Nongenital Warts Treatment & Management

Multiple modalities are available for the treatment of warts, but none is uniformly effective.^{[8, 9]} Start with the least painful, least expensive, and least time-consuming methods. Reserve the more expensive and invasive procedures for refractory extensive warts. Immunosuppressed individuals often are refractory to wart treatments. Various treatment methods are available.

Benign neglect

Providing no treatment at all is certainly safe and cost effective. Consider this as an option, since 65% of warts may regress spontaneously within 2 years. Without treatment, however, patients risk warts that may enlarge or spread to other areas. Treatment is recommended for patients with extensive, spreading, or symptomatic warts or warts that have been present for more than 2 years.

Topical agents

Salicylic acid is a first-line therapy used to treat warts. It is available without a prescription and can be applied by the patient at home. Cure rates from 70-80% are reported.

British, nonblinded, randomized controlled trial compared treatment of plantar warts with 50% salicylic acid topical (Verrugon) applied daily with cryotherapy with liquid nitrogen (up to 4 treatments 2-3 wk apart). The study found no significant difference between the treatments in clearance of the plantar warts at 12 weeks and again at 6 months.^[10] The lesser cost of the salicylic acid topical treatment made it more cost-effective than the liquid nitrogen treatment.

Several topical agents are available that can be applied by trained personnel in a physician's office. Cantharidin is an extract of the blister beetle that causes epidermal necrosis and blistering. Dibutyl squaric acid, also known as squaric acid dibutyl ester (SADBE), and diphencyclopropenone (DCP) are contact sensitizers. Trichloroacetic acid is a caustic compound that causes tissue necrosis. Podophyllin is a cytotoxic compound used more commonly in the treatment of genital warts. Aminolevulinic acid (ALA) is a photosensitizer that has been successfully used topically in combination with blue light to treat flat warts.^[11]

Several prescription medications have proven beneficial in treating warts. These can be applied at home by the patient. Imiquimod is an immune response modifier approved for the treatment of genital warts. Reports indicate successful treatment of common warts.^[12]

Cidofovir is an antiviral agent used for the treatment of cytomegalovirus infection in HIV patients. Reportedly, in 2 patients with recurrent persistent common warts in whom multiple standard therapies were not responsive, the warts were resolved using topical cidofovir gel applied 1-2 times per day. This remains an investigational drug for warts.^[13]

Podophyllotoxin is a purified ingredient of podophyllin. Since it tends to work better on mucosal surfaces, it is used primarily to treat genital warts. Little information is available regarding treatment of nongenital warts with this medication.

5-Fluorouracil is a topical chemotherapeutic agent primarily used to treat actinic keratoses. It has been reported to be effective in treating warts when used under occlusion daily for up to 1 month. It has been used in children.^[14]

Tretinoin is a topical retinoic acid that primarily is used to treat acne. It has been successful in treating flat warts.

Intralesional injections

When warts are persistent and refractory to topical agents, consider intralesional injections as an alternative.

Intralesional immunotherapy using injections of Candida, mumps, or Trichophyton skin test antigens has been shown to be effective in the treatment of warts, with reports of success in up to 74% of patients.^[15] (A clinical trial recruiting as of May 5, 2009 is Study With Candida Antigen for Treatment of Warts.)

Bleomycin is a chemotherapeutic agent that inhibits DNA synthesis in cells and viruses. Cure rates have ranged from 33-92%.^{[16, 17]}

Interferon-alfa is a naturally occurring cytokine with antiviral, antibacterial, anticancer, and immunomodulatory effects. Cure rates of 36-63% have been reported.

Photodynamic therapy

In one study, photodynamic therapy with topical 5-aminolevulinic acid applied to the warts,

followed by photoactivation with red 633-nm light-emitting diodes at 2- to 3-week

intervals resulted in 68% improvement.^[18] .

Systemic agents

Systemic agents that have been used to treat warts include cimetidine, retinoids, and intravenous cidofovir.

Cimetidine is a type-2 histamine receptor antagonist commonly used to treat peptic ulcer disease. Because of its immunomodulatory effects at higher doses, cimetidine was considered a possible treatment for warts; however, results have varied. Double-blind placebo-controlled studies have shown no benefit.^[19]

Retinoids are synthetic vitamin A analogs that may help with extensive disabling hyperkeratotic warts in immunocompromised patients. They may help alleviate pain and facilitate the use of other treatments. Retinoids also have helped reduce the number of lesions in immunosuppressed renal transplant patients. The limiting side effects include liver function abnormalities, increased serum lipid levels, and teratogenicity. (A clinical trial recruiting as of May 5, 2009 is bLAC - Treatment of Cutaneous Warts in Immune Suppressed, Kidney Transplanted Patients.)

Two reports have described intravenous cidofovir used for the treatment of extensive, disfiguring, and refractory warts. This should be used with caution because of the risk of nephrotoxicity.^{[20, 21]}

Alternative treatments

Several alternative treatments have been reported as successful in treating warts, including adhesiotherapy, hypnosis, hyperthermia, garlic, and vaccines.^{[22, 23]}

Adhesiotherapy is performed by applying duct tape to the wart daily. This method is painless and inexpensive and has reports of good success.

Hypnosis has been used to treat refractory warts.^[24] Several published studies have documented the success of hypnotherapy. Cure rates have been reported from 27-55%, with prepubertal children more likely to respond than adults. Patients in whom hypnotherapy fails may respond to hypnoanalysis for warts.

Hyperthermia involves immersing the involved surface in hot water (113ºF) for 30-45 minutes, 2-3 times per week.

Propolis has been reported to be significantly more effective than Echinacea or placebo as an immunomodulating treatment for common and planar warts.^[25]

Raw garlic cloves have been demonstrated to have antiviral activity. This can be rubbed onto the wart nightly, followed by occlusion.^[26]

Tea tree oil applied topically has also been reported as successful.^[27]

Vaccines currently are in development.

Cryosurgery ^[28]

Liquid nitrogen (-196ºC) is the most effective method of cryosurgery. Apply liquid nitrogen using a cotton bud applicator or cryospray to the recommended 1-2 mm rim of normal skin tissue around the wart. Repeat every 1-4 weeks for approximately 3 months, as needed. Warn patients about pain and possible blistering after treatment.

Use with caution on the sides of fingers, since it can injure underlying structures and nerves. Other side effects may include scarring, ulceration, or pigment alteration. Cure rates of 50-80% have been reported. Paring the wart, in addition to 2 freeze-thaw cycles, has been a valuable adjunct to cryosurgery for plantar warts.^[29]

Lasers

This is an expensive treatment, and is reserved only for large or refractory warts. Multiple treatments may be required. Local or general anesthesia may be necessary. A potential risk of nosocomial infection also exists in health care workers, since HPV can be isolated in the plume and can be inhaled.^[30]

Carbon dioxide lasers have successfully treated resistant warts; however, the procedure can be painful and leave scarring. One retrospective study revealed a cure rate of 64% at 12 months with carbon dioxide lasers.^[31]

The flashlamp-pumped pulse dye laser has shown mixed results in treating warts, with decreased risk of scarring and transmission of HPV in the smoke plume.^[32]

Nd:YAG laser may be used for deeper, larger warts.

Electrodesiccation/curettage and surgery

Although electrodesiccation and curettage may be more effective than cryosurgery, it is painful, more likely to scar, and HPV can be isolated from the plume. Avoid using surgical excision in most circumstances because of the risks of scarring and recurrence.