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Warts are common, benign, epidermal lesions caused by 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 destructive methods (eg, excision, cautery, cryotherapy, liquid nitrogen) and topical or injected agents.
Warts are almost universal in the population; they affect patients of all ages but are most common among children and are uncommon among the elderly.
Warts are caused by human papillomavirus (HPV) infection; there are over 100 HPV subtypes. 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 those with HIV infection or a kidney transplant) are at particular risk of developing generalized lesions that are difficult to treat. Humoral immunity provides resistance to HPV infection; cellular immunity helps established infection to regress.
Warts are named by their clinical appearance and location; different forms are linked to different HPV types (for unusual manifestations, see Table: Wart Variants). Most types are usually asymptomatic. However, some warts are tender, so those on weight-bearing surfaces (eg, bottom of the feet) may cause mild pain.
Common warts (verrucae vulgaris) are caused by HPV types 1, 2, 4, 27, and 29. They are usually asymptomatic but sometimes cause mild pain when they are located on a weight-bearing surface (eg, bottom of the feet). Common warts 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) appear most frequently on the head and neck, especially the scalp and beard area.
Flat warts, caused by HPV types 3, 10, 28, and 49, are smooth, flat-topped, yellow-brown, pink, or flesh-colored papules, most often located on the face and along scratch marks; they are more common among children and young adults and develop by autoinoculation. They generally cause no symptoms but are usually difficult to treat.
These warts, caused by HPV type 1, occur on the palms and soles; they are 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.
These warts appear as thickened, fissured, cauliflower-like skin around the nail plate. They are usually asymptomatic, but the fissures cause pain as the warts enlarge. Patients frequently lose the cuticle and are susceptible to paronychia. Periungual warts are more common among patients who bite their nails or who have occupations where their hands are chronically wet such as dishwashers and bartenders.
Genital warts manifest as discrete flat to broad-based smooth to velvety papules to rough and pedunculated excrescences on the perineal, perirectal, labial, and penile areas. Infection with high-risk HPV types (most notably types 16 and 18) is the main cause of cervical cancer. These warts are usually asymptomatic. Perirectal warts often itch.
Diagnosis of warts 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 of warts includes the following:
Corns (clavi): May obscure skin lines but do not have thrombosed capillaries when shaved
Lichen planus: May mimic flat warts but may be accompanied by lacy oral lesions and Wickham striae and may be symmetrically distributed
Seborrheic keratosis: May appear more stuck on, be pigmented, and include keratin-filled horn cysts
Skin tags (achrocordon): May be pedunculated and smoother and more flesh-colored than warts
Squamous cell carcinoma: May be ulcerated, persistent, and grow irregularly
DNA typing of the virus is available in some medical centers but is generally not needed.
Many warts regress spontaneously (particularly common warts); 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 subject to local trauma (eg, athletes, mechanics, butchers) may have recalcitrant and recurrent HPV infection. Genital HPV infection has malignant potential, but malignant transformation is rare in HPV-induced skin warts, except among immunosuppressed patients.
There are no firm indications for treatment of warts. Treatment should be considered for warts that are cosmetically unacceptable, in locations that interfere with function, or painful. Patients should be motivated to adhere to treatment, which may require a prolonged course and can be unsuccessful. Treatments are less successful in patients with impaired immune systems.
Mechanisms of many irritants include eliciting an immune response to HPV. Such irritants include salicylic acid (SCA), trichloroacetic acid, 5-fluorouracil, podophyllum resin, tretinoin, and cantharidin.
Topical imiquimod 5% cream induces skin cells to locally produce antiviral cytokines. Topical cidofovir, HPV vaccines, and contact immunotherapy (eg, squaric acid dibutyl ester and Candida allergen) have been used to treat warts. Warts can first be soaked in hot water at 113° F for 30 min ≥ 3 times/wk. After soaking, the skin is more permeable to topical drugs.
Oral treatments include cimetidine (which has questionable efficacy), isotretinoin, and zinc. IV cidofovir can also be used. In most instances, modalities should be combined to increase the likelihood of success. Direct antiviral effects can be achieved with intralesional injection of bleomycin and interferon alfa-2b, but these treatments are reserved for the most recalcitrant warts.
These drugs can be used in combination with a destructive method (eg, cryosurgery, electrocautery, curettage, excision, laser) because even though a wart may be physically removed by a destructive method, virus may remain in the tissues and cause recurrence.
In immunocompetent patients, common warts usually spontaneously regress within 2 to 4 yr, but some linger for many years. Numerous treatments are available. Destructive methods include electrocautery, cryosurgery with liquid nitrogen, and laser surgery. Salicylic acid (SCA) preparations are also commonly used.
Which method is used depends on the location and severity of involvement.
The most common topical agent to be used is SCA. SCA is available as a liquid or plaster or impregnated within tape. For example, 17% liquid SCA can be used on the fingers, and 40% plaster SCA can be used on the soles. Patients apply SCA to their warts at night and leave it on for 8 to 48 h depending on the site.
Cantharidin can be used alone or in combination (1%) with SCA (30%) and podophyllum (5%) 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, laser surgery, or both is effective and indicated for isolated lesions but may cause scarring. Recurrent or new warts occur in about 35% of patients within 1 yr; therefore, methods that scar should be avoided as much as possible so that multiple scars do not accumulate. When possible, scarring treatments are reserved for cosmetically unimportant areas and recalcitrant warts.
Treatment of filiform warts 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, because hypopigmentation or hyperpigmentation frequently occurs after treatment with liquid nitrogen. Patients with darkly pigmented skin can develop permanent depigmentation.
Treatment of flat warts is difficult, and flat warts are often longer-lasting than common warts, recalcitrant to treatments, and, in cosmetically important areas, make the most effective (destructive) methods less desirable. Usual first-line treatment is daily tretinoin (retinoic acid 0.05% cream). If peeling is not sufficient for wart removal, another irritant (eg, 5% benzoyl peroxide) or 5% SCA cream can be applied sequentially with tretinoin. Imiquimod 5% cream can be used alone or in combination with topical drugs or destructive measures. Topical 5-fluorouracil (1% or 5% cream) can also be used.
Treatment of plantar warts is vigorous maceration with 40% SCA plaster kept in place for several days. The wart is then debrided while damp and soft, followed by destruction 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.
Combination therapy with liquid nitrogen and imiquimod 5% cream, tretinoin, or SCA is effective and usually safer than liquid nitrogen or cautery.
Several methods whose long-term value and risks are not fully known are available for the treatment of recalcitrant warts. Intralesional injection of small amounts of a 0.1% solution of bleomycin in saline often cures stubborn plantar and periungual warts. However, Raynaud syndrome or vascular damage may develop in injected digits, especially when the drug is injected at the base of the digit, so caution is warranted. Interferon, especially interferon alfa, given intralesionally (3 times/wk for 3 to 5 wk) or IM, has also cleared recalcitrant skin and genital warts. Extensive warts sometimes abate or clear with oral isotretinoin or acitretin. HPV vaccine has been reported as useful for recalcitrant warts in children, but efficacy of this intervention is not proved (1).
1. Abeck D, Fölster-Holst R: Quadrivalent human papillomavirus vaccination: A promising treatment for recalcitrant cutaneous warts in children. Acta Derm Venereol 95(8):1017–1019, 2015. doi: 10.2340/00015555-2111.
Cutaneous warts are caused by human papillomaviruses, are very common, and have multiple forms.
Spread is usually by autoinoculation and is facilitated by trauma and maceration.
Most warts are asymptomatic but can be mildly painful with pressure.
Most warts resolve spontaneously, particularly common warts.
Treatments, when indicated, commonly include topical irritants (eg, salicylic acid, cantharidin, podophyllum resin) and/or destructive methods (eg, cryosurgery, electrocautery, curettage, excision, laser).
Drug NameSelect Trade
bleomycinNo US brand name
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