WARTS

WARTS - Herbert P.Goodheart, MD
BASICS
DESCRIPTION
Warts (verrucae) are benign growths that are confined to the epidermis. All warts are caused by the human papillomavirus (HPV).
• Warts often vary widely in shape, size, and appearance, and the different names for them generally reflect their clinical appearance, location, or both.
• For example, filiform warts are threadlike, planar warts are flat, and plantar warts are located on the soles of the feet.
• Genital warts, or condyloma acuminatum, may be large and cauliflowerlike, or they may consist of small papules.
• 5 types of warts are caused by specific genotypes of HPV
- Common wart (verruca vulgaris)
- Plantar wart (verruca plantaris)
- Flat wart (verruca plana)
- Venereal wart (condyloma acuminatum); see separate topic in this volume
• Epidermodysplasia verruciformis is a very rare, lifelong, hereditary disorder characterized by chronic infection with HPV.
• System(s) Affected: Skin/Exocrine
EPIDEMIOLOGY
• Predominant age: Young adults and children
• Predominant sex: Female = Male
Incidence
An estimated 20% of school-age children will at some time have at least one wart.
Prevalence
• ~7-10% of the US population
• Common warts appear ~2 times as frequently in whites as in African Americans or Asians.
RISK FACTORS
• AIDS and other immunosuppressive diseases (e.g., lymphomas)
• Immunosuppressive drugs that decrease cell-mediated immunity (e.g., prednisone, cyclosporine, and chemotherapeutic agents)
• Pregnancy
• Handling raw meat, fish, or other types of animal matter in one's occupation, e.g., butchers
ETIOLOGY
• Various strains of a DNA HPV virus: To date, >150 different subtypes have been identified.
• Common warts: HPV types 2 and 4 (most common), followed by types 1, 3, 27, 29, and 57
• Palmoplantar warts: HPV type 1 (most common), followed by types 2, 3, 4, 27, 29, and 57
• Flat warts: HPV types 3, 10, and 28
• Butcher warts: HPV type 7
• The virus is passed primarily through skin-to-skin contact or from the recently shed virus kept intact in a moist, warm environment.
• HPV infects epidermal keratinocytes, which stimulates cell proliferation.

DIAGNOSIS
• Most often made on clinical appearance
• Skin biopsy, if necessary
SIGNS AND SYMPTOMS
Common wart: Rough-surfaced, hyperkeratotic, papillomatous, raised, skin-colored to tan papules 5-10 mm in diameter; may coalesce into a mosaic 1-3 cm in diameter
• Most frequently seen on hands, knees, and elbows
• Usually asymptomatic, but may cause cosmetic disfigurement or tenderness
Variant
• Filiform warts: These are long, slender, delicate, fingerlike growths, usually seen on the face around the lips, eyelids, or nares.
• Plantar warts appear on the plantar surface of the feet in children and young adults.
- Can be tender and painful, and extensive involvement on the sole of the foot may impair ambulation, particularly when present on a weight-bearing surface
- Most often seen on the metatarsal area, heels, and toes in an asymmetric distribution
- Frequently attain 2-3 cm in diameter
- Pathognomonic "black dots" (thrombosed dermal capillaries). Punctate bleeding becomes more evident after paring with a #15 blade.
- Both common and plantar warts generally demonstrate the following clinical findings:
- A loss of normal skin markings (dermatoglyphics) such as finger, foot, and hand prints
- Lesions may be solitary or multiple, or they may appear in clusters (mosaic warts)
• Flat wart: Slightly elevated, flat-topped, skin-colored or tan papules, small (1-3 mm) in diameter
- Commonly found on the face, arms, dorsa of hands, shins (women)
- Sometimes exhibit a linear configuration caused by autoinoculation
- In men, shaving spreads flat warts
- In women, they often occur on the shins, where leg shaving spreads lesions.
• Epidermodysplasia verruciformis: Widespread flat, reddish-brown pigmented papules and plaques that present in childhood with lifelong persistence on the trunk, the hands, the upper and lower extremities, and the face, are characteristic.
- Lesions may transform into carcinomas, usually after age 30 years. Skin cancers initially appear on sun-exposed areas.
Physical Exam
Warts may develop anywhere on the body, but they are most often found at sites subject to frequent trauma, such as the hands and feet.
• Distribution is generally asymmetric, and lesions are often clustered.
TESTS
Lab
• HPV cannot be cultured.
• Definitive diagnosis can be achieved by
- Electron microscopy
- Viral DNA identification using Southern blot hybridization used to identify the specific HPV type present in tissue
- Polymerase chain reaction may be used to amplify viral DNA for testing.
Pathological Findings
• Histopathologic features of common warts include digitated epidermal hyperplasia, acanthosis, papillomatosis, compact orthokeratosis, hypergranulosis, dilated tortuous capillaries within the dermal papillae, and vertical tiers of parakeratotic cells with entrapped red blood cells above the tips of the digitations.
• In the granular layer, HPV-infected cells may have coarse keratohyaline granules and vacuoles surrounding wrinkled-appearing nuclei. These koilocytic (vacuolated) cells are pathognomonic for warts.
DIFFERENTIAL DIAGNOSIS
Pediatric
Molluscum contagiosum
Adults/Elderly
• Seborrheic keratosis
• Acrochordon (skin tag)
• Solar keratosis and cutaneous horn
• Squamous cell carcinoma
• Keratoacanthoma
• Subungual squamous cell carcinoma can easily be misdiagnosed as a subungual wart or onychomycosis.
• Plantar warts
• Corns (clavi) are sometimes difficult to distinguish from warts. Like calluses, corns are thickened areas of the skin and most commonly develop at sites subjected to repeated friction and pressure, such as the tops and the tips of toes and along the sides of the feet.
- They are usually hard and circular-shaped, with a polished or central translucent core, like the kernel of corn from which they take their name.
- Corns do not have "black dots,"and skin markings are retained except for the area of the central core.
ALERT
• Melanoma can mimic a plantar wart.
• Verrucous carcinoma, a slow growing, locally invasive, well-differentiated squamous cell carcinoma, may also be easily mistaken for a common or plantar wart.
TREATMENT
GENERAL MEASURES
• The clinical management of verrucae vulgaris is often challenging, and there is no ideal treatment.
• In children, most warts tend to regress spontaneously, which is probably related to a host immune response.
• In many adults and immunocompromised patients, however, warts often prove difficult to eradicate.
• Painful, aggressive therapy should be avoided unless there is a pressing need to eliminate the wart(s).
• For surgical procedures, especially in anxious children, pretreatment with anesthetic cream such as EMLA (emulsion of lidocaine and prilocaine):
- Benign neglect: Providing no treatment at all is certainly safe and cost effective as most may regress spontaneously within 2 years.
- If warts are extensive, spreading, or symptomatic, the method of treatment will depend upon the age of the patient, the patient's pain threshold, the type of wart, and its location.
- A cure is achieved when the skin lines are restored to a normal pattern and there is no recurrence.
Complementary and Alternative Medicine
• Occlusion: Easiest and least expensive. Cover wart with waterproof tape (e.g., duct tape) and leave on for 6 days, then soak, pare with emery board, leave uncovered overnight, then reapply tape cyclically for 8 cycles
• Hyperthermia: Safe and inexpensive approach; immerse affected area into 45C water bath for 30 minutes 3 times per week
ALERT
Pregnancy Considerations
• The use of many of the following topical chemical approaches may be contraindicated during pregnancy or in women who are likely to become pregnant during the treatment period.
• Refer to the manufacturer's profile of each drug.
MEDICATION (DRUGS)
First Line
The abundance of treatment modalities described below is a reflection of the fact that none of them is uniformly effective.
• Keratolytic (peeling) agents, primarily containing salicylic or salicylic acid plus lactic acid, are available in numerous OTC preparations that are self-administered. Best treatment for small children in whom warts are usually self-limiting. For best results and increased penetration with any of following keratolytic agents, the affected area should be hydrated 1st by soaking it in warm water for 5 minutes before application.
• Duofilm
• Occlusal-HP
• Trans-Ver-Sal
- Office-based and prescription treatment
• Combination cantharidin; 30% salicylic acid, 2% podophyllin, and 19% cantharidin in flexible collodion: Applied in a thin coat, occluded 4-6 hours, then washed off
• Aldara (imiquimod) 5% cream, a local inducer of interferon, is applied at home by the patient. It is approved for external genital and perianal warts and is used "off-label" and applied under duct tape occlusion applied at bedtime and washed off after 6-10 hours.
• Aldara is applied to flat warts without occlusion.
Second Line
Immunotherapy: Induction of delayed-type hypersensitivity with
• Diphencyprone
• Dinitrochlorobenzene (DNCB)
• Squaric acid dibutylester (SADBE)
• Possible mutagenicity and side effects with these agents
• Bleomycin: Intradermal injection is expensive and causes severe pain.
- Alpha-2 interferon
- Intralesional mumps or candida antigen
- Oral high dose cimetidine: Possibly works better in children
- Topical retinoids for facial flat warts
- Acitretin (an oral retinoid)
- Others: Dichloroacetic acid, trichloroacetic acid, podophyllin, formic acid, 5-fluorouracil, silver nitrate, formaldehyde, levamisole, topical or IV cidofovir for recalcitrant warts in the setting of HIV, glutaraldehyde, have all been used with varying results
SURGERY
• Duct tape: Cover wart with waterproof tape (e.g., duct tape) and leave on for 6 days, then soak, pare with emery board, leave uncovered overnight, then reapply tape cyclically for 8 cycles; 85% resolved compared to 60% efficacy with cryotherapy
• Cryotherapy with liquid nitrogen (LN2) may be applied with a cotton swab or with a cryotherapy gun (Cryogun).
- Best for warts on hands.
- Fast; can treat many lesions per visit
- Painful; not tolerated well by young children
- Freezing periungual warts may result in nail deformation.
- In darkly pigmented skin, treatment can result in hypo- or hyperpigmentation.
• Light electrocautery with or without curettage:
- Best for warts on the knees, elbows, and dorsa of hands
- Also good for filiform warts
- Tolerable in most adults
- Requires local anesthesia
- May cause scarring
• Photodynamic therapy
• CO2 or pulse-dye laser ablation: Expensive and requires local anesthesia
• Filifarm warts
- An almost painless method is to dip a hemostat into LN2 for 10 seconds and then gently grasp the wart for ~5-10 seconds. The frozen wart is generally shed in 7-10 days.
FOLLOW-UP
COMPLICATIONS
• Autoinoculation ("pseudo Koebner") reaction
• Scar formation
• Chronic pain after plantar wart removal or scar formation
• Nail deformity after injury to nail matrix
PATIENT MONITORING
One third of the warts of epidermodysplasia may become malignant.
REFERENCES
1. Micali G et al. Use of squaric acid dibutylester (SADBE) for cutaneous warts in children. Pediatr Dermatol. 2000;17:315-318.
2. Rogers J, et al. Cimetidine therapy for recalcitrant warts in adults: Is it any better than placebo? J Am Acad Dermatol. 1999;41:123-127.
3. Robson KJ, et al. Pulsed-dye laser versus conventional therapy in the treatment of warts: A prospective randomized trial. J Am Acad Dermatol. 2000;43(2 pt 1):275-280.
4. Silverberg NB, Lim JK, Paller AS, Mancini AJ. Squaric acid immunotherapy for warts in children. J Am Acad Dermatol. 2000;42(5 pt 1):803-808.
5. Stender IM et. al. Photodynamic therapy with 5-aminolevulinic acid or placebo for recalcitrant foot and hand warts: Randomized double-blind trial. Lancet. 2000;355:963-966.