Patient Presentation
A 4-year-old male came to clinic for treatment of plantar warts that had been present for less than a month. His mother had tried salicylic acid inconsistently and wanted cryotherapy. The past medical history showed a healthy male and the review of systems was normal.

The pertinent physical exam a healthy male with normal vital signs and growth parameters. On the ball of the left foot and great toe he had two flat, but cauliflower-like lesions of ~3-4 mm in size that were relatively superficial. The diagnosis of plantar warts was made. The resident was reviewing his treatment plan with his attending and said that he was going to write a prescription for “WartPEEL®” as one of his other attendings liked that medication instead of plain salicylic acid. His current supervisor asked him what was in the medication and a website showed that it was 5-Fluorouracil and salicylic acid in a proprietary formula. The attending asked the resident about if there was any data that 5FU was more efficacious than plain salicylic acid and what was the difference in cost. The resident wasn’t sure so he said he would try to look into this over the next few days.

Discussion
Veruccae plantaris or plantar warts are caused by Human papillomavirus which causes benign epidermal tumors that often have a cauliflower pattern on the foot that may be elevated or flush with the surrounding skin. Lesions may resemble calluses but the normal footprint pattern is disrupted. The lesions often have pinpoint hemorrhages that appear as black dots. In an immunocompetent individual, the lesions usually have spontaneous resolution within 2 years but the infection may spread to create additional lesions. The lesions may also cause pain or discomfort because of their size or location.

Plantar warts are often difficult to treat. Treatments include keratolytics (e.g. salicylic acid (SA) or tricholoacetamic acid), cryotherapy with liquid nitrogen, electrodesiccation, or direct surgical removal. Suffocation by duct tape and plastic have also been used. Immunotherapy with candida, mumps or trichophytin antigens have been used more recently. These are felt to induce a local and distant immunoresponse that destroys the lesions.

5-Fluorouracil (5FU) is an antineoplastic and antimetabolite that inhibits DNA and RNA synthesis which is believed to be the mechanism that stops wart proliferation WartPEEL®. WartPEEL® is a compounded medication available only in certain locations in the United States and is not FDA approved currently.

Learning Point
Warts are difficult to treat. It takes a long time to treat them. Relapse and spread are common. There can be pain and discomfort with each treatment or with no treatment also. Cost and often daily treatments makes the treatment often difficult to comply with.

Placebo cure rates for wart treatment are around 20-40% for many trials and trials often have end points between 3-6 months.

Topical 5FU compared to placebo shows ~50% cure rate for several trials. Topical 5FU/SA compared to placebo shows 46% versus 19% cure rate. Topical 5FU versus occlusion with duct tape showed 85% cure versus 10% after 6 months of treatment.

5FU is also used as an intralesional treatment. Studies have found intralesional 5FU compared to placebo have a cure rate of 64-70% versus 29-35%.

Questions for Further Discussion
1. 5FU is used for what other disease processes?
2. How effective is intralesional candida treatment? Click Here

Related Cases

Disease: Warts | HPV

Symptom/Presentation: Papulosquamous Lesions

Specialty: Dermatology | Immunology | Infectious Diseases | Pharmacology / Toxicology

Age: Preschooler

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Warts and Human Papillomavirus.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Zschocke I, Hartmann A, Schlöbe A, Cummerow R, Augustin M. Efficacy and benefit of a 5-FU/salicylic acid preparation in the therapy of common and plantar warts–systematic literature review and meta-analysis. J Dtsch Dermatol Ges. 2004 Mar;2(3):187-93. [Abstract only in English]

Salk RS, Grogan KA, Chang TJ. Topical 5% 5-fluorouracil cream in the treatment of plantar warts: a prospective, randomized, and controlled clinical study. J Drugs Dermatol. 2006 May;5(5):418-24.

Kwok CS, Gibbs S, Bennett C, Holland R, Abbott R. Topical treatments for cutaneous warts. Cochrane Database Syst Rev. 2012 Sep 12;9:CD001781.

Author

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital