How To Treat Recalcitrant Plantar Warts

Christina A. Weber, DPM, FACFAS, and Kristine M. Hoffman, DPM

A Closer Look At Options For Topical Treatment

Imiquimod (Aldara, Medicis). Imiquimod is an immunomodulatory agent that acts to enhance cell mediated immunity. The drug previously received approval for the treatment of several conditions including basal cell carcinoma, superficial squamous cell carcinoma and anogenital warts. Two studies have shown the effectiveness of imiquimod for the treatment of recalcitrant cutaneous warts.3,4 These studies showed daily application for five days per week for up to 16 weeks resulted in complete clearance of verrucae in 80 percent of immunocompetent patients.

   5-fluorouracil (Efudex, Valeant Pharmaceuticals). Fluorouracil is an antineoplastic drug that inhibits thymidylate synthase causing cell death due to a lack of thymidine triphosphate, an essential precursor to DNA replication.5 Studies have demonstrated that fluorouracil has cure rates for cutaneous warts ranging from 50 to 95 percent.6,7 A meta-analysis of randomized controlled studies showed that the combination of 5-fluorouracil with 10% salicylic acid led to a threefold improvement in the cure rate of warts.8 The recommended use is 5% Efudex cream applied to verrucae two to three times daily for up to 12 weeks.

Can Intralesional Injections Have An Impact?

Bleomycin sulphate. Bleomycin is a glycopeptide produced by the bacteria Streptomyces verticillus, which has antiviral and antineoplastic actions. In their review of intralesional bleomycin for wart treatment, Lewis and Nydorf showed bleomycin cure rates ranging from 14 to 99 percent.9 The majority of studies show bleomycin to be an effective treatment in over two-thirds of reported cases with minimal side effects.9 The recommended dosage is 0.1-2.0 IU per lesion via an intralesional injection every two to four weeks.

   Bleomycin injection can cause moderate to severe pain, secondary to the intralesional nature of the injection and due to the bleomycin compound itself. A local anesthetic block is recommended prior to the intralesional injection of bleomycin.

   Candida antigen. Candida antigen intralesional immunotherapy is a newer modality for the treatment of recalcitrant warts that works by using the ability of the immune system to recognize fungal antigens. The hypothesis is that intralesional injection of Candida antigen creates a delayed type hypersensitivity reaction that increases the immune system’s ability to recognize and clear HPV.

   Success rates range from 47 to 70 percent for intralesional immunotherapy with Candida antigen.10,11 Studies on the use of Candida antigen for the treatment of warts have additionally shown regression of warts at sites distant to the initial intralesional injection.10 This is a unique benefit that you don’t see with other treatment modalities. The recommended treatment is to administer the Candida skin test as a local injection every three to four weeks for an average of three treatments. Side effects include pain localized to the injection site and rare influenza-like symptoms.12

   Interferon-alpha. Interferons are proteins that cells release in response to pathogens such bacteria, viruses or parasites. These proteins facilitate communication between cells to activate the immune system to eliminate the offending pathogen. Leukocytes produce interferon-alpha and it is involved in the immune response against viral infection. Researchers have shown that sublesional interferon-alpha injection is an effective treatment for verrucae. Aksakal and colleagues showed a single sublesional dose of 4.5 MU interferon-alpha is an effective treatment for plantar verruca lesions.13

A Roundup Of Oral Treatment Options

Retinoids. Retinoids are a class of chemical compounds that are chemically related to vitamin A. As a wart treatment, retinoids are useful due to their ability to alter keratinization and induce irritant dermatitis. A study conducted by Gelmetti showed an 80 percent success rate of acitretin (Soriatane, Stiefel Laboratories) for the treatment of extensive warts in children.14 The recommended treatment for acitretin is 1 mg/kg per day for no more than three months.

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