WARTS (VERRUCAE VULGARIS)

WARTS (VERRUCAE VULGARIS)

Warts (verrucae vulgaris) are common, benign epidermal lesions associated with human papillomavirus infection. They can appear anywhere on the body in a variety of morphologies. Diagnosis is by examination. Warts are usually self-limited but may be treated by excision, cautery, cryotherapy, liquid nitrogen, and topical or injected agents.

Warts are almost universal in the population and affect all ages but are most frequent in children and uncommon in the elderly. Warts are caused by human papillomavirus (HPV) infection; at least 70 HPV types are linked to skin lesions. Trauma and maceration facilitate initial epidermal inoculation. Spread may then occur by autoinoculation. Local and systemic immune factors appear to influence spread; immunosuppressed patients (especially HIV and renal transplant patients) are at particular risk for developing generalized lesions that are difficult to treat. Humoral immunity provides resistance to HPV infection, although cellular immunity helps established infection to regress.

Symptoms and Signs

Warts are named by their clinical appearance and location; different forms are linked to different HPV types. Unusual manifestations are listed in Table 1: Viral Skin Diseases: Wart Variants and Clinical Correlations.

Table 1
Wart Variants and Clinical Correlations Clinical Form Human Papillomavirus Clinical Correlations Bowenoid papulosis 16, 18, 33, 39 Flat brown verrucous papules on the vulva and penis (benign); affected women and women partners should be followed closely for cervical cancer Buschke Lowenstein tumor 6, 11 Large cauliflower-like tumors Butcher's (meat handler's) 7 Common warts, usually benign Cutaneous squamous cell carcinoma 38, 41, 48 Early lesions can mimic warts Epidermodysplasia verruciformis 1–5, 7–9, 10, 12, 14, 15, 17–20, 23–25, 36, 47, 50 May develop cutaneous malignancy such as squamous cell carcinoma Keratoacanthoma 77 Thought to be a well differentiated squamous cell carcinoma Oral focal epithelial hyperplasia (Heck's disease) 13, 32 Benign Warts in renal transplant patients 75–77 Often multiple and difficult to treat

Common warts (verrucae vulgaris) are caused by HPV 1, 2, 4, 27, and 29. Generally, they are asymptomatic but sometimes cause mild pain, especially when they are located on a weight-bearing surface such as the bottom of the feet. They are sharply demarcated, rough, round or irregular, firm, and light gray, yellow, brown, or gray-black nodules 2 to 10 mm in diameter. They appear most often on sites subject to trauma (eg, fingers, elbows, knees, face) but may spread elsewhere. Variants of unusual shape (eg, pedunculated or resembling a cauliflower) are most frequent on the head and neck, especially the scalp and beard.

Filiform warts are long, narrow, frondlike growths usually on the eyelids, face, neck, or lips. They too are usually asymptomatic. This morphologically distinct variant of the common wart is benign and easy to treat.

Flat warts, caused by HPV 3, 10, 28, and 49, are smooth, flat-topped, yellow-brown papules most often on the face and along scratch marks; they are more common in children and young adults and develop by autoinoculation. They generally cause no symptoms but can be difficult to treat.

Palmar and plantar warts, caused by HPV 1, are warts on the palms and soles flattened by pressure and surrounded by cornified epithelium. They are often tender and can make walking and standing uncomfortable. They can be distinguished from corns and calluses by their tendency to pinpoint bleeding when the surface is pared away. Classically, warts hurt with “side to side” pressure, and calluses hurt with direct pressure; in reality, this is not a reliable sign.

Warts (Palmar and Plantar)

Mosaic warts are plaques formed by the coalescence of myriad smaller, closely set plantar warts. As with other plantar warts, they are often tender.

Periungual warts appear as thickened, fissured cauliflower-like skin around the nail plate. Patients frequently lose the cuticle and are susceptible to paronychia. These warts are more common in patients who bite their nails.

Genital warts manifest as discrete flat to broad-based smooth to velvety papules on the perineal, perirectal, labial, and penile areas. Infection with high-risk HPV types (most notably types 16 and 18) are the main causes of cervical cancer. They are generally asymptomatic.

Diagnosis

Diagnosis is based on clinical appearance; biopsy is rarely needed. A cardinal sign of warts is the absence of skin lines crossing their surface and the presence of pinpoint black dots (thrombosed capillaries) or bleeding when warts are shaved. Differential diagnosis includes corns (clavi), lichen planus, seborrheic keratosis, skin tags, and squamous cell carcinomas. DNA typing is available in some medical centers but is generally not needed.

Prognosis and Treatment

Many warts regress spontaneously; others persist for years and recur at the same or different sites, even with treatment. Factors influencing recurrence appear to be related to the patient's overall immune status as well as local factors. Patients who subject themselves to local trauma (eg, athletes, mechanics, butchers) can have recalcitrant and recurrent HPV. Genital HPV infection has malignant potential, but (except in immunosuppressed patients) malignant transformation has not been generally observed in HPV-induced skin warts.

Treatment is aimed at eliciting an immune response to HPV. In most instances, this is achieved by applying an irritant (eg, salicylic acid Some Trade Names
MEDIPLAST
PROPA PH
STRI-DEX
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[SCA], trichloroacetic acid, 5- fluorouracil Some Trade Names
ADRUCIL
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, podophyllum resin, tretinoin Some Trade Names
RETIN-A
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, cantharidin).

These compounds can be used in combination or with a destructive method (eg, cryosurgery, electrocautery, curettage, excision, laser). Direct antiviral effects can be achieved with bleomycin Some Trade Names
BLENOXANE
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and interferon-α2b, but these treatments are reserved for the most recalcitrant warts. Topical imiquimod Some Trade Names
ALDARA
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5% cream induces skin cells to locally produce antiviral cytokines. Topical cidofovir Some Trade Names
VISTIDE
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, HPV vaccines, and contact immunotherapy (eg, squaric acid dibutyl ester and Candida allergen) have been used to treat warts. Oral treatments include cimetidine Some Trade Names
TAGAMET
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, isotretinoin Some Trade Names
ACCUTANE
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, and oral zinc. In most instances, modalities should be combined to increase the likelihood of success.

Common warts: In immunocompetent hosts, common warts usually spontaneously regress within 2 yr, but some linger for many years. Numerous treatments are available. Destructive methods include electrocautery, cryosurgery with liquid nitrogen, and SCA preparations. Application of these methods varies depending upon the location and severity of involvement. For example, 17% liquid SCA can be used on the fingers, and 40% plaster SCA can be used on the soles.

The most common topical agent to be used is SCA. SCA is available in a liquid, plaster, or impregnated within tape. Patients apply SCA to their warts at night and leave on for 8 to 48 h depending on the site.

Cantharidin can be used alone or in combination (1%) with SCA (3%) podophyllum (2%) in a collodion base. Cantharidin alone is removed with soap and water after 6 h; cantharidin with SCA or podophyllum is removed in 2 h. The longer these agents are left in contact with the skin, the more brisk the blistering response.

Cryosurgery is painful but extremely effective. Electrodesiccation with curettage and/or laser surgery is effective and indicated for isolated lesions but may cause scarring. Recurrent or new warts occur in about 35% of patients within 1 yr, so methods that scar should be avoided as much as possible.

Filiform warts: Treatment is removal with scalpel, scissors, curettage, or liquid nitrogen. Liquid nitrogen should be applied so that up to 2 mm of skin surrounding the wart turns white. Damage to the skin occurs when the skin thaws, which usually takes 10 to 20 sec. Blisters can occur 24 to 48 h after treatment with liquid nitrogen. Care must be taken when treating cosmetically sensitive sites, such as the face and neck, since hypopigmentation frequently occurs after treatment with liquid nitrogen. Patients with darkly pigmented skin can develop permanent depigmentation.

Flat warts: Treatment is daily tretinoin Some Trade Names
RETIN-A
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(retinoic acid 0.05% cream). If peeling is not sufficient for wart removal, another irritant (eg, 5% benzoyl peroxide Some Trade Names
BENZAC AC
BENZAGEL
NEUTROGENA ACNE MASK
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) or 5% SCA cream can be applied sequentially with tretinoin Some Trade Names
RETIN-A
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. Imiquimod Some Trade Names
ALDARA
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5% cream can be used alone or in combination with topical drugs or destructive measures. Topical 5- fluorouracil Some Trade Names
ADRUCIL
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(1% or 5% cream) can also be used. Spontaneous resolution may follow unprovoked inflammation of the lesions; however, flat warts are frequently recalcitrant to treatment.

Plantar warts: Treatment is vigorous maceration with 40% SCA plaster kept in place for several days. The wart is debrided while damp and soft, then destroyed by freezing or using caustics (eg, 30 to 70% trichloroacetic acid). Other destructive treatments (eg, CO₂ laser, pulsed-dye laser, various acids) are often effective. Duct tape is effective when applied for 6-day intervals, followed by debridement of macerated tissue.

Periungual: Combination therapy with liquid nitrogen and imiquimod Some Trade Names
ALDARA
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5% cream, tretinoin Some Trade Names
RETIN-A
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, or SCA is effective.

Refractory: Several methods whose long-term value and risks are not fully known are available for recalcitrant warts. Intralesional injection of small amounts of a 0.1% solution of bleomycin Some Trade Names
BLENOXANE
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in saline often cures stubborn plantar and periungual warts. However, injected digits may develop Raynaud's phenomenon or vascular damage (especially when injected at the base of the digit), warranting caution. Interferon, especially interferon-α, administered intralesionally (3 times/wk for 3 to 5 wk) or IM, has also cleared recalcitrant skin and genital warts. Extensive warts sometimes improve or clear with oral isotretinoin Some Trade Names
ACCUTANE
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or acitretin Some Trade Names
SORIATANE
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. Cimetidine Some Trade Names
TAGAMET
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at doses up to 800 mg po tid has been used with success but is more effective when combined with another therapy.

Treatments and drugs

Plantar warts usually go away on their own, but most people would rather treat them than wait for them to disappear. Unless you have an impaired immune system or diabetes or are pregnant, there's no reason you can't treat warts with over-the-counter remedies. But you may wish to consult your doctor for help. He or she may suggest a combination of over-the-counter and office treatments for plantar warts.

No wart treatment works 100 percent of the time. In general, your doctor will recommend the least painful — and least destructive — methods first, especially for children.

Common treatments for simple plantar warts
Your doctor may suggest trying these common treatments one at a time or in combination:

§  Salicylic acid. Wart medications and patches are available at drugstores. To treat plantar warts, you'll need a 40 percent salicylic acid solution or patch (Curad Mediplast, Dr. Scholl's Clear Away Plantar, others), which peels off the infected skin a little bit at a time. Apply the solution once or twice each day, being careful to avoid healthy skin, which can become irritated from the acid. In between applications, pare away the dead skin and wart tissue using a pumice stone or emery board. You may need to repeat this process for up to three or four weeks to completely eliminate warts.

§  Duct tape. In a well-publicized 2002 study, duct tape wiped out more warts than freezing (cryotherapy) did. Study participants who used "duct tape therapy" covered their warts in duct tape for six days, then soaked their warts in water, and gently rubbed warts with an emery board or pumice stone. They repeated this process for up to two months or until their warts went away. Researchers hypothesize that this unconventional therapy may work by irritating warts and the surrounding skin, prompting the body's immune system to attack. Today, duct tape is commonly used to treat warts, especially for children who may find freezing painful or scary. It's often combined with salicylic acid.

§  Freezing (cryotherapy). Freezing is one of the most common treatments for plantar warts and is usually effective, but may require multiple trips to your doctor every two to four weeks. Your doctor can apply liquid nitrogen with a spray canister or cotton-tipped applicator. The chemical causes a blister to form around your wart, and the dead tissue sloughs off within a week or so. Freezing isn't commonly used in young children because it can be painful.

§  Cantharidin. Doctors and healers have used cantharidin — a substance extracted from the blister beetle — to treat warts for centuries. Today, this therapy is sometimes paired with salicylic acid. Your doctor paints this beetle juice onto your wart and covers it with clear tape. The application is painless, but it causes the skin under the wart to blister, lifting the wart off the skin. Your doctor can then clip away the dead part of the wart in about a week. However, some doctors are hesitant to use cantharidin because it's not approved by the Food and Drug Administration for the treatment of warts.

Aggressive treatments for persistent plantar warts
If your warts don't respond to common treatments, your doctor may suggest one or more of these other options:

§  Minor surgery. This involves cutting away the wart or destroying the wart by using an electric needle in a process called electrodesiccation and curettage. This treatment is effective, but may leave a scar if not done carefully. Your doctor will anesthetize your skin before this procedure.

§  Laser surgery. Doctors can use several types of lasers to eliminate stubborn warts. But laser surgery is expensive and painful and may take longer to heal than do other treatments.

§  Immunotherapy. This therapy attempts to harness your body's natural rejection system to remove tough-to-treat warts. This can be accomplished in a couple of ways. Your doctor may inject your warts with interferon, a medication that boosts your immune system's instinct to reject warts. Or your doctor may inject your warts with a foreign substance (antigen) that stimulates your immune system. Doctors often use mump antigens, because many people are immunized against mumps. As a result, the antigen sets off an immune reaction that may fight off warts.

§  Imiquimod (Aldara). This prescription cream is an immunotherapy medication that encourages your body to release immune system proteins (cytokines) to help ward off warts. You can apply this cream directly to your warts. Imiquimod is approved by the Food and Drug Administration for the treatment of genital and perianal warts, but it's also successful in treating common warts and plantar warts.

§  Other medications. In severe cases that haven't cleared with other therapies, your doctor may inject each wart with a medication called bleomycin, which kills the virus. This medication is given systemically in higher doses to treat some kinds of cancer. The injections for wart treatment can be painful and can cause rashes or itching. They're not used if you're pregnant or breast-feeding or if you have circulation problems.