Atlas of Vascular Medicine : A Case-Based Approach to Current Management [1 ed.] 9781617050596, 9781936287291

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A Case-Based Approach to Current Management Emile R. Mohler III, MD Harold I. Litt, MD, PhD

Atlas of Vascular Medicine Features: w Comprehensive coverage of major entities in vascular medicine w Concise summaries of management principles

A Case-Based Approach to Current Management

Atlas of Vascular Medicine provides concise overviews of current management of vascular diseases utilizing a case-based format. A wide range of cases is presented encompassing arterial, venous, and lymphatic diseases. The atlas covers the major areas of vascular medicine in eight sections. Each section includes a concise overview of the area, followed by discussions of the major disease entities within that area. Each disease entity is introduced by an illustrative case presentation and is followed by a detailed topic review including clinical features, laboratory and imaging workup, treatment and prognosis, clinical pearls, discussion of differential diagnoses, and review questions. The presentations are well illustrated to provide a visual, user-friendly approach. Each case presentation has been selected to provide representative examples of the most likely presentation in clinical practice, with complications and variants discussed in the management summary concluding the case.

Vascular Medicine

Vascular Medicine

Atlas of

Atlas of

Atl a s o f

Vascular Medicine A Case-Based Approach to Current Management

w Case approach showing application of principles in clinical practice

w Clinical Pearls, Differential Diagnoses, and Questions and Answers conclude each case w Expert faculty contributors

Recommended Shelving Category:

Cardiology

11 W. 42nd Street New York, NY 10036 www.demosmedpub.com

9 781936 287291

Mohler • Litt

w Highly illustrated with high-quality images from frequently encountered modalities

EDITORS

E m i l e R . Mo h l er I I I H a ro l d I . Litt

Atlas of Vascular Medicine A Case-Based Approach to Current Management

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Atlas of Vascular Medicine A Case-Based Approach to Current Management EDITORS

Emile R. Mohler III, MD Harold I. Litt, MD, PhD

New York

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ISBN: 978-1-936287-29-1 e-book ISBN: 978-1-617050-59-6 Acquisitions Editor: Rich Winters Compositor: S4Carlisle Publishing Services Visit our website at www.demosmedpub.com © 2012 Demos Medical Publishing, LLC. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher. Medicine is an ever-changing science. Research and clinical experience are continually expanding our knowledge, in particular our understanding of proper treatment and drug therapy. The authors, editors, and publisher have made every effort to ensure that all information in this book is in accordance with the state of knowledge at the time of production of the book. Nevertheless, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, express or implied, with respect to the contents of the publication. Every reader should examine carefully the package inserts accompanying each drug and should carefully check whether the dosage schedules mentioned therein or the contraindications stated by the manufacturer differ from the statements made in this book. Such examination is particularly important with drugs that are either rarely used or have been newly released on the market. Library of Congress Cataloging-in-Publication Data Atlas of vascular medicine : a case-based approach to current management / editors, Emile R. Mohler III, Harold Litt ; section editors, Emil M. deGoma ... [et al.]. p. ; cm. Includes bibliographical references. ISBN-13: 978-1-936287-29-1 ISBN-10: 1-936287-29-3 ISBN-13: 978-1-61705-059-6 (e-book) ISBN-10: 1-61705-059-8 (e-book) I. Mohler, Emile R. II. Litt, Harold. [DNLM: 1. Vascular Diseases—therapy—Atlases. 2. Vascular Diseases—therapy—Case Reports. 3. Blood Vessels—pathology— Atlases. 4. Blood Vessels—pathology—Case Reports. WG 17] 616.13—dc23 2011039929

Special discounts on bulk quantities of Demos Medical Publishing books are available to corporations, professional associations, pharmaceutical companies, health care organizations, and other qualifying groups. For details, please contact: Special Sales Department Demos Medical Publishing, LLC 11 West 42nd Street, 15th Floor New York, NY 10036 Phone: 800-532-8663 or 212-683-0072 Fax: 212-941-7842 E-mail: [email protected] Printed in the United States of America at Bradford & Bigelow. 11 12 13 14 / 5 4 3 2 1

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Editors

EDITORS Emile R. Mohler III, MD Director of Vascular Medicine University of Pennsylvania Medical Center

Harold I. Litt, MD, PhD Associate Professor of Radiology University of Pennsylvania Medical Center

SECTION EDITORS Emil M. deGoma, MD – Section 3 Instructor in Medicine Cardiovascular Division, Vascular Medicine Section University of Pennsylvania School of Medicine Luis H. Eraso, MD – Section 1 Fellow Cardiovascular Division, Vascular Medicine Section University of Pennsylvania School of Medicine Jay Giri, MD – Section 5 Fellow Cardiovascular Division, Vascular Medicine Section University of Pennsylvania School of Medicine Supratik Moulik, MD – Section 4 Fellow Department of Radiology Cardiovascular Imaging Section University of Pennsylvania School of Medicine

Michael T. Mullen, MD – Section 2 Instructor in Neurology Department of Neurology Division of Stroke and Neurocritical Care University of Pennsylvania School of Medicine Geoffrey O. Ouma, DO – Sections 6 & 8 Fellow Cardiovascular Division, Vascular Medicine Section University of Pennsylvania School of Medicine H.D. Sara Rovno, MD – Section 4 Fellow Department of Radiology Cardiovascular Imaging Section University of Pennsylvania School of Medicine M. Haris U. Usman, MD – Section 7 Fellow Cardiovascular Division, Vascular Medicine Section University of Pennsylvania School of Medicine

v

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Contributors

Joshua F. Baker, MD Internal Medicine University of Pennsylvania School of Medicine

Benjamin Jackson, MD Department of Surgery, Division of Vascular Surgery University of Pennsylvania School of Medicine

Anthony Chung-Kai Chyou, MD Johns Hopkins University School of Medicine Baltimore, Maryland

Gaurav Jindal, MD Fellow Department of Radiology, Division of Neuroradiology University of Pennsylvania School of Medicine

Christopher Dibble, MD Fellow Cardiovascular and Pulmonary Divisions, University of Pennsylvania School of Medicine Eri Fukaya, MD, PhD Resident Department of Medicine Beth Israel Medical Center Albert Einstein College of Medicine New York, New York Deeba Faruq, MD Research Fellow Cardiovascular Division, Vascular Medicine Section University of Pennsylvania School of Medicine Naeema Ginwala, MD Resident Einstein/Montefiore Department of Medicine Albert Einstein College of Medicine of Yeshiva University New York, New York Bruce Gray, DO Greenville, South Carolina Atul Jain, MD Research Fellow Cardiovascular Division, Vascular Medicine Section University of Pennsylvania School of Medicine

Rebecca A. Jonas, BA Research Coordinator University of Pennsylvania School of Medicine Elena Ladich, MD, PhD Chief of Anatomic Pathology CVPath Institute Gaithersburg, Maryland Scott M. Lilly, MD Cardiovascular Division Vascular Medicine Section University of Pennsylvania School of Medicine Timothy R. Miller, MD Fellow Department of Radiology, Division of Neuroradiology University of Pennsylvania School of Medicine Michael T. Mullen, MD Instructor in Neurology Department of Neurology Division of Stroke and Neurocritical Care University of Pennsylvania School of Medicine Jose Pascual, MD Department of Surgery and Trauma University of Pennsylvania School of Medicine

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Contributors

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Atif N. Qasim, MD Fellow Cardiovascular Division University of Pennsylvania School of Medicine Kamin Patel, MD Cardiovascular Division, Vascular Medicine Section University of Pennsylvania School of Medicine Amresh Raina, MD Fellow Cardiovascular Division University of Pennsylvania School of Medicine David Z. Rose, MD Fellow Department of Neurology Division of Stroke and Neurocritical Care University of Pennsylvania School of Medicine

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Igor Rybinnik, MD Fellow Department of Neurology Division of Stroke and Neurocritical Care University of Pennsylvania School of Medicine Shivang Shah, MD Internal Medicine University of Pennsylvania School of Medicine Hadas Shiran, MD Fellow Cardiovascular Medicine Stanford University School of Medicine Eugene Yuriditsky, MD Internal Medicine University of Pennsylvania Hospital

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Contents

Editors v Contributors Preface xiii

Section I.

Case 9. Symptomatic Carotid Disease Michael T. Mullen Timothy R. Miller

vii

Case 10. Extracranial Vertebral Artery Stenosis 49 David Z. Rose Gaurav Jindal Michael T. Mullen

Peripheral Artery Disease

Section Editor: Luis H. Eraso Case 1. Aorto-Iliac Disease 1 Luis H. Eraso Supratik Moulik Case 2. Infra-Inguinal Disease Eri Fukaya Supratik Moulik Luis H. Eraso

7

Case 3. Upper Extremity Arterial Disease Naema Ginwala Supratik Moulik Jay Giri

13

Case 4. Popliteal Cystic Adventitial Disease Luis H. Eraso Supratik Moulik Bruce Gray

19

Section 2.

Case 11. Extracranial Carotid and Vertebral Artery Dissection 55 Igor Rybinnik Timothy R. Miller Michael T. Mullen Case 12. Intracranial Stenosis David Z. Rose Gaurav Jindal Michael T. Mullen Case 13. Lacunar Infarction Igor Rybinnik Timothy R. Miller Michael T. Mullen

Case 5. Popliteal Artery Entrapment Syndrome (PAES) 23 Luis H. Eraso Supratik Moulik Case 6. Popliteal Artery Aneurysm Luis H. Eraso Supratik Moulik

Section 3.

61

67

Aortic Disease

Section Editor: Emil M. deGoma Case 14. Acute Aortic Dissection—Type A Hadas Shiran Emil M. deGoma Supratik Moulik

27

Cerebrovascular Disease

Case 15. Acute Aortic Dissection—Type B Hadas Shiran Emil M. deGoma

Section Editor: Michael T. Mullen Case 7. Aortic Arch Atheroma 31 Michael T. Mullen Atif N. Qasim Case 8. Asymptomatic Carotid Stenosis Michael T. Mullen Timothy R. Miller

43

37

71

79

Case 16. Penetrating Atherosclerotic Ulcer and Intramural Hematoma 83 Emil M. deGoma Supratik Moulik H. D. Sara Rovno ix

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Contents

x

Case 17. Thoracic Aortic Aneurysm Eugene Yuriditsky H. D. Sara Rovno Supratik Moulik Emil M. deGoma Case 18. Abdominal Aortic Aneurysm Scott M. Lilly Supratik Moulik Emil M. deGoma

Section 4.

Case 28. Vasculitides: Kawasaki Disease Geoffrey O. Ouma Supratik Moulik

87

Case 29. Vasculitides: Mixed Cryoglobulinemia Geoffrey O. Ouma Elena Ladich Rebecca A. Jonas

93

Mesenteric Disease

Section Editors: Supratik Moulik, H.D. Sara Rovno Case 19. Acute Mesenteric Ischemia 99 Supratik Moulik M. Haris U. Usman Case 20. Budd-Chiari Syndrome Supratik Moulik M. Haris U. Usman

105

Case 21. Chronic Mesenteric Ischemia M. Haris U. Usman Supratik Moulik Case 22. Visceral Arterial Aneurysms Supratik Moulik M. Haris U. Usman

Section 5.

113

Renovascular Disease 117

Section 6. Vasculitis and Vasospastic Diseases

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Case 31. Vasculitides: Takayasu’s Arteritis Geoffrey O. Ouma Supratik Moulik Joshua F. Baker

157

163

Section 7.

Venous Disease

Section Editor: M. Haris U. Usman Case 34. Superficial and Deep Venous Thrombosis 183 Kamin Patel M. Haris U. Usman

Case 24. Fibromuscular Dysplasia 121 Anthony Chung-Kai Chyou Supratik Moulik Jay Giri

Case 27. Vasculitides: Henoch–Schönlein Purpura 139 Geoffrey O. Ouma Supratik Moulik Elena Ladich

Case 30. Vasculitides: Polyarteritis Nodosa Geoffrey O. Ouma Supratik Moulik Elena Ladich

Case 33. Vasculitides: Granulomatosis With Polyangiitis (GPA, Formerly Wegener’s) 175 Geoffrey O. Ouma Supratik Moulik Joshua F. Baker Elena Ladich

Section Editor: Jay Giri Case 23. Atherosclerotic Renal Artery Stenosis Shivang Shah Supratik Moulik Jay Giri

Case 26. Vasculitides: Giant Cell Arteritis Geoffrey O. Ouma Supratik Moulik Elena Ladich

151

Case 32. Vasculitides: Thromboangiitis Obliterans 169 Geoffrey O. Ouma Supratik Moulik Rebecca A. Jonas

109

Section Editor: Geoffrey O. Ouma Case 25. Churg–Strauss Syndrome (Allergic Granulomatous Angiitis) Geoffrey O. Ouma Supratik Moulik Elena Ladich

145

127

133

Case 35. Pulmonary Embolism Christopher Dibble Amresh Raina Supratik Moulik M. Haris U. Usman

187

Case 36. Varicose Veins 193 Atul Jain Deeba Faruq Supratik Moulik M. Haris U. Usman Case 37. Venous Thoracic Outlet Syndrome Supratik Moulik M. Haris U. Usman Case 38. Superior Vena Cava Syndrome Supratik Moulik M. Haris U. Usman

197

201

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Contents

Case 39. May–Thurner Syndrome Supratik Moulik M. Haris U. Usman

xi

205

Case 40. Deep Venous Phlegmasia With Phlegmasia Cerulea Dolens 209 Jose Pascual Benjamin Jackson Supratik Moulik M. Haris U. Usman

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Section 8.

Lymphedema

Section Editor: Geoffrey O. Ouma Case 41. Lymphedema 213 Atul Jain Geoffrey O. Ouma Deeba Faruq Index

217

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Preface

The current practice of vascular medicine integrates traditional patient history and physical examination findings with advanced imaging and molecular diagnostic technologies. This case-based atlas of vascular disease incorporates many high-quality images from frequently encountered modalities. A wide range of clinical cases is

presented, encompassing arterial, venous, and lymphatic diseases. Key points and review questions conclude each case to reinforce learning objectives. It is hoped that the case-based format will facilitate rapid learning and serve as a quick reference. Emile R. Mohler III and Harold I. Litt

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1

Aorto-Iliac Disease Luis H. Eraso and Supratik Moulik

HIP, BUTTOCK, AND THIGH CLAUDICATION A 63-year-old male with history of single vessel coronary artery disease, hypercholesterolemia, hypertension, heavy smoking, and osteoarthritis consulted with progressive pain with ambulation in the left hip, buttock, and thigh. Pain and muscle tightness were initially present only with brisk walking or exercise. However, despite physical and medical therapy for osteoarthritis, he reports worsening symptoms in the last few months when walking less than one block that resolve with 3 to 10 minutes of rest. He denies pain at rest, leg numbness, weakness, or skin abnormalities. In addition, he denies chest pain, dyspnea on exertion, lower extremity edema, or fatigue. On physical examination he has normal carotid upstroke with no bruits, normal heart sounds, and no evidence of bruits or pulsatile masses in the abdomen. In the lower extremities, right femoral pulse is weak and left femoral pulse is absent. Positional evaluation revealed dependent rubor in the left foot. Noninvasive hemodynamic assessment of the lower extremities showed a reduced thigh/brachial index bilaterally, a mildly reduced ankle–brachial index on the right (0.7) and significantly reduced on the left (0.54). A computerized tomography angiogram (CTA) of the distal aorta with runoff revealed a high-grade stenosis of the left common iliac artery with distal occlusion, collateral flow, and reconstitution of the left superficial femoral artery flow. Atherosclerotic plaque and extensive calcification was also present in the distal aorta, right iliac, and femoral arteries with evidence of moderate to severe stenosis.

■ DEFINITION/BACKGROUND/EPIDEMIOLOGY Peripheral arterial disease (PAD) is the preferred term to describe a flow-limiting lesion to the lower or upper extremity arteries. By far (up to 90%) the most common cause is atherosclerosis. However, other conditions such as thrombosis, embolic disease, large and medium arteritis, fibromuscular dysplasia, endofibrosis, and entrapment syndromes should be considered in special circumstances. The prevalence of PAD, defined as a ratio of less than 0.9 between the systolic ankle and brachial

pressures (usually referred to as the ankle-brachial index or ABI), varies from less than 4% at age 40 to 20% or higher in those 65 years or older. It is well established that risk factors for coronary atherosclerosis are also major determinants of atherosclerosis in the peripheral arteries. Smoking, diabetes, hyperlipidemia, hypertension, and chronic kidney disease have been identified as PAD risk factors in different populations. Novel risk factors include C-reactive protein, fibrinogen, and hyperhomocystenemia. In particular, smoking and diabetes are not only risk factors for PAD, but are strong 1

Peripheral Artery Disease

2

modifiers of the prognosis and clinical presentation of the disease. Smoking increases the risk for PAD more than it does for coronary artery disease, and more than 85% of subjects with claudication are current smokers. Diabetes predisposes to a more extensive and diffuse form of PAD characterized by advanced calcification and predisposition for infra-popliteal artery involvement.

■ CLINICAL FEATURES The cardinal symptom of PAD is intermittent claudication (IC), while rest pain and other features of critical limb ischemia (CLI) develop at advanced stages of the disease (Table  1.1). Claudication is typically reported as exertional pain, cramping or tightness that occurs in a defined muscle groups, whereas joints are spared. It usually occurs at a consistent walking distance and level of activity, and resolves completely after 3 to 8  minutes of rest. Only 10% to 35% of patients with PAD present with classical IC, whereas 50% to 90% are asymptomatic or exhibit atypical leg symptoms. A small group (1% to 2%) progress to CLI in which resting and night pain is usually present. Other features of CLI include loss of skin integrity, muscle atrophy, neuropathy, ulcerated lesions, or even frank gangrene. PAD is a multivessel disease in 64% of cases; among them 51% will have aorto-iliac disease, 65% will have femoro-popliteal disease, and up to 71% will have some degree of infra-popliteal disease. In other studies evaluating single segmental distribution of PAD, it has been found that femoro-popliteal disease is present in 44% of the subjects, whereas only 17% to 22% had exclusively aorto-iliac involvement. The relationship between the muscle group impaired by IC and the localization of the arterial segment occlusion

is relatively well established. Occlusive arterial disease of the common or external iliac arteries in general presents as a unilateral pain and claudication in the hip, buttock, upper thigh, and calf, whereas bilateral symptoms and erectile dysfunction (vasculogenic impotence or Leriche syndrome) are consistent with aorto-iliac disease. Unusual cases of aorto-iliac disease with lower lumbar arteries involvement may present as “sciatica” and lower back discomfort. Clinical examination of the patient with PAD entails a comprehensive clinical history to identify co-morbidities (i.e., coronary artery disease, diabetes, congestive heart failure or chronic obstructive pulmonary disease, smoking) that modify the prognosis of the disease and clinical risk of therapeutic interventions. In addition to the routine physical examination, a focused vascular examination entails measurement of blood pressure on both arms, auscultation of the neck for presence of carotid bruits, auscultation, and palpation of the abdomen to identify bruits and palpable pulsatile masses, and palpation, auscultation, or Doppler identification the brachial, radial, femoral, popliteal, posterior tibial, and dorsalis pedis pulses. Skin should be carefully evaluated for atrophy, alopecia, fissures, calluses, and other pre-ulcerative abnormalities characteristic of CLI. Similarly, musculature of the hip, buttock, thigh, and calf should be evaluated for atrophy or regional weakness. Positional evaluation of the legs may be helpful to identify elevation pallor and dependent rubor.

■ LABORATORY AND IMAGING WORK Laboratory evaluation in PAD is directed to identify modifiable risk factors, such as fasting glucose and glycosylated hemoglobin for diabetes, and fasting lipid profile for hyperlipidemia. A baseline assessment of kidney function is indicated to direct future imaging evaluation and interventions.

Table 1.1 Peripheral Arterial Disease Clinical Classifications Rutherford Clinical Categories of Chronic Limb Ischemia

Fontaine Classification of Peripheral Arterial Disease

Grade

Stage

Category 0

I

II

III

Clinical Description Asymptomatic, not hemodynamically correct

Clinical Description

I

Asymptomatic

1

Mild claudication

II

Intermittent claudication

2

Moderate claudication

IIa

Pain-free, claudication walking >200 m

3

Severe claudication

IIb

Pain-free, claudication walking 3 BP medications • History of multivessel CAD • History of PVD • Abdominal bruit • Unexplained pulmonary edema • ARAS diagnostic tests • Doppler ultrasound • CTA/MRA • Angiography—gold standard • ARAS treatment • Medical management with ACEi/ARBs, diuretics, and lifestyle modifications • Percutaneous intervention with stent placement

■ DIFFERENTIAL DIAGNOSES The remainder of the blood work is used to rule out other secondary causes of hypertension. The main differential diagnoses to consider are • Pheochromocytoma—presents with resistant and accelerated hypertension that tends to be more episodic in nature. Plasma-free metanephrines, urine metanephrines, catecholamines, and plasma normetanephrine can help differentiate from ARAS when they are elevated.

Renovascular Disease

120

• Primary hyperaldosteronism—presents similarly to ARAS with resistant hypertension. Imaging such as adrenal CT may show an adrenal adenoma. Plasma aldosterone/renin ratio can be measured and can help differentiate from ARAS when the ratio is >20. • Fibromuscular dysplasia—typically presents in women 10% on WBC count

Mononeuropathy or polyneuropathy

Development of mononeuropathy, multiple mononeuropathies, or polyneuropathy (i.e., glove-stocking distribution) attributable to vasculitis

Pulmonary infiltrates nonfixed

Migratory or transitory pulmonary infiltrates on radiographs (not including fixed infiltrates) attributable to systemic vasculitis

Paranasal sinus abnormality

History of acute or chronic paranasal sinus pain or tenderness or radiographic opacification of the paranasal sinuses

Extravascular eosinophils

Biopsy, including artery, arteriole, or venule, showing accumulation of eosinophils in extravascular area

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counts may show normochromic, normocytic anemia, and leukocytosis. Elevated IgE and complement levels may occur, as well as positive rheumatoid factor. Acute phase reactants such as the ESR and C-reactive protein (CRP) may be elevated, but their usefulness in CSS is unclear because they are nonspecific. Imaging evaluation includes chest radiography and high-resolution chest computed tomography (HRCT). Chest radiography abnormalities may include transient and patchy opacities (75% of patients) without lobar or segmental distribution, symmetrical opacities in an axillary and peripheral distribution, opacities from the hilum with hilar adenopathy, diffuse interstitial opacities, widespread shadowing form pulmonary hemorrhage, bilateral, nodules without cavitation, hilar adenopathy (rare), and pleural effusions (30% of patients). Typically, HRCT findings in CSS are not specific and may include peribronchial thickening, septal thickening, and patchy opacities.

Vasculitis and Vasospastic Diseases

CLINICAL PEARLS • The combination of asthma, eosinophilia, and symptoms of vasculitis has a 85% sensitivity and 99% specificity for the diagnosing CSS. • Mononeuritis multiplex is the neurological disturbance most commonly seen in patients presenting with CSS. • Bilateral patchy pulmonary infiltrates are often seen on the initial chest radiograph and can be misdiagnosed as other forms of pneumonias. • Asthma and other allergies precede the onset of CSS. • There are three distinct phases in the evolution of CSS: (1) prodromal phase with adult onset asthma predating the onset of vasculitis, (2) eosinophilic phase characterized by elevated peripheral and tissue eosinophilia leading to eosinophilic pneumonia, (3) a vasculitic phase with multisystem involvement.

■ TREATMENT AND PROGNOSIS The aim of therapy in CSS is to minimize or prevent irreversible organ damage and to suppress the disease activity. The treatment of CSS is similar to that of other systemic vasculitides. Initial therapy in less severe disease is corticosteroids, e.g., prednisone 1  mg/ kg/day for 1 to 2  months or until disease severity is improved, then tapered. In the case of severe disease, cyclophosphamide may be administered in combination with prednisone at a dose of 2  mg/kg/day over 6 months. Azathioprine and methotrexate may be used for remission maintenance and steroid sparing purposes. Studies have shown no significant difference in mortality and outcomes when plasmaphoresis is used as compared to medical management. Limited evidence exists supporting the use of interferon-alpha or antitumor necrosis factor (TNF) for the treatment of cyclophosphamide refractory CSS. CSS treatment does not eliminate asthma and other allergies, and these disorders still need long-term therapy. The use of corticosteroid therapy in the treatment of CSS has significantly improved survival from 50% within 3  months of diagnosis in the pre-steroid era to 90% at 1 year, 62% to 75% at 5  years, and 50% at 7  years. Predictors of poor prognosis include renal disease, gastrointestinal involvement, (perforation, hemorrhage, and bowel ischemia), cardiomyopathy, central nervous system involvement, weight loss of greater than 10% of total body weight, and age greater than 50  years. The majority of patients do maintain remission, but some relapse requiring lifelong therapy. The three main causes of death in CSS are the involvement of the cardiovascular system, central nervous system, and gastrointestinal tract.

■ DIFFERENTIAL DIAGNOSES • Asthma, sinusitis, and rhinitis—These disorders precede the onset of CSS and are part of the clinical syndrome. However, the degree of eosinophilia in asthma, sinusitis, or rhinitis is less as compared to CSS and does not involve other organs. • Hypereosinophilic syndrome (HES)—HES may also present with history of allergy, rash, pulmonary infiltrates, and eosinophilia, which can be identical to those seen in CSS. In contrast, the eosinophilia in HES is usually refractory to steroid therapy and systemic vasculitis and granulomas are absent. • Chronic eosinophilic pneumonia (CEP)—CEP may mimic CSS, but CEP usually lacks granulomas on biopsy and generally does not involve organs other than the lung and is common in females than males. • Hypersensitivity vasculitis—May also show some degree of eosinophilia, especially on tissue biopsy, but the disorder is mainly limited to the skin, and frequently presents as urticaria. • Polyarteritis nodusa (PAN)—Although PAN presents with eosinophilia, it is less intense than in CSS, and intravascular granulomas are rarely seen. PAN is also commonly associated with microaneurysms formation, a feature not seen in CSS. • Granulomatosis with polyangiitis (GPA), (Wegener’s)— May mimic CSS by being ANCA positive vasculitis. However, asthma and eosinophilia are not seen in GPA (Wegener’s). CSS has extrapulmonary findings commonly seen in the gastrointestinal tract, spleen, and heart, rather than the upper airways and the

Vasculitides: Churg–Strauss Syndrome (Allergic Granulomatous Angiitis)

kidney as found in WG. The type of ANCA seen in CSS is typically anti-myeloperoxidase, whereas in WG, it is more likely anti-proteinase 3. • Microscopic polyangiitis (MPA)—MPA is a small vessel vasculitis that also tests ANCA positive, typically anti-myeloperoxidase type, as also seen in CSS. However, renal disease in CSS is uncommon and is less aggressive as compared to MPA, which is common and more aggressive (rapidly progressive glomerulonephritis).

■ QUESTIONS AND ANSWERS 1. A 45-year-old female with a history of CSS diagnosed 5 years ago and treated with combination of pulse doses of corticosteroids and cyclophosphamide, now presents with a new onset bilateral lower extremity numbness, weakness, and difficulty ambulating. She has a history of remote stroke and hepatitis B viral infection. The previous day, her right leg “gave out” and she could not bear weight on it. She reports no other weakness elsewhere. Which of the following is the most likely complication of CSS in this case? a. b. c. d.

Cyclophosphamide toxicity Mononeuritis multiplex with foot drop A new stroke Complications from hepatitis B

Answer: b 2. All of the following are commonly affected in CSS EXCEPT the a. b. c. d. e.

Nervous system Gastrointestinal tract Lungs Heart Eyes

Answer: e

131

3. Churg–Strauss syndrome is a. A small-vessel vasculitis that includes other vasculitides such as WG, microscopic polyangiitis, hypersensitivity vasculitis, and mixed essential cryglobulinemia b. A large vessel vasculitis resembling Takayasu’s arteritis and giant cell arteritis c. Medium vessel arteritis that includes Kawasaki disease and PAN d. A secondary arteritis from asthma and eosinophilia e. None of the above Answer: a

■ SUGGESTED READINGS 1. Churg J, Strauss L. Allergic granulomatosis, allergic angiitis, and periarteritis nodosa. Am J Pathol. 1951;27(2):277–301. 2. Guillevin L, Cohen P, Gayraud M, Lhote F, Jarrousse B, Casassus P. Churg–Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore). 1999;78(1):26–37. 3. Lanham  JG, Elkon  KB, Pusey  CD, Hughes  GR. Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg–Strauss syndrome. Medicine (Baltimore). 1984; 63(2):65–81. 4. Lanham JG, Churg J. Churg–Strauss syndrome. In: Churg A, Churg J, eds. Systemic Vasculitides. Tokyo, Japan: Igaku-Shoin; 1990. 5. Masi  AT, Hunder  GG, Lie  JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg– Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990;33(8):1094–1100. 6. Pagnoux C, Guillevin L. Churg–Strauss syndrome: evidence for disease subtypes? Curr Opin Rheumatol. 2010;22(1):21–28. 7. Sinico RA, Di Toma L, Maggiore U, et al. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg–Strauss syndrome. Arthritis Rheum. 2005;52(9):2926–2935.

26

Vasculitides: Giant Cell Arteritis Geoffrey O. Ouma, Supratik Moulik, and Elena Ladich

JAW CLAUDICATION AND HEADACHES A 58-year-old female was admitted to the hospital complaining of bilateral temporal headaches, jaw discomfort, tender scalp, fever, and muscle aches that started over 2  weeks ago. On presentation to the hospital, she reports acute onset of visual changes. Her medical history includes hypertension, coronary artery disease, hypercholesterolemia, and prior stroke. She denies tobacco, alcohol, or illicit drug use. On physical examination, she is febrile, other vital signs being normal. Head, ears, eyes, nose, and throat examination revealed visual acuity of 20/25 bilateral eyes with pupils that reacted sluggishly to light. An ophthalmoscopic examination revealed a pale and swollen optic nerve in the left eye and a normal optic nerve on the right eye. There were tender nonpulsatile dilated bilateral temporal arteries. Cardiopulmonary examination revealed grade 3/6 systolic murmur with decreased pulmonary breath sounds. Vascular examination was normal without bruits and distal pulses were intact. Laboratory evaluation revealed elevated erythrocyte sedimentation rate (ESR) of 96  mm/hour, as well as C-reactive protein of 63  mg/dL. There was leukocytosis of 15,160/μL with 95% neutrophils as well as normochromic, normocytic anemia. Serum electrolytes, renal function tests, liver function tests, and creatinine kinase levels were all normal. With these findings, a provisional diagnosis of giant cell arteritis was made and treatment with corticosteroids was started. Biopsies were obtained from the temporal arteries and histologic evaluation revealed a dense infiltrate of the media with lymphocytes and giant cells with destruction of the internal elastic lamina (Figure  26.1). Figure  26.2 shows a normal histological architecture of temporal artery. These features confirmed the diagnosis of giant cell arteritis (GCA). Further evaluation by magnetic resonance angiography (MRA) of the chest and neck revealed arteritis involving the left subclavian artery proximally and the descending thoracic aorta (Figures 26.3 and 26.4).

133

Vasculitis and Vasospastic Diseases

134

Normal Histology of Temporal Artery Biopsy

a systemic vasculitis that is increasingly seen in extracranial vessels such as abdominal visceral arteries, subclavian arteries, axillary arteries, brachial arteries, and iliac and femoral popliteal arteries. GCA is also associated with polymyalgia rheumatica (PMR), arthralgias, tenosynovitis, and systemic constitutional symptoms such as fatigue, weight loss, and low-grade fever. The prevalence of GCA in the United States is estimated at 200 per 100,000 persons age 50 or older and the frequency in Northern Europe is estimated to be twice that of the United States. The median age at diagnosis is between 70 and 75 years and females predominate over males (F:M ratio of 3:2). GCA is also common among people of European descent and is less seen in African-Americans and Asians.

■ CLINICAL FEATURES

Figure 26.1 Normal temporal artery: Most temporal biopsies are non-diagnostic. The intima may appear somewhat thick (I) because of vasoconstriction. A = adventitia, M = media. The internal elastic lamina (arrowhead) is intact, there is no inflammation, and the intima is regularly thickened without fibrosis.

The onset of GCA may be acute or insidious with initial symptoms being constitutional such as low-grade fever, myalgias, anorexia, fatigue, and weight loss, lasting for a few days to weeks. However, the classic presentation of GCA is new-onset headache, usually localized to the temporal or occipital region. Associated with the headache is scalp tenderness distributed over the temporal region. Other headache-associated symptoms are jaw claudication, temporal pulselessness, facial pain, earache, toothache, tongue and palate pain, and odynophagia. Visual change in GCA is common and is a true emergency, especially if it is an acute painful episode. The neuro-ophthalmic symptoms may include diplopia, ptosis, nystagmus, ophthalmoplegia, and papillary abnormalities. The cause of visual loss is anterior ischemic optic neuropathy (AION), which is due to ischemia of the optic nerve head. Involvement of the aorta may present with chest or back pain as a result of aortic aneurysm or dissection. These may extend and involve the heart with coronary

■ DEFINITION/BACKGROUND/EPIDEMIOLOGY Giant cell arteritis (GCA), also known as temporal arteritis, is the most common form of vasculitis with predilection to the medium- and large-sized arteries, and almost exclusively affects individuals over the age of 50 years. The typical vessels affected are the aorta and its branches. Historically, GCA was believed to be a localized disease confined to the cranial arteries, particularly the temporal arteries, and the artery of the retina and the optic nerve. This was particularly explained by the characteristic symptoms of GCA, such as tender and swollen temporal arteries, temporal headaches, jaw claudication, and visual loss. However, it is now known that GCA is

Histopathology of Temporal Artery in a Patient With GCA

A

B

Figure 26.2 Histopathology of temporal artery biopsy in a patient with giant cell arteritis. This shows a cross section at high magnification (Movat elastic stain). Note destruction of IEL (arrowheads, panel B) with surrounding giant cells (arrows, panel A) and other inflammatory cells.

Vasculitides: Giant Cell Arteritis

135

Axial Magnetic Resonance Angiography (MRA) of the Chest in a Patient With GCA

and extremities muscle atrophy. Patient may complain of arm fatigue as a result of ischemic stenosis of the subclavian or axillary arteries. Lower extremity claudications due to obstruction of the iliac and femoropopliteal arteries have been reported, but their true frequency is not known. Cerebrovascular disease can occur in up to 25% of patients and is the most common cause of death in patients with GCA. The neurological symptoms may include neuropsychiatric disorders, peripheral neuropathy, and seizures.

■ LABORATORY AND IMAGING WORK UP Like other vasculitides, GCA is a clinical diagnosis based on the demographic features, clinical features, inflammatory markers, or favorable response to glucocorticoids. Laboratory values are used to predict the extent and severity of systemic disease and to discriminate GCA from other large vessel vasculitides. Normochromic, normocytic anemia is common during the acute phase, but white blood cell count and platelet count are usually normal. Kidney function is often normal. Liver function tests may be elevated. Erythrocyte sedimentation rate (ESR) is often elevated to the excess of >100 mm/ hour, and is rarely normal, although its absence does not completely exclude GCA. C-reactive protein (CRP) is elevated as well and has a higher sensitivity and specificity in the diagnosis of GCA than ESR. Fibrinogen may also be elevated.

Figure 26.3 Axial dark blood MR figure through the mid chest demonstrates marked crescentic thickening of the mid descending aorta (arrowhead).

artery aneurysm and aortic valve regurgitation. Physical examination findings involving extracranial peripheral arteries may include pulselessness, decreased blood pressure measurements, axillary artery bruits,

Sagittal MRA of the Neck and Chest in a Patient With GCA

A

B

Figure 26.4 Pre- (A) and post-contrast (B) oblique sagittal MRA image of the chest demonstrates diffuse enhancement of the descending aortic wall (arrows). There is also ostial stenosis of the left common carotid artery, which is partially seen on this image (white arrow).

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136

Sagittal MRA of the Neck and Chest Posttherapy in a Patient With GCA

A

B

Figure 26.5 Pre- (A) and post-contrast (B) oblique sagittal MRA image of the chest demonstrates near resolution of the enhancement of the descending aortic wall (arrows) 2 years posttherapy. Courtesy of Harold Litt, MD, PhD. Chief, Cardiovascular Imaging Section. University of Pennsylvania Medical School, Philadelphia, PA.

The American College of Rheumatology (1990) criteria for the diagnosis of GCA is as follows: (a) age of onset at 50 years; (b) new headache; (c) abnormalities of the temporal arteries, ESR of 50 mm/hour; (d) positive result of a temporal artery biopsy (vasculitis characterized by a predominance of mononuclear infiltrates or granulomas, usually with multinucleated giant cells). Biopsy is mandated to confirm the diagnosis if the clinical features suggest GCA. The characteristic histopathologic features are infiltration of all the arterial layers by T-lymphocytes and macrophages. Multinuclear giant cells are typically found in the proximity of the elastic lamina. Activated CD4+ T cells are the main inflammatory cells involved in this disease. Imaging modalities that may be used to assist in the diagnosis of GCA include invasive angiography, computed tomography (CT), and magnetic resonance imaging (MRI). Angiography is sensitive but nonspecific. However, angiography is helpful when an area must be chosen after the initial biopsy result is negative for repeat biopsy. Aortic arch and cerebral angiography may show occlusion and alternating stenotic areas. CT/MRA can also be used especially to detect inflammation in the arterial wall as well as demonstrate disease anatomy such as luminal narrowing and aneurysms. Magnetic resonance angiography (MRA) has the added advantage because it can detect edema and is able to demonstrate inflammation more accurately that conventional angiography or CTA.

Color duplex ultrasonography of the temporal arteries has been studied and has a potential to be a compliment biopsy in the diagnosis of GCA. The classical sign of a dark halo in the temporal artery has a sensitivity of 73% and specificity of 100%. This feature represents vessel wall edema. This modality could be useful in the diagnosis of GCA without biopsy, but more studies are needed for validation. The other issue with duplex ultrasound is that it is operator dependent and can confound diagnosis accuracy. Fluorine-18-desoxyglucose positron emission tomography (18F-FDG-PET) has recently shown promising results for the detection of arterial wall inflammation, but it also needs further studies for its validation.

■ TREATMENT AND PROGNOSIS The key to the treatment of GCA is to prevent irreversible blindness as a result of ophthalmic artery occlusion. Treatment should therefore be started immediately in patients with the characteristic findings suggesting GCA. Therefore, temporal artery biopsy should be obtained to confirm the diagnosis after the initiation of steroid therapy. High-dose oral corticosteroids are the effective treatment regimen at the dose of 40 to 60 mg per day tapered over 2 to 4 weeks. A lower dose may then be given for up to 9 months, based on the clinical response to the initial high dose. Data have shown reduction in ischemic events when aspirin is used in patients with newly diagnosed GCA.

Vasculitides: Giant Cell Arteritis

CLINICAL PEARLS • Giant cell arteritis is predominantly a mediumto-large vessel vasculitis that commonly affects individuals over the age of 50 years. • Temporal artery biopsy is the gold standard for the diagnosis of GCA. • The onset of scalp necrosis in GCA is associated with high risk of visual loss and increased mortality. • Therapy should be initiated immediately followed by confirmatory diagnostic testing in patients who present with characteristic symptoms and clinical findings suggesting GCA in order to prevent visual loss. • The classical sign on duplex ultrasound is a dark halo in the temporal artery which has a sensitivity of 73% and specificity of 100% in the diagnosis of GCA.

The use of pulse dose of corticosteroids remain controversial, but a recent study showed that induction therapy with methylprednisolone at a dose of 15  mg/kg/day had better outcome compared to oral prednisone at 40 mg/day over 3 days. However, up to 50% of patients on oral steroids therapy relapse. These patients are restarted on even higher doses of corticosteroids for a longer period of time. Methotrexate can be used as a steroid sparing drug in case of a relapse. Limited data exist for the use of tumor necrosis factor alpha inhibitors. Vascular intervention in patients with large vessel disease is an option but is a difficult decision. The general rule is to postpone vascular reconstruction until remission is established in GCA. Stenosis of the subclavian and axillary arteries is occasionally treated by percutaneous transluminal angioplasty (PTA), with long-term patency rate of 65%. There is limited data available for bypass surgery in patients with GCA. The most common complication of GCA is blindness. Visual loss may be partial or permanent and may occur without warning. More so, the onset of scalp necrosis is associated with high risk of visual loss and increased mortality. Aortic aneurysm, aortic regurgitation, and aortic dissection occur less commonly. However, the involvement of the aorta still puts patients at a major risk of mortality from sudden death.

■ DIFFERENTIAL DIAGNOSES The differential diagnoses of GCA include a number of disorders that are similar in their clinical presentation. PMR (muscle pain and stiffness, especially on the neck,

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Table 26.1 Key Distinguishing Features Between GCA and Takayasu’s Arteritis Features

Giant Cell Arteritis Takayasu’s Arteritis

Female: Male ratio

3:2

7:2

Age of onset

>50

50 mm/hour CT angiogram of the neck Temporal artery biopsy Ultrasound of the temporal artery

Answer: e 2. Treatment with prednisone is initiated. Which of the following statements is true regarding the initiation of therapy? a. Patients with GCA should be treated until ESR is 1.5 mg/dL) • Evidence of HBV infection via serum antibody or antigen serology • Characteristic arteriographic abnormalities not resulting from noninflammatory disease process • Biopsy of small- or medium-sized artery containing polymorphonuclear cells

liver function tests, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hepatitis panel (HBV and hepatitis C virus [HCV]), and urinalysis. Others are ANCA, antinuclear antibody (ANA), rheumatoid factor (RF), antibodies to cyclic citrullinated peptides (anti-CCP), antibodies to double-stranded DNA including anti-Smith, anti-Ro/SSA, anti-La/SSB and anti-RNP, cryoglobulins, and complement levels. The American College of Rheumatology has established diagnostic criteria that can be utilized as a guideline (Table 30.1). The documentation of at least three of 10 findings has a sensitivity and specificity of 82% and 87%, respectively. Tissue biopsy of affected organ is mandated to confirm the diagnosis of PAN. Characteristic findings on renal biopsy may include diffuse inflammation with polymorphonuclear cells (PMNs) of the adventitia and proliferation and fibrosis of the media and intima. The internal and external elastic lamina is destroyed. The vessel lumen will eventually occlude due to thrombosis. Necrotizing glomerulonephritis without immune complex deposition may also be seen. Imaging is done if biopsy is inconclusive and the clinical suspicion for PAN is high. Arteriogiography is the preferred imaging modality, though the less invasive angiography techniques such as CT and magnetic resonance (MR) angiography may also be used. The typical finding on arteriogram is multiple microaneurysms and irregular constrictions in the larger vessels with occlusion of smaller arteries.

CLINICAL PEARLS • PAN is a necrotizing vasculitis of primarily medium-sized arteries with no granuloma formation, no ANCA association, and sparing of pulmonary arteries. • Biopsy of the affected organs is needed to make a definitive diagnosis and to start therapy. • The hallmark arteriographic findings in PAN are microaneurysms and irregular constrictions in the larger vessels with occlusion of smaller arteries. Perirenal hematoma with ruptured vessels may also be seen. • Check hepatitis B serology before therapy. • Pathology is characterized by focal and segmental transmural necrotizing inflammation with fibroid inflammation of medium size vessels. • HBV-associated PAN has become rare since the introduction of effective immunization programs against the virus.

is vidarabin and plasmapherosis in addition to steroids, which help to reduce viral load and remove immune complexes. In less severe cases, intravenous (IV) pulse dose of steroids is used which can be switched to oral form and tapered over 6  weeks. If steroids fail to maintain remission, then cyclophosphamide may be added at an IV pulse dose of 0.5 to 2.5 g/kg/day for up to 3 months. The oral dose is 2 g/kg/day for up to 9 months to 1 year. Methotrexate can also be used as steroids sparing or if steroids fail to maintain remission. The recommended dose is PO methotrexate at 25  mg/week for 6 months and titrated according to the patient’s response. Limited data support the use of IV immune globulins (IVIG) or antitumor necrosis factors (anti-TNF). The prognosis of PAN depends on the organ(s) involved and the severity of the disease. The scoring system used to predict survival rate utilizes the five factors score (FFS) and includes the following parameters linked to increased mortality: proteinuria >1 g/day; renal insufficiency with creatinine >140  μmol/L; cardiomyopathy; gastrointestinal manifestations; and central nervous system involvement. FFS of 0, 1, and ≥2 are associated with 12%, 26%, and 46% 5-year mortality rates, respectively. In addition, age >50 and weight loss >10% are associated with a poor prognosis.

■ TREATMENT AND PROGNOSIS Treatment of PAN is similar to the treatment of other vasculitides. However, it is important to treat the underlying course of PAN first (e.g., HBV-associated PAN) before initiating therapy with cytotoxic drugs. With active HBV infection present, the recommended regimen

■ DIFFERENTIAL DIAGNOSES The differential diagnoses of PAN represent a spectrum of clinical manifestations with striking similarities. To be considered are disorders such as the primary

Vasculitides: Polyarteritis Nodosa

161

vasculitides, processes that lead to the loss of vascular integrity and blood vessel occlusion, and syndromes associated with secondary vasculitis. Particularly, the ANCA-associated small vessel vasculitides such as granulomatosis with polyangiitis (Wegener’s), Churg–Strauss syndrome, microscopic polyangiitis, can be similar to PAN. The key to differentiate these disorders from PAN is to demonstrate the lack of ANCA association in PAN. Other small vessel vasculitides to consider are Henoch–Schonlein purpura, drug-induced vasculitis, and cryoglobulinemia. Infectious etiologies with secondary vasculitides can also mimic PAN, particularly cytomegalovirus infection, parvovirus B19, Rickettsiae and Borrelia burgdorferi infection, staphylococcal, streptococcal, and pseudomonal infection, among others. PAN secondary to autoimmune and malignant disorders should also be considered. Livedo reticularis and cholesterol emboli as well as pyoderma gengrinosa can also mimic PAN and should be considered. .

■ QUESTIONS AND ANSWERS 1. The hallmark arteriographic findings in polyarteritis nodosa (PAN) may include a. Irregularly narrowed vessels with multiple collaterals b. Smooth tapered narrowing of large caliber vessels c. Multiple microaneurysms and irregular constrictions in the larger vessels with occlusion of smaller arteries d. Perirenal hematoma with ruptured vessels e. c and d f. None of the above Answer: e 2. Which of the following arteries is most likely to be affected by PAN? a. Dermal arteries and their arterioles b. Subclavian artery

c. Mesenteric artery d. Carotid artery e. The aorta Answer: c 3. The prevalence of HBV associated PAN is in decline in the United States primarily because of which of the following? a. Decrease in the prevalence and incidence of hepatitis C infection and vaccinations against hepatitis C b. Decrease in the prevalence and incidence of hepatitis B infection and vaccinations against hepatitis B c. Early diagnosis and effective therapy for nonHodgkin lymphoma d. Chronic hepatitis B infection is in the decline due the availability of superior antiviral medications e. The routine use of corticosteroids and cyclophosphamide in the treatment of other forms of vasculitides Answer: b

■ SUGGESTED READINGS 1. Balow, JE. Renal vasculitis. Kidney Int. 1995;27:954. 2. Cohen RD, Conn DL, Ilstrup DM. Clinical features, prognosis, and response to treatment in polyarteritis. Mayo Clin Proc. 1980; 55:146. 3. Guillevin  L, Lhote  F, Gayroud  M, et  al. Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients. Medicine (Baltimore). 1996;75(1):7–28. 4. Lightfoot  RW, Jr, Michel  BA, Bloch  DA, et  al. The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Artheritis Rheum. 1990;33:1088. 5. Moore  PM. Neurological manifestation of vasculitis: update of immunopathologic mechanisms and clinical features. Ann Neurol. 1995;37 Suppl 1:S131.

31

Vasculitides: Takayasu’s Arteritis Geoffrey O. Ouma, Supratik Moulik, and Joshua F. Baker

INTRACRANIAL HEMORRHAGE AND ABDOMINAL PAIN An 18-year-old Puerto Rican female was admitted complaining of sudden onset of headache, restlessness, and confusion. A month prior, she developed intermittent postprandial abdominal pain. The patient has a history of well-controlled asthma. There was no history of autoimmune or vascular diseases in her family. She is a college student who denies smoking or illicit drug use. She denies recent fatigue, fevers, weight loss, visual changes, rash, ulcers, alopecia, photosensitivity, joint pains, myalgias, melena, and blood in the stool, chest pain, and shortness of breath, hematuria, or extremity pain. However, she admits to chronic constipation as well as arm fatigue while combing her hair. On physical examination, she was somnolent but arousable, with a drooping right nasolabial fold. She was afebrile and had normal oxygen saturation on room air. The blood pressure was elevated at 170/130 mm Hg on the right arm and 150/120 mm Hg on the left. Head and neck exam were normal. Auscultation of the heart and lungs was normal. Vascular examination was remarkable for a left carotid bruit, right subclavian bruit, and a mid epigastric bruit. There were decreased brachial and radial pulses bilaterally. Allen test was negative. Abdominal examination was normal. Neurological examination revealed a flattened affect, drooping of her right nasolabial fold with normal strength and sensation throughout bilateral extremities. Skin and musculoskeletal exams were normal. Laboratory values revealed white blood count of 18,800/μL with a normal hemoglobin and platelet count. A metabolic panel was notable for sodium of 131 mmol/L and a creatinine of 0.7 mg/dL. Urinalysis revealed 100 mg of protein and 5 to 10 red blood cells. Erythrocyte sedimentation rate (ESR) was 58 mm/hour antinuclear antibody (ANA), antineutrophilic cytoplasmic antibody (ANCA), SSA/B, rapid plasma reagin (RPR), human immunodeficiency virus (HIV), complement levels, and toxicology screen were normal. A computed tomography (CT) scan of the head demonstrated a left frontal parenchymal hemorrhage as shown (Figure 31.1). Aortic arch angiography is also shown (Figure  31.2). Magnetic resonance angiography (MRA) of the aorta and its major branches as well as a runoff are also shown (Figures 31.3 and 31.4). A clinical diagnosis of Takayasu’s arteritis was made based on fulfillment of five out of six criteria defined in 1990 by the American College of Rheumatology (Table  31.1). The criteria met included her age of 10 mm Hg in systolic blood pressure between arms Bruits audible on auscultation over one or both subclavian arteries or abdominal aorta Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the proximal upper or lower extremities, not caused by arteriosclerosis, fibromuscular dysplasia, or similar causes; changes usually focal or segmental

1. Age at disease onset ≤40 years 2. Claudication of extremities 3. 4. 5. 6.

Decreased brachial artery pulse Blood pressure difference >10 mm Hg Bruit over subclavian arteries or aorta Arteriogram abnormality

Table 31.2 Takayasu’s Arteritis: Percent Arterial Involvement and Associated Clinical Findings and Symptomatology Vessel

Percent Involvement

Symptoms

Percent Involvement

Symptoms

Percent Involvement

Subclavian artery

54%–92%

Bruit

80%–94%

Limb claudication

Aorta

53%–80%

Pulselessness

53%–96%

Cerebrovascular

20%

Renal artery

38%–62%

Hypertension (coarctation of the aorta plus RAS)

33%–72%

Cardiovascular

28%

disease course. Tissue biopsy is rarely done. Angiography remains the gold standard for the diagnosis of TA, even though less invasive imaging modalities such as CT or magnetic resonance angiography (MRA) are used more often in clinical practice. 18F-fluorodeoxyglucose PET (18FFDG)-PET metabolic imaging is increasingly being used in the investigation of TA; however, its exact role in the disease management is yet to be defined. High-resolution duplex ultrasound can be used in the assessment of the common carotid and proximal subclavian arteries. However, apart from the identification and monitoring of abdominal aortic aneurysms, its use is limited in TA.

■ TREATMENT AND PROGNOSIS Corticosteroids are the mainstay therapy for TA. However, approximately 50% of patients treated with steroids will respond and the other half will fail therapy. Therefore, other immunosuppressive drugs have been used in those patients who do not respond to steroids; agents including methotrexate, cyclophosphamide, and azathioprine. Methotrexate is often preferred over other cytotoxic drugs because of its better tolerability and side effect profile. However, up to 25% of patients will fail nonsteroid therapies. Emerging therapies with antitumor necrosis factor inhibitors are being considered for this patient population, but further studies are still needed. Management of hypertension and treatment of thrombosis are also crucial. Management of hypertension can be challenging especially in the setting of steroid use. Care should be taken when using angiotensin converting enzyme inhibitors in the setting of renal artery

29%–62%

stenosis and renal function should be monitored. Surgical therapy with bypass grafts or angioplasty with stent placement is indicated in the presence of hypertension with critical renal artery stenosis, functionally limiting extremity claudication, cerebrovascular ischemia or critical stenosis of three or more cerebral vessels, moderate aortic regurgitation, and myocardial ischemia confirmed with coronary angiography. However, surgery should not be performed during the acute phase of inflammation, but should be reserved when the disease activity is quiescent to avoid complications such as restenosis, anastomotic failure, thrombosis, hemorrhage, and infection. A recent recommendation by the National Institutes of Health suggests that critical stenosis of the aortic arch should be corrected to prevent stoke, with grafts originating from the ascending aorta. Renal artery stenosis should be treated by angioplasty with stent placement, especially in the setting of ostial lesions, long segments lesions, incomplete relief of stenosis, or dissection/ aneurysm. Surgical correction of thoracic aorta aneurysm is recommended especially if rupture is imminent. Patients with uncomplicated TA have good prognosis. In patients with severe disease, early aggressive treatment is associated with better prognosis. However, patients treated with chronic immunosuppressive drugs have increased morbidity and mortality. Long-term follow-up is recommended, especially with imaging modalities such as CT angiography, MRA, or duplex ultrasound if clinically indicated. The uses of acute phase reactants such are ESR and CRP have been shown to have poor correlation with disease activity when following up patients for disease recurrence. Physical examination findings such as bruit in the

Vasculitides: Takayasu’s Arteritis

CLINICAL PEARLS • TA is a rare disorder that affects mainly women of Japanese, South East Asia, Indian, or Mexican descent and usually presents in the 2nd or 3rd decade of life. • Red flags for TA include unexplained acute phase response, carotidynia, hypertension, discrepancy in blood pressure readings between the arms (>10 mm Hg), claudication, arterial bruit, and angina. • Angiography is the gold standard for the diagnosis of TA. • The four most common complications are Takayasu’s retinopathy, secondary hypertension, aortic regurgitation, and aneurysm formation. • About 50% of patients treated with steroids respond, and the other 50% respond to methotrexate. • The aim of therapy is to control disease activity and preserve vascular integrity while minimizing long-term side effects.

setting of symptoms are good markers of disease recurrence and need to resume therapy.

167

■ QUESTIONS AND ANSWERS A 22-year-old Mexican American presented complaining of new onset right upper extremity claudication associated with right cold hand, abdominal pain, bilateral lower extremity claudication, and headaches. She denied shortness of breath or chest pain. She was previously healthy without any medical problems. She does not smoke or use illicit drugs and has negative cardiovascular risk factors. On physical examination, her blood pressure is 180/88 mm Hg on the right arm and 145/60 mm Hg on the left arm. Auscultation of heart and lungs are within normal limits without any murmurs or wheezing. The right brachial pulse is diminished with bruit over the right carotid and subclavian arteries. Lower extremities pulses are diminished. 1. What is the best imaging modality to diagnose this patient? a. b. c. d.

Angiography Transthoracic echocardiography CTA of the head and neck Duplex ultrasound of the neck and abdominal aorta e. Diagnosis is clinical and no further imaging is needed

Answer: a 2. What is the most likely diagnosis?

■ DIFFERENTIAL DIAGNOSES The differential diagnosis of TA includes other causes of large vessel vasculitis including secondary inflammatory aortitis (tuberculosis, syphilitic, spondyloarthropathies, lupus, and rheumatoid arthritis); primary vasculitides such as Kawasaki disease and giant cell arteritis; developmental disorders such as Marfan syndrome and coarctation of the aorta. Most of these disorders have specific features that help distinguish them from TA. However, tuberculosis remains the single most important differential diagnosis of TA. The distinguishing features associated with tuberculosis aortitis are erosion of the vessel wall with the formation of aneurysms, particularly in the descending thoracic and abdominal aorta. While stenosis is a common complication in TA, dissection, and rupture are common in tuberculosis aortitis. Syphilitic aortitis often affects older patients and is associated with calcification of the aorta without stenosis. Fibromuscular dysplasia should also be considered in the setting of renal artery involvement. Giant cell arteritis is similar to TA in many features, but still can be discriminated based on their distinct clinical presentations. Age of onset of less than 40 years is the single most important distinguishing feature that separates TA from giant cell arteritis. Other clinical considerations include ethnic background and signs of extremity claudication and scalp tenderness.

a. b. c. d. e.

Giant cell arteritis Kawasaki disease Lupus aortitis Behcet disease Takayasu’s arteritis

Answer: e 3. Medical therapy is recommended. All of the following therapies are appropriate EXCEPT a. b. c. d. e.

Methotrexate Prednisone Cyclophosphamide Warfarin Metoprolol

Answer: d

■ SUGGESTED READINGS 1. Arend WP, Michael BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu’s arteritis. Arthritis Rheum. 1990;33:1129–1134. 2. Giordano  JM.  Surgical treatment of Takayasu’s arteritis. Int J Cardiol. 2000;75:S123–S128. 3. Johnston  SL, Lock  RJ, Gompels  MM.  Takayasu’s Arteritis: a review. J Clin Pathol. 2002;55:481–486. 4. Mason  JC. Takayasu’s arteritis—advances in diagnosis and management. Nat Rev Rheumatol. 2010;6:406– 415.

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Vasculitides: Thromboangiitis Obliterans Geoffrey O. Ouma, Supratik Moulik, and Rebecca A. Jonas

GANGRENOUS FINGERTIPS A 45-year-old black male tobacco smoker presented complaining of progressive bilateral Raynaud’s phenomena and digital ulceration of the bilateral ring fingertips (Figure 32.1). For the past 6 weeks, he reported on and off flu-like symptoms with fever, malaise, and arthralgias of his bilateral wrist and fingers. For the past 2 weeks, he noted increasing upper extremity digital pain with bluish-to-purple discoloration of his bilateral ring finger tips. Three days ago, he noticed ulcerations turning black. He has been otherwise healthy with no significant medical history. He works as a truck driver, has a 20 pack-year history of smoking, takes no other medications, and denies illicit drug use. On physical examination, he was afebrile with normal vital signs. Vascular examination was normal to auscultation without bruits. The bilateral radial pulses were diminished but lower extremity pulses were palpable. Allen test was positive bilaterally. There was digital ischemia of the bilateral ring fingertips. Laboratory evaluations were all normal, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complete blood cell count, fasting glucose, liver enzymes, and metabolic panel. Serological markers for autoimmune disorders were also normal, including antinuclear antibody, rheumatoid factor, anticentromere antibody, and anti-SCL-70. Lupus anticoagulant and anticardiolipin antibodies as well as antineutrophilic cytoplasmic antibody (ANCA), complement profile, and cryoglobulins were normal. Echocardiography excluded proximal source of emboli. A clinical diagnosis of thromboangiitis obliterans was considered and a digital MR angiogram revealed the characteristic changes with distal artery occlusions and corkscrew collaterals (Figure 32.2).

■ DEFINITION/BACKGROUND/EPIDEMIOLOGY Thromboangiitis obliterans (TAO) also known as Buerger’s disease, is a segmenta nonatherosclerotic obliterative inflammatory disease of the small to medium vessels and nerves

of the extremities. TAO was first described by Felix Von Winiwater in 1879. Leo Buerger then published a detailed case series and pathological findings in patients with TAO in 1908. TAO is characterized by a highly cellular and inflammatory obliterative thrombus with skip 169

170

Computed Tomography Angiography (CTA) of Distal Aorta With Runoff With Evidence of 90% Stenosis of the Distal Superficial Femoral Artery (SFA)

Vasculitis and Vasospastic Diseases

lesions and the sparing of the vessel wall. The etiology is unknown, but patients are often young adult tobacco users (3 d, or major surgery requiring regional or general anesthetic in past 4 wk

1

Alternative diagnosis at least as likely

–2

Superficial and Deep Venous Thrombosis

Figure 34.2 Duplex ultrasonography of left great saphenous vein with evidence of thrombosis and venous reflux.

Direct noninvasive visualization: Duplex ultrasonography of the veins is the screening method of choice for patients with either a high probability of or with elevated D-dimer. It is principally useful in the diagnosis of proximal lower extremity DVT, where the sensitivity and specificity are 95% and 96%, respectively. This diminishes to 60% to 70% for below knee DVTs, especially isolated calf vein DVTs. Due to this reason, some studies advocate repeat ultrasonography in 7 to 10 days to confirm a previous finding of calf vein DVT and to exclude proximal extension especially in patients with a high likelihood. Figure 34.2 presents an algorithm for management of suspected VTE. Magnetic resonance venography of the veins is useful for identification of VTE above the level of the inguinal ligament especially in patients with high probability of DVT with recurrent nondiagnostic duplex ultrasounds, patients with evidence of anatomical substrates (MayThurner syndrome), or patients with evidence of venous compression with associated ischemia (phlegmasia dolens). However, this procedure is expensive and should not be employed on a routine basis.

■ TREATMENT AND PROGNOSIS The mainstay of treatment for uncomplicated DVTs is institution of anticoagulation to minimize progression of disease and ensuing complications. Treatment is initiated with either intravenous UH or subcutaneous low molecular weight heparin (LMWH) or fondaparinoux followed by transition to oral anticoagulation with warfarin. Adjunctive measures including leg elevation and institution of oxygen for patients with concomitant pulmonary emboli are also useful. Prior to anticoagulation commencement, patients, bleeding risk should be assessed to ascertain the risk-benefit ratio of institution of anticoagulation.

185

UF catalyzes the anticoagulant function of antithrombin III and augments the inactivation of factors II, X, and IX. It is administered intravenously with a loading dose of either 80 IU/kg or a fixed dose of 5000 IU followed by a continuous infusion of 18 IU/kg hour or a fixed dose of 30,000 to 35,000 IU per 24 hours targeting an activated partial thromboplastin time of 2 to 3.5 times normal. Alternative options to UH are LMWHs (dalteparin, enoxaparin, or tinzaparin). Enoxaparin is instituted at 1  mg/kg twice daily or 1.5  mg/kg daily. LMWHs have the advantage of longer half-life and hence ease of administration, longer bioavailability, and presumably lower hemorrhagic complications. LMWHs are contraindicated in patients with a glomerular filtration rate of 30 and in the obese due to bioavailability uncertainty. For most patients, warfarin can be initiated within 24 hours of UH or LMWH initiation, typically at a dose of 5 to 10 mg at titrated to target an INR of 2 to 3. Due to variability in response to therapy, warfarin contends management difficulties that have led to the development of newer oral anticoagulants. Two novel agents that are farthest along in development are Dabigatran and Rivaroxaban. Dabigatran is a direct thrombin inhibitor that has currently been approved by the Food and Drug Administration for fixed twice-daily dosing for stroke prevention in atrial fibrillation. Large randomized controlled trials DVT prevention and treatment have shown equal efficacy without evidence for increased bleeding when compared to warfarin. Rivaroxaban is a once daily factor Xa inhibitor with a similar clinical trial outcome profile. Both drugs have the advantage of immediate fixed-dose initiation and lack of need for monitoring. The role of thrombolytic therapy for treatment of DVT is dependent on the presence of hemodynamically significant PEs or in patients with extensive iliofemoral DVTs and high risk for postthrombotic syndrome. Inferior vena cava (IVC) filters are generally not indicated unless anticoagulation is contraindicated, there are recurrent PEs despite adequate anticoagulation, or in patients with chronic pulmonary hypertension and reduced cardiac reserve. Patients with persistent DVTs who require surgery may potentially benefit from transient IVC filter institution. Lower extremity venous compression stockings at a strength varying from 20 to 50 are mandated for long-term prevention of venous insufficiency and stasis dermatitis resulting from postthrombotic syndrome especially in patients with iliofemoral DVTs. Patients should initiate stocking use once the initial swelling has subsided and continue them for at least 6 to 8 months. Currently the eighth American College of Chest Physician consensus recommends anticoagulation for both proximal and distal lower extremity DVTs, although there is controversial evidence to suggest lack of embolization of the latter. SVTs typically do not require

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on placebo). In the absence of guidelines, it may be advisable to individualize therapy to target patients with thrombophilia, malignancy, or other risk factors for continued thrombosis. Patients without relatively low risk may be conservatively managed with observation and repeat ultrasonography in 7 to 10 days for assessment of progression.

■ DIFFERENTIAL DIAGNOSES

Figure 34.3 Duplex venous ultrasonography showing chronic thrombosis in the peroneal veins.

anticoagulation in the absence of underlying risk factors for thrombosis especially if the thrombus is isolated to the superficial veins. Recent evidence suggests that fondaparinux 2.5 mg SQ daily significantly reduces the progression of SVTs to full fledge DVTs (0.9% versus 5.4%

• Baker’s cyst is a swelling of one of the two fluidfilled sacs (anatomic bursae) located behind the knee (popliteal space). This typically presents as popliteal fossa swelling without evidence of generalized swelling of the knee. • Congestive heart failure can present as bilateral lower extremity swelling and is more chronic in nature with reversal on leg elevation. • Varicose veins (varicosities) are enlarged, tortuous veins with weak or nonfunctioning valves that typically present in the absence of leg swelling. Although they may be associated with DVT, varicose veins typically are superficial without evidence of superimposed thrombosis. • Lymphedema typically manifests as bilateral chronic pitting edema with swelling and tension of the digital dermal surfaces (Stemmler’s sign). • Cellulitis presents as unilateral erythema, typically without overt swelling.

CLINICAL PEARLS • Typically asymptomatic although swelling of extremity is an important diagnostic clue. • Duplex ultrasonography is the mainstay of diagnosis for patients at high probability and D-dimer testing should be conducted prior to imaging in patients with low to moderate risk. • Anticoagulation remains mainstay of therapy for prevention of progression, recurrence, and embolization, and fibrinolytic therapy should be instituted in patients with obstructive iliofemoral DVT to prevent postthrombotic complications.

■ SUGGESTED READINGS 1. Rajagopalan S, Mukkerjee D, Mohler R, eds. Manual of vascular diseases. Lippincott Williams and Wilkins, 2005:287–292. 2. Creager M, Dzau V, Beckman J, Loscalzo J, eds. Vascular medicine: A companion to Braunwald’s heart disease. 7th ed. Philadelphia, PA: Philadelphia; 2006:209–410. 3. Bounameaux H, Perrier A, Righini M. Diagnosis of venous thromboembolism: an update. Vasc Med. Oct 2010;15(5):399–406. 4. Kitchens CS. How I treat superficial venous thrombosis. Blood. Jan 6, 2011;117(1):39–44. 5. Turpie  AG. Direct Factor Xa and direct thrombin inhibitors: a clinical trial update. Curr Opin Drug Discov Devel. Jul  2009; 12(4):497–508. 6. Wells  PS, Owen  C, Doucette  S, Fergusson  D, Tran H. Does this patient have deep vein thrombosis?. JAMA. 2006;295(2):199–207.

35

Pulmonary Embolism Christopher Dibble, Amresh Raina, Supratik Moulik, and M. Haris U. Usman

SHORTNESS OF BREATH A 28-year-old African-American female presents with sudden onset of shortness after taking a 2-hour flight to visit her grandmother. She also reports sharp left-sided chest pain exacerbated with inspiration and relieved with rest. She has no past medical history and reports no previous surgeries. Her mother has a history of “blood clots” and had been placed on blood thinners. She does not have any allergies and has been on an oral contraceptive formulation combining estrogen and progesterone. On physical examination her vitals are a BP of 90/60, HR of 120, RR of 30, and pulse oximetry of 83% on room air. There is evidence of a tender and slightly swollen right leg with normal pulses and the jugular venous pressure is elevated at 8 cm H2O. The left lower extremity is normal in size with normal pulses. A 12-lead EKG is remarkable for sinus tachycardia with right ventricular strain, and computed tomography (CT) of the chest reveals a large filling defect at the level of the pulmonary artery bifurcation consistent with a pulmonary embolus. She is placed on intravenous fluids, unfractionated heparin, and supplemental oxygen, and bedside echocardiography reveals right ventricular dilatation and hypokinesis. Her heparin infusion is held and she is administered 100 mg tissue plasminogen activator (t-PA) over 2 hours. Her blood pressure increases from 90/60 mm Hg to 120/78 mm Hg and she reports improvement in symptoms with decreased shortness of breath. Her heparin is re-initiated 4  hours later and 2  days after t-PA administrations, she is placed on warfarin to target an INR of 2 to 3. Genotyping reveals a prothrombin gene (G20210A) mutation and she is advised to remain on anticoagulation for life.

■ DEFINITION/BACKGROUND/EPIDEMIOLOGY Pulmonary embolism (PE) is one of the three conditions that constitute venous thromboembolism (VTE) and carries a mortality of 15% in the first 3 months of diagnosis with sudden death being the initial manifestation in as many as one in every four patients. Most PEs originate from thrombi in the deep venous system of the lower extremities although the frequency of PE in the

setting of upper extremity DVT ranges from 3% to 33%. These emboli may obstruct either a major pulmonary artery or one of its branches with resultant hypoxemia and increase in pulmonary vascular resistance and right heart afterload. PEs with RV dilatation and hypokinesis are classified as massive PEs if associated with hemodynamic compromise and submassive PEs if not. Risk factors for PEs are similar to those for other elements of VTE including hypercoagulability, advanced 187

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Figure 35.1 Axial contrast-enhanced CT image in the pulmonary arterial phase of enhancement, through the level of the main and branch pulmonary arteries. There are filling defects in the bilateral main pulmonary arteries (white arrow) with a thin band of connecting thrombus (arrowhead) bridging the main pulmonary artery bifurcation. This is a typical appearance for saddle embolus.

Figure 35.3 Coronal reformatted figure from a contrastenhanced CT demonstrates a column of contrast within the SVC (arrowhead). There is reflux of contrast into the hepatic veins (wavyarrow), which is a sign of right heart failure.

type of formulation especially in patients with underlying thrombophilia. It is therefore advisable to conduct thrombophilia testing in these patients, especially in circumstances where the magnitude of thrombosis is severe.

■ CLINICAL FEATURES

Figure 35.2 Axial contrast-enhanced CT image at the level of the pulmonary arteries in a different patient demonstrates enlargement of the main pulmonary artery (white arrow) which is larger than the adjacent normal sized aorta (arrowhead).

age, postoperative state, and malignancy. In patients under 50  years of age, without any underlying malignancy and recent hospitalization or surgical procedure, testing for hypercoagulability disorders is advisable and genetic testing can be conducted at the time of initial evaluation. Testing for antithrombin III should be conducted 6  weeks after discontinuation of heparin while protein C and S testing should be conducted 6 weeks after discontinuation of warfarin. The use of oral contraceptive pills increases PE risk two- to threefold irrespective of the

Clinical presentation of PE is determined by the size of the embolus and its location in the pulmonary circulation. Symptoms may vary from chest pain, unexplained dyspnea, and cough to overt hemoptysis due to pulmonary infarction. Most common signs include tachypnea and tachycardia and occasionally cyanosis. Massive pulmonary emboli result in right heart strain with an accentuated pulmonic component of the second heart sound as well as the fourth heart sound. Occasionally patients may present with atrial fibrillation, paradoxical arterial embolism due to the presence of a patent foramen ovale, or unexplained wheezing. Clinical probability assessment using the Wells, and most recently, Revised Geneva (RG) scores, is useful for guiding choice of testing. Scores of 100 3. Surgery or immobilization within past 4 wk

+1.5

Heart rate >95/min

+5

1. Clinically suspected DVT 2. Alternative diagnosis to PE less likely

+3.0

Unilateral limb edema with pain on deep palpation

+4

1. Active cancer 2. Hemoptysis

+1.0

1. Previous DVT 2. Unilateral limb pain 3. Heart rate 75–94/min

1. Active cancer 2. Surgery or hip fracture in 1 mo 3. Hemoptysis

+2

Source: Adapted from Wells et al. (5) and Le Gal et al. (6).

70% with a higher likelihood of diagnosing central rather than peripheral emboli, the advancement of technology with introduction of the multidetector CT angiography has raised the diagnostic accuracy rate to 96.5% with a 3-month thromboembolic risk of only 1.5% in patients in whom PE was excluded. This has obviated the need for conducting additional supportive tests like the ventilation-perfusion scan. Ventilation-perfusion imaging used to be the first test of choice for PE. However, about two-thirds of tests resulted in nondiagnostic findings in patients with high probability prompting the use of alternative supportive imaging. The advancement of MDCT technology and the speed of acquisition of CT results have resulted in decreased utilization of V/Q scanning. Pulmonary angiography is considered the gold standard for diagnosis of PE, but due to its invasive nature is seldom utilized.

dilatation and hypokinesis. For patients with submassive PEs without evidence of hemodynamic compromise but with RV dilatation, individualization of therapy to adjust for bleeding risk is advised. Intravenous heparin should be administered upon immediate suspicion to patients with high probability for PE and need for thrombolysis. Heparin should be held during fibrinolysis and resumed without bolus once the aPTT has fallen below 80 seconds after thrombolysis and should be titrated to target aPTT of 80 seconds. Volume support should be judiciously administered to target a central venous pressure of 12 to 15 mm Hg and inotopic support with dopamine, norepinephrine, or epinephrine should be instituted if there is evidence of hemodynamic compromise. In patients with increased bleeding risk, surgical embolectomy may be a viable alternative although catheter-directed thrombolysis has also been attempted with success. The use of IVC filters has not been evaluated in clinical trials, but retrievable filters may be an option in patients with recurrent emboli.

■ TREATMENT AND PROGNOSIS The mainstay of treatment for uncomplicated PEs is institution of anticoagulation to minimize progression of disease and ensuing complications. Treatment is initiated with either intravenous unfractionated heparin or subcutaneous low molecular weight heparin or fondaparinoux followed by transition to oral anticoagulation with warfarin. Adjunctive measures including leg elevation and institution of oxygen. Prior to anticoagulation commencement, patients, bleeding risk should be assessed. Thrombolytic therapy remains pivotal for rapid reversal of hemodynamic compromise and gas exchange derangements. Because massive PEs result in elevation of RV afterload with resultant decrease in systemic perfusion, thrombolytic administration improves systemic perfusion. The 2008 ACCP guidelines consider thrombolytic therapy as a life-saving measure in patients with PE and hemodynamic compromise and evidence of RV

CLINICAL PEARLS • Variable presentation ranging from tachycardia and palpitations to chest pain and shortness of breath. • Multidetector CT angiography is the mainstay of diagnosis for patients at high probability and D-dimer testing should be conducted prior to imaging in patients with low to moderate risk. • Anticoagulation remains mainstay of therapy for prevention of progression, recurrence, and embolization, and thrombolytic therapy should be instituted in patients with evidence of hemodynamic compromise.

Pulmonary Embolism

Despite therapeutic advances, short-term mortality rates for acute PE patients presenting in shock or requiring cardiopulmonary resuscitation ranges from 25% to 65%. Further advancement in thrombolytic therapy may improve these outcomes.

■ DIFFERENTIAL DIAGNOSES • Myocardial infarction manifests as a crushing leftsided chest pain and typically with EKG evidence of ST or T changes. • Pneumothorax can present as sudden sharp chest pain in association with shortness of breath and evidence of decreased breath sounds on chest examination. • Pneumonia is typically slowly progressive without evidence of tachycardia or hemodynamic compromise. Patients also have associated evidence of systemic infection like fever and productive cough. • Pericarditis occurs typically after viral illnesses and has respiratory association without evidence of hyperoxemia. • Chostocondritis is more localized without evidence of hypoxia or hemodynamic compromise.

■ QUESTIONS AND ANSWERS 1. A 54-year-old male presents with new onset chest pain and shortness of breath that occurred suddenly while he was lying in bed. Pain is right sided and pleuritic in character. Patient has a history of nonsmall cell lung cancer with resection and radiation therapy. His heart rate is 110 and regular and he is tachypneic with a pulse oximetry of 89% on room air. What is the first next best management option? a. b. c. d. e.

Anticoagulation with intravenous heparin D-dimer CT angiogram of chest Electrocardiogram Aspirin

Answer: a

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2. For the patient in question 1, CT angiogram of the chest reveals massive saddle embolus at the pulmonary artery bifurcation. His blood pressure drops from 130/80  mm Hg to 85/45  mm Hg and he remains severely tachypneic despite being on 100% nonrebreather mask. What would be the next step in management? a. Thrombolytic therapy with tissue plasminogen activator b. Echocardiogram c. Oral warfarin therapy to target INR of 2 to 3. d. Oral dabigatran 150 mg daily e. Percutaneous coronary intervention Answer: b

■ SUGGESTED READINGS 1. Bounameaux H, Perrier A, Righini M. Diagnosis of venous thromboembolism: an update. Vasc Med. Oct 2010;15(5):399–406. 2. Goldhaber SZ. Pulmonary embolism for cardiologists. J Am Coll Cardiol. Nov 1, 1997;30(5):1172–1173. 3. Piazza G, Goldhaber SZ. Fibrinolysis for acute pulmonary embolism. Vasc Med. Oct 2010;15(5):419–428. 4. Pollack CV, Schreiber D, Goldhaber SZ, et al. Clinical characteristics, management, and outcomes of patients diagnosed with acute pulmonary embolism in the emergency department initial report of EMPEROR (Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry). J Am Coll Cardiol. Feb 8, 2011;57(6):700–706. 5. Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D, Forgie M, Kovacs G, Ward J, Kovacs MJ. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. Ann Intern Med. 2001 Jul 17;135(2):98–107. 6. Le Gal G, Righini M, Roy PM, et al. (February 2006). “Prediction of pulmonary embolism in the emergency department: the revised Geneva score”. Ann of Intern Med. 144 (3): 165–71.

36

Varicose Veins Atul Jain, Deeba Faruq, Supratik Moulik, and M. Haris U. Usman

SUPERFICIAL VARICOSITIES IN A PATIENT WITH KLIPPEL–TRENAUNAY SYNDROME A 26-year-old Caucasian female presented with left lower extremity swelling that developed 24  hours prior to presentation. She denied any pain, paresthesias, or claudication-like symptoms. Physical examination is remarkable for a markedly swollen left lower extremity with right thigh hemangioma measuring 3 × 4 cm in diameter in association with left anterior thigh and upper leg varicosities. The right lower extremity is normal in size with normal bilateral lower extremity pulses. Past medical history is significant for hypertension and Klippel-Trenaunay syndrome diagnosed in childhood. She also reported a history of deep venous thrombosis six years prior to evaluation for which she received anticoagulation for 3 months. Current medications are amlodipine and seroquel and she reports no allergies. Duplex ultrasonography of the lower extremities revealed left femoral deep venous thrombosis and multiple superficial varicosities without evidence of superficial venous thrombosis. She was placed on subcutaneous enoxaparin for 5 days and transitioned to warfarin for the ensuing 6 months.

■ DEFINITION/BACKGROUND/EPIDEMIOLOGY Varicose veins are pathologically enlarged subcutaneous venous channels measuring greater than 3 mm and generally affecting the lower extremity and particularly involving the superficial, extrafascial, or great or small saphenous veins. They are characterized either as primary varicose veins, resulting from defects within the structure of the superficial venous conduits without evidence of involvement of the deep or extrafascial vessels, or secondary varicose veins, resulting from transmission of deep venous pressure to the superficial veins through the communicating perforator veins. Primary varicose veins may either be inherited isolated venous structural defects or a part of a larger group

of congenital disorders. These disorders include the Klippel–Trenaunay syndrome, which is characterized by the triad of superficial port-wine capillary malformations, limb hypertrophy, and varicose veins. These larger varicosities are predisposed to higher rates of thrombosis that may progress to deep venous thrombosis as was the case in this patient. Half of the patients presenting with primary varicose veins have a family history of this disorder. Secondary varicose veins typically result from either prolonged central venous pressure (due to congestive heart failure or prolonged standing) or due to elevated deep venous pressure being transmitted to the superficial venous system through perforator veins (due to deep venous thrombosis or postphlebitic syndrome). 193

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Figure 36.1 Frontal and lateral views, respectively, of the left leg of a patient with Klippel–Trenaunay syndrome with associated varicosities (arrows) of the leg and hemangioma in anterolateral thigh (arrowhead).

■ CLINICAL FEATURES Varicose veins are more commonly of cosmetic than clinical concern, but may occasionally manifest with superficial thrombosis or thrombophlebitis. Superficial venous thrombosis is typically painless without physical evidence to corroborate occurrence and progression. Superficial thrombophlebitis typically manifests as painful swelling.

■ LABORATORY AND IMAGING WORKUP Direct noninvasive visualization: Primary and secondary varicosities can be often differentiated by the Brodie-Trendelenburg test. The affected extremity is raised to empty the superficial veins and a tourniquet is placed above the knee to obstruct blood flow. The leg is subsequently lowered and the varicosity refill time is noted. Prompt refilling of the varicosity suggests transmission of deep venous blood through incompetent perforator veins while a delay of >20 seconds with prompt refilling on tourniquet removal is consistent with reflux and incompetence of the superficial venous system exclusively without involvement of the deep venous system.

Figure 36.2 Coronal fat-saturated T2-weighted image through the level of the knee posteriorly demonstrates extensive subcutaneous venous varicosity (arrowhead). There is also an incidental large Baker’s cyst present (wavy arrow).

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Endovenous laser ablation either using laser or radiofrequency microwaves is a minimally invasive effective procedure for varicosities larger than 3  mm and with associated superficial venous reflux. This procedure is typically under local anesthesia using ultrasound guidance with up 90% closure of the affected vein. This procedure is less invasive and equally efficacious as surgical stripping or ligation of the superficial veins.

■ DIFFERENTIAL DIAGNOSES Figure 36.3 Duplex ultrasonography with B-mode imaging showing perforator venous reflux (between wavy arrows).

Duplex ultrasonography of the superficial or deep veins is only required when there is evidence of erythema, tenderness, or swelling in the affected extremity to preclude superficial or deep venous thrombosis.

• Deep venous thrombosis may manifest with elevated venous pressure proximal to the superficial varicosity and manifests principally as swelling of the lower extremity. • Ruptured Baker’s cyst manifests as painless swelling at the level of the popliteal fossa. • Cellulitis typically presents as erythema with disruption of dermal surface. Generalized symptoms may include fever, chills, nausea, and vomiting. • Stasis dermatitis manifests bronze discoloration at the gaiter region of the lower extremity.

■ TREATMENT AND PROGNOSIS Management is typically conservative unless there are cosmetic needs that need to be addressed. Graduated external compression stockings with pressures at the ankle ranging from 20 to 60 mm Hg aid in alleviating associated venous insufficiency and further expansion of the varicosities. If symptomatic or progressive, superficial varicosities may require further intervention. Sclerotherapy using an injectable sclerozing agent is most effective in telangiectasias, small (1 to 3  mm) varicosities without saphenous vein reflux or residual or early recurrence varicosities after saphenous vein intervention.

CLINICAL PEARLS • Visibly pronounced tortuous enlargement of the subcutaneous veins that is typically painless. • Pain, erythema, or swelling at the varicosity is suggestive of superimposed thrombophlebitis and mandates further investigation using duplex ultrasonography. • Concomitant presence of other vascular and limb abnormalities needs to be assessed in patients with suspicion for congenital anomalies.

■ QUESTIONS AND ANSWERS 1. Which of the following questions about superficial varicosities is false? a. Varicose veins primarily affect the superficial venous system. b. They are never a result of previous deep venous thrombosis. c. Primary varicose veins are typically a result of incompetence of the sapheno-femoral or perforator valves. d. There is a familial predisposition in certain people. Answer: b. Superficial varicosities can occasionally result from increased venous pressure developing after deep venous thrombosis.

■ SUGGESTED READINGS 1. Arneja  JS, Gosain  AK. Vascular malformations. Plast Reconstr Surg. Apr 2008;121(4):195e–206e. 2. Gloviczki  P, Duncan  A, Kalra  M, et al. Vascular malformations: an update. Perspect Vasc Surg Endovasc Ther. Jun 2009; 21(2):133–148. 3. Legiehn GM, Heran MK. Venous malformations: classification, development, diagnosis, and interventional radiologic management. Radiol Clin North Am. May 2008;46(3):545–597, vi.

37

Venous Thoracic Outlet Syndrome Supratik Moulik and M. Haris U. Usman

PAINLESS SWELLING OF THE LEFT UPPER EXTREMITY A 20-year-old male presents with a swollen left upper extremity developing acutely 10 hours prior to presentation. He was working out at the time and claims to have had similar but less intense episodes bilaterally in the past. The swelling extends from the level of the left shoulder through the hand. There is no associated pain or loss of sensory or motor functions. He denies associated chest pain, shortness of breath, or dysphagia. He has no past medical history and the only medications he takes are antihistamines for allergies. CT venogram was performed to evaluate the anatomic relationship between the musculoskeletal structures of the thoracic outlet and the vasculature. Venography of his left shoulder region reveals narrowing of the subclavian vein at the level of the first rib. There is a small amount of nonocclusive thrombus noted. Provocative maneuvers demonstrate obliteration of flow in the subclavian vein. He was placed on intravenous unfractionated heparin to maintain an activated partial thromboplastin time between two and three times the amount considered to be normal. He underwent operative resection of his first rib with balloon venoplasty of the left subclavian vein with evidence of recanalization of the vein after the procedure. He was anticoagulated with warfarin to maintain an international normalized ratio (INR) between 2 and 3 for the ensuing 6 months. His symptoms completely abated without evidence of recurrence and anticoagulation was subsequently discontinued.

■ DEFINITION/BACKGROUND/EPIDEMIOLOGY Thoracic outlet syndrome (TOS) refers to “effort related” obstruction of the brachial plexus, subclavian artery, or subclavian vein as they traverse through the triangle formed by the anterior and medial scalene muscles and first rib. Neurogenic TOS comprises the most common form of TOS (90%) followed by venous (~9%) and arterial (14 days duration and almost 100% for acute thrombosis. Due to the presence of external compression causing intrinsic venous scarring, the addition of venoplasty and stenting to thrombolysis is typically mandated. Most patients with persistent occlusion require surgical resection of the first rib for alleviation of external compression. Decompression should be planned within 6 weeks of thrombolysis. Anticoagulation is advocated for 6  months after acute intervention, and is typically not

required for longer durations unless there is evidence of superimposed thrombophilia.

CLINICAL PEARLS • Typically painless swelling of one or both upper extremities extending from the shoulder joint to the level of the shoulder joint to the hand. Typically presenting within 12 hours of upper extremity exertion. • Venography is the mainstay of diagnosis as well as intervention. • Venoplasty followed by surgical resection of the first rib is typically advocated in patients with persistent obstruction.

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■ DIFFERENTIAL DIAGNOSES • Deep venous thrombosis related to intravenous catheters present with similar symptoms, however without antecedent history of vigorous upper extremity exercise. • Congestive heart failure can present with bilateral upper extremity swelling, although it more commonly manifests as lower extremity swelling and is more chronic in nature with reversal on leg elevation. • Dialysis fistula malfunction with resultant increase in venous outflow can result in swelling of the upper extremity. • Lymphedema typically manifests as bilateral chronic pitting edema with swelling and tension of the digital dermal surfaces (Stemmler’s sign). • Cellulitis presents as unilateral erythema typically without overt swelling.

■ QUESTIONS AND ANSWERS An 18-year-old male presents with sudden onset of shortness of breath after a recent gym workout session. For the past 2 weeks he had been involved in excessive upper extremity workouts. He had experienced discomfort in the right antecubital fossa with associated palpable firmness of the basilic and axillary veins during gym workout about 2  days prior to presentation but continued his routine. On presentation, besides

shortness of breath, he complained of sharp pleuritic left-sided chest pain. Continued physical activity exacerbated the swelling, and lifting his right arm above the head relieved the swelling but caused paresthesias in his right hand and fingers. This sensation resolved on lowering the arm. 1. The most likely cause of his shortness of breath is a. b. c. d. e.

Superior vena cava syndrome Right-sided venous TOS Pulmonary embolism Acute myocardial infarction Congestive heart failure

Answer: c 2. What should be the first line of investigation/therapy? a. b. c. d. e.

CTA of pulmonary arteries Intravenous heparin to target a PTT 2 to 2.5 normal Warfarin 10 mg orally Ultrasound of upper extremities Echocardiogram

Answer: b

■ SUGGESTED READINGS 1. Illig KA, Doyle AJ. A comprehensive review of Paget-Schroetter syndrome. J Vasc Surg. Jun 2010;51(6):1538–1547. 2. Landry  GJ, Liem  TK. Endovascular management of PagetSchroetter syndrome. Vascular. Sep-Oct 2007;15(5):290–296.

38

Superior Vena Cava Syndrome Supratik Moulik and M. Haris U. Usman

LEFT UPPER EXTREMITY AND FACIAL SWELLING A 57-year-old Caucasian male presents with facial and left upper extremity swelling that has progressively worsened over the past 2 weeks. He has also developed hoarseness with associated dyspnea and orthopnea over the past 2 days. All symptoms are exacerbated in the supine position and relieved with recumbency. He has been undergoing intravenous (IV) antibiotic therapy for left foot osteomyelitis that developed after he stepped on a rusted nail 6  weeks ago. For this purpose, he underwent placement of a peripherally inserted central catheter in his left axillary vein. Other medical problems include diabetes and depression. He is currently on metformin and wellbutrin and denies any allergies. Physical examination is remarkable for a markedly swollen left arm with visible varicosities across the shoulder region in association with swelling of the neck and face. The left upper extremity central venous catheter is obstructed at all three access ports. A CT scan of the chest and upper extremities was performed which demonstrated diminutive caliber of the SVC and extensive chest wall and left upper extremity collateral vessels. His upper extremity central venous catheter is removed and he is placed on IV unfractionated heparin. After obtaining percutaneous access through the internal jugular vein and placement of a 6F sheath, recombinant tissue plasminogen activator (r-TPA) was infused for thrombolysis. Once reperfusion was established, primary percutaneous transluminal balloon angioplasty (PTA) of the superior vena cava (SVC) was conducted followed by stent placement. His symptoms improved over the next few days with resolution of facial and upper extremity swelling. He was placed on aspirin and clopidogrel and after 3 months, a repeat computed tomography (CT) scan of the chest revealed patency of the SVC stent.

■ DEFINITION/BACKGROUND/EPIDEMIOLOGY The superior vena cava is the major venous collection channel from the head and upper extremities to the heart. Its principal blood return tributaries are the azygos, hemiazygos, and internal mammary veins supplying blood from the upper extremities and the long thoracic venous system draining the lower extremities. Hence, obstruction of the SVC results in backflow of blood to these

structures with resultant tissue engorgement and edema. Although historically related to malignancy (breast and lung), benign SVC syndrome has recently increased from causes like radiation-induced mediastinal fibrosis and iatrogenic SVC compression related to central venous catheters and cardiac pacemakers and defibrillators. Recent reports suggest that SVC syndrome occurs in 1% to 3% of patients with central venous catheters and in 0.2% to 3.3% of patients with implanted pacemakers. 201

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Figure 38.1 Axial and oblique-reformatted computed tomographic (CT) images demonstrate a shrunken and sclerotic superior vena cava (SVC) from chronic central venous catheter.

Figure 38.2 Volume-rendered CT figures from a contrast-enhanced CT demonstrate extensive chest wall and left upper extremity collateral vessel.

■ CLINICAL FEATURES The most common clinical presentations are facial or neck swelling, arm swelling, dyspnea, cough, and dilated chest veins. Less common presentations include chest pain, dysphagia, hoarseness, headache, confusion, dizziness, and syncope. Dyspnea is exacerbated in the supine position since a supine position will increase the amount of blood flow to the upper torso. Duration of symptoms and comorbidities provide clues to the etiology of the syndrome. In most cases, symptoms develop over the course of several weeks allowing for collateral circulations to develop. The presence of stridor, is indicative of laryngeal edema, and can be associated with serious or fatal outcomes. Similarly, confusion and obtundation may be ominous signs related to cerebral edema.

Physical examination findings include face and upper torso swelling with evidence of collateral veins on the chest. Facial swelling and plethora are typically exacerbated in the supine position with resultant cyanosis. The presence of lymphadenopathy may be a harbinger of malignancy especially in patients with high risk for malignancy.

■ LABORATORY AND IMAGING WORK CT scan of the chest is the imaging procedure of choice for initial assessment and establishment of the level and extent of the blockage as well as collateral pathways of drainage. It also permits identification of the cause of the obstruction.

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Venography is primarily utilized if an intervention is planned and for postintervention follow-up.

measures like IV steroids and may require endotracheal intubation. Endovascular repair is the procedure of choice for SVC syndromes of both benign and malignant etiology. Primary patency rates are variable but range from 57% to 79%. Aspirin and clopidogrel should be administered for at least 3 months after stenting for maintenance of patency. Long-term followup data is still unknown. Restenosis is related to length of initial occlusion and typically lower in catheter-related SVC syndrome than with mediastinal fibrosis. Complications are rare and typically related to access site bleeding and hematoma formation. Pericardial tamponade is a rare severe complication that may be related to intrapericardial rupture. Thrombolysis prior to PTA and stenting is beneficial in occlusions related to indwelling catheters especially if less than 4  weeks old. Catheters should be removed prior to institution of therapy and reinserted after PTA and stenting. Concomitant radiation and chemotherapy is required for malignant SVC syndromes. Operative surgical repair with venous conduits and synthetic grafts is an alternative option in anatomically challenging cases or with recurrent restenosis.

■ TREATMENT AND PROGNOSIS Therapy is initiated with anticoagulation using IV unfractionated heparin. Adjunctive measures including oxygen administration, head elevation, and fluid restriction and diuretic therapy for symptomatic relief. Severe airway compromise should be addressed with temporizing

CLINICAL PEARLS • Facial and upper torso swelling in association with dyspnea that is exacerbated in supine position. • CT scan of the chest is the initial diagnostic study of choice. • Endovascular repair is principal intervention for alleviation of stenosis with symptom resolution within 24 to 72 hours of the procedure.

Figure 38.3 Axial contrast enhanced CT figure through the level of the carina in a separate patient demonstrates nonocclusive catheter-related acute thrombus in the SVC (arrow).

A

B

Figure 38.4 (A) Axial contrast-enhanced CT image through the level of the aortic arch demonstrates a right para-mediastinal mass (arrowhead) with shunting of blood from the occluded SVC to the azygus vein (arrow). (B) Axial contrast enhanced CT iamge through the level of the liver from the same scan demonstrates hyper-enhancement of the quadrate lobe of the liver (arrowhead) related to venous collaterals from the obstructed SVC “hot quadrate sign.”

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■ DIFFERENTIAL DIAGNOSES • Pancoasts syndrome, due to upper lobe lung tumors, may manifest as upper extremity and facial swelling typically in association with Horner’s syndrome. Symptoms may not be related to positional variation. • Superficial emphysema, resulting from iatrogenic air infiltration of superficial tissues, is associated with superficial crepitus and not dependent on position variation. • Thoracic outlet syndrome presents with upper extremity swelling exacerbated by arm abduction or neck rotation.

■ QUESTIONS AND ANSWERS 1. Which one of the following statements is false? a. Most patients with SVC syndrome gain significant symptomatic improvement with head elevation and supplemental oxygen. b. Brain edema, decreased cardiac output, or upper airway swelling require emergent therapy with steroids.

c. Radiation therapy is typically required for malignant causes and results in clinical improvement only when there is radiographic evidence of swelling reduction. d. SVC syndrome from thrombosis in or around a central venous catheter requires catheter removal and local thrombolysis. Answer: c. Radiation of tumors results in improvement of symptoms well before radiologic evidence of swelling reduction.

■ SUGGESTED READINGS 1. Rice TW, Rodriguez RM, Light RW. The superior vena cava syndrome: clinical characteristics and evolving etiology. Medicine (Baltimore) 2006;85:37–42. 2. Schifferdecker B, Shaw JA, Piemonte TC, Eisenhauer AC. Nonmalignant superior vena cava syndrome: pathophysiology and management. Catheter Cardiovasc Interv. 2005;65:416–423. 3. Rizvi AZ, Kalra M, Bjarnason H, Bower TC, Schleck C, Gloviczki P. Benign superior vena cava syndrome: stenting is now the first line of treatment. J Vasc Surg. Feb 2008;47(2):372–380.

39

May–Thurner Syndrome Supratik Moulik and M. Haris U. Usman

PAINLESS SWELLING OF THE LEFT LOWER EXTREMITY A 27-year-old Caucasian female presented with left lower extremity swelling that developed a few days after she sprained her left ankle during soccer practice. She denied any other complaints except mild soreness at the left ankle. She had no previous medical problems and the only outpatient medications she was taking were oral contraceptive pills after delivering a baby boy 7 months ago. She reported allergies to penicillin derivatives. Physical examination was remarkable for a markedly swollen left lower extremity with normal pulses. The right lower extremity was normal in size with normal pulses. Due to high clinical probability based on Wells scoring, she was placed on unfractionated heparin. Duplex ultrasonography of the lower extremities revealed sluggish flow in the left external iliac vein without evidence for thrombosis. Computed tomography (CT) scan of the lung did not reveal evidence for pulmonary embolism. Magnetic resonance imaging of the pelvis revealed large occlusive thrombus in the deep venous system of her left leg extending from the level of the common iliac vein to the proximal external iliac vein. She underwent catheter-based thrombolysis. Repeat venogram the following day revealed persistence of the left common iliac vein thrombus for which she underwent balloon angioplasty with stenting with repeat venography revealing clot resolution. She was placed on enoxaparin and then transitioned to warfarin to target an international normalized ratio (INR) of 2.0 to 3.0. At 3 months followup, thrombophilia testing (except for protein C and S deficiency) was negative. She was continued on warfarin for 1 year and after evidence of normal duplex ultrasound findings, her warfarin was discontinued.

■ DEFINITION/BACKGROUND/EPIDEMIOLOGY May–Thurner syndrome is a compression syndrome of the left common iliac vein by the overlying right iliac artery and underlying vertebra. It is presumed to develop from chronic scarring of the common iliac vein by pulsations of the common iliac artery with resultant flow compromise and thrombus development. Patients with this syndrome commonly present with left-leg deep venous thrombosis (DVT)

but may also present with left-leg pain, edema, and venous insufficiency in the absence of DVT findings on ultrasonography. The estimated incidence of May–Thurner syndrome in patients with left iliofemoral DVT is 50%. May–Thurner syndrome is commonly seen in women in their 30s to 50s and it typically presents either as a large iliofemoral deep vein thrombosis or as chronic venous insufficiency. Chronic venous insufficiency typically manifests as symptoms related 205

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Venous Disease

Magnetic Resonance Venogram of the Pelvic Veins Showing Similarity to External Iliac Vein Thrombosis

Figure 39.1 Axial contrast-enhanced computed tomography (CT) images through the level of the aortic bifurcation and left thigh. There is thrombus in the left common iliac artery (arrowhead) as well as associated asymmetric swelling in the left thigh from thrombosis (arrowhead). Venogram Showing Clot Resolution

Venogram Showing Stent in Common Iliac Vein After Angioplasty and Stent Placement

Figure 39.2 Contrast-enhanced magnetic resonance angiography (MRA) in the equilibrium phase demonstrates compression of the left common iliac vein (white arrow) by the right common iliac artery (black arrowhead). The vein demonstrates dilation proximal to the area of compression.

Figure 39.3 Digital subtracted venogram of the left iliac venous system demonstrates irregular filling defects throughout the left common iliac vein (arrowhead).

to chronic venous hypertension, such as leg pain and swelling, varicose veins, or venous ulcerations.

ischemia of the limb. Patients may occasionally present with pulmonary embolism resulting from clot dislodgement.

■ CLINICAL FEATURES

■ LABORATORY AND IMAGING WORK

Most common presentation is left leg swelling. Patients may occasionally manifest with evidence of phlegmasia dolens with diminished pulses in association with cyanosis or

D-dimer carries a high sensitivity (95%) and accurately rules out the likelihood of venous thromboembolism (VTE) in patients with low to intermediate probability.

May–Thurner Syndrome

In patients with a high likelihood, duplex ultrasonography should be proceeded to directly. Direct noninvasive visualization: Duplex ultrasonography of the veins is the screening method of choice for patients with a either a high probability or elevated Ddimer. In patients with May–Thurner syndrome, duplex ultrasonography may not reveal thrombosis but sluggish flow suggestive of stenosis in the upstream pelvic veins. Magnetic resonance venography (MVR) of the veins is typically employed for identification of VTE above the level of the inguinal ligament especially in patients with high probability of DVT with recurrent nondiagnostic duplex ultrasounds, patients with evidence of anatomical substrates (May–Thurner Syndrome) or patients with evidence of venous compression with associated ischemia (phlegmasia dolens). Venogram is the gold standard for pelvic vein imaging, but due to its invasive nature, is only utilized for institution of thrombolysis or as followup to balloon angioplasty and stenting. Intravascular ultrasound imaging is an important adjunct to venography and is particularly useful in delineating intraluminal recanalized flow from perivenous collateral channels in chronic iliac vein occlusion.

■ TREATMENT AND PROGNOSIS All patients should undergo administration of intravenous unfractionated heparin and fluid intake should be judiciously monitored to avoid further swelling. Catheterdirected thrombolysis (CDT) remains the therapy of choice for most cases of May–Thurner syndrome for initial clot resolution. Although it lack clinical trial supporting, CDT has been shown in smaller studies, to be an effective agent for thrombolysis as well as preservation of venous valve function with a resultant decrease in incidence of chronic venous insufficiency. Mechanical thrombectomy using the percutaneous approach is a feasible alternative in patients with contraindication for thrombolysis. Balloon angioplasty and intravascular stenting is being increasingly embraced as a useful alternative to

207

surgery in patients with persistant thrombosis and evidence for venous obstruction. Several prospective and retrospective studies endorse this finding with evidence for high rates of technical success, low rates of complications, and primary patency rates of 79% to 100% at 1 to 3 years after stenting. Long-term outcomes of this treatment strategy, as well as CDT remain unknown at present.

■ DIFFERENTIAL DIAGNOSES The differential diagnosis for this disorder is the same as DVT.

■ QUESTIONS AND ANSWERS A 34-year-old patient presents with 2-month history of left leg swelling in association with stasis dermatitis at the level of the left medial malleolus. Past medical history is significant for left iliac vein thrombosis in association with May–Thurner syndrome, which was subsequently revascularized and stented. The patient says the swelling worsens with prolonged standing and is alleviated with leg elevation. What is the likely diagnosis? a. b. c. d. e.

Recurrent iliac vein thrombosis In-stent restenosis Embolism from aortic source Chronic venous insufficiency Congestive heart failure

Answer: d What is the next step in management? a. b. c. d. e.

Compression wraps Compression stockings Duplex ultrasonography of left leg D-dimer testing Intravenous heparin

Answer: c

■ SUGGESTED READINGS CLINICAL PEARLS • Left leg swelling is the most common presentation. • MRV is the mainstay of diagnosis for patients at high probability and with negative duplex ultrasounds. • CDT followed by balloon angioplasty and stenting remains mainstay of therapy for clot resolution as well as prevention of progression symptoms and development of chronic venous insufficiency.

1. Coss  E, Geske  JB, Mueller  PS. 57-year-old woman with acute lower extremity pain and swelling. Mayo Clin Proc. Oct 2009; 84(10):e1–e4. 2. Fazel  R, Froehlich  JB, Williams  DM, Saint  S, Nallamothu  BK. Clinical problem-solving. A sinister development–a 35-year-old woman presented to the emergency department with a 2-day history of progressive swelling and pain in her left leg, without antecedent trauma. N Engl J Med. Jul 2007;5:357(1):53–59. 3. May R, Thurner J. The cause of predominantly sinistral occurrence of thrombosis of the pelvic veins. Angiology. 1957;8(5):419–427. 4. Moudgill N, Hager E, Gonsalves C, Larson R, Lombardi J, DiMuzio P. May-Thurner syndrome: case report and review of the literature involving modern endovascular therapy. Vascular. Nov–Dec 2009;17(6):330–335.

40

Deep Venous Thrombosis With Phlegmasia Cerulea Dolens Jose Pascual, Benjamin Jackson, Supratik Moulik, and M. Haris U. Usman

PAINFUL LEFT LOWER EXTREMITY SWELLING WITH CYANOSIS A 72-year-old African-American female presented with right lower extremity swelling 2 days after being admitted for small-cell lung cancer. Physical examination is remarkable for a markedly swollen right lower extremity with decreased popliteal and dorsalis pedis pulses and bluish discoloration of the left great toe. The left lower extremity is normal in size with normal pulses. Past medical history is significant for chronic obstructive pulmonary disease, dyslipidemia, and seasonal allergies. She is currently on the inhaled diskus combination of fluticasone 250  mcg and salmeterol 50  mcg twice daily, as well as an albuterol inhaler and atorvastatin and reports no allergies. Duplex ultrasonography of the lower extremities revealed right iliofemoral deep venous thrombosis without evidence of extension to the popliteal veins. Arterial duplex ultrasonography revealed decreased right superficial femoral artery velocities consistent with decreased arterial flow. She was placed on intravenous unfractionated heparin but the swelling worsened further. Magnetic resonance venogram revealed extension of the thrombus to the inferior vena cava (IVC). Intravenous heparin was discontinued and she underwent emergent fasciotomy followed by catheter-directed thrombolysis.

■ DEFINITION/BACKGROUND/EPIDEMIOLOGY Phlegmasia dolens is a disorder of total thrombotic venous occlusion of the lower extremity, which may manifest as either phlegmasia cerulea dolens and/or phlegmasia alba dolens. Phlegmasia alba dolens is massive thrombosis of both the deep and superficial venous systems of the affected limb with patent venous collaterals and preservation of the limb. In contrast, phlegmasia cerulea dolens results in complete venous shutdown with concomitant obstruction of the collateral veins with resultant venous gangrene, systemic hypovolemic shock, and arterial compromise.

Combined, both syndromes are associated with a mortality rate of 25%, with a third of these being from pulmonary embolism. The limb amputation rate in survivors ranges from 12% to 25%. The incidence is higher in women and left leg is typically more frequently affected than the right. Common causes include malignancy, hypercoagulable disorders, postoperative states and compression disorders like the May–Thurner syndrome. The resultant rise in intravascular pressure is associated with the compartment syndrome with subsequent arterial compromise and gangrene. 209

210

Figure 40.1 Image of cyanotic edematous left foot with associated blistering and weeping (arrows).

Venous Disease

Figure 40.2 Duplex venous ultrasonography of right femoral vein showing obstructive thrombosis (arrowhead).

Figure 40.3 Multiple contrast-enhanced computed tomography (CT) images through the mid abdominal inferior vena cava (IVC) (on left), and at the level of the renal veins (right) demonstrates extensive occlusive thrombus with slight expansion of the IVC (arrowheads).

■ CLINICAL FEATURES Phlegmasia dolens usually presents clinically as a triad of pain, swelling, and cyanosis of the extremity. Progression of symptoms due to edema increases intravascular

pressure with resultant diminution or complete loss of pulses. Phlegmasia alba dolens is characterized classically by a white extremity due to drainage of cyanotic blood by collateral vessels while phlegmasia cerulea dolens is typically purple due to pooling of deoxygenated blood.

Deep Venous Thrombosis With Phlegmasia Cerulea Dolens

Figure 40.4 Contrast-enhanced CT image through the level of the aortic bifurcation demonstrates stranding surrounding the thrombosed IVC.

211

Figure 40.6 Image of cyanotic lower extremity after fasciotomy (arrowhead) showing swollen left lower extremity but with evidence of resolution of cyanosis.

Venography is required for direct visualization of the extent of thrombosis prior to catheter-directed thrombolysis.

■ TREATMENT AND PROGNOSIS Treatment revolves around preventing further thrombus propagation and alleviating the risk of leg ischemia and compartment syndrome by decreasing edema. Leg elevation, medical anticoagulation with heparin, and thrombectomy are typically required. Fasciotomy for compartment syndrome, followed by surgical thrombectomy or endovascular thrombolysis is the best approach for refractory cases. Prognosis remains poor with high morbidity and mortality and chance for limb amputation. Figure 40.5 Catheter-directed venographic image of the abdomen in a separate patient demonstrates numerous irregular filling defects throughout the infrarenal IVC (arrowhead).

■ LABORATORY AND IMAGING WORKUP Direct noninvasive visualization: Venous compression duplex ultrasonography is diagnostic of deep and superficial venous thrombosis. Lack of venous luminal compression is pathognomonic for a thrombus and reduced arterial flow velocities are proof of ischemic risk. Where diagnosis is uncertain, magnetic resonance venography (MVR) is able to differentiate acute from chronic thrombi and visualizes the lower extremity veins as well as the IVC.

CLINICAL PEARLS • Characteristics of clinical findings are pain, swelling, and cyanosis of the lower extremities especially in patients with underlying malignancies. • Duplex ultrasonography is the screening method of choice and should be further consolidated with MRV for further characterization of thrombus burden and degree of propagation. • Fasciotomy for compartmental syndrome, followed by thrombectomy and anticoagulation is paramount for limb salvage.

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■ DIFFERENTIAL DIAGNOSES • Critical peripheral artery disease is less likely to have associated limb swelling. • Peripheral embolization, typically without associated swelling or cyanosis and usually in association with a recent history of arterial manipulation. • Nonobstructive deep venous thrombosis, characterized by painless swelling and no evidence of hemodynamic compromise. • Ruptured Baker’s cyst, presents as painless fullness in the popliteal fossa with occasional extension into the lower thigh or upper leg.

■ QUESTIONS AND ANSWERS 1. Which of the following is not recommended following catheter-directed thrombolysis for phlegmasia cerulean dolens? a. Angiojet thrombectomy b. Intravenous hydration c. Urine alkalinization with sodium bicarbonate

d. Discontinue anticoagulation when the urine turns red Answer: d. Hemoglobinuria presenting as “hematuria” is common after angiojet thrombectomy and should not be a contraindication to anticoagulation.

■ SUGGESTED READINGS 1. Gociman B, Castillo-Sang M, Margni M, Almaroof B, Nazzal M. Successful treatment of phlegmasia cerulea dolens with combination surgical and catheter-assisted thrombectomy. Vascular. Mar–Apr 2009;17(2):108–111. 2. Perkins JM, Magee TR, Galland RB. Phlegmasia caerulea dolens and venous gangrene. Br J Surg. 1996;83:19.

41

Lymphedema Atul Jain, Geoffrey O. Ouma, and Deeba Faruq

LOWER EXTREMITY EDEMA A 53-year-old female with a past medical history of deep vein thrombosis, lymphedema, and colonic polyps was referred for evaluation of leg swelling. She has been complaining of swelling of the lower extremity, right greater than left, accompanied by knee and bilateral foot pain for the past 3 months. The pain is throbbing in nature and not relieved with rest or standing. She has no history of trauma and denies chest pain, shortness of breath, palpitations, or calf discomfort. She does report joint pain. On physical examination, she is well developed and nourished and the only pertinent finding is nonpalpable bilateral dorsalis pedis and posterior tibial pulses due to swelling. Figure 41.1 is a photograph of the lower extremity swelling. Figure 41.2 is a lymphoscintigram, and Figure 41.3 is a bone scan showing characteristic uptake seen in lymphedema.

■ DEFINITION/BACKGROUND/EPIDEMIOLOGY Lymphedema is characterized by regional accumulation of excessive amounts of interstitial protein-rich fluid. It is related to an abnormality in the lymphatic drainage of the extremities and is generally painless. Lymphedema can be classified as primary or secondary. Primary lymphedema generally occurs before the age of 35 and is sometimes associated with congenital abnormalities. There are three subtypes of primary lymphedema: (1) congenital lymphedema, (2) lymphedema praecox, and (3) lymphedema tarda. Secondary lymphedema is usually diagnosed after the age of 35, and as the name suggests is secondary to preexisting disease or trauma. However, secondary lymphedema is more common then primary lymphedema. The prevalence of primary lymphedema within North America has been estimated as 1.15 per 100,000

children, primarily affecting females close to menarche. Secondary lymphedema (i.e., arm swelling following breast cancer treatment) reportedly affects 15% to 20% of women undergoing axillary dissection and/or radiotherapy as part of their breast cancer therapy. Due to the fact that in the steady state, interstitial fluid is removed from the tissues by the lymphatics and not by venous reabsorption, lymphatic failure is the main cause of chronic edema. In a study of a population of 619,000 adults in London, 823 were found to have chronic edema. The estimated prevalence of chronic limb edema was 1.33 out of 1,000 people within the general population, increasing to 5.4 out of 1,000 in patients over 65  years of age. Fewer than 25% of the cohort experienced chronic edema as a result of cancer therapy. A total of 29% of patients had experienced recurrent cellulitis—acute inflammatory episodes secondary to predominantly streptococcal bacterial infection. 213

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Figure 41.1 Edema and skin changes in a patient with lymphedema of the lower extremity. Notice the “squared” appearance of the toes. This is a result of edema involving the toes, and is a characteristic finding in patients with lymphedema (edema due to other causes spares the toes).

Figure 41.2 Single anteroposterior planar image from a lymphoscintigraphy exam at the level of the pelvis demonstrates normal appearing lymphatic activity on the left and significantly diminished activity on the right, typical findings in lymphedema.

Figure 41.3 Frontal projection figure from a bone scan demonstrates marked asymmetry in the size of the lower extremities. There is additionally asymmetric increased methylene diphosphonate (MDP) uptake within the right leg, which is consistent with the patient’s diagnosis of lymphedema.

■ CLINICAL FEATURES The clinical presentation in lymphedema has a wide spectrum ranging from subtle skin changes to progressive infection of the soft tissue. Potential associated symptoms are high fever, cellulitis, and worsening edema. Sometimes patients experience a dull pain in the leg and a heavy sensation, as well as cosmetic alterations. In early stages, lymphedema is usually soft but the tissue becomes indurated and fibrotic as the condition worsens. There is also loss of normal contour and the toes become squared (Stemmer sign). Congenital lymphedema in the primary type appears shortly after birth and can be an autosomal dominant trait. This type of lymphedema accounts for 10% to 25% of all primary lymphedema. It can also be associated with several chromosomal abnormalities such as Turner syndrome, Milroy disease, Kleinfelter syndrome, and Noonan syndrome. The second type of primary lymphedema is lymphedema praecox (Meige disease); it is one of the familial forms and may be inherited in an autosomal dominant fashion, becoming evident during puberty. This type of lymphedema accounts for 65% to 80% of all cases. The third type of primary lymphedema is lymphedema tarda and occurs after the age of 35. This type of lymphedema is the most rare and accounts for only 10% of cases.

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Secondary lymphedema can be caused by damage to or obstruction of previously healthy lymphatics. Common causes are tumors, which can affect the lymphatic vessels, surgery, and radiation therapy. Other less common causes include recurrent lymphangitis, bacterial lymphangitis, tuberculosis, pregnancy, or following application of a tourniquet. See Table 41.1 for further classification.

■ LABORATORY AND IMAGING WORKUP A thorough medical history and physical is performed in order to exclude other causes of leg swelling, such as edema. For clinical purposes, lymphoscintography is the gold standard technique used to diagnose lymphedema. With lymphoscintography, the anatomy and the patency of the lymphatic channels can be defined. Other tests that complement lymphoscintography, such as MRI and CT, help in further functional assessment of lymphedema. Available tests besides lymphoscintography are lymphography, lymphatic capillaroscopy, axial tomography, and ultrasonography.

Table 41.1 Causes of Lymphedema Type

Examples

Primary

Congenital (including Milroy disease) Lymphedema praecox (includes Meige disease) Lymphedema tarda

Secondary

Recurrent lymphangitis Filariasis Tuberculosis Neoplasm Surgery Radiation therapy

Table 41.2 Stages of Lymphedema

CLINICAL PEARLS • History of malignancy—Eighty percent of lymphedema patients are thought to have a disease secondary to cancer or cancer-related treatment, particularly breast cancer. Lymphedema occurs in as many as 38% of women following mastectomy for breast cancer with axillary lymph node dissection and radiation. • History of travel to an endemic filariasis area— Wuchereria bancrofti and Brigia malayi, found in tropical regions of Africa and Asia, cause filiariasis by lymph channel obstruction or inflammation. • History of previous surgery—Most lymphedema patients have had a history of a surgical procedure such as nodal dissection. • History or radiation therapy—Fibrosis and lymphedema can be caused by radiation near axillary or groin lymph nodes. • Painless unilateral swelling of extremity or genitalia—Lower extremity affected in 90% of cases; 10% in upper extremities. Swelling is unilateral and begins distally and spreads proximally. • Involvement of distal extremity—Hands and feet may be involved at same time or alone. • Positive Stemmer sign—A positive Stemmer sign (inability to pinch the skin on the dorsum of the second toe between the thumb and forefinger) is useful to demonstrate distal involvement. A negative Stemmer sign does not exclude lymphedema.

■ TREATMENT AND PROGNOSIS

Stage

Description

Stage 0

A subclinical state where swelling is not evident despite impaired lymph transport. This stage may exist for many months or years before edema becomes evident.

Stage I

This represents early onset of lymphedema where there is accumulation of tissue fluid that reduces with limb elevation; pitting may be present; excess limb volume less than 20%.

Lymphedema cannot be cured, but compression treatments such as elastic sleeves/stockings, bandages, pneumatic compression devices, and manual compression may diminish edema. Preventive measures for those at risk for secondary lymphedema can help minimize swelling and associated symptoms. In severe cases, surgery can be performed to remove excess fluid and tissue. Chronic, long-term edema that persists for many years is associated with an increased risk of lymphangiosarcoma.

Stage II

Accumulation of fluid that does not reduce on elevation; may be nonpitting at later stages; excess volume of 20%–40%.

■ DIFFERENTIAL DIAGNOSES

Stage III

Fibrotic tissue and absent pitting; skin changes such as thickening, increased skin folds, and warty overgrowths may develop; excess limb volume over 40%.

• Chronic venous insufficiency—Damage to the peripheral venous system can lead to lower extremity edema.

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• Deep vein thrombosis—History of prior DVT, prolonged immobility, or hypercoagulable state. • Lipedema—Always affects pubertal females, typically bilaterally, and involves lower extremities sparing the feet due to obesity. • Congestive heart failure (CHF)—Characterized by generalized pitting edema that responds to elevation and diuretics. Because CHF is a systemic illness, extremity edema is typically bilateral, unlike lymphedema, which is usually unilateral. • Hypoalbuminemia—Through reduced intravascular osmotic pressure, pitting edema can occur due to renal failure and protein-losing enteropathies. • Malignancy—Malignant lesions including lymphangiosarcoma, angiosarcoma, and sarcoma should be considered when rapid swelling, weight loss, malaise, or pain occurs.

■ QUESTIONS AND ANSWERS 1. The following are clinical characteristics of congenital lymphedema, EXCEPT a. Lower limb lymphedema is often not associated with other vascular anomalies. b. Lymphedema is painless and nonpitting. c. There are no associated varicosities. d. There is no tendency to ulceration. e. It is a lifelong disease that does not affect longevity. Answer: a 2. All of the following are important in the differential diagnosis of congenital lymphedema EXCEPT a. b. c. d. e.

Turner syndrome Noonan syndrome Hydrops Down syndrome Klippel–Trenaunay syndrome

Answer: c

3. The single most important treatment in a patient with lymphedema to prevent infection is a. b. c. d.

Physical therapy Skin and nail care Prophylactic antibiotic Compression stockings

Answer: b

■ SUGGESTED READINGS 1. Clark B, Sitzia J, Harlow W. Incidence and risk of arm edema following treatment for breast cancer: a three-year follow-up study. Q J Med. 2005;98(5):343–348. 2. https://online.epocrates.com/noFrame/ 3. Mortimer PS, Levick JR. Chronic peripheral oedema: the critical role of the lymphatic system. Clin Med. 2004;4(5):448–453. 4. Slavin SA, Greene AK, Borud LJ. Lymphedema. In: Weinzweig J, ed. Plastic Surgery Secrets Plus. 2nd ed. Philadelphia, PA: Mosby; 2009. 5. Smeltzer  DM, Stickler  GB, Schirger  A. Primary lymphedema in children and adolescents: a follow-up study and review. Pediatrics. 1985;76(2):206–218. 6. Stemmer  R. A clinical symptom for the early and differential diagnosis of lymphedema. [Article in German] Vasa. 1976; 5:261–262. 7. Warren AG, Brorson H, Borud LJ, et al. Lymphedema: a comprehensive review. Ann Plast Surg. 2007;59:464–472. 8. Williams AF, Franks PJ, Moffatt CJ. Lymphoedema: estimating the size of the problem. Palliat Med. 2005;19:300–313.

Index

NOTE: Page numbers followed by ‘f’ indicate figures. AAA. See Abdominal aortic aneurysm (AAA) Abdominal abscess/infection, 115 Abdominal aortic aneurysm anatomy, 96 aneurysm sac, 96f clinical features, 93–94 connective tissue disease, 96 definition/epidemiology, 93, 96 differential diagnosis, 97 elective surgery, 96 laboratory and imaging workup, 94 risk, 96 screening, 96 treatment and prognosis, 94–97 Abdominal pain, 79, 99, 157 Abdominal ultrasonography, 80 Acetaminophen, 141 Acetylsalicylic acid, 10 Acute aortic dissection (AoD) clinical features, 83–84 definition/epidemiology, 83 differential diagnoses, 85 treatment and prognosis, 84–85 Acute aortic dissection, type A clinical features, 71 conditions associated, 73 definition/epidemiology, 71, 72, 73f diagnostic imaging modalities comparison, 76 differential diagnoses, 76 laboratory and imaging workup, 73, 74f, 75f treatment and prognosis, 73 Acute aortic dissection, type B clinical features, 79 definition/epidemiology, 79 differential diagnoses, 82 laboratory and imaging workup, 79–80

treatment and prognosis, 80–81 Acute aortic syndromes acute aortic dissection (AoD). See Acute aortic dissection intramural hematoma (IMH). See Intramural hematoma penetrating atherosclerotic ulcer (PAU). See Penetrating atherosclerotic ulcer versus thoracic aortic aneurysms (TAAs), 90 Acute arterial thrombosis, 99 Acute coronary syndromes versus thoracic aortic aneurysms (TAAs), 90 Acute embolic occlusion causes, 102 clinical findings, 102 diagnostic study, 102 treatment, 102 Acute kidney injury, 120 Acute limb ischemia, 9 Acute mesenteric ischemia (AMI) clinical features, 100 definition/epidemiology, 99–100 differential diagnosis, 102 laboratory and imaging workup, 101 treatment and prognosis, 101–102 Acute thrombotic occlusion causes, 102 clinical findings, 102 diagnostic study, 102 treatment, 102 Adjacent arterial steal syndrome, 109 Adjuvant therapy, 11 peripheral periarterial sympathectomy, 173 thromboangiitis obliterans (TAO), 173 Adult-onset asthma, 129 Aggressive medical therapy, 40

Alanine aminotransferase, 106 Allen test, 171 Allergic granulomatous angiitis. See Churg–Strauss syndrome (CSS) Alpha-interferon therapy, 153 Amaurosis fugax, 44, 137 American College of Rheumatology (1990) criteria, 129, 136 AMI. See Acute mesenteric ischemia Amlodipine, 99 ANCA. See Antineutrophil cytoplasmic antibody Aneurysmal disease, 15 Angina, 13 Angiotensin-converting enzyme inhibitor/angiotensin II receptor antagonist (ACEi/ARB), 117, 119, 124 Anterior ischemic optic neuropathy (AION), 134 Anti-tumor necrosis factor (TNF), 130 Antibodies to cyclic citrullinated peptides (anti-CCP), 160 Anticoagulation deep venous thrombosis (DVT), 185, 186 and dieresis, medical therapy with, 107 inferior vena cava (IVC) filters, 185 pulmonary embolism (PE), 190 risk–benefit ratio, 185 thrombosis risk factor, 186 warfarin, 190 Antiglomerular basement membrane disease (anti-GBM) granulomatosis with polyangiitis (GPA), 180

217

Index

218

Antineutrophil cytoplasmic antibodies (ANCA)-positive systemic vasculitis, 128 Antineutrophil cytoplasmic antibody (ANCA), 163 cANCA and pANCA, 178 gangrenous fingertips, 169 granulomatosis with polyangiitis (GPA), 161, 178 polyarteritis nodosa (PAN), 158, 159 vasculitis, 158 Antinuclear antibody (ANA), 160, 163 Aortic arch angiography bilateral subclavian arteries, 164f Takayasu’s arteritis (TA), 164f Aortic arch atheroma clinical features, 32–33 definition/epidemiology, 31–32 differential diagnoses, 34 grades, 33f laboratory and imaging workup, 33 treatment and prognosis, 33–34 Aortic rupture, 88 Aortic ulcer, 76 Aortic valvular murmur, 87 Aorto-iliac disease clinical features, 2 collateral flow pathways, 4 definition/epidemiology, 1–2 differential diagnoses, 5–6 intermittent claudication, 4 laboratory and imaging work, 2–3 Leriche syndrome, 4 treatment and prognosis, 3–5 Aorto-iliac system, MIP image from CTA, 4f Appendicitis, 102, 115 Arc of Riolan, 109 Arterial embolism aorto-iliac disease, 5 Arterial embolus, 11 Arthrosclerosis, 30 Aspirin, 33, 57, 64, 69, 99, 111, 119 intravenous immune globulin (IVIG), 147 Aspirin–dipyridamole, 69 Asthma, 130 Asymptomatic carotid artery stenosis (ACAS) trial, 39 Asymptomatic carotid stenosis clinical features, 37–38 definition/epidemiology, 37 laboratory and imaging workup, 38–39 treatment and prognosis, 39–40 Asymptomatic carotid surgery trial (ACST), 39 Ataxic hemiparesis, 69 Atheroembolism, 32 Atherosclerosis, 16, 31, 110 popliteal aneurysms, 29

Atherosclerotic disease, 13 Atherosclerotic lesions, 125 Atherosclerotic renal artery stenosis (ARAS) clinical features, 117–118 definition/epidemiology, 117 differential diagnoses, 119–120 hypertension, 117 laboratory and imaging workup, 118–119 treatment and prognosis, 119 Atherosclerotic vascular disease, 109 Atorvastatin, 99 Azathioprine, 130, 142, 166 Back pain, 79 Balloon angioplasty, 64, 207 BAV. See Bicuspid aortic valve Beta-blockers abdominal aortic aneurysm (AAA), 96–97 third-line antihypertensives, 119 Bicuspid aortic valve (BAV), 87, 88f Bilateral patchy pulmonary, 130 Biliary disease, 111, 115 Blindness, complication of giant cell arteritis (GCA), 137 Blood dyscrasias, 16 Blue toe syndrome, 29, 30, 32, 34 Breath shortness blood pressure, 187 computed tomography (CT), 187 physical examination, 187 Brigia malayi, 215 Brodie–Trendelenburg test varicose veins, 194 Budd-Chiari syndrome clinical features, 105 definition/epidemiology, 105 differential diagnoses, 107 laboratory and imaging work, 105–106 treatment and prognosis, 106–107 Buerger disease, 16 Burkland, 121 C-reactive protein (CRP), 130, 135 erythrocyte sedimentation rate, 171 gangrenous fingertips, 169 Kawasaki disease (KD), 147 polyarteritis nodosa (PAN), 158 serological markers, 170 Takayasu’s arteritis (TA), 165 CAD. See Cystic adventitial disease Cannabis arteritis, 173 Carotid artery stenting (CAS), 40, 46 Carotid atherosclerosis, 43 Carotid bruit, 37–38, 40 Carotid endarterectomy (CEA), 46, 47

Carotid revascularization endarterectomy versus stenting trial (CREST), 40, 46 Carotid stenosis carotid artery stenting (CAS), 46 limb shaking, 47 transient ischemic attack (TIA) and stroke, 45 women, 47 Carotid ultrasound, 38, 39f asymptomatic carotid stenosis, 38 Carpel tunnel syndrome, 173 CAS. See Carotid artery stenting Cather-directed venogram, 106f Catheter-directed angiogram multiple nonocclusive filling defects, 189f pulmonary artery injection, 190f Catheter-directed thrombolysis (CDT), 199 balloon angioplasty and stenting, 207 May–Thurner syndrome, 207 CDT. See Catheter-directed thrombolysis CEA. See Carotid endarterectomy Cellulitis thoracic outlet syndrome (TOS), 200 varicose veins, 195 Cerebral ischemia extracranial carotid and vertebral artery dissection, 57 Cervical lymphadenopathy, 145 Chest pain, 71 Chest radiography, 130 CHF. See Congestive heart failure Cholecystitis, 107 Cholelithiasis and biliary disease, 102 disease, 111, 115 Cholesterol crystal embolization, 32, 34 Cholesterol embolization syndrome, 33 Chostocondritis, pulmonary embolism, 191 Chronic eosinophilic pneumonia (CEP), 130 Chronic hepatitis, mixed cryoglobulinemia (MC), 153 Chronic kidney disease, 120 Chronic mesenteric ischemia (CMI). See also Acute mesenteric ischemia (AMI) cardiovascular risk modification, 111 clinical features, 110 definition/epidemiology, 109 differential diagnoses, 111 laboratory and imaging work, 110–111 treatment and prognosis, 111 Chronic venous insufficiency, 205–206, 215 Churg–Strauss syndrome (CSS), 161 antineutrophil cytoplasmic antibody assay (ANCA), 180

Index classification criteria of, 129 clinical features, 129 definition/epidemiology, 128 differential diagnoses, 130–131 laboratory and imaging work up, 129–130 treatment and prognosis, 130 Cigarette smoking abdominal aortic aneurysm (AAA), 93 accelerated aneurysm growth, 95 cool foot, 93 Claudication calf claudication, foot pain, foot numbness, 7 and discomfort left knee, 27 hip, buttock, and thigh, 1 intermittent claudication, 4 peripheral arterial disease (PAD), 2 venous claudication, 5 Clonidine, third-line antihypertensives, 119 Clopidogrel, 10, 64, 69, 111 Coarctation, of aorta, 120 Colchicine, 142 Cold stimulation test, 15 Color duplex ultrasonography, 136 Community-acquired pneumonia granulomatosis with polyangiitis (GPA), 180 Compartment syndrome fasciotomy, 211 risk, 211 Computed tomography (CT) acute stroke, 68 angiography, 190 aortic arch level, 203f carina level, 203f chest scan, 202 chest wall and left upper extremity collateral vessel, 202f coronal reformatted figure, 188 imaging modalities, 165 left frontal parenchymal hemorrhage, 163, 164f liver, 203f MDCT technology, 190 mixed cryoglobulinemia (MC), 153 penetrating atherosclerotic ulcer (PAU), 84f, 85f pulmonary arterial phase, 188 superior vena cava (SVC), 202f Takayasu’s arteritis (TA), 164f venography, thoracic outlet syndrome (TOS), 198 Computed tomography (CT) angiogram aortic root, 73 bicuspid aortic valve (BAV), 88f calcified atherosclerotic plaque, carotid arteries, 44f ECG-gated, chest, 88f primary intimal tear, 80f renal arteries, 80f

219

true lumen and false lumen, 76 type B dissection, 80f, 81, 82f Computed tomography angiography (CTA) abdominal aortic and iliac aneurysms, 96f abdominal aortic aneurysm (AAA) anatomy, 94 acute mesenteric ischemia (AMI), 101 asymptomatic carotid stenosis, 39 atherosclerotic disease, 172f bowel embolic occlusion, 101 chronic mesenteric ischemia (CMI), 110 distal aorta, 146f distal femur level, 28f extracranial vertebral artery stenosis, 51 fibromuscular dysplasia (FMD), 122, 123 fusiform dilation, 94f, 95f imaging modalities, 171 infra-inguinal disease, 9 axial postcontrast, mid-femurs level, 10f bilateral superficial femoral arteries occlusion, 11f superficial femoral and popliteal artery, multiplanar reformatted, 10f Kawasaki disease (KD), 147 left anterior descending (LAD) coronary arteries, 146f left subclavian artery, 16f lower extremities, 28f neck, stenosis, 39f polyarteritis nodosa (PAN), 158 popliteal artery aneurysm, 29 popliteal artery entrapment syndrome (PAES), 25 superficial femoral artery (SFA), 170 techniques, 160 vascular calcium, 95f visceral arterial aneurysms, 114, 115 Computerized tomography venography (CTV), 105–106 Congenital lymphedema, 214 Congenital vascular abnormalities, 72 Congestive heart failure (CHF), 216 venous thoracic outlet syndrome, 200 Conjunctival erythema, 145 Connective tissue disorders, 16 associated with dissection, 56 Contrast angiography, 29 in popliteal cystic adventitial disease, 20 Contrast enhanced magnetic resonance angiography (CE-MRA) popliteal artery aneurysm, 29 popliteal cystic adventitial disease, 20 Conventional angiography, 3

acute mesenteric ischemia (AMI), 101 venous phase imaging, 101 “Corkscrew” collateralization, 172 definition, 171–172 digital arteries, 170f thromboangiitis obliterans (TAO), 172 Coronary arteritis, 129 Coronary artery aneurysms Kawasaki disease (KD), 146, 149 Corticosteroids, 136–137 Churg–Strauss syndrome (CSS), 130 Kawasaki disease (KD), 148 Takayasu’s arteritis (TA), 166 CREST syndrome, 15, 173 Critical limb ischemia (CLI), 9 peripheral arterial disease (PAD), 2 Critical peripheral artery disease, 212 Crohn’s disease, 111, 143 CRP. See C-reactive protein CT. See Computed tomography Cushing syndrome, 120 Cyanosis lower extremity swelling, 209, 211f peripheral embolization, 212 phlegmasia dolens, 206, 210 Cyanotic edematous left foot, 210 Cyclophosphamide, 142, 160, 166 combination therapy, 179 granulomatosis with polyangiitis (GPA), 179 Cyclosporine A, 142 Cystic adventitial disease (CAD), 12. See also Popliteal cystic adventitial disease Cytoplasmic antineutrophil cytoplasmic antibody (cANCA) diffuse granular staining, 178 granulomatosis with polyangiitis (GPA), 178 D-dimer, 73, 184, 186, 206 Dabigatran, 185 Dapsone, 142 Deceleration trauma, 72 Deep venous thrombosis (DVT), 215 anticoagulation, 185 clinical features, 184 definition/epidemiology, 183–184 May–Thurner syndrome, 205, 207 with phlegmasia cerulea dolens clinical features, 210–211 definition/epidemiology, 209–210 differential diagnoses, 212 laboratory and imaging workup, 211 treatment and prognosis, 211 probability, 207 ultrasonography, 205 varicose veins, 195 venous thoracic outlet syndrome, 200 Wells criteria, diagnosis, 184

Index

220

Dexamethasone, 120 Diabetes, for lacunar stroke, 67 Diabetic and drug-induced myopathy, 6 Dialysis fistula malfunction venous thoracic outlet syndrome, 200 Digital subtraction angiography (DSA), 14f carotid and VA dissection, 57 carotid stenosis, 45 extracranial vertebral artery stenosis, 51 fibromuscular dysplasia (FMD), 122, 123 intracranial stenosis, 62–63 Digital subtraction venogram thoracic outlet syndrome (TOS), 199 Dihydropyridine calcium channel blockers, 15 Direct noninvasive visualization, 3, 105 acute mesenteric ischemia (AMI), 101 bowel infarction, 101 deep venous thrombosis (DVT), 185 duplex ultrasonography, 185, 198 May–Thurner syndrome, 207 varicose veins, 194 venous luminal compression, 211 venous thromboembolism (VTE), 185 Distal extremity hands and feet, 215 Dizziness. See Vertigo Dopamine, 190 Doppler flow in upper extremity (UE) arterial disease, 15 Doppler signal, 25 Doppler ultrasonography, 118 Double vision, 49 Duodenal ulceration, 111 Duodenum, 141 Duplex and color flow in upper extremity (UE) arterial disease, 15 Duplex ultrasonography Budd-Chiari syndrome, 105, 107 celiac artery, 100 chronic mesenteric ischemia (CMI), 110, 111 D-dimer testing, 184, 186 direct noninvasive visualization, 185 femoral vein thrombosis, 184f fibromuscular dysplasia (FMD), 122 infra-inguinal disease, 9 popliteal artery entrapment syndrome (PAES), 24–25 popliteal cystic adventitial disease, 20 thoracic outlet syndrome (TOS), 198 thrombosis and venous reflux, 185f varicose veins, 195 venous thromboembolism (VTE), 184 visceral arterial aneurysms, 114 Duplex venous ultrasonography, 211f DVT. See Deep venous thrombosis (DVT) Dysarthria, 61 Dysarthria clumsy-hand syndrome, 69

Echocardiography Kawasaki disease (KD), 147 Ectopic pregnancy, 102, 111, 115 Ehlers–Danlos syndrome, 87, 125 Endofibrosis aorto-iliac disease, 5 Endovascular treatment femoro-popliteal disease, 10 infra-popliteal disease, 10 Endovenous laser ablation superficial venous reflux, 195 Enoxaparin, 185 Eosinophilia, 129 Epinephrine, 190 Ergotamine abuse, 16 Erythrocyte sedimentation rate (ESR), 129, 135, 170 gangrenous fingertips, 169 Kawasaki disease (KD), 147 Takayasu’s arteritis (TA), 165 Esmolol, 80 ESR. See Erythrocyte sedimentation rate Eukocytoclastic vasculitis abundant neutrophils, 152f European League Against Rheumatism (EuLAR), 141 Exercise treadmill testing, 3 Exertional chronic compartment syndrome, 5–6 Extra-abdominal technique, 3f Extra-renal fibromuscular dysplasia, 122 Extracranial carotid and vertebral artery dissection clinical features, 56–57 definition/epidemiology, 55–56 differential diagnoses, 59 laboratory and imaging workup, 57 treatment and prognosis, 57–58 Extracranial vertebral artery stenosis clinical features, 50 definition/epidemiology, 49 differential diagnoses, 53 laboratory and imaging workup, 50–51 medical therapy, 52 treatment and prognosis, 51–52 Extravascular compression syndromes aorto-iliac disease, 5 F-PAES. See Functional popliteal entrapment syndrome Fat embolism, 59 Femoro-popliteal disease endovascular treatment of, 10 Fetal posterior cerebral artery, 58 Fever, 145, 157 Fibromuscular dysplasia (FMD), 120, 167 aorto-iliac disease, 5 categories of, 121 cerebrovascular symptoms, 122

clinical features, 122 definition/epidemiology, 121–122 differential diagnoses, 125 laboratory and imaging workup, 122–123 refractory hypertension, 121 treatment and prognosis, 123–125 Fibromuscular hyperplasia, 121 Five factors score (FFS), 160 Fluorine-18-desoxyglucose positron emission tomography (18F-FDG-PET), 136 FMD. See Fibromuscular dysplasia “Food fear,” 110 Frostbite, 17 Functional popliteal entrapment syndrome (f-PAES), 25 Gadolinium, 39 Gangrenous fingertips flu-like symptoms, 169 laboratory evaluation, 169 necrosis, 169, 170f Gastric carcinoma, 111 Gastric ulceration, 111 Giant cell arteritis (GCA), 16, 167 clinical features, 134–135 definition/epidemiology, 134 differential diagnoses, 137 headaches, 133 jaw claudication, 133 laboratory and imaging work up, 135–136 normal temporal artery, 134f treatment and prognosis, 136–137 Granulomatosis with polyangiitis (GPA), 130–131 clinical features, 177–178 definition/epidemiology, 177 differential diagnosis, 179–180 laboratory and imaging workup, 178–179 treatment and prognosis, 179 Gross hematuria, 141 Hemiparesis, 43, 61 Henoch–Schönlein purpura (HSP), 161 clinical features, 141 definition/epidemiology, 139–140 differential diagnoses, 142–143 laboratory and imaging workup, 141 mixed cryoglobulinemia (MC), 154 treatment and prognosis, 141–142 Hepatic artery aneurysms, 113 Hepatic carcinoma, 107 Hepatitis, 107 Hepatitis B virus (HBV) infection polyarteritis nodosa (PAN), 158 Hepatitis C virus (HCV) infection cryoglobulinemic vasculitis, 151

Index eradication rates, 153 laboratory tests, 153 mixed cryoglobulinemia (MC), 152 Hereditary connective tissue diseases, 72 High-resolution chest computed tomography (HRCT), 130 Hip, buttock, and thigh claudication, 1 Hollenhorst plaques, 44–45, 45f, 46–47 Homonymous hemianopsia, 55 Horner’s syndrome, 56, 58, 204 Hourglass sign, 21 Human immunodeficiency virus (HIV), 163 Hydralazine, third-line antihypertensives, 119 Hypercoagulability disorders, 187 Hypereosinophilic syndrome (HES), 130 Hyperglycemia, 59 Hypersensitivity vasculitis, 130, 139, 143 Hypertension, 72, 75 lacunar infarction, 69 lacunar stroke, 67 Hyperviscosity syndromes mixed cryoglobulinemia (MC), 154 Hypoalbuminemia, 216 Hypoglycemia, 59 Hypothenar hammer syndrome, 173 ICA. See Internal carotid artery IgA nephropathy, 141 IMA. See Inferior mesenteric artery Immunoglobulin mixed cryoglobulinemia (MC), 152 Incomplete Kawasaki disease, 147 Indirect luminal stenosis assessment popliteal cystic adventitial disease, 20 Infections, 59 Inferior mesenteric artery (IMA) hypertrophy, 165f Inferior vena cava (IVC) aortic bifurcation, 211f deep venous thrombosis (DVT), 185 direct noninvasive visualization, 211 filters, 185 lower extremity veins, 211 magnetic resonance venogram, 209 mid abdominal, 210f renal veins, 210f Infliximab, 148 Infra-inguinal disease clinical features, 9 definition/epidemiology, 7 differential diagnoses, 11–12 laboratory and imaging workup, 9 treatment and prognosis, 9–11 Infra-popliteal disease endovascular treatment of, 10 Interferon-alpha tumor necrosis factor (TNF), 130 Intermittent claudication, symptoms of, 122

221

Internal carotid artery (ICA), 37, 38f, 43 ophthalmologic manifestations, 56 stroke, 57 ultrasonography, 57 Intestinal obstruction, 102, 111 Intimal fibroplasia, 121 Intracranial hemorrhage and abdominal pain Allen test, 163 aortic arch angiography, 165f inferior mesenteric artery (IMA), 165f magnetic resonance angiography (MRA), 165f physical examination, 163 superior mesenteric artery (SMA), 165f Intracranial stenosis clinical features, 61–62 definition/epidemiology, 61 differential diagnoses, 64 laboratory and imaging work, 62–63 treatment and prognosis, 63–64 Intramural hematoma (IMH), 76 clinical features, 83–84 definition/epidemiology, 83 differential diagnoses, 85 laboratory and imaging workup, 84 treatment and prognosis, 84–85 Intravascular stenting, 207 Intravascular ultrasound imaging May–Thurner syndrome, 207 Intravenous (IV) antibiotic therapy heparin, 203 left foot osteomyelitis, 201 Intravenous (IV) steroids, 141, 142 Intravenous immune globulin (IVIG), 142 dosage, 148 Kawasaki disease (KD), 147–148 Invasive angiography giant cell arteritis (GCA), 136 Invasive contrast angiography thromboangiitis obliterans (TAO), 171 Ishikawa sign, 19, 21 IVC. See Inferior vena cava IVIG. See Intravenous immune globulin Jugular venous reflux, 105 Juvenile idiopathic arthritis Kawasaki disease (KD), 149 Kawasaki disease (KD), 167 clinical features, 146–147 definition/epidemiology, 146 differential diagnosis, 149 laboratory and imaging workup, 147 treatment and prognosis, 147–149 Klippel–Trenaunay syndrome varicose veins, 194

Labetalol, 80 Lacunar infarction clinical features, 67–68 definition/epidemiology, 67 laboratory and imaging work, 68–69 treatment and prognosis, 69 Laryngeal edema, 202 Leadbetter, 121 Left anterior descending (LAD) fusiform aneurysmal dilation, 146f Left common carotid artery (LCCA) transthoracic echocardiogram, 72f Left infra-popliteal disease, 7, 8f Left internal mammary artery (LIMA), 13, 14 faint antegrade flow, 14f Left main coronary artery (LMCA) Kawasaki disease (KD), 147 left-sided, 67 Left subclavian artery (LSCA), 16f transthoracic echocardiogram, 72f Left upper extremity swelling, 197, 201 Leriche syndrome, 4 Leukocytosis Kawasaki disease (KD), 147 Limb shaking, 47 Lipedema, 216 Lipid lowering therapy, 34 LMCA. See Left main coronary artery Loeffler syndrome, 129 Loeys–Dietz syndrome (LDS), 72, 87, 89 Loop diuretics, second-line antihypertensives, 119 Low molecular weight heparin (LMWH) enoxaparin, 185 oral anticoagulation, 185 warfarin, 185 Lower extremity claudications, 135 Lower extremity edema edema and skin changes, 213, 214f leg swelling, 213 lymphoscintigraphy exam, 214f methylene diphosphonate (MDP) uptake, 214f Lower gastrointestinal series, 140f LWWH. See Low molecular weight heparin Lymphadenopathy, 202 Lymphedema clinical features, 214–215 definition/epidemiology, 213–214 differential diagnoses, 215–216 laboratory and imaging workup, 215 stages, 215 treatment and prognosis, 215 venous thoracic outlet syndrome, 200 Lymphedema praecox, 214 Lymphedema tarda, 214 Lymphoproliferative disorders (LPDs) granulomatosis with polyangiitis (GPA), 180

Index

222

Magnetic resonance angiography (MRA), 119 asymptomatic carotid stenosis, 39 extracranial vertebral artery stenosis, 51 fibromuscular dysplasia (FMD), 122, 123 giant cell arteritis (GCA), 136 iliac vein and artery, 206f imaging modalities, 171 infra-inguinal disease, 9 Kawasaki disease (KD), 147 maximum intensity projection (MIP), 165f multifocal occlusions, 170f neck, cervical ICA dissection, 56f polyarteritis nodosa (PAN), 160 popliteal artery entrapment syndrome (PAES), 25 superficial femoral artery, 165f Takayasu’s arteritis (TA), 165f true lumen and false lumen, 76 visceral arterial aneurysms, 114, 115 Magnetic resonance imaging (MRI) acute dissection, neck, 56f brain, right basal ganglia infarction, 44 fat saturation, 21f distal femur, 29f granulomatosis with polyangiitis (GPA), 178 hypodensity, 32 lacunar infarction, 68, 69f mixed cryoglobulinemia (MC), 153 popliteal artery entrapment syndrome (PAES), 25 scattered infarcts in right cerebellum and pons, 50 Magnetic resonance venography (MRV), 106, 185, 207, 211 deep venous thrombosis (DVT), 185 thoracic outlet syndrome (TOS), 198 venous thromboembolism (VTE), 185 Malignancy, 215, 216 harbinger, 202 Marfan and Ehlers–Danlos syndrome, 30 Marfan syndrome, 75, 81, 87, 89, 125, 167 dilated aortic root and aortic regurgitation, 90f morphology characteristic of, 90f May–Thurner syndrome, 207, 209 aortic bifurcation level, 206f clinical features, 206 definition/epidemiology, 205–206 differential diagnosis, 207 laboratory and imaging work, 206–207 treatment and prognosis, 207 MC. See Mixed cryoglobulinemia McArdle syndrome, 6

MDCT. See Multi-detector computed tomography MDP. See Methylene diphosphonate Measles Kawasaki disease (KD), 149 Mechanical thrombectomy, 207 Medial fibroplasia, 121 Medial hyperplasia, 122 Membranoproliferative glomerulonephritis (MPGN) biopsy proofs, 153 mixed cryoglobulinemia (MC), 152 renal involvement, 152 Mesenteric blood flow, 109 Mesenteric fibromuscular dysplasia, 122 Mesenteric venous thrombosis, 105 Methotrexate, 130, 137, 160, 166 Methylene diphosphonate (MDP), 214 Methylprednisolone, 141 MI. See Myocardial infarction Microscopic polyangiitis (MPA), 131 antineutrophil cytoplasmic antibody assay (ANCA), 180 granulomatosis with polyangiitis (GPA), 180 Migraines, 59, 64 Minoxidil, third-line antihypertensives, 119 Mixed cryoglobulinemia (MC) clinical features, 152–153 definition/epidemiology, 152 differential diagnosis, 154 laboratory and imaging workup, 153 treatment and prognosis, 153–154 types, 152 Mononeuritis multiplex, 130 Morbidity outcomes, infra-inguinal lesions, 9 MPGN. See Membranoproliferative glomerulonephritis MRA. See Magnetic resonance angiography MRI. See Magnetic resonance imaging MRV. See Magnetic resonance venography Multi-detector computed tomography (MDCT) angiogram, 189–190 D-dimer testing, 189 Multiple sclerosis, 59 Muscle disease polyarteritis nodosa (PAN), 159 Myalgias, 157 Mycophenolate mofetil, 142 Myeloperoxidase (MPO) antineutrophil cytoplasmic antibody assay (ANCA), 178 Myocardial infarction (MI), 46 Kawasaki disease (KD), 149 pulmonary embolism, 191 Myositis, 6

Nasal biopsy, 176 Negative Stemmer sign, 215 Nephrogenic systemic fibrosis, incidence of, 119 Neuro-ophthalmic symptoms, 134 Neurogenic compression aorto-iliac disease, 5 Neurological disease polyarteritis nodosa (PAN), 159 Nicotine replacement therapy, 172 Nifedipine, 15 NOMI. See Nonocclusive mesenteric ischemia Noninvasive imaging extracranial carotid and vertebral artery dissection, 57 Noninvasive vascular tests, 3, 45 extracranial vertebral artery stenosis, 51 intracranial stenosis, 62 Noninvasive versus invasive visualization intracranial stenosis, 62, 63f Nonobstructive deep venous thrombosis, 212 Nonocclusive mesenteric ischemia (NOMI), 99 calcified atherosclerotic disease, 101 causes, 102 clinical findings, 102 diagnostic study, 102 treatment, 102 vascular hemodynamics monitoring, 101 Nonthrombocytopenic rash, 141 Norepinephrine, 190 Normochromic, 135 Normocytic anemia, 135 Numbness, 61 Occupational injury, 16–17 Optimal antithrombotic therapy, 33 Oral prednisone, 141 Otitis media granulomatosis with polyangiitis (GPA), 179 PAD. See Peripheral arterial disease PAES. See Popliteal artery entrapment syndrome Paget–Schroetter syndrome, 197 Painless unilateral swelling, 215 Palpable purpura, 141 PAN. See Polyarteritis nodosa Pancoasts syndrome upper extremity and facial swelling, 204 Paresthesias, symptoms of, 122 PE. See Pulmonary embolism Pediatric Rheumatology Society (PreS), 141

Index Penetrating atherosclerotic ulcer (PAU) clinical features, 83–84 definition/epidemiology, 83 differential diagnoses, 85 laboratory and imaging workup, 84 treatment and prognosis, 84–85 Percutaneous transluminal angioplasty (PTA), 3, 9, 10, 124, 203 Percutanous transluminal angioplasty (PTA), 124 Periarterial hyperplasia, 122 Pericarditis pulmonary embolism, 191 Perimedial fibroplasia, 121–122 Peripheral arterial disease (PAD) cardinal symptom, 2 clinical examination, 2 definition, 1 in infra-inguinal segments causes, 7 diagnosis, 9 prevalence, 7 laboratory evaluation, 2–3 risk factors, 1–2 treatment and prognosis, 3–6 Peripheral embolization cyanosis, 212 deep venous thrombosis with phlegmasia cerulea dolens, 212 Pharmacological therapy iloprost, 173 vasodilators, 173 Pheochromocytoma, 119 Phlegmasia alba dolens characterization, 210 collateral vessels, 210 Physiologic testing infra-inguinal disease, 9 Plasma aldosterone/renin ratio, 120 Plasmapheresis, 142 Pneumocystis carinii, 179 Pneumonia pulmonary embolism, 191 Pneumothorax pulmonary embolism, 191 Polyarteritis nodosa (PAN) clinical features, 159 definition/epidemiology, 158–159 differential diagnosis, 160–161 laboratory and imaging workup, 159–160 muscular artery with fibrinoid necrosis, 158f red blood cells, 158f treatment and prognosis, 160 Polyarteritis nodosa (PAN), 128, 130 Popliteal artery aneurysm, 11 clinical features, 29 definition/epidemiology, 27–29 laboratory and imaging workup, 29 treatment and prognosis, 29–30

223

Popliteal artery entrapment syndrome (PAES), 12, 173 clinical and anatomical classification, 24 clinical features, 24 definition/epidemiology, 23–24 laboratory and imaging workup, 24–25 treatment and prognosis, 25 Popliteal cystic adventitial disease clinical features, 19 definition/epidemiology, 19 differential diagnoses, 21 laboratory and imaging workup, 20 treatment and prognosis, 20 Positive Stemmer sign, 215 Posterior cerebral artery (PCA), 56f, 58 Postprandial abdominal pain, 109 Postprandial epigastric pain, 111 Postradiation vascular fibrosis aorto-iliac disease, 5 Poststreptococcal nephritis granulomatosis with polyangiitis (GPA), 180 Prednisone, 179 Primary hyperaldosteronism, 120 Primary lymphedema diagnosis, 213 prevalence, 213 subtypes, 213, 214 Pronator drift, 46 Prothrombin gene (G20210A) mutation, 187 Protoplasmic antineutrophil cytoplasmic antibody (pANCA) granulomatosis with polyangiitis (GPA), 178 myeloperoxidase (MPO), 178 PTA. See Percutaneous transluminal angioplasty Pulmonary angiography pulmonary embolism (PE), 190 Pulmonary embolism (PE) clinical features, 188–189 definition/epidemiology, 187–188 differential diagnosis, 191 laboratory and imaging workup, 189–190 right ventricular dilatation, 189f treatment and prognosis, 190–191 Pulmonary involvement. See Loeffler syndrome Pulse volume and contours, in upper extremity (UE) arterial disease, 15 Pure motor stroke, 69 Pure sensory stroke, 69 Radiation therapy, 215 Rapid plasma reagin (RPR), 163 Rapidly progressive glomerulonephritis (RPGN) polyarteritis nodosa (PAN), 160

Rash, 145 Kawasaki disease (KD). See Kawasaki disease mixed cryoglobulinemia (MC), 152f Raynaud’s syndrome, 13–14 Renal artery, 122 revascularization, 124 Renal artery stenosis angioplasty, 166 enzyme inhibitors, 165 Renal biopsy, histopathology from, 140f Renin–angiotensin–aldosterone system, 117, 119, 124 Resistive index (RI), of cortical blood vessels, 122–123 Resting segmental systolic pressures, 8f Revascularization, 40, 111 Revised Geneva (RG) scores versus Wells criteria, 190 Reye syndrome, 147 Rheumatoid arthritis (RA) granulomatosis with polyangiitis (GPA), 180 Rhinitis, 130 Ribavirin, 153–154 Rituximab, 153 Rivaroxaban, 185 Roseola infantum Kawasaki disease (KD), 149 RPGN. See Rapidly progressive glomerulonephritis Rubella Kawasaki disease (KD), 149 Ruptured Baker’s cyst, 212 extensive subcutaneous venous, 194f varicose veins, 195 Sarcoidosis granulomatosis with polyangiitis (GPA), 180 Scalded skin syndrome (SSS) Kawasaki disease (KD), 149 Scarlet fever Kawasaki disease (KD), 149 “Scimitar,” 20, 21 Sclerotherapy varicose veins, 195 Secondary lymphedema breast cancer therapy, 213 causes, 215 diagnosis, 213 Seizures, 59 Sensory-motor stroke, 69 Serum aspartate, 106 Serum potassium, 118 Sinusitis central cavitation, 176f cytoplasmic antineutrophil cytoplasmic antibody (cANCA), 176 glomerular lesions, 177f

Index

224

Sinusitis (continued) granulomatosis with polyangiitis (GPA), 176f, 179 lung biopsy specimen, 177f physical examination, 175 protoplasmic antineutrophil cytoplasmic antibody (pANCA), 176 right upper lobe, 176f serum levels, 175 symptoms, 175 Sinusitis, 130 SMA. See Superior mesenteric artery Small bowel inflammation polyarteritis nodosa (PAN), 159f Smoking peripheral arterial disease (PAD), 2 Splenic artery aneurysms, 113 Staphylococcus aureus, 179 Stasis dermatitis varicose veins, 195 Statin, 119 therapy, 33 Stenosis treatment, 14f Stenting, 40, 64 Steven–Johnson syndrome (SJS) Kawasaki disease (KD), 149 “String of beads,” 121, 123, 125 Stroke, 34, 59 carotid atherosclerosis, 43 extracranial vertebral artery stenosis, 50 internal carotid artery (ICA) stenosis, 43 Sulfamethoxazole, 179 Superficial emphysema, 204 Superficial femoral artery (SFA) stenosis, 146f Superficial thrombophlebitis thromboangiitis obliterans (TAO), 171 Superior mesenteric artery (SMA) common carotid artery, 165f computed tomography angiogram (CTA), 158f fusiform aneurysmal dilation, 158f hemodynamically significant stenosis, 100f jejunal branches, 102 thrombolysis, 101 transmural bowel infarction, 100 Superior vena cava (SVC) syndrome chronic central venous catheter, 202 clinical features, 202 definition/epidemiology, 201–202 differential diagnosis, 204 laboratory and imaging work, 202–203 treatment and prognosis, 203 Surgical complications asymptomatic carotid stenosis, 40 Surgical treatment

of infra-inguinal disease, 10–11 SVC syndrome. See Superior vena cava syndrome Symptomatic carotid disease clinical features, 43–45 definition/epidemiology, 43 differential diagnoses, 47 laboratory and imaging work, 45 treatment and prognosis, 45–47 Syphilis, 87 Syphilitic aortitis, 167 Systemic lupus erythematosus (SLE) granulomatosis with polyangiitis (GPA), 180 Systemic vasculitis, 130 TA. See Takayasu’s arteritis TAAs. See Thoracic aortic aneurysms Takayasu’s arteritis (TA), 5, 16, 87, 137, 173 clinical features, 165 definition/epidemiology, 164–165 differential diagnosis, 167 laboratory and imaging workup, 165–166 treatment and prognosis, 166 TAO. See Thromboangiitis obliterans TEE. See Transesophageal echocardiography Temporal arteritis. See Giant cell arteritis (GCA) Thiazide diuretics, 124 second-line antihypertensives, 119 Thoracic aortic aneurysms (TAAs), 166 clinical features, 88 definition/epidemiology, 87, 89 differential diagnoses, 90 laboratory and imaging workup, 88 prophylactic surgery, 89 treatment and prognosis, 88–89 Thoracic outlet syndrome, 16, 173, 204. See also Venous thoracic outlet syndrome Thromboangiitis obliterans (TAO), 16 aorto-iliac disease, 5 clinical features, 170–171 definition/epidemiology, 169–170 differential diagnosis, 173 laboratory and imaging workup, 171–172 treatment and prognosis, 172–173 Thromboembolism, 32 Thrombolytic therapy, 15, 190 deep venous thrombosis (DVT), 185 Thrombophilia disorders, 173 Thrombophilia testing, 188 TIAs. See Transient ischemic attacks Tissue biopsy, 160 “Todd’s phenomenon,” 59 Toxic shock syndrome (TSS)

Kawasaki disease (KD), 149 Transcranial doppler (TCD) ultrasound intracranial stenosis, 62, 63f Transesophageal echocardiography (TEE), 33, 73, 88 Transient ischemic attacks (TIAs), 61 extracranial vertebral artery stenosis, 50 internal carotid artery (ICA) stenosis, 43 Transient monocular blindness, 47 transient right, 31 Transthoracic echocardiogram, 71, 72f, 73f, 81 Transthoracic echocardiography (TTE), 88 Trauma, 12 Tricuspid regurgitation, 107 Trimethoprim, 179 TTE. See Transthoracic echocardiography Tumors, 59 Type A aortic dissection, 74f, 75 conditions associated with, 72 Type B aortic dissection. See Acute aortic dissection, type B Ultrasonography fusiform abdominal aortic aneurysm, 94f internal carotid artery (ICA) dissections, 57 Uncomplicated type B aortic dissection, 81 Upper extremity (UE) arterial disease clinical features, 13–14 definition/epidemiology, 13 differential diagnoses, 16–17 laboratory and imaging workup, 14–15 treatment and prognosis, 15–16 Urine sodium, 118 Valve-sparing procedures acute aortic dissection, type A, 73 Varicose veins clinical features, 194 definition/epidemiology, 193–194 differential diagnosis, 195 laboratory and imaging workup, 194–195 primary, 193 secondary, 193 treatment and prognosis, 195 Vascular compression syndromes, 173 Vascular inflammation, vasculitis, 72 Vasculitides Churg–Strauss syndrome, 127–131 giant cell arteritis, 133–138 granulomatosis with polyangiitis (GPA), 175–181

Index Henoch–Schönlein purpura, 139–144 Kawasaki disease (KD), 145–150 mixed cryoglobulinemia (MC), 151–155 polyarteritis nodosa (PAN), 157–161 Takayasu’s arteritis (TA), 163–167 thromboangiitis obliterans (TAO), 169–174 Venous claudication aorto-iliac disease, 5 Venous thoracic outlet syndrome clinical features, 198 definition/epidemiology, 197–198 differential diagnosis, 200 hypertrophied anterior scalene muscle, 198f laboratory and imaging workup, 198–199 treatment and prognosis, 199 Venous thromboembolism (VTE) clinical features, 184

225

definition/epidemiology, 183–184 differential diagnosis, 186 elements, risk factors, 187 identification, 207 laboratory and imaging workup, 184 pulmonary embolism (PE), 187 treatment and prognosis, 185–186 Ventilation–perfusion imaging pulmonary embolism (PE), 190 Vertebrobasilar system (VBS), 49 Vertigo, 49 extracranial vertebral artery stenosis, 53 Vidarabin, 160 Visceral arterial aneurysms clinical features, 113–114 definition/ epidemiology, 113 differential diagnoses, 115 laboratory and imaging workup, 114 left upper quadrant abdominal pain, 113

treatment and prognosis, 114–115 Vision loss, 44 VTE. See Venous thromboembolism Warfarin, 57, 64, 185, 190, 197 Warfarin–aspirin symptomatic intracranial disease (WASID) trial, 64 Wegener’s granulomatosis (WG), 128, 177. See also Granulomatosis with polyangiitis (GPA) Weight loss, 157 Wells criteria diagnosis, deep venous thrombosis, 184 probability, 184 Wood’s lamp illumination, 101 Wuchereria bancrofti, 215