Adjunctive Trichloroacetic Acid Therapy Enhances Response to Squaric Acid Response to Verruca Vulgaris

October 2012 | Volume 11 | Issue 10 | Original Article | 1228 | Copyright © October 2012

Squaric acid dibutyl ester (SADBE) is a commonly used treatment for verruca vulgaris of childhood. Few studies, however, have examined the role of SADBE in combination with other topical therapies for warts. We sought to determine if trichloroacetic acid 50% (TCA) and/or cantharidin 0.7% improve therapeutic response to SADBE. A retrospective chart review of 74 patients who were treated for warts at a pediatric dermatology practice in 2010 was performed. Cox regression analysis was used to identify determinants of 100% response to SADBE and found that number of warts was most important (P=0.002). Trichloroacetic acid + SADBE resulted in 100% clearance of warts in all subjects with the shortest time-to-clearance (hazard ratio [HR]: 2.45, 95% confidence interval [CI]: 1.14-5.25, P=0.02). In contrast, addition of cantharidin did not improve response to SADBE (HR: 1.13, 95% CI: 0.60-2.13, P=0.59) or TCA + SADBE (HR: 1.16, 95% CI: 0.65-2.07, P=0.61). These results suggest that combination treatment with TCA 50% and SADBE significantly improves the consistency and speed of SADBE-induced clearance of warts.

J Drugs Dermatol. 2012;11(10):1228-1230.


Warts are a common viral infection affecting an estimated 20% of children.1 Therapy for treatment-resistant warts with squaric acid dibutyl ester (SADBE) in acetone, consists of sensitizing with 1% to 2% SADBE on the inner arm, followed by application of 0.5% to 5% SADBE to the warts every 3 to 4 weeks results in wart clearance in 80% after an average of 5.7 sessions.2 Micali et al. were able to increase the complete clearance rate to 86.2% by sensitizing with 3% SADBE to lesions and application of 70% salicylic acid under occlusion for 2 to 3 days prior to each treatment session twice-weekly.3,4 The mean time to clearance was 10.17 weeks. The aim of this retrospective chart review was to determine if the addition of destructive agents, namely Trichloroacetic acid 50% (TCA) and/or cantharidin 0.7% would increase the efficacy of SADBE in children.


An IRB-exempt retrospective chart review of all children seen in a pediatric dermatology private practice was conducted to identify children who had received therapy for warts. Inclusion criteria were children and adolescents who received care at this practice from January to December 2010, aged 1 to 21 years, male or female, with complete follow-up. Exclusion criteria were history of immunosuppression, HIV infection, comorbid systemic autoimmune disease, and active primary cutaneous inflammatory disorders, eg, psoriasis or atopic dermatitis, at the same site as treated warts.

SADBE Treatment

Squaric acid dibutyl ester was administered in the office as follows: Lesions of warts that were hyperkeratotic were pared using a 15-blade and tangential debridement. Squaric acid dibutyl ester sensitization was conducted using 2% SADBE on all nonfacial warts, followed by a minimum of 4 hours occlusion, and site washing with soap and water when the bandages were removed. The initial session was followed every 2 to 3 weeks by 0.2% SADBE application to the residual lesions. In individuals who did not develop erythema, re-sensitization was done using 2% SADBE to all lesions a second time.

TCA Treatment

In some subjects, TCA 50% was applied to all the warts themselves 1 to 2 minutes immediately prior to application of SADBE. Prior to each treatment with SADBE, TCA 50% was applied. In children with pinpoint bleeding after paring, TCA 50% resulted clinically in cauterization of open vessels.

Cantharidin Treatment

In some subjects, cantharidin 0.7% in flexible collodion was applied to all the warts 1 to 2 minutes immediately after application of SADBE. Cantharidin was then applied after each treatment with SADBE.

Statistical Analysis

The baseline characteristics of patients were examined. All continuous variables of patient characteristics, including age, number, and duration of warts, were not normally distributed as judged by analysis of normality using residuals, Shapiro-Wilk and Kolmogorov-Smirnov tests (P<0.01).5,6 Therefore, data are presented as median, interquartile range (IQR), and range. All tests of significance were two-sided. Statistical analyses were performed using SAS 9.2 Software (SAS Institute Inc., Cary, NC).
Cox proportional hazards regression was used to determine which variables were associated with the shortest time to 100% clearance of warts. The time-to-clearance variable in all models was the time from first treatment to either 100% clearance of warts or censoring. The independent variables included age (continuous), sex (male/female), ethnicity (Caucasian/other), number of warts (continuous), duration of warts (continuous), development of new warts adjacent to previous warts (yes/no),