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Treatment of recurrent anogenital warts is often troublesome, because, among the various treatment modalities currently available, few are uniformly effective or virucidal.1 Currently, topical immunotherapy with squaric acid dibutylester (SADBE) represents an effective treatment in the management of multiple plantar and common warts (table 1 below).2–5 In the genital area the use of SADBE has some limitations, as it may be associated with a significant degree of irritation that produces considerable discomfort to the patient. Based on studies showing excellent results (87% of patients with complete resolution) achieved by some authors in treating condylomata acuminata of the endocervix with applications of dinitrochlorobenzene (DNCB), a substance similar to SADBE, utilising remote anatomical site applications to the skin of the arm,6 and our personal observation of spontaneous regression for untreated warts during contact immunotherapy with SADBE for alopecia areata,5 we decided to compare the results obtained in the management of multiple and resistant anogenital warts by applying SADBE directly to the lesions with those obtained by applying it to remote unaffected areas.
From June to December 1999, nine patients, seven adults (mean age 32 years) and two children (mean age 10.5 years), were treated. Following sensitisation by topical application of 3% SADBE in acetone directly to the skin of the pubic region in adults and to the back of the hands in children, serial dilutions (0.0003% to 3%) were tested 2 weeks later on the same skin area in order to evaluate the minimal concentration capable of eliciting an eczematous reaction. Subsequently, the application of the compound was performed in the clinic by trained staff twice a week. SADBE application varied by age of patients and anatomical site of lesion. In children, SADBE was applied to the dorsal left hand; in adults it was directly applied to lesions located on skin, or to the pubic area when lesions were located on mucosae. If an eczematous reaction was not elicited after 1 week, an incrementally higher concentration was applied. If a strong reaction ensued, the treatment was discontinued for 3–6 days and an incrementally lower concentration was used at the following visit.
A total of eight patients completed the therapy, showing complete resolution after a mean of 16 weeks of treatment, with variable concentrations of SADBE ranging from 0.0003% to 0.3% (table 1). Local side effects (erythema, desquamation, cutaneous oedema, pruritus, burning, and pain) were generally mild and well tolerated. No relapses occurred during an 18 month follow up.
Clinical resolution and length of treatment in patients treated by applications to remote areas was comparable with those in which SADBE was applied directly to lesions. These results not only substantiate the efficacy and safety of topical SADBE in the treatment of multiple recurrent/recalcitrant anogenital warts, but also indicate a possible systemic effect of contact immunotherapy, suggesting that the mechanism of action of SADBE could be more than a non-specific inflammatory reaction or a local cell mediated process triggered by a non-wart antigenic immune stimulus.
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