University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• You are seeing a teenager with multiple warts that have been refractory to standard topical therapy, and she is looking for an effective alternative. In teenagers with multiple recalcitrant warts, is oral cimetidine compared with placebo an effective treatment?

Clinical Bottom Lines

1. In patients with multiple warts who have failed previous topical treatments, oral cimetidine is not more effective than placebo in achieving complete cure.¹
2. No randomized placebo-controlled trials of cimetidine limited to children with multiple resistant warts have been done.

Summary of Key Evidence

1. Seventy patients (ages 4-39; average 15.4) were enrolled in a three month randomized, double-blind study conducted in Turkey comparing oral cimetidine (25-40 mg/kg/day¸ tid-qid) with placebo.¹ Males older than 16 years were excluded because cimetidine is not approved in Turkey for that age group.
2. Patients had 5 to >100 warts of varying types. "Most" had been previously treated with topical agents, liquid nitrogen cryotherapy or electrodessication & curettage. None had received treatment within 4 weeks of study entry.
3. Results were reported for only 54 out of 70 (77%) enrolled. The authors state that sixteen patients (seven cimetidine-treated & nine placebo-treated) failed to complete the study. Twelve were noncompliant and four used prohibited concomitant medication. This violates the "intention to treat" analysis.
4. Complete cure after 3 months was observed in 32% (9 of 28) of placebo-treated and 30.7% (8 of 26) of cimetidine-treated patients. This difference was not statistically significant (p=0.85).
5. Of those patients with complete cure, none was older than 15 (8 in placebo group, 9 in cimetidine group)

Additional Comments

• Cimetidine is an H2-receptor antagonist known to have immunomodulatory effects including enhancement of T-cell-dependent responses. It has been tested in the treatment of HSV, VZV & EBV infections as well as several systemic and dermatologic diseases associated with immunosuppression.
• Ten studies of cimetidine treatment for warts have been done; only three were double-blind, placebo-controlled; the remainder were either open-label studies, comparison with standard therapy, or case reports. Cure rates have ranged from 10%-82%. Results have suggested that younger patients have a greater response rate.²
• Children with multiple recalcitrant warts remain a unique population in whom effective, safe and painless systemic treatment would be advantageous. A randomized controlled trial focusing on this group should be conducted.
• More than 50% of warts in children will resolve spontaneously within 2 years. Cure rates for warts in placebo treatments have ranged from 10%-35% in the literature.²

Citation

1. Yilmaz E, Alpsoy E, Basaran E. Cimetidine therapy for warts: A placebo-controlled, double-blind study. J Am Acad Dermatol 1996; 34:1005-7.
2. Rogers CJ, Gibney MD, et al. Cimetidine therapy for recalcitrant warts in adults: Is it any better than placebo? J Am Acad Dermatol 1999; 41:123-7.

CAT Author: Amy E. Cooke, MD

CAT Appraisers: Katherine Layton, MD

Date appraised: August 24, 2001