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WARTS
Skin warts are benign tumours caused by infection of keratinocytes with HPV, visible as well‐defined hyperkeratotic protrusions
AETIOLOGY Human Papilloma Virus Over 200 distinct subtypes of HPV Association exists between HPV type and clinical disease caused
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PREDISPOSITION Predisposing conditions for extensive or recalcitrant involvement include: atopic dermatitis and conditions associated with decreased cell-mediated immunity (e.g. acquired
immune deficiency syndrome [AIDS], organ transplantation)
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Non genital warts
TRANSMISSION
transmitted through direct skin to skin contact and autoinoculation (pseudo Koebner’s phenomenon) If scratched or picked, viral particles may spread to another area of skin. The incubation period can be as long as twelve months (2-6 months usually) Frequent in children and young adults
Anogenital warts Sexual transmission – both heterosexual and homosexual More common in adolescents and adults Vertical transmission – during vaginal delivery, mother with anogenital warts can transmit infection to new born Manifests as laryngeal papilloma in infants
CLINICAL CLASSIFIATION Verruca vulgaris Palmoplantar warts Verruca plana Filiform warts Epidermodysplasia verruciformis Anogenital warts
VERRUCA VULGARIS (COMMON WARTS) Usually asymptomatic Morphology Single/multiple, circumscribed, firm , dome shaped papules with verrucous (hyperkeratotic) dry surface, stippled with black dots (d/t thrombosed capillaries). May be arranged linearly due to auto inoculation 60% resolve spontaneously Sites of Prediliction Anywhere in the body Frequently in trauma prone sites i.e dorsae of hands, fingers including peri/subungal areas, knees and feet
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PALMOPLANTAR WARTS I. Superficial palmoplantar warts C/f – Usually painless Hyperkeratotic papules and plaques consisting of multiple, small warts which are tightly packed Several contiguous warts fuse and appear as one, plaque known as mosaic wart Sites of predilection – Soles and less often palms
Multiple hyperkeratotic papules are present on the sole of the foot. Note the presence of thrombosed capillaries and the interruption of dermatoglyphics (skin lines).
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II. Deep palmoplantar warts (Myrmecia) C/f – Painful Hyperkeratotic, deep seated papules (barely visible above the skin surface), surrounded by a horny collar and wart actually becomes apparent as a soft, granular brown papule only when collar is pared Further paring may reveal punctate black dots (thrombosed capillaries) Almost always discrete 14
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VERRUCA PLANA (PLANE WARTS) Multiple Slightly elevated, flat, smooth papules Lesions may be arranged linearly (pseudo Koebners phenomenon), secondary to autoinoculation Site of predilection – face and dorsae of hands
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FILIFORM WARTS Asymptomatic Thin elongated, firm projections arising from a horny base Site of predilection – frequently on face (inoculation by shaving), neck and scalp
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EPIDERMODYSPLASIA VERRUCIFORMIS Rare autosomal recessive disorder Characterized by defective cell mediated immunity to certain types of HPV (3, 5, 8, 9) leading to wide spread lesions 2 types
A. Plane wart like lesions – many become confluent on face and acral parts B. Pityriasis versicolor like lesions – irregular scaly macules on trunk Development of Bowens disease and invasive squamous cell carcinoma is frequent on photoexposed parts
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ANOGENITAL WART Anogenital Warts: 6, 11, 16, 18, 31, 33 Sexually Transmitted Disease Transmitted both hetero and hemosexually and vertically during vaginal delivery Frequently on glans, perianal region, vulva and cervix Laryngeal papillomas in children Papillomatous cauliflower-like lesions with a moist macerated vascular surface
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CLINICAL FEATURES Morphological types
Condyloma acuminata – most common type
Soft, fleshy, sessile/pedunculated, pinkish or skin coloured papules, initially small Enlarge to form cauliflower tumours
Other types include – Papular anogenital warts, Bowenoid papulosis, giant anogenital warts (Buschke – Lowenstein tumor) Site of predilection • Males – Frenulum, coronal sulcus and inner lining of prepuce (all moist areas) • Females – Cervix, vulva, vagina
Condylomata acuminata: Cauliflower like, Bulky & Dry (contrast to condylomata lata which are smooth, flat & moist) Differentials of condylomata acuminata (anogenital warts) also include molluscum contagiosum, pearly penile papules & neoplastic lesions.
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DIAGNOSIS Usually clinical (rough, dry stippled surface) Presence of pseudo Koebner’s phenomenon especially in verruca plana Typical histology (hyperkeratosis, acanthosis, koilocytes, papillomatosis, dilated vessels) Presence of HPV DNA and specific HPV types can be determined on smears and lesional biopsy specimens by in situ hybridization Serologic tests for syphilis should be obtained on all patients with anogenital warts to rule out co-infection
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DIFFERENTIAL DIAGNOSIS
Smooth, dome shaped pearly white papules with central umbilication
Located at pressure points, skin markings uninterrupted, central keratinous core
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TREATMENT The aim of treatment is removal of the wart and amelioration of symptoms, if present Treatment of anogenital warts should be guided by wart size, number, and anatomic site; patient preference; cost of treatment; convenience; adverse effects; and provider experience Treatment regimens are classified as either patient-applied or provider-administered modalities
MANAGEMENT OF WARTS Topical agents: Salicylic acid (10-25%): Keratolytic, so reduces thickness of wart and induces an inflammatory response, stimulate local immunity. A 2012 meta-analysis of randomized trials found salicylic acid superior to placebo for clearance of warts (0 to 80%). Wart paint: Contains salicylic acid and lactic acid in a quick drying collodion or acrylate base. Treatment of choice for palomoplantar and periungual warts, especially in children. Should not be used on facial lesions and anogenital warts. May need to be used daily for 3 months. Retinoic acid (0.05-0.1%): Topically is used in plane warts because of keratolytic action.
Cryotherapy by thermal-induced cytolysis Cryogens: Liquid nitrogen, carbon dioxide and nitrous oxide. Pain
and post- treatment depigmentation can occur
Cure rates from cryotherapy in randomized trials range from 14 to more than 90 percent If no improvement after six treatment cycle, transition to an
alternative therapy
Electric cautery and radiofrequency ablation (RFA): Treatment of choice in filiform warts, verruca vulgaris if small and medium sized warts.
LESS COMMON TREATMENT MODALITIES Topical immunotherapy with contact allergens — such as squaric acid dibutylester (SADBE), dinitrochlorobenzene (DNCB), and diphenylcyclopropenone (DPCP)
Intralesional bleomycin Topical or intralesional fluorouracil (FU)
Cantharidin Duct tape Pulsed dye laser Oral cimetidine Topical 1 to 3% cidofovir Formaldehyde 0.5 to 3% solution
Glutaraldehyde 10 to 20% solution or gel Intralesional cidofovir Intradermal Bacillus Calmette-Guérin vaccine Oral acitretin Oral zinc sulfate Carbon dioxide laser therapy Thermotherapy Photodynamic therapy Topical viable Bacillus Calmette-Guérin 36
ANOGENITAL WARTS TREATMENT Patient Applied Imiquimod 5% or 3.75% topically active immune enhancer that stimulates production of interferon and other cytokines Imiquimod 5% cream should be applied once at bedtime, three times a week for up to 16 weeks 3.75% cream should be once at bedtime, every night. Treatment area should be washed with soap and water 6–10 hours after the application.
Podofilox (podophyllotoxin) 0.5% solution or gel is a patient-applied antimitotic drug that causes wart necrosis Podofilox solution (using a cotton swab) or podofilox gel (using a finger) should be applied to anogenital warts twice a day for days, followed by 4 days of no therapy. This cycle can be repeated, as necessary, for up to four cycles. The total wart area should not exceed 10 cm2, and the total volume of podofilox should be limited to 0.5 mL per day.
Sinecatechins 15% is a patient-applied, green-tea extract with an active product (catechins) that induces apoptosis, mediated by cell cycle deregulation Sinecatechins 15% ointment should be applied three times daily (0.5 cm strand of ointment to each wart) using a finger to ensure coverage with a thin layer of ointment until complete clearance of warts is achieved. This product should not be continued for longer than 16 weeks. The medication should not be washed off after use. 37
ANOGENITAL WARTS TREATMENT Provider Administered Cryotherapy with liquid nitrogen or cryoprobe Surgical removal either by tangential scissor, tangential shave excision, curettage, laser or electrosurgery Trichloroacetic acid (TCA) and Bichloroacetic acid (BCA) 80-90% solution destroy warts by chemical coagulation of proteins. A small amount should be applied only to the warts and allowed to dry (i.e. develop white frost on tissue) before the patient sits or stands. If pain is intense or an excess amount of acid is applied, the area can be covered with sodium bicarbonate (i.e. baking soda), washed with liquid soap preparations, or be powdered with talc to neutralize the acid or remove unreacted acid.
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SPECIAL CONSIDERATIONS Salicylic acid and cryotherapy is usually avoided in facial flat warts because of risk of excessive skin irritation and hypopigmentation respectively Podofilox (podophyllotoxin), podophyllin, and sinecatechins should not be used during pregnancy Imiquimod appears to pose low risk but should be avoided until more data are available. Rarely, HPV types 6 and 11 can cause respiratory papillomatosis in infants and children, although the route of transmission (i.e., transplacental, perinatal, or postnatal) is not completely understood Whether cesarean section prevents respiratory papillomatosis in infants and children is unclear
PROGNOSIS In healthy individuals, most warts resolve spontaneously (30% in 6 months and 60% in 1 year). Recurrence is common. Spontaneous remission of warts occurs in two-thirds of children within two years. Spontaneous resolution in adults tends to be slower and may take up to several years or longer. During the resolution process, punctate areas of blackish discoloration, secondary to capillary thrombosis appears on the surface. Warts resolve without a sequelae. Mosaic warts, however have intractable course In immunocompromised individuals, warts are persistent, extensive and may have an oncogenic potential 40
COMPLICATIONS Some HPV (16,18) – frequently associated with anogenital squamous atypia, less frequently with invasive carcinoma. Oncogenic potential enhanced in presence of HIV induced immune suppression Obstruction of labour by large vulval warts Vertical transmission – laryngeal papillomas Epidermodysplasia verruciformis – Bowen’s disease and invasive carcinoma in photo exposed parts
REFERENCES • Andrew’s Diseases of the Skin, Clinical Dermatology, 12th edition • Illustrated Synopsis of Dermatology and Sexually Transmitted diseases, Neena • • •
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Khanna, 5th Edition Rook’s Textbook of Dermatology, 8th Edition Clinical Dermatology, John Hunter, 3rd Edition Human papillomavirus infections: Epidemiology and disease associations, P. Joel et al. Cutaneous warts (common, plantar, and flat warts), Goldstein B et al Condylomata acuminata (anogenital warts): Management of external condylomata acuminata in men, Rosen Ted et al.
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