The Problem
A 36-year-old mechanic presents to you for a 4-week history of feeling as if he is "walking on a pebble." You examine his foot and determine that he has a plantar wart. You pare it down and apply liquid nitrogen. No specific follow-up plan was provided. He returns to you 5 weeks later with the same problem. You pare it down and freeze it again. He calls your office 1 month later and wonders if he should come in for freezing or if he should try an over-the-counter salicylic acid treatment that his cousin told him about. He continues to have pain with walking and is currently limping. You are uncertain as to which remedy – liquid nitrogen or salicylic acid – is better for the treatment of plantar warts.
The Question
In the treatment of patients with plantar warts, is liquid nitrogen or salicylic acid more effective?
By Jon O. Ebbert (left) and Eric G. Tangalos
The Search
You open PubMed (www.pubmed.gov), enter "plantar warts," and limit to "randomized controlled trial."
The Evidence
"Cryotherapy Versus Salicylic Acid for the Treatment of Plantar Warts (Verrucae): A Randomised Controlled Trial" (BMJ 2011;342:d3271).
• Study Design and Setting: This multicenter, randomized, controlled clinical trial involved 242 patients at 13 centers in the United Kingdom and 1 in the Republic of Ireland. Subjects were recruited from podiatry school clinics and U.K. National Health Service podiatry and primary care clinics.
• Participants: People were eligible for enrollment if they were at least 12 years old and had a plantar wart suitable for treatment. Potential subjects were excluded if they had impaired healing caused by diabetes or peripheral vascular disease; were immunocompromised or were taking immunosuppressants; had neuropathy; were receiving renal dialysis; had cold intolerance; had blood dyscrasias, cryoglobulinemia, cryofibrinogenemia, or a collagen or autoimmune disease; were unable to give informed consent; or were in a trial evaluating other plantar wart treatments.
• Intervention: Participants were randomized to either cryotherapy with liquid nitrogen, or daily self-treatment with an over-the-counter, 50% salicylic acid treatment. Subjects who received cryotherapy with liquid nitrogen received up to four treatments delivered 2-3 weeks apart by a clinician. Cryotherapy was delivered with a preferred method of a spray, but could also be applied with a probe. The treatment was delivered according to the site’s usual practice (for example, debridement prior to treatment, masking of the surrounding area, and padding after treatment). Subjects receiving salicylic acid were instructed on how to apply the 50% salicylic acid solution. The specific product (Verrugon) involved the use of an adhesive ring into which the acid was applied and over which plaster was placed, enclosing the ring. Treatment was repeated daily, after pumicing the verruca, for up to 8 weeks.
• Outcomes: The primary outcome was the clearance of the plantar wart 12 weeks after randomization. Clearance (defined as restoration of normal skin) was adjudicated by two independent evaluators who were blind to treatment assignment and who examined photographs. Discrepancies were referred to a third reviewer. If photographs were unavailable, outcome assessment by a clinician at the study site was used. If neither was available, outcomes were based upon the patient’s self-report. Secondary outcomes included patient preferences, time to clearance, and adverse events.
• Results: In all, 124 subjects were randomized to salicylic acid and 118 to cryotherapy. The mean number of cryotherapy visits was four, with a mean duration of 18 days between visits. Subjects applied salicylic acid on an average of 6 days per week in the first week and 5 days in week 3. Overall, 32 of the 229 patients who completed the study (14%) had complete clearance of all plantar warts at 12 weeks, corresponding to 17 per 119 patients (14%) in the salicylic acid group and 15 per 110 patients (14%) in cryotherapy (difference, 0.65%; P = .89). No difference existed in the time to clearance between the two groups. At week 12, more patients were unhappy with salicylic acid and more were very happy with cryotherapy. Cryotherapy was more expensive than salicylic acid therapy. No significant differences were observed between groups with respect to adverse events.
Our Critique
The study was well conducted with appropriate safeguards for bias with an open study (that is, independent adjudication of plantar wart clearance). Overall, 90% of subjects had an independent blinded assessment of clearance, with 2% of assessments by an unblinded clinician and 8% with self-report. The overall clearance rate in the current study was low (14%), compared with previous studies (range, 30%-68%), which may reflect enrollment of a population with more recalcitrant warts.