STUDY. Duct Tape for the Treatment of Common Warts in Adults

Transcription

1 STUDY Duct Tape for the Treatment of Common Warts in Adults A Double-blind Randomized Controlled Trial Rachel Wenner, MD; Sharone K. Askari, MD; Peter M. H. Cham, MD; Deborah A. Kedrowski, RN; An Liu, MS; Erin M. Warshaw, MD, MS Objective: To evaluate the efficacy of duct tape occlusion therapy for the treatment of common warts in adults. Design: Double-blind controlled clinical intervention trial. Setting: Veterans Affairs medical center. Participants: A total of 90 immunocompetent adult volunteers with at least 1 wart measuring 2 to 15 mm were enrolled between October 1, 2004, and July 31, Eighty patients completed the study. Intervention: Patients were randomized by a computergenerated code to receive pads consisting of either moleskin with transparent duct tape (treatment group) or moleskin alone (control group). Patients were instructed to wear the pads for 7 consecutive days and leave the pad off on the seventh evening. This process was repeated for 2 months or until the wart resolved, whichever occurred first. Follow-up visits occurred at 1 and 2 months. Main Outcome Measure: Complete resolution of the target wart. Secondary outcomes included change in size of the target wart and recurrence rates at 6 months for warts with complete resolution. Results: There were no statistically significant differences in the proportions of patients with resolution of the target wart (8 [21%] of 39 patients in the treatment group vs 9 [22%] of 41 in the control group). Of patients with complete resolution, 6 (75%) in the treatment group and 3 (33%) in the control group had recurrence of the target wart by the sixth month. Conclusion: We found no statistically significant difference between duct tape and moleskin for the treatment of warts in an adult population. Trial Registration: clinicaltrials.gov Identifier: NCT Arch Dermatol. 2007;143: Author Affiliations: Departments of Dermatology, University of Minnesota, Minneapolis (Drs Wenner and Warshaw) and Saint Louis University, St Louis, Mo (Dr Askari), and Dermatology Section (Drs Wenner, Cham, and Warshaw and Ms Kedrowski) and Centers for Chronic Disease Outcomes and Research (Ms Liu), Minneapolis Veterans Affairs Medical Center, Minneapolis. WARTS (VERRUCAE vulgaris) are benign skin tumors caused by doublestranded DNA viruses called papillomaviruses. Although the prevalence of common warts in the general population is unknown, warts occur in approximately 5% to 20% of children and young adults. 1-6 CME course available at The most common therapies for warts include destruction (cryotherapy, salicylic acid, laser, electrodesiccation, curettage, etc), topical immunotherapy, chemotherapy, occlusion, and even hypnosis. These treatments are limited by cost, poor patient compliance, pain, and/or efficacy. 7 A 2001 Cochrane review stated that there is a considerable lack of evidence on which to base the rational use of local treatments for common warts. 7 According to that review, the therapy with the best evidence reported was topical salicylic acid, which achieved 75% resolution rates among the compiled data. 7 Several reports have suggested that occlusion with adhesive tape is an effective treatment for warts. In 1978, Litt 8 reported that 9 patients (aged 7-20 years) with periungual warts had resolution within 3 months of beginning weekly occlusive white adhesive tape therapy. In a letter to the editor of American Family Physician in 1998, Walbroehl 9 reported a success rate of nearly 80% with this modality in his own practice after 4 weeks of therapy (details not reported). In 2002, Focht and colleagues 10 published the results of a prospective randomized controlled trial of 61 patients (aged 3-22 years) who received either cryotherapy (10 seconds every 2-3 weeks for up to 6 treatments) or duct tape occlusion ( stan- 309

2 dard duct tape [brand not reported] in 6-day increments) for up to 2 months. Eighty-five percent (22/26) of the patients using duct tape therapy had complete resolution of their warts compared 60% (15/25) of the patients receiving cryotherapy (P=.05). Although the results of that study were widely reported, it had several major limitations. There was likely incomplete blinding of the investigators and subjects, and follow-up was incomplete. A letter to the editor of American Family Physician 11 following the report of that study urged that larger randomized trials were necessary to assess the efficacy of duct tape therapy for warts in various anatomic locations and to evaluate recurrence rates. Another letter to the Archives of Pediatrics & Adolescent Medicine 12 stated, It would be premature to conclude that duct tape has special prowess in stimulating the immune system, and also stated that further investigations were warranted. Given that duct tape therapy is inexpensive and relatively painless, we were interested in further evaluating this therapy. The purpose of this study was to evaluate the efficacy of duct tape in a double-blind randomized controlled fashion in an adult population. METHODS STUDY POPULATION This study was approved by the Human Studies Subcommittee of the Minneapolis Veterans Affairs Medical Center. Inclusion criteria included the following: (1) ability to comprehend and provide informed consent; (2) age greater than 18 years; and (3) at least 1 common wart with a diameter of 2 to 15 mm. Exclusion criteria included any of the following: (1) pregnancy or lactation (in women); (2) treatment of the target wart within the past 4 weeks by any modality; (3) immunodeficiency (related to cancer chemotherapy, systemic corticosteroid therapy, genetic immunodeficiency, transplant status, etc); (4) presence of a genital wart only; or (5) history of hypersensitivity or allergy to adhesive tape or latex. INTERVENTION Patients were randomized to receive duct tape (treatment group) or moleskin (control group). Allocation to these 2 groups was determined by a computer-generated randomization log accessible only to a research pharmacist. The investigators and participants were blinded to the randomization status. This was achieved by disguising both modalities to appear identical. Duct tape (Scotch Transparent Duct Tape; 3M, St Paul, Minn) was applied to the adhesive side of moleskin (Dr Scholl s Moleskin Plus; Schering-Plough HealthCare Products, Memphis, Tenn) and cut into pads. The control group received cut moleskin pads without duct tape. Both the duct tape and moleskin pads had a waxed-paper backing covering the adhesive surface before use. In both study groups, the pads were cut into 3 different sizes to accommodate different wart diameters: small ( 5 mm), medium (6-10 mm), and large (10-15 mm). PROTOCOL The study protocol was based on the regimen of Focht et al. 10 Patients were seen 3 times during the study: at baseline, 1 month, and 2 months. At the baseline visit, the target wart was chosen as the largest wart fulfilling the study criteria. At each visit, the location, diameter, and height of all (target and nontarget) warts were documented. Only the target wart, however, was treated during the study period. The target wart was pared with a No. 15 scalpel blade, and the first application was demonstrated by the investigator. Patients were instructed to wear a single pad for 7 days, remove the pad on the evening of day 7, and use nothing on the wart overnight. The morning of day 8, patients were instructed to soak and lightly debride the target wart with a coarse-grit emery board (provided) and then apply a new pad. This cycle was repeated for the entire treatment period of 2 months. If a pad fell off before day 7, a new pad was applied. Reinforcing tape (Silopad Digital Cap [Silipos Inc, Niagara Falls, NY], Coban wrapping tape [3M], Tegaderm [3M], and/or Restore [Hollister Inc, Libertyville, Ill]) was also permitted, if required, to hold the pads in place. Nearly all subjects required some type of reinforcing tape. If the patient believed that there was complete resolution of the target wart before the next scheduled visit, the patient was seen as soon as possible in an ad hoc visit, during which final end points were collected and study treatment was discontinued. If there was complete resolution of the target wart during the study period, the patient was contacted by telephone 6 months after resolution to obtain information regarding recurrence of the target wart. During the study period, subjects were instructed not to use any over-thecounter or prescription wart preparations or therapies. Data were collected on all patients whether or not treatment was completed according to the protocol. ANALYSIS The objective of this intent-to-treat study was to determine the efficacy of duct tape occlusion for the treatment of verruca vulgaris. The primary outcome was complete resolution of the target wart (global assessment) anytime during the 2-month treatment period. Secondary outcomes included a change in the size of the target wart (diameter and height) and recurrence of the target wart at 6 months. The Fisher exact test was used to compare the differences between treatment groups in complete resolution of the target wart (global assessment) and recurrence rate of the target wart at 6 months. Two-sample t tests were used to compare differences between groups in the change in size of the target wart and time to resolution of the target wart. Logistic regression analyses were used to evaluate the association between duration and resolution. On the basis of the study by Focht et al, 10 which used a similar outcome measurement, we predicted that the mean difference in the proportion of patients with resolution of the target wart at the end of active treatment would be at least 35% between the treatment and control groups. We calculated that a sample size of 80 would provide 80% power and that a sample size of 90 would provide 96% power, assuming a 20% loss to follow-up and =.05. RESULTS BASELINE CHARACTERISTICS In all, 238 individuals were screened between October 1, 2004, and July 31, Ninety individuals with a total of 126 warts met the study criteria and were enrolled and randomized to either the control group (moleskin, n=46) or the treatment group (duct tape, n=44) (Figure). Baseline demographic data are summarized in the Table.No statistically significant differences were found between the treatment arms with respect to any of the categories at baseline. There was also no statistically significant dif- 310

3 39 Followed Protocol 238 Volunteers Were Screened 148 Were Not Enrolled 13 Declined/Were Unable to Consent 135 Did Not Meet Study Criteria 116 Had Other Lesion (SK, Skin Tag) 8 Had Target Wart That Was Too Small/Large 3 Were Enrolled in Different Study 8 for Other Reasons 5 Did Not Follow Protocol 2 Experienced Discomfort 1 Considered Wart Location Difficult 1 Experienced Adverse Event (Numbness) 1 for Other Reasons 90 Participants Were Randomized 44 Received Duct Tape 46 Received Moleskin (Treatment Group) (Control Group) 41 Followed Protocol 5 Did Not Follow Protocol 3 Considered Protocol Inconvenient 1 Experienced Adverse Event (Bleeding) 1 for Other Reasons 39 Completed Trial 41 Completed Trial Figure. Flow of the study participants. SK indicates seborrheic keratosis. ference in the number of warts between patients in the treatment and control groups. There were also no statistically significant differences in the numbers of patients who had 3 or more warts in the treatment (5/44 [11%]) and control (6/46 [13%]) groups (P=.43). The 2-month study was completed by 80 (89%) of the 90 study participants (39 [89%] of 44 in the treatment group and 41 [89%] of 46 in the control group). The reasons for discontinuation are shown in the Figure. RESOLUTION OF THE TARGET WART Table. Baseline Characteristics of the Study Population Characteristic Control (n = 46) Group Treatment (n = 44) At the end of treatment, there were no statistically significant differences in resolution rates of patients in the treatment group (8/39 [21%]) compared with the control group (9/41 [22%]) (P.99). Three of the 9 patients in the control arm who achieved complete resolution did so within the first month of treatment, whereas none in the treatment group achieved resolution of the target wart within the first month (P=.24). During the treatment period, the mean diameter and height of the target wart decreased regardless of study group assignment, and there were no statistically significant differences in the decrease in diameter or height between treatment groups at the 1- or 2-month visits (mean differences, all 0.4 mm; P.11 for all). There were also no statistically significant differences between the 2 treatment groups at the 1- and 2-month visits for the proportion of individuals with a diameter decrease of at least 1 mm and for the proportion of individuals with a diameter decrease of at least 2 mm. Neither the location of the target wart (all categories, finger vs nonfinger) nor prior treatment (liquid nitrogen or salicylic acid) was associated with resolution of the target wart at 1 or 2 months. Regardless of the treatment arm, Mantel-Haenszel and logistic regression analyses showed that the success of the therapy was not associated with the number of warts. Logistic regression analyses showed that duration of the target wart alone was associated with its complete resolution at month 2 (P=.006), after adjusting for treatment group effect (treatment group was not statistically significant; P=.30). Of the warts that achieved resolution, the duration of the wart prior to enrollment in the study was statistically significantly less than that of nonresolved warts (odds ratio,0.97; 95% confidence interval, ). RECURRENCE OF THE TARGET WART P Value Age, y Mean (SD) 53.5 (14.4) 54.4 (12.2).75 No. (%) (57) 26 (59) (43) 18 (41) Male sex, No. (%) 32 (70) 33 (75).64 No. of warts, mean (SD) 1.5 (0.9) 1.3 (0.7).36 Diameter of wart, mean (SD), mm [No.] Target 5.4 (3.1) [46] 5.2 (2.4) [44].75 Nontarget First 3.9 (3.5) [13] 4.8 (2.4) [8].55 Second 5.4 (4.7) [6] 4 (1.4) [5].54 Third 6.3 (2.1) [3] 3 [1]*.30 Height of target wart, 1.0 (0.8) 0.7 (0.7).11 mean (SD), mm Treatment history for target wart, No. (%) of patients Any Rx 31 (67) 28 (64).83 Liquid nitrogen 17 (37) 12 (27).37 Salicylic acid 17 (37) 16 (36).99 Debridement 10 (22) 12 (27).63 Other physician treatment 17 (37) 12 (27).37 Other treatment 6 (13) 6 (13).99 Disease duration.33 Mean (SD), y 11.5 (15) 8.3 (13.5) Range 3 d to 80 y 15 d to 61 y Location of target wart, No. (%).58 Finger 31 (67) 28 (64) Palm 3 (7) 0 Toe 2 (4) 2 (5) Plantar foot 8 (17) 12 (27) Periungual 1 (2) 1 (2) Other 1 (2) 1 (2) Abbreviation: Rx, physician-initiated treatment. *Indicates that there is no standard deviation because there was only 1 patient. One third of the patients in the control group (3/9) and 75% of the patients in the treatment group (6/8) who had complete resolution by the end of the study reported recurrence of the target wart at month 6 (P=.15). The earliest recurrence was at month 3 for the control group (mean time to recurrence, 3.7 months). The mean time to recurrence in the treatment group was 3.2 months. 311

4 ADVERSE EVENTS Only 2 individuals experienced adverse events. One participant reported numbness of the finger after wrapping a securing bandage too tightly over the study pad; another reported bleeding while using the control pad. RESOLUTION OF NONTARGET WARTS Resolution rates for nontarget warts were not statistically significantly different by study group at either the 1- or 2-month visit. Disregarding randomization, there was a borderline statistically significant association between resolution of the target wart (17/90 [19%]) and resolution of nontarget warts (6/15 [40%]) at month 2 (P=.05). COMMENT We found that occlusion with transparent duct tape was not statistically significantly more effective than moleskin for treating common warts in adults. To our knowledge, this is the first double-blind controlled trial investigating this therapy. The therapeutic mechanism for duct tape for treatment of verrucae is unknown, but several theories have been proposed. The lay media often propose the theory that occlusion leads to a deprivation of oxygen to the virus, essentially leading to suffocation. A second is that duct tape debrides and debulks the wart. 13 Allen and Dveirin 12 suggested that duct tape may work by psychological means, which may work better in children than in adults. Still another theory is that the duct tape occlusion creates a macerating and keratolytic environment, 14 which perhaps stimulates an immune response. The results of our study suggest that occlusion itself is not the therapeutic mechanism because the overall success rates were low in both treatment groups. The study by Focht et al 10 found that 22 (85%) of 26 pediatric patients achieved resolution of warts with duct tape therapy compared with 8 (21%) of 39 adult patients in our study. This difference could be due to several study design factors. The first major difference is in the age of the study populations. The study by Focht et al consisted primarily of children (mean age, 9 years) compared with our adult population (mean age, 54 years). In the pediatric population, it has been estimated that up to 65% of warts resolve spontaneously within 2 years, 15 whereas some researchers believe that spontaneous resolution of warts occurs rarely in adults. 16 A similar inverse relationship between age of subjects and response rates to wart treatment has been documented in the literature by Horn et al 17 in a 3-arm study that assessed the efficacy of antigen injection vs interferon injection vs control (isotonic sodium chloride solution) for the treatment of warts. In that study, the nonresponders tended to be older than the responders, and further analysis showed that age younger than 40 years was positively associated with probability of a response. 17 Preliminary results of interim data of a study by Salk et al 14 also reported only a 10% cure rate after duct tape occlusion in a study of adults (further details of the study were not reported). Second, the study by Focht et al 10 excluded warts that had been previously treated. Third, while the average size and location of the warts in the study by Focht et al were similar (mean diameter, 5.2 mm; 96% of the warts located on the hands and feet) to the warts in our study (mean diameter, 5.3 mm; 98% of the warts located on the hands and feet), it is likely that the patients in our study had more recalcitrant warts because the average disease duration was approximately 10 years (the disease duration was not reported in the study by Focht et al). Fourth, although the investigators in the study by Focht et al were blinded to treatment allocation, it is likely that this blinding was not completely effective; the clinical appearance of a wart treated with liquid nitrogen can be significantly different from that of a wart treated with tape occlusion. Standard cryotherapy often causes erythema, skin discoloration, crusting, and vesicles, whereas occlusion often causes maceration 2 very distinct clinical appearances. In our study, both study groups received an occlusive therapy, and the clinical appearance of the 2 interventions was indistinguishable. Finally, parental assessment of wart resolution was used as an end point for some of the patients in the study by Focht et al. In our study, all clinic visit assessments were performed by physicians. Another possible explanation for the different results between our study and the one by Focht et al is that the type of duct tape was different. To blind the treatment modality in our study, transparent duct tape was used. When we were designing the protocol for this study, a product manager at 3M (individual s name not recorded, oral communication, June 30, 2004) noted that all 3M duct tape, including the new transparent duct tape, consists of...arubber-based adhesive. It was therefore determined that transparent duct tape could be used as an adequate alternative to standard silver duct tape for blinding purposes. After completion of the study, however, conflicting information was obtained from 3M (and verified to be correct) that transparent duct tape actually contains an acrylic-based adhesive, whereas standard silver duct tape contains a rubber-based adhesive (Ron Flemming, Construction and Home Improvement Markets Division of 3M, oral communication, January 19, 2006). Moleskin also uses an acrylic-based adhesive. Thus, it is possible that the rubber-based adhesive or other components of an adhesive not found on our study tape are required for effective treatment of warts. This study had several limitations. First, many patients had difficulty keeping the pads in place despite the use of additional securing dressings. It can be assumed, therefore, that some warts were likely uncovered for periods of time. If large pieces of duct tape were used (as would be typical in clinical practice) rather than cut pads (such as were used as in our study), compliance with treatment would likely improve. Second, because the type of adhesive in the transparent duct tape used in this study differs from that of standard silver duct tape, it is possible that the adhesive (or some other component) of standard silver duct tape may be effective for the treatment of warts. Future studies evaluating different types of adhesives are needed to further elucidate this issue. 312

5 In conclusion, we found no statistically significant difference between occlusive therapy with transparent duct tape and therapy with moleskin alone for treatment of common warts in adults. Further studies are warranted to determine whether specific types of adhesive resins are important for a therapeutic effect of duct tape. Accepted for Publication: August 9, Correspondence: Rachel Wenner, MD, Department of Dermatology, Minneapolis Veterans Affairs Medical Center, One Veterans Dr, Mail Code 111K, Minneapolis, MN (wenn0032@umn.edu). Author Contributions: Drs Wenner and Warshaw had access to all the data in the study and take full responsibility for the integrity of the data and accuracy of the data analysis. Study concept and design: Wenner and Warshaw. Acquisition of data: Wenner, Askari, Cham, Kedrowski, and Warshaw. Analysis and interpretation of data: Wenner, Askari, Liu, and Warshaw. Drafting of the manuscript: Wenner, Askari, and Cham. Critical revision of the manuscript for important intellectual content: Wenner, Askari, Cham, Kedrowski, Liu, and Warshaw. Statistical analysis: Liu and Warshaw. Obtained funding: Wenner. Administrative, technical, and material support: Wenner, Askari, Cham, Kedrowski, and Warshaw. Study supervision: Warshaw. Financial Disclosure: None reported. Funding/Support: The conduct, management, and data interpretation of this study were supported by the Center for Chronic Disease Outcomes Research at the Minneapolis Veterans Affairs Medical Center and a medical student research grant from the Minnesota Medical Foundation (Dr Wenner). Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. REFERENCES 1. Kilkenny M, Marks R. The descriptive epidemiology of warts in the community. Australas J Dermatol. 1996;37: Williams HC, Pottier A, Strachan D. The descriptive epidemiology of warts in British schoolchildren. Br J Dermatol. 1993;128: Kilkenny M, Merlin K, Young R, Marks R. The prevalence of common skin conditions in Australian school students, 1: common, plane and plantar viral warts. Br J Dermatol. 1998;138: Popescu R, Popescu CM, Williams HC, Forsea D. The prevalence of skin conditions in Romanian school children. Br J Dermatol. 1999;140: Beutner KR, Becker TM, Stone KM. Epidemiology of human papillomavirus infections. Dermatol Clin. 1991;9: Kirnbauer R, Lenz P, Okun MM. Human papillomavirus. In: Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. Vol 1. London, England: Mosby; 2003: Gibbs S, Harvey I, Sterling J, Stark R. Local treatments for cutaneous warts. Cochrane Database Syst Rev. 2001;(2):CD Litt JZ. Don t excise exorcise: treatment for subungual and periungual warts. Cutis. 1978;22: Walbroehl G. Treating periungual warts with adhesive tape [letter]. Am Fam Physician. 1998;57: Focht DR III, Spicer C, Fairchok MP. The efficacy of duct tape vs cryotherapy in the treatment of verruca vulgaris (the common wart). Arch Pediatr Adolesc Med. 2002;156: Summers J, Kaminski J. Is duct tape occlusion therapy an effective treatment of warts [letter]? Am Fam Physician. 2003;68:1912, Allen JJB, Dveirin K. Mechanism of wart disappearance: an alternative hypothesis [letter]. Arch Pediatr Adolesc Med. 2003;157: Q&A online search: answer to question, How does duct tape occlusion work for treating cutaneous warts? wonders Arnold D. Dlin, MD, of Vancouver, BC: dermatology: old fashioned duct tape for warts. Parkhurst Exchange Web site. October 15, Accessed March 1, Salk R, Grogan K, Chang T, D Costa W. Exploring alternative treatment for resistant warts. Podiatry Today. 2004;17(5): Bauman C, Francis JS, Vanderhooft S, Sybert VP. Cimetidine therapy for multiple viral warts in children. J Am Acad Dermatol. 1996;35: Glass AT, Solomon BA. Cimetidine therapy for recalcitrant warts in adults. Arch Dermatol. 1996;132: Horn TD, Johnson SM, Helm RM, Roberson PK. Intralesional immunotherapy of warts with mumps, Candida, and Trichophyton skin test antigens: a singleblinded, randomized, and controlled trial. Arch Dermatol. 2005;141: