Combination approach effective for wart therapy

"The challenge in treating warts," Dr. Tyring tells Dermatology Times, "is not just to attain clearance but also to maintain it. For that reason, destructive methods that used to be the mainstay for treating warts before the turn of the 21st century are now antiquated for use as monotherapy. The current gold standard involves a multimodal approach that enables initial clearance but also prevents recurrence or at least markedly delays it."

Dr. Tyring is a professor of dermatology at the University of Texas, Houston.

"All patients in the imiquimod pivotal trials underwent surgical removal of any warts present at the end of the study. Over the next five to seven years of follow-up, the recurrence rate was 55 percent for the vehicle control group compared with only 15 percent for the imiquimod group, including both patients whose warts did and did not respond completely to the topical therapy alone," Dr. Tyring says.

However, he also adds that maintenance therapy may be needed to prevent wart recurrence in immunocompromised patients. This may be especially true for HIV-infected individuals who are responding poorly to their highly active antiretroviral therapy (HAART).

"Experience with this approach shows once weekly application of imiquimod to the area of previous involvement can indefinitely prolong the clearance," Dr. Tyring says.

Approaches for other wart types

Since imiquimod became available in the late 1990s, it has been used most widely by clinicians to treat warts in an off-label manner for lesions on the hands and feet.

For plantar warts, the hyperkeratotic layers should be pared away and then cryosurgery used to destroy another layer or two of tissue before beginning imiquimod. Patients are instructed to continue their treatment by applying salicylic acid plasters each morning, scraping away the macerated tissue at night, and then applying imiquimod under occlusion.

"The pad in a Band-Aid will absorb the cream, and so it is important that patients only use occlusive tape to cover the imiquimod-treated area. This regimen usually needs to be followed for four to eight weeks when treating hand warts and eight to 12 weeks for plantar warts," Dr. Tyring says.

Alternatives for refractory growths

For warts that fail to respond to these methods, there are other alternatives to try.

In immunocompetent patients, flat warts that do not require paring and liquid nitrogen can be treated with a topical retinoid in the morning and imiquimod at night. The retinoid helps to increase absorption of the immunomodulatory drug but also may enhance the response to imiquimod because it upregulates expression of proteins that modulate interferon signaling, Dr. Tyring explains.

Immunocompromised patients probably will derive greater benefit from using an oral retinoid, such as a daily dose of acitretin, with imiquimod applied under occlusion at night.

A number of studies also indicate that intralesional injection with skin test antigens (i.e., Candida, mumps and Trichophyton) may be effective to clear warts. This treatment works by nonspecifically boosting immunity and can result in clearing of injected as well as nearby lesions. Some ongoing studies suggest that a combination regimen using skin test antigen injection in combination with imiquimod can provide even better results.