(4):853-864. 2. Pichler WJ, Adam J, Daubner B, et al. Drug hypersensitivity reactions: pathomechanism and clinical symptoms. Med Clin North Am. 2010;94(4):645-664. 3. Phillips EJ, Chung WH, Mockenhaupt M, et al. Drug hypersensitivity: pharmacogenetics and clinical syndromes. JAllergy Clin Immunol. 2011;127(suppl 3):S60-S66. 4. Nigen S, Knowles SR, Shear NH. Drug eruptions: approaching the diagnosis o drug-induced skin diseases. J Drugs Dermatol. 2003;2(3):278-299. 5. Habi T. Skin Disease Diagnosis andTreatment. 2nd ed. Philadelphia, PA: Mosby; 2005. 6. Cacoub P, Musette P, Descamps V, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124(7):588-597.

PART 14 DERMATO LO GY 7. Kano Y, Ishida T, Kazuhisa K, Shiohara T. Visceral involvements and long-term sequelae in drug-induced hypersensitivity syndrome. Med Clin North Am. 2010;94(4):743-759. 8. van der Linden PD, van der Lei J, Vlug AE, Stricker BH. Skin reactions to antibacterial agents in general practice. J Clin Epidemiol. 1998;(51):703-708. 9. Gerson D, Sriganeshan V, Alexis JB. Cutaneous drug eruptions: a 5-year experience. J Am Acad Dermatol. 2008 Dec;59(6): 995-999. 10. Fernando SL, Broad oot J. Prevention o severe cutaneous adverse drug reactions: the emerging value o pharmacogenetic screening. CMAJ. 2010;182(5):476-480. 11. Scherer K, Bircher AJ. Danger signs in drug hypersensitivity. Med Clin North Am. 2010;94(4):681-689. 12. Chosidow OM, Stern RS, Wintroub BU. Cutaneous drug reactions. In: Kasper DL, Fauci AS, Longo DL, Braunwald EB, Hauser SL, Jameson JL, eds. Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2005:318-324. 13. Schnyder B. Approach to the patient with drug allergy. Med Clin North Am. 2010;94(4):665-679. 14. Alves DW, Chen IA. War arin-induced skin necrosis. Hosp Physician. 2002;38(8):39-42. 15. Stewart AJ, Penman ID, Cook MK, Ludlam CA. War arin-induced skin necrosis. Postgrad Med J. 1999;75:233-235. 16. Mockenhaupt M, Norgauer J. Cutaneous adverse drug reactions: Stevens-Johnson syndrome and toxic epidermal necrolysis. Allergy Clin Immunol Int. 2002;14:143-150.

1033

PART 14 DERMATO LO GY

1034

Ch a pt e r 202

202 KELO IDS E.J. Maye aux Jr, MD Richard P. Usatine , MD

PATIENT STO RY A 64-year-old black woman presents to the o ce with itching keloids on her chest (Figure 202-1). The horizontal keloid started during childhood when she was scratched by a branch o a tree. The vertical keloid is the result o bypass surgery 1 year ago. The lower portion o this area could be called a hypertrophic scar as it does not advance beyond the borders o the original surgery. The patient was happy to receive intralesional steroids to decrease her symptoms. Intralesional triamcinolone did, in act, decrease the itching and f atten the vertical keloid.

INTRO DUCTIO N Keloids are benign dermal broproli erative tumors that orm in scar because o altered wound healing. They orm as a result o overproduction o extracellular matrix and dermal broblasts that have a high mitotic rate.

SYNO NYMS Keloid is also known as cheloid.

FIGURE 202-2 A k loid on th a lob that sta t d f om i cing th (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

a.

• Men and women are generally a ected equally except that keloids are more common in young adult women—probably secondary to a higher rate o piercing the ears (Figure 202-2). 2 • Highest incidence is in individuals ages 10 to 20 years. 2,3

EPIDEMIO LO GY ETIO LO GY AND PATHO PHYSIO LO GY • Individuals with darker pigmentation are more likely to develop keloids. Sixteen percent o black persons reported having keloids in a random sampling. 1

• Keloids are dermal ibrotic lesions that are a variation o the normal wound-healing process in the spectrum o ibroproli erative disorders. • Keloids are more likely to develop in areas o the body that are subjected to high skin tension such as over the sternum (see Figure 202-1). • These can occur even up to a year a ter the injury and will enlarge beyond the scar margin. Burns and other injuries can heal with a keloid in just one portion o the area injured (Figure 202-3). • Wounds subjected to prolonged inf ammation (acne cysts) are more likely to develop keloids.

RISK FACTO RS • Darker skin pigmentation (A rican, Hispanic, or Asian ethnicity)3 • A amily history o keloids • Wound healing by secondary intention • Wounds subjected to prolonged inf ammation FIGURE 202-1 Two k loid s that c oss th ch st of a 64-y a -old b lack woman. Th ho izontal k loid cam f om a sc atch d u ing child hood , and th v tical k loid is a sult of o n h a t su g y. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Sites o repeated trauma • Pregnancy • Body piercings (Figure 202-4)

Ke LO IDS

FIGURE 202-3 A k loid on th a m of a His anic woman b u n d accid ntally b y a hot i on at th ag of 1 y a . Most of th b u n sca is not a k loid . Th k loid is at th d istal d g wh th skin is ais d nod ula and ink. Sh has u itus in that a a. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

FIGURE 202-5 Many k loid s in a woman who d v lo s k loid s with v n th most mino skin inju i s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

TYPICAL DISTRIBUTIO N

DIAGNO SIS

Anterior chest, shoulders, f exor sur aces o extremities, anterior neck, earlobes, and wounds that cross skin tension lines.

CLINICAL FEATURES

LABO RATO RY TESTING

• Some keloids present with pruritic pain or a burning sensation around the scar.

Biopsy is rarely needed to make a diagnosis because the clinical appearance is usually distinctive and clear.

• Initially mani est as erythematous lesions devoid o hair ollicles or other glandular tissue. • Papules to nodules to large tuberous lesions (Figure 202-5). • Range in consistency rom so t and doughy to rubbery and hard. Most o ten, the lesions are the color o normal skin but can become brownish red or bluish and then pale as they age. 4

DIFFERENTIAL DIAGNO SIS • Hypertrophic scars can appear similar to keloids but are con ned to the site o original injury.

• Lesions on neck, ears, and abdomen tend to become pedunculated.

• Acne keloidalis nuchae is an inf ammatory disorder around hair ollicles o the posterior neck that results in keloidal scarring (Figure 202-6). Although the scarring is similar to keloids the location and

FIGURE 202-4 This k loid fo m d at th sit of a b lly b utton i cing in this young woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 202-6 Acn k loid alis nucha on th ost io n ck of this young Af ican Am ican man. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

• May extend in a claw-like ashion ar beyond any slight injury.

1035

PART 14 DERMATO LO GY

1036

pathophysiology are unique. This process can also cause alopecia (see Chapter 116, Pseudo olliculitis and Acne Keloidalis Nuchae). • Dermato bromas are common button-like dermal nodules usually ound on the legs or arms. They may umbilicate when the surrounding skin is pinched. These o ten have a hyperpigmented halo around them and are less elevated than keloids (see Chapter 158, Dermato broma). • Dermato brosarcoma protuberans is a malignant version o the dermato broma. It usually presents as an atrophic, scar-like lesion developing into an enlarging, rm, and irregular nodular mass. I this is suspected, a biopsy is needed (see Chapter 158, Dermato broma).

MANAGEMENT • Patients requently want keloids treated because o symptoms (pain and pruritus) and concerns about appearance. • A 2006 systematic review o 396 studies and an accompanying metaanalysis o 36 articles concluded that no optimal evidence-based therapy exists and recommended choosing treatment based on cost and adverse e ect pro le. 5

Ch a pt e r 202

excision sites the night o the surgery and daily or 6 to 8 weeks postsurgery. Imiquimod 5% cream only temporarily prevented the recurrence o presternal keloids a ter excision. 11 SO R C • Intralesional verapamil 2.5 mg/ mL, bleomycin 1.5 IU/ mL, and inter eron-α 2b injections 1.5 million IU twice daily or 4 days are less-studied alternatives to corticosteroid treatment. 3 SOR C CO MPLEMENTARY AND ALTERNATIVE THERAPY No available evidence supports using nonprescription products such as Mederma and other creams, gels, and oils, to treat scars. 7 Limited clinical trials have ailed to demonstrate lasting improvement o established keloids and hypertrophic scars with onion extract topical gel (eg, Mederma) or topical vitamin E. 3 SO R B SURGICAL • Cryosurgery and intralesional triamcinolone have been used to treat smaller keloids (eg, secondary to acne) with similar success to other therapies. 3,12 SO R B

NO NPHARMACO LO GIC

• Combined cryosurgery and intralesional triamcinolone—The lesion is initially rozen with liquid nitrogen spray and allowed to thaw. Then it is injected with triamcinolone acetate (10-40 mg/ mL). SO R C

Silicone gel sheeting as a treatment or hypertrophic and keloid scarring is supported by poor-quality trials susceptible to bias. There is only weak evidence o a bene t o silicone gel sheeting as prevention or abnormal scarring in high-risk individuals. 6,7 SOR B

• Earlobe keloids can be surgically excised with a shave or excisional technique and then injected with triamcinolone acetate (10-40 mg/ mL) a ter hemostasis is obtained. The triamcinolone injection can be repeated in 1 month to decrease the chance o recurrence. 8 SO R B

MEDICATIO NS

• Keloids on the upper ear can be excised and the skin closed with sutures (Figure 202-8). SO R C

• Intralesional steroid injections—Intralesional injection o triamcinolone acetonide (10-40 mg/ mL) may decrease pruritus, as well as decreasing size and f attening o keloids (Figure 202-7). SO R C This may be repeated monthly as needed. 5,8 • Earlobe keloids can be treated with imiquimod 5% cream ollowing tangential shave excision on both sides o the earlobe. 9,10 SO R B Patients were instructed to administer imiquimod 5% cream to the

FIGURE 202-7 T iamcinolon inj ct d into this sym tomatic k loid on th ch st. Not how th k loid is b lanching whit , d monst ating that th st oid is o ly inj ct d into th b od y of th k loid . A Lu lock sy ing is us d to avoid th n d l o ing off d u ing th inj ction und ssu and a 27-g aug n d l is us d to minimiz ati nt d iscomfo t. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 202-8 Two la g k loid s on th a of this 23-y a -old man that sta t d aft h x i nc d t auma to th a . Both k loid s w xcis d o n 2 s a at occasions and th skin clos d with sutu s. Int al sional t iamcinolon was inj ct d to v nt g owth of th k loid s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 14 DERMATO LO GY

Ke LO IDS

• Pulsed-dye laser treatment can be bene cial or keloids. 13 Combination treatment with pulsed-dye laser plus intralesional therapy with corticosteroids and/ or f uorouracil 50 mg/ mL 2 to 3 times per week may be superior to either approach alone. 14 SO R C • Keloids can be treated with cryosurgery alone or in combination with intralesional steroids. In one, small, controlled study, 10 patients with keloids were treated with intralesional steroid and cryosurgery versus intralesional steroid or cryosurgery alone. 15 SO R B Patients were treated at least 3 times 4 weeks apart. Based on keloid thickness, the keloids responded signi cantly better to combined cryosurgery and triamcinolone versus triamcinolone alone or cryotherapy alone. Pain intensity was signi cantly lowered with all treatment modalities. Pruritus was lowered only with the combined treatment and intralesional corticosteroid alone. 15 • In another study, 20 patients with hypertrophic and keloidal scars received two 15-second cycles (total 30 seconds) o cryosurgery treatments once monthly or 12 months with intralesional injections o 10 to 40 mg/ mL triamcinolone once monthly or 3 months. 16 SO R B Topical application o silicone gel was added 3 times daily or 12 months. The control group included 10 patients who received treatment with silicone sheeting only. A ter 1 year there was improvement in all the parameters, especially in terms o symptoms, cosmetic appearance, and associated signs, compared to baseline and the control group. 16 SOR B • Layton et al. reported that the intralesional injection o a steroid is help ul but cryotherapy is more e ective (85% improvement in terms o f attening) or recent acne keloids located on the back. 17 Treatment with intralesional triamcinolone was bene cial, but the response to cryosurgery was signi cantly better in early, vascular lesions. 17 SO R B • I the keloid is older and/ or rmer, it may not respond to injection therapy as well as so ter and newer lesions. It may help to pretreat the keloid with cryotherapy. It is not necessary to reeze a margin o normal tissue. A ter liquid nitrogen or another reezing modality is applied to the keloid, it is allowed to thaw and develop edema. This generally takes 1 to 2 minutes, which allows an easier introduction o intralesional steroids into the lesions. SO R C • In one double-blind, clinical trial, 40 patients were randomized to receive intralesional triamcinolone (TAC) or a combination o TAC and 5-f uorouracil (5-FU). 18 Both groups received injections at weekly intervals or 8 weeks and lesions were assessed or erythema, pruritus, pliability, height, length, and width. Both groups showed an acceptable improvement in nearly all parameters, but these were more signi cant in the TAC plus 5-FU group (p 10 000) ■ Neutrophil predominance, typically 80% to 95% ° Glucose is less than 40 mg/ dL (2.22 mmol/ L) in about 50% to 60% o patients. ° Elevated protein (> 50 mg/ dL) is seen in nearly 100% o patients; however, this may be adjusted or increased protein caused by traumatic tap (subtract 1 mg/ dL [0.01 g/ L] protein per 1000 red blood cells/ mm3). ° Positive Gram stain results are seen in ■ 90% o cases o S. pneumonia ■ 86% o cases o H. inf uenza ■ 75% o cases o N. meningitides ■ 50% o cases o gram-negative bacilli ■ 33% o cases o L. monocytogenes

In f e c TIo u s DIs e As e s ° In the absence o a positive Gram stain, which has almost 100% specif city, no single CSF biochemical variable can reliably exclude bacterial meningitis in the setting o an elevated CSF white blood cell count.10 • In the presence o an elevated lactate concentration in postoperative neurosurgical patients, consider initiation o empirical antimicrobial therapy or CSF lactate concentrations o 4 mmol/ L (36 mg/ dL) or greater, pending other study results. SO R CSF lactate concentrations are not recommended or community-acquired meningitis. • Latex agglutination is not recommended or routine use but may be use ul or patients with negative CSF Gram stain and culture, especially those pretreated with antibiotics. 9 SO R • The In ectious Diseases Society o America (IDSA) recommends that i a CT or an LP is delayed, obtain blood cultures and start appropriate antibiotic and adjunctive therapy (Figure 216-5). 9 • I an LP is delayed and empiric antibiotic therapy initiated, the yield o a subsequent LP will be lower, and the use o blood tests (blood cultures, WBC count, glucose, C-reactive protein [CRP], or procalcitonin level) can be help ul in providing evidence or or against bacterial meningitis. 9 IMAGING • Head CT may be indicated prior to LP in specif c patients. IDSA guidelines or indication o CT scan prior to LP ° The 2004 include9 ■ Immunocompromised state ■ History o central nervous system disease (mass lesion, stroke, or ocal in ection) ■ New-onset seizure (within 1 week o presentation) ■ Papilledema ■ Abnormal level o consciousness ■ Focal neurologic def cit

Ba cte ria l Me ningitis ?

Immunocompromis e , Hx of CNS s hunts , hydroce pha lus , tra uma , s pa ce occupying le s ions , pos t CNS s urge ry, ne w s e izure , pa pille nde ma , ↓ le ve l of cons cious ne s s , foca l ne urologica l de ficits

No

Ye s

Blood culture a nd LP s ta t

Blood culture s s ta t

De xa me tha s one + a ntimicrobia l Rx

De xa me tha s one + a ntimicrobia l Rx

Ne ga tive he a d CT

P e rform lumba r puncture FIGURE 2 16 -5 The Infe ctious Dise ase s Socie ty of Ame rica (IDSA) re comme nd ations for manag e me nt if comp ute d tomog rap hic (CT) scanning or a lumb ar p uncture (LP) is d e laye d : o b tain b lo o d culture s and start ap p ro p riate antib io tic and ad junctive the rap y. CNS, ce ntral ne rvo us syste m; Hx, histo ry; Rx, p re scrip tion. (Ad ap te d fro m Tunke l AR, Hartman BJ, Kap lan SL, e t al. Practice g uid e line s fo r the manag e me nt o f b acte rial me ning itis. Clin Infe ct Dis. 2004;39(9):1267-1284.)

1093

PART 16

1094

In f e c TIo u s DIs e As e s DIf f ERENTIAL DIAGNO SIS • Aseptic meningitis is di erentiated by negative routine bacterial cultures. Viral meningitis is most common; however, aseptic meningitis also re ers to in ections rom other organisms, including ungal meningitis, spirochetal meningitis, and mycobacterial meningitis. • Drug-induced meningitis can be seen with several drugs, including nonsteroidal anti-in ammatory drugs, and is a diagnosis o exclusion. • Mollaret meningitis is characterized by 4 or more episodes o lymphocytic meningitis lasting several days with spontaneous resolution. • Carcinomatous meningitis rom seeding o the meninges rom lymphomas and acute leukemias is seen.

MANAGEMENT • Bacterial meningitis is a neurologic emergency, and appropriate therapy should be started as soon as possible a ter its diagnosis is considered likely. • The ollowing are 3 axioms o antibiotic therapy or bacterial meningitis: use o bactericidal drugs e ective against the in ecting organism, use o drugs that enter the CSF, and use o drugs with optimal pharmacodynamics. 11 • Delay in antibiotic therapy o more than 3 to 6 hours is associated with increased mortality in patients hospitalized with bacterial meningitis. • Empiric antibiotic choice9 ° No known immunodef ciency ■ Vancomycin 10 to 15 mg/ kg IV every 8 hours or 15 to 22.5 mg/ kg IV every 12 hours to maintain serum trough levels 15 to 20 mg/ mL ■ Ce triaxone (2 g IV every 12 hours or 4 g IV every 24 hours) or ce otaxime (8-12 g/ d IV with dosing every 4-6 hours) ■ Adults older than 50 years old: add ampicillin 2 g IV every 4 hours; state reasons or this • Dexamethasone may reduce rates o death, hearing loss, and neurological sequelae in adults with bacterial meningitis caused by suspected or proven pneumococcal meningitis. 9 SO R ° Dexamethasone is recommended in all adults with suspected or proven pneumococcal meningitis9 SO R but should not to be given to adults who have already received antibiotic therapy. ° Theoretically, dexamethasone may be harm ul in meningitis because o highly cephalosporin-resistant strains o pneumococcus; thereore, until the results o the culture and sensitivity are available, consider adding ri ampin 600 mg every 24 hours with dexamethasone. 9 SO R

• In patients with impaired cell-mediated immunity, additional coverage must be directed against L. monocytogenes and gram-negative bacilli (including Pseudomonas aeruginosa). 5,9 ° Vancomycin: 30 to 60 mg/ kg IV per day in 2 or 3 divided doses plus ■ Ampicillin—2 g IV every 4 hours plus either ■ Ce epime—2 g IV every 8 hours or ■ Meropenem—2 g IV every 8 hours ■ In patients allergic to b-lactams ° Vancomycin—30 to 60 mg/ kg IV per day in 2 or 3 divided doses plus ° Moxif oxacin—400 mg IV once daily plus ■ I Listeria coverage is required, trimethoprim-sul amethoxazole (10 to 20 mg/ kg) (o the trimethoprim component) IV per day every 6 to 12 hours. 3

Ch a pt e r 216

• In patients with bacterial meningitis a ter shunt placement ° Use direct instillation o antimicrobial agents into ventricles in patients unable to undergo surgical components o therapy or with shunt in ections that are di f cult to eradicate. 9 SO R • For shunt in ection with methicillin-resistant Staphylococcus aureus, shunt removal is recommended, and the shunt should not be replaced until CSF cultures are repeatedly negative SO R . 12

PRO GNO SIS AND CO MPLICATIO NS • In a study in the United States, the case- atality rate o bacterial meningitis in adults was 16.4%, and it was 22.7% in patients 65 years or older. 13 • Normal or marginally elevated CSF white cell counts occur in 5% to 10% o patients and are associated with adverse outcomes. 5 • Major complications o meningitis include cognitive def cit, bilateral hearing loss, motor def cit, seizures, visual impairment, and hydrocephalus. • Minor complications include behavioral problems, learning di f culties, unilateral hearing loss, hypotonia, and diplopia. • Risk o complication is 19.9% or any complication, 12.8% or major complication, and 8.6% or minor complication. 14

f O LLO W-UP The IDSA recommends repeat LP or CSF analysis or patients not responsive to antimicrobial therapy a ter 48 hours. SO R PATIENT RESO URCES

• Centers for Disease Control and Prevention. Meningococcal disease—http:/ / www.cdc.gov/ meningococcal/ about/ index.html. • MedlinePlus. Meningitis—http:/ / www.nlm.nih.gov/ medlineplus/ meningitis.html. PRO VIDER RESO URCES

• Infectious Disease Society of America guidelines on bacterial meningitis—http:/ / www.idsociety.org/ uploadedFiles/ IDSA/ Guidelines-Patient_Care/ PDF_Library/ Bacterial%20 Meningitis(1).pdf. REFERENCES 1. Schuchat A, Robinson K, Wenger JD, et al. Bacterial meningitis in the United States in 1995. Active Surveillance Team. N Engl J Med. 1997;337(14):970-976. 2. Scheld WM, Koedel U, Nathan B, Pf ster HW. Pathophysiology o bacterial meningitis: mechanism(s) o neuronal injury. J In ect Dis. 2002;186(suppl 2):S225. 3. Chaudhuri A, Martinez-Martin P, Kennedy PG, et al. EFNS guideline on management o community-acquired bacterial meningitis: report o an EFNS Task Force on acute bacterial meningitis in older children and adults. Eur J Neurol. 2008;15(7):649-659. 4. Durand ML, Calderwood SB, Weber DJ, et al. Acute bacterial meningitis in adults. A review o 493 episodes. N Engl J Med. 1993;328(1):21.

MENINGITIS

5. van de Beek D, de Gans J, Spanjaard L, Weis elt M, Reitsma JB, Vermeulen M. Clinical eatures and prognostic actors in adults with bacterial meningitis. N Engl J Med. 2004;351(18):1849. 6. Attia J, Hatala R, Cook DJ, Wong JG. The rational clinical examination. Does this adult patient have acute meningitis? JAMA. 1999;282(2):175-181. 7. Thomas KE, Hasbun R, Jekel J, Quagliarello VJ. The diagnostic accuracy o Kernig’s sign, Brudzinski’s sign, and nuchal rigidity in adults with suspected meningitis. Clin In ect Dis. 2002;35(1):46-52. 8. Waghdhare S, Kalantri A, Joshi R, Kalantri S. Accuracy o physical signs or detecting meningitis: a hospital-based diagnostic accuracy study. Clin Neurol Neurosurg. 2010;112(9):752-757. 9. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines or the management o bacterial meningitis. Clin In ect Dis. 2004;39(9):1267-1284. 10. Spanos A, Harrell FE Jr, Durack DT Di erential diagnosis o acute meningitis. An analysis o the predictive value o initial observations. JAMA. 1989;262(19):2700.

PART 16

In f e c TIo u s DIs e As e s 11. Sinner SW, Tunkel AR. Antimicrobial agents in the treatment o bacterial meningitis. In ect Dis Clin North Am. 2004;18(3):581. 12. Liu C, Bayer A, Cosgrove SE, et al; In ectious Diseases Society o America. Clinical practice guidelines by the In ectious Diseases Society o America or the treatment o methicillin-resistant Staphylococcus aureus in ections in adults and children. Clin In ect Dis. 2011;52(3):e18-e55. 13. Thigpen MC, Whitney CG, Messonnier NE, et al; Emerging In ections Programs Network. Bacterial meningitis in the United States, 1998-2007. N Engl J Med. 2011;364(21):2016. 14. Edmond K, Clark A, Korczak VS, Sanderson C, Gri f ths UK, Rudan I. Global and regional risk o disabling sequelae rom bacterial meningitis: a systematic review and meta-analysis. Lancet In ect Dis. 2010;10(5):317-328.

1095

1096

PART 16

In f e c TIo u s DIs e As e s

Ch a pt e r 217

217 O STEO MYELITIS Hannah Fe re nchick, MD

PATIENT STO RY A previously healthy 48-year-old man presents with a 2-week history o a low-grade ever and a new onset o back pain. The severity o the pain was increasing over the previous 4 days and woke him rom sleep at night. He denies any injury or any new activity. On examination, his temperature is elevated (100.2°F), and he has reproducible tenderness over the lower thoracic spine. A computed tomographic (CT) scan o the spine reveals destruction o the endplates between T11 and T12 consistent with osteomyelitis (Figure 217-1a and 217-1b). A subsequent bone biopsy and culture reveal methicillin-sensitive Staphylococcus aureus as the in ecting agent causing the osteomyelitis. A

INTRO DUCTIO N Osteomyelitis is an in ection contained in bone. There have been many advances since the 1970s in treating this disease, including the introduction o new antibiotics, new surgical techniques, and advancement in the delivery o antibiotics. Despite this, however, osteomyelitis can be a di cult clinical challenge or physicians in both its diagnosis and its treatment.

EPIDEMIO LO GY • Bone in ections are most common in patients younger than 20 years and older than 50 years. 1 • Estimated annual incidence o osteomyelitis in the United States is less than 2%. 1 • Incidence o vertebral osteomyelitis is 2.4 cases per 100,000 population. 2 ° Increasing incidence with increasing age rom 0.3 per 100,000 in 20 years and younger to 6.5 per 100,000 with persons older than 70 years. 2

ETIO LO GY/ PATHO PHYSIO LO GY • Osteomyelitis may result rom direct inoculation o bacteria into bone, contiguous seeding rom adjacent in ected tissues, or hematologic seeding. 3 • Direct inoculation and contiguous seeding usually result in a polymicrobial in ection. • Hematogenous osteomyelitis is nearly always caused by a single organism.3 hematogenous ° The most common pathogen in acute and chronic osteomyelitis in adults and children is S. aureus. 4 and ° In children, group A Streptococcus, Streptococcus pneumoniae, Kingella kingae are also common causes o osteomyelitis. 4 4 ■ Group B streptococcal in ection occurs almost solely in in ants. ° In adults with chronic osteomyelitis, Staphylococcus epidermidis, Pseudomonas aeruginosa, Serratia marcescens, and Escherichia coli may be implicated. 4

B FIGURE 217-1 (A, B) De struction o the in e rior e nd p late o T11 and sup e rior e nd p late o T12 with re active b ony scle rosis. Frontal vie w (A) in the comp ute d tomog rap hic (CT) scan and (B) late ral vie w. The re is loss o ve rte b ral b od y he ig ht o the T11 ve rte b rae o ap p roximate ly 60%. Pe rcutane ous CT-g uid e d b one asp iration o the a e cte d site re ve ale d g rowth o Stap hylococcus aure us. (Re p rod uce d with p e rmission from Michig an State Unive rsity Rad iolog y Te aching File s: Sharon Kre ue r, DO .)

are most common in patients ° Fungal and mycobacterial in ections with impaired immune unction. 4 • In children, hematogenous osteomyelitis most o ten a ects the metaphysis o long bones. In adults, it most o ten involves vertebral bodies. ° The metaphysis is likely involved because o the blood f ow and anatomy o long bones. ■ The major blood vessel to long bones enters in the diaphysis and travels to both metaphyses.

O STEO MYELITIS

It orms vascular loops be ore reaching the epiphyseal plates, and it is thought that the slowed blood f ow in these loops and the absence o a basement membrane predisposes this site to in ection. Vertebral marrow is highly vascularized in comparison to marrow o the long bone. Blood-borne bacteria that f ow throughout the vascular system (such as in intravenous drug users) may initiate in ection spontaneously. Disruptions in anatomy caused by prior or current bone injury may predispose to this. Segmental arteries that supply vertebrae split and run to 2 adjacent vertebral endplates. There ore, hematogenous vertebral osteomyelitis o ten a ects 2 neighboring vertebrae and their intervertebral disk.

■

° ° ° °

• Osteomyelitis can be directly introduced by surgical contamination or trauma (Figure 217-2). 3 • Contiguous ocus osteomyelitis occurs rom seeding rom adjacent so t-tissue in ections. This is most common in patients with

PART 16

In f e c TIo u s DIs e As e s predisposing diseases such as diabetes mellitus or peripheral vascular disease. 3 ° Patients with diabetic nephropathy have decreased awareness o wounds, which can lead to the development o unrecognized in ection. ° Associated with diabetes is peripheral vascular disease, which contributes to chronic wounds and so t-tissue in ection by delaying the body’s healing responses. Both o these conditions increase the risk o developing chronic osteomyelitis. 4 exudate that ° Acute osteomyelitis is characterized by suppurative develops in the marrow (see Figure 217-2). 3 ° Edema, vascular congestion, and small-vessel thrombosis can compromise blood supply as the in ection grows outward toward the bone cortex and periosteum. Necrosis can then occur and lead to the separation o dead pieces o bone (called sequestra). 3 o ° Acute osteomyelitis can be contained be ore the ormation 3 sequestra by early antibiotics and surgery i necessary. • Once sequestra have developed, the in ection is known as chronic osteomyelitis. ° Chronic osteomyelitis is characterized by necrotic bone, the development o new bone, and the exudation o polymorphonuclear leukocytes and other cells. 3 orms a sheath ° New bone growth in areas o periosteal damage around dead bone, called an involucrum. 3 ° The involucrum is o ten in ltrated with openings or sinuses through which purulent exudate drains to surrounding so t tissue and possibly to skin sur aces. 3 A ter the sequestrum is removed operatively or cleared through host immunological de enses, the cavity may ll in with new bone or remain cavitary. In adults, this cavity may ll with brous tissue and remain connected to the skin via a sinus tract (Figure 217-3). 3

A

B FIGURE 217-2 A. O ste omye litis at the me tatarsal joints in a te r amp utation o the ourth and f th rig ht toe s in a d iab e tic p atie nt. B. Close -up o the oste omye litis showing the p urule nce around the b one . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 217-3 A sinus tract in a p atie nt with chronic oste omye litis o the le t hip . (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

1097

PART 16

1098

In f e c TIo u s DIs e As e s

Ch a pt e r 217

RISK FACTO RS • • • •

Diabetes mellitus Peripheral vascular disease4 Peripheral neuropathy4 Risk actors or bacteremia ° Urinary tract in ection (UTI) ° Indwelling catheters ° Central lines ° Dialysis ° Sickle cell disease ° Intravenous drug use • Immunode cient conditions • Recent surgical operations • Penetrating trauma

DIAGNO SIS • Osteomyelitis o ten presents as a constellation o vague and nonspeci c symptoms, which can make the diagnosis di cult. ° Acute hematogenous and contiguous osteomyelitis may present with the onset o pain over several days, associated with localized signs such as swelling, erythema, warmth, and bony tenderness. Systemic signs such as ever, chills, night sweats, irritability, and lethargy can also occur.4 ° These symptoms may not all be present, however, and in sites such 2 as the vertebral column and pelvis, the only complaint may be pain. • Acute hematogenous and contiguous ocus osteomyelitis can both advance to a chronic condition. • Chronic osteomyelitis may present with nonspeci c complaints o pain and possibly low-grade ever or 1 to 3 months. ° Chronic in ection is requently associated with draining sinus tracts. • Erythrocyte sedimentation rate (ESR) is usually elevated, but leukocyte count may be normal. 3 HISTO RY/ SYMPTO MS • History o systemic symptoms: lethargy, malaise, extremity or back pain, ever4 • Predisposing actors: history o diabetes, peripheral vascular disease, intravenous drug use, trauma or invasive procedures4 PHYSICAL EXAMINATIO N Focus on locating a source o in ection • Assess peripheral vascular and sensory unction. • Look or cutaneous injury or diabetic ulcers (Figure 217-4). • Probing bone with a sterile probe within a diabetic oot ulcer is diagnostic or osteomyelitis; no urther imaging studies are needed. 4 • The ollowing are clinical signs to look or4: ° Exposed bone (see Figure 217-2) ° Persistent sinus tract (see Figure 217-3) ° Tissue necrosis overlying bone ° Chronic wounds overlying surgical hardware ° Chronic wound overlying racture (Figure 217-5) LABO RATO RY TESTING • The ESR is help ul in ollowing the e cacy o treatment. • C-reactive protein (CRP)

FIGURE 217-4 Diab e tic oot ulce r with oste omye litis o the me tatarsal b one and g ang re ne o the se cond toe in a woman with p oorly controlle d d iab e te s. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.) 4 ° Continuously normal CRP and ESR may rule out osteomyelitis. ° CRP levels correlate more closely with response to therapy than ESR; there ore, serial CRP levels can be used to gauge clinical response to treatment. 4

• White blood cell count ° O ten elevated with acute osteomyelitis but can be normal with chronic osteomyelitis. • Blood culture ° A positive blood culture eliminates the need or more invasive procedures, such as bone biopsy, to identi y microorganism (except i a polymicrobial in ection is suspected). 4 • Bone biopsy obtained through radiographic intervention or done surgically is crucial to diagnose osteomyelitis and to correctly identi y involved microorganisms. ° Two bone biopsy specimens are pre erred. 1. One is sent in sterile container or Gram stain and culture. 2. The other is sent in ormalin or histopathology to look or necrosis. ° Bone samples should be cultured or aerobic and anaerobic bacteria and ungi. ° Wound or sinus tract cultures do not reliably predict the in ecting organism in osteomyelitis, and they should not be used to direct treatment. 4 IMAGING • Plain radiograph (Figures 217-5B, 217-6A and B, and 217-7) 1 Widely available and inexpensive ° out other pathology, such ° Can be use ul as rst-line imaging to rule as metastases or osteoporotic ractures4 ° Disadvantages include ■ Sensitivity o 43% to 75% and a speci city o 75% to 83% in diagnosing osteomyelitis4 ■ Inability to diagnose in ection until late in its course • Osteomyelitis is not generally visible on radiograph until it is at least 1 cm in diameter and diminishes around 50% o bone structure. 1 • There ore, changes may not be visible until 5 to 7 days in children and 10 to 14 days in adults. 1

O STEO MYELITIS

PART 16

In f e c TIo u s DIs e As e s

A FIGURE 217-6 Sub cutane ous swe lling and e mp hyse ma in the me d ial asp e ct o the oot in this p atie nt with e xte nsive oste o mye litis and ove rlying ce llulitis. The re is also p e rioste al re action involving the f rst throug h third me tatarsals. This imag e also shows a p rior amp utation o the third d ig it at the le ve l o the me tacarp op halang e al joint. (Re p rod uce d with p e rmission from Rad io log y Te aching File s, Michig an State Unive rsity, Jarrod Yate s, DO .)

B FIGURE 217-5 A. O p e n wound ove rlying an are a o oste omye litis in a nonhe ale d racture o the tib ia in a re source -limite d country whe re acce ss to me d ical care was limite d at the time o the injury. B. Rad iog rap h showing nonhe ale d racture and the ong oing oste omye litis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Magnetic resonance imaging (MRI) may be needed i the diagnosis o osteomyelitis ° Expensive; however is questionable3 best ability or early detection o osteomyelitis (as early as ° Provides 1,4 3-5 days) ° Sensitivity o 82% to 100% and speci city o 75% to 96% or diagnosis o osteomyelitis tissues, which can assist in ° Also allows or assessment o surrounding the planning o surgical management1 ° Disadvantages include: ■ Inability to distinguish between in ections and reactive inf ammatory processes 1 ■ Inability to image sites with metallic implants

• Computed tomography ° May show bone changes earlier than plain radiographs so t tissue contrast as ° Less desirable than MRI because o “decreased well as exposure to ionizing radiation”1 ° Most help ul in diagnosis o chronic osteomyelitis because o its superior ability (vs. MRI) to detect sequestra, cloacas, and involucra1 ° Also may 1be help ul in guidance o needle biopsies and joint aspiration ° Sensitivity or diagnosis o chronic osteomyelitis 67% and speci city 50% • Ultrasound (US) ° Ultrasound is easily accessible and inexpensive and o ers real-time evaluation o pathology distinguish osteomyelitis rom tumors or nonin ec° Can be use ul to 1 tive conditions 1 Also use ul to guide needle aspirations and biopsies ° ° Disadvantages include ■ There is undetermined sensitivity and speci city in diagnosing osteomyelitis. 1 1 ■ Diagnosis is operator dependent. 1 ■ The US beam cannot pass through cortical bone. • Nuclear medicine imaging ° Examples: 3-phase technetium-99 bone scintigraphy and leukocyte scintigraphy and usually positive ° Can detect osteomyelitis be ore plain radiograph within a ew days o onset o symptoms4 ° Most agents highly sensitive but have a low speci city

1099

1100

PART 16

In f e c TIo u s DIs e As e s

Ch a pt e r 217

° Degenerative disk disease di erentiated by association with chronic back pain, typically better with rest and worse with activity, and an insidious onset (see Chapter 102, Back Pain) ° Spinal stenosis di erentiated by back and leg pain worse with walking and better with rest (see Chapter 103, Lumbar Spinal Stenosis) • Other ° Gout/ pseudogout di erentiated by the location (a joint) with a sudden onset o pain and inf ammation (see Chapter 105, Gout) ° Charcot joint di erentiated by the preexisting presence o neuropathy, such as seen in diabetes, and the absence o systemic symptoms (see Chapter 210, Charcot Arthropathy) ° Cellulitis di erentiated by acute, spreading bacterial inf ammation o the skin and subcutaneous tissue, commonly complicating skin trauma rom a wound, ulcer, or rash (see Chapter 122, Cellulitis)

MANAGEMENT

FIGURE 217-7 Chronic oste omye litis. AP rad iog rap h o the tib ia/f b ula showing larg e , e xp ansile and d iap hyse al le sion with onionskin b ony re mod e ling and an irre g ular ce ntral luce ncy (Re p ro d uce d with p e rmission fro m Te hranzad e h J. Musculoske le tal Imag ing Case s. Ne w York: McGraw-Hill, 2009.)

° Disadvantages include ■ Di culty to di erentiate osteomyelitis rom other processes, such as neoplasia, cellulitis, arthritis, ractures, and so on ■ Need or urther imaging ■ Low speci city ° May be use ul or supplemental studies when X-rays are compromised by pathologic or postsurgical changes or when MRI is not available or contraindicated1,4

DIFFERENTIAL DIAGNO SIS • Osteomyelitis o long bones ° Malignant or benign tumor is di erentiated by lack o ever; radiographic destruction may mimic osteomyelitis. ° Old trauma can be di erentiated with history and absence o ever. ° Bone in arct secondary to sickle cell anemia can be di erentiated by the diagnosis o sickle cell disease and the chronicity o the problem. • Vertebral osteomyelitis ° Pyelonephritis di erentiated by f ank pain and dysuria ° Pancreatitis di erentiated by the primary symptom o epigastric pain (radiating to the back) associated with excessive alcohol use or gallstones (see Chapter 75, Acute Pancreatitis) ° Osteoporotic racture di erentiated by sudden onset o pain, not associated with ever in a patient with preexisting osteoporosis (see Chapter 225, Osteoporosis and Osteopenia)

• Antibiotics and surgical debridement o in ected and necrotic tissue are the mainstays o treatment or osteomyelitis. ° Antibiotic choice should be tailored to susceptibility as determined by cultures. results return is ° Delaying antibiotics until culture and sensitivity pre erable, but only i clinically appropriate. 4 ° Duration o treatment depends on the clinical scenario: ■ For osteomyelitis in adults, a treatment regimen o anywhere rom 4 to 6 weeks to 3 months is recommended. Few data rom controlled trials are available to suggest optimal duration. 2 ■ For chronic osteomyelitis, parental therapy or 2 to 6 weeks with a total duration o treatment or 4 to 8 weeks has been recommended.4 • Speci c antibiotic regimens depend on the organism present: 2 ° S. aureus or coagulase-negative staphylococci (methicillin sensitive) ■ Na cillin or oxacillin 2 g IV every 6 hours ■ Alternative—Fluoroquinolone plus ri ampin (eg, levof oxacin 750 mg by mouth daily plus ri ampin 300 mg every 12 hours) (methicillin resistant) ° S. aureus or coagulase-negative staphylococci 2 ■ Vancomycin 1 g IV every 12 hours ■ Alternative—Fluoroquinolone plus ri ampin (such as levof oxacin 750 mg orally daily plus ri ampin 300 mg orally every 12 hours or trimethoprim/ sul amethoxazole 160/ 800 mg orally 3 times daily) ° Streptococcal species ■ Penicillin G 5 million units IV every 6 hours ■ Alternative—Ce triaxone 2 g IV daily ° Enterobacteriaceae, quinolone sensitive ■ Fluoroquinolone (eg, ciprof oxacin 750 mg orally every 12 hours) ■ Alternative—Ce triaxone 2 g IV daily ° Enterobacteriaceae, quinolone resistant ■ Ticarcillin/ clavulanate, 3.1 g IV every 4 hours or piperacillin/ tazobactam (Zosyn), 3.375 g IV every 6 hours 4 ■ Alternative—Ce triaxone, 2 g IV every 24 hours 4 ° Pseudomonas aeruginosa ■ Ce epime or ce tazidime 2 g every 8 hours plus ciprof oxacin 400 mg IV every 8 to 12 hours ■ Alternative: Piperacillin/ tazobactam 3.375 g IV every 6 hours plus ciprof oxacin 400 mg IV every 12 hours ° Anaerobes 2 ■ Clindamycin 300 to 600 mg IV every 6 to 8 hours ■ Surgical treatment is indicated in cases o antibiotic ailure, chronic osteomyelitis with necrotic bone, and in ected implanted hardware. 4

PART 16

O STEO MYELITIS

° Adequate surgical debridement decreases bacterial load, removes necrotic tissue, and gives a chance or the host immune system and antibiotics to arrest in ection. 5 ■ Appropriate debridement may create large bony de ects or dead space. Management o this space includes replacing dead bone and scar tissue with vascularized tissue, which is imperative to stop the disease process and maintain the integrity o the bone. 6

In f e c TIo u s DIs e As e s PATIENT RESO URCES

• PubMed Health. Osteomyelitis—http:/ / www.ncbi.nlm.nih .gov/ pubmedhealth/ PMH0001473/ . • Mayo Clinic. Osteomyelitis—http:/ / www.mayoclinic.com/ health/ osteomyelitis/ DS00759/ . • Medline Plus. Osteomyelitis—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000437.htm. PRO VIDER RESO URCES

PRO GNO SIS • Treatment ailure is predicted a ter 4 weeks with a CRP greater than 30 mg/ L and no pain reduction and persistent ever. • There is poor correlation between MRI changes and clinical improvement a ter 4 to 8 weeks; 85% o patients with clinical improvement had no change or worsening MRI ndings. 5

FO LLO W-UP • Monitor temperature and physical examination regularly. Examine venous access site, surgical access site, and site o persistent pain o osteomyelitis. • Monitor at regular intervals or persistently elevated WBC count, ESR, and CRP. • I using nephrotoxic antibiotics, adjust dose or renal unction and measure serum creatinine regularly.

PATIENT EDUCATIO N • Patients should be educated on the cause, symptoms, treatment, and course o osteomyelitis. ° Discuss symptoms o disease recurrence, such as prolonged pain, ever, or drainage and recommend that these be reported to a health care pro essional immediately. • Patients with diabetes mellitus should be educated on proper oot care, including daily inspection o eet, daily washing, and use o moisturizing cream. 3 • Patients with diabetes mellitus should also be educated to avoid unnecessary trauma by wearing properly tted shoes and avoiding bare oot walking. 3 • Educate patients on appropriate maintenance o venous access line and appropriate use o antibiotics. • Discuss possible adverse side e ects o antimicrobial agents, including Clostridium di f cile diarrhea, rash, and nephrotoxicity or ototoxicity.

• Medscape. Osteomyelitis—http:/ / emedicine.medscape .com/ article/ 1348767. • Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the In ectious Diseases Society o America or the treatment o methicillin-resistant Staphylococcus aureus in ections in adults and children. Clin. In ect Dis. 2011. doi:10.1093/ cid/ ciq146. http:/ / cid.oxfordjournals.org/ content/ early/ 2011/ 01/ 04/ cid .ciq146.full. • Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society o America clinical practice guideline or the diagnosis and treatment o diabetic oot in ections. Clin In ect Dis. 2012;54(12):132-173. http:/ / www.idsociety.org/ uploadedFiles/ IDSA/ Guidelines-Patient_Care/ PDF_ Library/ 2012%20Diabetic%20Foot%20Infections%20 Guideline.pdf. REFERENCES 1. Pineda C, Espinosa R, Pena A. Radiographic imaging in osteomyelitis: the role o plain radiography, computed tomography, ultrasonography, magnetic resonance imaging, and scintigraphy. Semin Plast Surg. 2009;23(2):80-89. 2. Zimmerli W. Clinical practice. Vertebral osteomyelitis. N Engl J Med. 2010;362(11):1022-1029. 3. Calhoun JH, Manring MM, Shirtli M. Osteomyelitis o the long bones. Semin Plast Surg. 2009;23(2):59-72. 4. Hatzenbuehler J, Pulling TJ. Diagnosis and management o osteomyelitis. Am Fam Physician. 2011;84(9):1027-1033. 5. Kowalski TJ, Berbari EF, Huddleston PM, Steckelberg JM, Osmon DR. Do ollow-up imaging examinations provide use ul prognostic in ormation in patients with spine in ection? Clin In ect Dis. 2006;43(2):172-179.

1101

PART 16

1102

In f e c TIo u s DIs e As e s

Ch a pt e r 218

218 SYPHILIS Richard P. Usatine , MD He id i Chumle y, MD

PATIENT STO RY A 39-year-old woman presents with a nonhealing ulcer over her upper lip or 1 week and a new-onset rash on her trunk (Figures 218-1 and 218-2). The ulcer on her upper lip was misdiagnosed as herpes simplex by the previous physician. Sexual history revealed that the patient had oral sex with a boy riend who had a lesion on his penis and she suspected that he had been having sex with other women. The examining physician recognized the nonpain ul ulcer and rash as a combination o primary and secondary (P&S) syphilis. A rapid plasma reagin (RPR) was drawn and the patient was treated immediately with IM benzathine penicillin. The RPR came back as 1:128 and the ulcer was healed within 1 week.

INTRO DUCTIO N Syphilis, caused by Treponema pallidum, is a systemic disease characterized by multiple overlapping stages: primary syphilis (ulcer), secondary syphilis (skin rash, mucocutaneous lesions, or lymphadenopathy), tertiary syphilis (cardiac or gummatous lesions), and early or late latent syphilis (positive serology without clinical mani estations). Neurosyphilis can occur at any stage. Diagnosis is made using treponemal and nontreponemal tests. Treatment is penicillin; the dose and duration depend on the stage.

SYNO NYMS AND ACRO NYMS • Lues is another word or syphilis. • Nontreponemal tests ° VDRL—Venereal Disease Research Laboratory • RPR

FIGURE 218-2 A nonp ruritic rash o s cond ary syp hilis on th ab d om n o th p ati nt shown in Fig ure 218-1. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

• Treponemal tests ° EIA—Enzyme immunoassay ° TPPA—T. pallidum particle agglutination ° FTA-ABS—Fluorescent treponemal antibody absorption ° MHA-TP—Microhemagglutination assay or T. pallidum

EPIDEMIO LO GY • P&S syphilis cases reported to Centers or Disease Control and Prevention (CDC) decreased rom 13,997 in 2009 to 13,774 in 2010, a decrease o 1.6%. The rate o P&S syphilis in the United States in 2010 (4.5 cases per 100,000 population) was 2.2% lower than the rate in 2009 (4.6 cases). This is the rst overall decrease in P&S syphilis in 10 years. 1 • The rate o P&S syphilis increased 1.3% among men ( rom 7.8 to 7.9 cases per 100,000 men) during 2009 to 2010. During this same period, the rate decreased 21.4% among women ( rom 1.4 to 1.1 cases per 100,000 women). 1 • In 2010, the rate o P&S syphilis was highest among persons aged 20 to 24 years and 25 to 29 years (13.5 and 11.3 cases per 100,000 population, respectively). 1 • The distribution o primary and secondary syphilis reported in 2010 di ered by gender and sexual pre erences—Among men who have sex with women only (MSW), 35.8% had primary syphilis and 64.2% had secondary syphilis. Among women, 16% had primary syphilis and 84% had secondary syphilis. Among men who have sex with men (MSM), 25% had primary syphilis and 75% had secondary syphilis. 1 • Syphilis by races/ ethnicities varied in 2010—Among women with P&S syphilis, 16.8% were white, 72.8% were black, 6.6% were Hispanic. Among MSW, 14.8% were white, 67% were black, 13.8% were Hispanic. Among MSM, 38.1% were white, 37% were black, 19.8% were Hispanic. 1 • In 2008, 63% o the reported cases o P&S were in MSM. 2

FIGURE 218-1 Primary syp hilis with a chancr ov r th lip o a woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• HIV-in ected patients were ound to have syphilis rates o 62.3 per 1000 compared to 0.8 per 1000 in HIV-unin ected patients in a population study in Cali ornia. 3

SYPHILIS

PART 16

In f e c TIo u s DIs e As e s

ETIO LO GY AND PATHO PHYSIO LO GY Syphilis is caused by the spirochete T. pallidum and contracted through direct sexual contact with primary or secondary lesions. Congenital syphilis can be contracted across the placenta.

RISK FACTO RS • Sexual contact with a person with primary or secondary syphilis • MSM • Prostitution • Sex or drugs • HIV/ AIDS

DIAGNO SIS

FIGURE 218-4 Primary syp hilis with a larg chancr on th g land s o th p nis. Th multip l small surround ing ulc rs ar p art o th syp hilis and not a s cond d is as . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

CLINICAL FEATURES • Primary syphilis is associated with a chancre—Usually a nonpain ul ulcer (Figures 218-1, 218-3, and 218-4). The presence o pain does not rule out syphilis, and the patient with a pain ul genital ulcer should be tested or both syphilis and herpes. • Secondary syphilis occurs when the spirochetes become systemic and may present as a rash with protean morphologies, condyloma lata, and/ or mucous patches (Figures 218-2 and 218-5 to 218-10). • Tertiary syphilis may be visualized with gummas on the skin, but many o the mani estations are internal such as the cardiac and neurologic diseases that occur (eg, aortitis, tabes dorsalis, and iritis). Figure 218-11 shows a gumma o the scrotum. • Neurosyphilis can occur at any stage. Clinical symptoms include cognitive dys unction, vision or hearing loss, uveitis or iritis, motor or sensory abnormalities, cranial nerve palsies, or symptoms o meningitis. TYPICAL DISTRIBUTIO N • Primary syphilis is usually a single ulcer (chancre) that is not pain ul in the genital region (see Figures 218-3 and 218-4). A chancre can be seen on the lip (see Figure 218-1).

FIGURE 218-3 A p ainl ss chancr at th location o tr p on mal ntry. (Re p rod uce d with p e rmission from the Pub lic He alth Imag e Lib rary, Ce nte rs for Dise ase Control and Pre ve ntion.)

FIGURE 218-5 Papular squamous ruption on th hands o a woman with s cond ary syphilis. (Reproduced with permission from Richard P. Usatine , MD.)

FIGURE 218-6 Pap ular sq uamous rup tion on th oot o th woman in Fig ure 218-5, with s cond ary syp hilis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

1103

1104

PART 16

In f e c TIo u s DIs e As e s

Ch a pt e r 218

A

FIGURE 218-7 Mucous p atch s on th lab ia o th wo man in Fig ure 218-5, with s cond ary syp hilis t ming with sp iroch t s. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

• Secondary syphilis may present with various eruptions on the trunk, palms, and soles (Figures 218-2, 218-5, 218-6, 218-8, and 218-12). Secondary syphilis may also present with a moth-eaten alopecia (Figure 218-13). • Mucous patches are on the genitals or in the mouth (see Figures 218-7 and 218-9). LABO RATO RY TESTING • Serologic tests are either nontreponemal (RPR or VDRL), which measure anticardiolipin antibodies, or treponemal (EIA, TPPA, FTA-ABS, or MHA-TP), which measure antibodies to T. pallidum.

FIGURE 218-8 Pink macul s on th t and wrists o a man with s cond ary syp hilis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

B FIGURE 218-9 A. Mucous p atch s on th p nis and scrotum o th sam man with s cond ary syp hilis in Fig ure 218-8. B. Sam man with oral l sion on th p alat . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 218-10 Cond ylomata lata (arrows) on th vulva o a woman with s cond ary syp hilis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

SYPHILIS

FIGURE 218-11 T rtiary syp hilis p r s nting as a swoll n scrotum, which was d iag nos d as a syp hilitic g umma o th t sticl . (Re p rod uce d with p e rmission from the Pub lic He alth Imag e Lib rary, Ce nte rs for Dise ase Control and Pre ve ntion.)

• There are 2 algorithms or laboratory testing currently in use around the world:

1. Start with a low-cost nontreponemal test and con rm a positive result with a treponemal test. 2. Start with the EIA treponemal test, ollowed by a nontreponemal test or con rmation. • In 2008, the CDC recommended a treponemal EIA initially, with positive results ollowed by a nontreponemal test or con rmation, a strategy that detected an additional 3% o positive samples not identi ed in the nontreponemal–treponemal sequence. 4

PART 16

In f e c TIo u s DIs e As e s

FIGURE 218-13 Moth- at n alop cia in a g ay man with s cond ary syp hilis. H p r s nt d with th hair loss and no oth r skin l sion. At f rst his RPR was n g ativ d u to th hig h antib od y load and th p ro zon a ct. A t r d ilution o th RPR, it was p ositiv at 1:32. (Re p rod uce d with p e rmission from Je ffre y Kinard , DO .)

• A positive EIA with a negative RPR can be a previous treated or untreated in ection, a alse-positive, or early primary syphilis. In this case, retest with a second treponemal test. • Dark- eld microscopy is use ul in evaluating moist cutaneous lesions, such as chancre, mucous patches, and condyloma lata (Figure 218-14). • Test all patients with syphilis or HIV (Figure 218-15).

• A nontreponemal test is required or con rmation, as a treponemal EIA indicates exposure but not active in ection.

• Patients with syphilis who have any signs or symptoms suggesting neurologic disease including vision or hearing need a cerebrospinal f uid (CSF) examination, a slit-lamp ophthalmologic examination, and an otologic examination to determine i neurosyphilis is present.

FIGURE 218-12 Mid d l -ag marri d man with d i us rup tion o s cond ary syp hilis rom n ck to t. Th rup tion r main d und iag nos d or months as th p ati nt d ni d any risk actors. His RPR was 1:256. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 218-14 Liv sp iroch t s o T. p allid um s n in a d ark-f ld p r p aration. (Re p rod uce d with p e rmission from the Pub lic He alth Imag e Lib rary, Ce nte rs for Dise ase Control and Pre ve ntion.)

1105

1106

PART 16

In f e c TIo u s DIs e As e s

Ch a pt e r 218

FIGURE 218-17 Chancroid l sions o th groin and p nis a cting th ipsilatral inguinal lymph nod s. (Reproduced with permission from CDC/J. Pledger.)

• Drug eruptions—Can be on the genital area such as seen in a xed drug eruption. Also whole-body drug eruptions can appear similar to secondary syphilis (see Chapter 201, Cutaneous Drug Reactions).

FIGURE 218-15 S cond ary syp hilis in a 20-y ar-old woman with a history o inj ction d rug us and multip l s xual p artn rs. H r HIV t st was also p ositiv so sh was work d up or n urosyp hilis. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

DIFFERENTIAL DIAGNO SIS • Herpes simplex—Most common cause o genital ulcers in the United States. These ulcers are pain ul and o ten start as vesicles (see Chapter 128, Herpes Simplex). • Chancroid—Pain ul bee y red ulcers on the penis or vulva, less common than syphilis. Chancroid is also known to cause large pain ul inguinal adenopathy (bubo) (Figures 218-16 and 218-17).

• Erythema multi orme—Can look like the rash o secondary syphilis but may have target lesions (see Chapter 175, Erythema Multi orme, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis). • Pityriasis rosea—A sel -limited cutaneous eruption that o ten begins with a herald patch and may have a Christmas tree distribution on the back (see Chapter 151, Pityriasis Rosea).

MANAGEMENT MEDICATIO NS Benzathine penicillin is the treatment o choice or all stages o syphilis. Dose and duration depend on stage. Treatment in ormation below is rom the CDC. 5 • Primary, secondary, and early latent (immunocompetent and nonpregnant) ° Adults—Benzathine penicillin G 2.4 million units IM 1 time ■ Penicillin allergy—Desensitize pregnant patients. Alternatives or nonpregnant adults include the ollowing: ° Doxycycline 100 mg twice daily × 14 days or ° Ce triaxone 1 g IM/ IV daily × 10 to 14 days (limited studies) or ° Azithromycin 2 g single oral dose; however, azithromycin resistance has been documented in several areas o the United States. Use only when penicillin or doxycycline cannot be used. Do not use in MSM. • Late latent syphilis or syphilis o unknown duration ° Adults—Benzathine penicillin G 2.4 million units IM every week or 3 weeks. ■ Penicillin allergy—Doxycycline 100 mg twice a day or 28 days (or tetracycline 500 mg 4 times a day or 28 days) are the only acceptable alternatives.

FIGURE 218-16 Chancroid ulc rs caus d b y th b act rium, Hae mop hilus d ucre yi. Th p ati nt was orig inally thoug ht to hav syp hilis. Chancroid al ulc rs ar classically p ain ul and b y b ut chancroid should b consid r d on th d i r ntial d iag nosis o any s xually acq uir d g nital ulc r. (Re p rod uce d with p e rmission from CDC/Dr. Pirozzi.)

• For the management o tertiary and neurosyphilis, see the Sexually Transmitted Diseases Treatment Guidelines published by the CDC in 2010: http:/ / www.cdc.gov/ std/ treatment/ 2010/ genital-ulcers .htm# syphilis.

PART 16

SYPHILIS

In f e c TIo u s DIs e As e s

REFERRAL O R HO SPITALIZATIO N Re er patients when the stage o syphilis is unclear. Consider re erral to an in ectious disease specialist in pregnant women with a penicillin allergy, patients with tertiary or neurosyphilis, or patients who have ailed treatment.

PREVENTIO N • Primary prevention: Sa e-sex practices—sexual transmission occurs when mucocutaneous syphilitic lesions are present. • Secondary prevention ° Treat presumptively (regardless o serology) sexual partners who were exposed within 90 days o the partner’s diagnosis o primary, secondary, or early latent syphilis. ° Consider presumptive treatment when exposure was greater than 90 days be ore partner’s diagnosis i serology is unavailable or ollow-up is uncertain. 5

PRO GNO SIS

A

When syphilis is recognized and appropriately treated, the prognosis is excellent.

FO LLO W-UP Reexamine clinically and serologically at 6 and 12 months. Consider treatment ailure i signs and/ or symptoms persist or the nontreponemal test titer does not decline by 2 dilutions a ter 6 to 12 months o therapy. Fi teen percent will not achieve this decline in titer a ter 1 year. 5 For treatment ailures retest or HIV and per orm a lumbar puncture or CSF analysis and treat or neurosyphilis i positive.

PATIENT EDUCATIO N Condoms can prevent the spread o syphilis. Patients should be advised to get HIV testing and need to know that syphilis is a risk actor or the spread o HIV. HIV/ AIDS is also a risk actor or acquiring syphilis (Figure 218-18) and syphilis is a risk actor or acquiring HIV (Figure 218-19). Patients should be advised o the importance o completing treatment and ollow-up to prevent complications.

B FIGURE 218-18 S cond ary syphilis in a young man with known HIV/AIDS. A. Imp r ssiv r d p ap ulosq uamous rup tion rom h ad to to is p r s nt. B. Clos -up showing th p almar p atch s and p laq u s. (Re p rod uce d with p e rmission from Jonathan B. Karne s, MD.)

PATIENT RESO URCES

• Centers for Disease Control and Prevention (CDC). Sexually Transmitted Diseases (STDs): Syphilis–CDC Fact Sheet—http:/ / www.cdc.gov/ std/ syphilis/ stdfact-syphilis.htm. PRO VIDER RESO URCES

• Medscape. Syphilis—http:/ / emedicine.medscape.com/ article/ 229461-overview. • The Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines—http:/ / www.cdc.gov/ std/ treatment/ 2010/ toc.htm. (Also available to download as an e-book or Apple iPad, iPhone, or iPod Touch—http:/ / www .cdc.gov/ std/ 2010-ebook.htm.)

FIGURE 218-19 Chancr o p rimary syp hilis in a g ay man. Not that g nital ulc rs incr as th risk o HIV transmission. (Re p rod uce d with p e rmission from Huse in Huse in-ElAhme d MD.)

1107

PART 16

1108

INFECTIO US DISEASES REFERENCES 1. Centers or Disease Control and Prevention (CDC). SexuallyTransmitted Diseases Surveillance. Syphilis. http:/ / www.cdc.gov/ std/ stats10/ Syphilis.htm. Accessed September 2, 2012. 2. Centers or Disease Control and Prevention (CDC). SexuallyTransmitted Diseases. Syphilis. http:/ / www.cdc.gov/ std/ syphilis/ . Accessed September 2, 2012. 3. Horberg MA, Ranatunga DK, Quesenberry CP, et al. Syphilis epidemiology and clinical outcomes in HIV-in ected and HIV-unin ected patients in Kaiser Permanente Northern Cali ornia. SexTransm Dis. 2010;37(1):53-58.

CHAPTe R 218

4. Centers or Disease Control and Prevention (CDC). Syphilis testing algorithms using treponemal tests or initial screening— our laboratories, New York City, 2005-2006. MMWR Morb MortalWkly Rep. 2008;57(32):872-875. 5. Centers or Disease Control and Prevention (CDC). SexuallyTransmitted DiseasesTreatment Guidelines, 2010: Diseases Characterized by Genital, Anal, or Perianal Ulcers. http:/ / www.cdc.gov/ std/ treatment/ 2010/ genital-ulcers.htm# syphilis. Accessed September 23, 2011.

PART 17

ENDO CRINE

*

St re ng t h o Re co mme nd at io n (SO R)

De f nit io n

A

Re comme nd ation b ase d on consiste nt and g ood -q uality p atie nt-orie nte d e vid e nce .*

B

Re comme nd ation b ase d on inconsiste nt or limite d -q uality p atie nt-orie nte d e vid e nce .*

C

Re comme nd ation b ase d on conse nsus, usual p ractice , op inion, d ise ase -orie nte d e vid e nce , or case se rie s or stud ie s o d iag nosis, tre atme nt, p re ve ntion, or scre e ning .*

Se e Ap p e nd ix A on p ag e s 1241-1244 or urthe r in ormation.

PART 17

1110

ENDO CRINE

Ch a pt e r 219

219 DIABETES O VERVIEW Mind y A. Smith, MD, MS

PATIENT STO RY A 66-year-old man with obesity and mild hypertension controlled with a diuretic presents with increasing nocturia and excessive thirst. He has no other urinary symptoms and denies any visual problems. His mother had diabetes and died at age 85 years rom a heart attack. His only other concern is a recurrent ungal in ection on his eet. His blood pressure in the o ce today is 135/ 85 mm Hg and his nger stick blood sugar is 220 mg/ dL. You explain that based on his elevated blood sugar, he has diabetes mellitus. Physical examination ndings con rm the diagnosis o tinea pedis (Figure 219-1). A mono lament test demonstrates normal sensation in his eet. You order a asting blood sugar, lipid pro le, serum electrolytes, creatinine, and hemoglobin A1C. You ask him to return next week or a more complete examination, review o his test results, and diabetes education. You ask him and his wi e to consider meeting with a nutritionist, and brief y review treatment options, including diet, exercise, and met ormin, as well as a possible need to improve his blood pressure control or switch to another agent. You suggest a nonprescription anti ungal cream and will see i he needs additional treatment or his eet at ollow-up. The patient is re erred to an ophthalmologist who nds diabetic nonproli erative retinopathy (Figure 219-2).

FIGURE 219-2 Nonp roli e rative d iab e tic re tinop athy, with scatte re d intrare tinal d ot-b lot and f ame he morrhag e s, along with macular e xud ate s. Macular e xud ate s can b e re late d to diab e tic macular e d e ma, which accounts or a larg e p ortion o p oor vision and d isab ility se cond ary to d iabe tic re tinop athy. (Re p rod uce d with p e rmission from And re w Sanche z, CO A.)

mellitus (DM) is a heterogeneous group o chronic disorders caused by a progressive insulin secretory de ect and increased glucose production in the setting o insulin resistance.

INTRO DUCTIO N Diabetes is a group o disorders caused by a complex interaction between genetic susceptibility, environmental actors, and personal li estyle choices that share the phenotype o hyperglycemia. Type 2 diabetes

EPIDEMIO LO GY • Prevalence—In the United States, 25.8 million adults and children (8.3% o the population), including 18.8 million who have been diagnosed, have diabetes. This includes 26.9% o people age 65 years and older. Type 2 DM is the most common orm, accounting or more than 90% o cases. 1 • Incidence—In the United States in 2010, there were 1.9 million new cases among individuals 19 years o age and older. • Highest rates o diabetes are in non-Hispanic blacks (12.6%), ollowed by Hispanics (11.8%), Asian Americans (8.4%), and non-Hispanic whites (7.1%). • In 2007, total costs o diagnosed DM in the United States were $174 billion ($116 billion in direct medical costs).

ETIO LO GY AND PATHO PHYSIO LO GY • Insulin resistance is attributed to obesity, inactivity, and genetic actors (including de ects in β-cell unction and insulin action). • Initially, the pancreatic β-cells increase insulin production to overcome insulin resistance and maintain euglycemia. Eventually, β-cells ail, resulting in hyperglycemia. • Other contributing actors include diseases o the pancreas (eg, pancreatitis, hemochromatosis), in ection (eg, cytomegalovirus), and other endocrinopathies (eg, hyperthyroidism [see Chapter 227, Hyperthyoroidism] and acromegaly [see Chapter 228, Acromegaly]). FIGURE 219-1 Patie nt with d iab e te s and tine a p e d is b e ing te ste d with a mono lame nt or se nsation. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Microvascular and macrovascular diseases may result rom hyperglycemia or other metabolic changes.

DIa Be t e S O Ve r VIe W

PART 17

ENDO CRINE

RISK FACTO RS • Obesity1-4* • Red meat consumption (relative risk [RR] 1.51; 95% con dence interval [CI], 1.25, 1.83 or 50 g processed red meat per day)5 • Physical inactivity (also television viewing 2 h/ d; odds ratio [OR] 1.20; 95% CI, 1.14-1.27)6* • Nonwhite race* • First-degree relative with diabetes, hypertension, or myocardial in arction* • Prior gestational diabetes* • Impaired glucose tolerance (hazard ratio [HR] 13.2, 95% CI, 10.8-16.2)7 • Polycystic ovarian syndrome • Coronary heart disease, hypertension* • Smoking (OR [current smoker] 1.44; 95% CI, 1.31 to 1.58) • Antipsychotic therapy or patients with schizophrenia or severe bipolar disease* • Previously identi ed glucose intolerance* • Prolonged use o oral corticosteroids *

Risk actors used by the American Association o Clinical Endocrinologists (AACE) in making decisions or screening patients or DM (see below). 4 Many risk models and scores have been developed to predict the development o DM. 8 Authors o a systematic review identi ed 7 risk scores that had high potential or use in practice based on similar components and discriminatory properties. 4 One o these, the Framingham O spring Study, 9 uses asting plasma glucose levels, body mass index, high-density lipoprotein cholesterol and triglyceride levels, and parental history o diabetes and blood pressure to determine risk. Un ortunately, none o the models were developed on a cohort recruited prospectively and no studies have demonstrated a reduction in incident DM using risk scoring and intervention.

FIGURE 219-3 Diab e tic d e rmop athy on the lowe r le g s that is p articularly p romine nt ove r the shins. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Patients with diabetic neuropathy may have abnormalities on mono lament, vibration, and super cial pain testing. • Skin changes in patients with DM include diabetic dermopathy in 15% to 40% o patients (Figure 219-3; see Chapter 221, Diabetic Dermopathy), 10 acanthosis nigricans in approximately one-third o patients (Figure 219-4; see Chapter 220, Acanthosis Nigricans), 11 diabetic oot ulcers (Figure 219-5; see Chapter 208, Ischemic Ulcer), and, uncommonly, necrobiosis lipoidica (Figure 219-6; see Chapter 222, Necrobiosis Lipoidica). • Hyperlipidemia may result in eruptive xanthomas (Figure 219-7) or xanthelasma (see Chapter 223, Hyperlipidemia).

DIAGNO SIS The AACE guideline de nes the diagnosis o diabetes as a asting (8 or more hours o no caloric intake) glucose level 126 mg/ dL or greater (≥7.0 mmol/ L), or a 2-hour plasma glucose 200 mg/ dL or greater (≥11.1 mmol/ L) on a 75-g oral glucose tolerance test, or a random plasma glucose level o greater than 200 mg/ dL with symptoms o diabetes, or a hemoglobin A1C level o 6.5% or higher. 4 SO R The same test should be repeated on a di erent day to con rm the diagnosis unless the patient has unequivocal hyperglycemia or severe metabolic stress. SO R

CLINICAL FEATURES • Many patients with type 2 DM are asymptomatic. • Patients may report polydipsia, polyuria, and blurred vision. • Funduscopic examination may reveal signs o retinopathy (hard exudates, hemorrhages) (see Figure 219-2; see Chapter 17, Diabetic Retinopathy).

FIGURE 219-4 Acanthosis nig ricans in a woman with typ e 2 d iab e te s and ob e sity. She is re q ue sting that he r skin tag s b e re mo ve d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

1111

1112

PART 17

ENDO CRINE

Ch a pt e r 219

FIGURE 219-5 Diab e tic oot ulce r that has occurre d at the amp utation site . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Patients with DM o prolonged duration may also have Charcot joints (Figure 219-8; see Chapter 210, Charcot Arthropathy). 12 LABO RATO RY TESTS • The American Diabetes Association (ADA) recommends several tests or diagnosing diabetes: a asting plasma glucose o 126 mg/ dL or greater, a hemoglobin A1C o greater than or equal to 6.5%, or a blood glucose o greater than or equal to 200 mg/ dL on either a random plasma glucose test or at 2 hours ollowing an oral glucose tolerance test. 13 A second con rming test is recommended. • A random capillary blood glucose may be a reasonable alternative. Compared with traditional criteria, a capillary blood glucose level o greater than 120 mg/ dL has a sensitivity o 75% and speci city o 88% or the diagnosis o type 2 DM. 14

FIGURE 219-7 Erup tive xanthomas on the e xtre mitie s and trunk o a young man with untre ate d typ e 2 d iab e te s and hyp e rlip id e mia. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• In cases where there is uncertainty regarding the diagnosis o type 1 or type 2 DM, glucagon-stimulated C-peptide, 2-hour postprandial urinary C-peptide-to-creatinine ratio, and 4-hour postprandial urinary C-peptide concentration can be used to help distinguish between the types.

MANAGEMENT The primary treatment goals or the patient with DM are to aggressively control blood pressure ( 150 min/ wk) signi cantly improves glycemic control in patients with type 2 DM. 26

ENDO CRINE In this meta-analysis, a combination o dietary and exercise advice also lowered hemoglobin A1C. 26 Individuals with type 2 DM are advised to get 30 to 90 min/ d (AACE) or 90 to 150 min/ wk (ADA) o exercise to improve glycemic control. 7,13 SO R

Education, sel -management, and sel -monitoring interventions • Group-based diabetes education is associated with reductions in hemoglobin A1C, systolic blood pressure, body weight, and the need or diabetic medications. 27 SO R In another Cochrane review, use o a specialized diabetes nurse or case manager improved short-term glycemic control but not improve longer-term outcomes, such as hospital admission rates and quality o li e. 28 Although one recent trial (N = 201) o behavioral support (video and 5 telephone sessions) or patients with poorly controlled DM did not show bene t on outcomes, 29 another trial (N = 222) using 5 educator-led group sessions or patients with poorly controlled DM did nd improved glycemic control over the control group, although there were no di erences in quality o li e or requency o diabetes sel -care. 30 • Authors o a Cochrane review o 12 trials on blood glucose sel -monitoring in patients with type 2 DM not using insulin ound a small e ect o sel -monitoring on glycemic control (reduced hemoglobin A1C) that lasted up to 6 months a ter initiation but not at or beyond 12 months. 31 There was no evidence that sel -monitoring a ected patient satis action, general well-being, or general health-related quality o li e. However, sel -monitoring o glucose may be use ul or assessing and preventing hypoglycemia and adjusting medications, medical nutrition therapy, and physical activity. 4 • Structured goal setting was shown in a RCT (N = 87) to improve glycemic control up to 1-year postintervention. 32 MEDICATIO NS Agents that can be used or initial blood pressure control include diuretics, angiotensin-converting enzyme (ACE) inhibitors, and β-blockers. The AACE considers ACE inhibitors or angiotensin II receptor blockers (ARBs) the pre erred choice in patients with DM. 7 Combinations o medications may be needed. The blood pressure target is less than 130/ 80 mm Hg. 4 SO R • In one trial, an ACE inhibitor plus an ARB increased the risk o advancement to renal dialysis. 33 • In the ACCORD trial o intensive blood pressure control in patients with type 2 DM (N = 4733), there were no additional cardiovascular bene ts to targeting a systolic blood pressure o 120 mm Hg versus 140 mm Hg. Patients treated with intensive blood pressure lowering were more likely to experience serious adverse e ects (3.3% vs 1.3%). 34 • In a subgroup analysis rom another large blood pressure (BP) trial, progressively greater systolic BP reductions were associated with reduced risk or the primary outcome (pooled cardiovascular [CV] death, non atal myocardial in arction or stroke, or hospitalized heart ailure) only i the baseline systolic BP levels ranged rom 143 to 155 mm Hg; there was no bene t in atal or non atal CV outcomes by reducing systolic BP below 130 mm Hg. 35 Agents used or glycemic control include met ormin (biguanide that suppresses hepatic glucose production), sul onylureas (eg, glyburide that potentiates insulin secretion), glinides (eg, nateglinide that potentiates insulin secretion), α -glucosidase inhibitors (eg, acarbose that decreases intestinal carbohydrate absorption), thiazolidinediones (eg, rosiglitazone that improves insulin sensitivity), incretin mimetic agent (Bydureon

1113

1114

PART 17

ENDO CRINE enhances insulin secretion and slows gastric emptying), and a dipeptidyl peptidase inhibitor (sitagliptin that improves glucagon-like peptide levels). Details on e cacy, dosing, and sa ety can be ound elsewhere. 4 • O the oral hypoglycemic agents, only met ormin and the sul onylureas have been shown to decrease long-term vascular complications and only met ormin decreases all-cause mortality (independently o its e ect on glycemic control). 36,37 SO R Monotherapy, although initially e ective or many patients, ails to sustain control in approximately hal o patients at 3 years. 38 • Addition o a second oral agent should be considered when monotherapy does not provide adequate control, usually a sul onylurea is added and is likely most cost-e ective. 39 SO R Sul onylureas, glinides, and α -glucosidase inhibitors appear equal in e ectiveness when added to met ormin. 40 A thiazolidinedione also can be used, but there is concern about increased risk o myocardial in arction; data are conf icting. • I dual therapy does not provide adequate control, options include adding a basal insulin analog (eg, glargine or detemir), a thiazolidinedione, or dipeptidyl peptidase inhibitor. A meta-analysis o 18 trials did not nd a clear di erence in bene t between drug classes when adding a third agent or patients who were already on met ormin and a sul onylurea.41 Bydureon, a once-weekly injection, although recently Food and Drug Administration (FDA) approved, is costly and data are limited as this is so new. In the United Kingdom Prospective Diabetes Study (UKPDS) trial, the use o insulin therapy or patients with type 2 DM was not associated with decreased CV or all-cause mortality despite reductions in blood sugar. 42 A Cochrane review o 6 trials also did not nd evidence o major clinical bene t or use o long-acting insulin analogues or patients with type 2 DM. 43 Finally, i insulin is added, continuing met ormin i possible is advised as there is less weight gain associated with this combination. 44 • Consultation with an endocrinologist is suggested i a third agent is needed and choice o agent should be made with consideration o the patient’s age (decline in renal and cardiac unction may preclude use o met ormin, a thiazolidinedione, or long-acting sul onylurea), weight (met ormin, acarbose, exenatide, sitagliptin, and human amylin are more o ten associated with weight loss or maintenance), and comorbidities. 4 SO R • I urther control is needed, options include discontinuing oral therapy and using combination insulin therapy. Agents used or lipid control in patients whose lipids are not controlled by diet and exercise is usually achieved with statin therapy. 4 I the initial statin does not result in adequate control, the AACE recommend intensiying that statin to meet the LDL cholesterol goals. 4 SO R I the LDL goal cannot be met with high-dose statin therapy, there is no evidence to prove that adding other LDL-lowering drug classes will improve outcomes or people with DM. Treatment o complications o DM is described in detail elsewhere. 4 CO MPLEMENTARY AND ALTERNATIVE THERAPY • Several Chinese herbal medicines (eg, Xianzhen Pian, Qidan Tongmai) show hypoglycemic e ects in patients with type 2 DM but current evidence does not support widespread use. 45 • In another Cochrane review o herbal mixtures, signi cant reductions in hemoglobin A1C, asting blood sugar or both were observed with Diabecon, Inolter, and Cogent db compared to placebo; however, small sample sizes precluded de nite conclusions regarding e cacy. 46

Ch a pt e r 219

REFERRAL O R HO SPITALIZATIO N • Consider re erral or bariatric surgery or patients with DM who have a body mass index (BMI) o 35 kg/ m2 or more as this acilitates weight loss and improvement or reversal o hyperglycemia4; surgery has not yet been shown to decrease all-cause mortality or provide long-term bene it, and long-term risk is unknown. SO R

• Consultation with a oot specialist is recommended or patients with DM and oot de ormity, in ected lesions, oot ulcers, or de ormed nails or thick calluses. 4 SO R • Re er patients with diabetic retinopathy to an ophthalmologist or evaluation and treatment. SO R • Consider consultation with a vascular surgeon or patients with peripheral vascular disease. SO R • Patients with type 2 DM may require hospitalization or hyperglycemic crises (eg, hyperosmolar hyperglycemic state, ketoacidosis).

PREVENTIO N AND SCREENING Primary prevention is considered or patients who have prediabetes, de ned by the AACE as the presence o impaired glucose tolerance (ie, an oral glucose tolerance test glucose value o 140 to 199 mg/ dL, 2 hours a ter ingesting 75 g o glucose and/ or a asting glucose value o 100 to 125 mg/ dL). 4 Each year 3% to 10% o individuals with prediabetes will progress to type 2 DM. 47 • Li estyle changes that can prevent or at least delay type 2 DM in persons who have prediabetes include weight loss o 5% to 10% o body weight in overweight individuals and participation in moderate physical activity. 4,48,49 SO R • Smoking cessation should be encouraged; tobacco smoking increases the risk o macrovascular complications approximately 4% to 400% in adults with type 2 DM (see Chapter 237, Tobacco Addiction). • Provide annual in luenza immunization and pneumococcal vaccine as needed; repeat the pneumococcal vaccine at 5 years or patients with nephrotic syndrome, or chronic renal disease, or who are immunocompromised, or who are receiving the vaccine be ore age 65 years i 5 years has passed since the primary vaccine was given. 4 • The AACE also recommends that met ormin be considered or those with prediabetes who are younger patients at moderate-to-high risk or developing DM; or patients with additional cardiovascular disease risk actors including hypertension, dyslipidemia, or polycystic ovarian syndrome; or patients with a amily history o DM in a rstdegree relative; and/ or or patients who are obese. 4 A recent RCT ound pioglitazone e ective in reducing the risk o conversion o impaired glucose tolerance to type 2 DM (annual incidence rate 2.1% vs 7.6% with placebo), but was associated with signi cant weight gain and edema. 50 • In a meta-analysis o li estyle and pharmacologic interventions or the prevention or delay o DM in patients with impaired glucose tolerance, the number needed to treat to bene t was 6.4 or li estyle (95% CI, 5-8.4), 10.8 or oral diabetes drugs (95% CI, 8.1-15), and 5.4 or orlistat (95% CI, 4.1-7.6). 51 SO R • Low-dose aspirin is recommended or patients with DM who have risk actors or CV disease and are older than age 40 years. 13

PART 17

DIa Be t e S O Ve r VIe W

Secondary prevention or micro- and macrovascular disease include the ollowing: • Use o an ACE inhibitor or ARB can prevent progression o diabetic nephropathy. 52 SO R • Patients with DM should undergo a dilated comprehensive eye examination at diagnosis and annually. 13 SO R Panretinal scatter photocoagulation reduces the risk o severe visual loss by more than 50% in eyes with high-risk characteristics, and immediate ocal laser photocoagulation reduces the risk o moderate visual loss by at least 50% in patients with clinically signi cant macular edema. 53 • Patients with DM should also undergo screening or peripheral neuropathy at diagnosis and annually, with inspection and assessment o pulses and sensation, using a mono lament and one additional sensory test (eg, pinprick, vibration perception). 13 Patients with peripheral vascular disease, oot ulcers, or diabetic oot de ormity should be considered or re erral (as above) to prevent limb loss. • As discussed above, patients with well-controlled BP, lipids, and good glycemic control have a lower risk o macrovascular and microvascular disease, and diabetic dermopathy. 4,10 For example, estimates or years o li e saved with lipid lowering in patients with diabetes are 3 years to 3.4 years or men and 1.6 years to 2.4 years or women; greater increases than or patients without diabetes. 54 • Screening or type 2 DM should be considered in the presence o risk actors or DM (see “Risk Factors” above) and or patients who have increased levels o triglycerides or low concentrations o high-density lipoprotein cholesterol. 4,55 SO R

ENDO CRINE patient has experienced symptoms o hypoglycemia and educate the patient on appropriate recognition, prevention, and management. They also recommend the ollowing4: ° Goal setting or nutrition and physical activity regularly. ° Monitor hemoglobin A1C every 3 to 6 months, LDL or asting lipid pro le yearly (unless stable and with no change in medication), and microalbuminuria annually with serum creatinine i albuminuria is abnormal. I microalbuminuria testing is positive (>30 mg/ g), repeat twice in the next 3 months. I 2 o 3 o these screening microalbuminuria tests are positive, the individual has microalbuminuria and interventions should be considered. 4 A negative nding should be ollowed yearly; a positive nding should be ollowed periodically to see i the interventions are e ective in diminishing the albuminuria. ° Remind the patient to schedule dilated ophthalmic examinations with an optometrist or ophthalmologist. ° Monitor oot examinations annually or more requently and educate the patient on appropriate recognition, prevention, and management o in ections.

PATIENT EDUCATIO N • Patient education includes in ormation about DM (eg, treatment options), primary and secondary prevention recommendations, and sel -management. • Recommended sel -management activities include goal setting, incorporating nutrition management and physical activity into li estyle, and prevention and early detection o complications (eg, medication adherence, oot care). 4

PRO GNO SIS PATIENT RESO URCES

• Sustained elevation in asting blood glucose levels and 2-hour postload glucose testing, even when below the threshold or a diabetes diagnosis, is signi cantly associated with uture CV events and mortality. Approximately 75% o patients with type 2 DM die o macrovascular complications, particularly CV disease. 4

• ADA. Provides information and support—http:/ / www .diabetes.org/ .

• In 2007, diabetes was listed as the underlying cause on 71,382 death certi cates and was listed as a contributing actor on an additional 160,022 death certi cates. 1 Complications o diabetes contributing to death included heart disease (noted on 68% o death certi cates among those age 65 years or older) and stroke (16%).

PRO VIDER RESO URCES

• Diabetes is the leading cause o new cases o blindness (4.4% have advanced diabetic retinopathy), kidney ailure (48,374 people began treatment or end-stage renal disease in 2008), and nontraumatic lower-limb amputation (65,700 amputations in 2006). 1

• ADA. Standards of medical care in diabetes–2008. Diabetes Care. 2008;31:S1-S108.

FO LLO W-UP • Routine ollow-up is recommended to continue to assist patients with risk actor reduction, adherence to treatment, screening or diabetes complications (including depression), and to provide ongoing support and guidance. Visit requency depends on the patient’s needs, recent changes in management, and severity o complications. The AACE recommends regular visits at least every 3 to 6 months to review and rein orce BP and blood glucose targets and management o ongoing risk actors (including alcohol and tobacco use). 4 • The AACE also recommends contact within 1 week a ter a major modi cation o the treatment plan. 4 At each encounter, ask i the

• MedlinePlus. Diabetes—http:/ / www.nlm.nih.gov/ medlineplus/ diabetes.html. • Handelsman Y, Mechanick JI, Blonde L, et al, AACE Task Force or Developing Diabetes Comprehensive Care Plan. AACE medical guidelines or clinical practice or developing a DM comprehensive care plan. Endocr Pract. 2011;17(suppl 2):1-53.

• Centers for Disease Control and Prevention. Diabetes Public Health Resource—http:/ / www.cdc.gov/ diabetes/ . • National Diabetes Information Clearing House. Diabetes—http:/ / diabetes.niddk.nih.gov/ . • National Institute of Diabetes and Digestive and Kidney Diseases. http:/ / www2.niddk.nih.gov/ . REFERENCES 1. Centers or Disease Control and Prevention. Diabetes Fact Sheet (2011). http:/ / www.cdc.gov/ diabetes/ pubs/ pd / nd s_2011.pd . Accessed August 2013. 2. Burch el CM, Hamman RF, Marshall JA, et al. Cardiovascular risk actors and impaired glucose tolerance: the San Luis Valley Diabetes Study. Am J Epidemiol. 1990;131(1):57-70.

1115

1116

PART 17

ENDO CRINE 3. Juonala M, Magnussen CG, Berenson GS, et al. Childhood adiposity, adult adiposity, and cardiovascular risk actors. N Engl J Med. 2011;365(20):1876-1885. 4. Handelsman Y, Mechanick JI, Blonde L, et al. AACE Task Force for Developing Diabetes Comprehensive Care Plan. American Association o Clinical Endocrinologists medical guidelines or clinical practice or developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011;17(suppl 2):1-53. 5. Pan A, Sun Q, Bernstein AM, et al. Red meat consumption and risk o type 2 diabetes: 3 cohorts o US adults and an updated meta-analysis. Am J Clin Nutr. 2011;94(4):1088-1096. 6. Grøntved A, Hu FB. Television viewing and risk o type 2 diabetes, cardiovascular disease, and all-cause mortality: a meta-analysis. JAMA. 2011;305(23):2448-2455. 7. Yeboah J, Bertoni AG, Herrington DM, et al. Impaired fasting glucose and the risk o incident diabetes mellitus and cardiovascular events in an adult population: MESA (Multi-Ethnic Study o Atherosclerosis). JAm Coll Cardiol. 2011;58(2):140-146.

Ch a pt e r 219

21. Nikooyeh B, Neyestani TR, Farvid M, et al. Daily consumption o vitamin D– or vitamin D + calcium-forti ed yogurt drink improved glycemic control in patients with type 2 diabetes: a randomized clinical trial. Am J Clin Nutr. 2011;93(4):764-771. 22. Jorde R, Figenschau Y. Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels. Eur J Nutr. 2009;48(6):349-354. 23. Mitri J, Muraru MD, Pittas AG. Vitamin D and type 2 diabetes: a systematic review. Eur J Clin Nutr. 2011;65(9):1005-1015. 24. Norris SL, Zhang X, Avenell A, et al. Long-term non-pharmacological weight loss interventions or adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2005;(3):CD004095. 25. Andrews RC, Cooper AR, Montgomery AA, et al. Diet or diet plus physical activity versus usual care in patients with newly diagnosed type 2 diabetes: the Early ACTID randomised controlled trial. Lancet. 2011;378(9786):129-139.

8. Noble D, Mathur R, Dent T, et al. Risk models and scores or type 2 diabetes: systematic review. BMJ. 2011;343:d7163.

26. Umpierre D, Ribeiro PA, Kramer CK, et al. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. JAMA. 2011;305(17):1790-1799.

9. Wilson PW, Meigs JB, Sullivan L, et al. Prediction of incident diabetes mellitus in middle-aged adults: the Framingham O spring Study. Arch Intern Med. 2007;167:1068-1074.

27. Deakin TA, McShane CE, Cade JE, Williams R. Group based training or sel -management strategies in people with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2005;(2):CD003417.

10. Sibbald RG, Landolt SJ, Toth D. Skin and diabetes. Endocrinol Metab Clin North Am. 1996;25(2):463-472.

28. Loveman E, Royle P, Waugh N. Specialist nurses in diabetes mellitus. Cochrane Database Syst Rev. 2003;(2):CD003286.

11. Litonjua P, Pinero-Pilona A, Aviles-Santa L, et al. Prevalence o acanthosis nigricans in newly-diagnosed type 2 diabetes. Endocr Pract. 2004;10:101-106.

29. Frosch DL, Uy V, Ochoa S, Mangione CM. Comparative e ectiveness o goal setting in diabetes mellitus group clinics: randomized clinical trial. Ann Intern Med. 2011;171(22):2011-2017.

12. van der Ven A, Chapman CB, Bowker JH. Charcot neuroarthropathy o the oot and ankle. JAmAcad Orthop Surg. 2009;17(9):562-571.

30. Weinger K, Beverly EA, Lee Y, et al. Quality o li e, glucose monitoring, and requency o diabetes sel -care. Arch Intern Med. 2011;171(22):1990-1999.

13. American Diabetes Association. Diagnosing Diabetes and Learning About Prediabetes. http:/ / www.diabetes.org/ diabetes-basics/ diagnosis/ ?loc= DropDownDB-diagnosis. Accessed August 2013. 14. Rolka DB, Narayan KM, Thompson TJ, et al. Performance of recommended screening tests or undiagnosed diabetes and dysglycemia. Diabetes Care. 2001;24:1899-1903. 15. Patel A, MacMahon S, Chalmers J, et al. The Advance Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560-2572. 16. Gerstein HC, Miller ME, Byington, RP, et al. Action to Control Cardiovascular Risk in Diabetes Study Group. E ects o intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-2559. 17. Hemmingsen B, Lund SS, Gluud C, et al. Intensive glycaemic control or patients with type 2 diabetes: systematic review with metaanalysis and trial sequential analysis o randomised clinical trials. BMJ. 2011;343:d6898. 18. Currie CJ, Peters JR, Tynan A, et al. Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study. Lancet. 2010;375(9713):481-489. 19. American Diabetes Association Position Statement. Standards o medical care in diabetes-2012. Diabetes Care. 2012;35 (suppl 1): S11-S63. 20. Thomas D, Elliott EJ. Low glycaemic index, or low glycaemic load, diets or diabetes mellitus. Cochrane Database Syst Rev. 2009;(1):CD006296.

31. Malanda UL, Welschen LM, Riphagen II, et al. Sel -monitoring o blood glucose in patients with type 2 diabetes mellitus who are not using insulin. Cochrane Database Syst Rev. 2012;(1):CD005060. 32. Naik AD, Palmer N, Petersen NJ, et al. Comparative effectiveness o goal setting in diabetes mellitus group clinics: randomized clinical trial. Arch Intern Med. 2011;171(5):453-459. 33. Mann JF, Schmieder RE, McQueen M, et al, for the ONTARGET investigators. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008;372:547-553. 34. ACCORD Study Group, Cushman WC, Evans GW, Byington RP. E ects o intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575-1585. 35. Redon J, Mancia G, Sleight P, et al. Safety and ef cacy of low blood pressures among patients with diabetes: subgroup analyses rom the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial). JAm Coll Cardiol. 2012;59(1):74-83. 36. Inzucchi SE. Oral antihyperglycemic therapy or type 2 diabetes. Scienti c review. JAMA. 2002;287:360-372. 37. Saenz A, Fernandez-Esteban I, Mataix A, et al. Met ormin monotherapy or type 2 diabetes mellitus. Cochrane Database Syst Rev. 2005;(3):CD002966. 38. Turner RC, Cull CA, Frighi V, et al. Glycemic control with diet, sul onylurea, met ormin, or insulin in patients with type 2 diabetes

DIa Be t e S O Ve r VIe W

mellitus: progressive requirement or multiple therapies (UKPDS 49). JAMA. 1999;281:2005-2012. 39. Klarenbach S, Cameron C, Singh S, Ur E. Cost-e ectiveness o second-line antihyperglycemic therapy in patients with type 2 diabetes mellitus inadequately controlled on met ormin. CMAJ. 2011;183(16):E1213-E1220. 40. Monami M, Lamanna C, Marchionni N, Mannucci E. Comparison o di erent drugs as add-on treatments to met ormin in type 2 diabetes: a meta-analysis. Diabetes Res Clin Pract. 2008;79(2):196-203. 41. Gross JL, Kramer CK, Leitao CB, et al. Effect of antihyperglycemic agents added to met ormin and a sul onylurea on glycemic control and weight gain in type 2 diabetes: a network meta-analysis. Ann Intern Med. 2011;154(10):672-679. 42. E ect o intensive blood-glucose control with met ormin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352(9131):854-865. 43. Horvath K, Jeitler K, Berghold A, et al. Long-acting insulin analogues versus NPH insulin (human isophane insulin) or type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007;(2):CD005613. 44. Goudswaard AN, Furlong NJ, Valk GD, et al. Insulin monotherapy versus combinations o insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2004;(4):CD003418. 45. Liu JP, Zhang M, Wang W, Grimsgaard S. Chinese herbal medicines or type 2 diabetes mellitus. Cochrane Database Syst Rev. 2004;(3):CD003642. 46. Sridharan K, Mohan R, Ramaratnam S, Panneerselvam D. Ayurvedic treatments or diabetes mellitus. Cochrane Database Syst Rev. 2011;(12):CD008288.

PART 17

ENDO CRINE 47. Twigg SM, Kamp MC, Davis TM, et al. Prediabetes: a position statement rom the Australian Diabetes Society and Australian Diabetes Educators Association. Med JAust. 2007;186(9):461-465. 48. Lindström J, Ilanne-Parikka P, Peltonen M, et al, for the Finnish Diabetes Prevention Study Group. Sustained reduction in the incidence o type 2 diabetes by li estyle intervention: ollow-up o the Finnish Diabetes Prevention Study. Lancet. 2006;368(9548): 1673-1679. 49. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in li estyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344(18):1343-1350. 50. DeFronzo RA, Tripathy D, Schwenke DC, et al. Pioglitazone or diabetes prevention in impaired glucose tolerance. N Engl J Med. 2011;364(12):1104-1115. 51. Gillies CL, Abrams KR, Lambert PC, et al. Pharmacological and li estyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and metaanalysis. BMJ. 2007;334(7588):299. 52. Strippoli GFM, Craig ME, Craig JC, et al. Antihypertensive agents or preventing diabetic kidney disease. Cochrane Database Syst Rev. 2005;(4):CD004136. 53. Neubauer AS, Ulbig MW. Laser treatment in diabetic retinopathy. Ophthalmologica. 2007;221(2):95-102. 54. Grover SA, Coupal L, Zowall H, et al. Evaluating the bene ts o treating dyslipidemia: the importance o diabetes as a risk actor. Am J Med. 2003;115(2):122-128. 55. U.S. Preventive Services Task Force. Screening or type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;148(11):846-854.

1117

PART 17

1118

ENDO CRINE

220 ACANTHO SIS NIGRICANS Mind y A. Smith, MD, MS

PATIENT STO RY A 25-year-old woman with obesity and recently diagnosed type II diabetes mellitus (DM) presents to her physician with concerns about a “dirty area” under her arms and on her neck that “could not be cleaned” (Figure 220-1). The physician makes the diagnosis o acanthosis nigricans (AN).

INTRO DUCTIO N AN is a localized orm o hyperpigmentation that involves epidermal alteration. AN is usually associated with insulin resistance and is seen in patients with endocrine disorders (eg, type II DM, Cushing syndrome, acromegaly), obesity, and polycystic ovary syndrome.

EPIDEMIO LO GY

Ch a pt e r 220

• Although most cases are idiopathic, there are also genetic causes o AN.4 • A condition o hyperandrogenism (HA), insulin resistance (IR), and AN called HAIR-AN syndrome occurs in approximately 1% to 3% o women with HA. 5 This syndrome may also be seen in patients with autoimmune disorders like Hashimoto thyroiditis. • AN can be an adverse e ect rom hormonal therapies. 6

ETIO LO GY AND PATHO PHYSIO LO GY • AN results rom long-term exposure o keratinocytes to insulin. • Keratinocytes have insulin and insulin-like growth receptors on their sur ace and the pathogenesis o this condition may be linked to insulin binding to insulin-like growth receptors in the epidermis. • Fibroblast growth actor receptor 3 (FGFR3) gene mutations should be considered in patients with coexistent AN and skeletal dysplasia. 7

DIAGNO SIS The diagnosis o AN is made clinically in a patient with or at risk or IR who has the characteristic lesions. CLINICAL FEATURES

• In a cross-sectional study conducted in a southwestern practice-based research network (N = 1133), AN was ound in 21% o adults. 1 • In another study, AN was present in 36% o patients with newly diagnosed DM. 2 • AN is sometimes associated with malignancy, primarily adenocarcinoma (60%) o the stomach, gallbladder, colon, ovary, pancreas, rectum, and uterus. 3,4

• AN ranges in appearance rom di use streaky thickened brown velvety lesions to leathery verrucous papillomatous lesions (Figures 220-1 to 220-8). • Women with HAIR-AN syndrome have evidence o virilization (eg, increased body hair in male distribution, enlarged clitoris) in addition to AN. 5 TYPICAL DISTRIBUTIO N • Commonly located on the neck (see Figures 220-2 to 220-4) or skin olds (ie, axillae [see Figures 220-1 and 220-8], in ramammary olds, groin, and perineum).

FIGURE 220-1 Acanthosis nig ricans in the rig ht axilla of a 25-ye ar-old woman with typ e 2 d iab e te s. The skin ap p e ars ve lve ty. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 220-2 Acanthosis nig ricans on the ne ck of an ob e se Hisp anic woman with typ e 2 d iab e te s. Note that multip le skin tag s are also p re se nt. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

a Ca Nt h O SIS NIGr ICa NS

FIGURE 220-3 Acanthosis nig ricans on the ne ck of an ob e se woman with typ e II d iab e te s. Note the hyp e rtrop hic thicke ning of the d arke r skin. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 17

ENDO CRINE

FIGURE 220-6 Acanthosis nig ricans on the d orsum of the hand in a morb id ly ob e se young man. Note the hyp e rp ig me ntation and the p re se nce of tiny p ap ule s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Less o ten AN can be seen on the nipples or areolae, perineum, groin, and extensor sur aces o the legs. 4 • Verrucous AN may a ect the eyelids, lips, and buccal mucosa. 4 • In patients with malignancy, the onset o AN can be abrupt and the distribution o lesions is more widespread and may include the palms and soles. 8

FIGURE 220-4 Acanthosis nig ricans with a ve lve ty ap p e arance on the ne ck of a Hisp anic woman with ob e sity and typ e 2 d iab e te s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 220-5 Acanthosis nigricans on the e lb ow of a young obe se Hispanic woman. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 220-7 Acanthosis nig ricans on the hand and wrist of a morb id ly ob e se yo ung man with wid e sp re ad acanthosis. No te the te xture of the skin along with the skin d arke ning . (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

1119

PART 17

1120

ENDO CRINE

Ch a pt e r 220

(to lighten the lesion), combination tretinoin cream with 12% ammonium lactate cream, or topical vitamin D ointments, 10 may be use ul. 4 SO R

• Met ormin11 and octreotide have also been used to manage AN. SO R

CO MPLEMENTARY AND ALTERNATIVE THERAPY The use o omega-3- atty acid and dietary f sh oil supplementation has also been reported to improve AN. 12 SO R PRO CEDURES • Long-pulsed alexandrite laser therapy13 and dermabrasion are alternative treatments. 4 • Some patients have many skin tags within the area o acanthosis and they request them to be removed (see Figure 220-8). (See Chapter 155, Skin Tag or details on treatment.)

PRO GNO SIS AN usually regresses when the underlying condition (eg, diabetes, malignancy) is treated. 4 FIGURE 220-8 Acanthosis nig ricans in the axilla of a man with typ e 2 d iab e te s. Note the many skin tag s also p re se nt. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

BIO PSY • May be needed in unusual cases. • Histologic examination reveals hyperkeratosis and papillary hypertrophy, although the epidermis is only mildly thickened. 9

DIFFERENTIAL DIAGNO SIS Other hyperpigmented lesions that may be con used with AN include the ollowing: • Seborrheic keratosis (see Chapter 156, Seborrheic Keratosis)—Most commonly ound on the trunk or the ace; these lesions are more plaquelike with adherent, greasy scale and have a “stuck-on” appearance. • Pigmented actinic keratosis (see Chapter 164, Actinic Keratosis and Bowen Disease)—Usually in sun-exposed areas; the lesions can be macular or papular with dry, rough adherent scale.

MANAGEMENT NO NPHARMACO LO GIC • Patients with AN are at higher risk o metabolic syndrome, and lipid screening should be considered along with consideration o testing or DM.

PATIENT EDUCATIO N Patients who are overweight should be encouraged to lose weight through diet and exercise because weight loss o ten resolves this condition. PATIENT RESO URCES

• PubMed Health. Acanthosis nigricans—http:/ / www.ncbi.nlm .nih.gov/ pubmedhealth/ PMH0001855/ . • MedlinePlus. Acanthosis nigricans—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000852.htm. PRO VIDER RESO URCES

• Diabetes Public Health Resource, National Center or Chronic Disease Prevention and Health Promotion o the Centers or Disease Control and Prevention—http:/ / www.cdc.gov/ diabetes/ . REFERENCES 1. Kong AS, Williams RL, Smith M, et al. Acanthosis nigricans and diabetes risk actors: prevalence in young persons seen in southwestern US primary care practices. Ann Fam Med. 2007;5:202-208. 2. Litonjua P, Pinero-Pilona A, Aviles-Santa L, et al. Prevalence o acanthosis nigricans in newly-diagnosed type 2 diabetes. Endocr Pract. 2004;10:101-106.

• Weight loss through diet and exercise helps reverse the process, probably by reducing both IR and compensatory hyperinsulinemia.

3. Rendon MI, Cruz PD, Sontheimer RD, Bergstresser PR. Acanthosis nigricans: a cutaneous marker o tissue resistance to insulin. JAm Acad Dermatol. 1989;29(3 pt 1):461-469.

MEDICATIO NS

4. Kapoor S. Diagnosis and treatment o acanthosis nigricans. Skinmed. 2010;8(3):161-164.

• Keratolytic agents (eg, salicylic acid) can improve the cosmetic appearance. Other topical therapies, including 0.1% tretinoin cream

5. Elmer KB, George RM. HAIR-AN syndrome: a multisystem challenge. Am Fam Physician. 2001;63:2385-2390.

a Ca Nt h O SIS NIGr ICa NS

6. Downs AM, Kennedy CT. Somatotrophin-induced acanthosis nigricans. Br J Dermatol. 1999;141:390-391. 7. Blomberg M, Jeppesen EM, Skovby F, Ben eldt E. FGFR3 mutations and the skin: report o a patient with a FGFR3 gene mutation, acanthosis nigricans, hypochondroplasia and hyperinsulinemia and review o the literature. Dermatology. 2010;220(4):297-305. 8. Stulberg DL, Clark N. Hyperpigmented disorders in adults: part II. Am Fam Physician. 2003;68:1963-1968. 9. Sibbald RG, Landolt SJ, Toth D. Skin and diabetes. Endocrinol Metab Clin North Am. 1996;25(2):463-472. 10. Hermanns-Le T, Scheen A, Pierard GE. Acanthosis nigricans associated with insulin resistance: pathophysiology and management. Am J Clin Dermatol. 2004;5(3):199-203.

PART 17

ENDO CRINE 11. Wasniewska M, Arrigo T, Crisa ulli G, et al. Recovery o acanthosis nigricans under prolonged met ormin treatment in an adolescent with normal weight. J Endocrinol Invest. 2009;32:939-940. 12. Sheretz EF. Improved acanthosis nigricans with lipodystrophic diabetes during dietary f sh oil supplementation. Arch Dermatol. 1988;124:1094-1096. 13. Rosenbach A, Ram R. Treatment o acanthosis nigricans o the axillae using a long-pulsed (5-msec) alexandrite laser. Dermatol Surg. 2004;30(8):1158-1160.

1121

PART 17

1122

ENDO CRINE

221 DIABETIC DERMO PATHY Mind y A. Smith, MD, MS

Ch a pt e r 221

diabetic dermopathy; the authors concluded that because the majority o patients were well controlled ( asting blood sugar < 130 mg/ mL in 60%), cutaneous signs o chronic hyperglycemia were decreased. 3 • Sometimes seen in persons without DM, especially patients with circulatory compromise.

PATIENT STO RY A 60-year-old woman with diabetes mellitus (DM) or the past 10 years began to notice reddish-colored lesions on both anterior shins that turned brown over the past year (Figure 221-1). She reported no pain with the hyperpigmented areas but does have oot pain secondary to neuropathy. The patient is diagnosed with diabetic dermopathy, and she begins working with her physician on achieving better control o her diabetes.

INTRO DUCTIO N Diabetic dermopathy is a constellation o well-demarcated, hyperpigmented, atrophic depressions, macules, or papules located on the anterior sur ace o the lower legs that is usually ound in patients with DM. It is the most common cutaneous marker o DM.

EPIDEMIO LO GY • Diabetic dermopathy is ound in 12.5% to 40% o patients and most o ten in the elderly. It is less common in women. 1 • In a case series o 100 consecutive inpatients or outpatients in India with DM and skin lesions, diabetic dermopathy was ound in 36%. 2 The incidence was much lower in a second case series o 500 patients attending a diabetes clinic in India, with only 0.2% diagnosed with

ETIO LO GY AND PATHO PHYSIO LO GY The cause o diabetic dermopathy is unknown. • Diabetic dermopathy may be related to mechanical or thermal trauma, especially in patients with neuropathy. • Lesions have been classi ed as vascular because histology sections demonstrate red blood cell extravasation and capillary basement membrane thickening. In one study, patients with type 1 DM and diabetic dermopathy had marked reduction in skin blood f ow at normal-appearing skin areas on the pretibial sur ace o the legs compared with type 1 control and nondiabetic control patients. 4 • There is an association between diabetic dermopathy and the presence o retinopathy, nephropathy, and neuropathy. 5,6 In a Turkish study, women with diabetic dermopathy appeared to have a more severe sensorial neuropathy (eg, loss o deep tendon ref exes, super cial sensory loss, and the loss o vibration sense) than did patients without these skin lesions; a high prevalence o carpel tunnel syndrome (63.8%) was also ound in these patients. 7

DIAGNO SIS CLINICAL FEATURES The diagnosis is usually clinical. Lesions o ten begin as pink patches (0.5-1 cm), which become hyperpigmented with sur ace atrophy and ne scale (Figures 221-1 to 221-4). TYPICAL DISTRIBUTIO N It is ound in pretibial and lateral areas o the cal (see Figures 221-1 to 221-4). BIO PSY Histology shows epidermal atrophy, thickened small super cial dermal blood vessels, increased epidermal melanin and hemorrhage with hemosiderin deposits. These ndings are not all present in biopsy specimens; in an autopsy series, only 4 o 14 skin biopsies o diabetic dermopathy lesions showed moderate-to-severe wall thickening o arterioles or medium-sized arteries, 11 o 14 showed mild basement membrane thickening, and 9 o 14 had markedly increased epidermal melanin. 8

DIFFERENTIAL DIAGNO SIS Consider the ollowing when evaluating patients with similar skin conditions: FIGURE 221-1 Le sions o d iab e tic d e rmop athy (also calle d p ig me nte d p re tib ia l p ap ule s) o n b o th lo we r e xtre mitie s o a 60-ye ar-o ld wo ma n with d iab e te s. The skin ap p e ars atro p hic and the le sio ns are at and hyp e rp ig me nte d . (Re p rod uce d with p e rmissio n from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

• Early lesions o necrobiosis lipoidica diabeticorum—Erythematous papules or plaques beginning in the pretibial area, but become larger and darker with irregular margins and raised erythematous borders. Telangiectasias, atrophy, and yellow discoloration may be seen. The lesion may be pain ul (see Chapter 222, Necrobiosis Lipoidica).

PART 17

DIa Be t IC De r MO pa t h Y

ENDO CRINE

FIGURE 221-4 Close -up o d iab e tic d e rmop athy on the rig ht le g showing atrop hy, hyp e rp ig me ntation, a shallow ulce r, and f ne scale . The hyp e rp ig me ntation is rom he mosid e rin d e p osition. (Re p rod uce d with p e rmission from Dan Stulb e rg , MD.)

FIGURE 221-2 Diab e tic d e rmop athy on the le g showing p re tib ial hyp e rp ig me ntation and he ale d ulce rs with hyp op ig me ntation. The re are also sig ns o e rythe ma and f ne scale . (Re p rod uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

• Schamberg disease (pigmented purpuric dermatosis) is a capillaritis that produces brown hemosiderin deposits along with visible pink-to-red spots like cayenne pepper on the lower extremities. It is not more common in diabetes but may resemble diabetic dermopathy. A biopsy could be used to distinguish between them (see Chapter 177, Vasculitis). • Stasis dermatitis—The typical site is the medial aspect o the ankle. Early lesions are erythematous, scaly, and sometimes pruritic, becoming progressively hyperpigmented (see Chapter 51, Venous Stasis). • Traumatic scars—There is no scale, lesions are permanent, and edema is not usually present.

MANAGEMENT • There is no e ective treatment. • It is not known whether the lesions improve with better control o diabetes. • One in ormal case report stated that patients may bene t rom 15- to 25-mg chelated zinc daily or several weeks. 9 SO R C

PREVENTIO N It is possible that patients with well-controlled DM have a lower risk o diabetic dermopathy.

PRO GNO SIS Lesions may resolve spontaneously.

PATIENT EDUCATIO N Reassure patients that the lesions are asymptomatic and may resolve spontaneously within 1 to 2 years, although new lesions may orm.

PATIENT RESO URCES

• American Diabetes Association. Skin Complications—http:/ / www.diabetes.org/ living-with-diabetes/ complications/ skin-complications.html?loc= DropDownLWD-skin. PRO VIDER RESO URCES FIGURE 221-3 Diab e tic d e rmop athy on b oth lowe r e xtre mitie s o a mid d le -ag e d man with d iab e te s. The sp arse hair is se cond ary to his vasculop athy. (Re p rod uce d with p e rmission from Dan Stulb e rg , MD.)

• Skinsight. Diabetic Dermopathy—http:/ / www.skinsight.com/

adult/ diabeticDermopathy.htm

1123

PART 17

1124

ENDO CRINE REFERENCES 1. Sibbald RG, Landolt SJ, Toth D. Skin and diabetes. Endocrinol Metab Clin North Am. 1996;25(2):463-472. 2. Goyal A, Raina S, Kaushal SS, et al. Pattern o cutaneous mani estations in diabetes mellitus. Indian J Dermatol. 2010;55(1):39-41. 3. Ragunatha S, Anitha B, Inamadar AC, et al. Cutaneous disorders in 500 diabetic patients attending diabetic clinic. Indian J Dermatol. 2011;56(2):160-164. 4. Brugler A, Thompson S, Turner S, et al. Skin blood f ow abnormalities in diabetic dermopathy. JAmAcad Dermatol. 2011;65(3):559-563. 5. Shemer A, Bergnan R, Linn S, et al. Diabetic dermopathy and internal complications in diabetes mellitus. Int J Dermatol. 1998;37(2):113-115.

Ch a pt e r 221

6. Abdollahi A, Daneshpazhooh M, Amirchaghmaghi E, et al. Dermopathy and retinopathy in diabetes: is there an association. Dermatology. 2007;214(2):133-136. 7. Kiziltan ME, Benbir G. Clinical and nerve conduction studies in emale patients with diabetic dermopathy. Acta Diabetol. 2008;45(2):97-105. 8. McCash S, Emanuel PO. De ning diabetic dermopathy. J Dermatol. 2011;38(10):988-992. 9. DiabetesNet.com. Skin Complications: Necrobiosis Lipoidica. http:/ / www.diabetesnet.com/ diabetes_complications/ diabetes_skin_ changes.php. Accessed November 2011.

PART 17

Ne Cr O BIO SIS LIpO IDICa

222 NECRO BIO SIS LIPO IDICA Mind y A. Smith, MD, MS

ENDO CRINE • NL primarily a ects women (80%), particularly those with type 1 DM, but it can occur with type 2 DM. 1,2 Approximately 75% o patients with NL have or will develop DM. 5 • Average age o onset is 34 years. 1,2 • NL has also been reported in patients with Hashimoto thyroiditis. 3

PATIENT STO RY A 30-year-old woman presents with discoloration on both lower legs. She has no personal history o diabetes; however, type 2 diabetes does run in her amily. Visible inspection o the lesions is highly suggestive o necrobiosis lipoidica (NL) (Figure 222-1). There is hyperpigmentation, yellow discoloration, atrophy, and telangiectasias. The patient is not overweight and had no symptoms o diabetes. Her blood sugar at this visit is 142 a ter eating lunch 1 hour prior to testing. The ollowing day, the patient’s asting blood sugar is 121, with a glycosylated hemoglobin o 6.1. The patient is in ormed o her borderline diabetes, and diet and exercise are prescribed. She is disturbed by her skin appearance and chooses to try a moderate-strength topical corticosteroid or treatment.

INTRO DUCTIO N NL is a chronic granulomatous skin condition with degenerative connective tissue changes most o ten seen in patients with diabetes mellitus (DM). It was previously called necrobiosis lipoidica diabeticorum be ore the recognition o a signi cant minority o patients with NL who do not have DM.

EPIDEMIO LO GY • NL is a rare condition that occurs in approximately 1% (0.3%-2.3%) o patients with DM. 1-4

FIGURE 222-1 Ne crob iosis lip oid ica in a 30-ye ar-old woman with imp aire d g lucose tole rance (b ord e rline d iab e te s). Note the b rown p ig me ntation and p romine nt b lood ve sse ls. (Re p rod uce d with p e rmission from Suraj Re d d y, MD.)

• Cases o amilial NL not associated with DM have also been reported. 6

ETIO LO GY AND PATHO PHYSIO LO GY • The cause o NL remains unknown. • Angiopathy leading to thrombosis and occlusion o the cutaneous vessels has been implicated in its etiology. However, microangiopathic changes are less common in lesions on areas other than the shins and, there ore, are not necessary or developing the lesions. 2 In addition, one study ound that NL lesions exhibited signi cantly higher blood f ow rates than areas o una ected skin close to the lesions. 7 • Antibodies and C3 have been ound at the dermal–epidermal junction, suggesting vasculitis. • The presence o brin in these lesions associated with palisading histiocytes may indicate a delayed hypersensitivity reaction. • In a study using ocus-f oating microscopy, a modi ed immunohistochemical technique was developed to detect Borrelia spirochetes. Borrelia was detected in 75% o NL lesions overall and 92.7% o inf ammatoryrich (38 o 41) versus inf ammatory-poor (4 o 15, 26.7%) cases.8 The authors posit that these ndings indicate a potential role or Borrelia burgdorferi or other similar strains in the development o or trigger or NL.

DIAGNO SIS CLINICAL FEATURES • The lesions begin as erythematous papules or plaques in the pretibial area and become larger and darker with irregular margins and raised erythematous borders (Figures 222-1 to 222-4). The lesion’s center atrophies and turns yellow in color, appearing waxy (Figures 222-3, 222-4, and 222-5A).

FIGURE 222-2 Ne crob iosis lip oid ica in a p atie nt with typ e 1 d iab e te s. Note the p ink are a at the site o a he ale d sup e rf cial ulce r. (Re p rod uce d with p e rmission from Amb e r Tully, MD.)

1125

1126

PART 17

ENDO CRINE

Ch a pt e r 222

FIGURE 222-3 Ne crob iosis lip oid ica on the le g o a man with typ e 2 d iab e te s. No te the ce ntral atrop hy and ye llow d isco loration with a we lld e marcate d b rown b o rd e r. (Re p ro d uce d with p e rmission fro m the Unive rsity of Te xas He alth Scie nce s Ce nte r, Divisio n of De rmatolog y.)

A

• There is o ten a prominent brown color or hyperpigmentation visible (see Figures 222-1 to 222-4). • The lesions may ulcerate (occurs in approximately one-third) and become pain ul (Figure 222-5B).

B FIGURE 222-5 A. Ne crob iosis lip oid ica on the le g o a woman with no d iab e te s. It was b iop sy p rove n and tre ate d . B. Worse ning and ulce rations o ne crob io sis lip oid ica d e sp ite tre atme nt with top ical ste roid s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Telangiectasias and prominent blood vessels may be seen within the lesions (see Figures 222-1 to 222-4). • The yellow color may be because o lipid deposits or β-carotene. TYPICAL DISTRIBUTIO N FIGURE 222-4 Multip le le sio ns o ne crob iosis lip oid ica in a young ad ult with typ e 1 d iab e te s. No te the ce ntral ye llo w d isco lo ratio n and we llcircumscrib e d b rown b ord e rs. (Re p rod uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

• The lesions are usually located on the shins (90%) (see Figures 222-1 to 222-4). • NL lesions have been reported on many skin areas, including the ace, scalp, and penis. 9,10

PART 17

Ne Cr O BIO SIS LIpO IDICa

BIO PSY • Biopsy is usually not needed as the clinical picture is usually clear. The dangers o a biopsy include delayed healing and in ection in a patient who o ten has diabetes. The shin region o the leg is notorious or delayed healing even in healthy persons and so biopsy should be avoided in most cases. • I the diagnosis is uncertain, a punch biopsy will show a thin atrophic epidermis with dermal granulomatous inf ammation and obliterative endarteritis. The dermal change shows increased necrobiosis or degeneration o collagen with absence o elastic tissue.

DIFFERENTIAL DIAGNO SIS NL may be con used with the ollowing conditions: • Erythema nodosum (EN) is an inf ammatory panniculitis that occurs in the same areas (especially shins) as NL. These nodules are pink in color and the skin is smooth above them. The color and lack o epidermal changes should di erentiate EN rom NL (see Chapter 176, Erythema Nodosum). • Granuloma annulare—Appears as asymmetric annular red plaques on the dorsum o the hands, extensor sur ace o the extremities, or posterior neck. They lack the yellow discoloration o NL. These lesions are so visibly like red raised rings that they should appear di erent rom NL. I biopsy is needed, the presence o abundant mucin deposits helps to distinguish these lesions rom NL (see Chapter 171, Granuloma Annulare). 2 • Lichen simplex chronicus—A chronic pruritic eczematous lesion. The lesions are well-circumscribed plaques or papules with licheni ed or thickened skin caused by chronic scratching or rubbing. Lesions are commonly located on the ankles, wrists, or posterior nuchal region. The prominent scale and licheni cation should help di erentiate these lesions rom NL (see Chapter 143, Atopic Dermatitis). • Sarcoidosis skin lesions—Including EN, maculopapular eruptions on the ace, nose, back, and extremities; skin plaques that are o ten purple and raised; and broad macules with telangiectasias that are most commonly seen on the ace or hands. Punch biopsy will distinguish between sarcoidosis and NL (see Chapter 173, Sarcoidosis). • Stasis dermatitis—Occurs on the lower extremities secondary to venous incompetence and edema. 11 A ected patients are usually older, and the typical site is the medial aspect o the ankle. Early lesions are erythematous, scaly, and sometimes pruritic that progressively become hyperpigmented. These lesions are rarely well circumscribed, as seen in NL (see Chapter 51, Venous Stasis).

ENDO CRINE • Local application o potent steroids or intralesional injections o 2.5 mg/ mL o triamcinolone. 2 SOR C The major risk o these treatments includes increasing the existing atrophy, so patients should be in ormed o risks and bene ts be ore initiating steroid treatments. • Topical tacrolimus (0.1% ointment twice daily or 8 weeks ollowed by once daily or 8 weeks) was success ul in a single case report. 12 SO R C • Pentoxi ylline (400 mg 2-3 times daily), an agent that improves blood f ow and decreases red cell and platelet aggregation, was shown in 2 case reports to completely resolve the lesions at 8 weeks in one3 and at 6-month ollow-up in the other. 4 The latter patient continued therapy and remained in remission at a 2-year ollow-up. SO R C • Ulcerative NL has been reported to respond to tetracycline, 13 antimalarial agents (eg, hydroxychloroquine), 14 clo azimine, 15 systemic steroids, 16 antiplatelet therapy, 17 and biologic agents (eg, inf iximab in usion, subcutaneous etanercept). 18,19 SO R C REFERRAL • Re er patients with intractable skin ulcers. In one study that included patients with NL, application o allogeneic cultured dermal substitute was success ul in improving healing. 20 • Topical photodynamic therapy may also be success ul in treating re ractory NL lesions; in one case series (N = 18), overall response rate was 39% with complete resolution in 1 patient and partial resolution in 6 patients. 21 SO R C

PRO GNO SIS • Spontaneous resolution occurs in 10% to 20% o cases. • In a study o patients with DM undergoing pancreatic transplantation (N = 11), all 5 patients with NL achieved resolution o NL ollowing transplantation; 1 patient had recurrent NL associated with transplant rejection. 22 The single patient with NL who underwent kidney transplantation had persistent NL.

PATIENT EDUCATIO N • Patients with NL without DM should be advised about the increased risk o developing the disease and counseled about symptoms and periodic surveillance. • NL may resolve spontaneously and does respond to several treatments.

PATIENT RESO URCES

• American Diabetes Association—http:/ / www.diabetes.org.

MANAGEMENT Evaluate patients not previously diagnosed with DM or diabetes. Even though glycemic control does not correlate with progression o these lesions, DM should be treated to decrease the risk o macro- and microvascular complications. MEDICATIO NS Data on success ul treatment is largely based on case reports. Necrobiosis lesions may respond to the ollowing treatments:

• American Diabetes Association. Skin Complications—http:/ / www.diabetes.org/ living-with-diabetes/ complications/ skin-complications.html?loc=DropDownLWD-skin. • American Osteopathic College of Dermatology. Necrobiosis Lipoidica Diabeticorum—http:/ / www.aocd.org/ skin/ dermatologic_diseases/ necrobiosis_lipoid.html. PRO VIDER RESO URCES

• Medscape. Necrobiosis Lipoidica—http:/ / emedicine.medscape .com/ article/ 1103467-overview.

1127

PART 17

1128

ENDO CRINE REFERENCES 1. Noz KC, Korstanje MJ, Vermeer BJ. Cutaneous mani estations o endocrine disorders: a guide or dermatologists. Am J Clin Dermatol. 2003;4(5):315-331. 2. Sibbald RG, Landolt SJ, Toth D. Skin and diabetes. Endocrinol Metab Clin North Am. 1996;25(2):463-472. 3. Ahmed K, Muhammad Z, Qayum I. Prevalence o cutaneous maniestations o diabetes mellitus. JAyub Med Coll Abbottabad. 2009;21(2):76-79. 4. Pavlovi´c MD, Milenkovi´c T, Dini´c M, et al. The prevalence o cutaneous mani estations in young patients with type 1 diabetes. Diabetes Care. 2007;30(8):1964-1967. 5. O’Reilly K, Chu J, Meehan S, et al. Necrobiosis lipoidica. Dermatol Online J. 2011;17(10):18. 6. Roche-Gamón E, Vilata-Corell JJ, Velasco-Pastor M. Familial necrobiosis lipoidica not associated with diabetes. Dermatol Online J. 2007;13(3):26. 7. Ngo B, Wigington G, Hayes K, et al. Skin blood f ow in necrobiosis lipoidica diabeticorum. Int J Dermatol. 2008;47(4):354-358. 8. Eisendle K, Baltaci M, Kutzner H, Zelger B. Detection o spirochaetal microorganisms by ocus f oating microscopy in necrobiosis lipoidica in patients rom central Europe. Histopathology. 2008;52(7):877-884. 9. Lynch M, Callagy G, Mahon S, Murphy LA. Arcuate plaques o the ace and scalp. Atypical necrobiosis lipoidica (ANL) o the ace and scalp. Clin Exp Dermatol. 2010;35(7):799-800. 10. Alonso ML, Riós JC, González-Beato MJ, Herranz P. Necrobiosis lipoidica o the glans penis. Acta DermVenereol. 2011;91(1):105-106. 11. Mistry N, Chih-Ho Hong H, Craw ord RI. Pretibial angioplasia: a novel entity encompassing the clinical eatures o necrobiosis lipoidica and the histopathology o venous insu ciency. J Cutan Med Surg. 2011;15(1):15-20. 12. Patsatsi A, Kyriakou A, Sotiriadis D. Necrobiosis lipoidica: early diagnosis and treatment with tacrolimus. Case Rep Dermatol. 2011;3(1):89-93.

Ch a pt e r 222

13. Mahé E, Zimmermann U. Signi cant improvement in ulcerative necrobiosis lipoidica with doxycycline. Ann DermatolVenereol. 2011;138(10):686-688. 14. Durupt F, Dalle S, Debarbieux S, et al. Success ul treatment o necrobiosis lipoidica with antimalarial agents. Acta DermVenereol. 2009;89(6):651-652. 15. Benedix F, Geyer A, Lichte V, et al. Response o ulcerated necrobiosis lipoidica to clo azimine. Acta DermVenereol. 2010;90(1):104-106. 16. Tan E, Patel V, Berth-Jones J. Systemic corticosteroids or the outpatient treatment o necrobiosis lipoidica in a diabetic patient. J DermatologTreat. 2007;18(4):246-248. 17. Moore AF, Abourizk NN. Necrobiosis lipoidica: an important cutaneous mani estation o diabetes that may respond to antiplatelet therapy. Endocr Pract. 2008;14(7):947-948. 18. Hu SW, Bevona C, Winter eld L, et al. Treatment o re ractory ulcerative necrobiosis lipoidica diabeticorum with inf iximab: report o a case. Arch Dermatol. 2009;145(4):437-439. 19. Suárez-Amor O, Pérez-Bustillo A, Ruiz-González I, RodríguezPrieto MA. Necrobiosis lipoidica therapy with biologicals: an ulcerated case responding to etanercept and a review o the literature. Dermatology. 2010;221(2):117-121. 20. Taniguchi T, Amoh Y, Tanabe K, et al. Treatment o intractable skin ulcers caused by vascular insu ciency with allogeneic cultured dermal substitute: a report o eight cases. JArtif Organs. 2012;15(1):77-82. 21. Berking C, Hegyi J, Arenberger P, et al. Photodynamic therapy o necrobiosis lipoidica—a multicenter study o 18 patients. Dermatology. 2009;218(2):136-139. 22. Souza AD, El-Azhary RA, Gibson LE. Does pancreas transplant in diabetic patients a ect the evolution o necrobiosis lipoidica? Int J Dermatol. 2009;48(9):964-970.

h Ype r LIpIDe MIa a ND Xa Nt h O Ma S

PART 17

ENDO CRINE

223 HYPERLIPIDEMIA AND XANTHO MAS Mind y A. Smith, MD, MS

PATIENT STO RY A 27-year-old Hispanic man reported new pain ul nonpruritic bumps, which started 6 months ago, over his entire body. The patient had not seen a physician or 10 months and had run out o his oral medicines or type 2 diabetes mellitus. His grandmother had a milder version o bumps like this years ago. The rm yellowish papules were present all over his body rom the neck down (Figures 223-1 to 223-3). Laboratory evaluation revealed a random blood sugar o 203, a asting triglyceride (TG) level greater than 7000 mg/ dL, and total cholesterol greater than 700 mg/ dL. High-density lipoproteins (HDLs) were 32 mg/ dL, and there were no chylomicrons present. The patient was diagnosed with xanthomas, poorly controlled diabetes mellitus, and hyperlipidemia, and was started on met ormin, gem brozil, and a β-hydroxy-β-methylglutarylcoenzyme A (HMG-CoA)-reductase inhibitor.

INTRO DUCTIO N Hyperlipidemia re ers to an elevated concentration o one or more o the measured serum lipid components (total cholesterol [TC], low-density lipid [LDL], HDL, and TGs). Xanthomas are a skin mani estation o amilial or severe secondary hyperlipidemia, although they can occur in patients with normal lipid levels. Hyperlipidemia is a major modi able risk actor or cardiovascular disease.

FIGURE 223-1 Close -up of e rup tive xanthomas on the arm of a 27-ye ar-old man with untre ate d hyp e rlip id e mia and d iab e te s.1 (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

chronic kidney disease, cholestatic liver disease), cigarette smoking, obesity, or drugs (eg, corticosteroids, estrogens, retinoids, high-dose β-blockers). • Increased circulating LDL becomes incorporated into atherosclerotic plaques. These plaques can grow to block blood supply and oxygen delivery resulting in ischemia to vital organs. In addition, i the plaque ruptures, it can precipitate a clot, causing or example myocardial in arction (MI). • Elevated TG is an independent risk actor or coronary heart disease (CHD) and increases the risk o hepatomegaly, splenomegaly, hepatic

EPIDEMIO LO GY • During 2005 to 2006, 15.7% o adults in the United States had a high serum TC level. 1 The average cholesterol level o adults ages 20 to 74 years decreased rom 222 mg/ dL in 1959 to 1962 to 197 mg/ dL in 2007 to 2008, reaching the Healthy People 2010 goal. 2 • An estimated 34% o the adult population had high LDL-C during 2005 to 2008 (LDL-C levels above the recommended goal levels or reported current use o cholesterol-lowering medication). 3 • Among young adults (ages 12-19 years), 20.3% had abnormal lipids; boys are more likely than girls to have at least one lipid abnormality (24.3% vs 15.9%, respectively). 4 • Patients with heterozygous amilial hypercholesterolemia (FH) (1 in 500 persons worldwide) can present as adults with tendon xanthomas.

ETIO LO GY AND PATHO PHYSIO LO GY • Lipoproteins are complexes o lipids and proteins essential or transporting cholesterol, TGs, and at-soluble vitamins. • Elevated levels can result rom genetically based derangement o lipid metabolism and/ or transport or rom secondary causes such as diet, medical disorders (eg, type 2 diabetes mellitus [DM], hypothyroidism,

FIGURE 223-2 Erup tive xanthomas on the arm and trunk of the man in Fig ure 223-1. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

1129

1130

PART 17

ENDO CRINE

Ch a pt e r 223

FIGURE 223-5 Erup tive xanthomas o n the kne e s in the p atie nt in Fig ure 223-4. (Re p rod uce d with p e rmission from Richard P. Usatine , MD. Pre viously p ub lishe d in the We ste rn Journal of Me d icine .)

FIGURE 223-3 Erup tive xanthomas cove ring mo st of the b od y o f the man in Fig ure 223-1. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

steatosis, and pancreatitis. Contributing actors include obesity, physical inactivity, cigarette smoking, excess alcohol intake, medical diseases (eg, type 2 DM, chronic renal ailure, nephrotic syndrome), drugs (as above), and genetic disorders (eg, amilial combined hyperlipidemia). 5 • Xanthomas are deposits o lipid in the skin or subcutaneous tissue, usually occurring as a consequence o primary or secondary hyperlipidemia. Xanthomas can also be seen in association with monoclonal gammopathy. 6 There are 5 basic types o xanthomas: ° Eruptive xanthomas (also called tuberoeruptive) are the most common orm. These appear as crops o yellow or hyperpigmented papules with erythematous halos in white persons (see Figures 223-1 to 223-3), appearing hyperpigmented in black persons (Figures 223-4 and 223-5).

FIGURE 223-4 Erup tive xanthomas on the e lb ows o f a hyp e rlip id e mic b lack man with typ e 2 d iab e te s. His trig lyce rid e s and total chole ste rol le ve ls we re hig h.1 (Re p rod uce d with p e rmission from Richard P. Usatine , MD. Pre viously p ub lishe d in the We ste rn Journal of Me d icine .)

° Tendon xanthomas are requently seen on the Achilles and extensor nger tendons. ° Plane xanthomas are f at and commonly seen on the palmar creases, ace, upper trunk, and on scars. ° Tuberous xanthomas are ound most requently on the hand or over large joints. ° Xanthelasma are yellow papules ound on the eyelids (Figure 223-6). Fi ty percent o individuals with xanthelasmas have normal lipid pro les.

RISK FACTO RS Risk actors to consider or treatment decisions or patients with hyperlipidemia include the ollowing: • Type 2 DM • Family history o early CHD or amilial hyperlipidemia • Cardiac risk actors (cigarette smoking, obesity, hypertension, or sedentary li estyle)

FIGURE 223-6 Xanthe lasma around the e ye s (xanthoma p alp e b rarum); most ofte n se e n on the me d ial asp e ct of the e ye lid s, with up p e r lid s b e ing more commonly involve d than lowe r lid s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 17

h Ype r LIpIDe MIa a ND Xa Nt h O Ma S

ENDO CRINE

DIAGNO SIS CLINICAL FEATURES • Most patients with hyperlipidemia are asymptomatic. • A very high TC level (> 2000 mg/ dL) may result in eruptive xanthomas or lipemia retinalis (white appearance o the retina; also seen with isolated high TG). Very high LDL may lead to the ormation o tendinous xanthomas. • Xanthomas mani est clinically as yellowish papules, nodules, or tumors (see Figure 223-1). • Eruptive xanthomas (see Figures 223-2 to 223-5) begin as clusters o small papules on the elbows, knees, and buttocks that can grow to the size o grapes. • There is a case report o a patient with normolipidemic xanthomatosis with lesions involving the bones and mucous membranes in addition to skin. 7 TYPICAL DISTRIBUTIO N Xanthomas are most commonly ound in super cial so t tissues, such as skin and subcutis, or on tendon sheaths. LABO RATO RY TESTING • The National Cholesterol Education Program (NCEP) III recommends a asting lipid pro le (FLP) as the initial test5; alternatively patients may be tested initially with a random TC and HDL. • I the TC is greater than 200 mg/ dL or the HDL less than 40 mg/ dL or men or less than 50 mg/ dL or women, an FLP is obtained or LDL determination.5 LDL cannot be determined i TG is greater than 400 mg/ dL. • I thyroid dys unction is suspected, obtain a thyroid-stimulating hormone level to determine whether thyroid dys unction is contributing to the lipid abnormalities. • Other secondary causes to consider include anorexia nervosa, Cushing syndrome, hepatitis, nephrotic syndrome, renal ailure, and systemic lupus erythematosus. • I a statin is under consideration, a baseline creatine phosphokinase (CPK) is recommended be ore starting statin therapy. BIO PSY Biopsy is rarely needed and shows collections o lipid- lled macrophages.

DIFFERENTIAL DIAGNO SIS Other skin papules that can be mistaken or xanthomas include the ollowing: • Gouty tophi—Deposits o monosodium urate that are usually rm and occasionally discharge a chalky material (Figure 223-7, see Chapter 105, Gout). • Pseudoxanthoma elasticum—A disorder caused by abnormal deposits o calcium on the elastic bers o the skin and eye. • Molluscum contagiosum—Caused by a virus; lesions can be papular and widespread but generally have a central depression (see Chapter 129, Molluscum Contagiosum). The patient in Figures 223-1 to 223-3 was originally misdiagnosed with molluscum.

FIGURE 223-7 Ear g outy top hus in a young man with g out. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

MANAGEMENT Management o patients with hyperlipidemia emphasizes reduction o cardiovascular risk actors (as noted above) and targets elevated LDL cholesterol or the goal o cholesterol-lowering therapy. 5 Optimal LDL is considered to be less than 100 mg/ dL, near optimal LDL is 100 to 129 mg/ dL, and high LDL is equal to or greater than 160 mg/ dL. The Institute or Clinical Systems Improvement (ICSI) suggests consideration o a goal o less than 70 mg/ dL or patients with established CHD, noncardiac atherosclerosis, or CHD equivalent. 8 • The intensity o therapy should be based on the patient’s risk status. 5 The recommended LDL goal is less than 160 or individuals with zero to 1 risk actor (or 10-year CHD risk o < 10%), less than 130 mg/ dL or 2 or more risk actors, and less than 100 mg/ dL or those with CHD or CHD equivalents (eg, DM or 10-year CHD risk o >20%). • For those with 2 or more risk actors, a 10-year risk assessment is conducted using the Framingham scoring system (http:/ / hp2010.nhlbihin.net/ atpiii/ calculator.asp) to help identi y which individuals would bene t most rom intensive treatment. NO NPHARMACO LO GIC • Smoking cessation should be encouraged and attempts actively supported; cessation lowers both cardiovascular risk and lipid levels. SOR A

• Patients should be encouraged to modi y their risk actors through exercise and dietary changes. High cholesterol can be lowered through dietary changes. SO R A

1131

PART 17

1132

ENDO CRINE • Patients who are overweight should be encouraged to reduce calories to achieve weight loss. SO R C • Features o a lipid-lowering diet include reducing intake o total ats to 25% to 35% o total calories (provided trans atty acids and saturated ats are kept low [ 6 months) e ects o a low- at diet in patients with hyperlipidemia. 9 • Similarly, o 11 small trials o dietary intervention identi ed by authors o a Cochrane review, only short-term outcomes were reported. 10 There were no di erences between low-cholesterol diets and other dietary interventions (eg, omega-3 atty acids, soya proteins, plant sterols or plant stanols), with the exception o plant sterols lowering TC signi cantly more than a cholesterol-lowering diet.10 • Reducing saturated at through at modi cation diets reduces the risk o cardiovascular events by 14% (relative risk [RR] 0.86, 95% con dence interval [CI] 0.77-0.96). 11 SO R A This reduction in cardiovascular events was directly related to the degree o e ect on serum total and LDL cholesterol and TGs. The strongest evidence was or trials o at least 2 years, duration and in studies o men (not o women). However, there were no clear e ects o dietary at changes on total mortality (RR 0.98, 95% CI 0.93-1.04) or cardiovascular mortality (RR 0.94, 95% CI 0.85-1.04). • NCEP recommends beginning with li estyle therapies and reassessing LDL a ter 6 weeks. I the LDL goal is not met, rein orce li estyle change along with adding plant sterols and ber; also consider dietician re erral. I the LDL goal is not met at the next 6-week visit, consider medications. 5 Patients hospitalized or a coronary event or procedure should be discharged on drug therapy i their LDL is equal to or greater than 130 mg/ dL. 5 • Addition o plant sterols/ stanols up to 2 g/ d should be considered, particularly i the initial LDL goal is not met with diet modi cation and exercise. SO R B • Treatment should also be initiated or patients with high TG (> 200-499 mg/ dL) or very high TG (≥500 mg/ dL) beginning with weight reduction and exercise; or those with very high TGs, a verylow- at diet is used (≤15% o calorie intake). • Initial treatment o xanthomas should target the underlying hyperlipidemia (when present). MEDICATIO NS In addition to primary interventions noted above, secondary therapy includes statins, niacin, bric acids, ezetimibe, and a bile acid sequestrant.4,8 The use o combination therapy has not been supported by outcome-based studies. • Statins (HMG-CoA reductase inhibitors; lovastatin [20-80 mg], pravastatin [20-40 mg], simvastatin [20-80 mg], f uvastatin [20-80 mg], atorvastatin [10-80 mg], and cerivastatin [0.4-0.8 mg]) are considered rst line or most patients. Evidence supports use o statins in patients with risk actors or CHD (lowers all-cause mortality [odds ratio (OR) 0.88, 95% CI 0.81-0.96], major coronary events [OR 0.70, 95% CI 0.61-0.81], and major cerebrovascular events [OR 0.81, 95% CI 0.71-0.93])12 and in patients with CHD or CHD equivalent (reduces mortality risk rom CHD and possibly overall mortality). 13 SO R A Number needed to treat (NNT) to prevent one additional death in patients with CHD is approximately 30 to 50. There do not appear to be important di erences by type o statin.14

Ch a pt e r 223

• Statin side e ects include myopathy and increased liver enzymes; statins are associated with a small increase in the risk o developing DM (number needed to harm = 255). 15 The major contraindication is liver disease. • Niacin (immediate release [crystalline] nicotinic acid [1.5-3 g], extended-release nicotinic acid [Niaspan] [1-2 g], sustained release) is considered a second-line agent to be used in combination with a statin i the LDL goal is not achieved with intensi ying monotherapy or as rst-line agent or patients with very high TG. Evidence supports reduction in major CHD events with niacin. SOR A Niacin is nonprescription. • Niacin side e ects include gastrointestinal (GI) distress, f ushing, hyperuricemia, hyperglycemia in patients with DM, and hepatotoxicity. Contraindications are chronic liver disease and severe gout; use with caution in patients with DM, hyperuricemia, peptic ulcer disease. • Fibrates (gem brozil [600 mg bid], eno brate [200 mg], clo brate [1000 mg bid]) is a second-line agent shown to reduce major CHD events but not overall mortality. 16 SO R A Fibrates can be used as primary therapy or very high TG. Side e ects include dyspepsia, gallstones, myopathy, and unexplained non-CHD deaths. Contraindications are severe renal or hepatic disease. • Bile acid sequestrants (cholestyramine [4-16 g], colestipol [5-20 g], colesevelam [2.6-3.8 g]) are second-line agents shown to reduce CHD mortality. 11 SOR A Side e ects include GI distress, constipation, and decreased absorption o other drugs. Contraindications are dysbetalipoproteinemia or TG greater than 400 mg/ dL. Hypolipidemic drug treatment o ten results in regression o xanthomas. SOR C In patients with xanthomas associated with monoclonal gammopathy, hematologic remission ollowing chemotherapy was associated with improvement in the xanthomas in several patients. 6 CO MPLEMENTARY AND ALTERNATIVE THERAPY • Artichoke lea extract, red yeast rice, and several Chinese herbal medicines (in particular Xuezhikang) lower cholesterol compared with placebo; data on patient-oriented outcomes are lacking. 17-19 • It is not clear whether supplementing with omega-3 atty acids reduces mortality when combined primary and secondary prevention data are analyzed. A 2006 meta-analysis ailed to nd a reduction in overall mortality or cardiovascular events. 20 • Bene t is suggested or whole f axseed and lignan, especially or women, but not or f axseed oil. 21 • In a randomized crossover trial, consuming walnuts (42.5 g walnuts/ 10.1 mJ) and atty sh (113 g salmon, twice a week) in a healthy diet signi cantly lowered serum cholesterol and triglyceride concentrations, respectively. 22 In a meta-analysis, nut consumption (67 g) reduced lipid levels. 23 SURGICAL PRO CEDURES • Between 1975 and 1983, a randomized controlled trial was conducted primarily o male patients ollowing a rst MI (N = 838) o partial ileal bypass surgery or no surgery. The initial report ound improved lipid patterns in patients in the intervention arm, 24 and a 25-year ollow-up study ound improved survival and cardiovascular disease- ree survival in the surgery arm. 25 • Xanthelasma lesions may be treated or cosmetic purposes. Methods o treatment include surgery, electrosurgery, cryotherapy, and laser therapy.

PART 17

h Ype r LIpIDe MIa a ND Xa Nt h O Ma S

In a case report o 24 patients, argon laser coagulation was welltolerated and the cosmetic outcome was considered to be good in 85% o patients. 26 SO R C When standard therapy ails, LDL apheresis has lowered lipid levels with subsequent regression o tendon xanthomas. 27 SO R C REFERRAL Re erral or nutritional counseling should be considered, especially i initial attempts at dietary control ail. Dietary advice has been shown to result in modest improvements in cardiovascular risk actors, such as blood pressure, and total and LDL-cholesterol levels. 28 SO R A

ENDO CRINE FO LLO W-UP • NCEP recommends reassessing LDL approximately every 6 weeks until the LDL goal is met, then every 6 to 12 months. 5 • It is not clear i monitoring liver enzymes in patients on statins is necessary. 35 Repeat a CPK i a patient experiences symptoms o myopathy. Statin therapy should be discontinued i the CPK is more than 10 times normal. For patients with myopathy and moderate or no CPK elevation, conduct weekly monitoring until symptoms improve or discontinue statins i there is worsening or ailure to resolve. 36

PATIENT EDUCATIO N PREVENTIO N AND SCREENING • The United States Preventive Services Task Force (USPSTF) strongly recommends screening men age 35 years and older or lipid disorders. 29 SOR A There is strong evidence that drug therapy reduces CHD events and mortality in middle-aged men (ages 35-70 years) with abnormal lipids and a potential risk o CHD events greater than 1% per year. A Cochrane review con rmed reductions in all-cause mortality, major vascular events, and revascularizations with no cancer excess in 14 trials, 11 recruiting patients with risk actors. 30 In one meta-analysis, NNT or primary prevention in patients (primarily men) with risk actors was 173 to prevent 1 premature death, 81 to prevent 1 CHD event, and 245 to prevent 1 stroke. 12 • The USPSTF strongly recommends screening women age 45 years and older i they are at increased risk or CHD. 29 SOR A The USPSTF also recommends screening men ages 20 to 35 years and women ages 20 to 45 years i they are at increased risk or CHD. 29 SO R B There is less direct evidence suggesting e ectiveness o drug therapy in other adults, including men older than age 70 years and middle-aged and older women (age 45 years and older) with similar levels o risk. 31 In act, in a meta-analysis o primary prevention trials including women, there was insu cient evidence o reduced risk o any clinical outcome in women. 32 • Secondary prevention trials do show reductions in CHD mortality, CHD events, non atal MI, and revascularization or women that is similar to reductions seen or men and demonstrate decreased mortality or older men. 33 • Retesting every 1 to 5 years is recommended by the USPSTF based on CHD risk. 29 • Studies are not available to assess the e cacy o screening children and adolescents or dyslipidemia or delaying the onset and reducing the incidence o CHD-related events.

PRO GNO SIS • Based on observational data, each 30-mg/ dL increase in LDL increases the relative risk o CHD by 30%. • Use o strategies to lower elevated lipid levels will likely reduce CHD events and possibly overall mortality. • With medical (diet or drugs) treatment o hyperlipidemia, many xanthomas and about hal o xanthelasma resolve or improve with surgical treatment, recurrence is uncommon. 34

• Patients should be counseled about bene ts and risks o screening. • Li estyle changes should be stressed as primary prevention or patients with hyperlipidemia. • I persistent elevations in lipids continue despite li estyle change, those with high risk or CHD should consider medications. • Patients with hyperlipidemia and/ or DM should be encouraged to establish and maintain good control o these diseases, as this o ten results in regression o xanthomas. PATIENT RESO URCES

• MedlinePlus. High blood cholesterol levels—http:/ / www.nlm.nih. gov/ medlineplus/ ency/ article/ 000403.htm. • MedlinePlus. Familial Hypercholesterolemia—http:/ / www.nlm. nih.gov/ medlineplus/ ency/ article/ 000392.htm. • MedlinePlus. Xanthoma—www.nlm.nih.gov/ medlineplus/ ency/ article/ 001447.htm. PRO VIDER RESO URCES

• Medscape. Familial Hypercholesterolemia—http:/ / emedicine. medscape.com/ article/ 121298. • Medscape. Xanthomas—http:/ / emedicine.medscape.com/ article/ 1103971.

REFERENCES 1. Centers or Disease Control and Prevention. Schober SE, Carroll MD, Lacher DA, Hirsch R. High serum total cholesterol—an indicator or monitoring cholesterol lowering e orts: U.S. adults, 2005-2006. NCHS Data Brie . http:/ / www.cdc.gov/ nchs/ data/ databrie s/ db02.pd . Accessed August 2013. 2. QuickStats: Average total cholesterol level among men and women aged 20-74 years—National Health and Nutrition Examination Survey, United States, 1959-1962 to 2007-2008. MMWR Morb Mortal Wkly Rep. September 25, 2009;58(37):1045. http:/ / www.cdc.gov/ mmwr/ preview/ mmwrhtml/ mm5837a9.htm. Accessed September 2012. 3. Vital signs: prevalence, treatment, and control o high levels o lowdensity lipoprotein cholesterol—United States, 1999-2002 and 2005-2008. MMWR Morb MortalWkly Rep. 2011;60(04):109-114. http:/ / www.cdc.gov/ mmwr/ preview/ mmwrhtml/ mm6004a5. htm?s_cid=mm6004a5_w. Accessed January 2012.

1133

1134

PART 17

ENDO CRINE 4. Prevalence o abnormal lipid levels among youths—United States, 1999-2006. MMWR Morb MortalWkly Rep. 2010;59(02):29-33. http:/ / www.cdc.gov/ mmwr/ preview/ mmwrhtml/ mm5902a1. htm. Accessed August 2013. 5. Third report o the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment o High Blood Cholesterol in Adults. (Adult Treatment Panel III), Executive Summary. (NCEP/ NHLBI., 2004-07-13). http:/ / www .nhlbi.nih.gov/ guidelines/ cholesterol/ index.htm. Accessed August 2013. 6. Szalat R, Arnul B, Karlin L, et al. Pathogenesis and treatment o xanthomatosis associated with monoclonal gammopathy. Blood. 2011;118(14):3777-3784. 7. Akasaka E, Matsuzaki Y, Kimura K, et al. Normolipidaemic xanthomatosis with systemic involvement o the skin, bone and pharynx. Clin Exp Dermatol. 2012;37(3):305-307. 8. Institute or Clinical Systems Improvement (ICSI). Lipid Management in Adults. Bloomington, MN: Institute or Clinical Systems Improvement (ICSI); 2009, updated 2011. http:/ / www.guideline.gov/ content.aspx?id=36062. Accessed August 2013. 9. Smart NA, Marshall BJ, Daley M, et al. Low- at diets or acquired hypercholesterolaemia. Cochrane Database Syst Rev. 2011;(2):CD007957. 10. Sha q N, Singh M, Kaur S, Khosla P, Malhotra S. Dietary treatment or amilial hypercholesterolaemia. Cochrane Database Syst Rev. 2010;(1):CD001918. 11. Hooper L, Summerbell CD, Thompson R, et al. Reduced or modi ed dietary at or preventing cardiovascular disease. Cochrane Database Syst Rev. 2011;(7):CD002137. 12. Brugts JJ, Yetgin T, Hoeks SE, et al. The bene ts o statins in people without established cardiovascular disease but with cardiovascular risk actors: meta-analysis o randomised controlled trials. BMJ. 2009;338:b2376.

Ch a pt e r 223

21. Pan A, Yu D, Demark-Wahne ried W, et al. Meta-analysis o the e ects o f axseed interventions on blood lipids. Am J Clin Nutr. 2009;90(2):288-297. 22. Rajaram S, Haddad EH, Mejia A, Sabaté J. Walnuts and atty sh inf uence di erent serum lipid ractions in normal to mildly hyperlipidemic individuals: a randomized controlled study. Am J Clin Nutr. 2009;89(5):S1657-S1663. 23. Sabaté J, Oda K, Ros E. Nut consumption and blood lipid levels: a pooled analysis o 25 intervention trials. Arch Intern Med. 2010;170(9):821-827. 24. Buchwald H, Varco RL, Matts JP, et al. E ect o partial ileal bypass surgery on mortality and morbidity rom coronary heart disease in patients with hypercholesterolemia. Report o the Program on the Surgical Control o the Hyperlipidemias (POSCH). N Engl J Med. 1990;323(14):946-955. 25. Buchwald H, Rudser KD, Williams SE, et al. Overall mortality, incremental li e expectancy, and cause o death at 25 years in the program on the surgical control o the hyperlipidemias. Ann Surg. 2010;251(6):1034-1040. 26. Basar E, Oguz H, Ozdemir H, et al. Treatment o xanthelasma palpebrarum with argon laser photocoagulation. Argon laser and xanthelasma palpebrarum. Int Ophthalmol. 2004;25(1):9-11. 27. Scheel AK, Schettler V, Koziolek M, et al. Impact o chronic LDL apheresis treatment on Achilles tendon a ection in patients with severe amilial hypercholesterolemia: a clinical and ultrasonographic 3-year ollow-up study. Atherosclerosis. 2004;174(1):133-139. 28. Brunner E, Rees K, Ward K, Burke M, Thorogood M. Dietary advice or reducing cardiovascular risk. Cochrane Database Syst Rev. 2007;(4):CD002128. 29. United States Preventive Services Task Force. Screening for Lipid Disorders in Adults. 2008. http:/ / www.uspreventiveservicestask orce. org/ uspst / uspschol.htm. Accessed January 2012.

13. Studer M, Briel M, Leimenstoll B, Glass TR, Bucher HC. E ect o di erent antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med. 2005;165:725-730.

30. Taylor F, Ward K, Moore THM, et al. Statins or the primary prevention o cardiovascular disease. Cochrane Database Syst Rev. 2011;(1):CD004816.

14. Zhou Z, Rahme E, Pilote L. Are statins created equal? Evidence rom randomized trials o pravastatin, simvastatin, and atorvastatin or cardiovascular disease prevention. Am Heart J. 2006;151:273-281.

31. Pignone MP, Phillips CJ, Lannon CM, et al. Screening for Lipid Disorders. April 2001. http:/ / www.uspreventiveservicestask orce.org/ uspst 08/ lipid/ lipides.pd . Accessed January 2012.

15. Sattar N, Preiss D, Murray HM, et al. Statins and risk o incident diabetes: a collaborative meta-analysis o randomised statin trials. Lancet. 2010;375:735-742.

32. Grady D, Chaput L, Kristo M. Systematic Review of Lipid Lowering Treatment to Reduce Risk of Coronary Heart Disease inWomen. Rockville, MD: Agency or Healthcare Research and Quality; 2003.

16. Abourbih S, Filion KB, Joseph L, et al. E ect o brates on lipid pro les and cardiovascular outcomes: a systematic review. Am J Med. 2009;122:962.e1-e8.

33. Hel and M, Carson S. Screening for Lipid Disorders in Adults: Selective Update of 2001 US Preventive ServicesTask Force Review. June 2008. http:/ / www.ncbi.nlm.nih.gov/ books/ NBK33494/ . Accessed August 2013.

17. Wider B, Pittler MH, Thompson-Coon J, Ernst E. Artichoke lea extract or treating hypercholesterolaemia. Cochrane Database Syst Rev. 2009;(4):CD003335. 18. Becker DJ, Gordon RY, Halbert SC, et al. Red yeast rice or dyslipidemia in statin-intolerant patients: a randomized trial. Ann Intern Med. 2009;150(12):830-839. 19. Liu ZL, Liu JP, Zhang AL, et al. Chinese herbal medicines or hypercholesterolemia. Cochrane Database Syst Rev. 2011;(7):CD008305. 20. Hooper L, Thompson RL, Harrison RA, et al. Risks and bene ts o omega 3 ats or mortality, cardiovascular disease, and cancer: systematic review. BMJ. 2006;332:752-760.

34. Fair KP. Xanthoma treatment and management. In: emedicine. Medscape. http:/ / emedicine.medscape.com/ article/ 1103971treatment# a1128. Accessed August 2013. 35. Cohen DE, Anania FA, Chalasani N; National Lipid Association Statin Sa ety Task Force Liver Expert Panel. An assessment o statin sa ety by hepatologists. Am J Cardiol. 2006;97:C77-C81. 36. Pasternak RC, Smith SC Jr, Bairey-Merz CN, et al; American College o Cardiology American Heart Association National Heart, Lung and Blood Institute. ACC/ AHA/ NHLBI clinical advisory on the use and sa ety o statins. JAm Coll Cardiol. 2002;40:567-572.

PART 17

O Be SIt Y

224 O BESITY Mind y A. Smith, MD, MS

ENDO CRINE • At the 6-year ollow-up o the Nurses’ Health Study (NHS; a prospective cohort study o 50,277 women), 3757 (7.5%) women who had a BMI o less than 30 in 1992 became obese (BMI ≥30). 2 • The yearly medical care costs o obesity in the United States are approximately $147 billion. 3

PATIENT STO RY Diane is a 35-year-old woman who has struggled with obesity or most o her li e. Her current body mass index (BMI) is 36. She has tried “every kind o diet you can imagine” but has always gotten stuck a ter losing the rst 10 lb and gets discouraged. She is not currently exercising regularly. She is concerned about all the skin tags on her neck and wants them removed i possible. You obtain a random blood sugar because o the acanthosis and obesity (Figure 224-1). The result is 150 mg/ dL and you order a asting blood sugar (FBS) be ore her next visit, at which time you will remove her skin tags. A ter discussing diet and exercise, you encourage her to pursue Weight Watchers or a similar program.

INTRO DUCTIO N Obesity is de ned as a BMI greater than or equal to 30. BMI is calculated as weight in kilograms divided by height in meters squared, rounded to 1 decimal place. 1 Adults with a BMI greater than 40 have substantially more serious health consequences, including heart disease and diabetes, and a reduced li e expectancy.

EPIDEMIO LO GY • Based on the National Health and Nutrition Examination Surveys, more than one-third o US adults (35.7%) and 16.9% o children and adolescents are obese (2010). 1 Slightly more women than men are obese (35.8% vs 35.5%). The prevalence o obesity has dramatically increased over the past 20 years.

ETIO LO GY AND PATHO PHYSIO LO GY Obesity is a complex problem involving genetics, health behaviors, environment, and sometimes medical diseases (see “Di erential Diagnosis” later) or drugs (eg, steroids, antidepressants). The simplest explanation o obesity is an imbalance between intake (calories eaten) and output (physical activity). GENETICS The genetic contribution to interindividual variation in common obesity has been estimated at 40% to 70%. 4 Despite this relatively high heritability, the search or obesity susceptibility genes has been di cult. At least 5 variants in 4 candidate genes are associated with obesity-related traits. Although genome-wide linkage studies have been unable to pinpoint genetic loci or common obesity, high-density genome-wide association studies have discovered at least 15 previously unanticipated genetic loci associated with BMI and extreme obesity risk.4 Genetic inf uences, however, cannot explain the recent increased prevalence in the rate o weight gain by age; rather signi cant changes in li estyle actors are likely responsible. 5 • Two gastrointestinal (GI) “hormones” that appear to integrate into the brain may regulate appetite; these hormones—ghrelin (increases appetite) and obestatin (slows gastric emptying, blocking ghrelin action)—may also play a role in obesity. A meta-analysis concluded that obestatin and total and active ghrelin were signi cantly higher in normal weight subjects than those o obese groups.6 It is not clear why this occurs but lower levels o ghrelin in obese subjects may be a response to hyperinsulinemia. HEALTH BEHAVIO RS Li estyle actors associated with obesity include physical activity level (low levels and associated behaviors such as television viewing), diet, and sleep. • In the NHS, each 2-hour per day increment in TV watching was associated with a 23% (95% con dence interval [CI], 17%-30%) and each 2-hour per day increment in sitting at work was associated with a 5% (95% CI, 0%-10%) increase in obesity. 2 • In one study, belie that obesity was inherited was associated with lower reported levels o physical activity and ruit and vegetable consumption while the belie that obesity was caused by li estyle behaviors was associated with greater reported physical activity but not diet. 7 • In a study o Latino men and women, men who did not exercise, rarely trimmed at rom meat, and ate ried oods the previous day were 16 lb heavier than men with healthier habits. 8 Women who had limited exercise (1 cm or >0.8 inch) can alert the clinician to osteoporosis. • Kyphosis and cervical lordosis (dowager’s hump). • Acute pain is o ten the rst symptom rom a racture, usually o the vertebrae (vertebral body collapse), hip or orearm, especially

• Laboratory testing is recommended or women with osteoporosis to identi y secondary causes including a complete blood cell count ( or anemia or malignancy), serum chemistry (calcium, phosphorus, total protein, albumin, liver enzymes, alkaline phosphatase, creatinine, and electrolytes), 24-hour urine collection (calcium, sodium, and creatinine excretion to identi y calcium malabsorption or hypercalciuria), and serum 25-hydroxyvitamin D. 3 • Other laboratory tests may be indicated or patients with suspected secondary causes (eg, serum thyrotropin, erythrocyte sedimentation rate, testosterone, acid-base studies). 3,4 • Central dual-energy X-ray absorptiometry (DEXA) measurement o BMD is the accepted gold standard or diagnosis (T-score less than or equal to –2.5 in the spine, emoral neck, or hip in the absence o racture) (Figures 225-4 and 225-5). • Additional imaging with X-ray can con rm osteoporosis-related racture (see Figures 225-1 and 225-3). • The presence o a hip or vertebral racture in the absence o other bone conditions can also be considered as osteoporosis. 3 Two types o hip ractures related to osteoporosis are emoral neck ractures (Figure 225-6) and intertrochanteric ractures.

PART 17

O St e O pO r O SIS a ND O St e O pe NIa

ENDO CRINE

TABLE 225-1 Factors Associate d With O ste op orosis

Ge ne t ic fact o rs White or Asian e thnicity Family history of oste op orosis * Low b od y we ig ht ( 2 U/d )* GI, g astrointe stinal GnRH, g onad otrop in-re le asing hormone . * Also risk factors for oste op orosis-re late d fracture s. Data from Kap lan-Machlis B, Bors KP, Brown SR. O ste op orosis. In: Smith MA, Shimp LA, e d s. Twe nty Common Prob le ms in Wome n’s He alth Care . Ne w York, NY: McGraw Hill; 2000; O ste op orosis. In: Eb e ll MH, Fe re nchik G, Smith MA, e t al, e d s. Esse ntial Evid e nce Plus. Hob oke n, NJ: John Wile y; 2009; Watts NB, Bile zikian JP, Camacho PM, e t al. Ame rican Association of Clinical End ocrinolog ists me d ical g uid e line s for clinical p ractice for the p re ve ntion and tre atme nt of p ostme nop ausal oste op orosis: 2010 e d ition. End ocr Pract. 2010;16(sup p l 3):1-37.

DIFFERENTIAL DIAGNO SIS Thoracic kyphosis o recent onset in adults can also be caused by the ollowing: • Degenerative arthritis o the spine—Pain and swelling in other joints, morning sti ness • Ankylosing spondylitis—Male gender, night pain, and limited motion in sacroiliac joints, uveitis • Tuberculosis (TB) and other in ections o the spine—History o TB, positive cultures, X-ray showing joint destruction (see Chapter 64, Tuberculosis) • Cancer—History o cancer, imaging distinguishes

MANAGEMENT NO NPHARMACO LO GIC • Identi y and treat secondary causes (see Table 225-1). FIGURE 225-3 We d g e comp re ssion fracture of T11 ve rte b ra in a p ostme nop ausal woman on long -te rm p re d nisone for d e rmatomyositis. The p atie nt p re se nte d with acute b ack p ain. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Dietary advice includes adequate calcium, vitamin D, and protein intake. 3 SO R B • Recommend regular weight-bearing exercise. 3 Institute or Clinical Systems Improvement (ICSI) notes that 3 components o an exercise

1143

PART 17

1144

ENDO CRINE

Ch a pt e r 225

FIGURE 225-4 Dual-e ne rg y X-ray ab sorp tiome try b one d e nsity scan showing oste op orosis in the ve rte b ral sp ine showing 5% loss of ve rte b ral b one d e nsity in 1 ye ar. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

program are needed or strong bone health: impact exercise (eg, jogging, brisk walking, stair climbing), strengthening exercise with weights, and balance training such as Tai Chi or dancing. 4 • Encourage smoking cessation and moderate alcohol use (< 3 drinks per day). 3 SOR B • Hip protectors may reduce hip ractures in the nursing home. 7 SO R B • Address other risk actors or alling (eg, low vision, gait disturbance, use o sedatives) and consider re erral or physical or occupational therapy, i indicated. MEDICATIO NS • Calcium (1200 mg/ d rom diet plus supplement) and vitamin D (at least 800 IU/ d). 8,9 SO R A One study ound that a single large dose o vitamin D (100,000 IU given orally every 4 months) over 5 years reduced ractures in elderly British women (NNT = 20). 10 • Women with osteoporosis or previous hip or spine ractures should receive medication therapy, beginning with a bisphosphonate. 3,4 Women should also be considered or medication i they have a T-score o between –1.0 and –2.5, i FRAX major osteoporotic racture

probability is equal to or greater than 20%, or hip racture probability is equal to or greater than 3%. 3 • First-line agents include alendronate, risedronate, and zoledronic acid. SOR A Based on a Cochrane review o 11 studies, use o alendronate prevented hip (absolute risk reduction [ARR] 1%), vertebral (ARR 6%), and nonvertebral ractures (ARR 2%). 11 Potential side e ects o bisphosphonates include rare atypical emoral sha t racture (0.13% in the subsequent year or women with at least 5 years o treatment)12 and jaw osteonecrosis (0.7 per 100,000 patient-years with oral bisphosphonate therapy). 13 • Other drug therapies approved by the US FDA to reduce ractures include parathyroid hormone (PTH, teriparatide [eg, Forteo]), raloxiene (a selective estrogen receptor modulator [SERM]), and estrogen (women only). The ICSI recommends PTH as a rst-line agent or patients with the highest racture risk. Second-line agents recommended by American Association o Clinical Endocrinologists (AACE) are ibandronate and raloxi ene. 3 Choice o second-line medications should be based on the patient’s clinical situation, pre erences, and the tradeo between bene ts and harms. AACE recommends against combination therapy. SO R B

PART 17

O St e O pO r O SIS a ND O St e O pe NIa

ENDO CRINE

FIGURE 225-5 Dual-e ne rg y X-ray ab sorp tiome try b one d e nsity scan showing oste op orosis of the hip s with 2% g ain of b one d e nsity in 1 ye ar. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• The irst-line agents listed above or treatment o osteoporosis have been approved or use in men as well as women; however, data are limited or men, especially or racture reduction. In a randomized controlled trial (RCT) o 265 men on glucocorticoid therapy, both risedronate and zoledronic acid prevented bone loss in the prevention population while zoledronic acid increased BMD slightly more than risedronate (4.7% vs 3.3% lumbar spine and 1.8% vs 0.2% total hip, respectively) in the treatment group. 14 • Denosumab is a human monoclonal antibody that inhibits osteoclastmediated bone resorption; denosumab was shown to reduce new vertebral ractures in women with multiple and/ or severe prevalent vertebral ractures (ARR 9.1%) and hip ractures in subjects age 75 years or older (ARR 1.4%). Both denosumab and zoledronic acid appear to reduce racture risk in men with castration-resistant prostate cancer metastatic to bone and denosumab and toremi ene (a SERM) reduced osteoporotic racture risk in men on androgen-deprivation treatment. 15 Denosumab has not been compared with bisphosphonates or other interventions. AACE considers this a rst-line agent but it is very

expensive. 3 SO R A Risks o treatment include endocarditis, cancer, and skin rash. • Nasal calcitonin may preserve BMD and reduce new vertebral ractures; this drug also has an analgesic e ect or some women with painul acute vertebral ractures. 16 AACE recommends calcitonin as a last line o therapy or treatment o osteoporosis. 3 CO MPLEMENTARY AND ALTERNATIVE THERAPY Limited data support use o phytoestrogens, synthetic isof avones such as iprif avone or natural progesterone cream or prevention or treatment o osteoporosis. A 2-year multicenter, randomized trial o iprif avone showed some e ect on total body BMD but no signi cant e ect on regional bone density at common racture sites. 17 REFERRAL AACE recommends re erral o patients to a clinical endocrinologist i a patient with a normal BMD sustains a low-trauma racture, has recurrent ractures or continued bone loss despite therapy, has unexpectedly severe

1145

PART 17

1146

ENDO CRINE

Ch a pt e r 225

treatment i BMD declines substantially, bone turnover markers increase, or a racture occurs.

PATIENT EDUCATIO N • Encourage home-based all prevention by removing throw rugs, reducing clutter in high tra c areas, increasing lighting, use o sa ety step stools and sa ety hand rails in the bathroom, and walking aids. • Encourage healthy li estyle and diet. PATIENT RESO URCES

• MedlinePlus. Osteoporosis—http:/ / www.nlm.nih.gov/ medlineplus/ osteoporosis.html. • MedlinePlus. Kyphosis—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 001240.htm. FIGURE 225-6 Fe moral ne ck fracture (arrow) in an e ld e rly woman with oste op orosis. The woman fe ll on he r le ft hip whe n coming out of the showe r. (Re p rod uce d with p e rmission from Re b e cca Lore d o-He rnand e z, MD.)

osteoporosis or unusual eatures, or has a complicating condition (eg, renal ailure). 3 SO R C

PREVENTIO N AND SCREENING • The AACE guideline recommends adequate calcium and vitamin D intake to reduce bone loss. 3 SO R A Maintaining an active li estyle SO R B , smoking cessation SO R B , limiting alcohol intake SO R B , and limiting ca eine intake SO R C are also recommended. • The United States Preventive Services Task Force (USPSTF) and AACE recommend screening or osteoporosis or women 65 years o age and older and or younger women whose racture risk is the same as or greater than that o a 65-year-old white woman who has no additional risk actors (9.3% risk over 10 years). 2 • Screening should be done with DEXA o the hip or lumbar spine or quantitative ultrasonography o the calcaneus; appropriate cuto s or diagnosis and treatment using ultrasound, however, have not been established. Other guidelines have similar risk-based recommendations, although the age o initial assessment (all adults, adults age 50 years, or postmenopausal women) di ers and the groups do not recommend use o ultrasound or screening. 18 • Bisphosphonate therapy should be considered in patients starting glucocorticoid therapy planned or over 3 months and those on chronic glucocorticoid therapy i their T-score is less than –1.0. 19

FO LLO W-UP • Repeat DEXA (same machine i possible) every 1 to 2 years until ndings are stable and then continue with ollow-up DEXA every 2 years or less (see Figures 225-4 and 225-5). 3,4 • Consider discontinuation o a bisphosphonates a ter 4 to 5 years o stability or a ter 10 years o stability or high-risk patients. 3 Reinstitute

• Osteoporosis Foundation—http:/ / www.no .org/ . PRO VIDER RESO URCES

• National Institute of Arthritis and Musculoskeletal and Skin Diseases. The NIH Osteoporosis and Related Bone Diseases National Resource Center—http:/ / www.niams.nih.gov/ Health_In o/ Bone/ de ault.asp. • American Association of Clinical Endocrinologists. Medical Guidelines for Clinical Practice for the Diagnosis and Treatment for Postmenopausal Osteoporosis—https:/ / www.aace.com/ f les/ osteo-guidelines-2010.pd . • The FRAX tool has been developed by the World Health Organization (WHO) to evaluate racture risk o patients. It can be very help ul in making treatment choices: http:/ / www.she .ac.uk/ FRAX/ . It is also available as an iTunes app. REFERENCES 1. The WHO Study Group. Assessment of Fracture Risk and Its Application to Screening for Postmenopausal Osteoporosis. Technical Report Series. No. 843. Geneva, Switzerland: World Health Organization; 1994. 2. U.S. Preventive Services Task Force. Screening or osteoporosis: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2011;154(5):356-364. 3. Watts NB, Bilezikian JP, Camacho PM, et al. American Association o Clinical Endocrinologists medical guidelines or clinical practice or the prevention and treatment o postmenopausal osteoporosis: 2010 edition. Endocr Pract. 2010;16(suppl 3):1-37. https:/ / www .aace.com/ les/ osteo-guidelines-2010.pd . Accessed August 2013. 4. Institute or Clinical Systems Improvement (ICSI). Diagnosis and Treatment of Osteoporosis. http:/ / www.guideline.gov/ content.aspx?id =34270&search=osteoporosis. Accessed August 2013. 5. Kanis JA, Borgstrom F, De Laet C, et al. Assessment o racture risk. Osteoporos Int. 2005;16:581-589. 6. Mauck KF, Cuddihy MT, Atkinson EJ, Melton LJ 3rd. Use o clinical prediction rules in detecting osteoporosis in a population-based sample o postmenopausal women. Arch Intern Med. 2005;165:530-536. 7. Sawka AM, Boulos P, Beattie K, et al. Hip protectors decrease hip racture risk in elderly nursing home residents: a bayesian metaanalysis. J Clin Epidemiol. 2007;60:336-344.

O St e O pO r O SIS a ND O St e O pe NIa

PART 17

ENDO CRINE

8. Bischo -Ferrari HA, Willett WC, Wong JB, et al. Prevention o nonvertebral ractures with oral vitamin D dose dependency. A meta-analysis o randomized controlled trials. Arch Intern Med. 2009;169(6):551-561.

14. Sambrook PN, Roux C, Devogelaer JP, et al. Bisphosphonate and glucocorticoid osteoporosis in men: results o a randomized controlled trial comparing zoledronic acid with risedronate. Bone. 2012;50(1):289-295.

9. Avenell A, Gillespie WJ, Gillespie LD, O’Connell D. Vitamin D and vitamin D analogues or preventing ractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev. 2009;(2):CD000227.

15. Saylor PJ, Lee RJ, Smith MR. Emerging therapies to prevent skeletal morbidity in men with prostate cancer. J Clin Oncol. 2011;29(27):3705-3714.

10. Trivedi DP, Doll R, Khaw KT. E ect o our monthly oral vitamin D3 (cholecalci erol) supplementation on ractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326:469-472. 11. Wells GA, Cranney A, Peterson J, et al. Alendronate or the primary and secondary prevention o osteoporotic ractures in postmenopausal women (Cochrane Review). Cochrane Database Syst Rev. 2008;(1):CD001155. 12. Park-Wyllie LY, Mamdani MM, Juurlink DN, et al. Bisphosphonate use and the risk o subtrochanteric or emoral sha t ractures in older women. JAMA. 2011;305:783-789. 13. Ruggiero SL, Dodson TB, Assael LA, et al. Association o Oral and Maxillo acial Surgeons. American Association o Oral and Maxillo acial Surgeons position paper on bisphosphonate-related osteonecrosis o the jaws. J Oral Maxillofac Surg. 2009; 67(suppl 5):2-12.

16. Chesnut CH, Silverman S, Andriano K, et al. A randomized trial o nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence o osteoporotic ractures study. Am J Med. 2000;109:267-276. 17. Wong WW, Lewis RD, Steinberg FM, et al. Soy isof avone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial. Am J Clin Nutr. 2009;90(5):1433-1439. 18. Guideline synthesis. Screening and Risk Assessment for Osteoporosis in PostmenopausalWomen. http:/ / www.guideline.gov/ syntheses/ synthesis. aspx?id=38658&search=osteoporosis. Accessed August 2013. 19. Recommendations or the prevention and treatment o glucocorticoid-induced osteoporosis: 2001 update. American College o Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum. 2001;44:1496-1503.

1147

PART 17

1148

ENDO CRINE

Ch a pt e r 226

226 HYPO THYRO IDISM Mind y A. Smith, MD, MS

PATIENT STO RY A 55-year-old woman presented with a several-month history o atigue and weight gain. She reported that she elt pu y and swollen. She had di culty buttoning the top button o her blouse because her neck was so large, but she reported no neck pain. Review o systems was positive or constipation, dry skin, and cold intolerance. On physical examination, a large goiter was ound (Figure 226-1). Laboratory testing revealed an elevated thyroidstimulating hormone (TSH) and a low ree thyroxine (FT4) level con rming hypothyroidism. The patient was started on levothyroxine.

INTRO DUCTIO N

FIGURE 226-2 Massive g oite r in an Ethiop ian woman who live s in an e nd e mic are a or g oite rs. Many ad ults have larg e g oite rs in Ethiop ia whe re the re is little iod ine in the ir d ie ts. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Goiter is a spectrum o changes in the thyroid gland ranging rom di use enlargement to nodular enlargement depending on the cause. In the United States, the most common etiology o goiter with normal thyroid unction or transient dys unction is thyroiditis.

• Most goiters are not associated with thyroid dys unction.

• Hypothyroidism is a condition caused by lack o thyroid hormone and usually develops as a result o thyroid ailure rom intrinsic thyroid disease. The most common cause o goitrous hypothyroidism is chronic lymphocytic (Hashimoto) thyroiditis.

• Subclinical hypothyroidism is present in 3% to 10% o population groups and in 10% to 18% o elderly persons. 2,3

• Subclinical thyroid disease re ers to a patient with no or minimal thyroid-related symptoms but abnormal laboratory values (elevated TSH and thyroxine level within the normal range).

EPIDEMIO LO GY • Worldwide, goiter is the most common endocrine disorder with rates o 4% to 15% in areas o adequate iodine intake and more than 90% where there is iodine de ciency. 1 Endemic goiter is de ned as goiter that a ects more than 5% o the population (Figure 226-2).

• The prevalence o goitrous hypothyroidism varies rom 0.7% to 4% o the population.

• The emale-to-male ratio o goiter is 3:1, and 6:1 or goitrous hypothyroidism. • The annual incidence o autoimmune hypothyroidism is 4 in 1000 women and 1 in 1000 men, with a mean age at diagnosis o 60 years. 4

ETIO LO GY AND PATHO PHYSIO LO GY Following are the contributing actors or goiter: • Iodine de ciency or excess (see Figure 226-2) • TSH stimulation • Drugs, including lithium, amiodarone, and α -inter eron • Autoimmunity/ heredity Hypothyroidism may be caused by disease o the thyroid gland itsel (eg, Hashimoto thyroiditis), radioiodine thyroid ablation, thyroidectomy, high-dose head and neck radiation therapy, and medications (as above), or, rarely, by pituitary or hypothalamic disorders (eg, tumors, inf ammatory conditions, in ltrative diseases, in ections, pituitary surgery, pituitary radiation therapy, and head trauma). 2 • Hashimoto thyroiditis is caused by thyroid peroxidase (TPO) antibodies. • Human leukocyte antigen-D related (HLA-DR) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) are the best-documented genetic risk actors or this disorder. 4 • There is marked lymphocytic in ltration o the thyroid in Hashimoto thyroiditis; the in ltrate is composed o activated CD4+ and CD8+ T cells, as well as B cells.

FIGURE 226-1 Goite r that e xte nd s ap p roximate ly 2 cm orward whe n vie we d rom the p atie nt’s sid e . (Re p rod uce d with p e rmission from Dan Stulb e rg , MD.)

• Thyroid destruction in Hashimoto thyroiditis is believed to be primarily mediated by CD8+ cytotoxic T cells.

PART 17

h YpO t h Yr O IDISM

A

ENDO CRINE

B

FIGURE 226-3 A. A 36-ye ar-old woman with larg e g oite r. B. The re se cte d g oitrous thyroid g land . (Re p rod uce d with p e rmission from Frank Mille r, MD.)

RISK FACTO RS Risk actors or hypothyroidism include the ollowng2: • Symptoms o thyroid hormone de ciency • Goiter • Personal or amily history o thyroid disease • Personal treatment o thyroid disease • History o autoimmune disease, especially diabetes mellitus • High-dose head and neck radiation therapy Myxedema coma usually occurs in elderly patients with untreated or inadequately treated hypothyroidism who develop a precipitating event, such as myocardial in arction, stroke, sepsis, or prolonged cold exposure. 2 FIGURE 226-4 Massive multinod ular g o ite r b e ore surg e ry. (Re p ro d uce d with p e rmission from Frank Mille r, MD.)

DIAGNO SIS CLINICAL FEATURES The history can be the key to the diagnosis: • A pain ul neck mass is usually a orm o thyroiditis. • Large goiters are easily visible be ore palpating the neck (Figures 226-1 to 226-4). • Asymmetric goiters can shi t the trachea away rom the midline (Figure 226-5). Following are the common signs and symptoms o hypothyroidism: • Fatigue and/ or weakness. • Dry and cool skin. • Di use hair loss or thinning o the lateral eyebrows. • Di culty concentrating. • Pu y ace/ hands/ eet rom myxedema (Figure 226-6). • Bradycardia.

FIGURE 226-5 Asymme tric multinod ular g oite r causing trache a to d e viate rom the mid line p rior to re se ction. (Re p rod uce d with p e rmissio n from Frank Mille r, MD.)

1149

PART 17

1150

ENDO CRINE

Ch a pt e r 226

• In the uture, re erence limits may need to change as TSH distribution and re erence limits have been shown to shi t to higher concentrations with age and are unique or di erent racial/ ethnic groups. 7

DIFFERENTIAL DIAGNO SIS Goiter presenting as a pain ul neck mass is most commonly caused by subacute granulomatous (de Quervain) thyroiditis (likely viral) or hemorrhage into a thyroid cyst or adenoma. Other causes include the ollowing: • Pain ul Hashimoto thyroiditis—Hypothyroidism with the presence o antibodies helps to con rm this diagnosis. • In ected thyroglossal duct or branchial cle t cyst—Mass palpates as cystic and may be f uctuant; ocal (eg, erythema and warmth) and systemic symptoms o in ection (eg, ever) may be present. Even a noninected thyroglossal duct cyst can be con used or an enlarged thyroid (Figure 226-7). • Acute suppurative thyroiditis (microbial)—Focal (eg, erythema and warmth) and systemic symptoms o in ection (eg, ever) are usually present. FIGURE 226-6 Myxe d e ma o the ace with p u f ne ss aro und the e ye . (Re p rod uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

• Thyroid carcinoma—Hard mass within thyroid gland (Figure 226-8). Painless goiter and hypothyroidism are most o ten caused by Hashimoto thyroiditis, but may also be caused by the ollowing:

• Delayed deep tendon ref ex relaxation.

• Environmental goitrogens (eg, excess iodine, oods such as cassava, cabbage, and soybeans).

• Weight gain despite poor appetite.

• Iodine de ciency.

• Constipation.

• Pharmacologic inhibition (rare)—Drugs include lithium, amiodarone, and inter eron-α .

• The most use ul signs or diagnosing hypothyroidism are pu ness (likelihood ratio positive [LR+ ] 16.2) and delayed ankle ref ex (LR+ 11.8). 5 Clues to a central cause o hypothyroidism include a history o pituitary/ hypothalamic surgery or radiation, headache, visual eld de ects, or ophthalmoplegia. 2 Physical examination maneuvers that help detect goiter are as below6: • Neck extension

Painless goiter and hyperthyroidism may be caused by the ollowing: • Graves disease (common, 0.5%-2.5% o the population)—Symptoms o nervousness, atigue, weight loss, heat intolerance, palpitations, and exophthalmus (see Chapter 227, Hyperthyroidism). • Postpartum thyroiditis (2%-16% within 3-6 months o delivery)— Recent delivery.

• Observation rom the side • Palpation by locating the isthmus rst • Having the patient swallow • Myxedema coma LABO RATO RY STUDIES Laboratory tests include an erythrocyte sedimentation rate (ESR) i thyroiditis is suspected, and TSH (elevated in hypothyroidism and subclinical disease) and FT4 levels (low in hypothyroidism). • In acute granulomatous thyroiditis, ESR is greater than 50 (LR+ 95) and the TSH and FT4 are usually normal. • In primary hypothyroidism, the TSH is greater than 10 mU/ L (LR+ 16) and FT4 is less than 8 (LR+ 11). • The presence o antibodies to TPO and thyroglobulin help establish the diagnosis o Hashimoto thyroiditis but is unnecessary or treatment. TPO antibodies will be positive in 90% to 95% o patients. 4 • In pituitary causes o hypothyroidism (central hypothyroidism), the TSH may be normal or elevated but FT4 will be low. 2

FIGURE 226-7 Thyrog lossal d uct cyst in the mid line sup e rior to the thyroid . (Re p rod uce d with p e rmissio n from Frank Mille r, MD.)

PART 17

h YpO t h Yr O IDISM

ENDO CRINE Patients with Hashimoto thyroiditis and low FT4 are treated with levothyroxine as ollows: • Younger patients start with 50 to 100 µg/ d increasing by 25 to 50 µg/ d at 6- to 8-week intervals until the TSH is normal (approximately 1.6 µg/ kg per day o levothyroxine). 2,8 SOR B • Older patients or those with cardiac disease start with 25 µg/ d and increase by 12.5 to 25 µg/ d every 6 to 8 weeks to normalize the TSH (approximately 1 µg/ kg per day o levothyroxine). SOR C • Dosing in the evening appears to normalize the laboratory values more e ectively, but in one study, did not inf uence symptoms or quality o li e. 2,10 A Cochrane review o 12 small randomized controlled trials (RCTs) determined that treatment o subclinical hypothyroidism did not improve survival or decrease cardiovascular morbidity. 11

FIGURE 226-8 A 93-ye ar-old woman with thyroid cance r that we nt untre ate d or 3 ye ars. Two larg e f rm masse s are visib le in the ne ck. (Re p ro d uce d with p e rmission from Dustin Williams, MD.)

• Toxic nodular goiter (uncommon)—Usually in the elderly; thyroid gland eels nodular (see Figure 226-4) and thyroid scan shows multiple oci o increased uptake.

• Patients with subclinical hypothyroidism should be considered or treatment i they have symptoms o thyroid de ciency, are at high likelihood o progression to hypothyroidism (eg, TSH >10 mIU/ L), or are pregnant.2,3 • For patients with TSH levels o 5 to 10 mIU/ L, other actors to consider in a treatment decision include presence o goiter, bipolar disorder or depression, in ertility or ovulatory dys unction, presence o antithyroid antibodies, young age, patient pre erence, and possibly hyperlipidemia. 3 • A dose o 50 to 75 µg/ d is usually su cient or those with subclinical hypothyroidism. SO R C

MANAGEMENT NO NPHARMACO LO GIC For nonendemic goiter, identi y and remove goitrogens. MEDICATIO NS Patients with endemic goiter should be provided with iodine. For nonendemic goiter, also consider the ollowing: • TSH suppression with levothyroxine (1-2.2 mg/ kg/ d) (variable but limited e ect on goiter size and can cause hyperthyroidism). 8 SO R

B

• Radioactive iodine treatment i enough unctioning tissue is present. SOR C

Treat patients with acute microbial thyroiditis with antibiotics against the most common pathogens (ie, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae). Alternative agents, used or 7 to 10 days, include the ollowing: SO R C • Amoxicillin/ clavulanate (500 mg 3 times daily) • A rst- or second-generation cephalosporin (eg, cephalexin 500 mg 4 times daily) • Penicillinase-resistant penicillin (eg, dicloxacillin 500 mg 4 times daily) In patients with subacute thyroiditis ollowing are the treatments: • Oral corticosteroids can reduce pain and swelling. SO R C • Symptoms o hyperthyroidism can be treated with β-blockers or calcium channel blockers. 9 SO R B • Symptoms o hypothyroidism can be treated with levothyroxine. 8 SOR B

REFERRAL • Large goiters that impinge on the trachea or do not respond to medications may be treated with surgery (see Figure 226-3). • Subtotal thyroidectomy can be considered or nodular goiters but recurrence rates can be high. 12 SOR A • Consultation with an endocrinologist may be help ul i the diagnosis is uncertain and or patients with central hypothyroidism, severe hypothyroidism (ie, myxedema coma), or coexisting cardiovascular disease. 2 • Patients with myxedema coma should be hospitalized in an intensive care unit; without treatment, mortality approaches 100%.

PREVENTIO N AND SCREENING • There is insu cient evidence to support screening or hypothyroidism.13 • One expert panel recommended TSH testing in women with symptoms o thyroid dys unction, personal or amily history o thyroid disease, an abnormal thyroid gland on palpation, or type 1 diabetes mellitus or other autoimmune disorders. 14 In support o this approach, a clinical trial o universal screening versus case nding did not demonstrate a di erence in adverse outcomes; however, treatment o women with thyroid dys unction identi ed by screening a low-risk group was associated with a lower rate o adverse outcomes. 15

PRO GNO SIS • In the most extensive community survey on goiter (Whickham, England), goiter was present in 15.5% o the population. 1 At the 20-year ollow-up, 20% o women and 5% o men no longer had goiter and 4% o women and no men had acquired a goiter.

1151

PART 17

1152

ENDO CRINE

Ch a pt e r 226

• Suppression o TSH with levothyroxine e ectively reduces the goiter o Hashimoto thyroiditis and should be continued inde nitely. In one study, withdrawal o medication a ter 1 year resulted in only 11.4% remaining euthyroid. 16

4. Jameson JL, Weetman AP. Disorders o the thyroid gland. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds. Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2005:2109-2113.

• Large goiter, TSH greater than 10 mU/ L, and a amily history o thyroid disease are associated with ailure to recover normal thyroid unction and treatment should continue inde nitely.

5. Zulewski H, Müller B, Exer P, et al. Estimation o tissue hypothyroidism by a new clinical score: evaluation o patients with various grades o hypothyroidism and controls. J Clin Endocrinol Metab. 1997;82:771-776.

• In patients with subclinical hypothyroidism, progression to clinically overt hypothyroidism is 2.6% each year i TPO antibodies are absent, and 4.3% i they are present. 17

FO LLO W-UP • TSH should be rechecked approximately 6 to 8 weeks a ter initiation o levothyroxine therapy and again in 4 to 6 months i normal, and annually therea ter unless otherwise clinically indicated. 18 SOR C • Although the need or thyroid replacement is li elong, dose requirements may change over time. Thyroxine dose may need to be increased during pregnancy (20%-40%), with use o estrogens, or in situations o weight gain, malabsorption, Helicobacter pylori-related gastritis and atrophic gastritis and with use o some medications. Requirements may decrease with increased age, androgen use, reactivation o Graves disease, or the development o autonomous thyroid nodules. 2 • There is some evidence that use o ultrasound can help predict progression to overt hypothyroidism in patients with subclinical hypothyroidism19; in one study, patients with TPO antibodies and/ or ultrasound abnormalities had a greater progression to overt disease than those without either nding (31.2% vs 9.5% at 3 years). 20 • The requency o other autoimmune disease is increased in patients with Hashimoto thyroiditis (14.3% in one study), including rheumatoid arthritis, pernicious anemia, systemic lupus erythematosus, Addison disease, celiac disease, and vitiligo, and increased monitoring should be considered. 21 PATIENT RESO URCES

• Information from the American Thyroid Association—http:/ / www.thyroid.org/ patient-thyroid-information/ . • Web-based resources—http:/ / www.nlm.nih.gov/ medlineplus/ thyroiddiseases.html. PRO VIDER RESO URCES

• Baskin HJ, Cobin RH, Duick DS, et al; American Association o Clinical Endocrinologists. American Association o Clinical Endocrinologists medical guidelines or clinical practice or the evaluation and treatment o hyperthyroidism and hypothyroidism. Endocr Pract. 2002;8(6):457-469. REFERENCES 1. Wang C, Crapo LM. The epidemiology o thyroid disease and implications or screening. Endocrinol Metab Clin North Am. 1997;26(1):189-218. 2. McDermott MT. In the clinic. Hypothyroidism. Ann Intern Med. 2009;151(11):ITC61. 3. Fatourechi V. Subclinical hypothyroidism: an update or primary care physicians. Mayo Clin Proc. 2009;84(1):65-71.

6. Siminoski K. Does this patient have a goiter? JAMA. 1995;273(10):813-819. 7. Surks MI, Boucai L. Age- and race-based serum thyrotropin re erence limits. J Clin Endocrinol Metab. 2010;95(2):496-502. 8. Zelmanovitz F, Genro S, Gross JL. Suppressive therapy with levothyroxine or solitary thyroid nodules: a double-blind controlled clinical study and cumulative meta-analyses. J Clin Endocrinol Metab. 1998;3:3881-3885. 9. Singer PA, Cooper DS, Levy EG, et al. Treatment guideline or patients with hyperthyroidism and hypothyroidism. JAMA. 1995;273(10):808-812. 10. Bolk N, Visser TJ, Nijman J, et al. E ects o evening vs morning levothyroxine intake: a randomized double-blind crossover trial. Ann Intern Med. 2010;170(22):1996-2003. 11. Villar HCCE, Saconato H, Valente O, Atallah ÁN. Thyroid hormone replacement or subclinical hypothyroidism. Cochrane Database Syst Rev. 2007;(3):CD003419. 12. Rojdmark J, Jarhult J. High long term recurrence rate a ter subtotal thyroidectomy or nodular goitre. Eur J Surg. 1995;161:725-727. 13. United States Preventive Services Task Force. Screening forThyroid Disease. http:/ / www.uspreventiveservicestask orce.org/ uspst / uspsthyr.htm. Accessed August 2013. 14. Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scienti c review and guidelines or diagnosis and management. JAMA. 2004;291:228-238. 15. Negro R, Schwartz A, Gismondi R, et al. Universal screening versus case nding or detection and treatment o thyroid hormonal dysunction during pregnancy. J Clin Endocrinol Metab. 2010;95(4): 1699-1707. 16. Comtois R, Faucher L, Laf eche L. Outcome o hypothyroidism cause by Hashimoto’s thyroiditis. Arch Intern Med. 1995;155(13):1404-1408. 17. Vanderpump MP, Tunbridge WM, French JM, et al. The incidence o thyroid disorders in the community: a twenty-year ollow-up o the Whickham Survey. Clin Endocrinol (Oxf). 1995;43(1):55-68. 18. Wirsing N, Hamilton A. How o ten should you ollow up on a patient with newly diagnosed hypothyroidism? J Fam Pract. 2009;58(1):40-41. 19. Shin DY, Kim EK, Lee EJ. Role o ultrasonography in outcome prediction in subclinical hypothyroid patients treated with levothyroxine. Endocr J. 2010;57(1):15-22. 20. Rosário PW, Bessa B, Valadão MM, Purisch S. Natural history o mild subclinical hypothyroidism: prognostic value o ultrasound. Thyroid. 2009;19(1):9-12. 21. Boelaert K, Newby PR, Simmonds MJ, et al. Prevalence and relative risk o other autoimmune diseases in subjects with autoimmune thyroid disease. Am J Med. 2010;123(2):183.e1-e9.

PART 17

h Ype r t h Yr O IDISM

227 HYPERTHYRO IDISM Mind y A. Smith, MD, MS

PATIENT STO RY A 29-year-old woman presents with anxiety, palpitations, insomnia, and atigue. She also reports eeling warm all the time. On physical examination she is ound to have a di usely enlarged thyroid gland without any palpable nodules. (Figure 227-1). She also has bilateral proptosis. A ne tremor is detected with her hands outstretched and her deep tendon

A

ENDO CRINE ref exes are brisk. Her skin eels warm and somewhat moist. Her resting pulse is 120 beats/ min. The clinical diagnosis is clearly Graves disease (GD) and the patient is started on propranolol 40 mg bid to treat her symptoms. Laboratory testing reveals a low thyroid-stimulating hormone (TSH) and an elevated ree thyroxin level (T4) to con rm the diagnosis o hyperthyroidism. The patient reports eeling much improved on the β-blocker and chooses radioactive iodine or the de nitive treatment o the Graves disease. Her thyroid scan showed a di usely enlarged thyroid gland (5 times normal) with increased uptake (54%) (Figure 227-2) con rming Graves disease. The patient is treated with an appropriate dose o radioactive iodine (RAI) based on the calculations per ormed in the nuclear medicine department. Her TSH is ollowed periodically and 1 year later she required levothyroxine treatment.

B

C FIGURE 227-1 Grave s d ise ase p re se nting in a 29-ye ar-old A rican Ame rican woman with the typ ical symp toms o anxie ty, p alp itations, e e ling warm, and ushe d . A. Note the d i use ly e nlarg e d thyroid g land . B. Goite r se e n rom the sid e . C. Prop tosis se cond ary to the Grave s d ise ase . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

1153

PART 17

1154

ENDO CRINE

Ch a pt e r 227

ETIO LO GY AND PATHO PHYSIO LO GY • The hyperthyroidism o GD results rom circulating immunoglobulin (Ig) G antibodies that stimulate the TSH receptor. 2 These antibodies are synthesized in the thyroid gland, bone marrow, and lymph nodes. Activation o the TSH receptor stimulates ollicular hypertrophy and hyperplasia causing thyroid enlargement (goiter) and an increase in thyroid hormone production with an increased raction o triiodothyronine (T3) relative to T4 ( rom approximately 20% to up to 30%). 2 • The etiology is seen as a combination o genetic (human leukocyte antigen-D related [HLA-DR] and cytotoxic T-lymphocyte antigen 4 [CTLA-4] polymorphisms) and environmental actors, including physical and emotional stress (eg, in ection, childbirth, li e events). 2 In addition, insulin-like growth actor-1 receptor (IGF-1R)-bearing broblasts and B cells exhibiting the IGF-1R(+) phenotype may be involved in the connective tissue mani estations. 4 Siblings have higher incidence o both GD and Hashimoto thyroiditis (see Chapter 226, Hypothyroidism).

FIGURE 227-2 Nucle ar scan o the thyroid in Grave s d ise ase showing incre ase d up take (54%) in a d i use ly e nlarg e d thyroid g land (5 time s normal with a homog e ne ous p atte rn). (Re p rod uce d with p e rmission fro m Richard P. Usatine , MD.)

INTRO DUCTIO N GD is an autoimmune thyroid disorder characterized by circulating antibodies that stimulate the TSH receptor and resulting in hyperthyroidism. 1

SYNO NYMS GD is also known as thyrotoxicosis (clinical state resulting rom inappropriately high thyroid hormone levels); hyperthyroidism (thyrotoxicosis caused by elevated synthesis and secretion o thyroid hormone).

EPIDEMIO LO GY • GD is a common disorder a ecting 0.5% to 1.2% o the population. • There is a emale-to-male ratio o 5 to 10:1. • Among patients with hyperthyroidism, 60% to 80% have GD; younger patients (younger than age 64 years) with hyperthyroidism are more likely to have GD than are older patients with hyperthyroidism. • Graves ophthalmopathy (see “Clinical Features” later) occurs in more than 80% o patients within 18 months o diagnosis o GD. The ophthalmopathy is clinically apparent in 30% to 50% o patients. 2 • Goiter is present in 90% o patients younger than age 50 years (vs 75% in older patients with GD). 1 • Untreated hyperthyroidism can lead to osteoporosis, atrial brillation, cardiomyopathy, and congestive heart ailure; thyrotoxicosis (thyroid storm) has an associated mortality rate o 20% to 50%. 3

• The ophthalmopathy is believed to result rom an autoimmune response directed toward an antigen shared by the thyroid and the eye’s orbit. There is in ltration o the extraocular muscles by activated T cells, which release cytokines, activating broblasts ( brosis can lead to diplopia) and increasing the synthesis o glycosaminoglycans (water trapping causes swelling). 2

RISK FACTO RS • Family history o thyroid disease, especially in maternal relatives • Smoking (a strong risk actor or Graves ophthalmopathy)

DIAGNO SIS There are several guidelines available or the diagnosis and management o thyroid disease ound under provider resources. CLINICAL FEATURES Symptoms depend on the severity o thyrotoxicosis, duration o disease, and age ( ndings are more subtle in the elderly). More than hal o patients diagnosed with GD have the ollowing common symptoms: • Nervousness • Fatigue • Weight loss • Heat intolerance • Palpitations Signs o disease include the ollowing: • Tachycardia (atrial brillation is common in patients > 50 years o age). 2 • Goiter—Listening over the goiter with a stethoscope may reveal a thyroid bruit (Figure 227-3). • Resting tremor. • Hyperref exia. • Flushing and temporal wasting (Figure 227-4).

h Ype r t h Yr O IDISM

FIGURE 227-3 This 37-ye ar-old wo man has Grave s d ise ase and a loud b ruit ove r he r e nlarg e d hyp e ractive thyroid g land . She was thyrotoxic at this time . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Skin and nail changes include the ollowing: ° Warm, erythematous, moist skin ( rom increased peripheral circulation). ° Palmer erythema. ° Pretibial myxedema—Occurring in a small percentage o patients (0.5%-4%), it consists o nonpitting scaly thickening and induration o the skin usually on the anterior shin and dorsa o the eet (Figures 227-5 and 227-6). 5 It can also appear as a ew welldemarcated pink, f esh-colored, or purple-brown papules or nodules. ° Nails are so t and shiny and may develop onycholysis (distal separation o the nail plate rom the underlying nail bed).

PART 17

ENDO CRINE

FIGURE 227-4 Flushe d skin and te mp oral wasting in this thyrotoxic woman with ne w-onse t Grave s d ise ase . He r thyroid g land was d i use ly e nlarg e d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

and 0.01, respectively. 6 These antibodies are not usually required or diagnosis. • I the clinical picture is uncertain or there is thyroid nodularity, obtain a RAI scan and uptake. 7 Elevated uptake (> 30%) and a homogeneous pattern on scan are diagnostic (see Figure 227-2).

• Eye involvement may occur be ore hyperthyroidism (in 20% o patients) and gradually progresses with only mild discom ort (a gritty sensation with increased tearing is the earliest mani estation). The eye ndings in GD1,2 are as below: ° Lid retraction (drawing back o the eyelid allowing more sclera to be visible) (Figures 227-1 and 227-7). ° Frank proptosis (displacement o the eye in the anterior direction); occurs in one-third (see Figures 227-1 and 227-7). ° It is possible to have unilateral eye involvement with Graves ophthalmopathy (Figure 227-8). ° Extraocular muscle dys unction (eg, diplopia). ° Corneal exposure keratitis or ulcer. ° Periorbital edema, chemosis, and scleral injection. LABO RATO RY TESTING AND IMAGING • With typical symptoms, you can con rm the diagnosis o GD with a low or undetectable sensitive assay or TSH and an elevated ree T4 level. • The presence o TSH receptor antibodies (present in 70%-100% o patients at diagnosis) has a positive and negative likelihood ratio o 247

FIGURE 227-5 Early b ilate ral p re tib ial myxe d e ma in a p atie nt with Grave s d ise ase . The se asymme trical e rythe matous p laq ue s and nod ule s are f rm and nonp itting . (Re p rod uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

1155

1156

PART 17

ENDO CRINE

Ch a pt e r 227

FIGURE 227-8 Woman with unilate ral Grave s op hthalmop athy and vitilig o. The re is a strong association b e twe e n autoimmune thyroid d ise ase s and vitilig o. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.) FIGURE 227-6 Pre tib ial myxe d e ma in a p atie nt with Grave s op hthalmop athy. Hair ollicle s are p romine nt, g iving a p e au d ’orang e ap p e arance . (Re p rod uce d with p e rmission from the Unive rsity of Te xas He alth Scie nce s Ce nte r, Division of De rmatolog y.)

DIFFERENTIAL DIAGNO SIS Other causes o hyperthyroidism are as ollow: • Autonomous unctioning nodule—This is an uncommon cause o thyrotoxicosis (present in 1.6%-9% o patients with hyperthyroidism), 8

and most nodules do not cause hyperthyroidism. These present as a discrete swelling in an otherwise normal thyroid gland, and thyroid scan would show a discrete nodule. • Toxic multinodular goiter—More common cause o hyperthyroidism in the elderly; thyroid scan shows multiple oci o increased uptake. • Thyrotropin-secreting pituitary adenoma (rare)—Adenomas may cause visual disturbance (in the absence o exophthalmos), and other hormonal stimulation may occur (eg, elevated serum prolactin). • Thyroiditis—May be painless or pain ul, short duration, low update on RAI scan. • Exogenous thyroid hormone ingestion—History o overdosage o prescribed or acquired thyroid medication. The di erential diagnoses or the eye ndings include the ollowing: • Metastatic disease to the extraocular muscles. • Pseudotumor—This condition’s rapid onset and pain di erentiate it rom Graves ophthalmopathy.

MANAGEMENT Three options are available to treat the hyperthyroidism: antithyroid drugs, RAI therapy, and surgery, as discussed below. 1,2 SOR A NO NPHARMACO LO GIC Supportive measures or eye symptoms include dark glasses, arti cial tears, propping up the head and taping the eyelids closed at night. MEDICATIO NS

FIGURE 227-7 Bilate ral e xophthalmos that has bee n present or 5 years since patient was diagnosed with Graves disease. Although the radioactive iodine returned her thyroid unction to normal, the exophthalmos continues to bother the patie nt. (Re produced with p ermission from Richard P. Usatine, MD.)

• Symptoms o hyperthyroidism can be controlled with β-adrenergic blockers (eg, propranolol, 10-40 mg bid–qid) or calcium channel blockers (eg, diltiazem, 30-90 mg bid). SOR B Authors o a recent guideline recommend β-adrenergic blockage in elderly patients with symptomatic disease, those who are thyrotoxic with cardiovascular disease or a resting heart rate greater than 90 beats/ min, and prior to RAI treatment in patients with GD at risk or complications o extreme hyperthyroidism (eg, highly symptomatic). 7

PART 17

h Ype r t h Yr O IDISM

• Antithyroid drugs (methimazole 10-20 mg/ d or propylthiouracil [PTU], 100-200 mg every 8 hours). Potential side e ects o these medications include rash, joint pain, liver inf ammation, and, rarely, agranulocytosis. 2 Baseline liver enzymes and complete blood count (CBC) (including white blood cells [WBCs] and di erential) is recommended. 7 Methimazole is pre erred except in patients during the rst trimester o pregnancy, those being treated or thyroid storm, or or those who have reactions to methimazole. 7 • The drug dose may be reduced a ter the patient is euthyroid (typically PTU 50-100 mg/ d and methimazole 2.5-10 mg/ d). • Antithyroid drugs are pre erred during pregnancy and can be considered in patients with mild disease, small goiter, and lower antibody levels. Pretreatment with methimazole prior to RAI is suggested or patients with GD who are at high risk or complications o extreme hyperthyroidism. 7 They are also used more commonly as primary treatment in Europe and Asia. • The optimal duration o titrated antithyroid drug therapy is 12 to 18 months to minimize relapse. 7,9 SO R A • In a randomized controlled trial (RCT) o 159 patients with mild Graves orbitopathy who were given selenium (100 µg twice daily), pentoxi ylline (600 mg twice daily), or placebo (twice daily) orally or 6 months, selenium signi cantly improved quality o li e, reduced ocular involvement, and slowed progression o the disease compared to the other treatments. 10 • Patients with severe (and possibly moderate) Graves orbitopathy are usually treated with a 12-week course o high-dose intravenous glucocorticoid pulses (total < 8 g o methylprednisolone); approximately 80% o patients respond to this regimen. 11,12 Liver ailure is a serious but rare side e ect.

ENDO CRINE • In most cases or patients with GD, pretreatment with methimazole until euthyroid is recommended prior to surgery and levothyroxine is started ollowing surgery. 7 • Following surgery, small remnants o thyroid tissue ( 8 g) have higher rates o recurrent hyperthyroidism (15%). • With respect to the eye ndings, most symptoms except or proptosis improve with control o the hyperthyroidism. In one study, 64% o the patients spontaneously improved, 22% stabilized, and 14% progressed.13 REFERRAL • Patients with signi cant eye symptoms or clinical ndings should be re erred to an ophthalmologist. • Treatment options or the persistent severe ophthalmopathy include high-dose systemic steroids (40-80 mg/ d), orbital radiotherapy, and orbital decompression surgery. 14 SOR B

PRO GNO SIS • With use o antithyroid medications, symptoms improve in 3 to 4 weeks; weight gain (about 4.5 kg) o ten occurs as metabolism normalizes. 2 Remission rates ollowing antithyroid drugs vary rom 37% to 70% and occur within 6 to 8 weeks. • Following RAI, 50% to 75% o patients become euthyroid a ter 5 to 8 weeks, but 50% to 90% o patients with GD eventually become hypothyroid (10%-20% in year 1 and 5% per year a terward). Retreatment with radioiodine may be needed in 14% o patients with GD, 10% to 30% o patients with toxic adenoma, and 6% to 18% o patients with toxic nodular goiter. 3

• RAI—It is the most commonly prescribed treatment in the United States, but is contraindicated in pregnancy or with breast- eeding and should be used with caution in patients with cardiovascular disease.

• In a RCT comparing GD treatments, relapse rates were higher among patients who received antithyroid drugs (approximately 40% [range 34% (elderly) to 42% (young)]) versus patients ollowing RAI (21%) and surgery (5% [3% (young) to 8% (elderly)]). 15

• RAI may also be used a ter initial treatment with antithyroid drugs; these drugs should be discontinued or 3 to 7 days be ore treatment. 2

• Goiter and exophthalmos can persist years a ter the hyperthyroidism has been treated (Figure 227-9).

RADIO THERAPY

• The hal -li e o iodine-131 is about 1 week; however, it is recommended that women not attempt pregnancy or 6 to 12 months a ter RAI treatment. • RAI may cause pain ul thyroid inf ammation or a ew weeks in approximately 1% o patients; this condition can be treated with nonsteroidal anti-inf ammatory agents, β-blockers, and possibly steroids. 3 Approximately 5% o patients with toxic nodular goiter treated with RAI develop GD. 3 • In addition, radiation-induced thyroiditis can aggravate ophthalmopathy. This side e ect can be minimized by early levothyroxine replacement and prednisone (60-80 mg/ d starting at the time o RAI treatment and tapering, a ter 2-4 weeks, over the next 3-12 months). 13 One author believed that moderate-to-severe ophthalmopathy was a contraindication or RAI. 3 SURGICAL TREATMENT • Near-total to total thyroidectomy by a high-volume thyroid surgeon is recommended or patients with GD. 7 • Indications or surgery are very large goiters, presence o suspicious nodules, pregnant women requiring high doses o antithyroid drugs, and allergy or ailure o other therapies.

FO LLO W-UP • The goals o therapy are to resolve hyperthyroid symptoms and to restore the euthyroid state. Close ollow-up is needed in the initial treatment period; medications or symptoms o hyperthyroidism may be withdrawn slowly ollowing treatment. • Antithyroid drug dosages may be reduced a ter the patient is euthyroid (typically PTU 50-100 mg/ d and methimazole 2.5-10 mg/ d), but drugs should be continued or 12 to 18 months to minimize relapse. SOR A • Following treatment with RAI, most patients eventually become hypothyroid (20% within the rst year) and so periodic monitoring o thyroid unction is important. Follow-up within the rst 1 to 2 months ( ree T4 and T3) is recommended and then at 4 to 6 weeks i hyperthyroidism continues; consider retreatment with RAI i there is minimal response at 3 months or hyperthyroidism persists at 6 months. 7 • Following surgery, patients may become hypothyroid or have a recurrence o hyperthyroidism, depending on the size o the remnant remaining; patients should be monitored with periodic blood tests and or symptoms. For those with GD ollowing surgery and levothyroxine, a TSH is recommended at 6 to 8 weeks postoperation. 7

1157

PART 17

1158

ENDO CRINE

A

Ch a pt e r 227

B

FIGURE 227-9 Pe rsiste nt g oite r and e xop hthalmos a te r tre atme nt o Grave s d ise ase with rad ioactive iod ine . Eve n thoug h a p atie nt is no long e r hyp e rthyroid the e nlarg e d thyroid (A) and e ye f nd ing s (B) d o not ne ce ssarily re solve . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• An in-o ce exophthalmometer can be used to track changes in eye prominence over time. 2 • Patients with GD are at high risk or development o other autoimmune disease; in one cross-sectional study in the United Kingdom o patients attending a thyroid clinic, the requency o another autoimmune disorder (eg, rheumatoid arthritis [3.15%], pernicious anemia, systemic lupus erythematosus, Addison disease, celiac disease, and vitiligo) was 9.67% in patients with GD. 16

PATIENT EDUCATIO N • Patients should be told that the goals o therapy are to resolve the symptoms o thyroid excess and to restore the thyroid unction to normal. • The treatment choices should be discussed, as each has advantages and disadvantages; treatment should be individualized. • Regardless o the therapy chosen, long-term ollow-up is needed to monitor thyroid status; there is a high risk o becoming hypothyroid in the uture or to relapse again into hyperthyroidism. Patients should be made aware o symptoms to watch or and to report any recurrent symptoms. • Following RAI, patients should avoid intimate contact (including kissing) and contact with children or 5 days; avoid contact with pregnant women or 10 days (maintain distance o approximately 6 t); limit close contact with other adults to 2 hours or 5 days; sit while voiding and f ush twice with the lid closed; not share toothbrushes, utensils, dishes, towels, or clothes, and wash these separately. 3

PATIENT RESO URCES

• Information from the American Thyroid Association—http:/ / www.thyroid.org/ patient-thyroid-information/ . • National Library of Medicine—http:/ / www.nlm.nih.gov/ medlineplus/ thyroiddiseases.html. • National Graves’ Disease Foundation—http:/ / www.ngdf.org. PRO VIDER RESO URCES

• Bahn RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes o thyrotoxicosis: management guidelines o the American Thyroid Association and the American Association o Clinical Endocrinologists. Thyroid. 2011;21(6):593-641. • Stagnaro-Green A, Abalovich M, Alexander E, et al. American Thyroid Association Task orce on thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081-1125.

REFERENCES 1. Jameson JL, Weetman AP. Disorders o the thyroid gland. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds. Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2005:2109-2113. 2. Brent GA. Graves’ disease. N Engl J Med. 2008;358(24):2594-2605. 3. Ross DS. Radioiodine therapy or hyperthyroidism. N Engl J Med. 2011;364:542-550.

• Ophthalmopathy usually runs its own course independent o the thyroid unction. Additional treatment may be needed in consultation with an ophthalmologist.

4. Douglas RS, Naik V, Hwang CJ, et al. B cells rom patients with Graves’ disease aberrantly express the IGF-1 receptor: implications or disease pathogenesis. J Immunol. 2008;181(8):5768-5774.

• Smoking cessation may have a bene cial e ect on the course o ophthalmopathy.

5. Jabbour SA. Cutaneous mani estations o endocrine disorders. Am J Clin Dermatol. 2003;4(5):315-331.

• Siblings and children should be made aware o their increased risk o developing thyroid disease or associated disorders and should monitor themselves or symptoms.

6. Costagliola S, Marganthaler NG, Hoermann R, et al. Second generation assay or thyrotropin receptor antibodies has superior diagnostic sensitivity or Graves’ disease. J Clin Endocrinol Metab. 1999;84:90-97.

h Ype r t h Yr O IDISM

7. Bahn RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes o thyrotoxicosis: management guidelines o the American Thyroid Association and the American Association o Clinical Endocrinologists. Thyroid. 2011;21(6):593-641. 8. Siegel RD, Lee SL. Toxic nodular goiter—toxic adenoma and toxic multinodular goiter. Endocrinol Metab Clin North Am. 1998;27(1): 151-166. 9. Abraham P, Avenell A, Watson W, et al. Antithyroid drug regimen or treating Graves’ hyperthyroidism. Cochrane Database Syst Rev. 2005;2:CD003420.

PART 17

ENDO CRINE 12. Bartalena L, Baldeschi L, Dickinson AJ, et al. Consensus statement o the European Group on Graves’ Orbitopathy (EUGOGO) on management o Graves’ orbitopathy. Thyroid. 2008;18(3):333-346. 13. Kaplan MM, Meier DA, Dworkin HJ. Treatment o hyperthyroidism with radioactive iodine. Endocrinol Metab Clin North Am. 1998;27(1):205-222. 14. Boulos PR, Hardy I. Thyroid-associated orbitopathy: a clinicopathologic and therapeutic review. Curr Opin Ophthalmol. 2004;15(5): 389-400.

10. Marcocci C, Kahaly GJ, Krassas GE, et al. Selenium and the course o mild Graves’ orbitopathy. N Engl J Med. 2011;364(20): 1920-1931.

15. Törring O, Tallstedt L, Wallin G, et al. Graves’ hyperthyroidism: treatment with antithyroid drugs, surgery, or radioiodine— a prospective, randomized study. J Clin Endocrinol Metab. 1996;81: 2986-2993.

11. Zang S, Ponto KA, Kahaly GJ. Clinical review: Intravenous glucocorticoids or Graves’ orbitopathy: e cacy and morbidity. J Clin Endocrinol Metab. 2011;96(2):320-332.

16. Boelaert K, Newby PR, Simmonds MJ, et al. Prevalence and relative risk o other autoimmune diseases in subjects with autoimmune thyroid disease. Am J Med. 2010;123(2):183.e1-e9.

1159

PART 17

1160

ENDO CRINE

Ch a pt e r 228

228 ACRO MEGALY Mind y A Smith, MD, MS

PATIENT STO RY A 60-year-old man presents to his amily physician with severe headache and weakness (Figure 228-1). He also noted enlargement o his hands (Figure 228-2), which made him remove his wedding ring when it became too tight, and eet (his shoe size had increased). He said his voice seemed to be deeper and his hands eel doughy and sweaty. Laboratory testing reveals an elevated insulin-like growth actor (IGF)-1, and there is a ailure o growth hormone (GH) suppression ollowing an oral glucose load con rming the diagnosis o acromegaly. Computed tomography (CT) scan o the head demonstrates a pituitary adenoma.

FIGURE 228-2 The man in Fig ure 228-1 with acrome g aly p rod ucing hand s that are larg e and d oug hy with wid e ne d f ng e rs. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

INTRO DUCTIO N Acromegaly is a condition o excessive linear and organ growth usually caused by autonomous GH hypersecretion rom a pituitary tumor.

EPIDEMIO LO GY • Rare (5/ 1,000,000 adults). 1 • Most typically caused by a pituitary somatotrope macroadenoma. It may also be caused by growth hormone–releasing hormone (GHRH) excess rom lesions o the pancreas, lung, or ovaries, or rom a chest or abdominal carcinoid tumor.

• The disorder is usually sporadic, but may be amilial (50%). It is considered third-line therapy. 7 Radiation has been used in an attempt to discontinue medical therapy. ° Five-year remission rates rom gamma kni e 7radiotherapy (a ter surgical debulking) are between 29% and 60%. ° Conventional radiotherapy has potential risks o second tumors (approximately 1% intracranial) and cerebrovascular events, but long-term data are lacking. 7

PRO GNO SIS • A ter surgical resection, 70% to 95% o patients with microadenomas and 40% to 68% o patients with macroadenomas have normalization o IGF-1. 6,7 ° Irradiation o adenomas results in attenuation o 7 IGF-1 secretion in more than 60% o subjects a ter 10 to 15 years. ° Less than hal o patients (44%) receiving somatostatin analogs achieve normal IGF-1 levels, and a third achieve normal GH levels. 7 • An MRI ollowing surgery demonstrating a hypotense MRI signal in the remaining tumor may be use ul in predicting good response to subsequent somatostatin analog treatment. 8 • In the past, patients with acromegaly had a 10-year reduction in li e span because o cardiac (heart ailure, arrhythmia), cerebrovascular, metabolic (diabetes, osteoporosis), and respiratory (airway obstruction rom macroglossia and hypertrophied mucosal tissues, sleep apnea) disease; radiotherapy may also increase the mortality rate. 1 Both IGF-1 and GH levels correlate with mortality and normalizing these levels (IGF-1 to age/ sex standards and GH 6 mm Cus hing Dis e a s e

Tumor not found or is 15 days per month) TTH has a prevalence o 3.3% in adults. 1 • Migraine has a prevalence o 14.7% in adults (8% in men, 17.6% in women). 1

RISK FACTO RS • For migraines—Family history • For medication overuse headache—Regular use o any medication used to treat acute headaches, most commonly simple analgesics and triptans

DIAGNO SIS

• Chronic daily headache has li etime prevalence o 4% to 5%. 2

CLINICAL FEATURES

• Medication overuse contributes to daily headache in approximately 1% o adults in the general population. 1

• Red f ags or dangerous secondary cause—Sudden onset; persistent headache with nausea, vomiting; worsening pattern; history o cancer, HIV, or systemic illness ( ever, rash, etc); ocal neurologic signs or seizures; vision changes; papilledema; headache worsened by Valsalva, exertion, or position changes; new headache during pregnancy or postpartum; new headache a ter age 55 years. 2,3,6

• Cluster headache has a li etime prevalence o 0.2% to 0.3%. 1

ETIO LO GY AND PATHO PHYSIO LO GY • TTH etiology is uncertain, but likely caused by activation o peripheral a erent neurons in head and neck muscles. 3 • Migraine headache is thought to be caused by central sensory processing dys unction, which is genetically inf uenced. 4 Nociceptive input rom the meningeal vessels is abnormally modulated in the dorsal raphe nucleus, locus coeruleus, and nucleus raphe magnus. This activation can be seen on positron emission tomography (PET) scan during an acute attack (Figure 230-1). • Cluster headache is caused by trigeminal activation with hypothalamic involvement, but the inciting mechanism is unknown. 5

• Episodic TTH—At least 10 episodes o bilateral, mild-to-moderate, pressure (nonpulsating) type pain without nausea or vomiting, not aggravated by exertion, and rare photophobia or phonophobia, occurring less than 15 days per month. 7 • Migraine headache—At least 5 episodes o unilateral, pulsating, moderate-to-severe headache lasting 4 to 72 hours, aggravated by physical activity, accompanied by nausea or emesis or photophobia and phonophobia. 7 • Chronic daily headache (CDH)—A primary headache 15 or more days per month, or 4 or more hours per day, or 3 months. 2 Four types o CDH are as below:

PART 18

h e a Da Ch e

° Chronic migraine—Episodic migraines increase in requency while associated symptoms decrease; resembles tension headache with occasional typical migraine; o ten accompanied by medication overuse.2 without nausea. Photopho° Chronic TTH—Bilateral, nonpulsating, 2 bia or phonophobia can be present. ° New daily persistent headache—Abrupt onset o daily headache in patient without a history o a headache disorder; patient o ten remembers exactly where and when the headaches started. 2 ° Hemicrania continua—Chronic unilateral pain with2exacerbations, o ten associated with ipsilateral autonomic eatures. • Medication overuse headache—Accompanies one o the CDHs; acute medications, such as triptans or opiates are taken more than 10 days a month, or analgesics more than 15 days a month, or more than 3 months.7 • Cluster headache—The most common type o trigeminal autonomic cephalalgias; can be episodic or chronic; sharp stabbing unilateral pain in trigeminal distribution, lasting 15 minutes to 3 hours, with ipsilateral autonomic eatures2 (Figure 230-2).

NEURO LO GY DIFFERENTIAL DIAGNO SIS • Common primary headaches include episodic TTH, migraine, and chronic daily headache. • Secondary causes o headache are uncommon and include systemic illnesses/ in ections, brain masses, subarachnoid hemorrhage (Figure 230-3), or increased intracranial pressure. • Medication overuse headache is predominately seen with a primary headache, but may also accompany a secondary headache.

MANAGEMENT Ep isod ic TTH

• Generally not indicated.

• Acute therapy. ° Aspirin 500 to 1000 mg is the most e ective treatment or acute episode. Nonsteroidal anti-inf ammatory drugs (NSAIDs) are more e ective than acetaminophen. 3 ° Avoid opiates. ° Limit acute medications to less than 33 times a week to reduce the risk o medication overuse headache. • Consider preventive therapy i headaches occur once a week. 3 Amitriptyline 75 to 150 mg a day is the most e ective medication. ° 3 Bio eedback may be e ective. ° 3 ° Acupuncture may be help ul.

• May be used when a secondary cause, such as in ection is suspected.

Mig raine he ad ache

• Sinus headache—Purulent nasal discharge, co-onset o sinusitis, headache localized to acial and cranial areas. TYPICAL DISTRIBUTIO N • Tension headaches are typically bilateral. • Migraine and cluster headaches are typically unilateral. LABO RATO RY TESTING

IMAGING • Generally not indicated.

• Use a stepped approach to treat acute migraine episodes. ° Start with8 simple analgesics. Aspirin and ibupro en are o ten e ective.

• Magnetic resonance imaging (MRI) when red f ags are present.

FIGURE 230-2 Lacrimation, p tosis, and lid e d e ma se e n in cluste r he ad ache . (Re p rod uce d with p e rmissio n rom The Inte rnational He ad ache Socie ty. http ://ihs-classif cation.org /e n/. Cop yrig ht www.ihs-classif cation.org ; Cop yrig ht (2012) Pro . Hartmut Göb e l, Ge rmany, www.schme rzklinik.d e .)

FIGURE 230-3 Sud d e n onse t o a thund e rclap he ad ache p romp te d imag ing that showe d d i use sub arachnoid he morrhag e with associate d ve ntricular he morrhag e . Top arrow ind icate s b lood in inte rhe misp he ric f ssure . Bottom arrow ind icate s b lood in late ral ve ntricle . (Re p rod uce d with p e rmission rom Jame s And e rson, MD, De p artme nt o Rad iolog y, O re g on He alth & Scie nce Unive rsity.)

1175

PART 18

1176

NEURO LO GY

•

• •

•

or try butorphanol nasal spray or an oral opiate ° Add an antiemetic combination. 8 c agents such as triptans or patients who ail ° Reserve migraine-speci the above therapies. 8 Consider prophylaxis or patients whose migraines have a negative impact on their lives or to decrease risk o developing medication overuse headache when requency requires use o simple analgesics more than 15 days a month or use o opioids, triptans, or combination analgesics more than 10 days a month. ° Amitriptyline (be ore bedtime starting with 10 or 25 mg and titrate up as needed and tolerated), divalproex sodium 500 to 1500 mg daily, topiramate 100 mg daily, venla axine 150 mg daily, and multiple β-blockers have each demonstrated 50% reduction in migraine requency. 9 ° Ribof avin 400 mg daily, coenzyme Q10 300 mg daily, butterbur 50 mg twice daily have each demonstrated 50% reduction in migraine requency. 9 reduces migraine requency ° Magnesium citrate 600 mg daily also and has an A rating in pregnancy. 9 Cognitive behavioral therapy, bio eedback, stress management, and li estyle modi cation may also be use ul. 8 IM injected onabotulinumtoxinA improves symptoms, unction, and quality o li e in patients with chronic migraine and is an option in patients who do not respond to oral prophylactic medications. 10 Acupuncture may provide additional bene t. 11

CDH • Tricyclic antidepressants signi cantly reduce the number o days with TTH compared to placebo. 12 Amitriptyline taken be ore bedtime starting with 10 or 25 mg and titrate up as needed and tolerated. • Acupuncture may be bene cial in chronic TTHs. 13 Cluste r he ad ache • Acute episode. 5 ° Inhaled high-f ow oxygen 10 to 15 L/ min. ° Sumatriptan 6 mg subcutaneously; contraindicated in pregnancy, lactation, coronary artery disease, stroke, and peripheral artery disease.5 • Several agents may be e ective or prophylactic therapy including verapamil or topiramate. 5 • Re er re ractory patients or evaluations or other medical or surgical therapies. Me d ication ove ruse he ad ache s • Educate patients that chronic medication use is contributing to their daily headaches. 14 • Abruptly stop (when sa e) or taper the overused medication. 14 • Inpatient withdrawal is recommended or patients overusing opiates, benzodiazepines, or barbiturates. 14 • Start prophylactic therapy with topiramate 100 to 200 mg daily prior to initiating withdrawal or as soon as possible a ter withdrawal has been initiated. 14 REFERRAL • Re er patients when the diagnosis is unclear or response to therapy is inadequate. • Consider re erral or medication overuse headaches as these are di cult to treat.

Ch a pt e r 230

PREVENTIO N • Closely monitor use o medications or acute episodes. Advise patients to limit simple analgesics to less than 15 days per month and triptans, opiates, and combination medications to less than 10 days per month. • Appropriately prescribe preventive therapies to reduce requency o headaches and avoid development o CDHs.

PRO GNO SIS • Tension headaches—Favorable; 45% o adults with requent episodic or chronic TTHs experienced remission be ore 3 years. 3 • Cluster headaches—Unknown; ranges rom total remission to chronic orm. 5

FO LLO W-UP • Dangerous causes o secondary headaches require immediate evaluation and management. • Frequency o ollow-up or primary headaches is determined by type and severity o headache and response to therapy.

PATIENT EDUCATIO N Advise patients to limit requency o acute medications to less than 2 to 3 times a week to reduce the risk o medication overuse headache.

PATIENT RESO URCES

National Headache Foundation has in ormation or patients on many topics including the ollowing: • Migraine—http:/ / www.headaches.org/ education/ Headache_Topic_Sheets/ Migraine. • Medication Overuse Headache—http:/ / www.headaches.org/ education/ Headache_Topic_Sheets/ Analgesic_Rebound. • Cluster Headache—http:/ / www.headaches.org/ education/ Headache_Topic_Sheets/ Cluster_Headaches. • New Daily Persistent Headache—http:/ / www.headaches.org/ education/ Headache_Topic_Sheets/ New_Daily_ Persistent_Headache. PRO VIDER RESO URCES

• The Institute for Clinical Systems Improvement has a comprehensive guideline on the diagnosis and treatment o headache—http:/ / www.icsi.org/ guidelines_and_more/ gl_os_prot/ other_ health_care_conditions/ headache/ headache__ diagnosis_and_treatment_o __guideline_.html. • The International Headache Society has a searchable website to assist with headache classi cation using ICHD-II criteria—http:/ / ihs-classif cation.org/ en/ 02_klassif kation/ .

h e a Da Ch e

REFERENCES 1. Stovner LJ, Andree C. Prevalence o headache in Europe: a review or the Eurolight project. J Headache Pain. 2010;11(4):289-299. 2. Bigal ME, Lipton RB. The di erential diagnosis o chronic daily headaches: an algorithmic-based approach. J Headache Pain. 2007;8(5):263-272. 3. Loder E, Rizzoli P. Tension-type headache. BMJ. 2008: 336(7635):88-92. 4. Sprenger T, Goadsby PJ. Migraine pathogenesis and state o pharmacological treatment options. BMC Med. 2009;7:71. 5. Leroux E, Ducros A. Cluster headache. Orphanet J Rare Dis. 2008;3:20. 6. Chandana SR, Mowa S, Arora M, Singh T. Primary brain tumors in adults. Am Fam Physician. 2008;77(10):1423-1430. 7. Headache Classi cation Subcommittee o the International Headache Society. The International Classif cation o Headache Disorders. 2nd ed.. Cephalalgia. 2004;24(suppl 1):9-160. 8. Buse DC, Rupnow MFT, Lipton RB. Assessing and managing all aspects o migraine: migraine attacks, migraine-related unctional impairment, common comorbidities, and quality o li e. Mayo Clin Proc. 2009;84(5):422-435.

PART 18

NEURO LO GY 9. Pringsheim T, Davenport WJ, Becker WJ. Prophylaxis o migraine headache. CMAJ. 2010;182(7):E269-E276. 10. Frampton JE. OnabotulinumtoxinA: a review o its use in the prophylaxis o headaches in adults with chronic migraine. Drugs. 2012;72(6):825-845. 11. Linde K, Allais G, Brinkhaus B, et al. Acupuncture or migraine prophylaxis. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD001218. 12. Jackson JL, Shimeall W, Sessums L, et al. Tricyclic antidepressants and headaches: systematic review and meta-analysis. BMJ. 2010;341:c5222. 13. Linde K, Allais G, Brinkhaus B, et al. Acupuncture or tension-type headache. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD007587. 14. Evers S, Jensen R. Treatment o medication overuse headache— guideline o the EFNS headache panel. Eur J Neurol. 2011;18(9):1115-1121.

1177

PART 18

1178

NEURO LO GY

Ch a pt e r 231

231 CEREBRAL VASCULAR ACCIDENT He id i Chumle y, MD

PATIENT STO RY A 65-year-old hypertensive black man presented to the emergency department with onset o right ace, arm, and hand paralysis, and di culty communicating. Rapid diagnostic testing using magnetic resonance imaging (MRI) revealed an ischemic in arct in the le t middle cerebral artery (Figure 231-1). He was evaluated by a stroke response team and was ound to be a candidate or tissue plasminogen activator (TPA). A ter the stroke, he was treated with aspirin, antihypertensives, and cholesterol-lowering medication. He recovered 80% o his neurologic de cit over the next 3 months. Figure 231-2 is a noncontrast computed tomography (CT) image o this patient 2 weeks later.

INTRO DUCTIO N Cerebral vascular accidents (CVAs) or strokes are common, especially in older populations. Most strokes are ischemic or hemorrhagic. Risk actors include hypertension, smoking, diabetes mellitus (DM), and atrial ibrillation. Thirty-day mortality or a irst stroke is greater than 20%.

FIGURE 231-2 Noncontrast CT imag e o a sub acute le t mid d le ce re b ral arte ry in arct (re d arrows). This was d one 2 we e ks a te r the stroke in the same p atie nt as Fig ure 231-1. CT f nd ing s occur late r than MRI f nd ing s in ische mic stroke s. (Re p rod uce d with p e rmission from Che n MYM, Pop e TL, O tt DJ. Basic Rad iolog y. Ne w York, NY: McGraw-Hill; 2004:338.)

SYNO NYMS CVA is also known as stroke.

EPIDEMIO LO GY • CVAs a ect approximately 700,000 people per year in the United States, most being older than age 65 years. 1 • Ischemic (66%) and hemorrhagic (10%) strokes account or most strokes. 1 • Prevalence o stroke and mortality are higher in blacks than in whites. Prevalence is 753 versus 424 per 100,000 and mortality is 95.8 versus 73.7 per 100,000 or black and white men, respectively. 1

ETIO LO GY AND PATHO PHYSIO LO GY • CVAs are typically classi ed into cardioembolic (15%-22%), large vessel (10%-12%), small vessel (15%-18%), other known cause (2%-4%), and undetermined cause (46%-51%). 2 • Ischemic CVAs occur when atherosclerosis progresses to a plaque, which ruptures acutely. Each step o this process is mediated by inf ammation.3 FIGURE 231-1 Acute le t mid d le ce re b ral arte ry in arct on MRI o a 65-ye ar-old hyp e rte nsive man. The MRI d e monstrate s incre ase d sig nal inte nsity (re d arrows). Ab normalitie s in MRI occur b e ore those se e n on CT d uring ische mic stroke s. (Re p rod uce d with p e rmission from Che n MYM, Pop e TL, O tt DJ. Basic Rad iolog y. Ne w York, NY: McGraw-Hill; 2004:338.)

• Hemorrhagic CVAs occur when vessels bleed into the brain, usually as the result o elevated blood pressure. • Other known causes o CVAs include inf ammatory disorders (giant cell arteritis, systemic lupus erythematosus [SLE], polyarteritis nodosa,

PART 18

Ce r e Br a L Va SCULa r a CCIDe Nt

NEURO LO GY

granulomatous angiitis, syphilis, and AIDS), bromuscular dysplasia, drugs (cocaine, amphetamines, and heroin), hematologic disorders (thrombocytopenia, polycythemia, and sickle cell), and hypercoagulable states.

RISK FACTO RS Hypertension (HTN)—The predominant risk actor or more than 50% o all strokes. Prehypertension (blood pressure in the range o 130 to 139/ 85 to 89) carries a hazard ratio o 2.5 or women and 1.6 or men. 4 • Cigarette smoking carries a hazard ratio o 1.62 or ischemic stroke and 2.56 or hemorrhagic stroke. 5 • Type 2 DM increases the risk o having a stroke 6 old. 4 • Black patients at ages 45 and 65 are 2.9 and 1.66 times more likely to have a stroke compared to white patients. 6 • Atrial brillation increases the risk o stroke. The CHADS2 (congestive heart ailure [CHF], HTN, age >75, DM, stroke) scoring system (see below) separates patients into low risk (stroke rate 1%-1.5% per year), moderate risk (2.5%), high risk (4%), and very high risk (7%). 4 • Body mass index (BMI) greater than 30 carries a hazard ratio o 1.45 or ischemic stroke but does not increase the risk o hemorrhagic stroke.5

DIAGNO SIS Diagnosis o CVA must be made expediently to minimize mortality and morbidity.

FIGURE 231-3 CT imag e o rig ht mid d le ce re b ral arte ry in arct; the hyp od e nse (d arke r) are a (re d arrows) ind icate s the in arct. The mid line structure s are shi te d to the le t. (Re p ro d uce d with p e rmission fro m Che n MYM, Pop e TL, O tt DJ. Basic Rad iolog y. Ne w York, NY: McGraw-Hill; 2004:335.)

CLINICAL FEATURES

• Complete blood count (CBC) or thrombocytosis or polycythemia

• History o risk actors, including older age, HTN, cigarette smoking, type 2 DM, or previous transient ischemic attack (TIA) or stroke.

• Erythrocyte sedimentation rate (ESR) or diseases such as giant cell arteritis or SLE

• Acute onset o neurologic signs and symptoms based on the site o the CVA (see “Typical Distribution” below).

• Testing or syphilis using a treponemal enzyme immunoassay (EIA), with positive results con rmed by a nontreponemal test (Venereal Disease Research Laboratory [VDRL])

TYPICAL DISTRIBUTIO N TIA or stroke can occur in any area o the brain; common areas with typical symptoms include the ollowing:

• Serum glucose to eliminate hypoglycemia as the cause o the neurologic symptoms

• Middle cerebral artery is the most common ischemic site (Figure 231-3). ° Superior branch occlusion causes contralateral hemiparesis and sensory de cit in ace, hand, and arm, and an expressive aphasia i the lesion is in the dominant hemisphere. ° In erior branch occlusion causes a homonymous hemianopia, impairment o contralateral graphesthesia and stereognosis, anosognosia and neglect o the contralateral side, and a receptive aphasia i the lesion is in the dominant hemisphere.

IMAGING

• Internal carotid artery (approximately 20% o ischemic strokes) occlusion causes contralateral hemiplegia, hemisensory de cit, and homonymous hemianopia; aphasia is also present with dominant hemisphere involvement.

CT or MRI can distinguish ischemic rom hemorrhagic and localize the lesion (Figure 231-4).

DIFFERENTIAL DIAGNO SIS Other causes o acute neurologic dys unction include the ollowing: • TIA—This precursor to a CVA can appear identical; however, no lesion is seen on imaging, and symptoms resolve within 48 hours.

• Posterior cerebral artery occlusion causes a homonymous hemianopia a ecting the contralateral visual eld.

• Multiple sclerosis—Multiple anatomically distinct neurologic signs and symptoms that occur over time and resolve; vision is o ten a ected. MRI ndings should help to distinguish multiple sclerosis rom CVA.

LABO RATO RY TESTING (INCLUDE ANCILLARY TESTING)

• Brain mass—More common presentation is headache or seizure; however, may present with ocal neurologic signs based on location. CT or MRI will help to diagnose a brain mass and di erentiate this rom stroke.

The ollowing tests may be help ul in the context o an acute stroke, particularly when the cause o the stroke is not immediately evident:

• Migraines—Throbbing, unilateral headache with photophobia, and nausea; hemiparesis or aphasia may be part o the aura.

1179

PART 18

1180

NEURO LO GY

Ch a pt e r 231

28%; number needed to treat [NNT] to prevent 1 stroke per year = 77). 4 SO R • Lower blood pressure (RR reduction 28%; NNT to prevent 1 stroke per year = 51). 4 Current data demonstrate that thiazide-type diuretic and angiotensin-converting enzyme inhibitor (ACEI) (or angiotensin receptor blocker [ARB]) may provide additional risk reduction beyond blood pressure (BP) control and should be used rst. ACEI and ARB may not be as e ective as monotherapy in black populations. 4 SO R • Lower low-density lipoprotein (LDL) cholesterol to less than 100 mg/ dL or patients with a prior stroke or who are at high risk o stroke using a statin (RR reduction 25%; NNT to prevent 1 stroke per year = 57).4 SOR

• Assist patients to stop smoking (RR reduction 33%; NNT to prevent 1 stroke per year = 43). 4 SO R • Advise patients to adopt a healthy li estyle by eating more ruits and vegetables, losing weight, and maintaining a physical exercise program. SOR

Consider the ollowing to urther decrease morbidity and mortality: • Avoid indwelling urinary catheters to reduce the risk o urinary tract in ection. • Encourage early ambulation to reduce the risk o a deep venous thrombosis. • Use antiembolism stockings to reduce the risk o a deep venous thrombosis. FIGURE 231-4 He morrhag ic stroke . CT imag e d e monstrate s b le e d ing in the rig ht b asal g ang lia (larg e arrow) into the ve ntricle s (re d arrows). Blood ap p e ars white on the CT scan. The white arrows illustrate mid line shi t. (Re p rod uce d with p e rmission from Che n MYM, Pop e TL, O tt DJ. Basic Rad iolog y. Ne w York, NY: McGraw-Hill; 2004:337.)

• Vertigo rom benign positional vertigo or acute labyrinthitis—Can mimic a CVA in the posterior circulation; however, symptoms such as dysarthria, dysphagia, and diplopia are typically absent. • Hypoglycemia—Con used state is similar to large stroke syndromes but is easily di erentiated by a blood glucose measurement.

MANAGEMENT ACUTE STRO KE (WITHIN THE FIRST 3 HO URS) • Rapidly evaluate or consult specialists to identi y candidates or TPA. Odds or a avorable 3-month outcome or TPA compared to no TPA are 2.8 (95% con dence interval [CI], 1.8-4.5) or 0 to 90 minutes, 1.6 (95% CI, 1.1-2.2) or 91 to 180 minutes. 7 SO R • Favorable outcomes at 90 days poststroke have also been demonstrated when TPA is given up to 4.5 hours a ter the onset o symptoms. 8 SO R

• Currently, only 3% o patients who meet the criteria receive TPA. 4 • Preliminary studies cautioned about using TPA in community settings; recent studies, however, indicate several options to improve outcomes, including telephone consultation with a regional stroke center. 9 • Acutely elevated blood pressure should not be aggressively treated in most cases. A ter stabilization, treat ischemic strokes with antithrombotic, antihypertensives, statins, and li estyle changes. • Prescribe 81-mg or 325-mg aspirin or secondary stroke prevention in patients with prior ischemic stroke or TIA (relative risk [RR] reduction

• Consider a swallowing study to identi y patients at risk o aspiration. SPECIAL SITUATIO NS • Hemorrhagic stroke ° Acutely—Do not aggressively lower BP. Some authorities recommend lowering BP only when mean arterial pressure (MAP) is more than 130 mm Hg (MAP = [(2 × diastolic BP) + systolic BP]/ 3). ° A ter the hemorrhagic stroke is over, treat BP aggressively; modest decreases (12/ 5 mm Hg) rom one o many classes o hypertensive drugs lower recurrent stroke risk by 50% to 75%. 4 • Nonvalvular atrial brillation (AF)—Use the CHADS2 scoring system to identi y patients with AF who can be managed with aspirin or should be anticoagulated with Coumadin.4 New oral anticoagulants such as apixaban, dabigatran, and rivaroxaban have decreased stroke risk in early trials.10 • The CHADS/ CHADS2 scoring table is shown below2: C: Congestive heart ailure H: HTN (or treated HTN) A: Age >75 years D: Diabetes S: Prior TIA or stroke

= = = = =

1 point 1 point 1 point 1 point 2 points

° For 0 to 1 point, use aspirin; 2 points, weigh risk o bleeding, adequacy o ollow-up versus bene t; 3 or greater, use war arin i at all possible. • Patients with symptomatic carotid stenosis—Re er or carotid endarterectomy patients with 70% to 99% carotid stenosis (without nearocclusion) with ipsilateral ocal neurologic signs (absolute risk reduction [ARR] 16%). 11 Consider re erring symptomatic patients with moderate stenosis o 50% to 69% (ARR 4.6%). 11 SO R • Patients with asymptomatic carotid artery stenosis greater than 60%— Consider re erral or carotid endarterectomy in patients younger than the age o 75 years (NNT = 20 to prevent 1 stroke in 5 years). 4

PART 18

Ce r e Br a L Va SCULa r a CCIDe Nt

PREVENTIO N • Address modi able risk actors—Control HTN, high cholesterol, and DM; stop smoking; and maintain a healthy body weight. • The US Preventive Services Task Force (USPSTF) recommends the use o aspirin or women ages 55 to 79 when the potential bene t o reduction in ischemic strokes outweighs the potential harm o an increase in GI hemorrhage. 12 • The USPSTF ound the evidence insu cient to recommend or or against the use o aspirin or stroke reduction in men. 12

PRO GNO SIS CVA prognosis varies based on size and location o ischemia or hemorrhage, time to TPA administration ( or ischemic stroke), and availability o aggressive poststroke rehabilitation. • The 30-day mortality rate a ter a rst or second stroke is 22% and 41%, respectively. 4 • Five-year observed survival is 40% to 68% or stroke. 13

FO LLO W-UP • Patients with symptoms o an acute stroke should be hospitalized, evaluated immediately or appropriateness o TPA and treatment o reversible causes, and managed, i possible, in a stroke unit or using the “best practices” associated with these units. • A ter a stroke and rehabilitation, patients should be ollowed at regular intervals to evaluate risk-reduction strategies.

PATIENT EDUCATIO N Educate patients who have had a stroke about the high risk o having a second stroke, the high morbidity and mortality associated with a recurrent stroke, and the need or li estyle modi cations and medications to reduce this risk. PATIENT RESO URCES

• The National Stroke Association has patient information including signs o a stroke and HOPE: The Stroke Recovery Guide—http:/ / www.stroke.org. • The Internet Stroke Center has a section for patients and families with patient education about signs o a stroke and living a ter a stroke—http:/ / www.strokecenter.org. • The National Institute of Neurologic Diseases and Stroke has written and auditory patient in ormation in English and Spanish— http:/ / www.ninds.nih.gov. PRO VIDER RESO URCES

• The Internet Stroke Center has a large collection of stroke scales and clinical assessment tools, a neurology image library, listings o pro essional resources, and evidence-based diagnosis and management strategies—http:/ / www.strokecenter.org. • Guidelines for early management of adults with ischemic stroke rom the American Heart Association and other partners— http:/ / stroke.ahajournals.org/ content/ 38/ 5/ 1655.full.

NEURO LO GY REFERENCES 1. Stansbury JP, Jia H, Williams LS, et al. Ethnic disparities in stroke: epidemiology, acute care, and postacute outcomes. Stroke. 2005;36(2):374-386. 2. Schneider AT, Kissela B, Woo D, et al. Ischemic stroke subtypes: a population-based study o incidence rates among blacks and whites. Stroke. 2004;35(7):1552-1556. 3. Elkind MS. Inf ammation, atherosclerosis, and stroke. Neurologist. 2006;12(3):140-148. 4. Sanossian N, Ovbiagele B. Multimodality stroke prevention. Neurologist. 2006;12(1):14-31. 5. Zhang Y, Tuomilehto J, Jousilahti P, et al. Li estyle actors on the risks o ischemic and hemorrhagic stroke. Arch Intern Med. 2011;171(20):1811-1818. 6. Howard G, Cushman M, Kissela BM, et al; Reasons or Geographic and Racial Di erences in Stroke (REGARDS) Investigators. Traditional risk actors as the underlying cause o racial disparities in stroke: lessons rom the hal - ull (empty?) glass. Stroke. 2011;42(12):3369-3375. 7. Tonarelli SB, Hart RG. What’s new in stroke? The top 10 or 2004/ 05. JAm Geriatr Soc. 2006;54(4):674-679. 8. Maiser SJ, Georgiadis AL, Suri MF, et al. Intravenous recombinant tissue plasminogen activator administered a ter 3 h ollowing onset o ischaemic stroke: a metaanalysis. Int J Stroke. 2011;6(1):25-32. 9. Frey JL, Jahnke HK, Goslar PW, et al. TPA by telephone: extending the bene ts o a comprehensive stroke center. Neurology. 2005;64(1):154-156. 10. Baker WL, Phung OJ. Systematic review and adjusted indirect comparison meta-analysis o oral anticoagulants in atrial brillation. Circ Cardiovasc Qual Outcomes. 2012;5(5):711-719. 11. Rerkasem K, Rothwell PM. Carotid endarterectomy or symptomatic carotid stenosis. Cochrane Database Syst Rev. 2011;13(4):CD001081. 12. United States Preventive Services Task Force, Aspirin for the Prevention of Cardiovascular Disease: Recommendation Statement, AHRQ Publication No. 09-05129-EF-2. Rockville, MD: Agency or Healthcare Research and Quality; 2009. http:/ / www.ahrq.gov/ clinic/ uspst 09/ aspirincvd/ aspcvdrs.htm. Accessed September 2, 2012. 13. Askoxylakis V, Thieke C, Pleger ST, et al. Long-term survival o cancer patients compared to heart ailure and stroke: a systematic review. BMC Cancer. 2010;10:105.

1181

PART 18

1182

NEURO LO GY

232 SUBDURAL HEMATO MA He id i Chumle y, MD

PATIENT STO RY A 70-year-old woman, currently anticoagulated or atrial brillation, ell and hit her head. She did not lose consciousness and did not seek care immediately. Approximately 12 hours later, she developed a headache and con usion, and was taken to the emergency department by a amily member. She was ound to have an acute subdural hematoma (SH) (Figure 232-1). She was hospitalized, and a neurosurgeon was consulted or surgical management.

INTRO DUCTIO N SHs can occur at any age, but are most common in older adults. Most SHs are caused by trauma. Symptoms are generally nonspeci c such as con usion or headaches. Treatment is prompt consultation with a neurosurgeon.

EPIDEMIO LO GY

Ch a pt e r 232

ETIO LO GY AND PATHO PHYSIO LO GY • Most SHs are caused by trauma, either accidental or intentional, rom a direct injury to the head. • Falls, motor vehicle accidents, and assault are the most common causes o traumatic SH. 1 • SHs have been reported rom chronic jarring rom rapid walking in older patients. • Motion o the brain within the skull causes a shearing orce to the cortical sur ace and interhemispheric bridging veins. 4 • This orce tears the weakest bridging veins as they cross the subdural space, resulting in an acute SH as seen in Figure 232-1. 4 • Three days to 3 weeks a ter the injury, the body breaks down the blood in an SH; water is drawn into the collection causing hemodilution, which appears less white and more gray on noncontrast computed tomography (CT). 4 • I the hematoma ails to resolve, the collection has an even higher content o water and appears darker on a noncontrast CT; it may have resh bleeding or may calci y (chronic SH; see Figure 232-2). 4 This is o ten o the same color as brain parenchyma on noncontrast CT. • Nontraumatic causes reported in the literature include spontaneous bleeding because o bleeding disorders or anticoagulation, meningitis, and complications o neurologic procedures, including spinal anesthesia.

• SHs occur at all ages. In adults, SHs are more common in men. 1 • Less than 1 in 100,000 adults per year have a traumatic SH. 1 • Forty-two o 100,000 hospitalizations or adult patients. 2 • Cost is $1.6 billion per year in 2007. 2 • Mortality rates in treated older adults are approximately 8% or patients younger than age 65 years and 33% or patients older than age 65 years. 3

FIGURE 232-1 CT scan of an acut sub d ural h matoma (arrow) s n as a hyp rd ns clot with an irr g ular b ord r. Th r is a mid lin shift from th mass ff ct of th accumulat d b lood . (Re p rod uce d with p e rmissio n from Kasp e r DL, Braunwald E, Fauci, AS, Hause r SL, Long o DL, Jame son JL. Harrison’s Princip l s of Int rnal M d icin . 16th e d . Ne w York, NY: McGraw-Hill; 2005:2450.)

RISK FACTO RS Increased mortality is seen in patients. • Older than 80 years o age2 • With lower income2 • With acquired clotting abnormalities2,5

FIGURE 232-2 CT scan of chronic b ilat ral sub dural h matomas. As subd ural h matomas ag , th s b com isod ns gray and th n hypod ns (dark r gray to b lack) compar d to th b rain. Som r solving b lood is still visib l on th l ft (arrows). (Rep roduced with p ermission from Kasp er DL, Braunwald E, Fauci, AS, Hauser SL, Longo DL, Jameson JL. Harrison’s Principl s of Int rnal M dicin . 16th e d. New York, NY: McGraw-Hill; 2005:2450.)

SUBDUr a L h e Ma t O Ma

PART 18

NEURO LO GY

• Who experienced trauma2 • With a higher APACHE (Acute physiology, Age, and Chronic Health Evaluation) III score on presentation5

DIAGNO SIS The clinical eatures are o ten nonspeci c, making the diagnosis di cult in the absence o known trauma. Older adults may present with headaches, con usion, subtle changes in mental status, gait disturbances, hemiparesis, or other ocal neurologic signs. 6 TYPICAL DISTRIBUTIO N SHs by de nition occur in the subdural space, most commonly seen in the parietal region. IMAGING Acute SHs are seen easily on a noncontrast CT scan (see Figure 232-1). Subacute and chronic SHs (see Figure 232-2) can be similar in color to the brain parenchyma and may be easier to see on a contrast CT or a magnetic resonance imaging (MRI).

DIFFERENTIAL DIAGNO SIS Other causes o nonspeci c symptoms seen with SH can be di erentiated by neuroimaging and include the ollowing: • In ections such as sepsis or meningitis—Fever, elevated white blood cells, positive blood cultures, and cerebral spinal f uid consistent with meningitis. • Hemorrhagic (Figure 232-3) or ischemic stroke or transient ischemic attacks—Consider risk actors or stroke such as hypertension,

FIGURE 232-4 This h ad CT d monstrat s an p id ural h matoma, with th typ ical b iconv x ap p aranc (arrows). Not how th b iconv x ap p aranc r s mb l s th l ns o f an y . (Re p rod uce d with p e rmission from Che n MYM, Pop e TL Jr., O tt, DJ. Basic Rad iolog y. Ne w York, NY: McGraw-Hill; 2004:346.)

diabetes, atrial brillation, and smoking (see Chapter 231, Cerebral Vascular Accident). • Dementia or depression—Less acute onset, advanced age, and other symptoms consistent with depression. • Primary or metastatic brain neoplasms—History o cancer and risk actors or cancer. Other causes o intracranial bleeding can also be di erentiated by neuroimaging and include the ollowing: • Epidural hematoma (Figure 232-4)—Well-de ned biconvex bright white density that resembles the shape o the lens o the eye. • Subarachnoid hemorrhage (Figure 232-5)—Bright white blood outlines cerebral sulci. • Hemorrhage in brain parenchyma—Bright white lesion apart rom dura.

MANAGEMENT Most SHs are managed surgically, and there is little evidence about conservative management. • Determine the Glasgow Coma Scale in patients with serious head trauma and consider airway protection in patients with a score less than 12. • Obtain an urgent noncontrast CT scan on any patient suspected o having an SH. • I the noncontrast CT scan is nonrevealing, obtain a contrast CT or MRI, particularly i the traumatic event occurred 2 to 3 days prior. FIGURE 232-3 H morrhag ic strok s n on CT. Th CT imag d monstrat s b l d ing in th rig ht b asal g ang lia (larg e b lack arrow) into th v ntricl s (small b lack arrows) with mid lin shift (white arrows). (Re p rod uce d with p e rmission from Che n MYM, Pop e TL Jr., O tt, DJ. Basic Rad iolog y. Ne w York, NY: McGraw-Hill; 2004:337.)

• Emergently re er patients with an SH and deteriorating neurologic status or evidence o brain edema or midline shi t to a hospital with neurosurgeons. • Consult a neurosurgeon expediently in patients with an SH and stable ocal neurologic signs.

1183

PART 18

1184

NEURO LO GY

CHAPTe R 232

• In patients older than age 65 years, the mortality rate or chronic SH remains elevated until 1 year a ter diagnosis independent o treatment. 7

FO LLO W-UP • Follow-up is determined by severity o SH and type o treatment. • Ideally, ollow-up is conducted jointly between the neurosurgeon and primary care physician to ensure resolution o the SH and maximal return o unction, especially in elderly patients.

PATIENT EDUCATIO N Advise patients to seek medical care immediately or head trauma, which can cause several emergencies including an SH. PATIENT RESO URCES

• MedlinePlus. Subdural Hematoma—http:/ / www.nlm.nih.gov/ medlineplus/ ency/ article/ 000713.htm. PRO VIDER RESO URCES FIGURE 232-5 A sub arachnoid h morrhag ap p ars as ar as of hig h d nsity (mor whit lik b on rath r than th d ark r g ray of b rain tissu ) in th sub arachnoid sp ac (arrows) of this CT scan. (Re p rod uce d with p e rmission from Aminoff MJ, Gre e nb e rg DA, Simon RP. Clinical N urolog y. 6th e d . Ne w York, NY: McGraw-Hill; 2005:77.)

• Consider neurosurgical consultation in asymptomatic patient or patients with only a headache and a small acute SH without brain edema or midline shi t. These patients may be ollowed by serial CT scans without surgical treatment, but this should be done in consultation with experts in CT interpretation and management o SHs. 6 SO R

PREVENTIO N • Follow sa ety measures that reduce motor vehicle accidents, and alls in the elderly. • Use recommended protective gear or sports and recreational activities and ollow guidelines or return to play a ter a head injury. • Care ully evaluate the risks and bene ts o chronic use o antiplatelet and anticoagulation medications.

PRO GNO SIS • In-hospital mortality or acute SH is 12%. 2,3 • In-hospital mortality or traumatic SH is 26%. 1 • Best predictor o in-hospital mortality is neurologic status on admission.7

• Medscape. Subdural Hematoma—http:/ / emedicine.medscape .com/ article/ 1137207. • MD+CALC. Glasgow Coma Scale Calculator—http:/ / www .mdcalc.com/ glasgow-coma-scale-score. REFERENCES 1. Tallon JM, Ackroyd-Stolarz S, Darim Sa, Clarke DB. The epidemiology o surgically treated acute subdural and epidural hematomas in patients with head injuries: a population-based study. Can J Surg. 2008;51(5):339-345. 2. Frontera JA, Egorova N, Moskowittz AJ. National trend in prevalence, cost, and discharge disposition a ter subdural hematoma rom 1998-2007. Crit Care Med. 2011;39(7):119-125. 3. Munro PT, Smith RD, Parke TR. E ect o patients’ age on management o acute intracranial haematoma: prospective national study. BMJ. 2002;325(7371):1001. 4. Minns RA. Subdural haemorrhages, haematomas, and e usions in in ancy. Arch Dis Child. 2005;90(9):883-884. 5. Bershad EM, Farhadi S, Suri MF, et al. Coagulopathy and inhospital deaths in patients with acute subdural hematoma. J Neurosurg. 2008;109(4):664-669. 6. Karnath B. Subdural hematoma. Presentation and management in older adults. Geriatrics. 2004;59(7):18-23. 7. Miranda LB, Braxton E, Hobbs J, Quigley MR. Chronic subdural hematoma in the elderly: not a benign disease. J Neurosurg. 2011;114(1):72-76.

PART 18

NO RMAL PRESSURE HYDRO CEPHALUS

NEURO LO GY

233 NO RMAL PRESSURE HYDRO CEPHALUS He id i Chumle y, MD

PATIENT STO RY A 68-year-old man presented with a gradual onset o di culty with his gait, increased urinary incontinence, and di culty with his memory during the past several months. His gait was wide-based and slow, with decreased step height and length. His Mini Mental State Examination was consistent with impaired cognition. As part o his workup, he had a noncontrast head computed tomography (CT), which demonstrated dilated ventricles (Figure 233-1) without extensive cortical atrophy. He had normal cell counts and opening pressure on a spinal tap. He was diagnosed with normal pressure hydrocephalus (NPH) and re erred to a neurosurgeon to be evaluated or a ventricular shunt. The patient had the shunt placed (Figure 233-2). His gait and urinary incontinence improved. Un ortunately, his cognitive impairments did not improve as is o ten the case.

INTRO DUCTIO N NPH can be idiopathic or secondary to meningitis, subarachnoid hemorrhage, or head trauma, and is caused by impaired reabsorption o spinal f uid. Patients present with gait abnormalities, urinary incontinence, and/ or cognitive impairment. Diagnosis is con rmed by radiographic evidence and a normal opening pressure on lumbar puncture.

FIGURE 233-2 Noncontrast CT shows ve ntricular shunt (re d arrow) in p lace . Late ral ve ntricle s re main e nlarg e d a te r shunting (white arrows). (Re p rod uce d with p e rmission from Re g inald Dusing , MD.)

EPIDEMIO LO GY • Prevalence—1 in 250 in those older than age 65 years; determined in a door-to-door survey in Germany. 1 • Incidence—1 to 2/ 100,000 population per year; determined by number o surgeries in Sweden. 2 • Most common between the ages o 60 to 70 years. • Five percent o dementias are caused by NPH. 3

ETIO LO GY AND PATHO PHYSIO LO GY • Cerebral spinal f uid (CSF) is produced by the choroid plexus, circulates through the ventricles, exits into the subarachnoid space, and is reabsorbed by the arachnoid granulations at the top o the brain. 3 • NPH is thought to be due to impaired reabsorption and can be idiopathic or secondary to meningitis, subarachnoid hemorrhage, or head trauma.

DIAGNO SIS NPH is a clinical diagnosis based on signs and symptoms, CSF studies, radiographic imaging, and a clinical response to ventriculoperitoneal (VP) shunting. CLINICAL FEATURES FIGURE 233-1 Noncontrast CT d e monstrate s e nlarg e d late ral ve ntricle s (white arrows) without sig ni cant ce re b ral atrop hy. (Re p rod uce d with p e rmission from Re g inald Dusing , MD.)

Classic triad is gait disturbance, urinary incontinence, and cognitive impairment.

1185

PART 18

1186

NEURO LO GY

Ch a pt e r 233

• Gait disturbances typically occur rst—Wide-based stance; slow, shu f ing steps; di culty with initiation. 3

• Chronic alcoholism—History o alcohol use, memory and learning di culties; cortical atrophy.

• Urinary incontinence usually with urgency; abnormal detrusor contractions on urodynamic studies. 3

• Multiin arct dementia, atherosclerotic disease, subdural hematomas, and tumors—Identi able on neuroimaging.

• Cognitive impairment—Di culty with attention and concentration (digit span, arithmetic) with sparing o orientation and general memory.4

• Intracranial in ections or carcinomatous meningitis—Abnormal CSF ndings.

LABO RATO RY TESTING • CSF had normal cell counts and opening pressure less than 200 mm Hg.3 • High-volume spinal tap (removal o 30-66 cc o CSF) or prolonged CSF drainage (3-5 days via an indwelling catheter) ollowed by clinical improvement can be help ul in selecting patients more likely to respond to VP shunting. 5 • Continuous monitoring o intracranial pressure demonstrates characteristic waves o NPH; however, this is done only in specialized centers. IMAGING

• Hypothyroidism—Has other symptoms such as atigue, weakness, dry and cool skin, di use hair loss, cold intolerance, constipation, and di culty concentrating. The thyroid-stimulating hormone (TSH) is elevated and there is no urinary incontinence (see Chapter 226, Hypothyroidism).

MANAGEMENT Re er to a neurosurgeon to evaluate or VP shunting (see Figure 233-2).

• Enlarged ventricles without substantial cerebral atrophy can be seen on CT or magnetic resonance imaging (MRI).

• VP shunting is the only known e ective treatment (see Figure 233-2). In larger retrospective studies, 39% to 75% o patients demonstrated improvement by 24 months. 5,7

• Cisternography, a nuclear medicine test, can demonstrate impaired clearing o CSF rom the lateral ventricles at 48 hours (Figure 233-3), which is use ul in predicting which patients respond to shunting. 6

• The risks o VP shunting can be substantial; moderate-to-severe complications occurred in 28% o patients in one study7; more recent reviews report a 6% complication rate. 8

DIFFERENTIAL DIAGNO SIS • Alzheimer disease—Impaired orientation and memory, which are o ten spared in NPH; cortical atrophy. • Parkinson disease—Tremor and rigidity in addition to bradykinesia and gait disturbances; normal neuroimaging.

• Repetitive lumbar punctures may be considered in patients who cannot undergo surgery. 9

PRO GNO SIS • In one study, patients demonstrated improvements in gait (81.1%), urinary incontinence (55.9%), and dementia (64.4%) a ter surgery. Surgical complications occurred in approximately 6% o patients. 8 • Favorable prognostic actors include gait abnormality as the presenting or dominant symptom, symptoms less than 6 months prior to treatment, and an identi ed cause (ie, because o head trauma). 10 • Poor prognostic actors include dementia preceding gait abnormality or dementia or more than 2 years. 10

FO LLO W-UP Long-term multidisciplinary ollow-up can acilitate gait and bladder retraining and early recognition o signs o shunt mal unction including vomiting, headache, ever, or seizures.

PATIENT EDUCATIO N Advise patients about improvements rom VP shunting. • Do not occur or all patients. • Appear slowly over several months. FIGURE 233-3 Late ral vie w on ciste rnog rap hy d e monstrate s incre ase d up take in the late ral ve ntricle (re d arrow). In this nucle ar me d icine stud y, ind ium is inje cte d into the ce re b ral sp inal f uid at the lowe r lumb ar sp ine and a scan is d one 48 hours late r. Normally, the ind ium-tag g e d sp inal f uid has b e e n re ab sorb e d at 48 ho urs, and the late ral ve ntricle d oe s not have incre ase d up take . (Re p rod uce d with p e rmission from Re g inald Dusing , MD.)

• May last several years. • Are more likely to involve gait disturbances rather than cognitive de cits. Advise patients to in orm any health care provider they see about their VP shunt.

NO r Ma L pr e SSUr e h YDr O Ce ph a LUS

PATIENT RESO URCES

• eMedicineHealth. Normal Pressure Hydrocephalus—http:/ / www .emedicinehealth.com/ normal_pressure_hydrocephalus/ article_em.htm. • The National Institute of Neurologic Disorders and Stroke. Normal Pressure Hydrocephalus Information Page—http:/ / www.ninds.nih .gov/ disorders/ normal_pressure_hydrocephalus/ normal_pressure_hydrocephalus.htm. PRO VIDER RESO URCES

• Medscape. Normal Pressure Hydrocephalus—http:/ / emedicine .medscape.com/ article/ 1150924. REFERENCES 1. Trenkwalder C, Schwarz J, Gebhard J, et al. Starnberg trial on epidemiology o Parkinsonism and hypertension in the elderly. Prevalence o Parkinson’s disease and related disorders assessed by a door-to-door survey o inhabitants older than 65 years. Arch Neurol. 1995;52(10):1017-1022. 2. Tisell M, Hoglund M, Wikkelso C. National and regional incidence o surgery or adult hydrocephalus in Sweden. Acta Neurol Scand. 2005;112(2):72-75. 3. Verrees M, Selman WR. Management o normal pressure hydrocephalus. Am Fam Physician. 2004;70(6):1071-1078.

PART 18

NEURO LO GY 4. Ogino A, Kazui H, Miyoshi N, et al. Cognitive impairment in patients with idiopathic normal pressure hydrocephalus. Dement Geriatr Cogn Disord. 2006;21(2):113-119. 5. McGirt MJ, Woodworth G, Coon AL, et al. Diagnosis, treatment, and analysis o long-term outcomes in idiopathic normal-pressure hydrocephalus. Neurosurgery. 2005;57(4):699-705; discussion 699-705. 6. Algin O, Hakyemez B, Ocakoglu G, Parlak M. MR cisternography: is it use ul in the diagnosis o normal-pressure hydrocephalus and the selection o “good shunt responders”? Diagn Interv Radiol. 2011;17(2):105-111. 7. Vanneste J, Augustijn P, Dirven C, et al. Shunting normal-pressure hydrocephalus: do the bene ts outweigh the risks? A multicenter study and literature review. Neurology. 1992;42(1):54-59. 8. Cage TA, Auguste KI, Wrensch M, et al. Sel -reported unctional outcome a ter surgical intervention in patients with idiopathic normal pressure hydrocephalus. J Clin Neurosci. 2011;18(5):649-654. 9. Lim TS, Yong SW, Moon SY. Repetitive lumbar punctures as treatment or normal pressure hydrocephalus. Eur Neurol. 2009;62(5):293-297. 10. Siraj S. An overview o normal pressure hydrocephalus and its importance: how much do we really know? JAm Med Dir Assoc. 2011;12(1):19-21.

1187

PART 18

1188

NEURO LO GY

234 BELL’S PALSY He id i Chumle y, MD

PATIENT STO RY Five years ago, a young woman awoke with the inability to move the le t side o her ace. She was pregnant at the time. On examination it was ound that she had absent brow urrowing, weak eye closure, and dropping o her mouth angle (Figure 234-1). She was diagnosed with Bell’s palsy and was provided eye lubricants and guidance on keeping her le t eye moist. Her physician discussed the available evidence about treatment with steroids. She chose not to take a course o steroids because o her pregnancy.

INTRO DUCTIO N Bell’s palsy is an idiopathic paralysis o the acial nerve resulting in loss o brow urrowing, weak eye closure, and dropped angle o mouth. Treatment is oral steroids as soon a ter the onset o symptoms as possible. Most patients have a ull recovery within 6 months.

SYNO NYMS Bell’s palsy is also known as idiopathic acial paralysis.

Ch a pt e r 234

EPIDEMIO LO GY • In a Canadian study, incidence was 13.1 to 15.2/ 100,000 adults. 1 • In a study o United States military members, the incidence was 42.77/ 100,000, with higher incidence in emales, blacks, and Hispanics; arid climate and cold months were independent predictors o risk with adjusted relative risk ratios o 1.34 and 1.31, respectively. 2 • Women who develop Bell’s palsy in pregnancy have a 5- old increased risk over national average o preeclampsia or gestational hypertension. 3 • Seventy percent o cases o acute peripheral acial nerve palsy are idiopathic (Bell’s palsy); 30% have known etiologic actors such as trauma, diabetes mellitus, polyneuritis, tumors, or in ections such as herpes zoster, leprosy (Figure 234-2) or Borrelia. 4

ETIO LO GY AND PATHO PHYSIO LO GY • Etiology o Bell’s palsy is currently unknown and under debate; the prevailing theory suggests a viral etiology rom the herpes amily. • The acial nerve becomes in amed, resulting in nerve compression. • Compression o the acial nerve compromises muscles o acial expression, taste f bers to the anterior tongue, pain f bers, and secretory f bers to the salivary and lacrimal glands. • This is a lower motor neuron lesion; the upper and lower portions o the ace are a ected (see Figure 234-1). In upper motor neuron lesions (eg, cortical stroke), the upper third o the ace is spared, while the lower two-thirds are a ected as a result o the bilateral innervation o the orbicularis, rontalis, and corrugator muscles, which allows sparing o upper ace movement.

DIAGNO SIS CLINICAL FEATURES • Weakness o all acial muscles on the a ected side—Loss o brow urrowing, weak eye closure, and dropped angle o mouth

FIGURE 234-1 Be ll’s p alsy with loss of b row furrowing and d rop p e d ang le of the mouth o n the affe cte d le ft sid e of he r face d e monstrate d d uring a re q ue st to smile and raise he r e ye b ro ws. The Be ll’s p alsy has b e e n p re se nt for 5 ye ars and the p atie nt is b e ing e valuate d b y e ar, nose , and throat (ENT) for surg e ry to re store facial move me nt. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 234-2 Be ll’s p alsy se cond ary to le p rosy. The hyp op ig me nte d p atche s on his b ack are furthe r sig ns of the le p rosy. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 18

Be LL’S pa LSY

NEURO LO GY

• Postauricular pain • Dry eyes • Involuntary tearing • Hyperacusis • Altered tastes LABO RATO RY TESTING Laboratory testing is not usually indicated. • Herpes virus titers are not usually help ul. • Consider serologic tests or Lyme disease in endemic areas. • Consider testing or diabetes mellitus in patients with risk actors. IMAGING Consider magnetic resonance imaging (MRI) to look or a spaceoccupying lesion with atypical presentations.

DIFFERENTIAL DIAGNO SIS • Upper motor neuron diseases including stroke—Normal brow urrowing, eye closure, and blinking. • Space-occupying lesion—Symptoms are dependent on the location o the mass; consider with an isolated acial nerve palsy that does not a ect all 3 branches o the acial nerve. • Lyme disease—Occurs in endemic area with skin rash, joint in ammation, and u-like symptoms. Bell’s palsy is the most common neurologic mani estation o Lyme disease (see Chapter 215, Lyme Disease).

FIGURE 234-3 Ptosis from an isolate d third ne rve p alsy in a p atie nt with d iab e te s. Note the symme try of the facial cre ase s, which would b e ab se nt in Be ll’s p alsy. This p atie nt would also have ab normal e ye move me nts. The e ye would d e viate d own and out, ad d uction would not p ass the mid line , and up ward g aze would b e imp aire d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

• Suppurative ear disease—Ear pain, abnormal tympanic membrane. • Facial nerve damage rom microvascular disease—Most commonly in diabetes mellitus. • Facial nerve damage rom trauma—History o trauma di erentiates this rom Bell’s palsy that is idiopathic or rom an in ectious etiology. • Isolated third nerve palsy—Mani estations include diplopia and drooping o the upper eyelid (ptosis) (Figure 234-3). The a ected eye may deviate out and down in straight-ahead gaze; adduction is slow and cannot proceed past the midline. Upward gaze is impaired. When downward gaze is attempted, the superior oblique muscle causes the eye to adduct. The pupil may be normal or dilated; its response to direct or consensual light may be sluggish or absent (e erent de ect). Pupil dilation (mydriasis) may be an early sign.

MANAGEMENT NO NPHARMACO LO GIC Provide eye protection with artif cial tears, lubricants, or closing o the eyelid. SO R MEDICATIO NS • New data and a Cochrane systematic review supports treating patients with systemic corticosteroids. Steroids signif cantly decrease a patient’s risk or incomplete recovery rom 33% to 23%, risk ratio 0.71. 5

and then gradually withdrawn or another 3 to 5 days to prednisone given as a single dose o 60 mg daily or 5 days, ollowed by a dose reduced by 10 mg/ d, with a total treatment o 10 days. One trial used high-dose prednisolone given intravenously. • A Cochrane systematic review does not support using antiviral medications. There is no signif cant benef t rom acyclovir or valacyclovir when compared to placebo. Antivirals are less likely than steroids to produce complete recovery. 6 SO R CO MPLEMENTARY AND ALTERNATIVE THERAPY Acupuncture has been studied; the data, however, are inadequate to determine the e f cacy. 7 REFERRAL In long-standing acial paralysis, consider re erral to an ear, nose, and throat (ENT) surgeon or plastic surgeon with experience in treating Bell’s palsy with surgery. It is possible to restore some acial movement with specialized surgical procedures including regional muscle trans er and microvascular ree tissue trans er. 8 SO R

PRO GNO SIS

SO R

• Dosing o steroids in the studies analyzed within the Cochrane review varied rom oral methylprednisolone 1 mg/ kg daily or 10 days,

Seventy-seven percent o patients treated with systemic steroids have complete recovery o acial motor unction in 6 months.

1189

PART 18

1190

NEURO LO GY FO LLO W-UP Consider seeing patients in 2 to 3 weeks to evaluate recovery and to reconsider diagnosis i there has been no recovery.

PATIENT EDUCATIO N Most patients recover spontaneously. Steroid treatment improves a patient’s chance o complete recovery.

Ch a pt e r 234

REFERENCES 1. Morris AM, Deeks SL, Hill MD, et al. Annualized incidence and spectrum o illness rom an outbreak investigation o Bell’s palsy. Neuroepidemiology. 2002;21(5):255-261. 2. Campbell KE, Brundage JF. E ects o climate, latitude, and season on the incidence o Bell’s palsy in the US Armed Forces, October 1997 to September 1999. Am J Epidemiol. 2002;156(1):32-39. 3. Shmorgun D, Chan WS, Ray JG. Association between Bell’s palsy in pregnancy and pre-eclampsia. QJM. 2002;95(6):359-362.

PATIENT RESO URCES

4. Berg T, Jonsson L, Engstrom M. Agreement between the Sunnybrook, House-Brackmann, and Yanagihara acial nerve grading systems in Bell’s palsy. Otol Neurotol. 2004;25(6):1020-1026.

• The American Academy of Family Physicians has written and auditory in ormation in English and in Spanish—http:/ / www .familydoctor.org.

5. Salinas RA, Alvarez G, Daly F, Ferreira J. Corticosteroids or Bell’s palsy (idiopathic acial paralysis). Cochrane Database Syst Rev. 2010;(3):CD001942.

• FamilyDoctor.org. Bell’s Palsy Overview—http:/ / familydoctor .org/ familydoctor/ en/ diseases-conditions/ bells-palsy .html.

6. Lockhart P, Daly F, Pitkethly M, et al. Antiviral treatment or Bell’s palsy (idiopathic acial paralysis.) Cochrane Database Syst Rev. 2009;(4):CD001869.

• The National Institute of Neurologic Disorders and Stroke has written and auditory patient in ormation in English and Spanish— http:/ / www.ninds.nih.gov/ disorders/ bells/ bells.htm.

7. Chen N, Zhou M, He L, et al. Acupuncture or Bell’s palsy. Cochrane Database Syst Rev. 2010;(8):CD002914.

PRO VIDER RESO URCES

• The Cochrane Collaborative contains updated systematic reviews of steroid and/ or antiviral treatment o Bell’s palsy—http:/ / onlinelibrary.wiley.com/ doi/ 10.1002/ 14651858 .CD001942.pub4/ full.

8. Chuang DC. Free tissue trans er or the treatment o acial paralysis. Facial Plast Surg. 2008;24(2):194-203.

PART 18

NEURO FIBRO MATO SIS

NEURO LO GY

235 NEURO FIBRO MATO SIS He id i Chumle y, MD

PATIENT STO RY A 44-year-old Hispanic man has neurof bromatosis type 1 (NF-1). He has typical eatures o NF-1, including 8 ca é-au-lait spots, axillary reckling, and neurof bromas all over his body (Figures 235-1 to 235-4). He states that he is used to having the NF and it does not currently a ect his work or li e. He is happily married but never had children. No intervention is necessary at this time other than recommending yearly visits to his primary care physician and ophthalmologist.

INTRO DUCTIO N NF-1 is a common autosomal dominant disorder that predisposes to tumor ormation. Ca é-au-lait spots are o ten the f rst clinical sign. Other clinical signs include neurof bromas, axillary or inguinal reckling, optic gliomas, Lisch nodules, and sphenoid bone dysplasia. Treatment at present is early recognition and monitoring or complications such as cognitive dys unction, scoliosis or other orthopedic problems, tumor pressure on vital structures, or malignant trans ormation.

EPIDEMIO LO GY • NF-1 is relatively common—Birth incidence is 1 in 3000 and prevalence in the general population is 1 in 5000. 1

FIGURE 235-2 Close -up o ne urof b romas on the b ack o the man in Fig ure 235-1. The se are so t and round . (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

• Autosomal dominant inheritance; however, up to 50% o cases are sporadic. 1 • Diagnosis is typically made during childhood.

ETIO LO GY AND PATHO PHYSIO LO GY • Mutations in the NF-1 gene (on the long arm o chromosome 17) result in loss o unction o neurof bromin, which helps keep protooncogene ras (which increases tumorigenesis) in an inactive orm. • Loss o neurof bromin results in increased protooncogene ras activity in neurocutaneous tissues, leading to tumorigenesis. 1

RISK FACTO RS A f rst-degree relative with NF-1.

FIGURE 235-1 A 44-year-old Hispanic man with neurof bromatosis type 1 showing all the typical f ndings including neurof bromas, ca é-au-lait spots, and axillary reckling. (Reproduced with permission from Richard P. Usatine, MD.)

FIGURE 235-3 Larg e ca é -au-lait sp ot on the b ack o the man in Fig ure 235-1. Ca é -au-lait sp ots are ovoid hyp e rp ig me nte d macule s, 10 to 40 mm in d iame te r, with smooth b ord e rs. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

1191

PART 18

1192

NEURO LO GY

Ch a pt e r 235

FIGURE 235-6 Ne urof b romatosis in a 62-ye ar-old b lack woman. Note how larg e some o the ne urof b romas can b e come . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.) FIGURE 235-4 Close-up o axillary reckling (Crow sign) with larg e ca é-au-lait sp ot on arm. (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

6. Dysplasia o the sphenoid bone or dysplasia/ thinning o long bone cortex 7. A f rst-degree relative with NF-1

DIAGNO SIS

CLINICAL FEATURES History and physical

For a diagnosis o NF-1, patients need to have at least 2 o the ollowing2: 1. Two or more neurof bromas (Figures 235-1 to 235-6) or one or more plexi orm neurof bromas (Figure 235-7) 2. Six or more ca é-au-lait spots, 0.5 cm or larger be ore puberty and 1.5 cm or larger a ter puberty (see Figures 235-3 and 235-4) 3. Axillary or inguinal reckling (see Figures 235-1 and 235-4) 4. Optic glioma

• Ninety-f ve percent have ca é-au-lait macules, mostly be ore the age o 1 year. • Ninety percent have axillary or inguinal reckling (see Figures 235-1 and 235-4). • Eighty-one percent have cognitive dys unction mani est as learning disorder, attention def cit hyperactivity disorder, or mild cognitive impairment. 3

5. Two or more Lisch nodules (melanotic iris hamartomas) (Figure 235-8)

FIGURE 235-5 A man with ne urof b romatosis cove re d with ne urof b romas. (Re p rod uce d with p e rmission from Jack Re sne ck, Sr., MD.)

FIGURE 235-7 Ple xi orm ne urof b roma on the the nar e mine nce e e ls like a b ag o worms in this man with ne urof b romatosis. It is a b e nig n tumor o the p e rip he ral ne rve she ath and is most o te n asymp tomatic. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PART 18

Ne Ur O FIBr O Ma t O SIS

FIGURE 235-8 Lisch nod ule s (me lanotic hamartomas o the iris) are cle ar ye llow-to-b rown, d ome -shap e d e le vations that p roje ct rom the sur ace o this b lue iris. The se hamartomas are the most common typ e o ocular involve me nt in ne urof b romatosis typ e 1 and d o not a e ct vision. (Re p rod uce d with p e rmission from Paul Come au.)

NEURO LO GY

FIGURE 235-9 Ang iof b romas (p re viously calle d ad e noma se b ace um) on the ace o a p atie nt with tub e rous scle rosis. The p atie nt was orig inally thoug ht to have ne urof b romato sis. He also has e p ile p sy and cog nitive imp airme nt, which accomp anie s with tub e rous scle rosis. (Re p rod uce d with p e rmission from Natalie Norman, MD.)

• Nerve sheath, intracranial, or spinal tumors. • Cutaneous or subcutaneous neurof bromas (see Figures 235-1 to 235-6). • Other bony pathology, including dysplasia o the sphenoid or long bones, scoliosis, or short stature.

• Bloom syndrome—Growth delay and short stature, increased risk o cancer, telangiectatic erythema on the ace, cheilitis, narrow ace, prominent nose, large ears, and long limbs.

• Eye abnormalities, including Lisch nodules or early glaucoma (see Figure 235-7).

• Ataxia telangiectasia—Progressive neurologic impairment, cerebellar ataxia, immunodef ciency, impaired organ maturation, ocular and cutaneous telangiectasia, and a predisposition to malignancy.

LABO RATO RY TESTING

• Proteus syndrome—Very rare condition with hamartomatous and multisystem involvement. Joseph Merrick (also known as “the elephant man”) is now, in retrospect, thought by clinical experts to have had Proteus syndrome and not NF.

Genetic testing or couples considering having children IMAGING Although not typically used or diagnosis, imaging may be needed i tumor compression o vital structures is suspected.

DIFFERENTIAL DIAGNO SIS NF-1 is the predominant cause o ca é-au-lait spots, which can also be seen in the ollowing cases: • Normal childhood—13% to 27% o children younger than 10 years o age have at least one spot. • Neurof bromatosis type 2 (NF-2)—Vestibular schwannomas, amily history o NF-2, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacities, or juvenile cortical cataracts. • Tuberous sclerosis—Angiof bromas (skin-colored telangiectatic papules most commonly in the nasolabial olds, cheek, or chin; Figure 235-9) and hypopigmented ovoid or ash lea -shaped macules. • McCune-Albright syndrome—Fibrous dysplasia o bone and endocrine gland hyperactivity. • Fanconi anemia—Decreased production o all blood cells, short stature, upper limb anomalies, genital changes, skeletal anomalies, eye/ eyelid anomalies, kidney mal ormations, ear anomalies/ dea ness, and gastrointestinal (GI)/ cardiopulmonary mal ormations. • Segmental NF—Cutaneous neurof bromas limited to specif c dermatome(s); very rare.

MANAGEMENT Management ocuses on early recognition and treatment o mani estations. • Evaluate adults annually. SO R • Screen or cognitive impairment and re er early or intervention. SO R

• Screen or scoliosis and treat accordingly. • Re er patients annually or ophthalmologic evaluation. • Consider treatment or re erral or treatment o ca é-au-lait spots i desired by the patient. Topical vitamin D3 analogs (calcipotriene [Dovonex]) and laser therapy independently may improve the appearance o ca é-au-lait spots. 4,5 SO R One small study suggests that intense pulsed light–radio requency (IPL-RF) in combination with topical application o vitamin D3 ointment may lighten small-pigmented lesions in patients with NF-1. 6 SO R Although calcipotriene is approved or use in psoriasis, it can be prescribed o -label to patients disturbed by their hyperpigmented macules. 4,6 SO R • Examine other undiagnosed f rst-degree relatives. SO R • Surgical excision o tumors is required or tumors pressing on vital structures (ie, spinal cord impingement) or when characteristics such as rapid enlargement are worrisome or malignant trans ormation.

1193

PART 18

1194

NEURO LO GY

CHAPTER 235

PATIENT RESO URCES

• Neuro bromatosis, Inc. has a variety of resources including NF specialists by location—http:/ / www.nf nc.org. PRO VIDER RESO URCES

• Neuro bromatosis, Inc. has a variety of patient education materials, in ormation about local support groups, ongoing clinical trials, and camp New Friends or children with NF—http:/ / www .nf nc.org. • The National Institute of Neurological Diseases and Stroke has patient in ormation at its Neurof bromatosis In ormation Page— http:/ / www.ninds.nih.gov/ disorders/ NF/ NF.htm. REFERENCES

FIGURE 235-10 Ne urof b romas on the lowe r lid with Lisch nod ule s (d ark b rown sp ots) on the iris o this 64-ye ar-old man with ne urof b romatosis typ e 1. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

PRO GNO SIS • Clinical mani estations are variable leading to di f culty in prognosis. • There is a 10% li etime risk o developing a malignant peripheral nerve sheath tumor.

FO LLO W-UP • Primary care evaluation annually or adults, including monitoring o blood pressure. • Ophthalmologic examination annually or early detection o optic gliomas and glaucoma. Neurof bromas and plexi orm neuromas can occur on the eyelids. Neurof bromas on the eyelids usually are not a problem (Figure 235-10) but a plexi orm neuroma can present with ptosis and need surgical intervention. • Genetic counseling or patients with NF-1 considering having children.

1. Yohay K. Neurof bromatosis types 1 and 2. Neurologist. 2006;12(2):86-93. 2. Hirsch NP, Murphy A, Radcli e JJ. Neurof bromatosis: clinical presentations and anaesthetic implications. Br JAnaesth. 2001;86(4): 555-564. 3. Hyman SL, Shores A, North KN. The nature and requency o cognitive def cits in children with neurof bromatosis type 1. Neurology. 2005;65(7):1037-1044. 4. Nakayama J, Kiryu H, Urabe K, et al. Vitamin D3 analogues improve ca é au lait spots in patients with von Recklinghausen’s disease: experimental and clinical studies. Eur J Dermatol. 1999;9(3):202-206. 5. Shimbashi T, Kamide R, Hashimoto T. Long-term ollow-up in treatment o solar lentigo and ca é-au-lait macules with Q-switched ruby laser. Aesthetic Plast Surg. 1997;21(6):445-448. 6. Yoshida Y, Sato N, Furumura M, Nakayama J. Treatment o pigmented lesions o neurof bromatosis 1 with intense pulsed-radio requency in combination with topical application o vitamin D3 ointment. J Dermatol. 2007;34(4):227-230.

Pa r t 19

SUBSTANCE ABUSE

*

St re ng t h o Re co mme nd at io n (SO R)

De f nit io n

A

Re comme nd ation b ase d on consiste nt and g ood -q uality p atie nt-orie nte d e vid e nce .*

B

Re comme nd ation b ase d on inconsiste nt or limite d -q uality p atie nt-orie nte d e vid e nce .*

C

Re comme nd ation b ase d on conse nsus, usual p ractice , op inion, d ise ase -orie nte d e vid e nce , or case se rie s or stud ie s o d iag nosis, tre atme nt, p re ve ntion, or scre e ning .*

Se e Ap p e nd ix A on p ag e s 1241-1244 or urthe r in ormation.

1196

PART 19

SUBSTANCE ABUSE

Ch a pt e r 236

236 SUBSTANCE ABUSE DISO RDER Richard P. Usatine , MD He id i Chumle y, MD Ke lli He jl Foulkrod , MS

PATIENT STO RY A 21-year-old mother and her 4 children are being seen in a ree clinic within a homeless shelter or various health reasons (Figure 236-1). The woman is currently clean and sober, but has a long history o cocaine use and addiction (Figure 236-2). Her children span the ages o 3 months to 5 years. She was recently living with her mother a ter the birth o her youngest child, but was kicked out o her mother’s home when she went out to use cocaine once again. The patient gave written consent to the photograph and when she was shown the image on the digital camera she noted how depressed she looked. She asked or us to tell the viewers o this photograph that these can be the consequences o drug abuse—being depressed, homeless, and a single mom.

INTRO DUCTIO N Addiction occurs when substance use has altered brain unction to an extent that an individual loses a degree o control over his or her behaviors. Addiction is an epigenetic phenomenon. Many genes in uence the brain unctions that a ect behavior and genetic variants. These genes di er in their susceptibility to environmental conditions, which trigger the changes in brain circuitry, and contribute to the development o addiction. Addiction must be recognized and treated as a chronic illness with an interpro essional team and social support.

EPIDEMIO LO GY • An estimated 69.6 million Americans age 12 years or older were current users o a tobacco product in 2010. This represents 27.4% o the population in that age range. In addition, 58.3 million persons (23% o

FIGURE 236-1 A cocaine -ad d icte d mothe r with he r child re n in a home le ss she lte r. He r d rug ad d iction re sulte d in the ir home le ssne ss. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE 236-2 Purif e d cocaine . (Re p rod uce d with p e rmission from DEA.)

the population) were current cigarette smokers, 13.2 million (5.2%) smoked cigars, 8.9 million (3.5%) used smokeless tobacco, and 2.2 million (0.8%) smoked tobacco in pipes. 1 • An estimated 22.6 million Americans age 12 years or older were current illicit drug users in 2010. This represents 8.9% o the population in that age range. 1 • Marijuana was the most commonly used illicit drug (17.4 million users) (Figures 236-3 and 236-4). It was used by 76.8% o current illicit drug users. Among current illicit drug users, 60.1% used only marijuana, 16.7% used marijuana and another illicit drug, and the remaining 23.2% used only an illicit drug other than marijuana. 1 • There were 1.5 million persons who were current cocaine users in 2010. 1 • There were 353,000 persons who were current methamphetamine users in 2010 (Figure 236-5). 1 • Hallucinogens were used by 1.2 million persons (0.5%) in 2010, including 695,000 (0.3%) who had used Ecstasy (Figure 236-6). 1 • In 2010, 140,000 persons used heroin or the f rst time (Figure 236-7).1

FIGURE 236-3 Home -g rown marijuana p lant. (Re p rod uce d with p e rmission from DEA.)

SUBSt a NCe a BUSe DISO r De r

FIGURE 236-4 Marijuana re ad y to b e smo ke d . (Re p rod uce d with p e rmission from DEA.)

• There were 9 million people age 12 years or older (3.6%) who were current users o illicit drugs other than marijuana in 2010. Most (7 million, 2.7%) used psychotherapeutic drugs (including prescription drugs) nonmedically. O these, 5.1 million used pain relievers, 2.2 million used tranquilizers, 1.1 million used stimulants, and 374,000 used sedatives. 1 • Among persons who used pain relievers nonmedically in the past 12 months, 55% reported that the source o the drug was rom a riend or relative or ree. Another 17.3% reported that they got the drug rom a physician. Only 4.4% obtained the pain relievers rom a drug dealer or other stranger, and only 0.4% reported buying the drug on the Internet. 1 ASSO CIATIO N WITH CIGARETTE AND ALCO HO L USE • In 2010, the rate o current illicit drug use was 8.5 times higher among youths age 12 to 17 years who smoked cigarettes in the past month (52.9%) than it was among youths who did not smoke cigarettes in the past month (6.2%). 1

PART 19

SUBSTANCE ABUSE

FIGURE 236-6 Ecstasy tab le ts use d at rave s whe re p e op le d ance all nig ht long and some collap se in d e hyd ration. (Re p rod uce d with p e rmission from DEA.)

[ie, at the same time or within a couple o hours] on each o 5 or more days in the past 30 days), 70.6% were also current illicit drug users, which was higher than among nondrinkers (5.1%). 1

ETIO LO GY AND PATHO PHYSIO LO GY • “Drug addiction is a brain disease. Although initial drug use might be voluntary, drugs o abuse have been shown to alter gene expression and brain circuitry, which in turn a ect human behavior. Once addiction develops, these brain changes inter ere with an individual’s ability to make voluntary decisions, leading to compulsive drug craving, seeking and use.”2

• Past month illicit drug use was also associated with the level o past month alcohol use. Among youths age 12 to 17 years in 2010 who were heavy drinkers (ie, drank 5 or more drinks on the same occasion

FIGURE 236-5 Me thamp he tamine ice with p ip e . (Re p ro d uce d with p e rmission from DEA.)

FIGURE 236-7 Black tar he roin or inje ction. (Re p ro d uce d with p e rmission from DEA.)

1197

PART 19

1198

SUBSTANCE ABUSE • Addiction is a polygenic disorder. Many genes have direct or indirect in uences on neurotransmitters, drug metabolic pathways, and behavioral patterns. For example, variants o receptors or dopamine or opiates in uence perceived reward. 3 • Epigenetic mechanisms, external in uences that trigger changes in gene expression, are believed to play a role through modulation o reward and emotion. 3 As such, both genetics and environment/ learned behaviors can increase a person’s risk or substance abuse. • Family, twin, and adoption studies convincingly demonstrate that genes play an important role in the development o alcohol dependence, with heritability estimates in the range o 50% to 60% or both men and women. Important genes include those involved in alcohol metabolism, and those involved in γ-aminobutyric acid (GABA), endogenous opioid, dopaminergic, cholinergic, and serotonergic transmission. 4 • Several drinking behaviors, including alcohol dependence, history o blackouts, age at f rst drunkenness, and level o response to alcohol are associated with single-nucleotide polymorphisms (SNPs) within 1 o 4 GABA receptor genes on chromosome 5q. 5 • Comorbid mental health issues and chronic pain disorders are highly prevalent among persons with substance abuse disorders. Commonly, a person begins using drugs to sel -treat eelings o depression and symptoms o pain.

Ch a pt e r 236

A problematic pattern o alcohol use leading to clinically signif cant impairment or distress, as mani ested by at least two o the ollowing, occurring within a 12-month period6: 1. Alcohol is o ten taken in larger amounts or over a longer period than was intended. 2. There is a persistent desire or unsuccess ul e orts to cut down or control alcohol use. 3. A great deal o time is spent in activities necessary to obtain alcohol, use alcohol, or recover rom its e ects. 4. Craving, or a strong desire or urge to use alcohol. 5. Recurrent alcohol use resulting in a ailure to ulf ll major role obligations at work, school, or home. 6. Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the e ects o alcohol. 7. Important social, occupational, or recreational activities are given up or reduced because o alcohol use. 8. Recurrent alcohol use in situations in which it is physically hazardous. 9. Alcohol use is continued despite knowledge o having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by alcohol.

• The medical consequences o addiction are ar reaching and very costly to society. Cardiovascular disease, stroke, cancer, HIV/ AIDS, hepatitis, and lung disease can all be increased by drug abuse. Some o these e ects occur when drugs are used at high doses or a ter prolonged use. Some consequences occur a ter just one use. 2

10. Tolerance, as def ned by either o the ollowing: • A need or markedly increased amounts o alcohol to achieve intoxication or desired e ect. • A markedly diminished e ect with continued use o the same amount o alcohol.

• Classes o substances that are requently abused and involved in addiction include the ollowing: ° Depressants—Alcohol, sedatives, hypnotics, opioids, and anxiolytics ° Stimulants—Cocaine, amphetamines, and nicotine ° Hallucinogens—Cannabis, phencyclidine (PCP), and lysergic acid diethylamide (LSD) ° Toxic inhalants

11. Withdrawal, as mani ested by either o the ollowing: • The characteristic withdrawal syndrome or alcohol (re er to Criteria A and B o the criteria set or alcohol withdrawal). • Alcohol (or a closely related substance, such as a benzodiazepine) is taken to relieve or avoid withdrawal symptoms.

• The onset o drug e ects is approximately the ollowing: ° Seven to 10 seconds or inhaling or smoking ° Fi teen to 30 seconds or intravenous injection ° Three to 5 minutes or intramuscular or subcutaneous injection ° Three to 5 minutes or intranasal use (snorting)

RISK FACTO RS • Family history • Personal history o prior addiction

DIAGNO SIS The diagnosis o a substance use disorder is based on a pathological pattern o behaviors related to use o the substance. 6 The DSM V uses 11 criteria to make this diagnosis. One example o these criteria is the ollowing 11 symptoms or alcohol abuse disorder. I one substitutes other substances, like cannabis or cocaine, the same criteria still apply.

Severity is graded based on the number o symptoms present: Mild: Presence o 2-3 symptoms. Moderate: Presence o 4-5 symptoms. Severe: Presence o 6 or more symptoms. 6 CLINICAL FEATURES VISIBLE WITH SUBSTANCE ABUSE With intoxication, the ollowing signs may be visible: • Via stimulants—Dilated pupils and increase in blood pressure, respiratory rate, pulse, and body temperature. • Via depressants—Decrease in blood pressure, respiratory rate, pulse, and body temperature. Opioids produce pinpoint pupils. Alcohol intoxication produces dilated pupils. • Withdrawal develops with decline o substance in the central nervous system (CNS). Withdrawal reactions vary by the substance used. Alcohol withdrawal is one o the most deadly and dangerous types o withdrawal.

LABO RATO RY TESTING • All injection-drug users and persons engaged in high-risk sexual activities should be screened or HIV (with consent), hepatitis B and hepatitis C, and syphilis (rapid plasma reagin [RPR]).

PART 19

SUBSt a NCe a BUSe DISO r De r

• Women should have Papanicolaou (Pap) smears per ormed and be screened or Chlamydia and gonorrhea based on age, risk actors, and previous history o screening. • Men or women who have multiple sex partners or use sex to obtain drugs are at high risk or sexually transmitted diseases (STDs) and should be tested. • Homeless, HIV-positive, and previously incarcerated patients should be screened or tuberculosis using a purif ed protein derivative (PPD) test. • Electrocardiography (ECG) is warranted i there are any cardiac symptoms or i the physical examination reveals signs o cardiac disease. • Urine screen or common drugs o abuse may reveal other drugs not admitted to in the history. Most laboratories can di erentiate prescription rom nonprescription drugs (ie, opiates) on request. Substances have di erent physiologic hal -lives in the body and show up or varying amounts o time in the urine. Marijuana has a long excretion hal -li e and may be detectable or 1 month a ter its use. Other substances may last or only days.

DIFFERENTIAL DIAGNO SIS Substance abuse disorders coexist with and complicate the course and treatment o numerous psychiatric conditions. • Mood/ anxiety disorders—Especially depression, bipolar a ective disorder, panic disorder, and generalized anxiety disorder. Persons with addictions can develop the symptoms o these disorders rom the drugs o abuse. However, mood and anxiety disorders can predate the use o drugs, and some o the motivation or drug use can stem rom the desire to sel -treat these psychological conditions. It is best to evaluate persons when they are o the drugs whenever possible. • Schizophrenia—Although drugs can cause temporary psychosis and paranoia, i these symptoms persist a ter the drugs are stopped or some time, consider schizophrenia and other causes o psychosis. • Personality disorders—These are a complicated set o disorders that can coexist and be con used with substance abuse disorder. An addict may appear to have an antisocial personality disorder when committing crimes to get money or expensive drugs. It is best to not use this diagnosis unless the behaviors continue when the person is o the drugs.

MANAGEMENT • Recognize addiction (re erred to as dependence in the DSM-IV criteria). One simple mnemonic device is the “3 C’s o addiction”: ° Compulsion to use ° Lack o Control ° Continued use despite adverse consequences • Use the “5 A’s”—Ask, Advise, Assess, Assist, and Arrange—to help smokers who are willing to quit. This model can be applied to any substance o abuse. 7 • O er counseling and pharmacotherapy to aid your patients to quit smoking. • Use the CAGE7 questionnaire when asking about alcohol use. ° Cut down (Have you ever elt you should cut down on your drinking?). ° Annoyed (Have people annoyed you by criticizing your drinking?). ° Guilty (Have you ever elt bad or guilty about your drinking?).

SUBSTANCE ABUSE ° Eye opener (Have you ever had a drink f rst thing in the morning to steady your nerves or get rid o a hangover (eye-opener)?). Interpreting the results: 1 positive suggests at risk, 2 positives suggest abuse, and 3 or 4 positives suggest dependence. This is just a screening tool, and urther evaluation is always needed. • Recommend the 12-step programs to your patients. These have been very e ective or millions o people worldwide. • Re er to substance abuse programs. Such programs include hospitaland community-based programs. Some programs include detoxif cation and others require the patient to have gone through detoxif cation be ore starting the program. There are residential treatment units, outpatient programs, and ongoing sel -help programs. Learn about the programs in your community and work with them. • When prescribing opioid analgesics or chronic pain consider the outcomes in 4 domains, or the “4 A’s.” ° Receiving adequate Analgesia? ° Experiencing improvements in Activities o daily li e? ° Experiencing any Adverse e ects? medication-taking behaviors that may be ° Demonstrating Aberrant linked to addiction?8 • When patients are exhibiting aberrant drug-taking behaviors, consider the ollowing: ° They may have an addiction. ° They may not be getting adequate pain relie taking the drug as prescribed. ° They may have a comorbid mental illness. 9 ° They may intend to distribute pain medications illegally. • Help your patients acknowledge that they have a problem and o er them help in a nonjudgmental manner. • Enlist amily members to help whenever the patient gives your permission to do so. • Demonstrate genuine concern and care; suspend judgment and you will have a higher chance o succeeding to help your patients overcome addiction. • Advanced brain imaging and genetic tests are helping us to understand the physiologic basis o addiction and will ultimately provide us with better treatments or the medical disease o addiction. PERSO NS IN RECO VERY • Be care ul how you prescribe medications to persons in recovery. A “simple” prescription or hydrocodone (Vicodin) postoperatively can start a recovered person down the road o active addiction. • Avoid giving opioids and benzodiazepines whenever there are good alternatives. Use nonsteroidal anti-in ammatory drugs (NSAIDs) or pain i possible. Use selective serotonin reuptake inhibitors (SSRIs), other antidepressants, or buspirone or anxiety i a medication is needed. • I an opioid is needed, work with the patient to monitor the amount and manner o use. Involving a third person or sponsor to help meter out the dose may prevent relapse. • Be up ront and honest about a shared goal to avoid relapse.

FO LLO W-UP • Follow-up is critical to the treatment o all types o substance abuse. Substance abuse is a chronic condition (similar to hypertension or diabetes mellitus) and requires ongoing intervention to maintain sobriety.

1199

1200

PART 19

SUBSTANCE ABUSE • The requency and intensity o ollow-up depends on the substance, the addiction, and the patient. • Do not give up on patients who relapse because it o ten takes more than one attempt be ore long-term cessation can be achieved.

PATIENT EDUCATIO N Explain to patients that addiction is a disease and not a ailing o their moral character. In orm patients about the existing treatment programs in their community and o er them names and phone numbers so that they may get help. I your patient is not ready or help today, give the numbers and names or tomorrow. Speak about the value o 12-step programs because these are e ective and everyone can a ord a 12-step program (they are ree). There are 12-step programs in the community or everyone, including nonsmokers and agnostics. PATIENT RESO URCES

• Alcoholics Anonymous (AA)—meetings and the Big Book are free. The Big Book is online or ree in three languages. http:/ / www .alcoholics-anonymous.org/ . • Narcotics Anonymous (NA)—meetings are free. The “Basic Text” costs $10; it is similar to the AA big book, but the language is more up to date and readable. http:/ / www.na.org/ index.htm. • Cocaine Anonymous (CA)—meetings are free. Their rst book “Hope, Faith and Courage: Stories rom the Fellowship o Cocaine Anonymous” was published in 1994 and sells or $10. http:/ / www.ca.org/ . • Crystal Meth Anonymous (12-step meetings) —http:/ / www .crystalmeth.org/ . PRO VIDER RESO URCES

• The National Institute on Drug Abuse (NIDA). Medical Consequences of Drug Abuse—http:/ / www.nida.nih.gov/ consequences/ . • Substance Abuse and Mental Health Services Administration— http:/ / www.samhsa.gov/ . • Drug Enforcement Agency. Multi-Media Library (includes many images o illegal drugs)—http:/ / www.usdoj.gov/ dea/ multimedia.html.

CHAPTER 236

REFERENCES 1. Substance Abuse and Mental Health Services Administration, Results from the 2010 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-41, HHS Publication No. (SMA) 11-4658. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2011. http:/ / www.samhsa.gov/ data/ NSDUH/ 2k10NSDUH/ 2k10Results.pd . 2. The National Institute on Drug Abuse (NIDA). Medical Consequences of Drug Abuse. http:/ / www.nida.nih.gov/ consequences/ . Accessed April 24, 2012. 3. Baler RD, Volkow ND. Addiction as a systems ailure: ocus on adolescence and smoking. JAmAcad Child Adolesc Psychiatry. 2011;50(4):329-339. 4. Dick DM, Bierut LJ. The genetics o alcohol dependence. Curr Psychiatry Rep. 2006;8:151-157. 5. Dick DM, Plunkett J, Wetherill LF, et al. Association between GABRA1 and drinking behaviors in the collaborative study on the genetics o alcoholism sample. Alcohol Clin Exp Res. 2006;30(7): 1101-1110. 6. The American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed (DSM-V). Washington, DC: American Psychiatric Association, 2013. 7. Fiore MC, Bailey WC, Cohen SJ, et al. TreatingTobacco Use and Dependence. Quick Reference Guide for Clinicians. Rockville, MD: U.S. Department o Health and Human Services, Public Health Service; 2000. 8. Ewing JA. Detecting alcoholism: the CAGE questionnaire. JAMA. 1984;252(14):1905-1907. 9. Passik SD, Kirsh KL, Whitcomb L, et al. A new tool to assess and document pain outcomes in chronic pain patients receiving opioid therapy. ClinTher. 2004;26(4):552-561.

PART 19

TO BACCO ADDICTIO N

237 TO BACCO ADDICTIO N Carlos Rob e rto Jaé n, MD, PhD

PATIENT STO RY A 55-year-old woman presents or ollow-up o hypertension. She has been smoking 1.5 packs o cigarettes per day since her late teens and reports that she is now ready to stop smoking. She realizes that smoking is bad or her health and does not like how smoking causes more wrinkles on the ace (Figure 237-1). She has tried unsuccess ully to stop smoking on 3 di erent occasions using nicotine replacement therapy (patches and gum) and bupropion. She has no history o a psychiatric or seizure disorder. She would like to try stopping smoking using varenicline. She is also willing to return or 4 ollow-up sessions at weekly intervals. She agrees to call a stop smoking telephone helpline (1-800-QUIT NOW) or counseling help. The patient tolerates the varenicline well and is able to stop success ully without any adverse e ects. Two years a ter treatment she continues to be abstinent and very glad o this outcome. The clinician used elements o the “5 A’s” model or treating tobacco use and dependence to success ully help this patient quit smoking. (Table 237-1).

INTRO DUCTIO N Hal o all deaths (more than 440,000) in the United States are attributed to tobacco addiction, including those caused by passive smoking. Tobacco addiction is a chronic disease, o ten developed during adolescence and early adulthood, that requires ongoing assessment and repeated intervention. There are e ective treatments that can signi cantly increase rates o long-term abstinence. There are also e ective preventive interventions that can prevent the initiation o tobacco use and reduce its prevalence among youth.

SUBSTANCE ABUSE SYNO NYMS Tobacco addiction is also known as tobacco use and dependence, tobacco use disorder, nicotine addiction, and tobacco dependence.

EPIDEMIO LO GY • Among adults who become daily smokers, nearly all rst use o cigarettes occurs by 18 years o age (88%), with 99% o rst use by 26 years o age. 1 • Almost 1 in 4 high school seniors is a current (in the past 30 days) cigarette smoker, compared with 1 in 3 young adults and 1 in 5 adults. Approximately 1 in 10 high school senior males is a current smokeless tobacco user, and approximately 1 in 5 high school senior males is a current cigar smoker. 1 • Signi cant disparities in tobacco use remain among young people nationwide. The prevalence o cigarette smoking is highest among American Indians and Alaska Natives, ollowed by whites and Hispanics, and then Asians and blacks. The prevalence o cigarette smoking is also higher among lower socioeconomic status youth. 1 • The latest data show the use o smokeless tobacco is increasing among white high school males, and cigar smoking may be increasing among black high school emales. 1 • Concurrent use o multiple tobacco products is prevalent among youth. Among those who use tobacco, nearly one-third o high school emales and more than one-hal o high school males report using more than one tobacco product in the last 30 days. 1 • Persons with psychiatric diagnoses have much higher rates o smoking than the general population. 2 • Persons with mental illness and/ or substance abuse consume 44% o all cigarettes sold in the United States, despite being only 22% o the population. 2

ETIO LO GY AND PATHO PHYSIO LO GY • The evidence on the mechanisms by which smoking causes disease indicates that there is no risk- ree level o exposure to tobacco smoke. 3 • Inhaling the complex chemical mixture o combustion compounds in tobacco smoke causes adverse health outcomes, particularly cancer and cardiovascular and pulmonary diseases, through mechanisms that include DNA damage, inf ammation, and oxidative stress. 3 • There is su cient evidence to in er that a causal relationship exists between active smoking and (a) impaired lung growth during childhood and adolescence; (b) early onset o decline in lung unction during late adolescence and early adulthood; (c) respiratory signs and symptoms in children and adolescents, including coughing, phlegm, wheezing, and dyspnea; and (d) asthma-related symptoms (eg, wheezing) in childhood and adolescence. 1 • The evidence is suggestive but not su cient to conclude that smoking by adolescents and young adults is not associated with signi cant weight loss, contrary to young people’s belie . 1 FIGURE 237-1 A 55-ye ar-old woman with p re mature wrinkling rom ye ars o he avy smoking . Note the nume rous line s around he r mouth and lip s. (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

• Through multiple de ned mechanisms, the risk and severity o many adverse health outcomes caused by smoking are directly related to the duration and level o exposure to tobacco smoke. 3

1201

PART 19

1202

SUBSTANCE ABUSE

Ch a pt e r 237

TABLE 237-1 The “5 A’s” Mod e l or Tre ating Tob acco Use and De p e nd e nce

Ask ab out tob acco use .

Id e nti y and d ocume nt tob acco use status or e ve ry p atie nt at e ve ry visit.

Ad vise to q uit.

In a cle ar, strong , and p e rsonalize d manne r, urg e e ve ry tob acco use r to q uit.

Asse ss willing ne ss to make a q uit atte mp t.

Is the tob acco use r willing to make a q uit atte mp t at this time ?

Assist in q uit atte mp t.

For the p atie nt willing to make a q uit atte mp t, o e r me d ication and p rovid e or re e r or counse ling or ad d itional tre atme nt to he lp the p atie nt q uit. For p atie nts unwilling to q uit at the time , p rovid e inte rve ntions d e sig ne d to incre ase uture q uit atte mp ts.

Arrang e ollow-up .

For the p atie nt willing to make a q uit atte mp t, arrang e or ollow-up contacts, b e g inning within the rst we e k a te r the q uit d ate . For p atie nts unwilling to make a q uit atte mp t at the time , ad d re ss tob acco d e p e nd e nce and willing ne ss to q uit at ne xt clinic visit.

Data rom Tre ating Tob acco Use and De p e nd e nce : 2008 Up d ate . US De p artme nt o He alth and Human Se rvice s; 2008. http ://www.ahrq .g ov/clinic/tob acco/tre ating _tob acco_use 08.p d .

• Sustained use and long-term exposures to tobacco smoke are caused by the power ul addicting e ects o tobacco products, which are mediated by diverse actions o nicotine and perhaps other compounds, at multiple types o nicotinic receptors in the brain. 3 • Nicotine stimulates the release o multiple neurotransmitters, including dopamine, norepinephrine, acetylcholine, glutamate, serotonin, β-endorphin, and γ-aminobutyric acid. 4 • Low levels o exposure, including exposures to secondhand tobacco smoke, lead to a rapid and sharp increase in endothelial dys unction and inf ammation, which are implicated in acute cardiovascular events and thrombosis. 3 • There is insu cient evidence that product modi cation strategies to lower emissions o speci c toxicants in tobacco smoke reduce risk or the major adverse health outcomes. 3

RISK FACTO RS Given their developmental stage, adolescents and young adults are uniquely susceptible to social and environmental inf uences to use tobacco. • Socioeconomic actors and educational attainment inf uence the development o youth smoking behavior. The adolescents most likely to begin to use tobacco and progress to regular use are those who have lower academic achievement. 1 • The evidence is su cient to conclude that there is a causal relationship between peer group social inf uences and the initiation and maintenance o smoking behaviors during adolescence. 1 • A ective processes play an important role in youth smoking behavior, with a strong association between youth smoking and negative e ect. 1 • The evidence is suggestive that tobacco use is a heritable trait, more so or regular use than or onset. The expression o genetic risk or smoking among young people may be moderated by small-group and larger social–environmental actors. 1

DIAGNO SIS CLINICAL FEATURES • History—Most tobacco users express a desire to stop using tobacco but report repeated ailures in their attempts. All patients should be asked i they use tobacco and should have their tobacco use status documented on a regular basis. Evidence shows that clinic screening systems, such as expanding the vital signs to include tobacco use status, or the use o other reminder systems, such as chart stickers or computer prompts, signi cantly increase rates o clinician intervention. 5 SOR • Physical—Individuals with tobacco addiction may easily be detected by the ollowing: ° Distinctive odor o tobacco smoke ° Smoker’s cough ° Raspy or hoarse voice (see Chapter 32, The Larynx [Hoarseness]) ° Pack o cigarettes in the ront pocket o the shirt ° Wrinkles in excess o what would be expected or their age (Figure 237-2) • Smoker’s face is described as the ollowing: ° “Lines or wrinkles on the ace, typically radiating at right angles rom the upper and lower lips or corners o the eyes, deep lines on the cheeks, or numerous shallow lines on the cheeks and lower jaw” (see Figure 237-2). eatures with prominence o the ° “A subtle gauntness o the acial underlying bony contours.”6 • The oral cavity o smokers o ten shows signs o prolonged exposure to tobacco in the orm o the ollowing: ° Yellow and brown teeth (Figures 237-3 to 237-5) ° Angular cheilitis (see Figure 237-3) (see Chapter 29, Angular Cheilitis) ° Gingivitis and periodontitis (see Figure 237-4) (see Chapter 35, Gingivitis and Periodontal Disease) • There may be other serious conditions within the oral cavity such as the ollowing:

t O Ba CCO a DDICt IO N

FIGURE 237-2 Smoke r’s ace d e scrib e d as “one or more o the ollowing : (a) line s or wrinkle s on the ace , typ ically rad iating at rig ht ang le s rom the up p e r and lo we r lip s or corne rs o the e ye s, d e e p line s on the che e ks, or nume rous shallow line s on the che e ks and lowe r jaw. (b ) A sub tle g auntne ss o the acial e ature s with p ro mine nce o the und e rlying b ony contours.6 (Re p rod uce d with p e rmission rom Usatine R, Moy R, Tob inick E, Sie g e l D. Skin Surg e ry: A Practical Guid e . St. Louis, MO : Mosb y; 1998.)

PART 19

SUBSTANCE ABUSE

FIGURE 237-5 Le ukop lakia on the b uccal mucosa and g ing iva in a tob acco smoke r. Althoug h much o the le ukop lakia is on the b ite line , the risk o sq uamous ce ll carcinoma o the oral cavity must b e asse sse d with ap p rop riate b iop sie s. (Re p rod uce d with p e rmissio n rom Richard P. Usatine , MD.)

° Leukoplakia—A premalignant condition (see Figure 237-5) (see Chapter 38, Leukoplakia) ° Nicotine stomatitis (Figure 237-6) ° Squamous cell carcinoma (Figures 237-7 and 237-8) (see Chapter 39, Oropharyngeal Cancer) • Withdrawal symptoms—Symptoms associated with tobacco addiction withdrawal include a dysphoric or depressed mood, insomnia, irritability, rustration or anger, anxiety, di culty concentrating, restlessness, decreased heart rate, and increased appetite or weight gain. 7 None o the withdrawal symptoms are li e threatening, as they can be with other drugs like alcohol and opiates. Their intensity peaks during the rst week and most last no more than 2 to 4 weeks ollowing abstinence. 8 • Complications—Continuing use o tobacco causes multiple cancers and the development and/ or exacerbation o multiple chronic diseases as summarized in Figure 237-9. FIGURE 237-3 Angular cheilitis and tobacco staining o the tong ue rom chewing tobacco. (Rep roduced with p ermission rom Richard P. Usatine, MD.)

FIGURE 237-4 Tob acco staining te e th and p e riod ontitis rom smoking to b acco. (Re p rod uce d with p e rmission rom Richard P. Usatine , MD.)

FIGURE 237-6 Nicotine stomatitis ove r the hard p alate rom smoking tob acco. (Re p rod uce d with p e rmission rom Rizzolo D, Chiod o TA. Le sion on the hard p alate . J Fam Pract. 2008;57(1):33-35. Re p rod uce d with p e rmission rom Frontline Me d ical Communications.)

1203

PART 19

1204

Ch a pt e r 237

SUBSTANCE ABUSE

FIGURE 237-7 Sq uamous ce ll carcinoma o b uccal mucosa in a man who use d che wing to b acco along with smoking . (Re p rod uce d with p e rmissio n rom Richard P. Usatine , MD.)

FIGURE 237-8 Sq uamous ce ll carcinoma o the inne r lip in a cig ar smoke r. (Re p rod uce d with p e rmission rom Ge rald Fe rritti, DDS.)

S mo king Canc e rs

S e c o ndhand S mo ke Expo s ure Chro nic Dis e as e s

Childre n

Adults

S troke Blindne s s, ca ta ra cts Oropha rynx

Pe riodontitis

La rynx

Aortic a ne urys m

Es opha gus

Corona ry he a rt dis e a s e

Tra che a , bronchus, a nd lung

P ne umonia

Acute mye loid le uke mia S toma ch Pa ncre a s

Athe ros cle rotic pe riphe ra l va s cula r dis e a s e Chronic obs tructive pulmona ry dis e a s e, a s thma , a nd othe r re s pira tory e ffe cts

Kidney a nd ure te r Ce rvix Bla dde r

Hip fra cture s

Middle e a r dis e a s e Re s pira tory symptoms, impa ire d lung function Lowe r re s pira tory illne s s

Na s a l irrita tion Lung ca nce r Corona ry he a rt dis e a s e

S udde n infa nt de a th syndrome Re productive e ffe cts in wome n: low brith we ight

Re productive e ffe cts in wome n (including re duce d fe rtility)

So u rc e237-9 : US DHHS FIGURE He alth2004. conse 2006. q ue nce s causally linke d to smoking and se cond hand smoking . (Re p rod uce d with p e rmission rom U.S. De p artme nt o He alth and Human Se rvice s. How Tob acco Smoke Cause s Dise ase : The Biolog y and Be havioral Basis or Smoking -Attrib utab le Dise ase : A Re p ort o the Surg e on Ge ne ral. Atlanta, GA: U.S. De p artme nt o He alth and Human Se rvice s, Ce nte rs or Dise ase Control and Pre ve ntion, National Ce nte r or Chronic Dise ase Pre ve ntion and He alth Promotion, O f ce on Smoking and He alth; 2010.)

PART 19

t O Ba CCO a DDICt IO N

• Emphysema may signi cantly impair lung unction and lead to death (see Chapter 56, Chronic Obstructive Pulmonary Disease). Centrilobular emphysema occurs with carbon deposits in the destroyed lung tissue. LABO RATO RY TESTING • Some specialized assessments o individual and environmental attributes provide in ormation or tailoring treatment and may predict quitting success. Specialized assessments re er to the use o ormal instruments (eg, questionnaires, clinical interviews, or physiologic indices such as carbon monoxide, serum nicotine/ cotinine levels, and/ or pulmonary unction) that may be associated with cessation outcome. In addition, clinicians may nd other assessments relevant to medication use and speci c populations when selecting treatment. The use o biochemical con rmation (use o biological samples, such as expired air, saliva, urine, or blood, to measure tobacco-related compounds, such as nicotine, cotinine, and carboxyhemoglobin) is particularly use ul to veri y abstinence during pregnancy treatment where reports o deception have been documented. 5 Variables targeted by specialized assessments that predict treatment success include the ollowing: ° High motivation ° Readiness to change in the next month ° Moderate-to-high sel -e cacy (con dence in his or her ability to stop using tobacco success ully) ° Supportive social network • Variables associated with lower abstinence rates include the ollowing: ° High nicotine dependence ° Psychiatric comorbidity and substance use (particularly elevated depressive symptoms, schizophrenia, and current alcohol abuse) ° High stress level 5 Exposure to other smokers ° IMAGING • There are currently no practical clinical applications or imaging studies that are help ul when treating individuals with tobacco addiction. Experimentally several magnetic resonance imaging (MRI), unctional MRI, and positron emission tomography (PET) scan studies provide help ul clues as to mechanisms o actions o tobacco addiction. 3 • The United States Preventive Services Task Force (USPSTF) now recommends one-time screening or abdominal aortic aneurysm (AAA) by ultrasonography in men aged 65 to 75 who have ever smoked (more than 100 cigarettes over a li etime). SO R This screening is not recommended or women or or men who never smoked. (http:/ / www.uspreventiveservicestask orce.org/ uspst 05/ aaascr/ aaars.pd )

MANAGEMENT The combination o counseling and medication is more e ective or smoking cessation than either medication or counseling alone. There ore, whenever easible and appropriate, both counseling and medication should be provided to patients trying to stop smoking. 5 SO R NO NPHARMACO LO GIC (CO UNSELING INTERVENTIO NS) • Minimal interventions lasting less than 3 minutes increase overall tobacco abstinence rates. Every tobacco user should be o ered at least a minimal intervention, whether or not he or she is re erred to an intensive intervention. 5 SO R

SUBSTANCE ABUSE • Two types o counseling and behavioral therapies result in higher abstinence rates: (a) providing smokers with practical counseling (problem-solving skills/ skills training), and (b) providing support and encouragement as part o treatment. These types o counseling elements should be included in smoking cessation interventions. 5 SO R

• There is a strong dose–response relationship between the session length o person-to-person contact and success ul treatment outcomes. Intensive interventions are more e ective than less-intensive interventions and should be used whenever possible. 5 SO R • Proactive telephone counseling, group counseling, and individual counseling ormats are e ective and should be used in smoking cessation interventions. 5 SO R • Person-to-person treatment delivered or 4 or more sessions appears especially e ective in increasing abstinence rates. There ore, i easible, clinicians should strive to meet 4 or more times with individuals quitting tobacco use. 5 SO R • Motivational interviewing or smokers not willing to make an attempt to stop tobacco use includes the ollowing: ° Motivational intervention techniques appear to be e ective in increasing a patient’s likelihood o making a uture quit attempt. There ore, clinicians should use motivational techniques to encourage smokers who are not currently willing to quit to consider making a quit attempt in the uture. 5 SO R ° The 4 general principles that underlie motivational intervention are (a) express empathy, (b) develop discrepancy, (c) roll with resistance, and (d) support self-ef cacy (Table 237-2). Motivational intervention researchers have ound that having patients use their own words to commit to change is more e ective than clinician exhortations, lectures, or arguments or quitting, which tend to increase rather than lessen patient resistance to change. 5 MEDICATIO NS Clinicians should encourage all patients attempting to quit to use e ective medications or tobacco dependence treatment, except where contraindicated or or speci c populations or which there is insu cient evidence o e ectiveness (eg, pregnant women, smokeless tobacco users, light smokers, and adolescents). 5 SO R • In the United States, there are 7 Food and Drug Administration (FDA)approved medications or treating tobacco use and these rst-line medications should be recommended: bupropion SR (Zyban), nicotine gum, nicotine inhaler, nicotine lozenge, nicotine nasal spray, nicotine patch, and varenicline (Chantix). Precautions, bene ts, and disadvantages or these 7 medications are ound in Boxes 237-1 to 237-7. • The clinician should consider the rst-line medications shown to be more e ective than the nicotine patch alone: 2 mg/ d varenicline or the combination o long-term nicotine patch use + ad libitum nicotine replacement therapy (NRT). 5 • Certain combinations o rst-line medications have been shown to be e ective smoking cessation treatments. There ore, clinicians should consider using these combinations o medications with their patients who are willing to quit. Following are the e ective combination medications: ° Long-term (> 14 weeks) nicotine patch + other NRT (gum and spray) ° The nicotine patch + the nicotine inhaler 5 SO R The nicotine patch + bupropion SR °

1205

1206

PART 19

SUBSTANCE ABUSE

Ch a pt e r 237

TABLE 237-2 Motivational Inte rvie wing Strate g ie s

Exp re ss e mp athy.

•

Use op e n-e nd e d q ue stions to e xp lore : ° The imp ortance o ad d re ssing smoking or othe r tob acco use (e g , “How imp ortant d o you think it is or you to q uit smoking ?”) ° Conce rns and b e ne ts o q uitting (e g , “What mig ht hap p e n i you q uit?”)

•

Use re f e ctive liste ning to se e k share d und e rstand ing : ° Re f e ct word s or me aning (e g , “So you think smoking he lp s you to maintain your we ig ht”). ° Summarize (e g , “What I have he ard so ar is that smoking is some thing you e njoy. O n the othe r hand , your b oy rie nd hate s your smoking , and you are worrie d you mig ht d e ve lop a se rious d ise ase .”).

De ve lop d iscre p ancy.

•

Normalize e e ling s and conce rns (e g , “Many p e op le worry ab out manag ing without cig are tte s.”).

•

Sup p ort the p atie nt’s autonomy and rig ht to choose or re je ct chang e (e g , “I he ar you saying you are not re ad y to q uit smoking rig ht now. I’m he re to he lp you whe n you are re ad y.”).

•

Hig hlig ht the d iscre p ancy b e twe e n the p atie nt’s p re se nt b e havior and e xp re sse d p rioritie s, value s, and g oals (e g , “It sound s like you are ve ry d e vote d to your amily. How d o you think your smoking is a e cting your child re n?”).

•

Re in orce and sup p ort “chang e talk” and “commitme nt” lang uag e : ° “So, you re alize how smoking is a e cting your b re athing and making it hard to ke e p up with your kid s.” ° “It’s g re at that you are g oing to q uit whe n you g e t throug h this b usy time at work.”

•

Build and d e e p e n commitme nt to chang e : ° “The re are e e ctive tre atme nts that will e ase the p ain o q uitting , includ ing counse ling and many me d ication op tions.” ° “We would like to he lp you avoid a stroke like the one your athe r had .”

Roll with re sistance .

•

Back o and use re f e ction whe n the p atie nt e xp re sse s re sistance : ° “Sound s like you are e e ling p re ssure d ab out your smoking .”

•

Exp re ss e mp athy: ° “You are worrie d ab out how you would manag e withd rawal symp toms.”

•

Ask p e rmission to p rovid e in ormation: ° “Would you like to he ar ab out some strate g ie s that can he lp you ad d re ss that conce rn whe n you q uit?”

Sup p ort se l -e cacy.

•

He lp the p atie nt to id e nti y and b uild on p ast succe sse s: ° “So you we re airly succe ss ul the last time you trie d to q uit.”

•

O e r op tions or achie vab le small ste p s toward chang e : ° Call the q uitline (1–800-Q UIT-NO W) or ad vice and in ormation. ° Re ad ab out q uitting b e ne ts and strate g ie s. ° Chang e smoking p atte rns (e g , no smoking in the home ). ° Ask the p atie nt to share his or he r id e as ab out q uitting strate g ie s.

Data rom Tre ating Tob acco Use and De p e nd e nce : 2008 Up d ate . US De p artme nt o He alth and Human Se rvice s; 2008. http ://www .ahrq .g ov/clinic/tob acco/tre ating _tob acco_use 08.p d .

PART 19

t O Ba CCO a DDICt IO N

Bo x 237-1 Nicotine Re p lace me nt The rap y: Gum

SUBSTANCE ABUSE Bo x 237-2 Nicotine Re p lace me nt The rap y: Loze ng e

Nicore tte , Ge ne ric (O TC)

Nicore tte Mini Loze ng e , Ge ne ric (O TC)

PRECAUTIO NS

PRECAUTIO NS

Re ce nt (≤2 we e ks) myocard ial in arction

Re ce nt (≤2 we e ks) myocard ial in arction

•

Se rious und e rlying arrhythmias

•

Se rious und e rlying arrhythmias

•

Se rious or worse ning ang ina p e ctoris

•

Se rious or worse ning ang ina p e ctoris

•

Te mp oromand ib ular joint d ise ase

•

Pre g nancy and b re ast e e d ing

•

Pre g nancy and b re ast e e d ing

•

Ad ole sce nts (< 18 ye ars)

•

Ad ole sce nts (5 crite ria p ositive • “Exte rnal” symp toms o d ys unction – Social and amily d isrup tion – Prob le ms with job , school, p are nting – Le g al p rob le ms (e g , DWI) • Maximum d rinks ab out 10-24 p e r d rinking d ay • Re curre nt e p isod e s ove r ye ars to d e cad e s (ave rag e o 5)

The ap p roach o DSM-V d iag nosis 13 (Re p rod uce d with p e rmission from Mark Wille nb ring , MD.)

PART 19

a LCO h O LISM (a LCO h O L USe DISO r De r )

BO X 238-2 Scre e ning Q ue stion Re comme nd e d b y the National Institute on Alcoho l Ab use and Alcoholism (NIAAA)

How many times in the past year have you had the ollowing? • 5 or more d rinks in a d ay? ( or me n) • 4 or more d rinks in a d ay? ( or wome n) O ne stand ard d rink is e q uivale nt to 12 oz o b e e r, 5 oz o wine , or 1.5 oz o 80-p roo sp irits. http ://www.niaaa.nih.g ov/g uid e .

SUBSTANCE ABUSE to be identi ed through screening, rather than presenting with this problem. • Patients with more severe, recurrent alcohol dependence o ten present with intoxication, withdrawal, or medical complications o heavy drinking, such as liver disease or pancreatitis. I these disorders are present, they demonstrate the expected physical mani estations. Like other patients with chronic, treatment-re ractory illness, they have a chronic course, with periodic relapses or even with ongoing chronic illness. TYPICAL DISTRIBUTIO N

(eg, “How much do you drink?”) is less likely to yield help ul answers. Box 238-2 states the speci c screening questions recommended by the NIAAA. • Most heavy drinkers are not symptomatic. Thus, they do not have alcohol-related symptoms. They can only be detected through screening or quantity and requency o drinking. Screening ocused on symptoms o alcohol use disorder, such as the well-known CAGE (“Have you ever tried to cut down on your drinking? Have you ever elt annoyed by criticism o your drinking? Have you ever elt guilty about your drinking? Have you ever had a morning eye-opener?”), will not detect asymptomatic at-risk drinkers, and it per orms poorly compared to almost all other methods. 12 It is important to enquire about quantity and requency o drinking in order to identi y at-risk drinkers and patients with unctional alcohol dependence. The Alcohol Use Disorders Identi cation Test (AUDIT) (Figure 238-3) is the gold standard or a written questionnaire; it only takes about 3 minutes to complete and is easy to score. A score o 8 or more or men or 4 or more or women suggests excessive drinking. 1 • Current diagnostic criteria or alcohol use disorder are based on the DSM-V. 13 The presence o any 2 o 11 symptoms (Box 238-3) is enough to establish a diagnosis, where the number o symptoms met is highly correlated with severity o the disorder. 13 • According to NIAAA, healthy adult men should not drink in excess o 4 standard US drinks in any day, or 14 in any week, and adult women should not exceed 3 drinks in any day and 7 in any week. 1 Low-risk drinking limits may be less or certain groups, such as adults older than age 65 years, or in the presence o medical illnesses, such as liver disease. Women who are pregnant or are trying to become pregnant should be advised to abstain completely. 14 • Drinking in excess o these limits is considered unhealthy, placing heavy drinkers at elevated risk or developing AUD and associated complications such as liver disease. 15 Approximately 30% o US adults age 18 years and older drink in excess o low-risk limits at least once in any year. About 4 o 5 o them do not meet diagnostic criteria or a disorder, and are considered to be “at-risk” or developing one. 1 In other words, this group has an asymptomatic risk actor similar to hypertension or hyperlipidemia. At-risk drinkers are typically unaware that their drinking constitutes a health risk. This does not ref ect “denial” but rather the lack o in ormation available to the public about what constitutes high-risk drinking or how to measure consumption. For example, how many standard US drinks are in a 7-oz martini? (Depending on the speci c way it is mixed, the answer is about 4.) It is much easier to obtain dietary in ormation about ood than in ormation about alcohol content in a beverage. • Patients with unctional alcohol dependence are aware o struggling with their alcohol consumption, but lack serious li e consequences at this time. Most are open to changing their drinking, but they may need

In a given year, 30% o the adult US population engages in unhealthy drinking at least once (see Figure 238-1). In an average primary care practice, approximately 10% to 15% o outpatients are heavy drinkers. LABO RATO RY TESTING • The most sensitive way to detect heavy drinking is to ask about the requency o heavy drinking. Use o a written questionnaire such as the AUDIT can be help ul (see Figure 238-3). 16 • The most sensitive but least speci c laboratory test is γ-glutamyltrans erase (GGT). Carbohydrate-de cient trans errin provides similar sensitivity but better speci city but is not widely available. 17 • Other transaminases such as aspartate aminotrans erase (AST) and alanine aminotrans erase (ALT) are less sensitive, and require hepatic cell destruction be ore they are elevated. Thus, they are not very sensitive or detecting heavy drinking but they may be help ul in ollowing patients who have elevated values at baseline. IMAGING There are no imaging tests that detect heavy drinking itsel . Abdominal ultrasound is o ten help ul in evaluating alcoholic liver disease.

DIFFERENTIAL DIAGNO SIS It is important to distinguish between AUD and asymptomatic at-risk drinking. AUD is characterized by preoccupation with and impaired control over drinking.

MANAGEMENT See Box 238-4. NO NPHARMACO LO GIC • Brie counseling and advice to reduce drinking is e ective or at-risk drinking, resulting in 15% to 20% reduction in drinking or at least 1 year. 2 • Alcohol dependence requires either more intensive counseling and/ or antirelapse medications. The relationship between intensity and setting (inpatient, residential, or outpatient) is complex. Most studies show no di erence in 1-year outcomes based on intensity or setting. 18 For example, in a highly controlled, well-done study, 174 persons with alcoholism were randomly assigned to partial hospital treatment or extended inpatient rehabilitation a ter inpatient evaluation and/ or detoxi cation. The outpatient group attended daily Monday through

1215

1216

PART 19

Ch a pt e r 238

SUBSTANCE ABUSE

AUDIT PATIENT: Because alcohol use can a ect your health and can interfere with certain medications and treatments, it is important that we ask some questions about your use of alcohol. Your answers will remain con dential, so please be honest. For each question in the chart below, place an X in one box that best describes your answer. NOTE: In the U.S., a single drink serving contains about 14 grams of ethanol or “pure” alcohol. Although the drinks below are di erent sizes, each one contains the same amount of pure alcohol and counts as a single drink: 12 oz. of beer (about 5% alcohol)

=

8-9 oz. of malt liquor

=

(about 7% alcohol)

Questions

5 oz. of wine

=

(about 12% alcohol)

1.5 oz. of hard liquor (about 40% alcohol)

0

1

2

3

4

0

1. How often do you have a drink containing alcohol?

Never

Monthly or less

2 to 4 times a month

2 to 3 times a week

4 or more times a week

0

2. How many drinks containing alcohol do you have on a typical day when you are drinking?

1 or 2

3 or 4

5 or 6

7 to 9

10 or more

0

3. How often do you have 5 or more drinks on one occasion?

Never

Less than monthly

Monthly

Weekly

Daily or almost daily

0

4. How often during the last year have you found that you were not able to stop drinking once you had started?

Never

Less than monthly

Monthly

Weekly

Daily or almost daily

0

5. How often during the last year have you failed to do what was normally expected of you because of drinking?

Never

Less than monthly

Monthly

Weekly

Daily or almost daily

0

6. How often during the last year have you needed a rst drink in the morning to get yourself going after a heavy drinking session?

Never

Less than monthly

Monthly

Weekly

Daily or almost daily

0

7. How often during the last year have you had a feeling of guilt or remorse after drinking?

Never

Less than monthly

Monthly

Weekly

Daily or almost daily

0

8. How often during the last year have you been unable to remember what happened the night before because of your drinking?

Never

Less than monthly

Monthly

Weekly

Daily or almost daily

0

9. Have you or someone else been injured because of your drinking?

No

0

Yes, but not in the last year

0

Yes, during the last year

0

10. Has a relative, friend, doctor, or other health care worker been concerned about your drinking or suggested you cut down?

No

0

Yes, but not in the last year

0

Yes, during the last year

0

Total

0

Note: is questionnaire (the AUDIT) is reprinted with permission from the World Health Organization. To re ect drink serving sizes in the United States (14g of pure alcohol), the number of drinks in question 3 was changed from 6 to 5. A free AUDIT manual with guidelines for use in primary care settings is available online at www.who.org.

Excerpted from NIH Publication No. 07-3769 National Institute on Alcohol and Alcoholism www.niaaa.nih.gov/guide

FIGURE 238-3 The AUDIT q ue stionnaire . Score s are ad d e d to d e te rmine the total. Positive scre e ns are ind icate d b y total score s g re ate r than o r e q ual to 8 in me n and g re ate r than or e q ual to 4 in wome n. Hig he r score s ind icate more se ve re alcohol involve me nt. Score s g re ate r than 16 sug g e st the p ossib ility o alcohol d e p e nd e nce .

a LCO h O LISM (a LCO h O L USe DISO r De r )

PART 19

SUBSTANCE ABUSE

BO X 238-3 DSM-V Crite ria or Alcohol Use Disord e r13

A p rob le matic p atte rn o alcohol use le ad ing to clinically sig ni cant imp airme nt or d istre ss, as mani e ste d b y at le ast 2 o the ollowing symp toms, occurring within a 12-month p e riod : 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

11.

Alcohol is o te n take n in larg e r amounts or ove r a long e r p e riod than was inte nd e d . The re is a p e rsiste nt d e sire or unsucce ss ul e orts to cut d own or control alcohol use . A g re at d e al o time is sp e nt in activitie s ne ce ssary to ob tain alcohol, use alcohol, or re cove r rom its e e cts. Craving , or a strong d e sire or urg e to use alcohol. Re curre nt alcohol use re sulting in a ailure to ul ll major role ob lig ations at work, school, or home . Continue d alcohol use d e sp ite having p e rsiste nt or re curre nt social or inte rp e rsonal p rob le ms cause d or e xace rb ate d b y the e e cts o alcohol. Imp ortant social, occup ational, or re cre ational activitie s are g ive n up or re d uce d b e cause o alcohol use . Re curre nt alcohol use in situations in which it is p hysically hazard ous. Alcohol use is continue d d e sp ite knowle d g e o having a p e rsiste nt or re curre nt p hysical or p sycholog ical p rob le m that is like ly to have b e e n cause d or e xace rb ate d b y alcohol. Tole rance , as d e ne d b y e ithe r o the ollowing : • A ne e d or marke d ly incre ase d amounts o alcohol to achie ve intoxication or d e sire d e e ct. • A marke d ly d iminishe d e e ct with continue d use o the same amount o alcohol. Withd rawal, as mani e ste d b y e ithe r o the ollowing : • The characte ristic withd rawal synd rome or alcohol (re e r to Crite ria A and B o the crite ria se t or alcohol withd rawal). • Alcohol (or a close ly re late d sub stance , such as a b e nzod iaze p ine ) is take n to re lie ve or avoid withd rawal symp toms.

Se ve rity is g rad e d b ase d on the numb e r o symp toms p re se nt as b e low: • Mild : Pre se nce o 2-3 symp toms. • Mod e rate : Pre se nce o 4-5 symp toms. • Se ve re : Pre se nce o 6 or more symp toms. BO X 238-4 Clinical Pre ve ntion and Tre atme nt o Alcohol Use Disord e r

Cat e g o ry

Manag e me nt

At-risk d rinke rs Goal: risk re d uction

• Brie counse ling to q uit or cut d own • Hand p atie nts Re thinking Drinking b ookle t • Re p e ate d counse ling incre ase s e e ctive ne ss

Functional alcohol use d isord e r Goal: long -te rm ab stine nce or low-risk d rinking (e g , re cove ry)

• Antire lap se me d ications – Naltre xone (oral, inje ction) – Top iramate (Top amax) – Disul ram (Antab use ) • Brie b e havioral sup p ort (me d ication manag e me nt) • Re comme nd Alcoholics Anonymous • O e r re e rral to ad d iction sp e cialist e sp e cially i ails to re sp ond to p rimary care tre atme nt

Se ve re re curre nt alcohol use d isord e r

• O e r re e rral to ad d iction sp e cialist • Re comme nd Alcoholics Anonymous

Goals: • Re d uce re q ue ncy, se ve rity and le ng th o re lap se s

• Me d ications – Tre at withd rawal i ne e d e d – Antire lap se me d ications

• Tre at comp lications

• Care coord ination

• Slow the rate o d e te rioration

• Inte g rate me d ical, p sychiatric, ad d iction tre atme nt

• Aim or ull re cove ry b ut re cog nize it may not b e achie ve d

• Tre atme nt or as long as ne e d e d , usually ye ars to d e cad e s

1217

PART 19

1218

SUBSTANCE ABUSE Friday therapy alongside the group that was assigned to 6 months o psychiatric inpatient hospitalization. The study ound no additional bene t to extended hospitalization. 19 • However, there are circumstances that make providing structured sober housing important: among people who are homeless, those who cannot stop drinking while living independently, and people with signi cant coexisting psychiatric illness. 18 The degree o housing structure required, however, is relatively independent o the intensity or type o treatment given. Some patients require a great deal o housing structure but very ew treatment services, whereas others are stably housed but require intensive and prolonged treatment. Thus it makes sense to uncouple housing structure rom treatment decisions, as there is no apparent bene t to having patients stay in a acility overnight while they are receiving treatment services. • Increasingly, treatment or recurrent AUD (dependence) is being conceptualized as management o a chronic illness. 20 A recent study ound that continued care that included primary care management as well as continued access to specialty addiction care resulted in improved outcomes and reduced costs. 21

Ch a pt e r 238

500 mg daily. Disul ram therapy is the most e ective or maintaining abstinence, because any signi cant alcohol use will cause a reaction. It works best when administration is monitored by a amily member, roommate, or riend. The most common side e ect is a metallic taste. Less common are peripheral neuropathy, optical neuritis, and delirium or psychosis. A rare but serious idiosyncratic risk is that o ulminant hepatitis, o ten leading to liver ailure and death. • Topiramate is thought to work by normalizing the γ-aminobutyric acid (GABA)-glutamate imbalance that occurs with severe alcohol dependence. It both reduces desire to drink and the reward that occurs with drinking. Because o side e ects, it is important to start at a low dose, or example, 25 mg be ore bedtime, and ramp up slowly over 4 to 8 weeks to a target dose o 200 to 800 mg daily. The most distressing side e ect is cognitive dys unction, best described as di culty with word nding. Perioral paresthesias are common but reversible. Because o induction o renal tubular acidosis topiramate increases excretion o calcium, thus increasing the risk or renal calculi, especially in patients with a previous history.

• Long-term regular medical ollow-up that simply attends to drinking and encourages abstinence is e ective or reducing drinking among patients with medical complications such as liver cirrhosis or pancreatitis. 22

• Acamprosate is licensed or alcohol dependence by the Food and Drug Administration (FDA) but the last 3 large multisite trials demonstrated no e ectiveness. 25-27 It is expensive and must be taken 3 times a day. I it is e ective at all, it would be in very severe dependence with a history o physical withdrawal.

MEDICATIO NS

CO MPLEMENTARY AND ALTERNATIVE THERAPY

• Several antirelapse medications are available or alcohol dependence. Their average e cacy is similar to that or selective serotonin reuptake inhibitor (SSRI) antidepressants in treating depression. 23,24

• No complementary or alternative therapies have proven e cacy in alcohol dependence.

• Naltrexone 50 mg daily or as needed or each drinking occasion reduces relapse rates and quantity o drinking per occasion. It reduces craving or alcohol and the reward or “kick” an individual experiences when rst beginning a drinking episode. This reduces the compulsive quality o drinking, making it easier to stop be ore a ull relapse occurs. Its e ectiveness is determined by genetic actors; it is most e ective among northern Europeans and least likely to be e ective among A rican Americans. In the author’s experience, naltrexone 25 to 50 mg as needed per drinking occasion may help at-risk drinkers reduce excessive alcohol use, especially in social situations. Approximately 10% o patients will experience nausea. Patients should be warned that usual doses o oral opioids such as hydrocodone will not work because o the opioid blockade, so naltrexone should be stopped at least 3 days prior to elective procedures. In emergencies the blockade can be overridden, but the therapeutic index is reduced. Although initially quite concerning, in practice this has not proved to be a signi cant problem. Naltrexone also is available in a long-acting injectable ormulation that only requires monthly administration. • Disul ram 250 mg daily acts by blocking the breakdown o ethanol, resulting in increased levels o acetaldehyde, which causes an adverse f ushing reaction. The disul ram-ethanol reaction is thus dose related; a small amount o alcohol such as might exist in wine vinegar, or example, might cause mild acial f ushing, whereas drinking several glasses o wine or beer, or several ounces o distilled spirits, will cause a more severe reaction. Disul ram-ethanol reactions may be very unpleasant but are unlikely to be harm ul in the absence o preexisting ischemic heart disease. Reactions can occur up to several days a ter discontinuation, so patients should be warned. Some patients will not develop a disul ram-ethanol reaction at the standard dose and require

• Un ortunately, some treatment programs continue to o er “nutritional therapy,” treatment guided by single-photon emission computed tomography (SPECT) scans, acupuncture and other unproven therapies, but there is no evidence o their e ectiveness. • Twelve-step community support groups such as Alcoholics Anonymous (AA) help some patients with severe alcohol dependence. People who a liate and stay with AA have better outcomes than those who do not. REFER O R HO SPITALIZE • Alcohol withdrawal is best managed in the hospital or patients with histories o alcohol withdrawal seizures or delirium, or who have medical conditions that might destabilize during withdrawal, such as ischemic heart disease or ragile diabetes. • Alcohol withdrawal delirium requires hospitalization, usually in an intensive care unit. • Most patients will not accept a re erral to an addiction rehab program, but will accept treatment by their primary care physician. Patients who are naïve to rehab programs may bene t rom re erral. However, rehab programs tend to o er the same programming no matter how many times an individual has been exposed to it. There is no reason to believe that repeated exposure to the same type o program improves outcomes. I an addiction medical specialist is available, re erral or patients not responding to initial primary care management is indicated. • Inpatient psychiatric hospitalization con erred no added bene t compared with outpatient treatment, but inpatient treatment might be use ul or patients who are unable to abstain or the 4 to 8 weeks necessary or outpatient treatment. 28 Sober housing coupled with an outpatient treatment program can also be bene cial or some.

PART 19

a LCO h O LISM (a LCO h O L USe DISO r De r )

A

SUBSTANCE ABUSE

B

C

FIGURE 238-4 A. Clinician’s Guid e and B. Pocke t Guid e ve rsions are availab le rom the National Institute on Alcohol Ab use and Alcoholism. The se Guid e s p rovid e p hysicians with the tools ne e d e d to scre e n or e xce ssive alcohol use , d iag nose alcohol use d isord e r, and p rovid e the ap p rop riate counse ling and p harmacothe rap y to the ir p atie nts. A comp anion vid e o case stud ie s training p rog ram o e rs p hysicians the op p ortunity to se e the Guid e s’ p rincip le s p ut into actio n, and includ e s CME cre d its. Bo th are availab le at http ://www.niaaa.nih.g ov/g uid e . C. Re thinking Drinking is a b ookle t or e xce ssive d rinke rs that p hysicians can hand out to p atie nts who d rink e xce ssive ly. It g re atly re d uce s the time re q uire d or counse ling ab out e xce ssive d rinking . It is availab le rom the National Institute on Alcohol Ab use and Alcoholism. A comp anion we b site has ad d itional e ature s (http ://re thinking d rinking .niaaa.nih.g ov).

• Antirelapse medication along with medical management is as e ective as high-quality addiction counseling or more unctional patients with alcohol dependence. 29 • Patients with severe recurrent alcohol dependence with medical comorbidities are best with long-term regular medical management, which includes discussion o alcohol consumption and its relationship to medical conditions, as well as encouragement to abstain. When sustained over 1 to 2 years, such medical management results in a substantial proportion o patients who are abstinent. 30 • The presence o severe psychiatric conditions such as psychosis, mania, or severe depression with suicidal ideation requires re erral to a psychiatrist or hospital. Long-term comanagement by primary care physicians and psychiatrists is likely to be necessary.

PREVENTIO N • Most heavy drinkers are asymptomatic, but are drinking at a rate that puts them at increased risk or developing alcohol addiction (dependence) and associated medical and social complications. These “at-risk” drinkers respond well to brie counseling by physicians, resulting in signi cant reductions in heavy drinking. This nding is based on extensive research, such that the US Prevention Task Force has rated screening and brie counseling to be a “B” recommendation, which also have been determined to be cost-e ective. 31 Because the prevalence o at-risk drinking is so high (26% o US adults in any given year), the

potential public health impact o broad implementation o screening and brie counseling is large. • The NIAAA has published a guide to help physicians with screening, assessment and brie counseling techniques (Figure 238-4). There is also an online continuing medical education (CME) activity available. This online training uses 4 video case series, along with advanced interactive educational techniques, to improve physicians’ skills and knowledge (available at http:/ / www.niaaa.nih.gov/ publications/ clinical-guidesand-manuals/ niaaa-clinicians-guide-online-training). CME credit is available and it has been approved by the American Academy o Family Physicians. • Rethinking Drinking, available as a booklet and online, is an educational tool or at-risk drinkers (available at http:/ / rethinkingdrinking.niaaa. nih). This publication takes the drinker through a process o increasing awareness o drinking, deciding whether to change and what the drinking goal is, and developing a plan to implement change. Using this publication substantially enhances the value while decreasing the time it takes to counsel a patient to reduce or stop drinking.

PRO GNO SIS • Most at-risk drinkers eventually reduce their drinking or abstain, and do not develop an AUD or other complications o heavy drinking. • Nearly three- ourths o people who have an episode where they meet criteria or an AUD experience remission o the disorder (either

1219

PART 19

1220

Ch a pt e r 238

SUBSTANCE ABUSE 70% 60% 50%

S till de pe nde nt Pa rtia l re mis s ion Asymptoma tic drinke r Abs ta ine r

40% 30%

o the disease and its medical complications, in spite o availability o all available current treatments and motivated e ort by the patient. The science o behavior change is in its in ancy, so much o what we do is nonspeci c and modestly e ective.

FO LLO W-UP

20% 10% 0% 30 g /wk o “ve ry p ote nt” corticoste roid s should b e limite d to 3-4 wk Child re n (> 10 g /wk) and e ld e rly are at hig he r risk b e cause o thinne r skin

APPENDIX B

APPENDICES

TABLE B-3 Intrale sional Ste roid s—Conce ntrations or Inje ction

Co nd it io n

Co nce nt rat io n o f Triamcino lo ne Ace t o nid e So lut io n (mg / cc)

Acne (Fig ure B-1)

2-2.5

Alop e cia are ata (Fig ure B-2)

5-10

Granuloma annulare

5-10

Psoriasis

5-10

Hyp e rtrop hic liche n p lanus

5-10

Prurig o nod ularis

10

Hid rad e nitis sup p urativa

10

Ke loid s and Hyp e rtrop hic Scars (Fig ure B-3)

10-40 FIGURE B-2 Inje cting alop e cia are ata with 5 mg /mL triamcinolone using a 27-g aug e ne e d le on a Lue r-Lok syring e . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE B-3 Inje cting a hyp e rtrop hic scar with 10 mg /mL triamcinolone using a 27-g aug e ne e d le on a Lue r-Lok syring e . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.) FIGURE B-1 Inje cting p ain ul cystic acne with 2 mg /mL triamcinolone using a 30-g aug e ne e d le . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

1247

1248

APPENDICES

APPENDIX C

APPENDIX C DERMO SCO PY Ashfaq A. Marg hoob , MD Natalia Jaime s, MD Richard P. Usatine , MD Dermoscopy allows the clinician to visualize structures below the level o the stratum corneum. These structures are not routinely discernible without dermoscopy. The presence or absence o specif c dermoscopic structures, their location and their distribution can assist the clinician in making a diagnosis or at least in narrowing the di erential diagnosis. The major goal o dermoscopy is to di erentiate benign rom malignant lesions on the skin so that one is less likely to miss a skin cancer (higher sensitivity) and less likely to per orm unnecessary biopsies (higher specif city). Together, this will increase your diagnostic accuracy. There are 3 major types o dermatoscopes: 1. Polarized 2. Nonpolarized 3. Hybrid, which combines a polarized mode with a nonpolarized mode in one dermatoscope Because some structures are better seen under polarized light and others best seen without polarization is help ul to purchase a hybrid dermatoscope. Dermatoscopes are currently manu actured by 3Gen, Welch Allyn, Canf eld, and Heine (Figures C-1 and C-2). A number o dermatoscopes work well while attached to the iPhone or easy image capture and ull screen images that can be shown to the patients. Dermoscopic diagnosis is based on the 2-step dermoscopy algorithm described in Figure C-3. Step 1 requires the observer to decide whether the lesion in question is o melanocytic origin (contains melanocytes and there ore could be a melanoma). I the lesion is deemed to be a melanocytic lesion then the

FIGURE C-2 No np olarize d contact d e rmatoscop e s ro m He ine and We lchAllyn. (Re p rod uce d with p e rmission fro m He ine , He rrsching , Ge rmany, and We lch Allyn, Skane ate le s Falls, NY.)

observer proceeds to step 2. In this phase o the evaluation, the observer needs to decide whether the lesion is a benign nevus or a melanoma. However, i during step 1 analysis the lesion does not display any eatures o a melanocytic lesion then the observer needs to decide i the lesion possesses any criteria or a basal cell carcinoma, seborrheic keratosis, hemangioma, or dermatof broma. I the lesion does not display any structures common to the a orementioned lesions then the lesion is considered nondescript or eatureless. The index o suspicion needs to remain high or all eatureless lesions as amelanotic melanoma can present as a completely structureless lesion. These eatureless lesions sometimes do reveal blood vessels and, i present, their morphology can o ten help in narrowing the di erential diagnosis.

STEP 1—LEVEL 1 A melanocytic lesion usually will display one o the ollowing structures: 1. Pigment network (Figure C-4). 2. Negative network (Figure C-5). 3. Streaks (Figure C-6).

FIGURE C-1 An assortme nt o p olarize d and hyb rid d e rmatoscop e s rom 3Ge n. (Re p rod uce d with p e rmission from Richard P. Usatine , MD and 3Ge n, San Juan Cap istrano, CA.)

FIGURE C-3 Two-ste p d iag nostic p roce d ure re q uire s se p arating all le sions into me lanocytic or nonme lanocytic as ste p . BCC, b asal ce ll carcinoma; CCA, cle ar-ce ll acanthoma; DF, d e rmato b roma; HG, he mang ioma; SCC, sq uamous ce ll carcinoma; SK, se b orrhe ic ke ratosis; STM, Short te rm monitoring . *Ne ve r monitor p alp ab le le sions.

APPENDIX C

FIGURE C-4 Pig me nt ne twork te lls us this b e nig n ne vus is a me lanocytic le sion in ste p 1 o the 2-ste p alg orithm, that is, it contains me lanocyte s. (Re p rod uce d with p e rmission from Ashfaq Marg hoob , MD.)

APPENDICES

FIGURE C-7 Homog e ne ous b lue p ig me ntation is a e ature o a me lanocytic le sion o the b lue ne vus typ e . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

4. Homogeneous blue pigmentation (Figure C-7). 5. Aggregated globules (Figure C-8). 6. Pseudonetwork ( acial skin) (Figure C-9). 7. Parallel pigment pattern (acral lesions) (Figure C-10). 8. There is one exception to including lesions with pigment network in the melanocytic category, that is, the dermatof broma in which the pattern trumps the network (Figure C-11).

FIGURE C-5 Ne g ative ne two rk in o rms us that this microinvasive me lanoma is a me lanocytic le sion. The ne g ative ne twork consists o d ark, e long ate d , and curve d g lob ular structure s surround e d b y re lative hyp op ig me ntation. (Re p rod uce d with p e rmission from Ashfaq Marg hoo b , MD.)

FIGURE C-6 Stre aks o the p se ud op od typ e in orm us that this is a me lanocytic le sion. The 360-d e g re e symme try is typ ical in a Sp itz ne vus. (Re p rod uce d with p e rmission from Ashfaq Marg hoob , MD.)

This lesion does not display any o the structures commonly seen in melanocytic lesions (ie, network, streaks, globules). It also does not have any eatures o a basal cell carcinoma, seborrheic keratosis, dermatof broma, or hemangioma. Thus, this is a eatureless lesion. However, it does display many irregular tortuous blood vessels, which may be a sign o neoangiogenesis. The possibility o melanoma needs to be entertained or such eatureless lesion.

FIGURE C-8 Ag g re g ate d g lob ule s in orm us that this b e nig n ne vus is me lanocytic. (Re p rod uce d with p e rmission from Ashfaq Marg ho ob , MD.)

1249

1250

APPENDICES

A

APPENDIX C

FIGURE C-10 Ne vus on the sole o the oot showing p aralle l ne twork p ig me nt in the urrows (valle ys) rathe r than the rid g e s. Note the white e ccrine g land op e ning s on the rid g e s which are wid e r than the urrows. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

7. Peripheral reticular with central globules (Figure C-19) 8. Globular (Figure C-20) 9. Two-component (Figure C-21) 10. Symmetric multicomponent (note this pattern should be interpreted with caution and a biopsy is probably warranted or dermoscopic novices) (Figure C-22) In contrast, melanomas tend to deviate rom the benign pattern described earlier. Furthermore, the structures in a melanoma are o ten distributed in an asymmetric ashion. Most melanomas will also reveal one or more o the melanoma-specif c structures (Figure C-23). MELANO MA-SPECIFIC STRUCTURES B FIGURE C-9 Pse ud one twork is the ne t-like p atte rn mad e b y white ad ne xal op e ning s on the ace within any p ig me nte d le sion. A. Pse ud one twork p atte rn is se e n on the ace in this cong e nital ne vus that is me lanocytic. B. Althoug h this solar le ntig o also has a p se ud one twork p atte rn cre ate d b y white ad ne xal op e ning s it is not me lanocytic. It d oe s have a typ ical moth-e ate n b ord e r ound in solar le ntig ine s and se b orrhe ic ke ratose s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

1. Atypical network (Figure C-24) 2. Streaks (pseudopods and radial streaming) (Figure C-25) 3. Negative pigment network (Figure C-26)

STEP 2 I the lesion is deemed to be o melanocytic origin, then one needs to decide whether the lesion is a benign nevus or a melanoma. Nevi tend to mani est one o the ollowing 10 benign patterns (Figure C-12) 1. Di use reticular (Figure C-13) 2. Patchy reticular (Figure C-14) 3. Peripheral reticular with central hypopigmentation (Figure C-15) 4. Peripheral reticular with central hyperpigmentation (Figure C-16) 5. Homogeneous (Figure C-17) 6. Peripheral globules/ starburst (Figure C-18)

FIGURE C-11 Patte rn trump s ne twork in this d e rmato b ro ma. Althoug h this ap p e ars to have p e rip he ral ne twork, the ce ntral ste llate scar make s this a d e rmato b roma, which is not a me lanocytic le sion. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

APPENDIX C

1251

APPENDICES

Be nign Nevi Pa tte rns

**

Diffus e Re tic ular

Patc hy Re tic ular

Pe riphe ral re tic ular with c e ntral hypo pig me ntatio n

Pe riphe ral re tic ular with c e ntral hype rpig me ntatio n

Ho mo g e ne o us

**

**

Pe riphe ral g lo bule s /s tarburs t

Pe riphe ral re tic ular with c e ntral g lo bule s

Glo bular

Two -c o mpo ne nts

Symme tric multic o mpo ne nt

* Benign patterns encountered in many acquired nevi and dysplastic nevi. Blue nevi, some Spitz nevi and congenital melanocytic nevi can also manifest some of these patterns. ** N.B. to novices: Nevi with this pattern should be interpreted with caution. FIGURE C-12 Ste p 2. Ne vus vs. Me lanoma. Be nig n ne vi te nd to ad he re to 1 o 10 re curre nt p atte rns. Me lanoma is a me lanocytic le sion that d e viate s rom the 10 b e nig n p atte rns. (Conce p t and d e sig n b y Natalia Jaime s, MD and Ashfaq A. Marg hoob , MD)

4. Shiny white lines (crystalline structures) (Figure C-27) 5. Atypical dots and or globules (Figure C-28) 4. O -center blotch (Figure C-29) 5. Peripheral tan structureless areas (Figure C-30) 6. Blue-white veil overlying raised areas (Figure C-31) 7. Regression structures (blue-white veil overlying macular areas, scar-like areas, and/ or peppering) (Figure C-32)

FIGURE C-13 Di use re ticular p atte rn in a b e nig n ne vus. Note the re g ular line thickne ss and the ad ing o the line s at the p e rip he ry. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

8. Atypical vascular structures (dotted vessels, serpentine vessels, polymorphous vessels, milky red areas, red globules, corkscrew vessels) (Figure C-33) Note that melanoma on the soles or palms may present with a parallel ridge pattern (Figure C-34). On the ace melanoma may present with rhomboidal structures (Figure C-35).

FIGURE C-14 Patchy re ticular p atte rn in a b e nig n ne vus. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

1252

APPENDICES

APPENDIX C

FIGURE C-15 Pe rip he ral re ticular p atte rn with ce ntral hyp op ig me ntation in a b e nig n ne vus. (Re p rod uce d with p e rmission from Ashfaq Marg hoob , MD.)

FIGURE C-18 Pe ripheral g lob ules that are symmetrically placed are visible in this b enign ne vus. (Re produced with p ermission from Ashfaq Marghoob , MD.)

FIGURE C-16 Pe rip he ral ne twork with a ce ntral hyp e rp ig me ntation in this b e nig n ne vus. The ce ntral hyp e rp ig me ntation may also b e calle d a typ ical b lotch. (Re p rod uce d with p e rmission from Ashfaq Marg hoo b , MD.)

FIGURE C-19 Peripheral reticular pattern with central globules in this benign congenital nevus. (Reproduced with permission from Richard P. Usatine, MD.)

FIGURE C-17 Homog e ne ous p atte rn with a b rown coloration in a b e nig n ne vus. The color may b e b rown, p ink, or b lue . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE C-20 Glob ular p atte rn in a b e nig n ne vus. Note the se g lob ule s have a cob b le stone p atte rn b ut othe r g lob ule s may b e round e d . (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

APPENDIX C

APPENDICES

FIGURE C-21 Two-comp one nt p atte rn with g lob ule s on the rig ht and a strictly re ticular p atte rn on the le t. (Re p rod uce d with p e rmission from Ashfaq Marg hoob , MD.)

FIGURE C-24 Atyp ical ne twork can b e se e n in this susp icious me lanocytic le sion. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

FIGURE C-22 Symme tric multicomp one nt p atte rn. Althoug h this turne d out to b e a b e nig n ne vus, only the most e xp e rie nce d d e rmoscop ist could a ord to call this b e nig n without a b iop sy. (Re p roduce d with p e rmission from Ashfaq Marg hoob , MD.)

FIGURE C-25 Pse ud op od s can b e se e n in this me lanoma. Pse ud op od s are stre aks with rad ial stre aming , a me lanoma-sp e ci c structure . (Cop yrig ht of Ashfaq Marg hoob , MD.)

FIGURE C-23 Me lanoma-sp e ci c structure s and od d s ratios that one o the se structure s p re d icts a d iag nosis o me lanoma.

FIGURE C-26 Ne g ative p ig me nt ne twork can b e se e n on the le t sid e o this me lanoma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

1253

1254

APPENDICES

APPENDIX C

FIGURE C-27 Shiny white line s are visib le in this me lanoma. Shiny white line s are also calle d chrysalis or crystalline structure s. (Re p rod uce d with p e rmission from Ashfaq Marg hoob , MD.)

FIGURE C-30 Pe rip he ral tan structure le ss are as are visib le on the b ottom le t p ortion o this me lanoma (arrow). Note that the re is also ne g ative ne twork visib le . (Re p rod uce d with p e rmission from Ashfaq Marg hoob , MD.)

FIGURE C-28 Atyp ical d ots and g lob ule s are se e n in this me lanoma. The d ots and g lob ule s are p e rip he ral and not symme trically p lace d . A b lue -white ve il is also visib le . (Re p rod uce d with p e rmission from Ashfaq Marg hoob , MD.)

FIGURE C-31 Blue -white ve il ove rlying raise d are a in a me lanoma. (Re p rod uce d with p e rmission from Ashfaq Marg hoob , MD.)

FIGURE C-29 O -ce nte re d b lotch in a me lanoma. Note the b lue -white ve il, atyp ical g lob ule s, atyp ical ne twork, and the p e rip he ral tan structure le ss are as. (Re p rod uce d with p e rmission from Ashfaq Marg hoo b , MD.)

FIGURE C-32 Re g re ssion structure s visib le in this me lanoma in situ. The re g re ssion structure s consist o b lue -white ve il ove rlying macular are as and “p e p p e ring .” (Re p ro d uce d with p e rmission from Richard P. Usatine , MD.)

APPENDIX C

APPENDICES

FIGURE C-36 Evaluating me lanocytic le sions with d e rmoscop y. (Conce p t and d e sig n b y Natalia Jaime s, MD and Ashfaq A. Marg hoob , MD)

STEP 2 FO R MELANO CYTIC LESIO NS FIGURE C-33 Atyp ical vascular structure s can b e se e n in this ame lanotic nod ular me lanoma. Dotte d and se rp e ntine ve sse ls are visib le . (Re p rod uce d with p e rmission from Ashfaq Marg hoob , MD.)

There are the ollowing 3 possible pathways (Figure C-36): 1. The lesion adheres to one o the benign nevus patterns (see Figures C-13 to C-22). Reassure the patient that the lesion is a benign nevus. 2. The lesion A. Adheres to one o the benign nevus patterns but also displays at least one o the melanoma-specif c structures. B. Does not adhere to one o the benign nevus patterns and does not have any o the melanoma-specif c structures. This is an indeterminate or suspicious lesion. The choices include per orm a biopsy now or per orm short-term mole monitoring with dermoscopic photographs and a 3-month ollow-up. (Caveat: Do not monitor a raised lesion because a nodular melanoma can grow quickly with a worsened prognosis in a short time.) 3. The lesion deviates rom the benign nevus patterns and has at least one melanoma-specif c structure (see Figures C-24 to C-33). Biopsy this lesion as a suspected melanoma (see Chapter 170, Melanoma).

STEP 1 FO R NO NMELANO CYTIC TUMO RS FIGURE C-34 Acrole ntig inous me lanoma on the oot with a p aralle l rid g e p atte rn. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

I the lesion is not o melanocytic origin then one needs to look or structures seen in the ollowing: • Dermatof bromas • Basal cell carcinomas • Seborrheic keratoses • Hemangiomas DERMATO FIBRO MA a. Peripheral delicate f ne network (Figure C-37) b. Central scar-like area (see Figure C-37) c. Blood vessels within the scar-like area (Figure C-38) d. Ring-like globular structures (Figure C-39) BASAL CELL CARCINO MA a. Arborizing vessels (Figure C-40) b. Spoke wheel-like structures/ concentric structures (Figure C-41) c. Lea -like areas (Figure C-42)

FIGURE C-35 Le ntig o malig na on the ace with rhomb oid al structure s. (Re p rod uce d with p e rmission from Ashfaq Marg hoob , MD.)

d. Large blue-gray ovoid nest (see Figure C-41) e. Multiple blue-gray globules (see Figure C-42)

1255

1256

APPENDICES

FIGURE C-37 Pe rip he ral d e licate ne ne twork with a ce ntral scar-like are a are visib le in this typ ical d e rmato b roma. (Re p rod uce d with p e rmissio n from Richard P. Usatine , MD.)

APPENDIX C

FIGURE C-40 Arb orizing b lood ve sse ls like b ranching tre e s in a b asal ce ll carcinoma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

. Ulceration (Figure C-43) g. Shiny white structures (crystalline structures) (see Figure C-43) SEBO RRHEIC KERATO SIS a. Multiple (>2) milia-like cysts (Figure C-44) b. Comedo-like openings (Figure C-45) c. Gyri and sulci ( at f nger-like structures) (Figure C-46) and cerebri orm (Figure C-47) d. Fingerprint-like structures (Figure C-48) e. Moth-eaten borders (see Figure C-48) . Additional eatures: sharp demarcation, negative wobble sign (the lesion slides) HEMANGIO MA

FIGURE C-38 Blood ve sse ls are visib le in the scar-like are a o the d e rmatob roma. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE C-39 Ring -like g lob ular structure s are visib le in the ce ntral scar-like are a o the d e rmato b roma. (Re p rod uce d with p e rmissio n from Ashfaq Marg hoob , MD.)

a. Red lacunae (Figure C-49) b. Blue lacunae (Figure C-50) c. Black lacunae = angiokeratoma (Figure C-51) Note that dermoscopy can be help ul in detecting the scabies mite without having to scrape and use the microscope (Figure C-52; see Chapter 141, Scabies).

FIGURE C-41 Sp oke whe e l-like structure s and isolate d b lue -g ray ovoid ne st on the le t o this b asal ce ll carcinoma. (Re p rod uce d with p e rmission from Ashfaq Marg hoob , MD.)

APPENDIX C

A

APPENDICES

FIGURE C-44 Se b orrhe ic ke ratosis with milia-like cysts and come d o-like op e ning s. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

B FIGURE C-42 A. Le a -like structure s in a p ig me nte d b asal ce ll carcinoma. B. Le a -like structure s and b lue -g ray ovoid ne st in b ottom le t hand corne r. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE C-43 Shiny white structure s visible in this basal ce ll carcinoma. Also calle d chrystalline and chrysalis structure s. (Re produce d with pe rmission from Ashfaq Marghoob, MD.)

FIGURE C-45 Many come d one -like op e ning s are visib le in this se b orrhe ic ke ratosis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE C-46 Fat ng e rs are visib le in this se b o rrhe ic ke ratosis. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

1257

1258

APPENDICES

APPENDIX C

FIGURE C-47 Ce re b ri orm se b orrhe ic ke ratosis with g yri and sulci. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE C-50 He mang ioma with re d and b lue lacunae . (Re p rod uce d with p e rmission from Ashfaq Marg hoob , MD.)

FIGURE C-48 Note the moth-e ate n b ord e rs and ng e rp rint-like structure s visib le in this e arly se b orrhe ic ke ratosis orming rom any solar le ntig o. (Re p rod uce d with p e rmission from Ashfaq Marg hoob , MD.)

FIGURE C-51 Ang ioke ratoma showing p urp le and b lack lacunae . (Re p rod uce d with p e rmission from Ashfaq Marg hoob , MD.)

FIGURE C-49 He mang ioma showing re d lacunae (lake s or lag oons o sharp ly d e marcate d vascular tissue ). (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

FIGURE C-52 Scab ie s mite s (arrows) visib le at the e nd o 2 inte rse cting b urrows. The he ad and le g s are most visib le and re se mb le arrowhe ad s p ointing away rom the b urrows. (Re p rod uce d with p e rmission from Richard P. Usatine , MD.)

APPENDIX C

APPENDICES

FIGURE C-53 Eig ht le ve ls that are p art o ste p 1 in the 2-ste p alg orithm. (Conce p t and d e sig n b y Natalia Jaime s, MD and Ashfaq A. Marg hoob , MD)

1259

1260

APPENDICES

APPENDIX C

FIGURE C-54 Exp lanation o the f ow d iag ram in Fig ure C-53. (Conce p t and d e sig n b y Natalia Jaime s, MD and Ashfaq A. Marg hoob , MD)

VASCULAR STRUCTURES Levels 5 and 6 (Figures C-53 and C-54.) in step 1 involve evaluating vascular structures in nonmelanocytic and melanocytic tumors. For urther in ormation about this more advanced steps see the resources below.

Marghoob A, Usatine R. Dermoscopy. In: Usatine R, P enninger J, Stulberg D, Small R, eds. Dermatologic and Cosmetic Procedures in O f ce Practice. Philadelphia, PA: Elsevier; 2012.

RESO URCES TO LEARN DERMO SCO PY

Marghoob AA, Usatine RP, Jaimes N. Dermoscopy. In: Usatine R, Smith M, Mayeaux EJ, Chumley H. Color Atlas o Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013

Dermoscopy. Website rom Italy that includes a ree dermoscopy tutorial—http:/ / www.dermoscopy.org/

Marghoob AA, Usatine RP, Jaimes N. Dermoscopy or the amily physician. Am Fam Physician. 2013 Oct 1;88(7):441-450.

Free dermoscopy app—Dermoscopy: Two-Step Algorithm. iTunes and http:/ / www.usatinemedia.com.

Courses (all taught by the authors of this chapter) are as below:

International Dermoscopy Society. http:/ / www.dermoscopy-ids.org/ . Johr R, Stolz W. Dermoscopy:An Illustrated Sel -Assessment Guide. New York, NY: McGraw-Hill; 2010, with an interactive app: see www.usatinemedia.com. Malvehy J, Puig S, Braun RP, Marghoob AA, Kop AW. Handbook o Dermoscopy. London, UK: Taylor & Francis; 2006. Marghoob A, Braun R, Kop A. Interactive CD-ROM o Dermoscopy. London, UK: In orma Healthcare; 2007. Marghoob AA, Malvehy J, Braun R, eds. Atlas o Dermoscopy. 2nd ed. London, UK: In orma Healthcare; 2012.

American Dermoscopy Meeting is held yearly in the summer in a national park: http:/ / www.americandermoscopy.com/ . Memorial Sloan-Kettering Cancer Center holds a yearly dermoscopy workshop each all in New York City: http:/ / www.mskcc.org/ events/ . American Academy o Family Physicians (AAFP) yearly all scientif c assembly o ers dermoscopy workshops: http:/ / www.aa p.org/

events/ assembly.html. AAFP sponsors a course on “Skin Problems and Diseases” that includes a dermoscopy workshop: http:/ / www.aa p.org/ cme/ .

INDEX Note: In this index, the letters b, f, and t denote boxes, f gures, and tables, respectively. A ABCD, 847 ABCDE, 790, 843, 843f, 844f, 847 ABCDEF, 973 Abdominal aortic aneurysm, 186-191. See also Aortic aneurysm vs. kidney stones, 400 Abscess, 584-586. See also specific types breast, 458-460 (See also Breast abscess) vs. breast cancer, 464 dental, 584, 584f (See also Abscess) diagnosis o , 584-585, 584f, 585f di erential diagnosis o vs. acne vulgaris cysts, 585 vs. cellulitis, 585 vs. epidermal inclusion cyst, 585, 586f vs. uruncles and carbuncles, 585 vs. hidradenitis suppurativa, 585 epidemiology o , 584 etiology and pathophysiology o , 584, 584f, 585f injection-drug use in, 1235f-1237f, 1236 undamentals o , 584 management o , 585-586, 585f patient education and ollow-up o , 586 patient story o , 584, 584f Pautrier microabscess, 875 perirectal, vs. hemorrhoids, 359, 360f peritonsillar, in pharyngitis, 143, 144f rom sinusitis brain, 134, 135f orbital, 134, 135f spinal, vs. back pain, 496 Absolute risk reduction (ARR), 1242, 1244b Abstinence periodic sexual, 11t Abuse intimate partner, 50-53 sexual, 55-58 Acantholysis, in pemphigus, 935, 938 Acanthosis nigricans, 767f, 1118-1120 with diabetes, 1111, 1111f diagnosis o , 712f, 1118-1120, 1118f-1120f di erential diagnosis o vs. actinic keratosis, 1120 vs. erythema ab igne, 1015 vs. seborrheic keratosis, 1120 epidemiology, etiology and pathophysiology o , 1118 undamentals o , 1118 management o , 1120, 1120f with obesity, 1135, 1135f, 1136, 1136f patient education on, 1120 patient story o , 1118, 1118f prognosis in, 1120 Accessory ossicles, vs. metatarsal racture, 520 Accidents de inition o , 14 epidemiology o , 14 on mortality, 15 motor vehicle, on mortality, 15 Accretion, 344

Achilles enthesopathy, rom psoriatic arthritis, 487, 487f Acidosis, metabolic, vs. heart ailure, 210 Acne conglobata, 541-542, 542f, 543f Acne ulminans, 542, 543f Acnei orm eruption, steroid-induced, 551, 552f Acne inversa, 558-561. See also Hidradenitis suppurativa Acne keloidalis nuchae, 554-557, 567f, 568 diagnosis o , 554f-556f, 555 di erential diagnosis o vs. acne vulgaris, 542, 556 vs. olliculitis, 556 vs. impetigo, 556 vs. keloids, 1035-1036, 1035f vs. psychocutaneous disorders, 714 vs. sarcoidosis, 870 epidemiology o , 554, 555f, 556f, 566, 567f etiology and pathophysiology o , 555, 555f undamentals o , 554 management o , 556-557, 556f, 557f patient education on, 557 patient story o , 554, 554f prevention o , 557 prognosis and ollow-up o , 557 risk actors or, 555 scarring alopecia in, 958t, 959-960, 960f Acne rosacea, 548-553. See also Rosacea Acne vulgaris, 540-546 diagnosis o , 540-541, 541f di erential diagnosis o vs. abscess, 585 vs. acne conglobata, 541-542, 542f, 543f vs. acne ulminans, 542, 543f vs. acne keloidalis nuchae, 542, 556 vs. actinic comedones, 542, 544f vs. olliculitis, 542, 570 vs. pseudo olliculitis, 556 vs. rosacea, 542, 544f, 551 epidemiology o , 540 etiology and pathophysiology o , 540, 541f ollow-up o , 546 undamentals o , 540, 541f management o , 542-546 combination therapies in, 545-546 complementary and alternative therapy in, 545 dietary changes in, 543 intense pulsed light and photodynamic therapy in, 546 medication cost in, 546 medications in, 543-545, 544f steroid injection in, 542f, 545, 1247f, 1247t therapy by severity in, 542f, 543f, 545, 546f patient education on, 546 patient story o , 540, 540f Acquired ichthyosis, vs. X-linked ichthyosis, 1042, 1043f

Acquired immunode iciency syndrome (AIDS) death rom, 15 Kaposi sarcoma in, 1072-1075 (See also Kaposi sarcoma) on mortality, 15 Acral lentiginous melanoma, 844-846, 845f, 846f Acrochordon. See Skin tag (acrochordon) Acrodermatitis enteropathica, rom zinc de iciency, 36 Acrolentiginous melanoma, 970, 971f, 972f. See also Nail disorders, pigmented vs. corns and calluses, 1052 Acromegaly, 1160-1162 diagnosis o , 1160-1161, 1160f, 1161f epidemiology, etiology and pathophysiology o , 1160 management o , 1161-1162 patient education on, 1162 patient story o , 1160, 1160f prognosis and ollow-up o , 1162 Acromioclavicular separation, 512, 513f vs. clavicle racture, 512, 512t, 513f Actinic cheilitis, 807-812, 807f. See also Actinic keratosis Actinic comedones, vs. acne vulgaris, 541, 542, 544f Actinic keratosis, 807-812, 834f diagnosis o , 807f-809f, 808 di erential diagnosis o vs. acanthosis nigricans, 1120 vs. basal cell carcinoma, 809, 829 vs. common warts, 619 vs. eczema, nummular, 809 vs. keratoacanthomas, 814 vs. lupus erythematosus, 905 vs. seborrheic keratosis, 773, 809 vs. squamous cell carcinoma, 839 epidemiology o , 807 etiology and pathophysiology o , 808 ollow-up o , 812 undamentals o , 807 management o , 809-810, 809f, 810t, 811f patient education on, 811 patient story o , 807, 807f prevention o , 812 prognosis in, 812 risk actors or, 808 squamous cell carcinoma rom, 834f, 837f Actinic super icial olliculitis, 568 Active empathic listening, 7 Acute chest syndrome, in sickle cell disease, 255, 256, 257 Acute closed-angle glaucoma, 87-89, 88f. See also Glaucoma Acute ebrile neutrophilic dermatosis, vs. pyoderma gangrenosum, 864, 864f Acute generalized exanthematous pustulosis, 1030, 1030f Acute intermittent porphyria, 942 Acute interstitial pneumonia, vs. pulmonary ibrosis, 308

1261

1262

INDEX Acute limb ischemia, 233, 236-237, 237f. See also Peripheral arterial disease Acute necrotizing ulcerative gingivitis, 163, 163f. See also Gingivitis Acute otitis media, 112-117 diagnosis o , 112f-114f, 113-114 di erential diagnosis o , 114-116 vs. bullous myringitis, 115, 115f vs. cholesteatoma, 114, 114f, 115f vs. chronic suppurative otitis media, 115 vs. oreign body, ear, 115, 123 vs. mastoiditis, 115, 115f vs. otalgia, re erred, 115 vs. otitic barotrauma, 114 vs. otitis externa, 114, 121 vs. otitis media with e usion, 114 vs. tympanic membrane per oration, 115, 116f epidemiology, etiology and pathophysiology o , 112 ollow-up or, 117 undamentals o , 112 management o , 116 patient education on, 117 patient story o , 112, 112f prevention o , 116, 116f prognosis in, 117 risk actors or, 112 Acute pain crises, in sickle cell disease, 254-255 Addiction, 15, 1196. See also Substance abuse disorder; specific substances epidemiology o , 1196-1197, 1196f, 1197f etiology and pathophysiology o , 1197-1198 risk actors or, 1198 tobacco, 1201-1212 (See also Tobacco addiction) Adenocarcinoma lung, 278-284, 280f (See also Lung cancer) mouth, 179, 179f Adenoid cystic carcinoma, vs. squamous cell carcinoma, 142, 142f Adenoma sebaceum, vs. neuro ibromatosis, 1193, 1193f Adenomatous polyp, 335-338 Adenomatous polyposis coli (APC) gene mutation, 336 Adenovirus conjunctivitis, 75-78 urethritis in men, 1077-1079 (See also Urethritis, in men) Adrenal adenoma vs. cocaine abuse, 1231 Cushing syndrome rom, 1164, 1164f, 1164t, 1165, 1169, 1169f (See also Cushing syndrome) Adrenal hyperplasia, vs. cocaine abuse, 1231 Adriamycin, cutaneous reactions to, 1024-1032, 1025f. See also Drug reactions, cutaneous Adult education, peer-to-peer, 33 Advance directives, 17 Age-related macular degeneration, 99-101 diagnosis o , 99-100, 99f, 100f di erential diagnosis o

vs. cataract, 100 vs. diabetic retinopathy, 100 vs. glaucoma, 100 epidemiology, etiology and pathophysiology o , 99 undamentals o , 99 management o , 101 patient education on, 101 patient story o , 99, 99f prevention o , 101 prognosis and ollow-up o , 101 risk actors or, 99 AIDS, Kaposi sarcoma and, 1072-1075. See also Kaposi sarcoma Albuminuria, 426 Alcoholic hepatitis, 365-371. See also Liver disease Alcoholism, 1213-1220. See also At-risk drinkers diagnosis o , 1198, 1214-1215, 1215t, 1216f, 1217t di erential diagnosis o , 1215 vs. normal pressure hydrocephalus, 1186 epidemiology o , 1213-1214, 1213f etiology and pathophysiology o , 1214 ollow-up o , 1220 undamentals o , 1213 liver disease rom, 365-371 (See also Liver disease) management o , 1215-1219, 1217t complementary and alternative therapy in, 1218 medications in, 1218 nonpharmacologic, 1215-1218 re erral and hospitalization in, 1218-1219 on mortality, 15 pancreatitis rom, 373 patient education on, 1219f, 1220 patient story o , 1213 prevention o , 1219, 1219f prognosis in, 1219-1220, 1220f risk actors or, 1214 substance abuse and, 1197 terminology or, 1213 types o unctional alcohol use disorder, 1214, 1214t, 1215, 1220 severe recurrent alcohol use disorder, 1214t, 1215, 1219, 1220 Alcohol use disorder. See Alcoholism Aldosterone antagonists, or heart ailure, 210 Aldosteronism, vs. renovascular hypertension, 419 Alkaptonuria, eye mani estations o , 70 Allergic contact dermatitis, 691-697, 926, 926f. See also Contact dermatitis Allergic granulomatosis, vs. vasculitis, 895 Allergic reactions. See specific types Allergic rhinitis, vs. sinusitis, 135 Allergic triad, 262, 263f Alopecia drug-induced, vs. scarring alopecia, 961 moth-eaten, in syphilis, 1104, 1105f

Alopecia, androgenetic vs. scarring alopecia, 961 vs. traction alopecia and trichotillomania, 956 Alopecia areata, 949-953 diagnosis o , 949f-952f, 950-951 di erential diagnosis o vs. anagen e luvium, 951 vs. ollicular mucinosis, 951, 952f vs. lupus erythematosus, 951 vs. psoriatic nails, 991 vs. scarring alopecia, 961 vs. syphilis, 951 vs. telogen e luvium, 951 vs. tinea capitis, 951 vs. traction alopecia, 956 vs. trichotillomania, 951, 956 epidemiology, etiology and pathophysiology o , 949 ollow-up o , 950f, 953 undamentals o , 949 management o , 951-953, 952f, 1247f, 1247t patient education and prognosis in, 952f, 953 patient story o , 949, 949f risk actors or, 949 Alopecia, scarring, 958-962 classi ication o , 958, 958t diagnosis o , 958-960, 959f-961f di erential diagnosis o vs. alopecia areata, 961 vs. androgenetic alopecia, 961 vs. drug-induced alopecia, 961 vs. metabolic and nutritional problems, 961 vs. sarcoidosis o scalp, 961 vs. seborrheic dermatitis, 961 vs. syphilis, 961 vs. telogen e luvium, 961 vs. tinea capitis, 961 vs. traction alopecia, 956, 961 vs. trichotillomania, 956, 961 epidemiology and pathophysiology o , 958, 958t ollow-up o , 962 undamentals o , 958 management o , 961-962 patient education on, 962 patient story o , 958, 958f Alopecia totalis, 949, 949f Alopecia universalis, 949 a 1-Antitrypsin de iciency, COPD rom, 270, 271, 273f, 275 Alveolar hemorrhage syndromes, vs. pulmonary ibrosis, 307 Alveolitis, cryptogenic ibrosing, 306-309. See also Pulmonary ibrosis Alzheimer disease, vs. normal pressure hydrocephalus, 1186 Amelanotic melanoma, 846, 846f, 847f vs. common warts, 619 vs. plantar warts, 635 vs. pyogenic granuloma, 783-784, 784f American Jewish Joint Distribution Committee, 25-26, 26f Amiodarone, or atrial ibrillation, 200-201, 200t, 201t

INDEX Amoxicillin, cutaneous reactions to, 1024-1032, 1024f, 1025f, 1029t. See also Drug reactions, cutaneous Amyloidosis o skin, vs. scleroderma, 920 Anabolic steroid abuse, injection diagnosis o , 1235f, 1236-1237, 1236f epidemiology o , 1235 etiology and pathophysiology o , 1235-1236, 1235f, 1236f Anaerobic vaginosis, 441-443. See also Bacterial vaginosis Anagen e luvium, vs. alopecia areata, 951 Anal issure vs. colon polyps, 337 vs. hemorrhoids, 359, 360f Anal tumor. See also Colon cancer vs. hemorrhoids, 360 Anasarca, in chronic kidney disease, 426, 427f Ancylostoma braziliense, 680 Ancylostoma caninum, 680 Ancylostoma duodenale, 1080-1083, 1080f. See also Intestinal worms and parasites Androgen ablation, or prostate cancer, 413 Androgenetic alopecia vs. scarring alopecia, 961 vs. traction alopecia and trichotillomania, 956 Anemia o chronic disease, vs. iron de iciency anemia, 246 sickle cell, 254-257 (See also Sickle cell disease) sideroblastic, vs. iron de iciency anemia, 246 Anemia, iron de iciency, 244-246 diagnosis o , 244-245, 244f, 245f di erential diagnosis o vs. anemia o chronic disease, 246 vs. hookworms, 1083 vs. lead poisoning, 246 vs. sideroblastic anemia, 246 vs. thalassemia, 245 epidemiology, etiology and pathophysiology o , 244 management o , 246 patient education on, 246 patient story o , 244, 244f prevention and screening or, 246 prognosis and ollow-up o , 246 risk actors or, 244 Aneurysm, aortic, 186-191. See also Aortic aneurysm “Angel’s kisses,” 1022f vs. vascular lesions, 1022, 1022f Angioedema, 716-721 diagnosis o , 717f, 718-719, 719f in drug-related angioedema, 1028 di erential diagnosis o , 719 epidemiology o , 716 etiology and pathophysiology o , 716-717, 717f, 718f ollow-up o , 721 undamentals o , 716 hereditary, 717, 718f, 719 management o , 719-721, 720f patient education on, 721

Angio ibroma, vs. neuro ibromatosis, 1193f Angiogram, coronary, 212, 213f Angiokeratoma, 1016-1019, 1016f, 1017f. See also Vascular skin lesions, acquired Angioma cherry, 1016-1019, 1016f (See also Vascular skin lesions, acquired) vs. Kaposi sarcoma, 1074 Angiomyolipoma, kidney, in tuberous sclerosis, 422f Angiosarcoma, cutaneous, 1016-1019, 1018f. See also Vascular skin lesions, acquired Angiotensin-converting enzyme (ACE) inhibitors or heart ailure, 210 or hypertension, 227 Angiotensin II receptor blocker, or heart ailure, 210 Angle-closure glaucoma, 87-89, 88f. See also Glaucoma Angle o circulatory su iciency, 243 Angular cheilitis, 138-140 with atopic dermatitis, 685, 687f diagnosis o , 138f, 139, 139f, 645, 645f di erential diagnosis o vs. herpes simplex, 139 vs. impetigo, 139 epidemiology, etiology and pathophysiology o , 138, 138f, 139f etiology and pathophysiology o smoking in, 1202, 1203f vitamin B12 de iciency in, 251, 252f management o , 140 patient education on, 140 patient story o , 138, 138f prevention o , 140 Angular cheilosis, 138-140, 138f, 139f Angular stomatitis, 138-140, 138f, 139f Ankle-brachial index (ABI), 232, 234 Ankylosing spondylitis, 492-494 diagnosis o , 473, 477t, 492-493, 492f, 493f di erential diagnosis o , 477t vs. arthritis, 477t vs. back pain, 496 vs. herniated disc, 493 vs. kidney diseases, 493 vs. lumbar strain or muscle spasm, 493 vs. osteoarthritis, 493 vs. osteoporosis and osteopenia, 1143 vs. pancreatitis, 493 vs. psoriatic spondyloarthritis, 493, 493f vs. spondyloarthritis, other, 493 vs. vertebral racture, 493 epidemiology, etiology and pathophysiology o , 492 undamentals o , 492 management o , 493-494 patient education on, 495 patient story on, 492, 492f prognosis and ollow-up o , 494 risk actors or, 492 uveitis in, 84 Anterior cruciate ligament (ACL) tear, 525-529 diagnosis o , 525-526, 526f, 527f di erential diagnosis o , 527-528, 527f, 528f

epidemiology o , 525, 526f etiology and pathophysiology o , 525 ollow-up and patient education on, 529 management o , 528 patient story o , 525, 525f prevention o , 528 prognosis in, 528 risk actors or, 525 Anterior uveitis, rom zoster ophthalmicus, 601-604, 601f. See also Zoster ophthalmicus Antiarrhythmic drugs or atrial ibrillation rate control in, 199 rhythm control in, 199-201, 200t, 201t classes o , 200t Anxiety disorder a ter sexual assault, 58 vs. substance abuse disorder, 1199 Anxiety, vs. heart ailure, 210 Aorta, coarctation o , vs. renovascular hypertension, 419 Aortic aneurysm, 186-191 classi ication o , 186, 187f de inition o , 186 diagnosis o , 188-189 di erential diagnosis o , 189 abdominal, vs. kidney stones, 400 dissecting, vs. pancreatitis, 374 vs. myocardial in arction, 189 vs. pneumothorax, 189 vs. pulmonary embolus, 189 epidemiology o , 186-187 etiology and pathophysiology o , 187, 187t, 188f ollow-up o , 191 management o medical, 190, 191t surgical, 190, 191t surveillance in, 189-190, 190t patient education on, 191 patient story o , 186, 186f prognosis in, 190-191 risk actors or, 188, 188f screening or, 188, 188t Aortic dissection, 186-191. See also Aortic aneurysm Aortic transection, 186-191. See also Aortic aneurysm Aphthous stomatitis, 169-173. See also Aphthous ulcer Aphthous ulcer, 169-173 diagnosis o , 169f, 170, 170f di erential diagnosis o vs. Behçet disease, 171, 171f vs. candidiasis, 171, 171f vs. erosive lichen planus, 171 vs. erythema multi orme, 171 vs. gingivostomatitis, 170 vs. hand, oot, and mouth disease, 171 vs. herpangina, 170, 171f vs. herpes simplex virus, 170 vs. lichen planus, erosive, 171 vs. oral cancer, 171

1263

1264

INDEX Aphthous ulcer (Cont.): epidemiology o , 169 etiology and pathophysiology o , 169-170 undamentals o , 169 management o , 172, 172t patient education on, 173 patient story o , 169, 169f prevention o , 172-173 risk actors or, 170 Apixaban, 204, 204t Appendicitis vs. colon cancer, 331 vs. diverticulitis, 342 vs. kidney stones, 400 vs. pancreatitis, 374 Areola, breast benign lichenoid keratosis o , 469, 469f eczema o , vs. Paget disease o breast, 468, 468f Arsenic toxicity, vs. pitted keratolysis, 573 Arterial ulcers, vs. venous insu iciency, 240 Arteriogram, coronary, 212, 212f Arteriovenous nicking, in hypertensive retinopathy, 93, 93f, 94, 94f Arthritis, 472-477. See also specific types diagnosis o clinical eatures in, 473 distribution in, 473-474, 473f-475f imaging in, 476, 476f, 477t laboratory testing in, 476 di erential diagnosis o vs. bursitis, 476 vs. ibromyalgia, 476 hip, vs. peripheral arterial disease, 235 vs. in lammatory myopathy or myositis, 476 vs. osteoporosis and osteopenia, 1143 vs. polymyalgia rheumatica, 476 vs. tendinitis, 476 epidemiology o , 472 etiology and pathophysiology o , 472, 473f ollow-up or, 477 undamentals o , 472 gouty, 504-507 (See also Gout) in lammatory rom Lyme disease, 1086, 1087 vs. Lyme disease, 1088 management o , 476-477 osteoarthritis, 478-481 (See also Osteoarthritis) patient education on, 477 patient story on, 472, 472f prognosis in, 477 psoriatic, 486-490 (See also Psoriatic arthritis) reactive (See Reactive arthritis) rheumatoid, 482-485 (See also Rheumatoid arthritis) types o , 477t Arthritis mutilans, in psoriatic arthritis, 475f, 488, 488f Arthropod bites vs. pyoderma gangrenosum, 864 vs. scabies, 677 Arthropod reaction, bullous, 926, 927f

Asboe-Hansen sign, 923, 924f, 926, 937 in pemphigus vulgaris, 934f, 937 Ascaris duodenale, 1080-1083 Ascaris, global health problem o , 35, 35f Ascaris lumbricoides, 1080-1083, 1081f. See also Intestinal worms and parasites Ascites, in liver disease, 367, 367f 5 A’s model, 1201, 1202t Aspergillus niger, otitis externa rom, 120 Aspirin or coronary artery disease, 213 cutaneous reactions to, 1024-1032 (See also Drug reactions, cutaneous) mouth burn rom, vs. leukoplakia, 175 Asteatotic dermatitis, vs. nummular eczema, 708 Asteatotic eczema, vs. X-linked ichthyosis, 1042-1043 Asthma, 260-268 diagnosis o , 260-264 clinical eatures in, 260-262, 263f imaging in, 264, 265f laboratory testing in, 261f, 262-263, 263f, 264f, 264t di erential diagnosis o vs. bronchitis, chronic, 264 vs. chronic obstructive pulmonary disease, 264, 272 vs. congestive heart ailure, 264 vs. cough, drug-induced, 264 vs. pneumonia, 264 vs. pneumonia, community-acquired, 292 vs. tuberculosis, 264 epidemiology o , 260 etiology and pathophysiology o , 260 ollow-up o , 267 undamentals o , 260 management o , 264-267 medications in, 265-267 nonpharmacologic, 265, 266f re erral in, 267 patient education on, 267-268 patient story o , 260, 261f, 262t prevention and screening in, 267 prognosis in, 267 risk actors or, 260 severity o , 263, 264t Ataxia telangiectasia, vs. neuro ibromatosis, 1193 Atelectasis in asthma, 264, 265f in community-acquired pneumonia, 292f Atherosclerotic disease cardiovascular, 232-238 (See also Peripheral arterial disease) rom chronic kidney disease, 427-428 coronary, 212-214 (See also Coronary artery disease) in peripheral arterial disease, 232 renovascular hypertension in, 415-420 (See also Hypertension, renovascular) Athlete’s oot, 658-662. See also Tinea pedis Atopic dermatitis, 683-689 diagnosis o , 684-687, 685f-688f di erential diagnosis o vs. contact dermatitis, 688, 695

vs. dermatophyte in ection, 688 vs. eczema, dyshidrotic, 687 vs. eczema, nummular, 708 vs. impetigo, 562, 564f vs. lichen simplex chronicus, 687-688 vs. methamphetamine abuse, 1226 vs. psoriasis, 687 vs. psychocutaneous disorders, 714 vs. scabies, 676-677, 688 vs. seborrheic dermatitis, 687 epidemiology o , 684 erythroderma with, 761, 762t, 763f etiology and pathophysiology o , 684, 684f ollow-up o , 689 undamentals o , 684 management o , 688-689, 689f, 689t other eatures/ conditions with angular cheilitis, 139, 139f, 685, 687f cutaneous in ection, 684f, 685 Dennie-Morgan lines, 685, 686f eczema herpeticum, 684, 684f eczema vaccinatum, 684, 684f eye indings, 687, 687f hand eczema, 701f hand or oot dermatitis, 685 ichthyosis, 685, 687f impetigo, 684 keratoconus, 687, 687f keratosis pilaris, 685, 686f nasal crease, horizontal, 687, 688f palmar or plantar hyperlinearity, 685 pityriasis alba, 685 xerosis, 685 patient education on, 689, 689t patient story o , 683, 683f Atopic eczema, 683-689. See also Atopic dermatitis Atopic triad, 262, 263f in atopic dermatitis, 683, 683f, 684-685, 688, 688f, 689f (See also Atopic dermatitis) Atrial dilation, in atrial ibrillation, 195, 195f Atrial ibrillation, 193-204 cerebral vascular accident with, 1179 classi ication o , 194, 194t de inition o , 193, 193f diagnosis o , 195-196, 196f, 196t di erential diagnosis o , 195 vs. atrial lutter, 195 epidemiology o , 193, 194-195 etiology and risk actors or, 195, 195f ollow-up o , 204 management o , 196-204 anticoagulants/ antithrombotics in, 202-204, 203t, 204t approach to, 198f, 199f cardioversion in ablation, 201, 202t anticoagulation in, 202 DC, 199-200, 201 objectives and goals o , 196 rate control in, 196-200, 200t rhythm control in, 200-201, 200t, 201t stroke risk assessment in, 201-202, 202t

INDEX pathophysiology o , 195 patient story o , 193, 193f Atrial lutter, vs. atrial ibrillation, 195, 197f Atrioventricular blockade, rom Lyme disease, 1086 At-risk drinkers de inition o , 1213, 1213f diagnosis o , 1215 epidemiology o , 1213-1214 ollow-up o , 1220 management o , 1215, 1217t, 1218 presentation o , 1214, 1214t prevention or, 1219 prevention in, 1219 prognosis in, 1219 Atrophic glossitis, rom vitamin B12 de iciency, 248f, 251 Atrophic vaginitis, 437-439 diagnosis o , 437f, 438, 438f di erential diagnosis o vs. contact dermatitis, 438 vs. lichen planus, vulvovaginal, 438 vs. lichen sclerosus, 438, 439f vs. sexually transmitted diseases, 438 vs. vaginal co-in ection, 438 epidemiology o , 437 etiology and pathophysiology o , 437, 437f ollow-up o , 439 undamentals o , 437 management o , 438-439 patient education on, 439 patient story o , 437, 437f risk actors or, 438 Atypical nevus, 802-805. See also Nevus, dysplastic AUDIT questionnaire, 1215, 1216f Auspitz phenomenon., 488 Auspitz sign, 732 Autoeczematization, tinea pedis, 658, 658f, 659 Autoimmune diseases, scleritis with, 80, 80f, 81f Autoimmune liver disease, 366. See also Liver disease Autosensitization, tinea pedis, 658, 658f, 659 Autosomal-dominant polycystic kidney disease, 406-408. See also Polycystic kidneys AV node ablation, or atrial ibrillation, 199 Avulsion racture, i th metatarsal, 519-520, 519f, 520f Axillary reckling, in neuro ibromatosis, 1191, 1191f, 1192, 1192f B B12 de iciency, 248-252. See also Vitamin B12 de iciency Baboon syndrome, 1030, 1030f Bacillary angiomatosis vs. Kaposi sarcoma, 1074, 1074f vs. pyogenic granuloma, 784, 1074f Back pain, 495-497 diagnosis o , 495-496 di erential diagnosis o vs. abdominal pathology, 497 vs. ankylosing spondylitis, 496 vs. compression ractures, 502

vs. herniated disc, 496, 496f vs. malignancy, 497 vs. osteoporotic vertebral racture, 496, 496f vs. spinal in ection/ abscess, 496 vs. spinal stenosis, 496 epidemiology, etiology and pathophysiology o , 495 undamentals o , 495 management o , 497 patient education on, 497 patient story o , 495, 495f prevention o , 497 prognosis and ollow-up o , 497 risk actors or, 495 Bacteria. See also specific types and infections lesh-eating, 588-591 (See also Necrotizing asciitis) Bacterial endocarditis, 220-223. See also Endocarditis, bacterial Bacterial olliculitis, 566-570, 566f, 568f. See also Folliculitis Bacterial in ections. See also specific types blistering eruption rom, 926-927 di erential diagnosis o vs. hidradenitis suppurativa, 560 vs. intestinal worms and parasites, 1083 Bacterial vaginosis, 434-436, 434f, 436t, 441-443 diagnosis o , 441f, 442-443, 442f di erential diagnosis o vs. atrophic vaginitis, 438 vs. Candida vaginitis, 443 vs. Candida vulvovaginitis, 447 vs. chlamydia, 443 vs. chlamydia cervicitis, 456 vs. gonorrhea, 443 vs. Trichomonas, 443 vs. Trichomonas vaginitis, 452 epidemiology o , 441 etiology and pathophysiology o , 441-442 ollow-up o , 444 undamentals o , 441 management o , 443, 443t patient education on, 444 patient story o , 441, 441f prevention o , 444 risk actors or, 442 a ter sexual assault, 57 Bacteriuria, with urinary tract in ection, 430f. See also Urinary sediment Bacteroides necrotizing asciitis, 588 (See also Necrotizing asciitis) otitis externa, 120 Baker cyst vs. deep venous thrombosis, 216 vs. peripheral arterial disease, 235 Balanitis, Candida, 644 Balanitis circinata, in reactive arthritis, 757-760, 758f Balsam o Peru contact dermatitis, 691 Barbiturates, cutaneous reactions to, 1024-1032. See also Drug reactions, cutaneous

Barotrauma, otitic, vs. acute otitis and otitis media with e usion, 114 Barrett esophagus, rom gastroesophageal re lux, 355, 355f, 356 Barton racture, 515, 515f Basal cell carcinoma, 825-833 diagnosis o , 825f-831f, 827-828 di erential diagnosis o vs. actinic keratosis, 809 vs. Bowen disease, 809 vs. hordeolum and chalazion, 66 vs. melanoma, 849-850, 849f, 850f vs. molluscum contagiosum, 615 or sclerosing BCC, vs. scars, 829 vs. seborrheic keratosis, 773, 774f vs. skin tag, 768 vs. skin tags, preauricular, 128, 128f vs. squamous cell carcinoma, 838, 840f di erential diagnosis o , or nodular BCC vs. ibrous papule o ace, 829 vs. intradermal (dermal) nevi, 825f, 829, 831f vs. keratoacanthoma, 829 vs. sebaceous hyperplasia, 776, 776f, 777f, 829, 832f vs. trichoepithelioma/ trichoblastoma/ trichilemmoma, 829 di erential diagnosis o , or super icial BCC vs. actinic keratoses, 829 vs. benign lichenoid keratosis, 829 vs. Bowen disease, 829 vs. discoid lupus erythematosus, 829 vs. eczema, nummular, 829 epidemiology o , 825, 825f-827f etiology and pathophysiology o , 825, 828f ollow-up o , 833 undamentals o , 825 management o , 830-832, 830f, 832f patient education on, 833 patient story o , 825, 825f prevention and screening or, 833 prognosis in, 832 risk actors or, 826 Basal nevus syndrome, vs. pitted keratolysis, 573 BATHE method, 8 Bathing trunk nevus, 793-797. See also Nevus, congenital Beau lines, 965-966, 966f vs. Mees and Muehrcke lines, 967, 967f, 968t in psoriatic nails, 989 Becker nevus, 787-789, 789f vs. congenital nevi, 795 Bedbugs, vs. scabies, 677, 677f Behçet disease (syndrome) vs. aphthous ulcer, 171, 171f vs. herpes simplex virus, 609, 609f uveitis in, 84 Bell’s palsy, 1188-1190 diagnosis o , 1188-1189 di erential diagnosis o vs. ear disease, suppurative, 1189 vs. acial nerve damage, 1189 vs. acial nerve palsy, isolated, 1189, 1189f vs. Lyme disease, 1088, 1189

1265

1266

INDEX Bell’s palsy, di erential diagnosis o (Cont.): vs. space-occupying lesion, 1189 vs. upper motor neuron diseases, 1189 epidemiology, etiology and pathophysiology o , 1188, 1188f Lyme disease in, 1086 ollow-up o , 1190 management o , 1189 patient education on, 1190 patient story o , 1188, 1188f prognosis in, 1189 Benign amilial pemphigus, vs. pemphigus vegetans, 938, 939f Benign ibrous histiocytoma, 778-781. See also Dermato ibroma Benign intracranial hypertension, 96-98. See also Papilledema Benign juvenile melanoma, 787, 788f Benign lichenoid keratosis, vs. basal cell carcinoma, 829 Benign migratory glossitis, 159-161. See also Geographic tongue Benign prostatic hyperplasia, vs. prostate cancer, 412 Bereavement ollow-up, 20 b-Blockers or atrial ibrillation, 196-198 or coronary artery disease, 213 or heart ailure, 210 Biliary cirrhosis, primary, 366. See also Liver disease Biliary colic vs. kidney stones, 400 vs. pancreatitis, 374 vs. peptic ulcer disease, 379 Bismuth subsalicylate ingestion, black tongue rom, 157 Bite trauma, vs. lichen planus, 755 Black hairy tongue, 156-158 rom antibiotics, 156, 156f diagnosis o , 157 di erential diagnosis o vs. candidiasis, oral, 157 vs. hairy leukoplakia, 157, 158f epidemiology, etiology and pathophysiology o , 156, 156f smoking in, 156, 156f, 157, 157f undamentals o , 156 management o , 157-158 patient story o , 156, 156f prevention o , 158 prognosis and patient education on, 158 risk actors or, 157 Blackheads, 541 vs. acne vulgaris, 542, 544f Black heel, vs. plantar warts, 635 Black recluse spider bite, vs. pyoderma gangrenosum, 864 Black warts, vs. plantar warts, 635 Bladder cancer, 390-393 de inition o , 390 diagnosis o , 390f, 391, 391f di erential diagnosis o , 391-392 epidemiology o , 390

etiology and pathophysiology o , 390-391, 390f, 391f ollow-up or, 393 management o , 392-393, 392t patient education on, 393 patient story o , 390, 390f prevention and screening or, 431 prevention o , 393 prognosis in, 392t, 393 risk actors or, 391 Blepharitis, red eye in, 110, 110f with ocular rosacea, 107t, 109, 109f Blindness rom Chlamydia trachomatis, 41-42, 41f, 42f rom diabetic retinopathy, 90-92 rom glaucoma, 87-89 Blisters riction, 926 vs. tinea pedis, 660 postburn, 926, 926f Blood pressure, increased. See Hypertension Bloom syndrome, vs. neuro ibromatosis, 1193 Blow, 1228-1233. See also Cocaine abuse Blue nevus, 787, 788f Blum, Dr. Alan, 7f, 17f Body lice, 668-672, 668f, 669f. See also Lice Bone cysts, vs. knee injuries, 528 Bone in ection, 1096-1101. See also Osteomyelitis Bone mineral density in osteopenia, 1141 in osteoporosis, 1141 Borrelia burgdorferi, 1085-1090, 1085f. See also Lyme disease Bouchard nodes, 473f, 478, 478f, 479 Bowen disease, 807-812 diagnosis o , 807f, 808, 809f di erential diagnosis o vs. basal cell carcinoma, 809, 829 vs. eczema, nummular, 809 vs. lichen planus, 754-755 vs. Paget disease o breast, 468 vs. seborrheic keratosis, 809 vs. squamous cell carcinoma, 839 epidemiology o , 807 etiology and pathophysiology o , 808 ollow-up o , 811 undamentals o , 807 management o , 811, 811t, 812f patient education on, 811 prevention o , 811 prognosis in, 811 risk actors or, 808 Brachytherapy, or prostate cancer, 413 Brain abscess, rom sinusitis, 134, 135f Brain cancer. See also specific types vs. subdural hematoma, 1183 Brain mass, vs. cerebral vascular accident, 1179 Brain parenchyma hemorrhage, vs. subdural hematoma, 1183 Branchial cle t cyst, vs. goitrous hypothyroidism, 1150 BRCA mutation, 462, 463, 464 Breast abscess, 458-460 de inition o , 458, 458f

diagnosis o , 458-459, 459f di erential diagnosis o vs. breast cancer, 464 vs. tinea corporis, 459 epidemiology o , 458 etiology and pathophysiology o , 458, 459f ollow-up o , 460 management o , 459, 459f patient education on, 459 Breast areola benign lichenoid keratosis o , 469, 469f eczema o , vs. Paget disease o breast, 468, 468f Breast cancer, 461-465 diagnosis o , 462f, 463, 463f di erential diagnosis o vs. breast abscess, 464 vs. cyst, benign, 464 vs. ductal ectasia with in lammation, 464 vs. ibroadenoma, 464 vs. leukemia in breast, 464 vs. mastalgia, bilateral, 464 vs. mastitis, in ectious, 464 vs. nipple discharge, 464 epidemiology o , 461-462, 461f-463f etiology and pathophysiology o , 462-463 ollow-up o , 464, 465f management o , 463f, 464 patient education on, 464 patient story o , 461, 461f prevention o , 464 risk actors or, 463 Breast cyst, benign, vs. breast cancer, 464 Breast eeding, HIV on, 33 Breathiness, 149-153. See also Hoarseness British Thoracic Society (BTS) rule, 292-293 Bronchitis, chronic vs. asthma, 264 vs. chronic obstructive pulmonary disease, 272 vs. community-acquired pneumonia, 292 Bronchoalveolar carcinoma, 278-284, 281f. See also Lung cancer Bronchopneumonia, 291, 292f, 293f. See also Pneumonia Buerger disease dry gangrene rom, 1069 in peripheral arterial disease, 232 Buerger test, 233-243 Bulimia, vs. dental caries, 182, 182f Bullosis diabeticorum, 923, 923f, 926, 926f Bullous arthropod reaction, 926, 927f Bullous diseases, 923-928 diagnosis o , 923-928 approach to, 923 biopsy in, 928 clinical eatures in, 923-927 autoimmune, 923-924, 923f-926f drug, 926, 927f hydrostatic (edema blisters), 927 immunologic, 925f, 926, 926f in ections and bites, 926-927, 927f metabolic (porphyria cutanea tarda), 925f, 926 traumatic/ physical stress, 926, 926f

INDEX urther evaluations in, 928 history in, 923 laboratory studies and work-up in, 927 physical examination in, 923, 924f di erential diagnosis o vs. herpes zoster, 598 vs. zoster ophthalmicus, 604 undamentals o , 923 patient story o , 923, 923f Bullous drug eruptions, 926, 927f Bullous impetigo, 926-927 Bullous myringitis, vs. acute otitis and otitis media with e usion, 115, 115f Bullous pemphigoid, 923, 923f, 924f, 929-932 diagnosis o , 929f, 930-931, 930f di erential diagnosis o vs. chickenpox, 594 vs. cicatricial pemphigoid, 931, 931f vs. cutaneous drug reactions, 1031 vs. dermatitis herpeti ormis, 931 vs. epidermolysis bullosa acquisita, 931 vs. erythema multi orme, 931 vs. hypersensitivity syndromes, 883 vs. impetigo, 564 vs. linear IgA dermatosis, 931 vs. pemphigus, 938 epidemiology o , 929 erythroderma with, 761, 762t etiology and pathophysiology o , 929, 929f, 930f ollow-up o , 932, 932f undamentals o , 929 management o , 931-932 patient education on, 932 patient story o , 929, 929f Bunion de ormity, 1054-1056 callus rom, 1050, 1051f diagnosis o , 1054f, 1055, 1055f di erential diagnosis o vs. gout or pseudogout, 1055 vs. rheumatoid arthritis, 1055 vs. septic joint, 1055 epidemiology, etiology and pathophysiology o , 1054 undamentals o , 1054 management o , 1055-1056, 1056f patient education on, 1056 patient story o , 1054, 1054f prevention o , 1056 prognosis and ollow-up o , 1056 risk actors or, 1054 Burn, second-degree, vs. impetigo, 564 Bursa, hemorrhage into, vs. olecranon bursitis, 509 Bursitis di erential diagnosis o vs. arthritis, 476 vs. osteoarthritis, 479 olecranon, 508-510 (See also Olecranon bursitis) rom gout, 474, 475f Buschke-Lowenstein tumor, vs. condylomata acuminata, 629, 629f Butter ly rash, 899f, 900, 901, 901t, 902f

C C, 1228-1233. See also Cocaine abuse Ca é-au-lait spots di erential diagnosis o , 1193 vs. congenital nevi, 795 in neuro ibromatosis, 1191-1194, 1191f (See also Neuro ibromatosis) CAGE questionnaire, 1215 Calcium channel blockers or atrial ibrillation, 198 or coronary artery disease, 213 or diastolic heart ailure, 210 Calcium pyrophosphate dihydrate disease, arthritis in, 472, 473, 474, 476 Calcium stones, 398-401. See also Kidney stones with polycystic kidneys, 407, 408 Calculi, ureteral, 395, 396f, 398-401. See also Kidney stones vs. diverticulitis, 341 Calcutta Rescue program, 30, 30f Calluses, 1050-1053 diagnosis o , 1050f, 1051, 1051f di erential diagnosis o vs. acrolentiginous melanoma, 1052 vs. Dupuytren disease, 531 vs. pachyonychia congenita, 1051f, 1052 vs. plantar warts, 634-635, 1052 vs. porokeratosis, 1052 vs. scars, hypertrophic, 1052 vs. skin cancer, nonmelanoma, 1052 epidemiology, etiology and pathophysiology o , 1050 ollow-up o , 1053 undamentals o , 1050 management o , 1050f, 1052 patient education on, 1053 patient story o , 1050, 1050f prevention o , 1052-1053 prognosis and ollow-up o , 1053 risk actors or, 1050-1051, 1051f Cancer. See also specific types death rom, 15 epidemiology o , 14 Candida, 638-642, 639f, 644-647. See also Candidiasis Candida albicans angular cheilitis, 138-140, 138f, 139f paronychia, 985-988, 986f vs. pharyngitis, 146 vulvovaginitis, 446, 446f Candida antigen, or lat warts, 624f, 625, 625f, 625t Candida glabrata vulvovaginitis, 446 Candida vaginitis, vs. Trichomonas vaginitis, 452 Candida vulvovaginitis, 445-449 cutaneous, 434-436, 436t diagnosis o , 446f, 447, 447f di erential diagnosis o vs. bacterial vaginosis, 443, 447 vs. Chlamydia, 447 vs. cytolytic vaginosis, 447 vs. Döderlein cytolysis, 447 vs. gonorrhea, 447 vs. trichomoniasis, 447

epidemiology o , 445, 446f etiology and pathophysiology o , 445f, 446, 446f ollow-up o , 448 undamentals o , 445 management o , 447-448, 448t patient education on, 449 patient story o , 445, 445f, 446f prevention o , 448 prognosis in, 448 risk actors or, 446-447, 446f Candidiasis. See also Fungal in ections onychomycosis, 979-983, 979f (See also Onychomycosis) patient education on, 647 patient story o (balanitis), 644, 644f risk actors or, 644 vulvovaginal, 434-436, 436t Candidiasis, dermal, 445-449, 644-647 bullous presentation o , 927 contact hand dermatitis in, 699, 701f diagnosis o , 644-645 antibiotic use in, 645, 645f nipple (in antile thrush), 644-645, 645f perlèche (angular cheilitis), 645, 645f thrush, 644-645, 645f di erential diagnosis o vs. aphthous ulcer, 171, 171f vs. erythrasma, 578, 646 vs. hand eczema, 701f, 702 vs. intertrigo, 645, 646f vs. inverse psoriasis, 646, 646f vs. leukoplakia, 175 vs. psoriasis, 738 vs. seborrhea, 646, 726 vs. tinea corporis and cruris, 645-646, 646f vs. tinea cruris, 656 epidemiology o balanitis, 644 thrush, 644, 644f etiology and pathophysiology o , 644 olliculitis rom, 568 undamentals o , 644 management o , 645f, 647, 647f Candidiasis, mucocutaneous (thrush), 638-642. See also Fungal in ections angular cheilitis rom, 138-140, 138f, 139f diagnosis o , 638-641, 639f di erential diagnosis o vs. black hairy tongue, 157 vs. lichen planus, 755 vs. pharyngitis, 146 management o , 641-642, 642t pathophysiology o , 638, 639f Canker sores, 169-173. See also Aphthous ulcer Capsulitis, vs. polymyalgia rheumatica, 535 Carbuncles, vs. abscess, 585 Carcinomatous meningitis, 1094 vs. normal pressure hydrocephalus, 1186 Cardiac tamponade, acute, with pericardial e usion, 229, 230 Cardiac tumors, vs. bacterial endocarditis, 222 Cardiomegaly in heart ailure, 209, 209f, 210f vs. pericarditis and pericardial e usion, 229f

1267

1268

INDEX Cardiovascular disease. See also specific types atherosclerotic, 232-238 (See also Peripheral arterial disease) rom chronic kidney disease, 427-428 epidemiology o , 14 Cardioversion, or atrial ibrillation ablation, 201, 202t anticoagulation in, 202 DC, 199-200, 201 Caries, adult, 181-183 diagnosis o , 182 di erential diagnosis o vs. bulimia, 182, 182f vs. luorosis, 182 vs. staining, 182 vs. tooth abrasion, 182 vs. tooth attrition, 182 vs. tooth erosion, 182 vs. tooth trauma, 182 epidemiology, etiology and pathophysiology o , 181, 181f undamentals o , 181 management o , 183 patient education on, 183 patient story o , 181, 181f prevention and screening or, 183 prognosis and ollow-up o , 183 risk actors or, 182 Caring, 7 Casts, urinary, 429-431, 430f. See also Urinary sediment Cataract, vs. age-related macular degeneration, 100 Catarrh, spring, 77 Cavernous sinus thrombosis, rom sinusitis, 134, 135f Cavitated lesions, 181-183. See also Caries, adult Cellulitis, 580-583 breast, 458, 458f, 459, 459f de inition o , 580 diagnosis o , 580-581, 580f-582f di erential diagnosis o vs. abscess, 585 vs. allergic reactions, 582, 582f vs. Charcot arthropathy, 1066 vs. deep venous thrombosis, 217, 217f vs. erythema nodosum, 888 vs. gout, 506, 582 vs. ingrown toenail, 976 vs. knee injuries, 528 vs. Lyme disease, 1087 vs. necrotizing asciitis, 582, 590 vs. thrombophlebitis, 582 vs. venous stasis and venous stasis dermatitis, 581f, 582 dissecting, scarring alopecia rom, 959, 960f epidemiology o , 580 etiology and pathophysiology o , 580, 580f, 581f management o , 582-583 patient education and ollow-up o , 583 patient story o , 580, 580f Central canal stenosis, 499-500, 499f, 500f Central centri ugal scarring alopecia, 958-962, 958t, 959f. See also Alopecia, scarring

Cerebral vascular accident, 1178-1181 diagnosis o , 1179, 1179f, 1180f di erential diagnosis o vs. brain mass, 1179 vs. hypoglycemia, 1180 vs. migraine headache, 1179 vs. multiple sclerosis, 1179 vs. transient ischemic attack, 1179 vs. vertigo, 1180 epidemiology o , 1178 etiology and pathophysiology o , 1178-1179 undamentals o , 1178 management o , 1180 patient education on, 1181 patient story o , 1178, 1178f prevention o , 1181 prognosis and ollow-up o , 1181 risk actors or, 1178, 1179 Cervical spine disease, vs. temporal arteritis, 535 Cestodes, 1080-1083. See also Intestinal worms and parasites CHADS2 scoring, 201, 202t CHADS2-VASc score, 201, 203t CHADS/ CHADS2 scoring table, 1180 Chalazion, 65-67 de inition o , 65 diagnosis o , 66, 66f di erential diagnosis o vs. basal cell carcinoma, 66 vs. hidrocystoma, 66, 66f vs. molluscum contagiosum, 66 vs. sebaceous cell carcinoma, 66 vs. xanthelasma, 66 epidemiology, etiology and pathophysiology o , 65 management o , 67 patient education o , 67 prevention o , 67 prognosis and ollow-up or, 67 risk actors or, 66 Chancre (syphilis), 1102f, 1103, 1103f, 1107f. See also Syphilis vs. herpes simplex virus, 609 Chancroid vs. herpes simplex virus, 609 vs. pyoderma gangrenosum, 864 vs. syphilis, 1107, 1107f Charcot arthropathy, 1065-1067 in diabetes, 1112, 1112f diagnosis o , 1065-1066, 1065f, 1066f di erential diagnosis o vs. deep venous thrombosis, 1066 vs. gouty arthropathy o oot/ ankle, 1066 vs. in ections, 1066 epidemiology, etiology and pathophysiology o , 1065 undamentals o , 1065 management o , 1067, 1067f patient education on, 1067 patient story o , 1065, 1065f prevention o , 1067 prognosis and ollow-up o , 1067 risk actors or, 1065

Charcot-Marie-Tooth disease, hammer toe rom, 1057, 1058f Chau eur’s racture, 516, 516f Cheilitis actinic, 807-812, 807f (See also Actinic keratosis) angular, 138-140, 138f, 139f (See also Angular cheilitis) rom smoking, 1202, 1203f with atopic dermatitis, 685, 687f Cheloids, 1034-1037. See also Keloids Chemical burn o mouth, vs. leukoplakia, 175 Cherry angioma, 1016-1019, 1016f. See also Vascular skin lesions, acquired Cherry hemangioma, vs. pyogenic granuloma, 784, 784f Chest pain in coronary artery disease, 212-214 (See also Coronary artery disease) di erential diagnosis o , 213 Chickenpox, 592-595 de inition o , 592 diagnosis o , 593-594, 594f di erential diagnosis o vs. dermatitis herpeti ormis, 594 vs. herpes simplex, 594 vs. impetigo, 594 vs. insect bites, 594 vs. pemphigus and bullous pemphigoid, 594 epidemiology o , 592, 592f, 593f etiology and pathophysiology o , 593, 593f ollow-up o , 595 management o , 594-595 patient education on, 595 patient story o , 592, 592f, 593f prevention o , 595 risk actors or, 593 Chlamydia cervicitis, 454-457 diagnosis o , 455-456, 455f di erential diagnosis o vs. bacterial vaginosis, 456 vs. gonorrhea, 456 vs. trichomoniasis, 456 epidemiology o , 454 etiology and pathophysiology o , 454 ollow-up o , 457 undamentals o , 454 management o , 456, 456t patient education on, 457 patient story o , 454, 454f prevention o , 456 prognosis in, 456 risk actors or, 454f Chlamydial pelvic in lammatory disease, with reactive arthritis, 757-760, 758f, 759f. See also Reactive arthritis Chlamydia trachomatis blindness rom, 41-42, 41f, 42f cervicitis rom, 454-457 (See also Chlamydia cervicitis) di erential diagnosis o vs. bacterial vaginosis, 443 vs. Candida vulvovaginitis, 447 vs. Trichomonas vaginitis, 452

INDEX epidemiology o , 454 trachoma rom, 77, 77f a ter sexual assault, 57 urethritis in men rom, 1077-1079, 1077f Chloasma, 996-999. See also Mask o pregnancy Choice, supporting, 7 Cholangitis, vs. pancreatitis, 374 Cholecystitis, vs. gallstones, 346 Cholecystitis, vs. pancreatitis, 374 Cholelithiasis vs. hydronephrosis, 396 vs. kidney stones, 400 Cholera, 34-35, 35f water and sanitation in, 35, 35f Cholestatic disease, 365-371. See also Liver disease Cholesteatoma, vs. acute otitis and otitis media with e usion, 114, 114f, 115f Cholesterol embolism, vs. vasculitis, 896 Cholesterol stones, 344-347. See also Gallstones Chondroblastoma, vs. knee injuries, 528 Chondrodermatitis nodularis (chronica) helicis, 126-129 diagnosis o , 126-127, 126f, 127f epidemiology, etiology and pathophysiology o , 126 ollow-up or, 128 management o , 128, 129f patient education on, 129 patient story o , 126, 126f vs. skin cancer, 128 Chordoma, vs. nasal polyps, 131 Chorioretinitis, 84-86 Choroiditis, 84-86 Chromophobic tumors, renal cell, 421 Chronic daily headache, 1174-1176. See also Headache Chronic hypersensitivity pneumonitis, vs. pulmonary ibrosis, 307 Chronic kidney disease, 426-428 clinical mani estations o , 426-427, 427f diagnosis o , 427 etiology, pathogenesis, and risk actors or, 426 undamentals o , 426 management o , 428 patient story o , 426, 426f prognosis and complications o , 427-428 Chronic obstructive pulmonary disease (COPD), 269-276 a 1-antitrypsin de iciency in, 270, 271, 273f, 275 clubbing in, 206-208, 207f diagnosis o , 270-272 clinical eatures in, 270, 270t imaging in, 269f, 271-272, 271f-273f laboratory testing in, 270-271 di erential diagnosis o vs. asthma, 264, 272 vs. bronchitis, chronic, 272 vs. heart ailure, 209-210, 272 vs. lung cancer, 272-273, 280-281 vs. pneumonia, 272 vs. tuberculosis, 272 epidemiology o , 14, 269, 270t

etiology and pathophysiology o , 269-270 ollow-up or, 276 undamentals o , 269 management o , 273-275, 274t complementary and alternative therapy in, 275 GOLD grade in, 273, 274t medications in or acute exacerbation, 275 or stable COPD, 274 or symptomatic relie , 274-275 nonpharmacologic, 273-274 re erral in, 275 surgery in, 275 patient education on, 276 patient story o , 269, 269f pneumothorax rom, 296 prevention and screening or, 275 prognosis in, 275-276 risk actors or, 270 Chronic pain syndromes. See also specific types in sickle cell disease, 255 Chronic suppurative otitis media vs. acute otitis and otitis media with e usion, 115 vs. ear oreign body, 124 vs. otitis externa, 119f, 121 Churg-Strauss syndrome, vs. vasculitis, 895 Chylothorax, 286-289. See also Pleural e usion Cicatricial alopecia, 958-962. See also Alopecia, scarring Cicatricial pemphigoid, 923-924, 928 vs. bullous pemphigoid, 931, 931f vs. pemphigus, 938 Cigarette use, 1201-1212. See also Tobacco addiction epidemiology o , 1196 substance abuse and, 1197 Ciliary lush, 84, 84f, 85f Circulatory su iciency, angle o , 243 Cirrhosis, 365-371. See also Liver disease primary biliary, 365 (See also Liver disease) Clark nevus, 802-805. See also Nevus, dysplastic Claudication, venous, vs. peripheral arterial disease, 235 Clavi, 1050-1053. See also Corns Clavicular racture, 511-513 diagnosis o , 511-512, 512t di erential diagnosis o vs. acromioclavicular separation, 512, 512t, 513f vs. pseudoarthrosis o clavicle, 512 vs. sternoclavicular dislocation, 512 epidemiology, etiology and pathophysiology o , 511 undamentals o , 511, 511f, 512f management o , 511f, 512-513, 512t patient education on, 513 patient story o , 511, 511f prognosis and ollow-up o , 513 Clear cell carcinoma, renal cell, 421 Clinical evidence, educating patients on, 8 Closed-angle glaucoma. See Glaucoma

Clostridial myonecrosis, vs. necrotizing asciitis, 590 Clostridium difficile diagnosis o , 326-327, 327f di erential diagnosis o , 326-329 vs. ischemic bowel, 327 vs. ischemic colitis, 363 vs. other pathogens, 327 epidemiology, etiology and pathophysiology o , 326 management o , 327-328 patient education on, 328 patient story o , 326, 326f prognosis and ollow-up o , 328 risk actors or, 326 Clubbing, 206-208 diagnosis o , 207, 207f di erential diagnosis o vs. hypertrophic osteoarthropathy, 207 in secondary clubbing, 207 epidemiology, etiology and pathophysiology o , 206 ollow-up and patient education on, 208 management and prognosis in, 208 patient story o , 206, 206f in pulmonary ibrosis, 307, 307f risk actors or, 206 Cluster headache, 1174-1176, 1175f. See also Headache vs. sinusitis, 135 vs. temporal arteritis, 535 Coarctation o aorta, vs. renovascular hypertension, 419 Cobalamin de iciency, 248-252. See also Vitamin B12 de iciency Cocaine abuse, 1196f, 1228-1233 death rom, 15 diagnosis o , 1198-1199, 1229-1231, 1229f-1231f, 1237-1238 di erential diagnosis o vs. adrenal hyperplasia/ adenoma, 1231 vs. delirium, 1232 vs. encephalitis, 1232 vs. hyperthyroidism, 1231-1232 vs. hypoglycemia, 1232 vs. meningitis, 1232 epidemiology o , 1196, 1228 etiology and pathophysiology o , 1198, 1228, 1229f ollow-up o , 1232-1233 orms o , 1228, 1229f undamentals o , 1228 injection, 1235-1239 diagnosis o , 1236-1237, 1236f, 1237f di erential diagnosis o , 1237 epidemiology o , 1235 etiology and pathophysiology o , 1235-1236 ollow-up o , 1239 undamentals o , 1235 management o , 1237-1238 patient education on, 1239 prevention and screening or, 1238-1239 prognosis in, 1239 risk actors or, 1236

1269

1270

INDEX Cocaine abuse (Cont.): levamisole-induced vasculitis rom, 1229-1230, 1230f, 1231f management o , 1232 patient education on, 1233 patient story o , 1196, 1196f, 1228, 1228f prevalence o , 14 prognosis in, 1232 puri ied, 1196f risk actors or, 1228-1229 skin popping o , 1229, 1230f, 1236, 1237f Coccidiomycosis erythema nodosum in, 887 vs. tuberculosis, 320 Cold sores. See also Herpes simplex virus vs. angular cheilitis, 139 Colic, biliary vs. kidney stones, 400 vs. pancreatitis, 374 vs. peptic ulcer disease, 379 Colitis in ectious vs. diverticulitis, 342 vs. ischemic colitis, 363 ischemic, 362-364 (See also Ischemic colitis) ischemic vs. ulcerative, 384, 384f vs. kidney stones, 400 NSAID-induced, 384 pseudomembranous, 326-329 (See also Clostridium difficile) ulcerative, 381-386 (See also In lammatory bowel disease) Collagen vascular disease, vs. pulmonary ibrosis, 307 Collateral ligament tears, 525-529. See also Knee injuries Colles racture, 514f, 515 Colon cancer, 329-333 diagnosis o , 329f, 330-331, 330f di erential diagnosis o vs. appendicitis, 331 vs. colon polyp, 331, 337 vs. diverticula, 331 vs. diverticulitis, 331, 342 vs. gastrointestinal in ection, 331 vs. hemorrhoids, 331, 360 vs. in lammatory bowel disease, 331 vs. ischemic colitis, 364 vs. vascular colonic ectasias, 331 epidemiology, etiology and pathophysiology o , 329 ollow-up o , 333 undamentals o , 329 management o , 331 patient education on, 333 patient story o , 329, 329f prevention and screening or, 329f, 330f, 331-332, 332f prognosis in, 333 risk actors or, 329-330 Colonic ectasias, vascular vs. colon cancer, 331 vs. colon polyps, 337

Colon polyps, 335-338 de inition o , 335 diagnosis o , 335f-337f, 336-337 di erential diagnosis o vs. anal issure, 337 vs. colon cancer, 331, 337 vs. diverticula, 337 vs. gastrointestinal in ection, 337 vs. hemorrhoids, 337 vs. in lammatory bowel disease, 337 vs. vascular colonic ectasias, 337 epidemiology o , 335 etiology and pathophysiology o , 335-336 ollow-up o , 338 management o , 337, 337f patient education on, 338 patient story o , 335, 335f prevention o , 337-338 prognosis in, 338 risk actors or, 336 Combination contraceptive patch, 12, 13f Comedonal acne, 540-546, 541f, 544f. See also Acne vulgaris Comedonal nevus, 789, 790f Commissural cheilitis, 138-140, 138f, 139f Common River, 32, 32f Common warts, 617-621. See also Warts, common Community-acquired methicillin-resistant Staphylococcus aureus. See Methicillinresistant Staphylococcus aureus (MRSA) Community-acquired pneumonia, 290-295. See also Pneumonia, community-acquired Compartment syndrome, vs. peripheral arterial disease, 235 Compound nevi, 786, 786f, 787, 787f, 790 Compression ractures, 501-503 diagnosis and screening or, 501f, 502, 502f di erential diagnosis o vs. back pain, nonspeci ic, 502 vs. osteomyelitis or discitis, 503 epidemiology o , 501 etiology and pathophysiology o , 501-502 undamentals o , 501 management o , 503 patient education on, 503 patient story o , 501, 501f prognosis and clinical course o , 503 Concretion, 344 Condoms, 11t Condylar split racture, lateral, 527f Condyloma lata vs. genital warts, 630, 630f with syphilis, 1103, 1104f Condylomata acuminata, 627-632. See also Warts, genital (condylomata acuminata) giant, 629, 630f vs. hemorrhoids, 359 Congenital heart disease, clubbing in, 206-208, 206f, 207f Congenital nevi, 793-797. See also Nevus, congenital Congestive heart ailure. See Heart ailure

Conjunctival melanoma, 68-70, 69f Conjunctival nevus, 68-70, 68f, 75f Conjunctival pigmentation, 68-70, 68f, 69f Conjunctival squamous cell carcinoma, 63 Conjunctivitis, 75-78 allergic, 75-78 diagnosis o , 75-76, 75f, 76f di erential diagnosis o vs. acute-angle closure glaucoma, 76 vs. corneal oreign body/ abrasion, 74 vs. corneal ulceration, 76 vs. episcleritis, 76, 82 vs. herpetic keratitis, 76, 77f vs. iritis, 76, 85 vs. pterygium, 63 vs. scleritis, 76, 82 vs. uveitis, 76, 85 vs. zoster ophthalmicus, 603 epidemiology, etiology and pathophysiology o , 75, 75f ollow-up o , 78 oreign body, 76-77, 77f giant papillary, 76, 76f gonococcus, 75-78, 76f management o , 78 patient education on, 78 patient story o , 75, 75f prevention o , 78 with reactive arthritis, 757-760, 758f red eye in, 106-110, 106f, 107t, 108f bacterial, 106f giant papillary, 106f trachoma, 77, 77f vernal (allergic, warm weather), 77 viral, 106, 106f rom zoster ophthalmicus, 603 Connective tissue disorders vs. bacterial endocarditis, 222 vs. osteoarthritis, 479 vs. rheumatoid arthritis, 484 Contact dermatitis, 691-697, 926, 926f allergic, 691, 926, 926f vs. impetigo, 564 diagnosis o , 691-695 clinical eatures in, 691f, 692-694, 693f-695f history in, 691-692, 691f-694f laboratory studies in, 694-695, 694f, 695f, 696t, 702, 702f di erential diagnosis o vs. atopic dermatitis, 688, 695 vs. atrophic vaginitis, 438 vs. cutaneous larva migrans, 681 vs. eczema, dyshidrotic, 695 vs. eczema, nummular, 708 vs. erythrasma, 578 vs. ungal in ections, 694f, 696 vs. immediate IgE contact reaction, 695 vs. melasma, 998 vs. methamphetamine abuse, 1226 vs. otitis externa, 121 vs. photodermatitis, 1006f, 1007f vs. psychocutaneous disorders, 714 vs. scabies, 677, 696

INDEX vs. seborrheic dermatitis, 726 vs. tattoo dye allergy, 696, 696f vs. tinea cruris, 656 vs. tinea pedis, 660, 660f epidemiology, 691, 691f erythroderma with, 761, 762t, 764f etiology and pathophysiology o , 691 ollow-up o , 697 undamentals o , 691 hand, 699-705, 699f, 701f irritant and occupational irritant, 691, 691f, 693f, 695f, 697f management o , 696-697, 697f patient education on, 697 patient story o , 691, 691f Contact lens conjunctivitis rom, 75, 76f giant papillary conjunctivitis rom, 76, 76f keratitis rom, 76, 77f Contraception, 10-13 choice and options in, 10-11, 11t newer methods, 11-12, 11t, 12f, 13f epidemiology o , 10 ollow-up with, 13 patient education on, 13 patient story o , 10, 10f risks, bene its, and barriers to, 10 with smoking, 11 Contraceptive patch, 11t combination, 12, 13f Control, supporting, 7 Copper-containing intrauterine device, 11t, 12 Cornea, 72 Corneal oreign body/ abrasion, 72-74 diagnosis o , 72-73, 73f di erential diagnosis o vs. conjunctivitis, 74 vs. corneal ulceration, 73-74, 73f vs. glaucoma, acute angle-closure, 74 vs. iritis, 73 vs. keratitis, 73-74, 73f vs. uveitis, 73 epidemiology, etiology and pathophysiology o , 72 ollow-up or, 74 management o , 72f, 73f, 74 metallic, 73, 73f, 77f patient education on, 74 patient story o , 72, 72f prevention o , 74 risk actors or, 72 wood chip, 72, 72f Corneal ulceration vs. conjunctivitis, 76 vs. corneal oreign body/ abrasion, 73-74, 73f red eye in, 108, 108f, 109, 109f vs. scleritis and episcleritis, 82 vs. uveitis and iritis, 85 Corns, 1050-1053 diagnosis o , 1051, 1051f, 1052f di erential diagnosis o vs. acrolentiginous melanoma, 1052 vs. pachyonychia congenita, 1051f, 1052 vs. plantar warts, 634-635, 1052

vs. porokeratosis, 1052 vs. scars, hypertrophic, 1052 vs. skin cancer, nonmelanoma, 1052 epidemiology, etiology and pathophysiology o , 1050 undamentals o , 1050 management o , 1052, 1052f, 1053f patient education on, 1053 prevention o , 1052-1053 prognosis and ollow-up o , 1053 risk actors or, 1050-1051, 1051f Cornu cutaneum, 821-823. See also Cutaneous horn Coronary artery disease, 212-214 diagnosis o , 213 di erential diagnosis o vs. costochondritis, 213 vs. gastroesophageal re lux, 213 vs. herpes zoster, 598 vs. pericarditis, 213 vs. pneumothorax, 213 epidemiology, etiology and pathophysiology o , 212, 213f ollow-up and patient education on, 214 management o , 213-214 patient story o , 212, 212f prevention o , 214 risk actors or, 212 Coronary heart disease epidemiology o , 212 etiology and pathophysiology o , 212 patient education on, 214 prevention o , 214 risk actors or, 212 Corticosteroids, topical and intralesional, 1245-1247 generic and trade names or, 1245t-1246t in ection technique or, 1247f injection concentrations o , 1247t potency chart or, 1245t-1246t side e ects o , common, 1246t Corynebacterium minutissimum, erythrasma rom, 575, 575f, 576f Corynebacterium, pitted keratolysis rom, 572 Corynebacterium vaginosis (vaginalis, vaginitis), 441-443. See also Bacterial vaginosis Costochondritis vs. coronary artery disease, 213 vs. pericarditis, 230 Cotton-wool spots di erential diagnosis o , 94 in hypertensive retinopathy, 93, 93f, 94, 94f in papilledema, 97f Roth spots, 220, 220f, 221, 221f, 222 Cough, drug-induced, vs. asthma, 264 Coumadin (war arin) cutaneous reactions to, 1024-1032 (See also Drug reactions, cutaneous) diagnosis o , 1025f, 1028, 1031f epidemiology o , 1025, 1025f etiology and pathophysiology o , 1025f, 1027 war arin-induced skin necrosis rom, 1024-1032 (See also Drug reactions, cutaneous) Cowden disease, gingival overgrowth rom, 166, 166f

Coxsackievirus A16, vs. pharyngitis, 146, 146f Coxsackie virus, conjunctivitis rom, 75-78 Crab lice, 668-672, 669f, 670f. See also Lice Crack, 1228-1233. See also Cocaine abuse Cradle cap, 723-727. See also Seborrhea (seborrheic dermatitis) Cranial nerve palsy, rom Lyme disease, 1086 Creeping eruption, 680-682, 680f, 681f CREST syndrome, 917, 917f-919f vs. vascular lesions, 1021 Crohn disease, 381-386. See also In lammatory bowel disease colon mucosa in, 861f vs. peptic ulcer disease, 379 pyoderma gangrenosum with, 861-867, 861f, 862f (See also Pyoderma gangrenosum) Cross-cultural events, patient encounters as, 7 Crow sign, in neuro ibromatosis, 1192f Cryotherapy, blistering a ter, 926, 926f Cryptogenic ibrosing alveolitis, 306-309. See also Pulmonary ibrosis Cryptogenic organizing pneumonia, vs. pulmonary ibrosis, 308 Cullen sign, in pancreatitis, 373, 374f Cup-to-disc ratio, in glaucoma, 87, 87f, 88, 88f Cushing syndrome, 1164-1170 diagnosis o , 1165-1169, 1166f-1168f, 1166t di erential diagnosis o vs. cocaine abuse, 1231 vs. obesity, 1137 vs. renovascular hypertension, 419 epidemiology o , 1164 etiology and pathophysiology o , 1164-1165, 1164f, 1164t, 1165f, 1168f ollow-up o , 1170 undamentals o , 1164 management o , 1169-1170, 1169f, 1170f patient education on, 1171 patient story o , 1164, 1164f prognosis in, 1170 Cusp prolapse, vs. bacterial endocarditis, 222 Cutaneous adverse reactions, 1024-1032. See also Drug reactions, cutaneous Cutaneous horn, 821-823 diagnosis o , 821f-823f, 823 di erential diagnosis o vs. common warts, 823 vs. keratoacanthomas, 814 epidemiology o , 821 etiology and pathophysiology o , 821-822, 821f, 822f management and ollow-up o , 823 patient story o , 821, 821f risk actors or, 822 Cutaneous larva migrans, 680-682 diagnosis o , 680, 680f, 681f di erential diagnosis o vs. contact dermatitis, 681 vs. erythema chronicum migrans o Lyme disease, 681 vs. ungal in ections, 680-681 vs. phytophotodermatitis, 681 vs. tinea corporis, 650

1271

1272

INDEX Cutaneous larva migrans (Cont.): epidemiology, etiology and pathophysiology o , 680 ollow-up o , 682 management and patient education on, 681 patient story o , 680, 680f Cutaneous lupus, chronic, 899-906 diagnosis o , 903f-905f biopsy in, 905 clinical eatures in, 901-902, 903f-905f distribution in, typical, 902-903 laboratory testing in, 904-905 di erential diagnosis o vs. actinic keratosis, 905 vs. basal cell carcinoma, 829 vs. dermatomyositis, 905 vs. drug-induced lupus, 905 vs. leukoplakia, 174, 175f vs. lichen planus, 905 vs. melasma, 998 vs. psoriasis, 905 vs. rosacea, 905 vs. sarcoidosis, 905 vs. scleroderma, 905, 920 vs. syphilis, 905 epidemiology o , 899-900 etiology and pathophysiology o , 900 ollow-up o , 906 undamentals o , 899 management o , 905-906 patient education on, 906 prevention o , 906 prognosis in, 906 risk actors or, 900 scarring alopecia in, 960, 961f Cutaneous sebaceous neoplasm, 813-815. See also Keratoacanthoma Cutaneous T-cell lymphoma, 873-878 complications o , potential, 878 diagnosis o , 873f-876f, 874-876 di erential diagnosis o vs. dermatitis, 877 vs. idiopathic guttate hypomelanosis, 877 vs. parapsoriasis, 876 vs. psoriasis, 737-738 vs. reactive in lammation in HIV, 877 vs. vasculitis, 895 vs. vitiligo, 873f, 877 epidemiology o , 873 erythroderma with, 762, 762t, 764f etiology and pathophysiology o , 873-874 undamentals o , 874 management o , 877 patient education on, 878 patient story o , 873, 873f prognosis and ollow-up o , 877 Cutaneous tuberculosis, 45, 45f Cutaneous vasculitis, 891-897. See also Vasculitis di erential diagnosis o vs. cutaneous T-cell lymphoma, 895 vs. erythema multi orme, 883 vs. hypersensitivity syndromes, 883

vs. idiopathic thrombocytopenic purpura, 895, 896f vs. meningococcemia, 895 rom levamisole-adulterated cocaine, 1229-1230, 1230f, 1231f Cutting, sel -, a ter sexual assault, 56, 56f Cyanocobalamin de iciency, 248-252. See also Vitamin B12 de iciency Cyst. See also specific types vs. polycystic kidneys, 407 vs. preauricular tags, 128, 128f Cystic disease, acquired, vs. polycystic kidneys, 407 Cystitis vs. diverticulitis, 341 hematuria in, 429, 430f management o , 431 urinary sediment in, 429-431 (See also Urinary sediment) white blood cell casts in, 429, 430f Cytolytic vaginosis, vs. Candida vulvovaginitis, 447 Cytomegalovirus, vs. pharyngitis, 146 D Dabigatran, 203, 204t Dactylitis, 487, 487f in reactive arthritis, 757f in sickle cell disease, 255, 255f, 257 Dancer racture, 519-520, 519f, 520f Dandru , 723-727. See also Seborrhea (seborrheic dermatitis) vs. lice, 671 Darier disease, 1039-1044 diagnosis o , 1039f-1042f, 1040 di erential diagnosis o vs. Grover disease, 1041 vs. Hailey-Hailey disease, 1040-1041, 1042f vs. psoriatic nails, 991, 991f vs. seborrheic dermatitis, 1041 epidemiology o , 1039 etiology and pathophysiology o , 1039 ollow-up o , 1044 management o , 1043-1044 patient education on, 1044 patient story o , 1039, 1039f, 1040f Darier-Roussy disease, 867-872, 869f. See also Sarcoidosis Darier sign, 719, 719f, 923 DaVinci robot, or prostate cancer surgery, 413, 413f DC cardioversion, or atrial ibrillation, 199-200, 201 Deconditioning, vs. heart ailure, 210 Deep venous thrombophlebitis. See Deep venous thrombosis (DVT) Deep venous thrombosis (DVT), 215-218 de inition o , 215 diagnosis o , 216, 216f, 216t di erential diagnosis o vs. Baker cyst, 216 vs. cellulitis, 217, 217f vs. Charcot arthropathy, 1066 vs. lymphedema o leg, 217, 218f

vs. muscle strain/ tear, 216 vs. peripheral arterial disease, 235 vs. super icial thrombophlebitis, 216, 217f vs. venous insu iciency, 216 epidemiology, etiology and pathophysiology o , 215 ollow-up o and patient education on, 218 management o , 217-218, 218t patient story o , 215, 215f prognosis and clinical course o , 218 pulmonary embolus rom, 299 risk actors or, 215 Degenerative arthritis o spine, vs. osteoporosis and osteopenia, 1143 Delirium, vs. cocaine abuse, 1232 Delusions o parasitosis, vs. psychocutaneous disorders, 714 Dementia death rom, 15 di erential diagnosis o vs. normal pressure hydrocephalus, 1186 vs. subdural hematoma, 1183 end o li e, patient story o , 14 Dennie-Morgan lines, with atopic dermatitis, 685, 686f Dental abscess, 584, 584f. See also Abscess Dental cavities, 181-183. See also Caries, adult Dental decay, 181-183. See also Caries, adult Dental hygiene, poor, vs. gingivitis, 163 Dental pain, vs. sinusitis, 136 Depo-Provera, 11t Depression a ter intimate partner violence, 51, 52, 53 a ter sexual assault, 55, 56, 58 vs. subdural hematoma, 1183 de Quervain tenosynovitis, vs. distal radius racture, 516 de Quervain thyroiditis, 1150 Dermal nevi, 787, 787f, 788f, 790 Dermatitis di erential diagnosis o vs. cutaneous T-cell lymphoma, 877 vs. lichen planus, 754 ex oliative, 761-766 (See also Erythroderma) nummular, 706-709 (See also Eczema, nummular) perioral vs. rosacea, 551, 552f vs. seborrheic dermatitis, 726 Dermatitis herpeti ormis, 924, 925f, 928, 947-948, 947f vs. bullous pemphigoid, 931 vs. chickenpox, 594 vs. eczema, nummular and dyshidrotic, 948 vs. pemphigus, 938 vs. porphyria cutanea tarda, 948, 948f vs. scabies, 947-948 Dermato ibroma, 778-781 diagnosis o , 778-779, 778f-780f di erential diagnosis o vs. dermato ibrosarcoma protuberans, 779, 781f vs. epidermal inclusion cyst, 779 vs. hypertrophic scar, 779

INDEX vs. Kaposi sarcoma, 1074 vs. keloids, 1036 vs. malignant ibrous histiocytoma, 779 vs. melanoma, 849 vs. molluscum contagiosum, 615 vs. neuro ibroma, 779 vs. pseudosarcomatous dermato ibrosarcoma, 779 vs. seborrheic keratosis, 779 epidemiology, etiology and pathophysiology o , 778 undamentals o , 778 management o , 779-781 patient education on, 781 patient story o , 778, 778f prognosis in, 781 Dermato ibrosarcoma protuberans vs. dermato ibroma, 779, 781f vs. keloids, 1036 Dermatographism, 717, 717f, 719 Dermatomyositis, 908-914 diagnosis o , 909-912 biopsy in, 912 clinical eatures in, 908f-910f, 910 distribution in, typical, 908f-912f, 910-911 5 criteria in, 909-910, 908f-910f laboratory studies and diagnostic tests in, 911-912 di erential diagnosis o vs. drug reaction, 912 vs. hypothyroidism, 912 vs. lupus erythematosus, 905 vs. overlap syndrome, 912 vs. photodermatitis, 1009 vs. photosensitivity reactions, 912 vs. polymorphous light eruption, 912 vs. polymyalgia rheumatica, 535 vs. polymyositis, 912 vs. porphyria cutanea tarda, 943 vs. rosacea, 912 vs. steroid myopathy, 912 epidemiology o , 909 etiology and pathophysiology o , 909 ollow-up o , 914 undamentals o , 908f, 909, 909f management o , 912-914 intravenous treatment in, 914 malignancy work-up in, 914 nonpharmacologic, 913 oral treatment in, 913 overview o , 912-913 topical treatment in, 913 overlap syndrome in, 912 patient education on, 914 patient story o , 908, 908f, 909f prognosis in, 914 Dermatophilus congolensis, pitted keratolysis rom, 572 Dermatophytes, 638-642. See also Fungal in ections vs. atopic dermatitis, 688 Dermatophytid reaction, tinea pedis, 658, 658f, 659

Dermatophytosis vs. erythrasma, 577 o nails, 979-983 (See also Onychomycosis) Dermatoses, sel -in licted, 710-715. See also Psychocutaneous disorders Dermatosis papulosa nigra, 772, 772f Dermoscopy, 1248 Diabetes mellitus, 1110-1115 acanthosis nigricans in, 1111, 1111f, 11181120 (See also Acanthosis nigricans) acrochordons in, 767, 767f, 768 Charcot arthropathy in, 1065-1067, 1112, 1112f (See also Charcot arthropathy) diabetic dermopathy in, 1110f, 1111, 1115, 1122-1123 (See also Diabetic dermopathy) diagnosis o , 1110f-1112f, 1111-1112 dry gangrene in, 1068-1069, 1068f, 1069f epidemiology o , 14, 1110 etiology and pathophysiology o , 1110 ollow-up in, 1115 oot ulcers in ischemic, 1061-1062, 1061f, 1062f, 1111, 1112f, 1114, 1115 neuropathic, 1063-1064, 1063f vs. venous insu iciency ulcers, 240 undamentals o , 1110 insulin resistance in, 1110, 1113 management o , 1112-1114 necrobiosis lipoidica in, 1111, 1112f, 11251127 (See also Necrobiosis lipoidica) osteomyelitis o oot in, 1096-1101, 1098f (See also Osteomyelitis) patient education in, 1115 patient story o , 1110, 1110f prevention and screening in, 1114-1115 prognosis in, 1115 psoriasis in, 740 risk actors or, 1111 tinea pedis in, 1110, 1110f xanthoma and xanthelasma in, 1111, 1112f, 1129-1133 (See also Xanthomas) Diabetic dermopathy, 1122-1123 diagnosis o , 1111, 1111f, 1122, 1122f, 1123f di erential diagnosis o vs. necrobiosis lipoidica, 1122 vs. scars, traumatic, 1123 vs. Schamberg disease, 1123 vs. stasis dermatitis, 1123 epidemiology, etiology and pathophysiology o , 1122 undamentals o , 1122 management and prognosis in, 1115, 1123 patient education in, 1123 patient story o , 1122, 1122f prevention o , 1124 Diabetic retinopathy, 90-92, 226f. See also Diabetes mellitus diagnosis o , 90f, 91, 91f, 1110f, 1111 di erential diagnosis o vs. age-related macular degeneration, 100 vs. HIV retinopathy, 91 vs. hypertensive retinopathy, 91 vs. hyphema, 104

epidemiology, etiology and pathophysiology o , 90, 90f etiology and pathophysiology o , 90f, 91f ollow-up and patient education on, 92 management o , 91, 92f re erral in, 1114 patient story o , 90, 90f, 1110, 1110f prevention o , 91-92 prognosis in, 1115 proli erative vs. nonproli erative, 90, 90f, 91f risk actors or, 90 vitreous hemorrhage rom, 91, 91f Diagnosis images in, 2 internal image banks or, expanding, 3 senses in, 2 using images or, 3, 3t Diaphragm with spermicide, 11t Diaphyseal stress racture, vs. metatarsal racture, 520 Diarrhea, in ectious, 327 Dietary approaches to stop hypertension (DASH), 227 Diet, on mortality, 15 Digoxin or atrial ibrillation, 198-199 or heart ailure, 210 “Dinner- ork” de ormity, 514-518. See also Radius racture, distal Diphtheria, vs. pharyngitis, 146 Diphyllobothrium latum, 1080-1083. See also Intestinal worms and parasites Disabilities, caring or those with, 27-28, 27f, 28f Disaster relie , 24-25, 24f, 25f Disc herniation vs. ankylosing spondylitis, 493 vs. back pain, 496, 496f Discitis, vs. compression ractures, 503 Discoid eczema, 706-709. See also Eczema, nummular Discoid hand dermatitis, 699, 700f Discoid lupus erythematosus, 899-906. See also Cutaneous lupus, chronic Dissecting cellulitis, scarring alopecia rom, 959, 960f Distal radius racture, 514-518. See also Radius racture, distal Diuretics, non–potassium-sparing, or heart ailure, 210 Diverticula vs. colon cancer, 331 vs. colon polyps, 337 Diverticular disease, 340 Diverticulitis, 340-343 complicated, 340 diagnosis o , 340f, 341, 341f di erential diagnosis o vs. appendicitis, 342 vs. colon cancer, 331, 342 vs. cystitis/ pyelonephritis, 341 vs. in ectious colitis, 342 vs. in lammatory bowel disease, 342 vs. ischemic colitis, 363

1273

1274

INDEX Diverticulitis, di erential diagnosis o (Cont.): vs. kidney stones, 341, 400 vs. ovarian cyst or ectopic pregnancy, 342 vs. small-bowel obstruction, 342 vs. ureteral calculi, 341 epidemiology, 340 etiology and pathophysiology o , 340-341 ollow-up o , 342-343, 342f undamentals o , 340 management o , 342 patient education on, 343 patient story o , 340, 340f prognosis and clinical course o , 342 risk actors or, 341 terminology or, 340, 340f Diverticulosis, 340, 340f asymptomatic, 3432f Docetaxel, or prostate cancer, 413 Doctor–patient reciprocity, 6 Doctor–patient relationship, 6-8 good, 7-8 humor in, 6 maximizing patient education in, 8 patient story in, 6 skills or, 8 what patients want rom their physician in, 6 what physicians want rom and or patients in, 6, 7f Doctors Without Borders, 23-24 patient stories rom, 23, 23f Döderlein cytolysis, vs. Candida vulvovaginitis, 447 Domestic violence, 50-53 Dowager’s hump, 1142. See also Osteoporosis and osteopenia Dowling-Meara epidermolysis bullosa simplex, 943-944, 945f Doxycycline, cutaneous reactions to, 1024-1032, 1027f. See also Drug reactions, cutaneous DRESS/ DIHS diagnosis o , 1029, 1030f, 1031 di erential diagnosis o , 1031 epidemiology o , 1025 Drink, 1213 Drinking, heavy, 1213-1220. See also Alcoholism Drug hypersensitivity, 1024 Drug-induced alopecia, vs. scarring alopecia, 961 Drug-induced bullous pemphigoid, 929 Drug-induced gingival overgrowth, 166-168. See also Gingival overgrowth Drug-induced liver disease, 365-371. See also Liver disease Drug-induced lupus, vs. lupus erythematosus, 905 Drug-induced meningitis, 1094 Drug-induced photosensitivity, 1006-1011, 1006f, 1007f, 1008t, 1009t. See also Photosensitivity Drug reactions, cutaneous, 1024-1032 bullous drug eruptions, 926, 927f diagnosis o , 1024f-1030f, 1028-1031, 1029t di erential diagnosis o vs. bullous pemphigoid, 1031

vs. dermatomyositis, 912 or DRESS/ DIHS, 1031 or erythema multi orme, 1031 vs. hematoma, war arin, 1031, 1031f vs. herpes simplex virus, 609 vs. pemphigus vulgaris, 1031 vs. pityriasis rosea, 1031 vs. Stevens-Johnson syndrome, 1028f, 1031 vs. syphilis, 1031, 1107 or toxic epidermal necrolysis, 1031 or urticaria, 1031 vs. viral exanthemas, 1031 epidemiology o , 1024-1026, 1024f-1028f, 1029t erythroderma rom, 761-766 (See also Erythroderma) etiology and pathophysiology o , 1025f, 1026-1027 undamentals o , 1024 management o , 1031-1032 patient education on, 1032 patient story o , 1024, 1024f pityriasis rosea rom, 746 prevention o , 1032 prognosis and ollow-up o , 1032 risk actors or, 1027-1028 Drug toxicity. See also specific drugs vs. pulmonary ibrosis, 307 Drumstick ingers, 206-208, 206f, 207f Drusen in age-related macular degeneration, 99-101, 99f, 100f (See also Age-related macular degeneration) di erential diagnosis o , 100 optic disc, 97 Dry gangrene, 1068-1069, 1068f, 1069f Dry mouth, dental caries with, 183 Ductal ectasia with in lammation, vs. breast cancer, 464 Duodenal ulcers, 377-380. See also Peptic ulcer disease Dupuytren disease (contractures), 530-531, 530f, 531f vs. ganglion cysts and palmar nodules, 531 vs. hand tumors, 531 vs. intrinsic joint contractures, 531 vs. occupational hyperkeratosis and callous, 531 vs. rheumatoid arthritis, 531 vs. trigger inger and stenosing tenosynovitis, 531 Dust mite control, 265, 266f Dye allergy, tattoo, vs. contact dermatitis, 696, 696f Dyscoria, 104f Dyshidrotic eczema, 699-705. See also Eczema, hand Dyspepsia, nonulcer or unctional, vs. peptic ulcer disease, 379 Dysphonia, 149-153. See also Hoarseness Dysplastic nevus, 802-805. See also Nevus, dysplastic Dyspnea, 150 Dyspnea scale, MMRC, 270, 270t

Dystrophic epidermolysis bullosa, 943-944, 944f vs. erythema multi orme bullosum, 944 vs. porphyria cutanea tarda, 943, 944 Dysuria, 1078 E Ear disease, suppurative, vs. Bell’s palsy, 1189 Ear oreign body, 123-125 beach sand, 124f bead, 124f di erential diagnosis o vs. acute otitis and otitis media with e usion, 115, 123 vs. chronic suppurative otitis media, 124 vs. otitis externa, 121, 123 insects, 123, 123f Eating disorder, a ter sexual assault, 58 Ecstasy, 1197f. See also Substance abuse disorder epidemiology o , 1196, 1197f (See also Substance abuse disorder) prevalence o , 15 Ecthyma, vs. pyoderma gangrenosum, 864 Ectopic pregnancy, vs. diverticulitis, 342 Eczema, 683-689. See also Atopic dermatitis atopic, 683-689 (See also Atopic dermatitis) di erential diagnosis o areola, vs. Paget disease o breast, 468, 468f asteatotic, vs. X-linked ichthyosis, 10421043 vs. porphyria cutanea tarda, 943 discoid, 706-709 microbial, 706-709 (See also Eczema, nummular) as photoallergic drug reaction, 1007f, 1008, 1009 seborrheic, 723-727 (See also Seborrhea (seborrheic dermatitis)) Eczema, hand, 699-705 allergens and types o atopic, 699, 700f chronic vesicular, 699, 701f contact, 699, 699f, 701f endogenous, 699 exogenous, 699 rictional, 699, 700f hyperkeratotic, 699, 700f in ectious, 699, 701f most requent, 699-701 nummular, 699, 700f pompholyx (dyshidrosis), 699, 700f rubber allergen, 701, 703t diagnosis o , 699f-702f, 701-702 di erential diagnosis o vs. Candida, 701f, 702 vs. knuckle pads, 702 vs. psoriasis, 702 vs. tinea manus, 702, 702f dyshidrotic, 699-705 (See also Eczema, hand) vs. atopic dermatitis, 687 vs. contact dermatitis, 695 vs. dermatitis herpeti ormis, 948 vs. tinea pedis, 660, 661f epidemiology o , 699

INDEX etiology and pathophysiology o , 699-701, 699f-701f ollow-up o , 705 undamentals o , 699 management o , 702-705, 703t, 704t patient education on, 703t patient story o , 699, 699f Eczema herpeticum with atopic dermatitis, 684, 684f vs. impetigo, 563 Eczema, nummular, 706-709 diagnosis o , 706-708, 706f-708f di erential diagnosis o vs. actinic keratosis and Bowen disease, 809 vs. asteatotic dermatitis, 708 vs. atopic dermatitis, 708 vs. basal cell carcinoma, 829 vs. contact dermatitis, 708 vs. dermatitis herpeti ormis, 948 vs. granuloma annulare, 857 vs. lichen simplex chronicus, 708 vs. mycosis ungoides, 708 vs. pityriasis rosea, 748 vs. psoriasis, 708, 738 vs. psychocutaneous disorders, 714 vs. squamous cell carcinoma, 839 vs. tinea corporis, 650, 708 epidemiology, etiology and pathophysiology o , 706 ollow-up o , 709 undamentals o , 706 hand, 699, 700f management o , 708-709 patient education on, 709 patient story o , 706, 706f Eczema, orbicular, 706-709. See also Eczema, hand Eczematous dermatitis, vs. lichen planus, 753 Eczema vaccinatum, with atopic dermatitis, 684, 684f Edema in nephrotic syndrome, 402, 402f, 403, 403f pitting in chronic kidney disease, 426, 427f in nephrotic syndrome, 402, 402f Edema blisters, 927 Edoxaban, 204 Education amily, end o li e, 19-20 patient end o li e, 19-20 on amily planning, 12 maximizing e ectiveness o , 8 E usion otitis media with, 112-117 (See also Otitis media with e usion) pericardial, 228-231 (See also Pericardial e usion) pleural in heart ailure, 210f vs. pericardial e usion, 230, 230f in pericarditis, 228, 230 Ehlers-Danlos syndrome, in peripheral arterial disease, 232

Embolus cholesterol, vs. vasculitis, 896 pulmonary, 299-304 (See also Pulmonary embolus) vs. thoracic aortic aneurysm, 189 Empathy, expressing, 7 Emphysema, 269-276. See also Chronic obstructive pulmonary disease (COPD) Empyema, 286-289. See also Pleural e usion Encephalitis, vs. cocaine abuse, 1232 Encephalomyelitis, vs. Lyme disease, 1088 “En coupe de sabre,” in linear morphea, 916f Endocarditis, bacterial, 220-223 diagnosis o , 220f-222f, 221-222 di erential diagnosis o vs. abdominal in ections, 222 vs. cardiac tumors, 222 vs. connective tissue disorders, 222 vs. cusp prolapse, 222 vs. ever o unknown origin, 222 vs. Lamb excrescences, 222 vs. myxomatous changes, 222 vs. nonin ective vegetations, 222 vs. rheumatoid arthritis, 484 epidemiology o , 220 etiology and pathophysiology o , 220-221, 221f injection-drug use in, 1236 undamentals o , 220 management o , 222-223 patient education on, 223 patient story o , 220, 220f, 221f prevention o , 223 prognosis and ollow-up o , 223 risk actors or, 221 End o li e, 14-21 clinical eatures o , 16 diagnosis o , 15-16 epidemiology o , 14 etiology and pathophysiology o , 14-15 ollow-up in, 19-20 management o , 16-19 advance directives in, 17 common symptom control in, 19 hospice care and services in, 17-18, 17f important actors in, 16-17 pain management in, 18 palliative care in, 18 patient and amily/ caregiver discussions in, 16 primary care provider role in, 16, 17f principles o , 16-17 P-SPIKES approach in, 16 social needs in, 19 spiritual needs in, 19 palliative care in, 14 patient and amily education on, 19-20 patient story o , 14 End-stage renal disease death rom, 15-16 incidence o , 426 Entamoeba histolytica, 1080-1083. See also Intestinal worms and parasites

Enterobacter olliculitis, 568 Enterobacteriaceae necrotizing asciitis, 588. See also Necrotizing asciitis Enterobius vermicularis, 1080-1083 Entropion, red eye in, 106, 110 Eosinophilic olliculitis, 566, 567f, 569 Epicondylitis, vs. olecranon bursitis, 509 Epidermal cyst, vs. hidradenitis suppurativa, 560 Epidermal hyperplasia, vs. skin tag, 768 Epidermal inclusion cyst vs. abscess, 585, 586f vs. dermato ibroma, 779 vs. sarcoidosis, 871 Epidermal nevus, 798 Epidermoid carcinoma, 278-284. See also Lung cancer Epidermolysis bullosa, 943-944, 944f, 945f vs. erythema multi orme bullosum, 944 vs. porphyria cutanea tarda, 943, 944 Epidermolysis bullosa acquisita, 924, 925f vs. bullous pemphigoid, 931 Epidermolysis bullosa simplex, 924, 925f Epidermophyton, 638. See also Fungal in ections Epidermophyton floccosum tinea pedis, 658 Epididymitis, vs. kidney stones, 400 Epidural hematoma, vs. subdural hematoma, 1183, 1183f Epiglottitis, vs. pharyngitis, 146 Episcleritis, 80-83 diagnosis o , 81-82, 81f di erential diagnosis o vs. acute-angle closure glaucoma, 82 vs. conjunctivitis, 76, 82 vs. corneal ulceration, 82 vs. iritis, 82, 85 vs. keratitis, 82 vs. uveitis, 82, 85 epidemiology o , 80 etiology and pathophysiology o , 81 undamentals o , 80 management o , 82 patient education on, 83 prognosis and ollow-up or, 82 red eye in, 106-110, 107t, 108, 108f, 109, 109f Episodic tension-type headache, 1174-1176. See also Headache Epithelial keratitis, rom zoster ophthalmicus, 601f, 603 Epithelioma intracutaneous corni ying, 813-815 (See also Keratoacanthoma) sel -healing squamous, 813-815 (See also Keratoacanthoma) Erosio interdigitalis blastomycetica, 701f Eruptive xanthelasma, in diabetes mellitus, 1111, 1112f Eruptive xanthomas, 1129-1133, 1129f, 1130f. See also Xanthomas with obesity, 1136, 1137f Erysipelas, 580, 581f. See also Cellulitis necrotizing, 588-591 (See also Necrotizing asciitis)

1275

1276

INDEX Erythema ab igne, 1012-1015 diagnosis o , 1012f-1014f, 1013-1014 di erential diagnosis o vs. acanthosis nigricans, 1015 vs. livedo reticularis, 1014, 1014f vs. poikiloderma atrophicans vasculare, 1014-1015 epidemiology o , 1012 etiology and pathophysiology o , 1012-1013 undamentals o , 1012 management o , 1015 patient education on, 1015 patient story o , 1012, 1012f prognosis and ollow-up o , 1015 risk actors or, 1013 Erythema annulare centri ugum, 1045-1047 de inition and synonyms or, 1045 diagnosis o , 1045f, 1046, 1046f di erential diagnosis o vs. erythema gyratum repens, 1046 vs. erythema migrans, 1046 vs. granuloma annulare, 857 vs. hypersensitivity syndromes, 883 vs. lupus, cutaneous, 1046-1047 vs. Lyme disease, 1046 vs. mycosis ungoides, 1047 vs. pityriasis rosea, 1046 vs. psoriatic plaques, 1046 vs. sarcoidosis, 1047 vs. tinea corporis, 650, 652f, 1046, 1046f, 1047f epidemiology o , 1045 etiology and pathophysiology o , 1045-1046 management o , 1047 patient education on, 1047 patient story o , 1045, 1045f prognosis and ollow-up o , 1047 Erythema chronicum migrans. See Erythema migrans, o Lyme disease Erythema exudativum perstans, 1045-1047. See also Erythema annulare centri ugum Erythema iguratum perstans, 1045-1047. See also Erythema annulare centri ugum Erythema gyratum perstans, 1045-1047. See also Erythema annulare centri ugum Erythema gyratum repens, vs. erythema annulare centri ugum, 1046 Erythema induratum o Bazin, vs. erythema nodosum, 888 Erythema induratum, vs. necrotizing asciitis, 590 Erythema marginatum perstans, 1045-1047. See also Erythema annulare centri ugum Erythema microgyratum perstans, 1045-1047. See also Erythema annulare centri ugum Erythema migrans vs. erythema annulare centri ugum, 1046 o Lyme disease, 1085f-1087f, 1086 vs. cutaneous larva migrans, 681 vs. erythema annulare centri ugum, 1046 Erythema multi orme, 879-884 diagnosis o , 880-884, 880f, 882f di erential diagnosis o vs. aphthous ulcer, 171

vs. bullous pemphigoid, 883, 931 vs. cutaneous drug reactions, 1031 vs. cutaneous vasculitis, 883 vs. erythema annulare centri ugum, 883 vs. pityriasis lichenoides et varioli ormis acuta, 946 vs. syphilis, 1107 vs. urticaria, 718f, 719, 883 drug-induced diagnosis o , 1027f, 1028, 1028f di erential diagnosis o , 1031 epidemiology o , 1025, 1027f, 1028f epidemiology o , 879-880 etiology and pathophysiology o , 880, 880f ollow-up and patient education on, 884 undamentals o , 879 management o , 884 prevention o , 884 prognosis in, 884 risk actors or, 880 Erythema multi orme bullosum vs. dystrophic epidermolysis bullosa, 944 vs. porphyria cutanea tarda, 943 Erythema nodosum, 886-889 diagnosis o , 886f, 887-888, 887f di erential diagnosis o vs. cellulitis, 888 vs. erythema induratum o Bazin, 888 vs. erythema nodosum leprosum, 888, 888f, 889f vs. necrobiosis lipoidica, 1127 vs. panniculitis, in ectious, 888 vs. sarcoid, nodular cutaneous/ subcutaneous, 888 epidemiology o , 886-887, 886f etiology and pathophysiology o , 886f, 887, 887f undamentals o , 886 management o , 888-889 patient education on, 889 patient story o , 886, 886f prevention o , 889 prognosis and ollow-up o , 889 risk actors or, 886f, 887 sarcoidosis-related, 868 Erythema nodosum leprosum, vs. erythema nodosum, 888, 888f, 889f Erythema perstans, 1045-1047. See also Erythema annulare centri ugum Erythema simplex gyratum, 1045-1047. See also Erythema annulare centri ugum Erythematotelangiectatic rosacea, 549f, 550. See also Rosacea Erythrasma, 575-579 de inition o , 575 diagnosis o , 576-577, 576f, 577f di erential diagnosis o vs. candidiasis, 578, 646 vs. contact dermatitis, 578 vs. dermatophytosis, 577 vs. intertrigo, 578 vs. psoriasis, 577 vs. tinea corporis, 650 vs. tinea cruris, 656, 656f

epidemiology o , 575 etiology and pathophysiology o , 575, 575f, 576f management o , 578 patient education on, 570 patient story o , 575, 575f prognosis and ollow-up o , 578 Erythroderma, 761-766 diagnosis o , 763-765, 765f di erential diagnosis o , 765 epidemiology o , 761 etiology and pathophysiology o , 761-763, 761f-765f, 762t ollow-up o , 766 undamentals o , 761 management o , 761f-765f, 765-766 patient education on, 766 patient story o , 761, 761f Erythroleukoplakia, 174-176. See also Leukoplakia in oropharyngeal cancer, 177, 177f (See also Oropharyngeal cancer) Erythroplakia, 174-176. See also Leukoplakia vs. geographic tongue, 160 vs. leukoplakia, 174, 175f in oropharyngeal cancer, 177, 178f (See also Oropharyngeal cancer) Erythroplasia, 174-176. See also Leukoplakia Erythroplasia o Queyrat, 807-812, 807f, 835, 835f. See also Bowen disease Escherichia coli olliculitis, 568 mastitis, 458 osteomyelitis, 1096-1101 (See also Osteomyelitis) Esophageal cancer, vs. gastric cancer, 352 Esophagitis, vs. gastric cancer, 352 Essure, 12, 12f, 13f Essure tubal occlusion device, 12, 12f, 13f Estrogen-containing contraceptives, smoking with, 11 Estrogen, postmenopause de iciency in, 437-439. See also Atrophic vaginitis Ethiopia Common River in, 32, 32f international humanitarian e orts in, 25-26, 26f pit latrine in, 33, 33f Etonogestrel implant, 11t, 12, 12f Evidence, 1242 Evidence-based medicine, 1242-1244 de inition o , 1242 history o , 1242 interpreting, 1242, 1243f, 1244f in this book, 1242 Exanthematous drug eruptions, 1024-1032. See also Drug reactions, cutaneous diagnosis o , 1024f, 1028 epidemiology o , 1024, 1024f Exanthem, viral, vs. cutaneous drug reactions, 1031 Excoriation, neurotic, 710-715. See also Neurotic excoriation Exercise, on mortality, 15

INDEX Ex oliative dermatitis, 761-766. See also Erythroderma Exophthalmos, Graves, 1153-1158, 1153f, 1156f, 1158f. See also Hyperthyroidism External beam radiation therapy, or prostate cancer, 413 Exudative e usions, vs. transudative e usions, 287-288, 287t Eyelid ecchymosis, 104f Eye trauma (hyphema), 103-105. See also Hyphema F Facial nerve damage, vs. Bell’s palsy, 1189 Facial nerve palsy vs. Bell’s palsy, 1189, 1189f rom Lyme disease, 1086 vs. Lyme disease, 1088 Facial paralysis, idiopathic, 1188-1190. See also Bell’s palsy Failure to thrive, end o li e, 15 False vocal cords, 149, 149f Familial adenomatous polyposis o colon, 335-338. See also Colon polyps Familial atypical mole and melanoma (FAMM) syndrome, 803, 805. See also Nevus, dysplastic Familial hypercholesterolemia, 1129 Familial hyperlipidemia, 1129, 1130 Family planning, 10-13 contraceptive choice and options in, 10-11, 11t new, 11-12, 11t, 12f, 13f epidemiology o , 10 ollow-up in, 13 patient education on, 13 patient story o , 10, 10f risks, bene its, and barriers to, 10 Fanconi anemia, vs. neuro ibromatosis, 1193 Felon vs. herpes simplex virus, 609 vs. paronychia, 987 Female sterilization, 11t Femoral neck racture, 522-524, 522f, 523f. See also Hip racture Ferritin, in iron de iciency anemia, 245 Fertility awareness, 11t Fever o unknown origin, vs. bacterial endocarditis, 222 Fibroadenoma, vs. breast cancer, 464 Fibroepithelial polyps, 767-769. See also Skin tag (acrochordon) Fibroma, vs. polymyalgia rheumatica vs., 535 Fibromuscular dysplasia peripheral arterial disease in, 232 renovascular hypertension in, 415-416, 416f (See also Hypertension, renovascular) Fibromyalgia vs. arthritis, 476 vs. osteoarthritis, 479 vs. rheumatoid arthritis, 484 Fibrous histiocytoma benign, 778-781 (See also Dermato ibroma) malignant, vs. dermato ibroma, 779

Fibrous papule o ace vs. basal cell carcinoma, nodular, 829 vs. sebaceous hyperplasia, 777 Fibrous papule, vs. pyogenic granuloma, 784, 784f Fi th metatarsal racture avulsion, at base, 519-520, 519f, 520f tuberosity, 519-520, 519f, 520f Fingernail clubbing, 206-208, 206f, 207f Fire ants, bullous bites rom, 926, 927f Fish tapeworm, 1080-1083. See also Intestinal worms and parasites Fissured tongue, vs. geographic tongue, 160, 160f Fitz-Hugh-Curtis syndrome, vs. pancreatitis, 374 5 A’s model, 1201, 1202t Fixed drug eruptions, 1024-1032. See also Drug reactions, cutaneous diagnosis o , 1026f-1027f, 1028, 1029f epidemiology o , 1025, 1026f-1027f Flake, 1228-1233. See also Cocaine abuse Flame hemorrhages in hypertensive retinopathy, 93, 93f, 94f in papilledema, 97f Flat warts, 623-625. See also Warts, lat Flesh-eating bacteria, 588-591. See also Necrotizing asciitis Fluid–air inter ace, in liver disease, 365 Fluorescein, or corneal oreign body/ abrasion, 73, 73f Fluoroquinolones, cutaneous drug reactions to, 1024-1032, 1029t. See also Drug reactions, cutaneous Folate de iciency, vs. vitamin B12 de iciency, 251 Follicular mucinosis, vs. alopecia areata, 951, 952f Folliculitis, 566-570. See also specific types diagnosis o , 566f, 569 di erential diagnosis o vs. acne keloidalis nuchae, 556 vs. acne vulgaris, 542, 570 vs. Grover disease, 569, 569f vs. herpes zoster, 598 vs. impetigo, 563, 570 vs. keratosis pilaris, 570 vs. miliaria, 569-570 vs. pseudo olliculitis, 556 epidemiology o , 566 acne keloidalis nuchae, 566, 567f eosinophilic olliculitis, 566, 567f MRSA, 566, 567f pseudo olliculitis, 566, 567f etiology and pathophysiology o , 566-569, 566f-569f acne keloidalis nuchae, 567f, 568 actinic super icial, 568 bacterial, 566f, 567, 568f eosinophilic, 567f, 569 olliculitis decalvans, 567f, 568 ungal, 568, 569f gram-negative, 568 herpetic, 568 Malassezia, 568 nonin ectious, 567

parasitic (mites), 567 Pityrosporum, 568, 569f pseudo olliculitis barbae, 567f, 568 Pseudomonas (“hot tub”), 566, 566f, 568 Staphylococcus, 567 tinea capitis, 568 tu ted olliculitis, 568, 568f viral, 568 ollow-up o , 570 undamentals o , 566 management o , 566f, 569f, 570 patient education on, 570 patient story o , 566, 566f Pityrosporum, 568, 569f, 666, 666f vs. tinea versicolor, 666, 666f Folliculitis decalvans, 567f, 568. See also Folliculitis scarring alopecia in, 958-962, 958f, 958t (See also Alopecia, scarring) Folliculitis keloidalis, 554-557. See also Acne keloidalis nuchae Folliculitis, tu ted, 568, 568f scarring alopecia in, 958-962, 958t diagnosis o , 959, 960f management o , 961-962 Foot dermatitis, with atopic dermatitis, 685 Foot ulcer ischemic, 1062, 1111, 1112f, 1114, 1115 vs. dry gangrene, 1069 vs. gangrene, 1062 vs. neuropathic ulcer, 1062, 1064 vs. wounds, in ected, 1062 neuropathic, 1063-1064, 1063f vs. ischemic ulcer o oot, 1062, 1064 Foreign body, ear, 123-125 beach sand, 124f bead, 124f di erential diagnosis o vs. acute otitis media, 114, 123 vs. chronic suppurative otitis media, 124 vs. otitis externa, 121, 123 vs. otitis media with e usion, 114 insects, 123, 123f Foreign body, eye conjunctival, conjunctivitis rom, 76-77, 77f corneal, 72-74 Foreign-body granuloma, vs. sarcoidosis, 871 Fournier gangrene, 588-591, 589, 589f. See also Necrotizing asciitis Fractures. See also specific types compression, 501-503 (See also Compression ractures) Fragrances, contact dermatitis rom, 691, 692f, 695, 696t. See also Contact dermatitis Friction blisters, 926 vs. tinea pedis, 660 Frontal ibrosing alopecia, 948t, 958-962, 959f. See also Alopecia, scarring Frostbite, dry gangrene rom, 1068-1079 Functional alcohol use disorder, 1214, 1214t, 1215, 1220 Functional dyspepsia, vs. peptic ulcer disease, 379 Fungal olliculitis, 568, 569f

1277

1278

INDEX Fungal in ections, 638-642. See also specific types diagnosis o , 638-641 distribution in, 639f, 640 laboratory studies in, 640t, 640-641, 640f, 641f tinea clinical eatures in, 638, 638f-641f, 640t, 642t di erential diagnosis o vs. contact dermatitis, 694f, 696 vs. cutaneous larva migrans, 680-681 vs. hand eczema, 701f, 702 vs. Lyme disease, 1087 vs. tuberculosis, 320 management o , 641-642, 642t pathophysiology o , 638, 638f, 639f patient story o , 638, 638f toenail, 979-983 (See also Onychomycosis) Furosemide, or heart ailure, 210 Furuncle, vs. abscess, 585 Future o Family Medicine (FFM) initiative, on physician–patient relationship, 6 G Gallbladder sludge, 344 Gallstone ileus, 346f Gallstones, 344-347 diagnosis o , 344f-346f, 345 di erential diagnosis o vs. cholecystitis, 345-346 vs. hepatitis, 346 vs. pancreatitis, 346 vs. peptic ulcer disease, 346 epidemiology, etiology and pathophysiology o , 344 ollow-up o , 347 undamentals o , 344 management o , 346-347 pancreatitis rom, 373 patient education on, 347 patient story o , 344, 344f prognosis in, 347 risk actors or, 344-345 Ganglion cysts, vs. Dupuytren disease, 531 Gangrene dry, 1068-1079, 1068f, 1069f Fournier, 588-591 (See also Necrotizing asciitis) hospital, 588-591 (See also Necrotizing asciitis) vs. ischemic ulcer o oot, 1062 necrotizing asciitis with, 588-591, 590f (See also Necrotizing asciitis) wet, 1069, 1069f Gardnerella vaginalis vaginitis, 434-436, 434f vaginosis, 441-443 (See also Bacterial vaginosis) Garment nevus, 793-797. See also Nevus, congenital Gastric cancer, 349-352 de inition o , 349 diagnosis o , 350 di erential diagnosis o vs. esophageal cancer, 352

vs. esophagitis, 352 vs. gastritis, chronic, 350-351 vs. nonulcer dyspepsia, 350 vs. peptic ulcer disease, 350, 379 epidemiology o , 349 management o , 352 pathology o , 349-350, 354f, 355f patient education on, 352 patient story o , 349, 349f prevention o , 352-353 prognosis and ollow-up o , 352 risk actors or, 350 Gastric ulcers, 377-380. See also Peptic ulcer disease Gastritis, chronic, vs. gastric cancer, 352 Gastroesophageal re lux (GERD), 354-356 diagnosis o , 355-356 di erential diagnosis o vs. angina, 355 vs. aortic dissection, 355 vs. coronary artery disease, 213 vs. esophageal spasm, distal, 355 vs. laryngopharyngeal re lux, 150 vs. peptic ulcer disease, 355, 379 vs. pericarditis, 355 vs. pulmonary embolism, 355 epidemiology o , 354 etiology and pathophysiology o , 354-355 management o , 356 patient education on, 356 patient story o , 354, 354f prognosis in, 356, 356f risk actors or, 355 Gastrointestinal blood loss, vs. intestinal parasites, 1083 Gastrointestinal in ection. See also specific types vs. colon cancer, 331 vs. colon polyps, 337 Genital herpes, 606-611, 606f, 608f, 609f. See also Herpes simplex virus Genital warts, 627-632. See also Warts, genital (condylomata acuminata) Genodermatoses, 1039-1044 callus rom, 1051, 1051f, 1052 diagnosis o , 1039f-1042f, 1040 di erential diagnosis o vs. acquired ichthyosis, 1042, 1043f vs. asteatotic eczema, 1042-1043 vs. Grover disease, 1041 vs. Hailey-Hailey disease, 1040-1041, 1042f vs. ichthyosis vulgaris, 1042, 1043f vs. lamellar ichthyosis, 1042 vs. seborrheic dermatitis, 1041 vs. xerosis, 1043 epidemiology o , 1039 etiology and pathophysiology o , 1039 ollow-up o , 1044 management o , 1043-1044 patient education on, 1044 patient story o , 1039, 1039f, 1040f Geographic stomatitis, 159-161. See also Geographic tongue Geographic tongue, 159-161 diagnosis o , 159, 159f-161f

di erential diagnosis o vs. erythroplakia or leukoplakia, 160 vs. issured tongue, 160, 160f vs. lichen planus, 160, 160f vs. psoriasis, 160, 160f vs. reactive arthritis, 160 epidemiology, etiology and pathophysiology o , 159 ollow-up o , 161 undamentals o , 159 management o , 160-161, 161f patient education on, 161 patient story o , 159, 159f Ghon complex, 317, 317f, 319 Ghrelin, 1135 Giant cell arteritis, 533-536. See also Temporal arteritis Giant condylomata acuminata, 629, 630f Giant condyloma, vs. genital warts, 629, 629f Giant hairy nevus, 793-797. See also Nevus, congenital Giant papillary conjunctivitis, 76, 76f red eye in, 106f Giant pigmented nevus, 793-797. See also Nevus, congenital Giant urticaria, 718f Giardia lamblia, 1080-1083, 1080f, 1082f. See also Intestinal worms and parasites Gigantism, 1160. See also Acromegaly Gingival cancer, 177-180. See also Oropharyngeal cancer Gingival ibromatosis, hereditary, 166-168. See also Gingival overgrowth Gingival hyperplasia, 166-168. See also Gingival overgrowth vs. gingivitis, 163 vs. pyogenic granuloma, 167, 167f Gingival overgrowth, 166-168 diagnosis o , 166f, 167, 167f di erential diagnosis o vs. gingivitis, generalized, 167 vs. gingivitis, pregnancy, 167 vs. leukemia, 167 vs. pregnancy tumor, 167, 167f vs. pyogenic granuloma, 167, 167f epidemiology, 166 etiology and pathophysiology o , 166-167 undamentals o , 166 management o , 167-168 patient education and ollow-up o , 168 patient story o , 166, 166f prevention o , 168 risk actors or, 167 Gingivitis, 162-164 acute necrotizing ulcerative, 163, 163f diagnosis o , 162f, 163, 163f di erential diagnosis o vs. gingival hyperplasia, 163 vs. gingival overgrowth, 167 vs. poor dental hygiene, 163 epidemiology o , 162, 164f etiology and pathophysiology o , 163, 163f undamentals o , 162 management o , 164

INDEX patient education and ollow-up in, 164 patient story o , 162, 162f prevention o , 164 risk actors or, 163 rom smoking, 1202 Gingivostomatitis, herpes, 606-611, 607f, 611f vs. aphthous ulcer, 170 vs. pharyngitis, 146 Glaucoma, 87-89 acute-angle closure vs. conjunctivitis, 76 vs. corneal oreign body/ abrasion, 74 vs. scleritis and episcleritis, 82 vs. uveitis and iritis, 85 diagnosis o , 88, 88f di erential diagnosis o vs. age-related macular degeneration, 100 with optic disc cupping, glaucomatous, 87f, 88 with optic disc cupping, without elevated IOP, 87f, 88 vs. zoster ophthalmicus, 603 epidemiology, etiology and pathophysiology o , 87 management o , 88, 88f patient education on, 89 prognosis and ollow-up or, 89 red eye in, 106, 107t, 109 risk actors or, 88 screening or prevention o , 88 Gleason grade and score, prostate cancer, 410, 412f Glioblastoma, vs. nasal polyps, 131 Global health, 32-46 behavioral changes in, long-term, 33 cholera in, 34-35, 35f Common River story in, 32, 32f de inition o , 32-33 epidemiology o , 33 ethical dilemmas in, 33 eye diseases in, trachoma, 41-42, 41f, 42f vs. international health, 32-33 intestinal parasites in, 35, 35f malnutrition in, 35-36 Mycobacterium in leprosy, 43-45, 43f-45f tuberculosis and HIV, 45, 45f nutrition transition and micronutrient de iciencies in, 36-38 iodine, 37, 37f iron, 37 vitamin A, 36 vitamin B3 (niacin), 37-38, 37f zinc, 36 peer-to-peer adult education in, 33 skin diseases in, in ectious, 42-43, 42f, 43f trust in local health care providers in, 33 typhoid ever in, 33-34 vector borne diseases in, 38-41 leishmaniasis, 39-40, 40f, 41f malaria, 38-39, 38f prevention o , 41 prognosis in, 41

water and sanitation in, 33, 33f, 35, 35f preventing contaminated-water–borne diseases in, 35, 35f Globe (eye) injury, red eye in, 109, 109f Globus pharyngeus, 150 Glomangiomas, 1016-1019, 1017f. See also Vascular skin lesions, acquired vs. vascular lesions, 1021 Glomerular disease diagnosis o , 431 RBC casts in, 429, 430f Glomerulocystic kidney, 406 Glomus tumor, vs. paronychia, 987 Glossitis, atrophic, rom vitamin B12 de iciency, 248f, 251 Glue ear, 112 Gluten-induced enteropathy, dermatitis herpeti ormis with, 947-948, 947f Goals, 4 Goiter, 1153-1158. See also Hyperthyroidism diagnosis o , 1148, 1148f di erential diagnosis o , 1150-1151 etiology and pathophysiology o , 1148, 1148f rom iodine de iciency, 37, 37f management o , 1149f, 1151 Goitrogens, environmental, vs. goitrous hypothyroidism, 1150 GOLD grade, 273 Gonococcal arthritis diagnosis o , 473, 476 vs. reactive arthritis, 759 Gonococcal conjunctivitis, 75-78, 76f Gonococcal urethritis, in men, 1077-1079, 1077f Gonorrhea (Neisseria gonorrhoeae) vs. bacterial vaginosis, 443 vs. Candida vulvovaginitis, 447 vs. Chlamydia cervicitis, 456 a ter sexual assault, 57 vs. Trichomonas vaginitis, 452 Goodpasture syndrome, vs. pulmonary ibrosis, 307 Gottron papules, in dermatomyositis, 908, 908f, 909-910, 910f Gout, 504-507 arthritis rom diagnosis o , 473, 474, 475f, 476 etiology and pathophysiology o , 472 diagnosis o , 504f-506f, 505-506 di erential diagnosis o vs. bunion de ormity, 1055 vs. cellulitis, 506, 582 vs. Charcot arthropathy, 1066 vs. hammer toe, 1058 vs. knee injuries, 528 vs. Lyme disease, 1088 vs. olecranon bursitis, 509 vs. osteomyelitis, 1100 vs. pseudogout, 506 vs. rheumatic arthritis, 506 vs. septic arthritis, 506 vs. xanthomas, 1131, 1131f epidemiology, etiology and pathophysiology o , 504 undamentals o , 504 management o , 506-507

patient education on, 507 patient story o , 504, 504f prevention o , 507 prognosis and ollow-up o , 507 risk actors or, 505 tophaceous, 475f Gouty arthritis, 504-507. See also Gout Gram-negative olliculitis, 568 Granular casts, 429-431, 430f. See also Urinary sediment Granuloma annulare, 855-859 diagnosis o , 855f-857f, 856-857 di erential diagnosis o vs. eczema, nummular, 857 vs. erythema annulare centri ugum, 857 vs. necrobiosis lipoidica, 1127 vs. pityriasis rosea, 857 vs. rheumatoid nodules, 857 vs. sarcoidosis, 870 vs. tinea corporis, 650, 652f, 857 epidemiology o , 855 etiology and pathophysiology o , 856 undamentals o , 855 management o , 857-859 or generalized/ disseminated disease, 859 or localized disease, 855f, 857-858, 858f or per orating, subcutaneous disease, 859 patient education on, 859 patient story o , 855, 855f prognosis and ollow-up o , 859 risk actors or, 856 Granuloma inguinale, vs. hidradenitis suppurativa, 560 Granulomatous rosacea, vs. sarcoidosis, 870 Granulomatous thyroiditis, 1150 Graves disease, 1153-1158. See also Hyperthyroidism Grie ollow-up, 20 Group A b-hemolytic Streptococcus (GABHS) cellulitis, 580 impetigo, 562-564 (See also Impetigo) pharyngitis, 143-147, 143f, 145f (See also Pharyngitis) erythema nodosum rom, 886f, 887 Group A Streptococcus, osteomyelitis, 1096-1101. See also Osteomyelitis Grover disease vs. Darier disease, 1041 vs. olliculitis, 569, 569f Gynecomastia, with cirrhosis rom alcoholism, 367, 368f H Habit-tic de ormity, 965-968 diagnosis o , 966 di erential diagnosis o , 966, 967 etiology and pathophysiology o , 966f, 967f management o , 968 risk actors or, 966 Haemophilus conjunctivitis, 75-78, 75f Haemophilus influenzae acute otitis media, 112 community-acquired pneumonia, 290 sinusitis, 133

1279

1280

INDEX Haemophilus vaginalis (vaginitis), 441-443. See also Bacterial vaginosis Hailey-Hailey disease vs. Darier disease, 1040-1041, 1042f vs. pemphigus vegetans, 938, 939f HAIR-AN syndrome, 1118 Hair casts, vs. lice, 671 Hairy leukoplakia vs. black hairy tongue, 157, 158f vs. leukoplakia, 175 Hairy tongue, black, 156-158, 156f-158f. See also Black hairy tongue Hal -and-hal nail, 967, 967f Hallucinogens, 1196, 1197f. See also Substance abuse disorder Hallux abducto valgus, 1054-1055. See also Bunion de ormity Hallux valgus, 1054-1056. See also Bunion de ormity Halo nevus, 786f, 787 vs. vitiligo, 1003 Hamman-Rich syndrome, vs. pulmonary ibrosis, 308 Hammer toe, 1057-1059 callus rom, 1050, 1051f diagnosis, 1057-1058, 1057f di erential diagnosis o vs. ractured toe, 1058 vs. gout and pseudogout, 1058 vs. Morton neuroma, 1058 vs. rheumatoid arthritis, 1058 vs. septic joint, 1058 epidemiology, etiology and pathophysiology o , 1057, 1058f undamentals o , 1057 management o , 1058-1059, 1059f patient education on, 1059 patient story o , 1057, 1057f prevention o , 1059 prognosis and ollow-up o , 1059 risk actors or, 1057, 1058f Hand dermatitis, 699-705. See also Eczema, hand with atopic dermatitis, 685 Hand eczema, 699-705. See also Eczema, hand Hand, oot, and mouth disease, vs. aphthous ulcer, 171 Hand- oot syndrome (dactylitis), in sickle cell disease, 255, 255f, 257 Hand tumors, vs. Dupuytren disease, 531 Hansen disease, 43-45, 43f-45f Hashimoto thyroiditis, 1148 vs. hypothyroidism, 1150 HbF, 256 Headache, 1174-1176 diagnosis o , 1174-1175, 1175f di erential diagnosis o cluster, vs. temporal arteritis, 535 migraine, vs. temporal arteritis, 535 vs. sinusitis, 135 vs. subarachnoid hemorrhage, 1175, 1175f epidemiology, etiology and pathophysiology o , 1174, 1174f undamentals o , 1174 management o , 1175-1176

patient education on, 1176 patient story o , 1174 prevention o , 1176 prognosis and ollow-up o , 1176 risk actors or, 1174 thunderclap, 1175, 1175f Head lice, 668-672, 669f, 670f. See also Lice Health care–associated pneumonia, 290-295. See also Pneumonia, community-acquired Hearing aid, otitis externa with, 120, 121f Heart block, vs. Lyme disease, 1088 Heart disease, 14, 15. See also specific types coronary epidemiology o , 212 etiology and pathophysiology o , 212 patient education on, 214 prevention o , 214 risk actors or, 212 Heart ailure, 209-211 de inition o , 209 diagnosis o , 209, 209f, 210f di erential diagnosis o vs. anxiety, 210 vs. asthma, 264 vs. chronic obstructive pulmonary disease, 209-210, 272 vs. deconditioning, 210 vs. metabolic acidosis, 210 vs. nephrotic syndrome, 404 vs. neuromuscular weakness, 210 vs. pericardial e usion, 230, 230f vs. pneumonia, 210 vs. pulmonary embolus, 302 epidemiology, etiology and pathophysiology o , 209 ollow-up and patient education on, 211 management o , 210-211 patient story o , 209, 209f pericardial e usion in, 230, 230f pleural e usion in, 286, 289 (See also Pleural e usion) prognosis in, 211 Heavy drinking, 1213-1220. See also Alcoholism Heberden nodes, 473f, 478, 478f, 479, 479f Heer ordt syndrome, 867-872. See also Sarcoidosis Helicobacter pylori colon polyps and, 336 peptic ulcer disease rom, 378-380 (See also Peptic ulcer disease) Heloma durum, 1050-1053. See also Corns Heloma molle, 1050-1053. See also Corns Hemangioma vs. Kaposi sarcoma, 1074 vascular, 1018f (See also Vascular skin lesions, acquired) Hematoma di erential diagnosis o vs. Kaposi sarcoma, 1074 war arin, vs. cutaneous drug reactions, 1031, 1031f intramural, 186-191 (See also Aortic aneurysm)

Hematoma, subdural, 1182-1184 diagnosis o , 1182f-1184f, 1183 di erential diagnosis o vs. brain cancer, 1183 vs. dementia or depression, 1183 vs. epidural hematoma, 1183, 1183f vs. hemorrhage, brain parenchyma, 1183f vs. hemorrhage, subarachnoid, 1183, 1184f vs. in ections (sepsis, meningitis), 1183 vs. stroke, 1183, 1183f epidemiology o , 1182 etiology and pathophysiology o , 1182, 1182f undamentals o , 1182 management o , 1184 patient education on, 1184 patient story o , 1182, 1182f prevention o , 1184 prognosis and ollow-up o , 1184 risk actors or, 1182-1183 Hematoma, subungual, 993-995 diagnosis o , 993f, 994 di erential diagnosis o vs. longitudinal melanonychia, 965f, 967, 974, 994 vs. nail bed nevus, 994 vs. splinter hemorrhage, 994 vs. subungual melanoma, 994 epidemiology o , 993 etiology and pathophysiology o , 993-994, 993f, 994f undamentals o , 993 management o , 993f, 994-995, 994f patient education on, 995 patient story o , 993, 993f, 994f prognosis and ollow-up o , 995 Hematuria, 429-431 in bladder cancer, 390-393, 390f (See also Bladder cancer) diagnosis o , 429f, 430f, 431 di erential diagnosis o , 400 epidemiology o , 429 etiology and pathophysiology o , 429-430, 429f, 430f management o , 431 patient story o , 429, 429f prevention and screening or, 431 in renal cell carcinoma, 421-424 (See also Renal cell carcinoma) risk actors or, 431 Hemochromatosis in liver disease, 365-371, 369t (See also Liver disease) vs. rheumatoid arthritis, 484 Hemoglobin SC disease, 256. See also Sickle cell disease Hemorrhagic stroke, vs. subdural hematoma, 1183, 1183f Hemorrhoids, 358-361 de inition o , 358 diagnosis o , 358f, 359, 359f di erential diagnosis o vs. anal issure, 359, 359f vs. anal tumor, 359 vs. colon cancer, 331

INDEX vs. colon polyps, 337 vs. condyloma acuminata, 359 vs. in lammatory bowel disease, 359 vs. perirectal abscess, 359, 360f vs. rectal in ection, 359, 360f vs. rectal prolapse, 359 epidemiology o , 358 etiology and pathophysiology o , 358, 358f management o , 359-361 patient education on, 360 patient story o , 358, 358f prognosis and ollow-up o , 360 risk actors or, 359 Hemosiderin deposition, lipodermatosclerosis with, 240f Henoch-Schönlein purpura, 891-897, 891f, 892f. See also Vasculitis vs. urticaria, 719, 720f Hepatic artery, 366 Hepatic dys unction, 365-371. See also Liver disease Hepatic ailure, 365-371. See also Liver disease Hepatitis, 365-371. See also Liver disease alcoholic, 365-371 Hepatitis A, 365 Hepatitis B, 365 Hepatitis B vaccination, a ter sexual assault, 57 Hepatitis C, 365 Hepatitis D, 365 Hepatitis E, 365-366 Hepatocellular disease, 365-371. See also Liver disease Hepatocytes, 366 Herald patch, 745, 746, 746f Hereditary angioedema, 717, 718f, 719 Hereditary gingival ibromatosis, 166-168. See also Gingival overgrowth Hereditary hemangiomatosis, 1020-1023, 1021f. See also Vascular lesions, hereditary and congenital Hereditary hemorrhagic telangiectasias, 10201023, 1020f, 1021f. See also Vascular lesions, hereditary and congenital Hereditary nonpolyposis colorectal cancer, 336 Herniated disc vs. ankylosing spondylitis, 493 vs. back pain, 496, 496f Heroin, 1197f black tar, 1197f Heroin abuse, 1196, 1197f. See also Substance abuse disorder injection, 1235-1239 diagnosis o , 1235f-1237f, 1236-1237 di erential diagnosis o , 1237 epidemiology o , 1196, 1235 etiology and pathophysiology o , 1235-1236 ollow-up o , 1239 undamentals o , 1235 management o , 1237-1238 overdose in, 1236 patient education on, 1239 patient story o , 1235, 1235f prevention and screening or, 1238-1239 prognosis in, 1239 risk actors or, 1236

Herpangina vs. aphthous ulcer, 170, 171f vs. pharyngitis, 146, 146f Herpes gingivostomatitis, 606-611, 607f, 611f vs. pharyngitis, 146 Herpes labialis, 606-611, 607f, 611f. See also Herpes simplex virus Herpes simplex virus, 606-611 blistering rom, 927, 927f conjunctivitis rom, 75-78 diagnosis o , 606f-609f, 608-609 di erential diagnosis o vs. angular cheilitis, 139 vs. aphthous ulcer, 170 vs. Behçet disease, 609f vs. chancroid, 609 vs. chickenpox, 594 vs. drug eruption, 609 vs. elon, 609 vs. herpes zoster, 598 vs. impetigo, 563 vs. paronychia, 609 vs. syphilis, 609, 1107 epidemiology o , 606-607, 606f, 607f etiology and pathophysiology o , 607-608, 608f ollow-up o , 611 undamentals o , 606 management o , 609-610, 610t, 611f, 611t patient education on, 611 patient story o , 606, 606f prevention o , 610, 611t risk actors or, 608 urethritis in men rom, 1077-1079 (See also Urethritis, in men) Herpes zoster (shingles), 596-599. See also Zoster blistering rom, 927, 927f vs. temporal arteritis, 535 Herpes zoster oticus, 597, 597f Herpetic olliculitis, 568. See also Folliculitis Herpetic keratitis, vs. conjunctivitis, 76, 77, 77f Herpetic whitlow, 607, 608, 608f. See also Herpes simplex virus vs. paronychia, 609, 987 Hidradenitis suppurativa, 558-561 diagnosis o , 558-560, 558f-560f di erential diagnosis o vs. abscess, 585 vs. bacterial in ections, 560 vs. epidermal cysts, 560 vs. granuloma inguinale, 560 vs. lymphogranuloma venereum, 560 epidemiology, etiology and pathophysiology o , 558, 558f-560f ollow-up and patient education on, 561 undamentals o , 558 management o , 560, 561f with obesity, 1136, 1137f patient story o , 558, 558f risk actors or, 558 Hidrocystoma, vs. hordeolum and chalazion, 66, 66f Hip arthritis, vs. peripheral arterial disease, 235 Hip, arti icial, 522f

Hip racture, 522-524 diagnosis o , 522-523, 522f, 523f di erential diagnosis o , 523 epidemiology, etiology and pathophysiology o , 522 management o , 523 patient education on, 523 patient story o , 522, 522f prevention o , 523 prognosis and ollow-up o , 523 risk actors or, 522 Hippocratic nails ( ingers), 206-208, 206f, 207f Histiocytoma, ibrous benign, 778-781 (See also Dermato ibroma) malignant, vs. dermato ibroma, 779 Histoplasmosis community-acquired pneumonia rom, 291, 293f (See also Pneumonia, communityacquired) vs. tuberculosis, 320, 321f HIV. See Human immunode iciency virus (HIV) Hives, 716-721. See also Urticaria HIV retinopathy, vs. diabetic retinopathy, 91 HLA-B27 positive, uveitis and iritis with, 84-86 Hoarseness, 149-153 diagnosis o , 150-151 di erential diagnosis o laryngeal papillomatosis in, 151, 151f, 152f laryngitis in, 151-152, 151f laryngopharyngeal re lux in, 151, 151f vocal cord nodule in, 151, 152f vocal cord polyp in, 152, 152f epidemiology o , 149 etiology and pathophysiology o , 149f, 150 ollow-up or, 152-153 undamentals o , 149 management o , 151-152 patient education on, 153 patient story o , 149 synonyms and de initions in, 149, 149f Hodes, Rick, 25-26, 26f Homeless, caring or, 28-30, 28f-30f Homicide, epidemiology o , 14 Homogenous leukoplakia, 174-176. See also Leukoplakia Hookworms, 1080-1083, 1080f, 1081f. See also Intestinal worms and parasites cutaneous larva migrans rom, 680-682, 680f, 681f global health problem o , 35, 35f Hordeolum, 65-67 de inition o , 65 diagnosis o , 65f, 66 di erential diagnosis o vs. basal cell carcinoma, 66 vs. hidrocystoma, 66, 66f vs. molluscum contagiosum, 66 vs. sebaceous cell carcinoma, 66 vs. xanthelasma, 66 epidemiology, etiology and pathophysiology o , 65 management o , 66 patient education on, 67 patient story o , 65, 65f

1281

1282

INDEX Hordeolum (Cont.): prevention o , 67 prognosis and ollow-up or, 67 risk actors or, 66 Hormonal vaginal ring, 10, 10f Horn, cutaneous, 821-823. See also Cutaneous horn Hospice care and services, 14, 17-18, 17f Hospital gangrene, 588-591. See also Necrotizing asciitis “Hot tub” olliculitis, 566, 566f, 568 Human immunode iciency virus (HIV) angular cheilitis rom, 138-140, 139f death rom, 15 on mortality, 15 postexposure prophylaxis against, a ter sexual assault, 57 reactive in lammation in, vs. cutaneous T-cell lymphoma, 877 skin viral in ections with, 43 tuberculosis co-in ection with, global, 45, 45f vs. vitamin B12 de iciency, 251 Humanitarian emergency, 23-24, 23f Human papillomavirus, 617 maternal, and juvenile onset recurrent respiratory papillomatosis, 149 (See also Recurrent respiratory papillomatosis) in oropharyngeal cancer, 177 warts rom (See also specific types) common, 617-621 lat, 623-625 genital, 627-632 plantar, 633-636 Humor, in patient–physician relationship, 6 Hunter glossitis, rom vitamin B12 de iciency, 248f, 251 Hurricane Katrina disaster relie , 24-25, 24f, 25f Hurt-Insult-Threat-Scream (HITS), 51 Hutchinson racture, 516, 516f Hutchinson sign in acral lentiginous melanoma, 846, 846f pigmented nail rom, 971f, 972, 972f, 972t pseudo-, 971, 972, 973f in zoster ophthalmicus, 602-603, 602f Hyaline casts, 429-431, 430f. See also Urinary sediment Hydrocephalus, normal pressure, 1185-1186, 1185f, 1186f Hydrocodone, cutaneous reactions to, 1024-1032, 1027f. See also Drug reactions, cutaneous Hydrogen peroxide–producing Lactobacillus, vaginal, 441-442 Hydronephrosis, 395-397 diagnosis o , 395-396, 395f, 396f di erential diagnosis o vs. cholelithiasis, 396 vs. pyelonephritis, 396 epidemiology, etiology and pathophysiology o , 395 undamentals o , 395 management o , 396-397 patient education on, 397 patient story o , 395, 395f

prevention and screening o , 397 prognosis and ollow-up or, 397 Hydrothorax, 286-289, 296f. See also Pleural e usion Hydroureter, 395f Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or coronary artery disease, 213 Hydroxyurea, or sickle cell disease, 256-257 Hyperglycemia, diabetic retinopathy rom, 90-92 Hyperkeratosis occupational, vs. Dupuytren disease, 531 o tongue, 156-158, 156f-158f (See also Black hairy tongue) Hyperkeratotic lesions, 1050-1053. See also Calluses; Corns Hyperlipidemia, 1130 xanthomas and, 1129-1133 diagnosis o , 1131 epidemiology o , 1129 etiology and pathophysiology o , 1129-1130, 1129f, 1130f undamentals o , 1129 management o , 1131-1133 patient education on, 1133 patient story o xanthomas in, 1129, 1129f, 1130f prevention and screening or, 1133 prognosis in, 1133 Hyperparathyroidism, vs. renovascular hypertension, 419 Hyperpigmentation, drug-induced diagnosis o , 1025f, 1028 epidemiology o , 1025, 1025f Hyperplastic polyp, 335-338. See also Colon polyps Hypersensitivity pneumonitis, vs. pulmonary ibrosis, 307 Hypersensitivity reactions, 1024-1032. See also Drug reactions, cutaneous Hypersensitivity syndromes, 879-884 diagnosis o , 879f-883f, 880-884 di erential diagnosis o vs. bullous pemphigoid, 883 vs. cutaneous vasculitis, 883 vs. erythema annulare centri ugum, 883 vs. staphylococcal scalded skin syndrome, 883 vs. urticaria, 883 epidemiology o , 879-880 etiology and pathophysiology o , 880, 880f ollow-up and patient education on, 884 undamentals o , 879 management o , 884 patient story o , 879, 879f prevention o , 884 prognosis in, 884 risk actors or, 880 Hypersensitivity vasculitis, 891-897. See also Vasculitis Hypertension, 225-227 acute, 226 benign intracranial, 96-98 (See also Papilledema)

cerebral vascular accident with, 1178, 1179 diagnosis o , 225f, 226, 226f di erential diagnosis o , 226 epidemiology, etiology and pathophysiology o , 225, 226f alse, 226 idiopathic intracranial (See also Papilledema) epidemiology o , 96 etiology and pathophysiology o , 96 papilledema rom, 96-98, 96f management o , 227 patient education on, 227 patient story o , 225, 225f prevention o , 227 prognosis and ollow-up o , 227 pulmonary in chronic obstructive pulmonary disease, 270, 271, 274 with pulmonary embolus, 301f, 303 renovascular, 415-420 diagnosis and screening or, 417-419, 418f di erential diagnosis o vs. aldosteronism, primary, 419 vs. coarctation o aorta, 419 vs. Cushing syndrome, 419 vs. hyperparathyroidism, 419 vs. hyperthyroidism, 419 vs. parenchymal renal disease, 419 vs. pheochromocytoma, 419 epidemiology o , 415 etiology o , 415-416, 416f undamentals o , 415, 415f management o , 419 pathophysiology o , 416-417 patient education on, 420 patient story o , 415, 415f prognosis in, 420 risk actors or, 225 secondary, di erential diagnosis o , 419 volume-expansion–related, 416 white-coat, 226 Hypertensive retinopathy, 93-95, 226, 226f. See also Retinopathy, hypertensive vs. diabetic retinopathy, 91 Hyperthyroidism, 1153-1158 diagnosis o , 1153f-1156f, 1154-1155 di erential diagnosis o vs. autonomous unctioning nodule, 1156 vs. cocaine abuse, 1231-1232 vs. hypothyroidism, 1150 vs. metastatic disease (extraocular muscles), 1156 vs. pituitary adenoma, thyrotropin secreting, 1156 vs. pseudotumor, eye, 1156 vs. thyroid hormone overdose, 1156 vs. thyroiditis, 1156 vs. toxic multinodular goiter, 1156 epidemiology o , 1154 etiology and pathophysiology o , 1154 ollow-up o , 1157-1158 undamentals o , 1154 management o , 1156-1157

INDEX patient education on, 1158 patient story o , 1153, 1153f prognosis in, 1157, 1158f vs. renovascular hypertension, 419 risk actors or, 1154 Hypertriglyceridemia, 1130 Hypertrophic osteoarthropathy, vs. clubbing, 207 Hypertrophic scars. See also Keloids cortisone injection o , 1247f, 1247t di erential diagnosis o vs. corns and calluses, 1052 vs. dermato ibroma, 779 vs. keloids, 1035 Hyperuricemia in gout, 505, 505f, 507 medications in, 505 Hyphema, 103-105 diagnosis o , 103, 103f, 104f di erential diagnosis o , 104 epidemiology, etiology and pathophysiology o , 103 undamentals o , 103 management o , 104 patient education on, 105 patient story o , 103, 103f prevention o , 104 prognosis and ollow-up or, 105 red eye in, 109, 109f Hypoalbuminemia, vs. nephrotic syndrome, 404 Hypoglycemia vs. cerebral vascular accident, 1180 vs. cocaine abuse, 1232 Hypopigmentation. See Vitiligo; specific disorders Hypopyon red eye in, 109, 110f in uveitis, 85, 85f Hypothyroidism, 1148-1152 diagnosis o , 1148f-1150f, 1149-1150 di erential diagnosis o vs. branchial cle t cyst, 1150 vs. dermatomyositis, 912 vs. environmental goitrogens, 1150 vs. Graves disease, 1150 vs. Hashimoto thyroiditis, 1150 vs. iodine de iciency, 1150 vs. normal pressure hydrocephalus, 1186 vs. postpartum thyroiditis, 1150 vs. suppurative thyroiditis, acute, 1150 vs. thyroglossal duct cyst, 1150, 1150f vs. thyroid cancer, 1150, 1151f toxic nodular goiter, 1149f, 1151 epidemiology o , 1148, 1148f etiology and pathophysiology o , 1148, 1148f ollow-up or, 1152 undamentals o , 1148 granulomatous thyroiditis in, 1150 management o , 1149f, 1151 patient story o , 1148, 1148f prevention and screening or, 1151 prognosis in, 1151-1152 risk actors or, 1149 Hysteroscopic tubal occlusion, 12, 12f, 13f

I Ibupro en, cutaneous reactions to, 1024-1032, 1026f. See also Drug reactions, cutaneous Ichthyosis acquired, 1042, 1043f with atopic dermatitis, 685, 687f lamellar, 1042, 1043f X-linked, 1039-1044 (See also X-linked ichthyosis) Ichthyosis vulgaris, vs. X-linked ichthyosis, 1042, 1043f Idiopathic cutaneous pseudoepitheliomatous hyperplasia, 813-815. See also Keratoacanthoma Idiopathic acial paralysis, 1188-1190. See also Bell’s palsy Idiopathic guttate hypomelanosis vs. cutaneous T-cell lymphoma, 877 vs. vitiligo, 1003, 1003f Idiopathic interstitial pneumonia, 306-309. See also Pulmonary ibrosis Idiopathic intracranial hypertension epidemiology o , 96 etiology and pathophysiology o , 96 papilledema rom, 96-98, 96f (See also Papilledema) Idiopathic thrombocytopenic purpura, vs. cutaneous vasculitis, 895, 896f Id reaction, tinea pedis, 658, 658f, 659 IgA bullous dermatosis, 924, 925f Ileus, gallstone, 346f Images or diagnosis, 2-4, 2f, 3f, 3t Internet sources or, 3, 3t or patient–physician relationship, 3-4 taking your own, 4 Immediate IgE contact reaction, vs. contact dermatitis, 695 Immunosuppression. See also specific disorders squamous cell carcinoma with, 834, 835, 837f, 838, 839f, 840, 841 Impetiginization, 562, 564f Impetigo, 562-564 with atopic dermatitis, 684 diagnosis o , 562, 562f-564f di erential diagnosis o vs. acne keloidalis nuchae, 556 vs. allergic contact dermatitis, 564 vs. angular cheilitis, 139 vs. atopic dermatitis, 562, 564f vs. bullous pemphigoid, 564 vs. burn, second-degree, 564 vs. chickenpox, 594 vs. eczema herpeticum, 563 vs. olliculitis, 563, 570 vs. herpes simplex virus, 563 vs. insect bites, 564 vs. pemphigus vulgaris, 564 vs. pseudo olliculitis, 556 vs. scabies, 563, 677 vs. staphylococcal scalded skin syndrome, 564 vs. sunburn, 564 vs. tinea corporis, 563

epidemiology, etiology and pathophysiology o , 562, 562f ollow-up and patient education on, 564 undamentals o , 562 as global health problem, 43, 43f management o , 562f, 563f, 564 patient story o , 562, 562f prevention o , 564 Impetigo herpeti ormis, erythroderma with, 761, 762t Inactivity, physical, on mortality, 15 Inborn errors o intracellular cobalamin de iciency, 250. See also Vitamin B12 de iciency Inclusion cyst, epidermal vs. abscess, 585, 586f vs. dermato ibroma, 779 vs. sarcoidosis, 871 In ectious colitis, vs. ischemic colitis, 363 In ectious mononucleosis vs. pharyngitis, 144f, 146 tonsillar exudate in, 144f In lammatory acne, 540-546, 541f, 542f. See also Acne vulgaris In lammatory bowel disease, 381-386 diagnosis o , 382-384 clinical eatures in, 382, 382f endoscopy and imaging in, 381f-384f, 383-384 laboratory tests in, 382-383 typical distribution in, 381f, 382 di erential diagnosis o vs. colon cancer, 331 vs. colon in ections, 384 vs. colon polyps, 337 vs. diverticulitis, 342 vs. in ections in immunocompromised, 384 vs. intestinal worms and parasites, 1083 vs. ischemic colitis, 384, 384f vs. kidney stones, 400 vs. NSAID colitis, 384 epidemiology o , 381 etiology and pathophysiology o , 381 ollow-up o , 386 undamentals o , 381 in ectious, 363 management o , 384-385 patient education on, 386 patient story o , 381, 381f prognosis in, 385-386, 385f risk actors or, 381 In lammatory breast cancer, 461-465. See also Breast cancer In lammatory linear verrucous epidermal nevus, 798-802, 798f. See also Nevus, epidermal In lammatory myopathy, vs. arthritis, 476 In luenza virus sinusitis, 133 Ingrown toenail, 975-977 diagnosis o , 975f, 976 di erential diagnosis o vs. cellulitis, 976 vs. paronychia, 976, 987

1283

1284

INDEX Ingrown toenail (Cont.): epidemiology, etiology and pathophysiology o , 975, 975f management o , 976-977, 976f, 977f patient education and ollow-up o , 977 patient story o , 975, 975f risk actors or, 975-976, 975f Injection-drug use, 1235-1239 complications o , 1235f-1237f, 1236 diagnosis o , 1235f-1237f, 1236-1237 di erential diagnosis o , 1237 epidemiology o , 1235, 1235f etiology and pathophysiology o , 1235-1236, 1236f ollow-up o , 1239 undamentals o , 1235 management o , 1237-1238 patient education on, 1239 patient story o , 1235, 1235f prevention and screening or, 1238-1239 prognosis in, 1239 risk actors or, 1236 Injury. See also specific types death rom, 15 eye globe, red eye in, 109, 109f retinal pigment epithelial, 99 rom intimate partner violence, 50-53 Lis ranc, 520 on mortality, 14 rom sexual abuse, adult, 55-58 Insect bites vs. chickenpox, 594 vs. herpes zoster, 598 vs. impetigo, 564 vs. urticaria, 719 Instructional directives, 17 Insulin resistance in diabetes mellitus, 1110 etiology and pathophysiology o , 1110 management o , 1113 Internally displaced persons, 23 International health, 32 International humanitarian e orts, in Ethiopia, 25-26, 26f Internet, images on, 3, 3t Interstitial pneumonia, 291, 293f, 306-309. See also Pulmonary ibrosis vs. pulmonary ibrosis, 308 Intertrigo vs. candidiasis, 645, 646f vs. erythrasma, 578 vs. tinea cruris, 656 Intertrochanteric racture, 522-524, 523f. See also Hip racture Interview motivational, or smoking cessation, 1205, 1206t patient-centered, 7, 8 Intestinal obstruction, vs. pancreatitis, 374 Intestinal worms and parasites, 1080-1083 diagnosis o , 1080f-1082f, 1082-1083 di erential diagnosis o vs. GI blood loss, 1083

vs. in ections, 1083 vs. in lammatory bowel disease, 1083 vs. iron-de iciency anemia, 1083 vs. irritable bowel disease, 1083 epidemiology o , 1080-1081, 1080f-1082f etiology and pathophysiology o , 1080f-1082f, 1081-1082 undamentals o , 1080 global health problem o , 35, 35f management o , 1083 patient education on, 1083 patient story o , 1080, 1080f prevention o , 1083 prognosis and ollow-up o , 1083 risk actors or, 1082 water and sanitation in, 35, 35f Intimate partner violence, 50-53 de inition o , 50 diagnosis o , 50f-52f, 51-52 epidemiology o , 50 ollow-up o , 53 management o , 52 patient education on, 53 patient story o , 50, 50f prognosis in, 53 risk actors or, 51 screening and prevention o , 52-53 Intra-articular ractures, 527, 527f. See also Knee injuries Intracranial pressure, increased epidemiology o , 96 etiology o , 96 papilledema rom, 96-98, 96f (See also Papilledema) Intracutaneous corni ying epithelioma, 813-815. See also Keratoacanthoma Intradermal melanocytic nevus, 787f, 788f Intradermal (dermal) nevi, 787, 787f, 788f, 790 vs. basal cell carcinoma, 825f, 829, 831f Intramural hematoma, 186-191. See also Aortic aneurysm Intrauterine device (IUD) copper-containing, 11t, 12 levonorgestrel, 10, 10f, 11t, 12 Inverse psoriasis, 2, 2f. See also Psoriasis diagnosis o , 729f, 731f, 733-734, 735f di erential diagnosis o vs. candidiasis, 646, 646f vs. tinea cruris, 656, 656f management o , 731f, 742 Involucrum, 1097, 1097f Iodine de iciency, 37, 37f vs. hypothyroidism, 1150 Iridocyclitis, 84-86 Iris, melanotic hamartomas o , in neuro ibromatosis, 1191-1194, 1193f, 1194f Iritis, 84-86 di erential diagnosis o vs. acute-angle closure glaucoma, 85 vs. conjunctivitis, 76, 85 vs. corneal oreign body/ abrasion, 73 vs. episcleritis, 82 vs. scleritis, 82, 85 management o , 85, 86f

patient education on, 86 prognosis and ollow-up o , 86 red eye in, 109, 109f traumatic, 84, 84f rom zoster ophthalmicus, 601-604, 601f Iron de iciency, 37 Iron de iciency anemia, 244-246. See also Anemia, iron de iciency Iron replacement, or iron de iciency anemia, 246 Irritable bowel disease, vs. intestinal parasites, 1083 Irritant contact dermatitis, 691-697, 691f, 693f, 695f, 697f. See also Contact dermatitis Ischemic bowel, vs. Clostridium difficile in ection, 327 Ischemic colitis, 362-364 diagnosis o , 362f, 363, 363f di erential diagnosis o vs. Clostridium difficile, 363 vs. colon cancer, 364 vs. diverticulitis, 363 vs. in ectious colitis, 363 vs. in lammatory bowel disease, 363 vs. mesenteric ischemia, 363 vs. ulcerative colitis, 384 epidemiology, etiology and pathophysiology o , 362 undamentals o , 362 management o , 364 patient education on, 364 patient story o , 362, 362f prognosis and ollow-up o , 364 risk actors or, 362-363 Ischemic stroke, vs. subdural hematoma, 1183 Ischemic ulcer, o oot, 1062, 1111, 1112f, 1114, 1115 vs. dry gangrene, 1069 vs. gangrene, 1062 vs. neuropathic ulcer, 1062, 1064 vs. wounds, in ected, 1062 J Jaccoud arthropathy, 474f Janeway lesions, 221, 221f, 222, 222f Jaundice, in liver disease, 366 Joint contractures, intrinsic, vs. Dupuytren disease, 531 Joint Distribution Committee, American Jewish, 25-26, 26f Joint sepsis, vs. olecranon bursitis, 509 Jones racture, 519-520, 520f Junctional nevi, 786, 787f Juvenile polyp, 335-338. See also Colon polyps Juvenile xanthogranuloma, vs. hyphema, 104 K Kala-azar, 39-40, 40f, 41f Kaposi sarcoma, 1072-1075 diagnosis o , 1072-1073, 1072f-1074f di erential diagnosis o vs. bacillary angiomatosis, 1074, 1074f vs. dermato ibroma, 1074

INDEX vs. hemangioma and angioma, 1074 vs. hematoma, 1074 vs. purpura, 1074 vs. syphilis, 1074, 1075f epidemiology, etiology and pathophysiology o , 1072, 1074, 1075f undamentals o , 1072 management o , 1073f, 1074-1075, 1075f patient education on, 1075 patient story o , 1072, 1072f prognosis and ollow-up o , 1075 risk actors or, 1072 Kayser-Fleischer ring, 367, 368f Keloidal olliculitis. See Acne keloidalis nuchae Keloids, 1034-1037. See also Hypertrophic scars diagnosis o , 1035, 1035f di erential diagnosis o vs. acne keloidalis, 1035-1036, 1035f vs. dermato ibromas, 1036 vs. dermato ibrosarcoma protuberans, 1036 vs. hypertrophic scars, 1035 epidemiology o , 1034, 1034f etiology and pathophysiology o , 1034, 1034f undamentals o , 1034 management o , 1036-1037, 1036f cortisone injection in, 1247f, 1247t patient education on, 1036f patient story o , 1034, 1034f prevention o , 1036f prognosis and ollow-up or, 1036f risk actors or, 1034 Keratitis di erential diagnosis o vs. conjunctivitis, 76, 77, 77f vs. corneal oreign body/ abrasion, 73-74, 73f vs. scleritis and episcleritis, 82 vs. uveitis and iritis, 85 herpetic, 76, 77, 77f vs. conjunctivitis, 76, 77, 77f red eye in, 106-110, 107t, 108, 108f, 109f rom zoster ophthalmicus, 601-604, 601f Keratoacanthoma, 813-815 diagnosis o , 813f-815f, 814 di erential diagnosis o vs. actinic keratosis, 814 vs. basal cell carcinoma, nodular, 829 vs. common warts, 619 vs. cutaneous horn, 814 vs. squamous cell carcinoma, 814, 838, 839f epidemiology, etiology and pathophysiology o , 813 ollow-up and patient education on, 815 undamentals o , 813 management o , 814-815 patient story o , 813, 813f prognosis in, 815 risk actors or, 813-814 Keratocarcinoma, 813-815. See also Keratoacanthoma Keratoconus, with atopic dermatitis, 687, 687f Keratoderma blenorrhagicum, in reactive arthritis, 757-760, 757f, 759f

Keratoderma, vs. tinea pedis, 660, 661f Keratosis, 1050-1053. See also Calluses; Corns Keratosis ollicularis, vs. psoriatic nails, 991, 991f Keratosis pilaris with atopic dermatitis, 685, 686f vs. olliculitis, 570 Keratotic melanocytic nevus, vs. skin tag, 768 Kidney disease, chronic, 426-428 clinical mani estations o , 426-427, 427f diagnosis o , 427 etiology, pathogenesis, and risk actors or, 426 undamentals o , 426 management o , 428 patient story o , 426, 426f prognosis and complications o , 427-428 Kidney stones, 398-401 diagnosis o , 398f-400f, 399 di erential diagnosis o vs. abdominal aortic aneurysm, 400 vs. appendicitis, 400 vs. cholelithiasis, 400 vs. colitis, 400 vs. diverticulitis, 400 vs. epididymitis, 400 vs. gynecologic conditions, 399-400 vs. peptic ulcer disease, 400 vs. prostatitis, 400 vs. testicular torsion, 400 vs. urinary tract in ection, 400 vs. urologic disorders, 400 epidemiology o , 398 etiology and pathophysiology o , 398-399, 399f ollow-up and patient education on, 401 undamentals o , 398 management o , 400 patient story o , 398, 398f with polycystic kidneys, 407, 408 prevention o , 400-401 prognosis in, 401 risk actors or, 399 Kingella kingae osteomyelitis, 1096-1101. See also Osteomyelitis “Kissing warts,” 617, 618f Klebsiella olliculitis, 568 Klebsiella pneumoniae community-acquired pneumonia, 290-295, 292f Kleinman, Arthur, 6 Klippel-Trenaunay, port-wine stains in, 1020, 1020f Knee anatomy, 526f Knee injuries, 525-529 diagnosis o , 525-527 clinical eatures in, 525 imaging in, 526, 526f, 527f physical examination in, 526 di erential diagnosis o vs. bone cysts and osteochondroma, 528 vs. gout or pseudogout, 528 intra-articular ractures in, 527, 527f vs. osteoarthritis, 528 vs. osteosarcoma or chondroblastoma, 528 patellar dislocation in, 527

vs. reactive arthritis, 527-528 vs. rheumatoid arthritis, 528 vs. septic arthritis, cellulitis, and osteomyelitis, 528, 528f epidemiology o , 525, 525f etiology and pathophysiology o , 525 ollow-up and patient education on, 529 undamentals o , 525 management o , 528 patient story o , 525, 525f prevention o , 528 prognosis in, 528 risk actors or, 525 Knuckle pads, 702 Koebner phenomenon, 488, 730t, 732, 734f in lichen planus, 750f, 751 Koilonychia, in iron de iciency anemia, 244, 245f KPS, 16 Kyphosis, 1142. See also Osteoporosis and osteopenia Kytococcus sedentarius, pitted keratolysis rom, 572 L Labial melanotic macules, vs. benign nevus, 790, 791f Lacrimal ducts, plugged, vs. mastitis, 459 Lactobacillus, hydrogen peroxide–producing, vaginal, 441-442 Lamb excrescences, vs. bacterial endocarditis, 222 Lamellar ichthyosis, vs. X-linked ichthyosis, 1042, 1043f Large-cell (anaplastic) cancer o lung, 278-284. See also Lung cancer Laryngeal cancer, squamous cell carcinoma, 149-153 diagnosis o , 150-151, 151f di erential diagnosis o , 151 epidemiology o , 149 etiology and pathophysiology o , 150 ollow-up o , 152-153 undamentals o , 149 management o , 152 patient education on, 153 patient story o , 149 Laryngeal papillomatosis, 149-153 diagnosis o , 150-151, 151f, 152f di erential diagnosis o , 151 epidemiology o , 149 etiology and pathophysiology o , 150 ollow-up o , 152-153 management o , 152 patient education on, 153 Laryngeal polyp, 149-153, 152f. See also Hoarseness Laryngitis, 149-153 diagnosis o , 150-151 di erential diagnosis o , 151 epidemiology o , 152, 152f etiology and pathophysiology o , 153 ollow-up o , 152-153 management o , 151-152 patient education on, 153

1285

1286

INDEX Laryngopharyngeal re lux, 149-153 diagnosis o , 150-151, 151f di erential diagnosis o , 151 vs. gastroesophageal re lux, 150 epidemiology o , 149 etiology and pathophysiology o , 150 ollow-up o , 153 management o , 152 patient education on, 153 Larynx, 149-153, 149f Latent tuberculosis in ection, 45 Lateral condylar split racture, 527f Lateral meniscal tear, 527f Lateral nail hypertrophy, 964-968, 965f. See also Onychogryphosis Latrines, pit, in Ethiopia, 33, 33f Lead poisoning, vs. iron de iciency anemia, 246 Ledderhose disease, 520f, 530-531, 531f Le t ventricular hypertrophy, 225, 225f, 226 Legionella community-acquired pneumonia, 290, 291, 293f Leg ulcer, in sickle cell disease, 254, 254f, 255, 257 Leishmaniasis, 39-40, 40f, 41f Lentigo maligna, 817-820 de inition o , 817 diagnosis o , 817f, 818, 818f di erential diagnosis o vs. lentigo maligna melanoma, 818f, 819 vs. seborrheic keratosis, 818-819 vs. solar lentigo, 818, 819f epidemiology, etiology and pathophysiology o , 817, 817f, 818f management o , 819 patient education on, 820 patient story o , 817, 817f prevention o , 819-820 prognosis and ollow-up o , 820 risk actors or, 817-818 Lentigo maligna melanoma, 819, 844, 845f, 846f diagnosis o , 818, 818f di erential diagnosis o , 818-819, 819f epidemiology, etiology and pathophysiology o , 817 prevention o , 818-819 risk actors or, 817 Leprosy, 43-45, 43f-45f Lesser-Trélat sign, 771f, 772 Leukemia in breast, vs. breast cancer, 464 vs. gingival overgrowth, 167 Leukocytoclastic vasculitis, 891-897, 892f, 893f. See also Vasculitis with lupus, 902, 902f Leukocytoclastic vasculitis, with lupus, 902, 902f Leukonychia, 964-968 diagnosis o , 964f, 965f, 966, 968t di erential diagnosis o , 968t vs. Beau lines, 967, 967f, 968t vs. hal -and-hal nails, 967, 967f vs. hematoma, 967 vs. Mee lines, 967, 967f, 968t vs. Muehrcke lines, 967, 967f, 968t

vs. onychomycosis, 981 vs. subungual melanoma, 967 epidemiology o , 964 etiology and pathophysiology o , 964-965, 964f, 965f management o , 968 patient story o , 964, 964f risk actors or, 966 Leukonychia punctata diagnosis o , 966, 967t epidemiology o , 964 etiology and pathophysiology o , 964-965, 965f risk actors or, 966 Leukoplakia, 174-176 diagnosis o , 174-175, 174f, 175f di erential diagnosis o vs. aspirin/ chemical burn, 175 vs. black hairy tongue, 157, 158f vs. candidiasis, 175 vs. discoid lupus, 175 vs. erythroplakia, 174, 175f vs. geographic tongue, 160 vs. hairy leukoplakia, 175 vs. lichenoid lesion, 175 vs. lichen planus, 175, 755 vs. linea alba, 175 vs. morsicatio, 175, 175f vs. nicotine stomatitis, 176, 176f vs. oropharyngeal cancer, 177f vs. snu patch, 176 vs. white sponge nevus, 176 epidemiology, etiology and pathophysiology o , 174 ollow-up and patient education on, 176 undamentals o , 174 management o , 176 oropharyngeal cancer and, 177, 177f patient story o , 174, 174f prevention and screening or, 176 prognosis in, 176 risk actors or, 174 rom smoking, 1203, 1203f Levamisole, in cocaine, 1229-1230, 1230f, 1231f Levonorgestrel intrauterine device, 10, 10f, 11t, 12 Lice, 668-672 diagnosis o , 668f-670f, 670-671 di erential diagnosis o vs. dandru , hair casts, and debris, 671 vs. scabies, 671 epidemiology o , 668, 668f etiology and pathophysiology o , 668-669, 669f, 670f ollow-up o , 672 undamentals o , 668 global health problem o , 42 management o , 671 patient education on, 672 patient story o , 668, 668f prevention o , 671 risk actors or, 670 Lichen aureus, vs. vasculitis, 894-895, 895f Lichen nuchae, 711, 712f

Lichenoid keratosis vs. basal cell carcinoma, 829 vs. Paget disease o breast, 469, 469f Lichenoid lesion, vs. leukoplakia, 175 Lichen planopilaris. See also Alopecia, scarring scarring alopecia in, 958-962, 958t, 959f Lichen planus, 750-755 diagnosis o , 750f-755f, 751-752 di erential diagnosis o vs. aphthous ulcer, 171 vs. bite trauma, 755 vs. Bowen disease, 754-755 vs. eczematous dermatitis, 753 vs. epidermal nevus and nevus sebaceous, 800, 800f vs. lat warts, 624 vs. geographic tongue, 160, 160f vs. leukoplakia, 175, 755 vs. lichen simplex chronicus, 755 vs. lupus erythematosus, 754, 905 vs. onychomycosis, 981 vs. pityriasis rosea, 754 vs. prurigo nodularis, 755 vs. psoriasis, 738, 753, 755 vs. sarcoidosis, 870 vs. stasis dermatitis, 754 vs. syphilis, 755 vs. thrush, 755 vulvovaginal, vs. atrophic vaginitis, 438 epidemiology o , 750 etiology and pathophysiology o , 750 ollow-up o , 755 undamentals o , 750 management o , 755 patient education on, 755 patient story o , 750, 750f, 751f prognosis in, 755 risk actors or, 750 Lichen sclerosus vs. atrophic vaginitis, 438, 439f vs. morphea, 920 Lichen simplex chronicus, 710-715 diagnosis o , 711f, 712f, 713-714 di erential diagnosis o , 714 vs. atopic dermatitis, 687-688 vs. eczema, nummular, 708 vs. lichen planus, 755 vs. necrobiosis lipoidica, 1127 vs. psoriasis, 738 epidemiology o , 711, 711f, 712f etiology and pathophysiology o , 711-713 ollow-up o , 715 management o , 714 patient education on, 714 Lichen striatus, vs. epidermal nevus and nevus sebaceous, 800, 800f Li e-sustaining treatment, withdrawal o , 20 Likelihood ratio (LR), 1242 Limb ischemia. See also Peripheral arterial disease acute, 233, 236-237, 237f Lindsay nails, 967, 967f Linea alba, vs. leukoplakia, 175 Linear immunoglobulin A (IgA) dermatosis bullous, 924, 925f

INDEX vs. bullous pemphigoid, 931 vs. pemphigus, 938 Lingua villosa nigra, 156-158, 156f-158f. See also Black hairy tongue Lip cancer, 177-180. See also Oropharyngeal cancer Lip licking, perlèche rom, 138-140, 139f Lipodermatosclerosis, with hemosiderin deposition, 239f, 240f Lipoma, vs. sarcoidosis, 871 Lipoproteins, 1130 Lisch nodules, in neuro ibromatosis, 1191-1194, 1193f, 1194f Lis ranc injury, vs. metatarsal racture, 520 Listening, active empathic, 7 Listeria monocytogenes meningitis, 1091-1094. See also Meningitis Livedo reticularis, vs. erythema ab igne, 1014, 1014f Liver disease, 365-371 diagnosis o , 366-368 biopsy in, 368 clinical eatures o , 365-368, 366f-368f imaging in, 368 laboratory testing or, 368, 369t di erential diagnosis o , 369t vs. pancreatitis, 374 end-stage, death rom, 16 epidemiology o , 365-366 etiology and pathophysiology o , 366 ollow-up o , 371 undamentals o , 365 management o , 370 patient education on, 371 patient story o , 365, 365f prevention and screening o , 370 prognosis in, 370-371 risk actors or, 366 Liver ibrosis, 365-371. See also Liver disease Living wills, 17 Lobar pneumonia, 290f-292f, 291. See also Pneumonia Lobular capillary hemangioma, 782-785. See also Pyogenic granuloma Locally advanced breast cancer, 461-465, 462f, 463f. See also Breast cancer Lö gren syndrome, 310, 311f, 314, 867-872, 886-889. See also Erythema nodosum; Sarcoidosis Longitudinal melanonychia, 970-974 diagnosis o , 966, 970f, 971f, 973 di erential diagnosis o vs. hematoma, 965f, 967 vs. pigmented lesions, 967, 974 vs. subungual hematoma, 974, 994 vs. subungual melanoma, 965, 967 epidemiology o , 964, 970 etiology and pathophysiology o , 965, 965f, 970-971, 970f undamentals o , 970 management o , 974 patient story o , 970, 970f prognosis and ollow-up o , 974 risk actors or, 966, 972t, 973

Lordosis, 1142. See also Osteoporosis and osteopenia Low back pain, 495-497. See also Back pain Lues, 1101-1107. See also Syphilis Lumbar degenerative spinal stenosis, 499-500, 499f, 500f Lumbar muscle spasm, vs. ankylosing spondylitis, 493 Lumbar spinal stenosis, 499-500, 499f, 500f Lumbar strain, vs. ankylosing spondylitis, 493 Lung cancer, 278-284 diagnosis o , 278f, 279-280, 280f, 281f di erential diagnosis o vs. chronic obstructive pulmonary disease, 272-273, 280-281 vs. pneumonia, 281 epidemiology o , 278-279 etiology and pathophysiology o , 279 ollow-up o , 283 undamentals o , 278 management o , 281-283 complementary and alternative therapy in, 282 imaging and staging in, 281-282, 282b medications in, 282 nonpharmacologic, 282 surgery and radiation in, 282-283 patient education on, 283-284 patient story o , 278, 278f prevention o , 283 prognosis in, 283 risk actors or, 279 Lung transplantation, or COPD, 275 Lung volume reduction surgery, or COPD, 275 Lupus systemic and cutaneous, 899 vs. erythema annulare centri ugum, 1046-1047 neonatal, 900f vs. osteoarthritis, 479 vs. polymyalgia rheumatica, 535 vs. rheumatoid arthritis, 484 Lupus erythematosus vs. alopecia areata, 951 vs. lichen planus, 754 Lupus panniculitis, 903, 905f Lupus pernio, 867-872, 867f, 868f. See also Sarcoidosis Lupus pro undus, 903, 905f Lupus vulgaris, vs. sarcoidosis, 870 Lyme disease, 1085-1090 arthritis in, 473 diagnosis o , 1085f-1087f, 1086-1087 di erential diagnosis o vs. arthritis, in lammatory, 1088 vs. cellulitis, 1087 vs. cutaneous larva migrans, 681 vs. encephalomyelitis, 1088 vs. erythema annulare centri ugum, 1046 vs. acial nerve (Bell) palsy, 1088, 1189 vs. ungal in ections, cutaneous, 1087 vs. heart block, 1088

vs. meningitis, viral, 1088 vs. peripheral neuropathy, 1088 vs. radiculoneuropathy, 1088 vs. Rocky Mountain spotted ever, 1087 vs. tick bite local reaction, 1087 vs. urticaria, 1087 epidemiology o , 1085, 1085f etiology and pathophysiology o , 1085 undamentals o , 1085 management o , 1088-1090, 1088f, 1089f patient education on, 1090 patient story o , 1085, 1085f prevention o , 1090 prognosis and ollow-up o , 1090 Lymphadenitis, tuberculous, 45, 45f Lymphedema o leg, vs. deep venous thrombosis, 217, 218f Lymphogranuloma venereum, vs. hidradenitis suppurativa, 560 Lymphomatoid papulosis, vs. pityriasis lichenoides et varioli ormis acuta, 946 M Macrolide antibiotics, cutaneous reactions to, 1024-1032, 1029t. See also Drug reactions, cutaneous Macular star, 94 Maculopapular eruptions, drug-related, 1024-1032. See also Drug reactions, cutaneous diagnosis o , 1024f, 1028 epidemiology o , 1024, 1024f Ma ucci syndrome, 1020-1023, 1021f. See also Vascular lesions, hereditary and congenital Malaria, 38-39, 38f Malar rash, 899f, 900, 901, 901t, 902f Malassezia olliculitis, 568 Malassezia furfur tinea versicolor, 664-666, 665f, 666f. See also Tinea versicolor Malassezia seborrheic dermatitis, 724 Male sterilization, 11t Malignant ibrous histiocytoma, vs. dermato ibroma, 779 Malignant melanoma vs. Paget disease o breast, 468, 469f vs. seborrheic keratosis, 773 Malnutrition, childhood, 35-36 Mammary Paget disease, 467-469. See also Paget disease o breast Mammogram breast cancer on, 461, 461f, 462f, 463, 464 Paget disease o breast on, 467, 468 Mar an syndrome, in peripheral arterial disease, 232 Marijuana, 15, 1196, 1196f, 1197f. See also Substance abuse disorder Marjolin ulcer, 835, 835f Mask o pregnancy, 996-999. See also Mask o pregnancy Mastalgia, bilateral, vs. breast cancer, 464 Mast cell releasability syndromes, vs. urticaria and angioedema, 716f-718f, 719

1287

1288

INDEX Mastitis, 458-460 de inition o , 458, 458f diagnosis o , 458-459, 458f di erential diagnosis o vs. breast cancer, 464 vs. lacrimal duct plugging, 459 vs. tinea corporis, 459 epidemiology o , 458, 458f etiology and pathophysiology o , 458, 458f ollow-up o , 460 management o , 458f, 459 patient education on, 459 patient story o , 458, 458f Mastoiditis, vs. acute otitis and otitis media with e usion, 115, 115f McCune Albright syndrome, vs. neuro ibromatosis, 1193 McMurray test, 526 Médecins sans Frontières, 23-24, 23f Medial meniscal tear, 527f Medicare Hospice Bene it, 17-18 Medication overuse headache, 1174-1176. See also Headache Mee lines, 967, 967f, 968t vs. Beau lines, 967, 967f Megaloblastosis, vs. vitamin B12 de iciency, 251 Meibomian gland, blockage or in ection o , 65, 65f Melanocytic nevus, 786-791. See also Nevus, benign; Nevus, dysplastic vs. dysplastic nevus, 804 intradermal, 787f, 788f vs. skin tag, 768 Melanocytosis, oculodermal, 70, 70f Melanoma, 842-853 amelanotic vs. common warts, 619 vs. plantar warts, 635 benign juvenile, 787, 788f in congenital nevus, 793, 793f conjunctival, 68-70, 69f diagnosis o , 843-849 ABCDE in, 843, 843f biopsy in, 848-849, 848b, 849f clinical eatures in, 843-847, 843f-847f dermoscopy in, 847-848, 848f distribution in, 847 di erential diagnosis o vs. basal cell carcinoma, 849-850, 849f, 850f vs. dermato ibromas, 849 vs. dysplastic nevus, 804, 849 vs. hyphema, 104 vs. nevus, benign, 790 vs. pyogenic granuloma, 849, 849f vs. seborrheic keratosis, 772f, 773, 773f, 844f, 849 vs. solar lentigines, 849 vs. vascular lesions, 1018 epidemiology o , 843 ollow-up o , 851, 852t-853t undamentals o , 842-843 management o , 850-851, 850t, 851f patient education on, 851

patient story o , 842, 842f prevention and screening or, 851 prognosis in, 851 risk actors or, 843 staging o , 848-849, 848b, 849f, 851, 852t-853t Melanoma, subungual, 970-974 diagnosis o , 971f, 972f, 972t, 973, 973f di erential diagnosis o , 974 vs. longitudinal melanonychia, 965, 966, 967 vs. subungual hematoma, 994 epidemiology o , 970 etiology and pathophysiology o , 971, 971f, 972f, 972t undamentals o , 970 management o , 974 prognosis and ollow-up o , 974 Melanonychia, vs. onychomycosis, 981, 982f Melanosis acquired primary, 68-70, 69f secondary, 70 eye physiologic (racial), 68-70, 68f primary acquired, 68-70, 69f Melanotic hamartomas o iris, 1191-1194, 1193f, 1194f Melasma, 996-999 diagnosis o , 996f, 997, 997f di erential diagnosis o vs. contact dermatitis, 998 vs. discoid lupus erythematosus, 998 vs. systemic lupus erythematosus, 998 epidemiology o , 996, 996f, 997f etiology and pathophysiology o , 996-997, 997f ollow-up o , 998 undamentals o , 996 management o , 998 patient education on, 999 patient story o , 996, 996f prevention o , 998 risk actors or, 997 Meningitis, 1091-1095 di erential diagnosis o carcinomatous, 1094 vs. normal pressure hydrocephalus, 1186 vs. cocaine abuse, 1232 vs. subdural hematoma, 1183 drug-induced, 1094 Mollaret, 1094 Meningitis (in ectious), 1091-1094 aseptic vs. septic, 1094 diagnosis o , 1091f-1093f, 1092-1093 di erential diagnosis o vs. aseptic meningitis, 1094 vs. carcinomatous meningitis, 1094 vs. drug-induced meningitis, 1094 vs. Lyme disease, 1088 vs. Mollaret meningitis, 1094 epidemiology o , 1091 etiology and pathophysiology o , 1091-1092, 1091f Lyme disease in, 1087 ollow-up o , 1094

undamentals o , 1091 management o , 1094 patient story o , 1091, 1091f prognosis and complications o , 1094 risk actors or, 1092 septic, 1094 Meningococcemia vs. vasculitis, 896f vs. vasculitis, cutaneous, 895 Meningoencephalitis, Lyme disease, 1087 Meningoencephalocele, vs. nasal polyps, 131 Meniscal tears, 525-529. See also Knee injuries lateral, 527f medial, 527f Menopause, 437 atrophic vaginitis a ter, 437-440, 437f (See also Atrophic vaginitis) Menzies method, 847 Merkel cell carcinoma, vs. squamous cell carcinoma, 839, 840f Mesenteric ischemia in ectious, 363 vs. pancreatitis, 374 Metabolic acidosis, vs. heart ailure, 210 Metal, contact dermatitis rom, 691, 692, 692f Metallic oreign body, eye, 73, 73f, 77f Metaphysis, osteomyelitis o , 1096-1101. See also Osteomyelitis Metatarsal racture, 519-520, 519f, 520f vs. accessory ossicles, 520 vs. diaphyseal stress racture, 520 vs. Lis ranc injury, 520 Metatarsus adductovarus, 1054-1056. See also Bunion de ormity Methamphetamine abuse, 1223-1227 death rom, 15 diagnosis o , 1224-1225 di erential diagnosis o vs. atopic dermatitis, 1226 vs. contact dermatitis, 1226 vs. neurodermatitis, 1226 vs. prurigo nodularis, 1226 vs. scabies, 1226 epidemiology o , 15, 1196, 1223-1224, 1223f, 1224f etiology and pathophysiology o , 1223f, 1224, 1225f, 1226f ollow-up or, 1226-1227 undamentals o , 1223 ice orm o , 1197f, 1223f management o , 1225f, 1226 meth lab production o , 1224, 1224f patient education on, 1227 patient story o , 1223, 1223f Methicillin-resistant Staphylococcus aureus (MRSA) abscess, 584-586, 585f (See also Abscess) cellulitis, 580, 583 (See also Cellulitis) community-acquired pneumonia, 290 olliculitis, 566, 567f impetigo, 562-564 (See also Impetigo) injection-drug use, 1236, 1237f management o , 566, 567f necrotizing asciitis, 588 (See also Necrotizing asciitis)

INDEX Meth lab(oratory), 1224, 1224f Meth mites, 1223, 1223f, 1224, 1226 Meth mouth, 1224, 1225f, 1226f Microadenoma, Cushing disease rom, 1165, 1165f, 1169-1170, 1170f. See also Cushing syndrome Microalbuminuria, 426 Microaneurysms, eye in diabetic retinopathy, 90, 90f, 91 in hypertensive retinopathy, 93, 93f, 94 (See also Retinopathy, hypertensive) Microbial agents. See also specific types on mortality, 15 Microbial eczema, 706-709. See also Eczema, nummular Micronutrient de iciencies, global, 36-38. See also specific types iodine, 37, 37f iron, 37 vitamin A, 36 vitamin B3 (niacin), 37-38, 37f zinc, 36 Micropapillomatosis o vulva, vs. genital warts, 630 Microsporum, 638, 771. See also Fungal in ections Middle-ear e usion, in acute otitis media, 112-117. See also Acute otitis media Miescher radial granuloma, 887 Migraine headache, 1174-1176. See also Headache vs. cerebral vascular accident, 1179 vs. sinusitis, 135 vs. temporal arteritis, 535 Migratory glossitis, benign, 159-161. See also Geographic tongue Miliaria (prickly heat), 926 vs. olliculitis, 569-570 Miliary pneumonia, 291. See also Tuberculosis (TB) Milia, vs. sebaceous hyperplasia, 777, 777f Minocycline black tongue rom, 157 cutaneous reactions to, 1024-1032 Mirena intrauterine device, 10, 10f, 12 Mites. See also Meth mites olliculitis rom, 567 (See also Folliculitis) Mixed connective disease, 912 MMRC Dyspnea Scale, 270 Modi ied British Medical Research Council (MMRC) Dyspnea Scale, 270 Modi ied Wells clinical score, 216, 216t Mohs surgery, 838, 840, 840t Moles, 786-791. See also Nevus, benign Mollaret meningitis, 1094 Molluscum contagiosum, 613-616 diagnosis o , 613f, 614-615, 614f di erential diagnosis o vs. basal cell carcinoma, 615 vs. dermato ibroma, 615 vs. genital warts, 615, 630 vs. herpes zoster, 598 vs. hordeolum and chalazion, 66 vs. scabies, 615 vs. sebaceous hyperplasia, 777 xanthoma, 1129f, 1130f, 1131

epidemiology o , 613, 613f, 614f etiology and pathophysiology o , 613-614 olliculitis rom, 568 ollow-up o , 616 undamentals o , 613 management o , 615, 615f patient education on, 616 patient story o , 613, 613f prevention o , 615 prognosis in, 615 risk actors or, 614, 614f Molluscum pseudocarcinomatosum, 813-815. See also Keratoacanthoma Molluscum sebaceum, 813-815. See also Keratoacanthoma Moniliasis, 445-449. See also Candida vulvovaginitis Monoarticular in lammatory arthritis, 472, 473 Monoarticular nonin lammatory arthritis, 472, 473 Mononucleosis, in ectious vs. pharyngitis, 144f, 146 tonsillar exudate in, 144f Monosodium urate crystal deposition, 504, 504f Mood disorder, vs. substance abuse disorder, 1199 Moraxella catarrhalis acute otitis media, 112 sinusitis, 133 Morbus Dupuytren, 520f, 530-531, 531f Morphea, 916-921 diagnosis o , 916f, 919-920, 921f di erential diagnosis o , 920 epidemiology o , 916 etiology and pathophysiology o , 916-919, 916f undamentals o , 916 management o , 920-921 patient education on, 921 patient story o , 916, 916f prognosis and ollow-up o , 921, 921f vs. sarcoidosis, 870 Morsicatio, vs. leukoplakia, 175, 175f Morton neuroma, vs. hammer toe, 1058 Mosaic wart, 633, 634f. See also Warts, plantar Moth-eaten alopecia, in syphilis, 1104, 1105f Motivational interviewing, or smoking cessation, 1205, 1206t Motor vehicle accidents, on mortality, 15 Mouth cancer, 177-180. See also Oropharyngeal cancer Mucha-Habermann disease, 945-946, 945f, 946f Mucopyocele, 135f Mucormycosis sinusitis, 133, 134f. See also Sinusitis Mucous membrane pemphigoid. See Cicatricial pemphigoid Mucus cyst, vs. paronychia, 987, 987f Muehrcke lines, 967, 967f, 968t vs. Beau lines, 967, 967f Multiin arct dementia, vs. normal pressure hydrocephalus, 1186 Multiple sclerosis, vs. cerebral vascular accident, 1179

Murine typhus, erythroderma with, 762, 764f Muscle strain/ tear, vs. deep venous thrombosis, 216 Mycobacterium in ection, in global health leprosy, 43-45, 43f-45f tuberculosis and HIV in, 45, 45f Mycobacterium tuberculosis community-acquired pneumonia, 290 tuberculosis, 316, 317f Mycoplasma genitalium urethritis, in men, 10771079. See also Urethritis, in men Mycosis ungoides vs. alopecia areata, 951, 952f vs. eczema, nummular, 708 vs. erythema annulare centri ugum, 1047 erythroderma with, 764f vs. pyoderma gangrenosum, 864 vs. sarcoidosis, 870 vs. scleroderma, 920 Myelodysplastic syndromes, vs. vitamin B12 de iciency, 251 Myocardial in arction vs. pancreatitis, 374 vs. pericarditis, 230 vs. thoracic aortic aneurysm, 189 Myositis, in lammatory, vs. arthritis, 476 Myringitis, bullous, vs. acute otitis and otitis media with e usion, 115, 115f Myrmecia, 633-636. See also Warts, plantar Myxedema diagnosis o , 1149, 1150f pretibial, in hyperthyroidism, 1155, 1155f, 1156f vs. scleroderma, 920 Myxedema coma, 1150 management o , 1151 risk actors or, 1149 Myxomatous changes, vs. bacterial endocarditis, 222 N Nail bed lesions, pigmented, 967 Nail bed nevus, vs. subungual hematoma, 994 Nail disorders, pigmented, 970-974 diagnosis o , 972t, 973, 973f di erential diagnosis o vs. longitudinal melanonychia, 974 vs. subungual hematoma, 974 epidemiology o , 970 etiology and pathophysiology o , 970-972, 970f-973f undamentals o , 970 management o , 973f, 977 patient story o , 970, 970f prognosis and ollow-up o , 974 Nail old picking, vs. onychomycosis, 981 Nail hypertrophy, 964, 965, 965f lateral, 964-968, 965f (See also Onychogryphosis) Nail splitting, 993, 994f, 995 Nails, psoriatic, 488, 488f, 989-992. See also Psoriatic nails Nail trauma, 993-995. See also Hematoma, subungual vs. onychomycosis, 981

1289

1290

INDEX Nail unit, 964, 964f Nail variants, normal, 964-968 Beau lines, 967, 967f, 968t diagnosis o , 966, 968t di erential diagnosis o vs. hal -and-hal nails, 967, 967f vs. hematoma, 967 vs. Mee and Muehrcke lines, 967, 967f, 968t vs. pigmented lesions o nail bed, 967 vs. subungual melanoma, 965, 966, 967 vs. twenty-nail dystrophy, 967, 968f epidemiology o , 964 etiology and pathophysiology o , 964-966, 964f-966f undamentals o , 964 habit-tic de ormity, 965-968, 966f, 967f hal -and-hal nails, 967, 967f leukonychia, 964-968, 964f, 968t (See also Leukonychia) leukonychia punctata, 964-968, 965f, 968t longitudinal melanonychia, 964-968, 964f, 965f (See also Leukonychia) management o , 967-968 onychogryphosis, 964-968, 965f (See also Onychogryphosis) patient story o , 964, 964f risk actors or, 966 transverse striate leukonychia, 964-968, 964f Nasal crease, horizontal, with atopic dermatitis, 687, 688f Nasal polyps, 130-131, 130f, 131f vs. chordoma, 131 vs. glioblastoma, 131 vs. meningoencephalocele, 131 vs. nasopharyngeal carcinoma, 131 vs. papilloma, 131 vs. pyogenic granuloma, 131 Nasopharyngeal carcinoma, vs. nasal polyps, 131 Natriuresis, pressure, 416 Necator americanus, 1080-1083, 1080f. See also Intestinal worms and parasites Neck in ections, deep, vs. pharyngitis, 146 Necrobiosis lipoidica, 1125-1127 diagnosis o , 1111, 1112f, 1125-1127, 1125f, 1126f di erential diagnosis o vs. diabetic dermopathy, 1122 vs. erythema nodosum, 1127 vs. granuloma annulare, 1127 vs. lichen simplex chronicus, 1127 vs. sarcoidosis, 870, 1127 vs. stasis dermatitis, 1127 epidemiology, etiology and pathophysiology o , 1125 undamentals o , 1125 management o , 1127 patient education on, 1127 patient story o , 1125, 1125f prognosis in, 1127 Necrotizing angiitis, with lupus, 902, 902f Necrotizing erysipelas, 588-591. See also Necrotizing asciitis

Necrotizing asciitis, 588-591 diagnosis o , 588f-590f, 589-590 di erential diagnosis o vs. cellulitis, 582, 590 vs. clostridial myonecrosis, 590 vs. erythema induratum, 590 vs. pyomyositis, 590 vs. streptococcal or staphylococcal toxic shock syndrome, 590 epidemiology, etiology and pathophysiology o , 588 undamentals o , 588 management o , 590-591 patient education on, 591 patient story o , 588, 588f prognosis and ollow-up or, 591 risk actors or, 588-589 saltwater variant, 588 Necrotizing so t tissue in ection, 588-591. See also Necrotizing asciitis Neisseria meningitides meningitis, 1091-1094. See also Meningitis Nematodes, 1080-1083, 1080f, 1081f. See also Intestinal worms and parasites global health problem o , 35, 35f Neomycin contact dermatitis, 691, 692, 693f, 696t. See also Contact dermatitis; Drug reactions, cutaneous Neonatal lupus, 900f Neovascularization, eye, vs. hyphema, 104 Nephrolithiasis, 398-401. See also Kidney stones vs. ankylosing spondylitis, 493 vs. diverticulitis, 341 Nephrotic syndrome, 402-405 diagnosis and screening or, 402-404, 402f-404f di erential diagnosis o vs. heart ailure, 404 vs. hypoalbuminemia, 404 epidemiology, etiology and pathophysiology o , 402 ollow-up and patient education on, 405 undamentals o , 402 management o , 404 patient story o , 402, 402f, 403f prognosis and clinical course o , 404-405 Nerve root compression, vs. peripheral arterial disease, 235 Neurodermatitis, 710-715. See also Neurotic excoriation vs. methamphetamine abuse, 1226 Neurodermatitis circumscripta, 710-715. See also Psychocutaneous disorders Neuroendocrine carcinoma o skin, vs. squamous cell carcinoma, 839, 840f Neuro ibroma vs. dermato ibroma, 779 vs. skin tag, 768, 768f Neuro ibromatosis, 1191-1194 diagnosis o , 1191f-1193f, 1192-1193 di erential diagnosis o vs. ataxia telangiectasia, 1193 vs. Bloom syndrome, 1193 vs. Fanconi anemia, 1193

vs. McCune Albright syndrome, 1193 vs. neuro ibromatosis type 2, 1193 vs. Proteus syndrome, 1193 vs. segmental neuro ibromatosis, 1193 vs. tuberous sclerosis, 1193, 1193f epidemiology, etiology and pathophysiology o , 1191 ollow-up o , 1194 undamentals o , 1191 management o , 1193 patient story o , 1191, 1191f prognosis in, 1194 risk actors or, 1191 Neurologic disease. See also specific types death rom, 15 Neuroma, Morton, vs. hammer toe, 1058 Neuromuscular weakness, vs. heart ailure, 210 Neuropathic ulcer o oot, 1063-1064, 1063f vs. ischemic ulcer o oot, 1062, 1064 Neuropathy, vs. Lyme disease peripheral, 1088 radiculoneuropathy, 1088 Neurosyphilis, 1102, 1103, 1105, 1106-1107. See also Syphilis Neurotic excoriation, 710-715 diagnosis o , 711f, 713-714 di erential diagnosis o , 714 epidemiology o , 711 etiology and pathophysiology o , 713 ollow-up o , 715 management o , 714 patient education on, 714 patient story o , 710, 710f Nevus with architectural disorder, 802-805 (See also Nevus, dysplastic) di erential diagnosis o nail bed, vs. subungual hematoma, 994 white sponge, vs. leukoplakia, 176 Nevus anemicus, 789, 789f vs. vitiligo, 1003, 1004f Nevus, benign, 786-791 diagnosis o , 787f, 788f, 790 di erential diagnosis o vs. dysplastic or atypical nevi, 790 vs. labial melanotic macules, 790, 791f vs. melanomas, 790 vs. seborrheic keratoses, 790 epidemiology o , 786 etiology and pathophysiology o , 786-789, 786f-788f eye conjunctival, 68-70, 68f, 75f scleral, 68-70, 68f ollow-up o , 791 undamentals o , 786, 786f management o , 791 patient education on, 791 patient story o , 786, 786f prevention o , 791 prognosis in, 791 Nevus comedonicus, 789, 790f Nevus, congenital, 793-797 de inition o , 793

INDEX diagnosis o , 793f-796f, 794-795 di erential diagnosis o vs. Becker nevus, 795 vs. ca é-au-lait spots, 795 epidemiology o , 793 etiology and pathophysiology o , 794 ollow-up o , 797 management o , 793f, 794f, 796, 796f, 797f patient education on, 796 patient story o , 793, 793f tardive, 794 Nevus depigmentosus, 789, 789f vs. vitiligo, 1003, 1003f Nevus, dysplastic, 802-805 diagnosis o , 802f, 803-804, 803f di erential diagnosis o vs. benign nevus, 790 vs. melanocytic nevi, 804 vs. melanoma, 804, 849 epidemiology o , 802-803 etiology and pathophysiology o , 802f, 803 ollow-up o , 804-805, 804f, 805f undamentals o , 802 management o , 804, 804f patient education on, 805 patient story o , 802, 802f prevention o , 804 prognosis in, 804 Nevus, epidermal, 789, 798-802 diagnosis o , 798f, 799-800 di erential diagnosis o vs. lichen striatus, 800, 800f vs. linear lichen planus, 800, 800f vs. syringoma, 800, 800f epidemiology o , 798-799 etiology and pathophysiology o , 798f, 800 ollow-up o , 801 undamentals o , 798 management o , 800-801 patient story o , 798, 798f prognosis in, 801 Nevus lammeus, 1020-1023, 1020f. See also Vascular lesions, hereditary and congenital Nevus, melanocytic, 786-791. See also Nevus, benign di erential diagnosis o vs. dysplastic nevus, 804 vs. skin tag, 768 intradermal, 787f, 788f Nevus o Ota, 70, 70f, 787, 788f Nevus pigmentosus, 793-797. See also Nevus, congenital Nevus pigmentosus et pilosus, 793-797. See also Nevus, congenital Nevus sebaceous, 798-802 diagnosis o , 798f, 799f, 800 di erential diagnosis o vs. lichen striatus, 800, 800f vs. linear lichen planus, 800, 800f vs. syringoma, 800, 800f epidemiology o , 799 etiology and pathophysiology o , 799, 799f ollow-up o , 801

undamentals o , 798 management o , 800-801 prognosis in, 801 Nevus spilus, 787, 788f, 795f Nevus, Spitz, 787, 788f Nexplanon, 12, 12f Niacin de iciency, 37-38, 37f Nickel contact dermatitis, 691, 692f, 695, 696f, 696t, 697. See also Contact dermatitis Nicotine addiction, 1201-1212. See also Tobacco addiction Nicotine stomatitis, 1203, 1203f vs. leukoplakia, 176, 176f Ni edipine or atrial ibrillation, 198 or diastolic heart ailure, 210 Nikolsky sign, 923, 926, 937 in pemphigus vulgaris, 934f, 937 Nipple adenoma, vs. Paget disease o breast, 469 Nipple discharge, vs. breast cancer, 464 Nitrates, or coronary artery disease, 213 Nitro urantoin, cutaneous reactions to, 1024-1032, 1029t. See also Drug reactions, cutaneous Nitroglycerin, or coronary artery disease, 213 Nits (lice), 669, 669f, 670, 670f, 671. See also Lice Nodular leukoplakia, 174-176. See also Leukoplakia Nodular melanoma, 842f, 844, 845f Nodule Lisch, 1191-1194, 1193f, 1194f (See also Neuro ibromatosis) palmar, vs. Dupuytren disease, 531 rheumatoid arthritis, 473, 474f, 483, 483f vs. granuloma annulare, 857 vs. sarcoidosis, 870 thyroid, autonomous unctioning, 1156 vocal cord, 149-153, 152f (See also Vocal cord nodules) Nodulocystic acne, 540-546, 540f. See also Acne vulgaris Nomogram, 1242 Nonalcoholic atty liver disease diagnosis o , 366, 368 epidemiology o , 365 etiology and pathophysiology o , 366 management o , 370 with obesity, 1136 prevention and screening or, 370 risk actors or, 366 Noncontact sexual abuse, 55 Nonhomogenous leukoplakia, 174-176. See also Leukoplakia Nonin ective vegetations, vs. bacterial endocarditis, 222 Non-neoplastic hamartoma, 335-338. See also Colon polyps Non–potassium-sparing diuretics, or heart ailure, 210 Nonsteroidal antiin lammatory drugs (NSAIDs) colitis rom, 384 cutaneous reactions to, 1024-1032, 1026f, 1029t (See also Drug reactions, cutaneous)

diagnosis o , 1028 etiology and pathophysiology o , 1027 peptic ulcer disease rom, 377-380 (See also Peptic ulcer disease) risk actors or GI events rom, 480, 482t Nonulcer dyspepsia vs. gastric cancer, 352 vs. peptic ulcer disease, 379 Normal pressure hydrocephalus, 1185-1186, 1185f, 1186f vs. alcoholism, chronic, 1186 vs. Alzheimer disease, 1186 vs. hypothyroidism, 1186 vs. in ections, intracranial, 1186 vs. meningitis, carcinomatous, 1186 vs. multiin arct dementia, 1186 vs. Parkinson disease, 1186 Number needed to harm (NNH), 1242 Number needed to treat (NNT), 1242, 1244b Nummular hand dermatitis, 699, 700f Nutrition transition, 36 NuvaRing, 10, 10f O Oat cell carcinoma o lung, 278-284. See also Lung cancer Obesity, 1135-1139 acanthosis nigricans in, 1118-1120, 1135, 1136 (See also Acanthosis nigricans) central, 1136, 1136f diagnosis o , 1135f-1137f, 1136-1137 di erential diagnosis o vs. Cushing syndrome, 1137 in genetic disorders, 1137 vs. polycystic ovary syndrome, 1137 in Prader-Willi syndrome, 1137 epidemiology o , 1135 etiology and pathophysiology o , 1135-1136 ollow-up or, 1139 undamentals o , 1135 as global health problem, 36 hidradenitis suppurativa with, 1136, 1137f management o , 1137-1138 patient education on, 1139 patient story o , 1135, 1135f prevention and screening or, 1138-1139 prognosis in, 1139 psoriasis in, 1136, 1136f risk actors or, 1136 skin tag in, 1135, 1135f varicose veins in, 1136, 1136f xanthomas with, 1129-1133 (See also Xanthomas) xanthoma with, eruptive, 1136, 1137f Obestatin, 1135 Obstructive acne, 540-546, 541f, 544f. See also Acne vulgaris Obstructive liver disease, 366 Occupational contact dermatitis, 691-697, 691f, 693f, 695f, 697f. See also Contact dermatitis Occupational hyperkeratosis, vs. Dupuytren disease, 531

1291

1292

INDEX Occupational lung disease, vs. pulmonary ibrosis, 307 Ocular herpes zoster, 601-604. See also Zoster ophthalmicus Ocular rosacea, 550-551, 550f, 551f, 552. See also Rosacea red eye in, 107t, 109, 109f Oculodermal melanocytosis, 70, 70f Oil drop sign, in psoriatic nails, 989, 989f, 990f Olecranon bursitis, 508-510 diagnosis o , 508-509, 508f, 509f di erential diagnosis o vs. epicondylitis, 509 vs. gout or pseudogout, 509 vs. hemorrhage into bursa, 509 vs. rheumatoid arthritis, 509 vs. septic joint, 509 vs. ulnar nerve entrapment, 509 epidemiology, etiology and pathophysiology o , 508 gout in, 474, 475f undamentals o , 508 management o , 509-510, 509f patient education on, 510 patient story o , 508, 508f prognosis and ollow-up o , 510 risk actors or, 508 Onychocryptosis, 975-977. See also Ingrown toenail vs. paronychia, 987 Onychogryphosis, 964-968 diagnosis o , 966, 979f, 980f etiology and pathophysiology o , 965, 965f management o , 967-968 risk actors or, 966 synonyms or, 964 Onychomycosis, 638-642, 979-983. See also Fungal in ections diagnosis o , 979f-981f, 980-981 di erential diagnosis o vs. leukonychia, 981 vs. lichen planus nails, 981 vs. melanonychia, 981, 982f vs. nail old picking, habitual, 981 vs. nail trauma, 981 vs. pseudomonal nail in ection, 981, 982f vs. psoriatic nails, 981, 991 epidemiology o , 979 etiology and pathophysiology o , 979-980, 979f, 980f Trichophyton rubrum in, 658 undamentals o , 979 management o , 981-983, 983t patient education on, 983 patient story o , 979, 979f prevention o , 982 prognosis and ollow-up o , 983 risk actors or, 980 with tinea pedis, 658, 659, 662 Open-angle glaucoma, 87-89. See also Glaucoma Operation Sa ety Net (OSN), 29-30 Oppression, recognition o , 7 Optic disc cupping, 88

di erential diagnosis o , 87f, 88 vs. glaucoma, 87f, 88 in glaucoma, 87, 87f, 88 normal, 87, 87f Optic disc drusen, 97 Optic disc swelling, in papilledema, 96-98. See also Papilledema Optic nerve atrophy, in glaucoma, 87, 87f Optic nerve swelling, 94 Optic neuropathies, 97 Oral cancer. See also Oropharyngeal cancer; specific types vs. aphthous ulcer, 171 Oral contraceptive pills ethinyl estradiol, 11, 11t ethinyl estradiol with drospirenone, 11 extended regimens o , 11 traditional, 11t use o , 10 Oral squamous cell carcinoma, 177-180. See also Oropharyngeal cancer Orbicular eczema, 706-709. See also Eczema, hand Orbital abscess, rom sinusitis, 134, 135f Orolabial herpes, 606-611, 607f. See also Herpes simplex virus Oropharyngeal cancer, 177-180 diagnosis o , 177-179, 177f-179f di erential diagnosis o , 179, 179f epidemiology, etiology and pathophysiology o , 177 undamentals o , 177 management o , 179 patient education on, 180 patient story o , 177, 177f prognosis and ollow-up o , 179 risk actors or, 177 Ortho Evra, 12, 13f Osler nodes, 221, 222, 222f Osler-Weber-Rendu syndrome, 1020-1023, 1020f. See also Vascular lesions, hereditary and congenital Ossicles, accessory, vs. metatarsal racture, 520 Osteoarthritis, 478-481. See also Arthritis de inition o , 478 diagnosis o , 473, 473f, 476, 476f, 478-479, 478f-480f Bouchard nodes in, 473f Heberden nodes in, 473f di erential diagnosis o , 477t vs. ankylosing spondylitis, 493 vs. bursitis, 479 vs. connective tissue diseases, 479 vs. ibromyalgia, 479 vs. knee injuries, 528 vs. lupus, 479 vs. polyarticular gout, 479 vs. polymyalgia rheumatica, 479, 535 vs. reactive arthritis, 479 vs. rheumatoid arthritis, 479, 480f vs. scleroderma, 479 vs. seronegative spondyloarthropathies, 479 epidemiology o , 478 etiology and pathophysiology o , 472, 478 ollow-up or, 481

management o , 480-481, 481t, 482t GI events rom NSAIDs in, 480, 482t patient education on, 481 patient story in, 478, 478f risk actors or, 478 Osteochondroma, vs. knee injuries, 528 Osteomyelitis, 1096-1101 diagnosis o , 1097f-1100f, 1098-1100 di erential diagnosis o vs. bone in arct, 1100 vs. bone tumor, 1100 vs. cellulitis, 1100 vs. Charcot arthropathy, 1066 vs. Charcot joint, 1100 vs. compression ractures, 503 vs. degenerative disk disease, 1100 vs. racture, osteoporotic, 1100 vs. gout/ pseudogot, 1100 vs. knee injuries, 528 vs. pancreatitis, 1100 vs. pyelonephritis, 1100 vs. spinal stenosis, 1100 vs. trauma, old, 1100 epidemiology o , 1096 etiology and pathophysiology o , 1096-1097, 1097f injection-drug use in, 1236, 1237f undamentals o , 1096 hematogenous, 1096 management o , 1100-1101 patient education on, 1101 patient story o , 1096, 1096f prognosis and ollow-up o , 1101 risk actors or, 1097 Osteopenia, 1141-1146. See also Osteoporosis and osteopenia Osteoporosis and osteopenia, 1141-1146 diagnosis o , 1141f-1146f, 1142, 1143t di erential diagnosis o vs. ankylosing spondylitis, 1143 vs. cancer, 1143 vs. degenerative arthritis o spine, 1143 vs. tuberculosis o spine, 1143 epidemiology o , 1141 etiology and pathophysiology o , 1141-1142, 1143f, 1143t ollow-up o , 1144f, 1145f, 1146 undamentals o , 1141 management o , 1143-1146, 1143t patient education on, 1146 patient story o , 1141, 1141f prevention and screening or, 1146 risk actors or, 1142, 1143t Osteoporotic vertebral compression ractures, 501-503. See also Compression ractures Osteoporotic vertebral racture, vs. back pain, 496, 496f Osteosarcoma, vs. knee injuries, 528 Otalgia, re erred, vs. acute otitis and otitis media with e usion, 115 Otitic barotrauma, vs. acute otitis and otitis media with e usion, 114

INDEX Otitis externa, 119-122 de inition o , 120 diagnosis o , 119f-121f, 120-121 di erential diagnosis o vs. acute otitis and otitis media with e usion, 114 vs. acute otitis media with per orated tympanic membrane, 121 vs. chronic suppurative otitis media, 119f, 121 vs. contact dermatitis, 121 vs. oreign body, ear, 121, 123 vs. otomycosis, 121 vs. seborrheic dermatitis, 120f, 121 epidemiology, etiology and pathophysiology o , 120 ollow-up and patient education on, 122 with hearing aid, 120, 121f malignant (necrotizing), 119, 119f management o , 121-122 patient story o , 119, 119f prevention o , 122 prognosis in, 122 risk actors or, 120 Otitis media with e usion, 112-117 diagnosis o , 112f-114f, 113-114 di erential diagnosis o , 114-116 vs. acute otitis media, 114 vs. bullous myringitis, 115, 115f vs. cholesteatoma, 114, 114f, 115f vs. chronic suppurative otitis media, 115 vs. oreign body, 115 vs. mastoiditis, 115, 115f vs. otalgia, re erred, 115 vs. otitic barotrauma, 114 vs. otitis externa, 114 vs. tympanic membrane per oration, traumatic, 115, 116f epidemiology, etiology and pathophysiology o , 112 ollow-up or, 117 undamentals o , 112 management o , 116 patient education on, 117 prevention o , 116, 116f prognosis in, 117 risk actors or, 112 Otomycosis, vs. otitis externa, 121 Ottawa rules or ankle injuries, 519, 520 or knee injuries, 526 Ovarian cyst, vs. diverticulitis, 342 Overlap syndrome, 912 Overnutrition, 35-36 Oyster-like de ormity, 964-968, 965f. See also Onychogryphosis P Pacemakers, or atrial ibrillation, 199 Pachyonychia congenita, vs. corns and calluses, 1051f, 1052 Paget disease o breast, 467-469 diagnosis o , 467f, 468, 468f di erential diagnosis o vs. benign lichenoid keratoses, 469, 469f

vs. Bowen disease, 468 vs. eczema o areola, 468, 468f vs. nipple adenoma, 469 vs. seborrheic keratoses, 469, 469f vs. super icial spreading malignant melanoma, 468, 469f epidemiology o , 467 etiology and pathophysiology o , 467, 467f management o , 469 patient education on, 469 patient story o , 467, 467f prognosis in, 469 Pain. See also specific types end-o -li e management o , 18 in sickle cell disease acute crises o , 254-255 chronic syndromes o , 255 Pain reliever addiction, 1197 Palliative care, 18 principles o , 14 Palliative per ormance scale, 16 Palmar erythema, in liver disease, 366, 367f Palmar ibromatosis, 520f, 530-531, 531f Palmar hyperlinearity, with atopic dermatitis, 685 Palmar nodules, vs. Dupuytren disease, 531 Palmoplantar eczema, 699-705. See also Eczema, hand Palmoplantar keratoderma, vs. plantar warts, 635, 635f, 636f Palmoplantar warts, 633-636. See also Warts, plantar Pancreatic divisum, 373 Pancreatitis, acute, 373-376 de inition o , 373 diagnosis and screening or, 373-374, 374f di erential diagnosis o vs. ankylosing spondylitis, 493 vs. aortic aneurysm, dissecting, 374 vs. appendicitis, 374 vs. cholangitis, 374 vs. cholecystitis and biliary colic, 374 vs. Fitz-Hugh-Curtis syndrome, 374 vs. gallstones, 346 vs. hepatitis, 374 vs. intestinal obstruction, 374 vs. mesenteric ischemia, 374 vs. myocardial in arction, in erior wall, 374 vs. peptic ulcer disease, per orating, 374 vs. pneumonia, 374 vs. pulmonary/ pleural disease, 374 epidemiology, etiology and pathophysiology o , 373, 373f management o , 375, 375f patient story o , 373, 373f prognosis and clinical course o , 375-376, 376t Panniculitis in erythema nodosum, 886-889 in ectious, vs. erythema nodosum, 888 Panuveitis, 84, 85 Papillary carcinoma, renal cell, 421 Papilledema, 96-98 diagnosis o , 96-97, 96f, 97f

di erential diagnosis o , 97 epidemiology, etiology and pathophysiology o , 96 undamentals o , 96 management o , 97 patient education on, 98 patient story o , 96, 96f prevention o , 97 prognosis and ollow-up in, 97 risk actors or, 96 Papillomatosis laryngeal, 149-153 (See also Hoarseness) micropapillomatosis o vulva, 630 recurrent respiratory, 151f hoarseness in, 149-153 (See also Recurrent respiratory papillomatosis) maternal HPV in ection and juvenile onset o , 149 Papilloma, vs. nasal polyps, 131 Papulopustular rosacea, 548, 548f, 552. See also Rosacea Parain luenza virus sinusitis, 133 Parakeratosis, in psoriatic nails, 989, 989f Paraneoplastic pemphigus, 934-940 diagnosis o , 937-938, 937f di erential diagnosis o , 938 epidemiology o , 935 etiology and pathophysiology o , 935-936 ollow-up o , 940 undamentals o , 934 management o , 938-940, 940f patient education on, 940 prognosis in, 940 Parapneumonic e usions, 286-289. See also Pleural e usion in community-acquired pneumonia, 292f Parapsoriasis variegata, 874f Parapsoriasis, vs. cutaneous T-cell lymphoma, 876 Parasites, intestinal, 1080-1083. See also Intestinal worms and parasites Parasitic olliculitis, 567. See also Folliculitis Parasitosis delusions, vs. psychocutaneous disorders, 714 Parenchymal renal disease, vs. renovascular hypertension, 419 Parkinson disease, vs. normal pressure hydrocephalus, 1186 Paronychia, 985-988 diagnosis o , 984f, 985f, 987 di erential diagnosis o vs. elon, 987 vs. glomus tumor, 987 vs. herpes simplex virus, 609 vs. herpetic whitlow, 987 vs. ingrown toenail, 987 vs. mucus cyst, 987, 987f vs. neoplasms, 987 epidemiology o , 985 etiology and pathophysiology o , 985, 985f, 986f undamentals o , 985 management o , 987 patient education on, 988

1293

1294

INDEX Paronychia (Cont.): patient story o , 985, 985f prevention o , 987 prognosis and ollow-up o , 988 risk actors or, 986-987, 986f Paronychia congenita callus rom, 1050, 1051f vs. corns and calluses, 1051f, 1052 Pasteurella multocida cellulitis, 580. See also Cellulitis Patch, contraceptive, 11t combination, 12, 13f Patch testing, 686t, 695, 695f, 696f, 702, 702f Patellar dislocation, 527. See also Knee injuries Patellar racture, nondisplaced, 527, 527f Pathergy, in pyoderma gangrenosum, 861, 861f, 863f, 864, 864f, 865 Patient learning rom, 7 what physicians want rom and or, 6, 7f Patient-centered interview, 7, 8 Patient–physician relationship, images or trust in, 3-4 Patient story, 6 Pautrier microabscess, 875 Pearly penile papules, vs. genital warts, 629, 629f Pediculus humanus capitis, 668-672, 669f, 670f Pediculus humanus corporis, 668-672, 668f, 669f Peer-to-peer adult education, 33 Pellagra, 37-38, 37f Pelvic in lammatory disease, chlamydial, 454 with reactive arthritis, 757-760, 758f, 759f (See also Reactive arthritis) Pemphigoid gestationis, 929 vs. urticaria, 719 Pemphigus, 934-940 diagnosis o , 934f-938f, 937-938 di erential diagnosis o vs. bullous pemphigoid, 938 vs. cicatricial pemphigoid, 938 vs. dermatitis herpeti ormis, 938 vs. Hailey-Hailey disease, 938, 939f vs. herpes zoster, 598 vs. linear IgA dermatosis, 938 vs. porphyria cutanea tarda, 938 vs. zoster ophthalmicus, 604 epidemiology o , 934-935, 934f-936f etiology and pathophysiology o , 935-936 ollow-up o , 940 undamentals o , 934 management o , 938-940, 940f patient education on, 940 patient story o , 934, 934f prognosis in, 940 Pemphigus erythematosus, 937, 938f. See also Pemphigus oliaceous Pemphigus oliaceous, 923, 923f, 934-940 diagnosis o , 935f, 936f, 937-938, 938f di erential diagnosis o , 938 epidemiology o , 934, 935f, 936f etiology and pathophysiology o , 935-936 ollow-up o , 940 undamentals o , 934 management o , 938-940, 940f

patient education on, 94 prognosis in, 940 Pemphigus gestationis, 923, 923f Pemphigus vegetans. See also Pemphigus vulgaris diagnosis o , 935f, 937-938 epidemiology o , 934, 934f, 935f undamentals o , 934 vs. Hailey-Hailey disease, 938, 939f Pemphigus vulgaris, 923, 923f, 934-940 black tongue in, 157, 157f diagnosis o , 934f-937f, 937-938 di erential diagnosis o , 938 vs. chickenpox, 594 vs. cutaneous drug reactions, 1031 vs. impetigo, 564 epidemiology o , 934, 934f, 935f etiology and pathophysiology o , 935-936 ollow-up o , 940 undamentals o , 934 management o , 938-940, 940f patient education on, 940 patient story o , 934, 934f prognosis in, 940 Penicillin, cutaneous reactions to, 1024-1032, 1025f, 1029t. See also Drug reactions, cutaneous Penile pyoderma gangrenosum, 863 Peptic ulcer disease, 377-380 de inition o , 377 diagnosis o , 377f, 378, 378f di erential diagnosis o vs. biliary colic, 379 vs. Crohn’s disease, gastroduodenal, 379 vs. unctional dyspepsia, 379 vs. gallstones, 346 vs. gastric cancer, 352, 379 vs. gastroesophageal re lux, 379 vs. kidney stones, 400 vs. nonulcer dyspepsia, 379 vs. pancreatitis, 374 epidemiology o , 377, 377f etiology and pathophysiology o , 377-378, 377f, 378f ollow-up or, 379-380 management o , 379 patient education on, 380 patient story o , 378 prevention o , 379 prognosis in, 379 risk actors or, 379 Peptostreptococcus necrotizing asciitis, 588 otitis externa, 120 Per ume, contact dermatitis rom, 699f, 703t Pericardial e usion, 228-231 diagnosis o , 228f-230f, 229-230 di erential diagnosis o vs. heart ailure, 230, 230f vs. pericarditis, acute, 230 vs. pleural e usion, 230, 230f epidemiology, etiology and pathophysiology o , 228 ollow-up and patient education on, 231 undamentals o , 228

management o , 231 patient story o , 228, 228f, 229f prognosis in, 231 risk actors in, 228-229 “water-bottle” heart in, 229f Pericarditis, 228-231 diagnosis o , 228f, 229-230, 229f di erential diagnosis o vs. coronary artery disease, 213 vs. costochondritis, 230 vs. myocardial in arction, 230 vs. pericardial e usion, 230 vs. pleurisy, 230 epidemiology, etiology and pathophysiology o , 228 ollow-up and patient education on, 231 undamentals o , 228 management o , 230 prognosis in, 231 risk actors in, 228-229 “water-bottle” heart in, 229f Periodontal anatomy, healthy, 162f Periodontal disease (periodontitis), 162-164 acute necrotizing ulcerative, 163, 163f diagnosis o , 162f, 163, 163f di erential diagnosis o vs. gingival hyperplasia, 163 vs. poor dental hygiene, 163 epidemiology o , 162, 164f etiology and pathophysiology o , 163, 163f undamentals o , 162 management o , 164 patient education and ollow-up in, 164 patient story o , 162, 162f prevention o , 164 risk actors or, 163 smoking and, 1202, 1203f Perioral dermatitis, 551, 552f Peripheral arterial disease, 232-238 with diabetes and dry gangrene, 1068 diagnosis and screening or, 233-235 examination in, 233-234 history and symptoms in, 233 imaging in, 234-235 laboratory testing in, 234 di erential diagnosis o vs. Baker cyst, symptomatic, 235 vs. compartment syndrome, chronic, 235 vs. deep venous thrombosis, 235 vs. hip arthritis, 235 vs. nerve root compression, 235 vs. spinal stenosis (pseudoclaudication), 235 vs. venous claudication, 235 epidemiology o , 232 etiology and pathophysiology o , 232-233 ollow-up o , 238 undamentals o , 232 management o , 235-237 or acute limb ischemia, 236-237, 237f goals o therapy in, 235 in ection treatment in, 236 pharmacotherapy in, 235-236 revascularization therapy in, 236, 236f, 237f risk actor modi ication in, 235

INDEX patient education on, 238 patient story o , 232, 232f prognosis in, 237 risk actors or, 233 Peripheral arterial occlusive disease. See Peripheral arterial disease Peripheral edema, in nephrotic syndrome, 402, 403, 403f Peripheral neuropathy, vs. Lyme disease, 1088 Peripheral retinal photocoagulation, or diabetic retinopathy, 91, 92f Perirectal abscess, vs. hemorrhoids, 359, 360f Peristomal pyoderma gangrenosum, 862 Peritonsillar abscess, in pharyngitis, 143, 144f Perlèche, 138-140, 138f, 139f. See also Angular cheilitis diagnosis o , 645, 645f Pernicious anemia, 248, 249, 251. See also Vitamin B12 de iciency Personality disorders, vs. substance abuse disorder, 1199 Petroleum products, contact dermatitis rom, 697f Pharyngitis, 143-147 diagnosis o , 143f-145f, 144-146 di erential diagnosis o vs. cytomegalovirus, 146 vs. diphtheria, 146 vs. epiglottitis, 146 vs. herpangina/ coxsackievirus, 146, 146f vs. herpes gingivostomatitis, 146 vs. in ectious mononucleosis, 144f, 146 vs. neck in ections, deep, 146 vs. oral Candida (thrush), 146 vs. sexually transmitted in ections, 146 vs. supraglottitis, 146 epidemiology o , 143 etiology and pathophysiology o , 143, 143f, 144f undamentals o , 143 management o , 146-147 patient education on, 147 patient story o , 143, 143f prognosis and ollow-up o , 147 risk actors or, 143 Pheochromocytoma, vs. renovascular hypertension, 419 Photoallergic drug reactions, 1006-1011, 1007f, 1009t. See also Photosensitivity eczema as, 1007f, 1008, 1009 Photoallergic eruptions, 1006-1011, 1007f, 1008t, 1009t. See also Photosensitivity Photocoagulation, peripheral retinal, or diabetic retinopathy, 91, 92f Photodermatitis prevention o , 1010, 1010t prognosis in, 1010 risk actors or, 1009 types o , 1006 UV light in, 1006 Photography, 4 Photosensitivity, 1006-1011 diagnosis o , 1006f, 1007f, 1009

di erential diagnosis o vs. contact dermatitis, 1010 vs. dermatomyositis, 912, 1009 vs. porphyria cutanea tarda, 1009 vs. systemic lupus erythematosus, 1009 epidemiology o , 1006-1008, 1006f erythroderma with, 761, 762t etiology and pathophysiology o , 1006f, 1007f, 1008, 1008t, 1009t ollow-up o , 1011 undamentals o , 1006f management o , 1010, 1010t patient education on, 1011 patient story o , 1006, 1006f prevention o , 1010, 1010t prognosis in, 1011 risk actors or, 1008 UV light in, 1006 Phototoxic drug reactions, 1006-1011, 1006f, 1007f, 1008t. See also Photosensitivity Phthirus pubis, 668-672, 669f, 670f Phymatous rosacea, 549, 549f, 550, 552. See also Rosacea Physical abuse, intimate partner, 50-53 Physical inactivity, on mortality, 15 Physical violence, 50 Physician desires or patients o , 6, 7f what patients want rom, 6 Physician orders or li e-sustaining treatment (POLST) Paradigm task orce, 17 Physiologic melanosis, eye, 68-70, 68f Phytophotodermatitis, 1006-1011, 1007f. See also Photosensitivity vs. cutaneous larva migrans, 681 Picker’s nodules, 710-715. See also Psychocutaneous disorders Pigmented hairy nevus, 793-797. See also Nevus, congenital Pigmented lesions o nail bed, 967 Pigmented nail disorders, 970-974. See also Nail disorders, pigmented Pigmented pretibial papules. See Diabetic dermopathy Pigmented purpuric dermatosis vs. diabetic dermopathy, 1123 o Majocchi type, vs. vasculitis, 895, 896f vs. vasculitis, 894-895, 895f Pigmented stones, 344-347. See also Gallstones Piles, 358-361. See also Hemorrhoids Pincer nail, 975, 975f Pinguecula, vs. pterygium, 63, 63f Pink eye, 75-78 Pinworm, 1080-1083. See also Intestinal worms and parasites Pit latrines, in Ethiopia, 33, 33f Pitted keratolysis, 572-573, 572f, 573f vs. arsenic toxicity, 573 vs. basal nevus syndrome, 573 vs. planar warts, 572 vs. tinea pedis, 660, 660f Pitting edema in chronic kidney disease, 426, 427f in nephrotic syndrome, 402, 402f

Pituitary adenoma (microadenoma) Cushing syndrome rom, 1164t, 1165, 1165f, 1169-1170, 1170f (See also Cushing syndrome) somatotrope, acromegaly rom, 1160-1162 (See also Acromegaly) thyrotropin-secreting, vs. hyperthyroidism, 1156 Pityriasis alba with atopic dermatitis, 685 vs. tinea versicolor, 665 Pityriasis lichenoides chronica, 946, 946f vs. pityriasis lichenoides et varioli ormis acuta, 946 Pityriasis lichenoides et varioli ormis acuta, 925f, 926, 945-946, 945f, 946f vs. erythema multi orme, 946 vs. lymphomatoid papulosis, 946 vs. pityriasis lichenoides chronica, 946, 946f vs. varicella, 946 Pityriasis rosea, 745-749 diagnosis o , 745f-748f, 746 di erential diagnosis o vs. cutaneous drug reactions, 1031 vs. eczema, nummular, 748 vs. erythema annulare centri ugum, 1046 vs. granuloma annulare, 857 vs. lichen planus, 754 vs. psoriasis, 738 vs. psoriasis, guttate, 748 vs. syphilis, 748, 1107 vs. tinea corporis, 748 vs. tinea versicolor, 665, 748 epidemiology o , 745 etiology and pathophysiology o , 745-746 ollow-up o , 749 undamentals o , 745 management o , 748 patient education on, 748 patient story o , 745, 745f Pityriasis rubra pilaris, erythroderma with, 761, 762t Pityriasis versicolor, 664-666. See also Tinea versicolor Pityrosporum, 638-642, 664, 665f, 666f. See also Fungal in ections pathophysiology o , 638, 639f seborrhea rom, 638, 664, 724, 771, 774t tinea versicolor rom, 638, 639f Pityrosporum olliculitis, 568, 569f, 666, 666f vs. tinea versicolor, 666, 666f Pityrosporum orbiculare, 664 Pityrosporum ovale, 664 PKD1/ PKD2 gene mutation, 406 Plane warts, 623-625. See also Warts, lat Plane xanthomas, 1130 Plantar hyperlinearity, with atopic dermatitis, 685 Plantar warts, 633-636. See also Warts, plantar Plaque, coronary, 212 Plasmodium falciparum, 38-39, 38f Plasmodium malariae, 38-39, 38f Plasmodium ovale, 38-39 Plasmodium vivax, 38-39

1295

1296

INDEX Pleural e usion, 286-289 complications o , 288-289, 288f diagnosis o , 286-288, 287f, 287t di erential diagnosis o vs. pericardial e usion, 230, 230f transudative vs. exudative e usions in, 287-288, 287t etiology and pathophysiology o , 286 ollow-up o , 289 undamentals o , 286 in heart ailure, 210f management o , 288, 288f patient education on, 289 patient story o , 286, 286f in pericarditis, 228, 230 Pleural luid, 286 Pleural space, 286 Pleurisy, vs. pericarditis, 230 Plumber’s itch, 680-682, 680f, 681f Pneumatosis, 362, 362f Pneumococcal vaccine, allergic reaction to, 582, 582f Pneumocystis carinii pneumonia, pneumothorax in, 296 Pneumonia cryptogenic organizing, vs. pulmonary ibrosis, 308 de inition o , 290 di erential diagnosis o vs. asthma, 264 vs. chronic obstructive pulmonary disease, 272 vs. heart ailure, 210 vs. lung cancer, 281 vs. pancreatitis, 374 vs. pulmonary embolus, 302 vs. tuberculosis, 319 health care–associated, 290-295 (See also Pneumonia, community-acquired) idiopathic interstitial, 306-309 (See also Pulmonary ibrosis) interstitial, 306-309 (See also Pulmonary ibrosis) Pneumonia, community-acquired, 290-295 diagnosis o , 290f-293f, 291 di erential diagnosis o vs. asthma, 292 vs. pulmonary embolus, 292 vs. upper respiratory illnesses, 292 epidemiology, etiology and pathophysiology o , 290 undamentals o , 290 management o , 292-294 patient education on, 295 patient story o , 290, 290f prevention o , 294 prognosis and ollow-up o , 294 risk actors or, 290-291 Pneumonia Severity Index, 292-293 Pneumonitis, chronic hypersensitivity, vs. pulmonary ibrosis, 307 Pneumococcal polysaccharide vaccine, 294 Pneumothorax, 296-298 de inition o , 296

diagnosis and clinical indings in, 297, 297f di erential diagnosis o vs. coronary artery disease, 213 vs. pulmonary embolus, 302 vs. thoracic aortic aneurysm, 189 epidemiology, etiology and pathophysiology o , 296, 297f management o , 297-298 patient education on, 298 patient story o , 296, 296f prognosis and clinical course o , 298 risk actors or, 297 tension, 296 Podagra, 505, 505f Poikiloderma, 911, 911f Poikiloderma atrophicans vasculare, vs. erythema ab igne, 1014-1015 Poisoning, on mortality, 15 Poison ivy/ oak, contact dermatitis rom, 691, 692, 693f, 694, 697, 926, 926f. See also Contact dermatitis POLST (physician orders or li e-sustaining treatment) Paradigm task orce, 17 Polyarticular gout vs. osteoarthritis, 479 vs. rheumatoid arthritis, 484 Polyarticular in lammatory arthritis, 473 Polyarticular nonin lammatory arthritis, 473 Polycystic kidneys, 406-408 diagnosis o , 406-407, 406f di erential diagnosis o vs. acquired cystic disease, 407 vs. simple cyst, 407 vs. tuberous sclerosis, 407 epidemiology, etiology and pathophysiology o , 406, 406f undamentals o , 406 management o , 407 patient education on, 408 patient story o , 406, 406f prognosis and ollow-up o , 408 Polycystic ovary syndrome, vs. obesity, 1137 Polymorphous light eruption, 1006-1011, 1006f. See also Photosensitivity vs. dermatomyositis, 912 Polymyalgia rheumatica, 533-536 diagnosis and screening or, 534-535 di erential diagnosis o vs. arthritis, 476 vs. dermatomyositis and polymyositis, 535 vs. ibroma, 535 vs. lupus and other vasculitides, 535 vs. osteoarthritis, 479, 535 vs. rheumatoid arthritis, 484 vs. shoulder disease, 535 epidemiology o , 533 etiology and pathophysiology o , 534 undamentals o , 533, 533f management o , 535-536 patient education on, 536 patient story o , 533, 533f prognosis and ollow-up o , 536 risk actors or, 534

Polymyositis vs. dermatomyositis, 912 vs. polymyalgia rheumatica, 535 Polyp colon, 335-338 (See also Colon polyps) vs. colon cancer, 331 laryngeal, 149-153, 152f (See also Hoarseness) nasal, 130-131, 130f, 131f vocal cord, 149-153 (See also Vocal cord nodules and polyps) Pompholyx, 699-705, 700f, 702f, 704t. See also Eczema, hand Pork tapeworm, 1080-1083. See also Intestinal worms and parasites Porokeratosis, vs. corns and calluses, 1052 Porphyria cutanea tarda, 925f, 926, 942-943, 942f di erential diagnosis o vs. dermatitis herpeti ormis, 948, 948f vs. dermatomyositis, 943 vs. eczema, dyshidrotic, 943 vs. epidermolysis bullosa, 943, 944 vs. erythema multi orme bullosum, 943 vs. pemphigus, 938 vs. photodermatitis, 1009 vs. systemic sclerosis, 943 etiology and pathophysiology o , 942 Port-wine stains, 1020-1023, 1020f. See also Vascular lesions, hereditary and congenital di erential diagnosis o , 1021 in Klippel-Trenaunay syndrome, 1020, 1021 in Sturge-Weber syndrome, 1020, 1021 Postburn blistering, 926, 926f Postcholecystectomy syndrome, 347 Postexposure prophylaxis against HIV, a ter sexual assault, 57 Postherpetic neuralgia, 596-599 etiology and pathophysiology o , 597 management o , 598, 599t prevention o , 599 risk actors or, 597 Postin lammatory hypopigmentation, 1002-1003, 1003f Postpartum thyroiditis, vs. hypothyroidism, 1150 Posttraumatic stress disorder a ter intimate partner violence, 52, 53 a ter sexual assault, 56, 58 Pott disease, rom tuberculosis, 318, 318f Pott’s pu y tumor, rom sinusitis, 134, 135f Prader-Willi syndrome, obesity in, 1137 Preauricular tags, 126-128 diagnosis o , 126-127, 127f di erential diagnosis o vs. basal cell carcinoma, 128, 128f vs. cysts, 128, 128f epidemiology, etiology and pathophysiology o , 126 management o , 128, 128f Preexcitation syndrome, rate control in, 199-200, 200t Preger, Jack, 30, 30f Pregnancy ectopic, vs. diverticulitis, 342

INDEX hydronephrosis in, 395 mask o , 996-998 (See also Melasma) rom rape, 57, 58 tubal, 454 Pregnancy tumor, vs. gingival overgrowth, 167, 167f Presbyphonia, 149-153 diagnosis o , 150-151 di erential diagnosis o , 151 etiology and pathophysiology o , 150 ollow-up o , 152-153 management o , 152 patient education on, 153 Pressure natriuresis, 416 Pretibial myxedema, in hyperthyroidism, 1155, 1155f, 1156f Prickly heat (miliaria), 926 vs. olliculitis, 569-570 Primary acquired melanosis, 68-70, 69f Primary biliary cirrhosis, 366. See also Liver disease Procainamide, 200 Progestin-only oral contraceptive pills, 11t Prostate cancer, 410-413 diagnosis o , 411-412 di erential diagnosis o vs. atypical glands on biopsy, 412 vs. benign prostatic hyperplasia, 412 vs. prostatic intraepithelial neoplasia, 412 vs. prostatitis, 412 epidemiology o , 410, 410f, 411f etiology and pathophysiology o , 410-411, 411f, 412f undamentals o , 410 management o , 412-413, 413f patient education on, 413 patient story o , 410, 410f prevention o , 413 prognosis in, 413 risk actors or, 411 Prostatectomy, or prostate cancer, 412 Prostate zones, 410, 411f Prostatic intraepithelial neoplasia, vs. prostate cancer, 412 Prostatitis vs. kidney stones, 400 vs. prostate cancer, 412 Prosthetic valve endocarditis, 220-223. See also Endocarditis, bacterial Proteus olliculitis, 568 Proteus syndrome, vs. neuro ibromatosis, 1193 Protozoa, 1080-1083, 1080f, 1082f. See also Intestinal worms and parasites Proxy designations, 17 Prurigo nodularis, 710-715 diagnosis o , 712f, 713-714, 713f di erential diagnosis o , 714 vs. lichen planus, 755 vs. methamphetamine abuse, 1226 epidemiology o , 711, 712f, 713f etiology and pathophysiology o , 711-713 ollow-up o , 715 management o , 714 patient education on, 714

Pruritic urticarial papules and plaques o pregnancy, vs. urticaria, 719, 720f PSA screening, 411 Pseudoarthrosis o clavicle, vs. clavicle racture, 512 Pseudoclaudication, vs. peripheral arterial disease, 235 Pseudocysts, pancreatic, 375, 375f Pseudo olliculitis, 554-557 diagnosis o , 554-555, 554f-556f di erential diagnosis o vs. acne vulgaris, 556 vs. olliculitis, 556 vs. impetigo, 556 epidemiology o , 554, 555f, 556f, 566, 567f etiology and pathophysiology o , 554-555 undamentals o , 554 management o , 556-557, 556f, 557f patient education on, 557 prevention o , 557 prognosis and ollow-up o , 557 risk actors or, 555 Pseudo olliculitis barbae, 554-557, 567f, 568. See also Pseudo olliculitis vs. sarcoidosis, 870 Pseudo olliculitis pubis, 554-557. See also Pseudo olliculitis Pseudogout vs. bunion de ormity, 1055 vs. gout, 506 vs. hammer toe, 1058 vs. knee injuries, 528 vs. Lyme disease, 1088 vs. olecranon bursitis, 509 vs. osteomyelitis, 1100 Pseudo-Hutchinson sign, 971, 972, 973f Pseudo-Jones racture, 519-520, 519f, 520f Pseudomembranous colitis, 326-329. See also Clostridium difficile Pseudomonas aeruginosa olliculitis, 566, 566f, 568 nail in ection, vs. onychomycosis, 981, 982f osteomyelitis, 1096-1101 (See also Osteomyelitis) otitis externa, 119, 119f, 120 paronychia, 985-988, 985f, 986f Pseudopapilledema, 97 Pseudosarcomatous dermato ibrosarcoma, vs. dermato ibroma, 779 Pseudotumor cerebri, 96-98. See also Papilledema Pseudotumor o eye, vs. hyperthyroidism, 1156 Pseudoxanthoma elasticum, vs. xanthomas, 1131 Psoralens, phototoxic reactions to, 1006-1011, 1007f. See also Photosensitivity Psoriasis, 729-743 with diabetes mellitus, 740 diagnosis o , 730-737 categories, AAE, 730 erythrodermic, 734-735, 736f guttate, 733, 734f imaging in, 736f, 737 inverse, 729f, 731f, 733-734, 735f laboratory studies in, 737, 737f

nail, 2, 3f, 731f, 736 palmar-plantar, 734, 735f plaque, 729f, 730-732, 730f, 732f-734f psoriatic arthritis, 732f, 736-737, 736f pustular, 735, 735f, 736f scalp, 730f, 733 severity in, disease, 737, 737f di erential diagnosis o vs. atopic dermatitis, 687 vs. candidiasis, cutaneous, 738 vs. cutaneous T-cell lymphoma, 737-738 vs. eczema, hand, 702 vs. eczema, nummular, 708, 738 vs. erythema annulare centri ugum, 1046 vs. erythrasma, 577 vs. geographic tongue, 160, 160f vs. lichen planus, 738, 753, 755 vs. lichen simplex chronicus, 738 vs. lupus erythematosus, 905 vs. pityriasis rosea, 738, 748 vs. reactive arthritis, 738 vs. seborrheic dermatitis, 725-726, 738 vs. syphilis, 738 vs. tinea corporis, 650, 652f, 734f, 738 vs. tinea cruris, 734f, 738 vs. tinea pedis, 660, 661f distribution o , 730, 732t epidemiology o , 729 erythroderma with, 761, 761f-763f, 762t etiology and pathophysiology o , 729 ollow-up o , 742 undamentals o , 729 inverse (See Inverse psoriasis; Psoriasis) management o , 738-742 biologic agents in, 741, 741t general, 738 methotrexate vs. biologic agents in, 741-742 phototherapy in, 739 systemic, 734f, 737f, 739-741, 740t topical treatments in, 731f, 738-739, 739f, 739t topic vehicle choice in, 738 by type erythrodermic/ generalized, 736f, 742 guttate, 734f, 742 inverse, 731f, 742 palmar-plantar, 742 plaque, 740t, 742 pustular, 737f, 742 scalp, 742 with obesity, 1136, 1136f patient education on, 742, 743t patient story o , 729, 729f prognosis in, 742 risk actors or, 729, 730t Psoriatic arthritis, 486-490 complications and ollow-up o , 490 diagnosis o , 473, 474f, 475f, 487-488, 487f-489f, 736f typical distribution in, 732t, 736-737 di erential diagnosis o , 477t vs. reactive arthritis, 759

1297

1298

INDEX Psoriatic arthritis (Cont.): epidemiology, etiology and pathophysiology o , 472, 487 undamentals o , 486 management o , 488-490, 489f patient education on, 490 patient story o , 472, 472f, 486, 486f prognosis and clinical course o , 490, 490f swan-neck de ormities in, 493f types o arthritis mutilans, 475f, 488, 488f asymmetric, 488, 488f distal interphalangeal predominant, 488, 488f spondylitis, 488 symmetric, 488, 489f Psoriatic nails, 488, 488f, 989-992 diagnosis o , 989f-991f, 990 di erential diagnosis o vs. alopecia areata, 991 vs. Darier disease, 991, 991f vs. onychomycosis, 981, 991 epidemiology o , 989, 989f etiology and pathophysiology o , 989-990, 989f undamentals o , 989-992 management o , 991-992 patient education on, 992 patient story o , 989, 989f prevention o , 992 prognosis and ollow-up o , 992 risk actors or, 990 Psoriatic spondyloarthritis, vs. ankylosing spondylitis, 493, 493f P-SPIKES approach, 16 Psychocutaneous disorders, 710-715 diagnosis o , 710f-713f, 713-714 di erential diagnosis o vs. acne keloidalis nuchae, 714 vs. atopic dermatitis, 714 vs. contact dermatitis, 714 vs. eczema, nummular, 714 vs. parasitosis, delusions o , 714 vs. scabies, 714 epidemiology o , 710f-713f, 711 etiology and pathophysiology o , 711-713 ollow-up o , 715 undamentals o , 711 management o , 714 patient education on, 710f, 714 patient story o , 710, 710f Psychotherapeutic drug abuse, 1197 Pterygium, 62-64 de inition o , 62 diagnosis o , 62-63, 62f, 63f di erential diagnosis o vs. conjunctivitis, 63 vs. pinguecula, 63, 63f vs. squamous cell carcinoma o conjunctiva, 63 epidemiology o , 62 etiology and pathophysiology o , 62 management o , 63, 63f nasal, 62, 62f, 64f

patient education on, 64 patient story o , 62, 62f prevention o , 63, 64f prognosis and ollow-up in, 64 red eye in, 109, 110f risk actors or, 62 Pubic lice, 668-672, 669f, 670f Pu iness, myxedema in hypothyroidism, 1149, 1150f Pulmonary disease. See also specific types death rom, 15 vs. pancreatitis, 374 Pulmonary embolus, 299-304 de inition o , 299 diagnosis o , 300-302 clinical eatures in, 300 history and physical exam in, 300, 300f imaging in, 299f-302f, 301-302 laboratory studies and ECG in, 300-301, 300f di erential diagnosis o vs. community-acquired pneumonia, 292 vs. heart ailure, 302 vs. pneumonia, 302 vs. pneumothorax, 302 vs. thoracic aortic aneurysm, 189 epidemiology o , 299 etiology and pathophysiology o , 299, 299f ollow-up or, 303 management o , 302-303 patient education on, 303-304 patient story o , 299, 299f prevention o , 303 prognosis in, 303 risk actors or, 299-300 Pulmonary ibrosis, 306-309 diagnosis o , 306-307, 306f, 307f di erential diagnosis o vs. acute interstitial pneumonia, 307 vs. alveolar hemorrhage syndromes, 307 vs. chronic hypersensitivity pneumonitis, 307 vs. collagen vascular disease, 307 vs. cryptogenic organizing pneumonia, 308 vs. drug toxicity, 307 vs. hypersensitivity pneumonitis, 307 vs. occupational lung disease, 307 epidemiology and risk actors or, 306 ollow-up o , 308-309 undamentals o , 306 management o , 308 patient story o , 306, 306f prognosis in, 308 Pulmonary unction tests abbreviations or, 261t or asthma, 261f, 262t, 263, 263f, 264f patient story o , 260, 261f Pulmonary hypertension in chronic obstructive pulmonary disease, 270, 271, 274 with pulmonary embolus, 301f, 303 Pulsus paradoxus, 262 Puncture wound, neuropathic ulcer rom, 1064 Purpura, vs. Kaposi sarcoma, 1074

Pyelonephritis diagnosis o , 431 di erential diagnosis o vs. ankylosing spondylitis, 493 vs. diverticulitis, 341 vs. hydronephrosis, 396 management o , 431 white blood cell casts in, 429, 430f Pyloric ulcers, 377-380. See also Peptic ulcer disease Pyoderma aciale, 551, 552f vs. acne vulgaris, 542, 544f Pyoderma gangrenosum, 861-865 diagnosis o , 861f-863f, 862-864 di erential diagnosis o vs. acute ebrile neutrophilic dermatosis, 864, 864f vs. black recluse spider bite, 864 di iculties in, 864 vs. ecthyma, 864 vs. mycosis ungoides, 864 vs. spider bites, 864 vs. sporotrichosis, 864, 864f vs. squamous cell carcinoma, 864 vs. STDS, ulcerative, 864 vs. vasculitis, systemic, 864 vs. venous insu iciency ulcers, 864, 865f epidemiology o , 861 etiology and pathophysiology o , 861, 861f ollow-up o , 865 undamentals o , 861 management o , 865 patient education on, 865 patient story o , 861, 861f prognosis in, 865 risk actors or, 861-862 Pyogenic granuloma, 782-785 diagnosis o , 782-783, 782f, 783f di erential diagnosis o vs. amelanotic melanoma, 783-784, 784f vs. bacillary angiomatosis, 784, 1074f vs. cherry hemangioma, 784, 784f vs. ibrous papule o nose, 784, 784f vs. gingival overgrowth, 167, 167f vs. melanoma, 849, 849f vs. nasal polyps, 131 epidemiology, etiology and pathophysiology o , 782 undamentals o , 782 on gums, 167, 167f management o , 784 patient education and ollow-up o , 784 patient story o , 782, 782f prognosis in, 784 risk actors or, 782 Pyomyositis, vs. necrotizing asciitis, 590 Pyostomatitis vegetans, 863 Pyuria, 429-431, 430f. See also Urinary sediment R Racial melanosis, eye, 68-70, 68f Radicular syndrome, 495 Radiculoneuropathy, vs. Lyme disease, 1088

INDEX Radius racture, distal, 514-518 classi ication o , 515-516, 515f, 516f, 517t diagnosis o , 514f-516f, 515-516 di erential diagnosis o vs. de Quervain tenosynovitis, 516 vs. scaphoid racture, 516 epidemiology o , 514 etiology and pathophysiology o , 514 ollow-up o , 518 undamentals o , 514 management o , 516-517, 517f, 517t, 518f patient education on, 518 patient story o , 514, 514f prevention o , 517 prognosis o , 517 risk actors or, 515 Ramsay Hunt syndrome, 597, 597f Ram’s horn nail, 964-968, 965f, 979f, 980f. See also Onychogryphosis Raspiness, 149-153. See also Hoarseness Rate control drugs, 196-200, 200t Rivaroxaban, 203-204, 204t Raynaud phenomenon, 916, 917f peripheral arterial disease with, 232 Razor bumps, 554-557, 567f, 568. See also Pseudo olliculitis Reactive arthritis, 757-760 with conjunctivitis, 757-760, 758f diagnosis o , 757f-759f, 758-759 di erential diagnosis o vs. geographic tongue, 160 vs. gonococcal arthritis, 759 vs. knee injuries, 527-528 vs. Lyme disease, 1088 vs. osteoarthritis, 479 vs. psoriasis, 738 vs. psoriatic arthritis, 759 vs. reactive arthropathies, 759 vs. rheumatoid arthritis, 484, 759 vs. spondyloarthropathies, 759 epidemiology o , 758 etiology and pathophysiology o , 758 Chlamydia in, 454 undamentals o , 757 management o , 760 patient education on, 760 patient story o , 757, 757f, 758f prognosis and ollow-up o , 760 risk actors or, 758 Reactive arthropathy, vs. reactive arthritis, 759 Reactive in lammation in HIV, vs. cutaneous T-cell lymphoma, 877 Rectal in ection, vs. hemorrhoids, 359, 360f Rectal prolapse, vs. hemorrhoids, 359 Recurrent aphthous ulcer, 169-173. See also Aphthous ulcer Recurrent respiratory papillomatosis, 149-153 diagnosis o , 150-151, 151f, 152f di erential diagnosis o , 151 epidemiology o , 149 etiology and pathophysiology o , 150 ollow-up o , 152-153 management o , 152

maternal HPV in ection and juvenile onset o , 149 patient education on, 153 Red blood cell casts, 429-431, 429f, 430f. See also Urinary sediment Red eye, 106-110, 107t di erential diagnosis o , 106-110, 106f-110f, 107t acute-angle closure glaucoma, 82, 85 conjunctivitis, 82, 85 corneal ulceration, 82, 85 episcleritis, 80-83, 85 iritis, 82 keratitis, 82, 85 scleritis, 80-83, 85 uveitis, 82 epidemiology, etiology and pathophysiology o , 106 undamentals o , 106, 107t management o , 85-86, 86f, 110 patient education on, 110 patient story o , 106, 106f prognosis and ollow-up o , 110 Re erred otalgia, vs. otitis media, 115 Re ugees, 23-24, 23f Relapsing polychondritis episcleritis with, 82, 82f scleritis with, 82, 82f vasculitis in, 891 Relative risk reduction (RRR), 1242 Renal artery stenosis, hypertension rom, 225, 226, 226f, 415-420. See also Hypertension, renovascular Renal calculus, 398-401. See also Kidney stones Renal cell carcinoma, 421-424 de inition o , 421 diagnosis o , 421-422, 421f, 422f di erential diagnosis o , 423 epidemiology, etiology and pathophysiology o , 421 ollow-up and prognosis in, 424 management o , 423-424 patient education on, 424 patient story o , 421, 421f risk actors or, 421 stages o , 423t Renal disease end-stage death rom, 15-16 incidence o , 426 parenchymal, vs. renovascular hypertension, 419 Renal stone, 398-401. See also Kidney stones Renin-angiotensin-aldosterone system, in renovascular hypertension, 416 Renovascular disease, 415-420. See also Hypertension, renovascular Renovascular hypertension, 415-420. See also Hypertension, renovascular Respect, or patient, 7 Retinal hemorrhages, in hypertensive retinopathy, 93, 93f, 94, 94f Retinal necrosis, rom zoster ophthalmicus, 603 Retinal pigment epithelial injury, 99

Retinoblastoma, vs. hyphema, 105 Retinopathy, diabetic, 90-92, 90f-92f, 226f vs. age-related macular degeneration, 100 vs. HIV retinopathy, 91 vs. hypertensive retinopathy, 91 Retinopathy, hypertensive, 93-95, 226, 226f diagnosis o , 93-94 di erential diagnosis o , 94 vs. diabetic retinopathy, 91 epidemiology, etiology and pathophysiology o , 93, 93f, 94f undamentals o , 93 management o , 94-95 patient education on, 95 patient story o , 93, 93f prevention o , 95 prognosis and ollow-up o , 95 Revascularization therapy, or peripheral arterial disease, 236, 236f, 237f Reverse Colles racture, 515, 515f, 516f, 517f Rheumatoid arthritis, 482-485 diagnosis o , 473, 473f, 474f, 476, 482f-484f, 483 nodules in, 473, 474f, 483, 483f di erential diagnosis o vs. ankylosing spondylitis, 477t vs. arthritis, other, 477t vs. bunion de ormity, 1055 vs. connective tissue disorders, 484 vs. Dupuytren disease, 531 vs. endocarditis, in ectious, 484 vs. ibromyalgia, 484 vs. gout, 506 vs. hammer toe, 1058 vs. hemochromatosis, 484 vs. knee injuries, 528 vs. Lyme disease, 1088 vs. olecranon bursitis, 509 vs. osteoarthritis, 479, 480f vs. polyarticular gout, 484 vs. polymyalgia rheumatica, 484, 535 vs. reactive arthritis, 484, 759 vs. seronegative spondyloarthropathies, 484 epidemiology o , 482 etiology and pathophysiology o , 472, 482 undamentals o , 482 management o , 484-485 patient education on, 485 patient story o , 482, 482f prognosis and ollow-up o , 485 risk actors or, 483 scleritis with, 80-83 vasculitis in, 891 Rheumatoid nodules vs. granuloma annulare, 857 vs. sarcoidosis, 870 Rhinocerebral mucormycosis, sinusitis rom, 133, 134f Rhinophyma, 549, 549f, 550, 552. See also Rosacea Rhinophymatous rosacea, 549, 549f, 550, 552. See also Rosacea Rhinosinusitis, 133-137 Rhinovirus sinusitis, 133

1299

1300

INDEX Rhus dermatitis, 691, 692, 693f, 694, 697, 926, 926f. See also Contact dermatitis Rhythm control, in atrial ibrillation, 199-201, 200t, 201t Ring, vaginal, 11t hormonal, 10, 10f, 12 Ringworm. See also Tinea vs. erythrasma, 577 Rivaroxaban, 203-204, 204t Robotic-assisted laparoscopic radical prostatectomy, 413, 413f Rockerbottom oot de ormity, 1065-1067, 1066f. See also Charcot arthropathy Rocky Mountain spotted ever vs. Lyme disease, 1087 vs. vasculitis, 895, 896f Rosacea, 548-553 diagnosis o , 548f-551f, 550 di erential diagnosis o vs. acne vulgaris, 542, 544f, 551 vs. dermatomyositis, 912 vs. lupus erythematosus, 905 vs. perioral dermatitis, 551, 552f vs. pyoderma aciale, 551, 552f vs. sarcoidosis, 551 vs. seborrheic dermatitis, 551, 726 vs. steroid-induced acnei orm eruptions, 551, 552f vs. systemic lupus erythematosus, 551, 551f, 905 epidemiology o , 548-549, 549f etiology and pathophysiology o , 549, 549f ollow-up or, 553 undamentals o , 548 management o , 551-552, 551f ocular, 550-551, 550f, 551f, 552 red eye in, 107t, 109, 109f patient education on, 553 patient story o , 548, 548f risk actors or, 549 sebaceous hyperplasia with, 777f Rosacea ulminans, 551, 552f vs. acne vulgaris, 542, 544f Rotator cu lesions, vs. polymyalgia rheumatica, 535 Roth spots, 220, 220f, 221, 221f, 222 Roundworm, 1080-1083, 1081f. See also Intestinal worms and parasites Rubber allergens, in hand eczema, 701, 703t S SAFE Kit, 56 Sa ety plan, 52 Salivary gland tumors, 178, 179f Salmonella typhi, 33-34 Salmon patch, 1022f vs. vascular lesions, 1022, 1022f Salmon spot, in psoriatic nails, 989, 989f, 990f Samitz sign, 910, 910f Sanitation, in world health, 33, 33f Sarcoid, nodular, vs. erythema nodosum, 888 Sarcoidosis, 310-314, 867-872 annular (circinate), 867f, 868, 870, 871f diagnosis o , 310-314, 867f-869f, 868-870

cardiac mani estations in, 312 clinical eatures in, 310, 311f diagnostic criteria in, 310 eye mani estations in, 311, 312f gastrointestinal mani estations in, 311 imaging in, 313-314 laboratory and selected studies in, 312-313, 313f musculoskeletal mani estations in, 312, 313f neurologic mani estations in, 311-312 pulmonary mani estations in, 310-311 skin mani estations in, 311, 311f, 312f di erential diagnosis o , 314 vs. acne keloidalis nuchae, 870 vs. carcinoma, metastatic, 871 vs. epidermal inclusion cyst, 871 vs. erythema annulare centri ugum, 1047 vs. erythema nodosum, 888 vs. oreign-body granuloma, 871 vs. granuloma annulare, 870, 870f vs. granulomatous rosacea, 870 vs. lichen planus, 870 vs. lipoma, 871 vs. lupus erythematosus, 905 vs. lupus vulgaris, 870 vs. morphea, 870 vs. mycosis ungoides, granulomatous, 870 vs. necrobiosis lipoidica, 870, 1127 vs. pseudo olliculitis barbae, 870 vs. rheumatoid nodules, 870 vs. rosacea, 551 vs. scarring alopecia, scalp, 961 vs. syringoma, 870 vs. tuberculosis, 320 vs. xanthelasma, 870 epidemiology o , 310, 867-868, 867f erythema nodosum in, 886-889, 886f (See also Erythema nodosum) etiology and pathophysiology o , 310, 868 ollow-up o , 314, 872 undamentals o , 314, 867 granulomas, 868, 869f, 870, 870f lupus pernio, 867f, 868, 868f, 871, 871f, 872, 872f maculopapular, 868, 868f management o , 314, 871-872, 871f, 872f nodular cutaneous and subcutaneous, 868, 869f patient education on, 314, 872 patient story o , 310, 310f, 867, 867f plaque, 867f, 868, 869f-871f prevention and screening or, 872 prognosis and complications o , 314, 872 risk actors or, 314, 868 Sausage digit, 487, 487f Scabies, 673-678 bullous presentation o , 927 diagnosis o , 673f-675f, 674-676 di erential diagnosis o vs. arthropod bites, 677 vs. atopic dermatitis, 676-677, 688 vs. bedbugs, 677, 677f vs. contact dermatitis, 677, 696

vs. dermatitis herpeti ormis, 947-948 vs. herpes zoster, 598 vs. impetigo, 563, 677 vs. lice, 671 vs. methamphetamine abuse, 1226 vs. molluscum contagiosum, 615 vs. psychocutaneous disorders, 714 vs. seborrheic dermatitis, 677 vs. tinea, 677, 677f epidemiology o , 673-674 etiology and pathophysiology o , 673f-675f, 674 ollow-up and patient education on, 678 as global health problem, 42, 42f management o , 678 patient story o , 673, 673f prevention o , 678 prognosis in, 678 risk actors or, 674 Scaphoid racture, vs. distal radius racture, 516 Scar vs. basal cell carcinoma, 829 rom cocaine, skin popping, 1229, 1230f vs. diabetic dermopathy, 1123 Scar, hypertrophic cortisone injection o , 1247f, 1247t di erential diagnosis o vs. corns and calluses, 1052 vs. dermato ibroma, 779 vs. keloids, 1035 Scarlatini orm rash, 143, 143f Scarlet ever, rash in, 143, 143f Scarring alopecia, 958-962. See also Alopecia, scarring Schamberg disease vs. diabetic dermopathy, 1123 vs. vasculitis, 894-895, 895f Schamroth sign, 207, 207f Schechtman, Andrew, 23-24, 23f Schistosomiasis, 35 Schizophrenia, vs. substance abuse disorder, 1199 Scleral nevus, 68-70, 68f Scleral pigmentation, 68-70, 68f Scleritis, 80-83 with autoimmune diseases, 80, 80f, 81f diagnosis o , 80f, 81-82, 81f di erential diagnosis o vs. conjunctivitis, 76, 82 vs. corneal ulceration, 82 vs. glaucoma, acute-angle closure, 82 vs. iritis, 82, 85 vs. keratitis, 82 vs. uveitis, 82, 85 epidemiology o , 80 etiology and pathophysiology o , 80, 80f undamentals o , 80 management o , 82 patient education on, 83 patient story o , 80, 80f prognosis and ollow-up or, 82 red eye in, 106-110, 107t, 108, 108f with relapsing polychondritis, 82, 82f Scleroderma, 916-921 diagnosis o , 917f-920f, 919-920

INDEX di erential diagnosis o vs. amyloidosis o skin, 920 vs. discoid lupus erythematosus, 920 vs. lichen sclerosis, 920 vs. lupus erythematosus, 905 vs. mycosis ungoides, 920 vs. myxedema, 920 vs. osteoarthritis, 479 vs. rheumatoid arthritis, 484 vs. systemic lupus erythematosus, 920 vs. systemic sclerosis–associated diseases, 920 epidemiology o , 916 etiology and pathophysiology o , 916-919, 916f-919f undamentals o , 916 management o , 920-921 patient education on, 921 prognosis and ollow-up o , 921 Sclerodermatomyositis, 912 Scro ula, 45, 45f Scro uloderma, rom tuberculosis, 318, 318f Scrotum, angiokeratosis o , 1016-1019, 1016f. See also Vascular skin lesions, acquired Scurvy, vs. vasculitis, 896, 897f Sebaceous cell carcinoma, vs. hordeolum and chalazion, 66 Sebaceous hyperplasia, 775-777 diagnosis o , 775-776, 775f, 776f di erential diagnosis o vs. basal cell carcinoma, nodular, 776, 776f, 777f, 829, 832f vs. ibrous papule o ace, 776 vs. milia, 777, 777f vs. molluscum contagiosum, 777 vs. syringoma, 777, 777f vs. xanthoma, 777 epidemiology, etiology and pathophysiology o , 775 undamentals o , 775 management o , 777, 777f patient story o , 775, 775f risk actors or, 775 with rosacea, 777f Seborrhea (seborrheic dermatitis), 723-727 diagnosis o , 723f-726f, 724-725 di erential diagnosis o vs. atopic dermatitis, 687 vs. candidiasis, 646, 726 vs. Darier disease, 1041 vs. dermatitis, contact, 726 vs. dermatitis, perioral, 726 vs. otitis externa rom, 120f, 121 vs. psoriasis, 725-726, 738 vs. rosacea, 551, 726 vs. scabies, 677 vs. scarring alopecia, 961 vs. syphilis, 726 vs. systemic lupus erythematosus, 726 vs. tinea capitis, 726 vs. tinea versicolor, 726 epidemiology o , 723 erythroderma with, 761, 762t, 764f etiology and pathophysiology o , 724 Pityrosporum in, 638, 639f, 664, 771, 774t

ollow-up o , 727 undamentals o , 723 management o , 726-727 patient education on, 727 patient story o , 723, 723f risk actors or, 724 o scalp (dandru ), 723-727 Seborrheic eczema, 723-727. See also Seborrhea (seborrheic dermatitis) Seborrheic keratosis, 770-774 diagnosis o , 770-773, 770f-773f di erential diagnosis o vs. acanthosis nigricans, 1120 vs. actinic keratosis, 773, 809 vs. basal cell carcinoma, 773, 774f vs. Bowen disease, 809 vs. dermato ibroma, 779 vs. genital warts, 629, 630f vs. lentigo maligna, 818-819 vs. malignant melanoma, 773 vs. melanoma, 772f, 773, 773f, 844f, 849 vs. nevus, benign, 790 vs. Paget disease o breast, 469, 469f vs. solar lentigo, 772f, 773 vs. warts, 773 vs. warts, common, 619 vs. warts, lat, 624 epidemiology o , 770 etiology and pathophysiology o , 770, 771f ollow-up and patient education on, 774 undamentals o , 770 management o , 773 patient story o , 770, 770f Secondary acquired melanosis, 70 Secondhand smoke, 1202, 1204f Sedative abuse, 1197 Sediment, urinary, 429-431. See also Urinary sediment Segmental neuro ibromatosis, vs. neuro ibromatosis, 1193 Sel -disclosure, 8 Sel -healing squamous epithelioma, 813-815. See also Keratoacanthoma Sel -in licted dermatoses, 710-715. See also Psychocutaneous disorders Senile vaginitis, 437-439. See also Atrophic vaginitis Senses, in diagnosis, 2 Sepsis, brain, vs. subdural hematoma, 1183 Septic arthritis diagnosis o , 474, 475f, 476 di erential diagnosis o vs. gout, 506 vs. knee injuries, 528, 528f etiology and pathophysiology o , 472 hospitalization or, 477 Septic joint vs. bunion de ormity, 1055 vs. hammer toe, 1058 Seronegative spondyloarthropathies di erential diagnosis o vs. osteoarthritis, 479 vs. rheumatoid arthritis, 484 scleritis and episcleritis with, 80, 82

Serratia marcescens osteomyelitis, 1096-1101. See also Osteomyelitis Seven-year itch, 673-678. See also Scabies Sexual abstinence, periodic, 11t Sexual abuse, noncontact, 55 Sexual assault, adult, 55-58 de inition o , 55 diagnosis o , 55, 55f, 56, 56f epidemiology o , 55-56 etiology and pathophysiology o , 56 ollow-up or, 58 by intimate partners, 50, 52 management o , 56-57 patient education on, 58 patient stories o , 55, 55f prevention o , 57-58 prognosis in, 58 Sexually transmitted in ections di erential diagnosis o vs. atrophic vaginitis, 438 vs. pyoderma gangrenosum, 864 on mortality, 15 a ter sexual assault, 56, 57 Sexual violence, 55 Sézary syndrome, 873-878. See also Cutaneous T-cell lymphoma Shave bumps, 554-557, 567f, 568. See also Pseudo olliculitis Shingles, 596-599. See also Zoster Shoes, contact dermatitis rom, 692, 694f, 696 Sickle-b + -thalassemia, 256. See also Sickle cell disease Sickle cell disease, 254-257 diagnosis o , 255-256, 255f, 256f epidemiology o , 254 etiology and pathophysiology o , 254-255 ollow-up o , 257 undamentals o , 254, 254f management o , 256-257 patient education on, 257 patient story o , 254, 254f prognosis and clinical course o , 254f, 255f, 257 Sideroblastic anemia, vs. iron de iciency anemia, 246 Sinus disease, vs. temporal arteritis, 535 Sinus headache, 1175. See also Headache Sinusitis, 133-137 diagnosis o , 134-135, 135f di erential diagnosis o vs. allergic rhinitis, 135 vs. cluster headache, 135 vs. dental pain, 136 vs. migraine headache, 135 vs. squamous cell carcinoma, 135 vs. temporal arteritis, 136 vs. trigeminal neuralgia, 136 vs. upper respiratory tract in ection, 135 epidemiology o , 133 etiology and pathophysiology o , 133-134, 134f undamentals o , 133 management o , 136 patient education on, 137

1301

1302

INDEX Sinusitis (Cont.): patient story o , 133, 133f prevention o , 136 prognosis and ollow-up o , 136 Sinus rhythm, drugs or maintenance o , 200, 201t Skin cancer vs. chondrodermatitis nodularis helicis, 128, 128f vs. corns and calluses, 1052 Skin diseases, in ectious, 42-43, 42f, 43f. See also specific types Skin popping, 1236, 1237f Skin tag (acrochordon), 767-769 de inition o , 767 in diabetes mellitus, 767, 767f, 768 diagnosis o , 767f, 768 di erential diagnosis o vs. basal cell carcinoma, 768 vs. common warts, 619 vs. epidermal hyperplasia (keratotic melanocytic nevus), 768 vs. neuro ibroma, 768, 768f vs. warts, 768 epidemiology o , 767 etiology and pathophysiology o , 767-768, 767f ollow-up and patient education on, 769 management o , 768-769, 768f, 769f in obesity, 1135, 1135f patient story o , 767 Skin tag (acrochordon), preauricular, 126-128 diagnosis o , 126-127, 127f di erential diagnosis o vs. basal cell carcinoma, 128, 128f vs. cysts, 128, 128f epidemiology, etiology and pathophysiology o , 126 management o , 128, 128f Skin tape, contact dermatitis rom, 692, 694f Sleep disorders, a ter sexual assault, 58 Slit lamp examination, o corneal oreign body/ abrasion, 72, 72f, 74 Small-bowel obstruction, vs. diverticulitis, 342 Small-cell carcinoma o lung, 278-284. See also Lung cancer Small-vessel vasculitis, 891-897. See also Vasculitis Smith racture, 515, 515f, 516f, 517f Smoker’s ace, 1201f, 1202, 1203f Smoking, 1201-1212. See also Tobacco addiction black hairy tongue rom, 156, 156f, 157, 157f chronic obstructive pulmonary disease rom, 269-276, 269f (See also Chronic obstructive pulmonary disease (COPD)) epidemiology o , 1196 with estrogen-containing contraceptives, 11 pneumothorax rom, 297, 298 substance abuse and, 1197 Smoking cessation counseling or, 1205 motivational interviewing or, 1205, 1206t Snow, 1228-1233. See also Cocaine abuse

Snu patch, vs. leukoplakia, 176 Social justice, 23-30 Calcutta Rescue program in, 30, 30f caring clinician stories in, 23 disabilities in, caring or those with, 27-28, 27f, 28f disaster relie in, Hurricane Katrina, 24-25, 24f, 25f Doctors Without Borders in, 23-24, 23f homeless in, caring or, 28-30, 28f-30f international humanitarian e orts in, Ethiopia, 25-26, 26f patient stories o , 23 re ugees and asylum seekers in, 23-24 So t tissue in ection, necrotizing, 588-591. See also Necrotizing asciitis Solar keratosis, 807-812. See also Actinic keratosis Solar lentigo vs. lentigo maligna, 818, 819f vs. melanoma, 849 vs. seborrheic keratosis, 772f, 773 Soluble trans errin receptor (sT R), in ironde iciency anemia, 245 Sotalol, or atrial ibrillation, 198, 200, 201t Space-occupying lesion, vs. Bell’s palsy, 1189 Speckled leukoplakia, 174-176. See also Leukoplakia Spermicide, 11t Spider angiomas, in liver disease, 366, 367f Spider bites vs. pyoderma gangrenosum, 864 vs. scabies, 677 Spinal in ection/ abscess, vs. back pain, 496 Spinal stenosis vs. back pain, 496 lumbar, 499-500, 499f, 500f vs. peripheral arterial disease, 235 Spitz nevus, 787, 788f Splinter hemorrhage, vs. subungual hematoma, 994 Spondyloarthritis, vs. ankylosing spondylitis, 493, 493f Spondyloarthropathies, vs. reactive arthritis, 759 Spongiotic dermatitis, as photoallergic drug reaction, 1007f, 1008. See also Photosensitivity Spontaneous pneumothorax, 296-298. See also Pneumothorax Sporotrichosis, vs. pyoderma gangrenosum, 864, 864f Spring catarrh, 77 Squamous cell carcinoma, 834-841 o conjunctiva, 63 diagnosis o , 835-838 biopsy in, 835 clinical eatures in, 835, 835f distribution in, typical, 834f, 835, 837f-839f metastatic potential o , 835f, 836-838, 837f, 839f di erential diagnosis o vs. actinic keratosis, 838 vs. basal cell carcinoma, 838, 840f

vs. Bowen disease, 838 vs. chondrodermatitis nodularis helicis, 128, 128f vs. eczema, nummular, 839 vs. keratoacanthoma, 814, 838, 839f vs. Merkel cell carcinoma, 839, 840f vs. pyoderma gangrenosum, 864 vs. sinusitis, 135 vs. torus palatinus, 142 vs. warts, common, 619, 619f vs. warts, lat, 624 vs. warts, plantar, 635 epidemiology, etiology and pathophysiology o , 834 smoking in, 1203, 1204f ollow-up o , 841 undamentals o , 834 in immunosuppressed, 834, 835, 837f, 838, 839f, 840, 841 laryngeal, 149-153 diagnosis o , 150-151, 151f di erential diagnosis o , 151 epidemiology o , 149 etiology and pathophysiology o , 150 ollow-up o , 152-153 undamentals o , 149 management o , 152 patient education on, 153 patient story o , 149 lung, 278-284, 278f (See also Lung cancer) management o , 839-840, 840t oral, 177-180 (See also Oropharyngeal cancer) pathophysiology o , 834 patient education on, 841 patient story o , 834, 834f prevention and screening or, 840-841 prognosis in, 841 risk actors or, 834-835 o skin, in situ, 807-812 (See also Bowen disease) Squamous epithelioma, sel -healing, 813-815. See also Keratoacanthoma Staghorn calculi, 399, 399f Standard Sexual Assault Forensic Evidence (SAFE) Kit, 56 Staphylococcal scalded skin syndrome vs. hypersensitivity syndromes, 883 vs. impetigo, 564 Staphylococcal toxic shock syndrome, vs. necrotizing asciitis, 590 Staphylococcus aureus acute otitis media, 112 bacterial endocarditis, 221, 223 (See also Endocarditis, bacterial) cellulitis, 580, 582f (See also Cellulitis) community-acquired pneumonia, 290 dermatitis atopic, 683 hand, 699 hordeolum, 66 impetigo, 562-564 (See also Impetigo) mastitis, 458 methicillin-resistant (MRSA) (See Methicillinresistant Staphylococcus aureus (MRSA))

INDEX necrotizing asciitis, 588 (See also Necrotizing asciitis) osteomyelitis, 1096-1101 (See also Osteomyelitis) otitis externa, 120 paronychia, 985-988, 985f, 986f Staphylococcus epidermis endocarditis, 221, 222 (See also Endocarditis, bacterial) osteomyelitis, 1096-1101 (See also Osteomyelitis) Staphylococcus olliculitis, 568-570. See also Folliculitis Stasis dermatitis vs. diabetic dermopathy, 1123 vs. lichen planus, 754 vs. necrobiosis lipoidica, 1127 Status asthmaticus, 262 Stenosing tenosynovitis, vs. Dupuytren disease, 531 Stenosis, coronary artery, 212-214, 212f, 213f. See also Coronary artery disease Sterilization emale, 11t male, 11t Nexplanon, 12, 12f Sternoclavicular dislocation, vs. clavicle racture, 512 Steroid abuse, anabolic injection diagnosis o , 1235f, 1236-1237, 1236f epidemiology o , 1235 etiology and pathophysiology o , 1235-1236, 1235f, 1236f Steroid-induced acnei orm eruption, 551, 552f Steroid myopathy, vs. dermatomyositis, 912 Stevens-Johnson syndrome, 879-884 diagnosis o , 879f, 881-883, 881f, 1028f, 1029-1030 di erential diagnosis o , 1028f, 1031 vs. bullous pemphigoid, 883 vs. staphylococcal scalded skin syndrome, 883 vs. vasculitis, 895 rom drugs, 1025, 1028f epidemiology o , 879, 1024, 1028f etiology and pathophysiology o , 880, 1027 ollow-up and patient education on, 884 undamentals o , 879 management o , 884 patient story o , 879, 879f prevention o , 884 prognosis in, 884 risk actors or, 880, 881f Stimulant abuse, 1197 Stomatitis angular, 138-140, 138f, 139f aphthous, 169-173 (See also Aphthous ulcer) geographic, 159-161 (See also Geographic tongue) nicotine, 1203, 1203f vs. leukoplakia, 176, 176f Stones gallbladder, 344-347 (See also Gallstones) kidney, 398-401 (See also Kidney stones)

Stork bite, 1022f vs. vascular lesions, 1022, 1022f Strawberry cervix, 450-453. See also Trichomonas vaginitis Street Medicine Institute, 30 Street medicine movement, 28-30, 28f-30f Strength o Recommendation (SOR) Taxonomy, 1241, 1242, 1243f, 1244f Streptococcal toxic shock syndrome, vs. necrotizing asciitis, 590 Streptococcus conjunctivitis, 75-78, 75f mastitis, 458 paronychia, 985-988, 985f, 986f Streptococcus bovis bacterial endocarditis, 221, 223. See also Endocarditis, bacterial Streptococcus mutans, dental caries rom, 181 Streptococcus pneumoniae acute otitis media, 112 community-acquired pneumonia, 290 meningitis, 1091-1094, 1091f (See also Meningitis) osteomyelitis, 1096-1101 (See also Osteomyelitis) Streptococcus pneumoniae sinusitis, 133 Streptococcus pyogenes necrotizing asciitis, 588. See also Necrotizing asciitis Stridor, 150 Stroke, 1178-1181. See also Cerebral vascular accident death rom, 17 hemorrhagic, vs. subdural hematoma, 1183, 1183f ischemic, vs. subdural hematoma, 1183 Stroke risk assessment, 201-202, 202t Stromal keratitis, rom zoster ophthalmicus, 603, 604 Strongyloides stercoralis, 1080-1083, 1081f. See also Intestinal worms and parasites in global health, 35, 35f Struvite kidney stones, 398-401. See also Kidney stones Stucco keratosis, 772, 773f Sturge-Weber syndrome, port-wine stains in, 1020f Stye, 65-67. See also Hordeolum Subacute granulomatous thyroiditis, 1150 Subarachnoid hemorrhage vs. headache, 1175, 1175f vs. subdural hematoma, 1183, 1184f Subconjunctival hemorrhage, 103, 104f rom cocaine, 1228, 1228f red eye in, 106, 107t, 108, 108f Subdural hematoma, 1182-1184. See also Hematoma, subdural Substance abuse disorder, 1196-1200 addiction and, 1196 cigarette and alcohol use and, 1197 diagnosis o , 1198-1199 di erential diagnosis o vs. anxiety disorder, 1199 vs. mood disorder, 1199 vs. personality disorders, 1199 vs. schizophrenia, 1199

epidemiology o , 1196-1197, 1196f, 1197f etiology and pathophysiology o , 1197-1198 ollow-up o , 1199-1200 undamentals o , 1196 management o , 1199 on mortality, 15 patient education on, 1200 patient story o , 1196, 1196f risk actors or, 1198 Subtrochanteric racture, 522-524. See also Hip racture Subungual hematoma, 993-995. See also Hematoma, subungual Subungual melanoma, vs. longitudinal melanonychia, 965, 966, 967 Suicide death rom, 15 epidemiology o , 14 Suicide attempt, a ter sexual assault, 56, 56f, 58 Sul a antibiotics, cutaneous reactions to, 1024-1032, 1028f. See also Drug reactions, cutaneous Sunburn blistering a ter, 926 vs. impetigo, 564, 564f Sunscreens, 1010, 1010t Super icial spreading (malignant) melanoma, 843f, 844, 844f vs. Paget disease o breast, 468, 469f Super icial thrombophlebitis, vs. deep venous thrombosis, 216, 217f Suppurative ear disease, vs. Bell’s palsy, 1189 Suppurative asciitis, 588-591. See also Necrotizing asciitis Suppurative thyroiditis, vs. hypothyroidism, 1150 Supraglottitis, vs. pharyngitis, 146 Swab test, 455, 455f Swan-neck de ormities in lupus erythematosus, 474f in psoriatic arthritis, 493f Sweet syndrome, vs. pyoderma gangrenosum, 864, 864f Sycosis barbae. See Pseudo olliculitis Syndesmophytes, 492, 492f, 493 Syphilis, 1102-1107 chancre in, 1102f, 1103, 1103f, 1107f diagnosis o , 1102f-1107f, 1103-1105 di erential diagnosis o vs. chancroid, 1107 vs. drug eruptions, 1107 vs. erythema multi orme, 1107 vs. herpes simplex, 1107 vs. Kaposi sarcoma, 1074, 1075f vs. lupus erythematosus, 905 vs. pityriasis rosea, 1107 epidemiology o , 1102 etiology and pathophysiology o , 1103 undamentals o , 1102 management o , 1107-1108 neurosyphilis, 1102, 1103, 1105, 1106-1107 patient education on, 1108, 1108f patient story o , 1102, 1102f prevention o , 1108 prognosis and ollow-up o , 1108

1303

1304

INDEX Syphilis (Cont.): risk actors or, 1103 secondary, 1102-1107, 1102f-1107f, 1103, 1231f vs. alopecia areata, 951 vs. cutaneous drug reactions, 1031 vs. herpes simplex, 609 vs. lichen planus, 755 vs. pityriasis rosea, 748 vs. psoriasis, 738 vs. pyoderma gangrenosum, 864 vs. scarring alopecia, 961 vs. seborrheic dermatitis, 726 vs. tinea versicolor, 665 tertiary, 1102, 1103, 1105f, 1106-1107 Syringocystadenoma papilli erum, 799f, 801 Syringoma vs. epidermal nevus and nevus sebaceous, 800, 800f vs. sarcoidosis, 870 vs. sebaceous hyperplasia, 777, 777f Systemic drug-related intertriginous and lexural exanthema, 1030, 1030f Systemic in lammatory response syndrome, pancreatic enzymes in, 373 Systemic lupus erythematosus, 899-906 arthritis rom autoimmune, 472 diagnosis o , 473, 474f, 476 scleritis and episcleritis with, 80, 80f diagnosis o , 901t biopsy in, 905 butter ly (malar) rash in, 899f, 900, 901, 901t, 902f clinical eatures in, 899-900, 899f, 901t, 902f distribution in, typical, 903 laboratory testing in, 904-905 di erential diagnosis o vs. actinic keratosis, 905 vs. alopecia areata, 951 vs. dermatomyositis, 905 vs. drug-induced lupus, 905 vs. lichen planus, 905 vs. melasma, 998 vs. photodermatitis, 1009 vs. psoriasis, 905 vs. rosacea, 551, 551f, 905 vs. sarcoidosis, 905 vs. scleroderma, 905, 920 vs. seborrheic dermatitis, 726 vs. syphilis, 905 epidemiology o , 899 etiology and pathophysiology o , 900 ollow-up o , 906 undamentals o , 899 management o , 905-906 patient education on, 906 patient story o , 899, 899f prevention o , 906 prognosis in, 906 risk actors or, 900 scleritis in, 80, 80f vasculitis in, 891, 892f

Systemic sclerosis, 916-921. See also Scleroderma vs. porphyria cutanea tarda, 943 Systemic vasculitis, vs. pyoderma gangrenosum, 864 T Tachyarrhythmia. See also specific types trigger actors or, 195 Taenia solium, 1080-1083 Tags, preauricular skin, 126-128 diagnosis o , 126-127, 127f di erential diagnosis o vs. basal cell carcinoma, 128, 128f vs. cysts, 128, 128f epidemiology, etiology and pathophysiology o , 126 management o , 128, 128f Tags, skin, 767-769. See also Skin tag (acrochordon) Tape, skin, contact dermatitis rom, 692, 694f Tapeworm, 1080-1083. See also Intestinal worms and parasites Tardive congenital nevus, 794 Tattoo dye allergy, vs. contact dermatitis, 696, 696f T-cell lymphoma, erythroderma with, 762, 762t, 764f Telogen e luvium vs. alopecia areata, 951 vs. scarring alopecia, 961 vs. traction alopecia and trichotillomania, 956 Temporal arteritis, 533-536 diagnosis and screening or, 535 di erential diagnosis o vs. cervical spine disease, 535 vs. cluster headache, 535 vs. herpes zoster (shingles), 535 vs. migraine, 535 vs. sinus disease, 535 vs. sinusitis, 136 vs. temporomandibular joint, 535 vs. transient ischemic attack, 535 epidemiology o , 533 etiology and pathophysiology o , 533-534, 533f, 534f undamentals o , 533 management o , 536 patient education on, 536 prognosis and ollow-up o , 536 risk actors or, 534 Temporomandibular joint, vs. temporal arteritis, 535 Tendinitis, vs. arthritis, 476 Tendon xanthomas, 1130 Tension pneumothorax, 296, 298 Tension-type headache, 1174-1176. See also Headache Testicular torsion, vs. kidney stones, 400 Tetracycline, cutaneous reactions to, 1024-1032, 1029t. See also Drug reactions, cutaneous Thalassemia vs. iron de iciency anemia, 245 sickle-b + , 256 (See also Sickle cell disease)

Thimerosal contact dermatitis, 691 Third nerve palsy, 1188-1190. See also Bell’s palsy isolated, vs. Bell’s palsy, 1189, 1189f Thoracic aortic aneurysm, 186-191. See also Aortic aneurysm Thoracic back pain, 495-497. See also Back pain Thoracic kyphosis, 1141-1146. See also Osteoporosis and osteopenia Thromboangiitis obliterans, in peripheral arterial disease, 232 Thromboembolic arterial occlusive disease, in peripheral arterial disease, 232 Thromboembolism, venous, 215-218. See also Deep venous thrombosis (DVT) Thrombophlebitis deep venous, 215-218 (See also Deep venous thrombosis (DVT)) di erential diagnosis o vs. cellulitis, 582 vs. deep venous thrombosis, 216, 217f Thrush (oral candidiasis), 638-642. See also Fungal in ections angular cheilitis rom, 138-140, 138f, 139 diagnosis o , 638-641, 639f, 644-645, 644f-646f di erential diagnosis o vs. black hairy tongue, 157 vs. lichen planus, 755 vs. pharyngitis, 146 epidemiology o , 644, 644f undamentals o , 644 management o , 641-642, 642t, 647, 939, 940f pathophysiology o , 638, 639f patient education on, 647 risk actors or, 644 Thunderclap headache, 1175, 1175f Thyroglossal duct cyst, vs. hypothyroidism, 1150, 1150f Thyroid cancer, vs. hypothyroidism, 1150, 1151f Thyroid disease, subclinical, 1148 Thyroid hormone overdose, vs. hyperthyroidism, 1156 Thyroiditis acute suppurative, vs. hypothyroidism, 1150 vs. hyperthyroidism, 1156 Thyroid nodule, autonomous unctioning, vs. hyperthyroidism, 1156 Thyrotoxicosis, 1153-1158. See also Hyperthyroidism Thyrotropin-secreting pituitary adenoma, vs. hyperthyroidism, 1156 Tick bite local reaction, vs. Lyme disease, 1087 Tier ell nevus, 793-797. See also Nevus, congenital Tinea vs. atopic dermatitis, 688 bullous presentation o , 927 hand dermatitis rom, 699 Tinea capitis laboratory studies in, 640-641, 640f, 641f, 642t

INDEX di erential diagnosis o vs. alopecia areata, 951 vs. scarring alopecia, 961 vs. seborrheic dermatitis, 726 vs. traction alopecia, 956 vs. trichotillomania, 956 olliculitis rom, 568 as global health problem, 43 management o , 641-642, 642t pathophysiology o , 638 Tinea corporis, 638-642, 648-653. See also Fungal in ections diagnosis o , 638-641, 649-650 clinical eatures in, 638, 638f, 639f, 640t, 648f, 649, 649f distribution in, typical, 639f, 640, 648f-651f, 649 laboratory studies in, 640-641, 640f, 641f, 642t, 649-650, 652f di erential diagnosis o vs. breast abscess, 459 vs. candidiasis, 645, 646f vs. cutaneous larva migrans, 650 vs. eczema, nummular, 650, 708 vs. erythema annulare centri ugum, 650, 652f, 1046, 1046f, 1047f vs. erythrasma, 650 vs. granuloma annulare, 650, 652f, 857 vs. impetigo, 563 vs. mastitis, 459 vs. pityriasis rosea, 748 vs. psoriasis, 650, 652f, 734f, 738 vs. scabies, 677, 677f vs. tinea versicolor, 665 epidemiology o , 648-649 etiology and pathophysiology o , 649 ollow-up o , 653 undamentals o , 648 management o , 641-642, 642t, 648f, 651-653, 651f pathophysiology o , 638, 638f, 639f patient education on, 653 patient story o , 638, 638f, 648, 648f prevention o , 653 risk actors or, 649 Tinea cruris, 638-642, 654-657. See also Fungal in ections de inition o , 654 diagnosis o , 638-641, 654-656 clinical eatures in, 638, 638f, 639f, 640t, 654, 655f distribution in, typical, 639f, 640, 655, 655f laboratory studies in, 640-641, 640f, 641f, 642t, 654f, 656 di erential diagnosis o vs. candidiasis, 645-646, 656 vs. contact dermatitis, 656 vs. erythrasma, groin, 656, 656f vs. intertrigo, 656 vs. inverse psoriasis, 656, 656f vs. psoriasis, 734f, 738 epidemiology o , 654 etiology and pathophysiology o , 654

ollow-up o , 657 management o , 641-642, 642t, 655f, 656, 657f pathophysiology o , 638, 639f, 640f patient education on, 657 patient story o , 654, 654f prevention o , 653 risk actors or, 654 Tinea aciei, 638-642. See also Fungal in ections diagnosis o , 638-641, 649f clinical eatures in, 638, 638f, 639f, 640t distribution in, 638, 638f laboratory studies in, 640-641, 640f, 641f, 642t management o , 641-642, 642t pathophysiology o , 638 Tinea incognito diagnosis o , 649-650, 650f, 651f on oot, 660, 660f di erential diagnosis o , 650 etiology o , 656, 657f management o , 651-653 patient story o , 648, 648f Tinea manus, 638-642 diagnosis o , 638-641 clinical eatures in, 638, 638f, 639f, 640t distribution in, typical, 639f, 640 laboratory studies in, 640-641, 640f, 641f, 642t vs. hand eczema, 702, 702f management o , 641-642, 642t pathophysiology o , 638, 639f Tinea pedis, 638-642, 658-662. See also Fungal in ections in diabetes, 1110, 1110f diagnosis o , 638-641, 658-659, 979, 979f clinical eatures in, 638, 639f, 640t, 658-659, 658f, 659f distribution in, typical, 639f, 640, 659 laboratory studies in, 640-641, 640f, 641f, 642t, 659, 660f di erential diagnosis o vs. contact dermatitis, 660, 660f vs. dyshidrotic eczema, 660, 661f vs. riction blisters, 660 vs. keratoderma, 660, 661f vs. pitted keratolysis, 660, 660f vs. psoriasis, 660, 661f epidemiology o , 658 etiology and pathophysiology o , 658 undamentals o , 658 management o , 641-642, 642t, 661-662, 661t, 662t pathophysiology o , 638, 639f patient education on, 662 patient story o , 658, 658f risk actors or, 658 types o in lammatory/ vesicular, 658, 658f, 661t interdigital, 658, 659f, 660f, 661t moccasin, 658, 659f, 661t ulcerative, 658, 659, 659f

Tinea unguium, 979-983. See also Onychomycosis Tinea versicolor, 638-642, 664-666. See also Fungal in ections diagnosis o , 638-641, 664-665 clinical eatures in, 638, 639f, 640t, 664, 664f, 665f distribution in, typical, 639f, 640, 664 laboratory studies in, 640-641, 640f, 641f, 642t, 664-665, 665f, 666f di erential diagnosis o vs. pityriasis alba, 665 vs. pityriasis rosea, 665, 748 vs. Pityrosporum olliculitis, 666, 666f vs. seborrheic dermatitis, 726 vs. syphilis, 665 vs. tinea corporis, 665 vs. vitiligo, 664f, 665 epidemiology, etiology and pathophysiology o , 664 ollow-up and patient education on, 666 undamentals o , 664 management o , 641-642, 642t, 666 pathophysiology o , 638 Pityrosporum in, 638, 639f, 640f patient story o , 664, 664f prevention o , 666 Tobacco addiction, 1201-1212 chronic obstructive pulmonary disease rom, 269-276, 269f (See also Chronic obstructive pulmonary disease [COPD]) diagnosis o clinical eatures in, 1202-1205, 1203f, 1204f imaging in, 1205 laboratory testing in, 1205 epidemiology o , 1196, 1201 etiology and pathophysiology o , 1201-1202 ollow-up or, 1211 undamentals o , 1201 management o , 1205-1211 5 A’s model in, 1201, 1202t complementary and alternative therapy in, 1211 counseling in, 1205, 1206t medications in, 1205-1211, 1207b-1210b re erral in, 1211 on mortality, 15 patient story o , 1201, 1201f, 1202t prevention o , 1211 prognosis in, 1211, 1211f risk actors or, 1202 secondhand smoke in, 1202, 1204f substance abuse and, 1197 Toe-brachial indices, 234 Toe racture, vs. hammer toe, 1058 Toenail ungus, 979-983. See also Fungal in ections; Onychomycosis Toenail, thickened, 964-968, 965f. See also Onychogryphosis Tolerance, 1198 Tooth decay, adult, 181-183. See also Caries, adult

1305

1306

INDEX Tooth (teeth) problems demineralization vs. remineralization o , 181 vs. dental caries abrasion, 182 attrition, 182 erosion, 182 staining, 182 trauma, 182 Tophaceous gout, 475f, 504-507 diagnosis o , 505-506, 506f di erential diagnosis o , vs. xanthoma, 1131, 1131f epidemiology, etiology and pathophysiology o , 504 management o , 506 patient story o , 504, 504f Torus mandibularis, vs. torus palatinus, 141, 142f Torus palatinus, 141-142, 141f vs. adenoid cystic carcinoma, 142, 142f vs. squamous cell carcinoma o palate, 142 vs. torus mandibularis, 141, 141f Toxic agents. See also specific types on mortality, 15 Toxic epidermal necrolysis, 879-884 diagnosis o , 881-883, 883f, 1029, 1030 di erential diagnosis o vs. bullous pemphigoid, 883 vs. cutaneous drug reactions, 1031 vs. staphylococcal scalded skin syndrome, 883 vs. vasculitis, 895 epidemiology o , 879 etiology and pathophysiology o , 880, 1027 ollow-up and patient education on, 884 undamentals o , 879 management o , 884 prevention o , 884 prognosis in, 884 risk actors or, 880, 881f Toxic multinodular goiter, vs. hyperthyroidism, 1156 Toxic nodular goiter, vs. goitrous hypothyroidism, 1149f, 1151 Toxicodendron (Rhus) dermatitis, 691, 692, 693f, 694, 697, 926, 926f. See also Contact dermatitis Toxic shock syndrome, vs. necrotizing asciitis, 590 Trabecular bone normal, 1143f osteoporotic, 1142-1143, 1143f Trachoma, 41-42, 41f, 42f, 77, 77f Chlamydia trachomatis, 77, 77f Traction alopecia, 954-956 diagnosis o , 954f, 955-956 di erential diagnosis o vs. alopecia areata, 956 vs. androgenic alopecia, 956 vs. scarring alopecia, 956, 961 vs. telogen e luvium, 956 vs. tinea capitis, 956 epidemiology o , 954, 954f etiology and pathophysiology o , 954-955, 954f

ollow-up and patient education on, 956 management o , 956 patient story o , 954, 954f Tranquilizer abuse, 1197. See also Substance abuse disorder Transient acantholytic dermatosis, vs. olliculitis, 569, 569f Transient ischemic attack vs. cerebral vascular accident, 1179 vs. temporal arteritis, 535 Transitional cell carcinoma, o bladder, 390-393, 390f, 391f Transplantation, lung, or COPD, 275 Transrectal ultrasound, 411-412 Transudative e usions, vs. exudative e usions, 287-288, 287t Transverse striate leukonychia, 964-968, 964f, 968t. See also Leukonychia Transverse striate punctata, 964-968. See also Leukonychia Trench mouth, 163, 163f Treponema pallidum, 1102, 1103, 1105f. See also Syphilis Trich, 450-453. See also Trichomonas vaginitis Trichilemmoma, 829 Trichoblastoma, 829 Trichoepithelioma, 829 Trichomonas vaginalis urethritis in men, 1077-1079 (See also Urethritis, in men) vaginitis, 434-436, 435f, 436t, 450-453 (See also Trichomonas vaginitis) Trichomonas vaginitis, 434-436, 435f, 436t, 450-453 diagnosis o , 450f, 451-452, 451f di erential diagnosis o vs. bacterial vaginosis, 443, 452 vs. Candida vaginitis, 452 vs. Chlamydia, 452 vs. gonorrhea, 452 epidemiology o , 450 etiology and pathophysiology o , 450-451 ollow-up o , 453 undamentals o , 450 management o , 452 patient education on, 453 patient story o , 450, 450f prevention o , 452, 452t risk actors or, 451 Trichomoniasis di erential diagnosis o vs. Candida vulvovaginitis, 447 vs. Chlamydia cervicitis, 456 a ter sexual assault, 57 Trichophagy, 955 Trichophyton, 638. See also Fungal in ections Trichophyton mentagrophytes onychomycosis, 980, 980f tinea pedis, 658 Trichophyton rubrum diagnosis o , 638-641, 640f, 641f management o , 641-642, 642t onychomycosis rom, 658, 979, 979f pathophysiology o , 638

tinea rom, 648 (See also specific types) tinea pedis rom, 658 Trichotillomania, 954-956 diagnosis o , 955-956, 955f di erential diagnosis o vs. alopecia areata, 951, 956 vs. androgenic alopecia, 956 vs. scarring alopecia, 956, 961 vs. telogen e luvium, 956 vs. tinea capitis, 956 epidemiology o , 954, 955f etiology and pathophysiology o , 955, 955f ollow-up and patient education on, 956 management o , 956 Trichuris, 35 Trichuris trichiura, 1080-1083, 1081f. See also Intestinal worms and parasites Tricky monkeys, 450-453. See also Trichomonas vaginitis Trigeminal nerve sensory distribution o , 602, 603f zoster ophthalmicus in, 601-604, 601f-603f (See also Zoster ophthalmicus) Trigeminal neuralgia vs. sinusitis, 136 vs. zoster ophthalmicus, 603 Trigger inger, vs. Dupuytren disease, 531 Triglycerides, high, 1130 Trimethoprim/ sul amethoxazole, cutaneous reactions to, 1024-1032, 1025f, 1026f. See also Drug reactions, cutaneous T.R.U.E. Test, 696t, 695, 695f, 696f, 702, 702f Tubal occlusion, hysteroscopic, 12, 12f, 13f Tubal pregnancy, 454 Tuberculosis (TB), 316-323 diagnosis o , 317-319 biopsy in, 319 clinical eatures in, 318, 318f imaging in, 316f, 317f, 319, 319f-321f laboratory and ancillary testing in, 317f, 319 skin testing and rapid testing in, 318-319 di erential diagnosis o vs. asthma, 264 vs. chronic obstructive pulmonary disease, 272 vs. coccidiomycosis, 320 vs. histoplasmosis, 320, 321f vs. osteoporosis and osteopenia, 1143 vs. pneumonia, 319 vs. respiratory in ections, ungal, 320 vs. sarcoidosis, 320 epidemiology o , 316 erythema nodosum in, 887 etiology and pathophysiology o , 316-317, 317f ollow-up o , 322-323 undamentals o , 316 HIV and, in global health, 45, 45f management o , 320-322 medications in, 321-322 nonpharmacologic, 320-321 patient education on, 323

INDEX patient story o , 316, 316f, 317f prevention o , 322 prognosis in, 322 risk actors or, 317 Tuberculous lymphadenitis, 45, 45f Tuberoeruptive xanthomas, 1129-1133, 1129f, 1130f. See also Xanthomas Tuberous sclerosis kidney angiomyolipomas in, 422f vs. neuro ibromatosis, 1193, 1193f vs. polycystic kidneys, 407 Tuberous xanthomas, 1130 Tu ted olliculitis, 568, 568f scarring alopecia in, 958-962, 958t, 960f Turner sign, in hemorrhagic pancreatitis, 373, 374f Twenty-nail dystrophy, 967, 968f Two- oot, one-hand syndrome, 639f, 702 Tyloma, 1050-1053. See also Calluses Tympanic membrane normal, 114f in otitis media with e usion, 113f Tympanic membrane per oration vs. acute otitis and otitis media with e usion, 115, 116f acute otitis media with, vs. otitis externa, 121 Tympanosclerosis, 116, 116f Tympanostomy tubes, 116, 116f Tyndall e ect, 787, 788f Typhoid ever, 33-34 water and sanitation in, 33f, 35, 35f Typhus, murine, erythroderma with, 762, 764f U Ulcer. See also specific types and disorders aphthous, 169-173 (See also Aphthous ulcer) corneal, red eye in, 108, 108f, 109, 109f oot ischemic, 1061-1062, 1061f, 1062f, 1111, 1112f, 1114, 1115 neuropathic, 1063-1064, 1063f gastric/ peptic, 377-380 (See also Peptic ulcer disease) Marjolin, 835, 835f pyloric, 377-380 (See also Peptic ulcer disease) Ulcerative colitis, 381-386. See also In lammatory bowel disease Ulnar nerve entrapment, vs. olecranon bursitis, 509 Uncinaria stenocephala, 680 Unguis incarnatus, 975-977. See also Ingrown toenail Upper motor neuron diseases, vs. Bell’s palsy, 1189 Upper respiratory tract in ections vs. pneumonia, community-acquired, 292 vs. sinusitis, 135 Ureaplasma urealyticum urethritis, in men, 1077-1079. See also Urethritis, in men Uremic rost, 426, 427f Ureteral stones (calculi), 395, 396f, 398-401. See also Kidney stones vs. diverticulitis, 341

Ureterolithiasis, 395, 396f, 398-401. See also Kidney stones Urethritis, in men, 1077-1079 diagnosis o , 1077-1078, 1077f di erential diagnosis o , 1078 epidemiology, etiology and pathophysiology o , 1077, 1077f management o , 1078 patient education on, 1079 patient story o , 1077, 1077f prevention o , 1078 prognosis and ollow-up o , 1078 Uric acid kidney stones, 398-401. See also Kidney stones with polycystic kidneys, 407, 408 Urinary casts, 429-431. See also Urinary sediment Urinary sediment, 429-431 diagnosis o , 430f, 431 epidemiology o , 429 etiology and pathophysiology o , 429-430, 430f undamentals o , 429 management o , 431 patient story o , 429, 429f prevention and screening or, 431 risk actors or, 431 Urinary tract in ection bacteriuria with, 430f diagnosis o , 431 vs. kidney stones, 400 pyuria with, 429, 430f Urinary tract stone, 398-401. See also Kidney stones Urogenital atrophy, 437-439. See also Atrophic vaginitis Urolithiasis, 398-401. See also Kidney stones Urticaria, 716-721 diagnosis o , 716f-719f, 718-719 di erential diagnosis o vs. cutaneous drug reactions, 1031 vs. erythema multi orme, 718f, 719, 883 vs. hypersensitivity syndromes, 883 vs. insect bites, 719 vs. Lyme disease, 1087 vs. mast cell releasability syndromes, 716f-718f, 719 vs. pemphigoid gestationis, 719 vs. pruritic urticarial papules and plaques o pregnancy, 719, 720f vs. urticarial vasculitis, 719, 720f epidemiology o , 716 etiology and pathophysiology o , 716-717, 717f, 718f ollow-up o , 721 undamentals o , 716 giant, 718f management o , 719-721, 720f, 721f patient education on, 721 patient story o , 716, 716f Urticarial drug reactions diagnosis o , 1025f, 1028 di erential diagnosis o , 1031 epidemiology o , 1025, 1025f etiology and pathophysiology o , 1026-1027

management o , 1031-1032 risk actors or, 1027-1028 Urticarial vasculitis, vs. urticaria, 719, 720f Urticaria pigmentosa, 717, 719, 719f Usatine, Richard, 24-25, 24f Uveal tract, 84 Uveitis, 84-86 acute anterior, with corneal endothelial white cell aggregates, 84, 84f in ankylosing spondylitis, 493 anterior, rom zoster ophthalmicus, 601-604, 601f (See also Zoster ophthalmicus) di erential diagnosis o vs. acute-angle closure glaucoma, 85 vs. conjunctivitis, 76, 85 vs. corneal oreign body/ abrasion, 73 vs. corneal ulceration, 85 vs. episcleritis, 82, 85 vs. keratitis, 85 vs. scleritis, 82, 85 hypopyon in, 85, 85f idiopathic intermediate, 84, 85, 85f management o , 85, 86f patient education on, 86 perilimbal injection in, 85, 85f, 88f posterior synechiae in, 84f, 85, 86f prognosis and ollow-up o , 86 red eye in, 106-110, 107t, 109, 109f UV light, 1006. See also Photosensitivity V Vaccine hepatitis B, a ter sexual assault, 57 pneumococcal, allergic reaction to, 582, 582f pneumococcal polysaccharide, 294 Vaginal atrophy, 437-439. See also Atrophic vaginitis Vaginal bacteriosis, 441-443. See also Bacterial vaginosis Vaginal discharge, 434-436, 434f, 435f, 436t Vaginal dryness, 437, 437f Vaginal ring, 11t hormonal, 10, 10f, 12 Vaginitis, 434-436 atrophic, 437-439 (See also Atrophic vaginitis) diagnosis o , 434f, 435, 435f, 436t epidemiology o , 434 etiology and pathophysiology o , 434-435, 434f, 435f undamentals o , 434 management o , 436 nonspeci ic, 441-443 (See also Bacterial vaginosis) patient story o , 434, 434f senile, 437-439 (See also Atrophic vaginitis) Trichomonas, 450-453 (See also Trichomonas vaginitis) yeast, 445-449 (See also Candida vulvovaginitis) Vaginosis anaerobic, 441-443 (See also Bacterial vaginosis) Gardnerella, 441-443 (See also Bacterial vaginosis)

1307

1308

INDEX Varicella-zoster virus, 596-599, 603. See also Chickenpox; Zoster chickenpox rom, 592-595 vs. pityriasis lichenoides et varioli ormis acuta, 946 Varicose veins, 239-241. See also Venous insu iciency with obesity, 1136, 1136f Variegate porphyria, 942 Vascular colonic ectasias vs. colon cancer, 331 vs. colon polyps, 337 Vascular lesions, hereditary and congenital, 1020-1023 diagnosis o , 1020f, 1021, 1021f di erential diagnosis o vs. CREST, 1021 vs. glomangioma, 1021 vs. port-wine stains, 1021 vs. salmon patches, 1022, 1022f epidemiology o , 1020, 1020f, 1021f etiology and pathophysiology o , 1021 ollow-up o , 1022 undamentals o , 1020 management o , 1022 patient education on, 1022 patient story o , 1020, 1020f Vascular skin lesions, acquired, 1016-1019 diagnosis o , 1016f-1018f, 1017-1018 di erential diagnosis o or angiokeratomas, 1018 or angiosarcoma, cutaneous, 1018-1019, 1018f or glomangiomas, 1018 or melanoma, 1018 epidemiology o , 1016-1017, 1016f-1018f etiology and pathophysiology o , 1016f-1018f, 1017 ollow-up o , 1019 undamentals o , 1016 management o , 1019 patient education on, 1019 patient story o , 1016, 1016f Vasculitis, 891-897 cutaneous, 891-897 di erential diagnosis o vs. cutaneous T-cell lymphoma, 895 vs. erythema multi orme, 883 vs. hypersensitivity syndromes, 883 vs. idiopathic thrombocytopenic purpura, 895, 896f vs. meningococcemia, 895 rom levamisole-adulterated cocaine, 1229-1230, 1230f, 1231f diagnosis o , 891f-894f, 893-894 di erential diagnosis o vs. cholesterol embolism, 896 vs. Churg-Strauss syndrome, 895 vs. cutaneous T-cell lymphoma, 895 vs. idiopathic thrombocytopenic purpura, 895, 896f vs. lichen aureus, 894-895, 895f vs. meningococcemia, 895, 896f

vs. pigmented purpuric dermatosis, 894-895, 895f vs. pigmented purpuric dermatosis o Majocchi type, 895, 896f vs. Rocky Mountain spotted ever, 895, 896f vs. scurvy, 896, 897f vs. Stevens-Johnson syndrome, 895 vs. toxic epidermal necrolysis, 895 vs. urticaria, 719, 720f vs. venous insu iciency, 240 vs. Wegener granulomatosis, 895 epidemiology o in Henoch-Schönlein purpura, 891, 891f, 892f in leukocytoclastic vasculitis, 892-893, 892f, 893f in systemic lupus erythematosus, 891, 892f etiology and pathophysiology o , 893 undamentals o , 891 in Henoch-Schönlein purpura, 891-897, 891f, 892f with lupus, 902, 902f management o , 896-897 patient education on, 897 patient story o , 891, 891f in peripheral arterial disease, 232 prognosis and ollow-up o , 897 risk actors or, 893, 894f systemic, vs. pyoderma gangrenosum, 864 Vasospastic disease, in peripheral arterial disease, 232 Vaughan Williams classi ication, 200, 200t Vector borne diseases, 38-41. See also specific types leishmaniasis, 39-40, 40f, 41f malaria, 38-39, 38f prevention o , 41 prognosis in, 41 Vegetations, nonin ective, vs. bacterial endocarditis, 222 Venous claudication, vs. peripheral arterial disease, 235 Venous insu iciency, 239-241 diagnosis o , 240, 240f di erential diagnosis o vs. arterial ulcers, 240 vs. deep venous thrombosis, 216 vs. diabetic ulcers, 240 vs. pyoderma gangrenosum, 864, 865f vs. vasculitides, 240 epidemiology, etiology and pathophysiology o , 239, 239f, 241 undamentals o , 239 management o , 241 patient education on, 240f, 241 patient story o , 239, 239f prevention o , 241 prognosis and ollow-up o , 241 risk actors or, 240 Venous lake, 1016-1019, 1016f diagnosis o , 1016f, 1017 di erential diagnosis o , 1018-1019 epidemiology o , 1016 etiology and pathophysiology o , 1016f, 1017

management o , 1019 patient education and ollow-up o , 1019 patient story o , 1016, 1016f Venous stasis, 239-241. See also Venous insu iciency vs. cellulitis, 581f, 582 vs. pyoderma gangrenosum, 864, 865f Venous thromboembolism, 215-218. See also Deep venous thrombosis (DVT) Ventricular hypertrophy, le t, 225, 225f, 226 Verapamil or atrial ibrillation, 198 or diastolic heart ailure, 210 Vernal conjunctivitis, 77 Verrucae, 617-621. See also Warts, common Verruca plana, 623-625. See also Warts, lat Verruca plana juvenilis, 623-625. See also Warts, lat Verruca plantaris, 633-636. See also Warts, plantar Verruca vulgaris, 617-621. See also Warts, common Verrucous leukoplakia, 174-176. See also Leukoplakia Verrugoma, 813-815. See also Keratoacanthoma Vertebral racture vs. ankylosing spondylitis, 493 vs. back pain, with osteoporosis, 496, 496f Vertigo, vs. cerebral vascular accident, 1180 Vibrio cholerae, 34-35, 35f Vibrio vulnificus cellulitis, 580, 581f (See also Cellulitis) necrotizing asciitis, 588 (See also Necrotizing asciitis) Villous polyp, 335-338. See also Colon polyps Vincent disease, 163, 163f Violence intimate partner, 50-53 physical, 50 prevention–intervention programs or, 57 sexual, 55 Viral exanthem, vs. cutaneous drug reactions, 1031 Viral hepatitis, 365-371. See also Liver disease Viral in ections. See also specific types and infections vs. intestinal worms and parasites, 1083 Virchow’s triad, 215 Vision loss age-related macular degeneration in, 99-101 (See also Age-related macular degeneration) blindness in rom Chlamydia trachomatis, 41-42, 41f, 42f rom diabetic retinopathy, 90-92 rom glaucoma, 87-89 di erential diagnosis o , 100 Vitamin A de iciency, 36 Vitamin B3 de iciency, 37-38, 37f Vitamin B12 de iciency, 248-252 diagnosis o , 250-251 di erential diagnosis o vs. olate de iciency, 251 vs. HIV, 251 vs. myelodysplastic syndromes, 251

INDEX epidemiology o , 248 etiology and pathophysiology o , 248-250 absorption in, 249-250 digestive causes in, 249 inborn errors o intracellular cobalamin de iciency in, 250 nutritional causes in, 249 transport in, 250 vitamin B12 pathway in, 248-249 undamentals o , 248 management o , 251 patient story o , 248, 248f prognosis and clinical course o , 248f, 251-252, 252f screening or, 251 Vitamin B12 injections, 251 Vitamin B de iciency, angular cheilitis rom, 138 Vitamin C de iciency, vs. vasculitis, 896, 897f Vitamin D, on insulin resistance, 1113 Vitiligo, 1000-1006 diagnosis o , 1000-1002, 1000f-1002f di erential diagnosis o vs. cutaneous T-cell lymphoma, 873f, 877 vs. halo nevus, 1003 vs. idiopathic guttate hypomelanosis, 1003, 1003f vs. nevus anemicus, 1003, 1004f vs. nevus depigmentosus, 1003, 1003f vs. postin lammatory hypopigmentation, 1002-1003, 1003f vs. tinea versicolor, 664f, 665 epidemiology o , 1000 etiology and pathophysiology o , 1000 undamentals o , 1000, 1000f management o , 1004, 1005f patient education on, 1004 patient story o , 1000, 1000f prognosis and ollow-up o , 1004 Vitreous hemorrhage, rom diabetic retinopathy, 91, 91f Vocal cord nodules and polyps, 149-153 diagnosis o , 150-151, 152f di erential diagnosis o , 151 etiology and pathophysiology o , 150 ollow-up o , 153 management o , 152 patient education on, 153 Vocal cord paresis and paralysis, 149-153 diagnosis o , 150-151 di erential diagnosis o , 151 ollow-up o , 152-153 management o , 152 patient education on, 153 Vocal cords alse, 149, 149f normal, 149f Vocal strain, 149-153. See also Hoarseness Volume-expansion–related hypertension, 416 Vulvar angiokeratosis, 1016-1019, 1017f. See also Vascular skin lesions, acquired Vulvar pyoderma gangrenosum, 863 Vulvovaginal atrophy, 437-439. See also Atrophic vaginitis

Vulvovaginal lichen planus, vs. atrophic vaginitis, 438 Vulvovaginitis, Candida, 445-449 W War arin, 202-203 cutaneous reactions to, 1024-1032, 1025f, 1031f (See also Drug reactions, cutaneous) diagnosis o , 1025f, 1028, 1031f epidemiology o , 1025, 1025f etiology and pathophysiology o , 1025f, 1027 War arin-induced skin necrosis, 1024-1032 diagnosis o , 1025f, 1028, 1031f epidemiology o , 1025, 1025f etiology and pathophysiology o , 1026f, 1027 Warm weather conjunctivitis, 77 Warts, common, 617-621 diagnosis o , 617f, 618, 618f di erential diagnosis o vs. acrochordon (skin tag), 619 vs. actinic keratosis, 619 vs. amelanotic melanoma, 619 vs. cutaneous horn, 823 vs. keratoacanthoma, 619 vs. seborrheic keratosis, 619, 773 vs. skin tag, 768 vs. squamous cell carcinoma, 619, 619f epidemiology o , 617, 617f etiology and pathophysiology o , 617, 618f ollow-up o , 617 undamentals o , 617 management o , 619-621, 620f, 621f mosaic, 633, 634f (See also Warts, plantar) patient education on, 621 patient story o , 617, 617f prevention o , 621 prognosis and ollow-up o , 621 risk actors or, 617, 618f Warts, lat, 623-625 diagnosis o , 623f, 624, 624f di erential diagnosis o vs. lichen planus, 624 vs. seborrheic keratosis, 624 vs. squamous cell carcinoma, 624 epidemiology o , 623, 623f, 624f etiology and pathophysiology o , 623 ollow-up and patient education on, 625 undamentals o , 623, 623f management o , 624-626, 624f, 625f, 625t patient story o , 623, 623f prevention o , 625 risk actors or, 623-624, 623f, 624f Warts, genital (condylomata acuminata), 627-632 diagnosis o , 627-629, 627f-629f di erential diagnosis o vs. Buschke-Lowenstein tumor, 629, 629f vs. condyloma lata, 630, 630f vs. hemorrhoids, 359 vs. malignant neoplasms, 630 vs. micropapillomatosis o vulva, 630 vs. molluscum contagiosum, 615, 630

vs. pearly penile papules, 629, 629f vs. seborrheic keratosis, 629, 630f epidemiology, etiology and pathophysiology o , 627 undamentals o , 627 management o , 631, 631f, 631t patient education on, 632 patient story o , 627, 627f prevention o , 632 prognosis and ollow-up o , 632 risk actors or, 627, 627f Warts, plantar, 633-636 diagnosis o , 633f, 634, 634f di erential diagnosis o vs. amelanotic melanoma, 635 vs. black heel, 635 vs. black warts, 635 vs. corns and calluses, 634-635, 1052 vs. palmoplantar keratoderma, 635, 635f, 636f vs. pitted keratolysis, 572 vs. squamous cell carcinoma, 635 epidemiology o , 633 etiology and pathophysiology o , 633, 633f, 634f undamentals o , 633 management o , 635-636 patient education on, 636 patient story o , 633, 633f prevention o , 636 prognosis and ollow-up or, 636 risk actors or, 633 Water contaminated, preventing diseases rom, 35, 35f in world health, 33, 33f “Water-bottle” heart, 229f Wegener’s granulomatosis episcleritis with, 80, 81f, 82 scleritis with, 80, 81f, 82 vs. vasculitis, 895 Wells clinical score, modi ied, 216, 216t Wet gangrene, 1069, 1069f Wheel-a-thon, 28f “Whi test,” 435, 436t Whipworm, 1080-1083, 1081f. See also Intestinal worms and parasites White blood cell casts, 429-431, 430f. See also Urinary sediment White-coat hypertension, 226 Whiteheads, 541 White nails, 964-968. See also Leukonychia White sponge nevus, vs. leukoplakia, 176 Wickham lines (striae), 751, 751f, 752, 754f Wilson disease, 366 Kayser-Fleischer rings in, 367, 368f laboratory testing or, 368, 369t liver disease rom, 366 management o , 370 Winakur, Jerry, 6f Withdrawal, 1198 as birth control, 11t o li e-sustaining treatment, 20 tobacco addiction, 1203

1309

1310

INDEX Withers, Jim, 28-30, 28f, 29f Wol -Parkinson-White syndrome atrial ibrillation with, 195, 195f rate control in, 199 Woman Abuse Screening Tool (WAST), 51 Woodard, Laurie, 27-28, 27f, 28f Wood chip, in cornea, 72, 72f Worms, intestinal, 1080-1083. See also Intestinal worms and parasites X Xanthelasma, 1130, 1131f in diabetes mellitus, 1111 di erential diagnosis o vs. hordeolum and chalazion, 66 vs. sarcoidosis, 870 in nephrotic syndrome, 403, 404f Xanthomas, 1129-1133 in diabetes mellitus, 1111, 1112f diagnosis o , 1131 di erential diagnosis o vs. gouty tophi, 1131, 1131f vs. molluscum contagiosum, 1131f vs. pseudoxanthoma elasticum, 1131f vs. sebaceous hyperplasia, 777 epidemiology o , 1129 etiology and pathophysiology o , 1129-1130, 1129f, 1130f undamentals o , 1129 management o , 1131-1133 in nephrotic syndrome, 403, 403f with obesity, 1136, 1137f patient education on, 1133 patient story o , 1129, 1129f, 1130f

prevention and screening or, 1133 prognosis in, 1133 Xerophthalmia, rom vitamin A de iciency, 36 Xerosis with atopic dermatitis, 685 vs. X-linked ichthyosis, 1043 Xerostomia, dental caries with, 183 X-linked ichthyosis, 1039-1044 diagnosis o , 1040, 1042f di erential diagnosis o vs. acquired ichthyosis, 1042, 1043f vs. asteatotic eczema, 1042-1043 vs. ichthyosis vulgaris, 1042, 1043f vs. lamellar ichthyosis, 1042 vs. xerosis, 1043 epidemiology o , 1039 etiology and pathophysiology o , 1039 ollow-up o , 1044 management o , 1043-1044 patient education on, 1044 Y Yeast in ection, 445-449. See also Candida vulvovaginitis Yeast onychomycosis, 979f, 980, 980f Yeast vaginitis, 445-449. See also Candida vulvovaginitis Z Zinc de iciency, 36 Zoster, 596-599 diagnosis o , 596f-598f, 597-598 di erential diagnosis o vs. coronary artery disease, 598

vs. olliculitis, 598 vs. herpes simplex, 598 vs. insect bites, 598 vs. molluscum contagiosum, 598 vs. pemphigus, 598 vs. scabies, 598 epidemiology o , 596 etiology and pathophysiology o , 596-597, 597f ollow-up and patient education on, 599 undamentals o , 596, 596f management o , 598, 598t, 599t patient story o , 596, 596f prevention o , 599 risk actors or, 597 Zoster ophthalmicus, 601-604 diagnosis o , 601f-603f, 603 di erential diagnosis o vs. abrasions, traumatic, 603 vs. conjunctivitis, 603 vs. glaucoma, 603 vs. pemphigus and bullous diseases, 604 vs. trigeminal neuralgia, 603 epidemiology o , 601 etiology and pathophysiology o , 601-603, 601f-603f ollow-up and patient education on, 604 undamentals o , 601 management o , 604 patient story o , 601, 601f prevention o , 604 prognosis in, 604 risk actors or, 603

TO PIC INDEX The topic index is for quick look up of the most common topics only. For a more complete index, look on page 1261. A Abscess, 584 Acanthosis Nigricans, 1118 Acne Keloidalis Nuchae, 554 Acne Vulgaris, 540 Acquired Vascular Skin Lesions, 1016 Acromegaly, 1160 Actinic Keratosis, 807 Acute Otitis Media, 112 Age-Related Macular Degeneration, 99 AIDS, 1072 Alcoholism (Alcohol Use Disorder), 1213 Alopecia Areata, 949 Angioedema, 716 Angular Cheilitis, 138 Ankylosing Spondylitis, 492 Aortic Aneurysm 186 Aphthous Ulcer, 169 Arthritis, 472 Asthma, 260 Atopic Dermatitis, 683 Atrial Fibrillation 193 Atrophic Vaginitis, 437 B B12 deficiency 248 Back Pain, 495 Bacterial Endocarditis, 220 Bacterial Vaginosis, 434 Basal Cell Carcinoma, 825 Bell Palsy, 1188 Benign Nevi, 786 Black Hairy Tongue, 156 Bladder Cancer, 390 Bowen Disease, 807 Breast Abscess, 458 Breast Cancer, 461 Bullous Diseases, 923 Bullous Pemphigoid, 923 Bunion Deformity, 1054

D Deep Venous Thrombosis 215 Dermatofibroma, 778 Dermatomyositis, 908 Dermoscopy, 1248 Diabetes, 1110 Diabetic Dermopathy, 1122 Diabetic Retinopathy, 90 Distal Radius Fracture, 514 Diverticulitis 340 Doctor–Patient Relationship, 6 Dry Gangrene, 1068 Dupuytren Disease, 530 Dysplastic Nevus, 802

C Callus, 1050 Candida Vulvovaginitis, 445 Candidiasis, 979 Caries, 181

St re ng t h o Re co mme nd at io n (SO R)

*

Cellulitis, 580 Cerebral Vascular Accident, 1178 Chalazion, 65 Charcot Arthropathy, 1065 Chickenpox, 592 Chlamydia Cervicitis, 454 Chondrodermatitis Nodularis Helicis, 126 Chronic Obstructive Pulmonary Disease, 269 Chronic Kidney Disease, 426 Clavicular Fracture, 511 Clostridium Difficile Infection 326 Clubbing, 206 Cocaine, 1196 Colon Cancer, 329 Colon Polyps, 335 Common Warts, 617 Compression Fractures 501 Congenital Nevi, 793 Congenital Vascular Lesions, 1020 Conjunctivitis, 75 Contact Dermatitis, 691 Corneal Abrasion, 73 Corneal Foreign Body, 73 Corns, 1050 Coronary Artery Disease, 212 Corticosteroids, Topical and Intralesional, 1245 Cushing Syndrome 1164 Cutaneous Drug Reactions, 1024 Cutaneous Horn, 821 Cutaneous Larva Migrans, 680 Cutaneous T-Cell Lymphoma, 873

De f nit io n

A

Re comme nd ation b ase d on consiste nt and g ood -q uality p atie nt-orie nte d e vid e nce .*

B

Re comme nd ation b ase d on inconsiste nt or limite d -q uality p atie nt-orie nte d e vid e nce .*

C

Re comme nd ation b ase d on conse nsus, usual p ractice , op inion, d ise ase -orie nte d e vid e nce , or case se rie s for stud ie s of d iag nosis, tre atme nt, p re ve ntion, or scre e ning .*

Se e Ap p e nd ix A on p ag e s 1241-1244 for furthe r information.

TO PIC INDEX E Ear Foreign Body, 123 End of Life, 14 Epidermal Nevus, 798 Episcleritis, 80 Erythema Ab Igne, 1012 Erythema Annulare Centrifugum, 1045 Erythema Multiforme, 879 Erythema Nodosum, 886 Erythrasma, 575 Erythroderma, 761 Evidence-Based Medicine (EBM), 1242 Eye Trauma, 103 F Family Planning, 10 Flat Warts, 623 Folliculitis, 566 Foreign Body, Ear, 123 Fungal Infections, 638 G Gallstones, 344 Gangrene, Dry, 1068 Gastric Cancer, 349 Gastroesophageal Reflux Disease 354 Genital Warts, 627 Genodermatoses, 1039 Geographic Tongue, 159 Gingival Overgrowth, 166 Gingivitis, 162 Glaucoma, 87 Global Health, 32 Goiter, 1153 Gout, 504 Granuloma Annulare, 855 Graves Disease and Goiter, 1153 H Hammer Toe, 1057 Hand Eczema, 699 Hand, Foot, and Mouth Disease, 171 Headache, 1174 Heart Failure, 209 Hemorrhoids, 358 Hereditary and Congenital Vascular Lesions, 1020 Herpes Simplex, 606 Hidradenitis Suppurativa, 558 Hip Fracture, 522 Hoarseness, 149 Hordeolum, 65 Hydrocephalus, Normal Pressure, 1185 Hydronephrosis, 395 Hyperlipidemia, 1130 Hypertension, 225 Hypertensive Retinopathy, 93 Hyperthyroidism, 1153 Hyphema, 103 Hypothyroidism, 1148

I Impetigo, 562 Inflammatory Bowel Disease, 381 Ingrown Toenail, 975 Injection-Drug Use, 1235 Intestinal Worms and Parasites, 1080 Intimate Partner Violence, 50 Iritis, 84 Iron Deficiency Anemia 244 Ischemic Colitis 362 Ischemic Ulcer, 1062 K Kaposi Sarcoma, 1072 Keloids, 1034 Keratoacanthoma, 813 Kidney Stones, 398 Knee, 525 L Larynx (Hoarseness), 149 Lentigo Maligna, 817 Leukoplakia, 174 Lice, 668 Lichen Planus, 750 Liver Disease, 365 Lumbar Spinal Stenosis 499 Lung Cancer, 278 Lupus: Systemic and Cutaneous, 899 Lyme Disease, 1085 M Mastitis, 458 Melanoma, 842 Melasma, 996 Meningitis, 1091 Metatarsal Fracture, 519 Methamphetamine, 1223 Molluscum Contagiosum, 613 Morphea, 916 N Nail Variants, Normal, 964 Nasal Polyps, 130 Necrobiosis Lipoidica, 1125 Necrotizing Fasciitis, 588 Neurofibromatosis, 1191 Neuropathic Ulcer, 1063 Nevus Sebaceous, 798 Normal Pressure Hydrocephalus, 1185 Nummular Eczema, 706 O Obesity, 1135 Olecranon Bursitis, 508 Onychomycosis, 638 Oropharyngeal Cancer, 177 Osteoarthritis, 478 Osteomyelitis 1096 (continued on next page)

TO PIC INDEX Osteopenia, 1141 Osteoporosis, 1141 Otitis Externa, 119 Otitis Media with Effusion, 112 Otitis Media, Acute, 112 P Paget Disease of the Breast, 467 Pancreatitis, 373 Papilledema, 96 Paronychia, 985 Pemphigus, 934 Peptic Ulcer Disease, 377 Pericardial Effusion, 228 Periodontal Disease, 162 Peripheral Arterial Disease, 232 Pharyngitis, 143 Photosensitivity, 1006 Pigmented Nail Disorders, 970 Pitted Keratolysis, 572 Pityriasis Rosea, 745 Plantar Warts, 633 Pleural effusions, 286 Pneumonia, 308 Pneumothorax, 296 Polycystic Kidneys, 406 Polymyalgia Rheumatica, 533 Preauricular Tags, 126 Prostate Cancer, 410 Pseudofolliculitis, 554 Psoriasis, 729 Psoriatic Arthritis, 486 Psoriatic Nails, 488 Pterygium, 62 Pulmonary Embolus, 299 Pulmonary Fibrosis, 306 Pyoderma Gangrenosum, 861 Pyogenic Granuloma, 782 R Radius Fracture, Distal, 514 Reactive Arthritis, 757 Red Eye, 106 Renal Artery Stenosis, 225 Renal Cell Carcinoma, 421 Renal Failure, 426 Rheumatoid Arthritis, 482 Rosacea, 548 S Sarcoidosis, 310 Scabies, 673 Scarlet Fever, 143

Scarring Alopecia, 958 Scleral Pigmentation, 68 Scleritis, 80 Scleroderma, 916 Sebaceous Hyperplasia, 775 Seborrheic Dermatitis, 723 Seborrheic Keratosis, 770 Self-Inflicted Dermatoses, 710 Sexual Assault, Adult, 55 Sickle Cell Disease, 254 Sinusitis, 133 Skin Tag, 767 Social Justice, 23 Squamous Cell Carcinoma, 834 Stevens-Johnson Syndrome, 879 Subdural Hematoma, 1182 Substance Abuse Disorder, 1196 Subungual Hematoma, 993 Syphilis, 1102 T Tinea Corporis, 638 Tinea Cruris, 638 Tinea Pedis, 638 Tinea Versicolor, 638 Tobacco Addiction, 1201 Torus Palatinus, 141 Toxic Epidermal Necrolysis, 879 Traction Alopecia, 954 Trichomonas Vaginitis, 434 Trichotillomania, 954 Tuberculosis, 316 U Urethritis in Men, 1077 Urinary Sediment, 429 Urticaria, 716 Uveitis, 84 V Vaginitis, 434 Vascular Lesions, Hereditary and Congenital, 1020 Vascular Skin Lesions, Acquired, 1016 Vasculitis, 891 Venous Insufficiency, 239 Vitiligo, 1000 X Xanthomas, 1129 Z Zoster, 596 Zoster Ophthalmicus, 601