Warts

Treatment of Warts in a Young Girl With Eczema

NICOLE D. CRESCE, SMITHA KUPPALLI, MD
and BARBARA B. WILSON, MD
University of Virginia

Ms Cresce is a third-year medical student, Dr Kuppalli is a dermatology resident, and Dr Wilson is associate professor of dermatology at the University of Virginia School of Medicine in Charlottesville.

Kirk Barber, MD, FRCPC––Series Editor:Dr Barber is a consultant dermatologist at Alberta Children’s Hospital and clinical asso-ciate professor of medicine and community health sciences at the University of Calgary in Alberta.

warts

CASE: A 6-year-old girl has had multiple cutaneous warts on her medial left thigh, knee, and calf for the past year (A). She has a life-long history of atopic dermatitis, which has been treated intermittently with triamcinolone, but is otherwise healthy. She desires removal of the warts, but avoiding any painful interventions is a priority. 

Topical treatments, such as salicylic acid and duct tape, are inconvenient because of the number of lesions and their location. Topical imiquimod is another option; however, English is the patient’s second language, and there is concern that complicated instructions might be difficult to follow.

What treatment would you recommend to eradicate the warts?

(Answer and discussion on next page.)

ANSWER:

Begin a trial of high-dose oral cimetidine and follow-up in 3 months.

The choice of wart therapy depends on important considerations such as location and number of lesions, age of the patient, and ability to effectively adhere to a treatment regimen. Cimetidine is a good choice for this girl for these reasons. It has a minimal side effect profile, thus the risk/benefit ratio of this treatment warranted a trial.

Why warts persist. Cutaneous warts are neoplasms caused by the infection of keratinocytes by human papillomavirus (HPV).1 The incidence of cutaneous warts is increased in childhood, peaking in adolescence.2 In patients with atopic dermatitis, such as our patient, there is increased risk of cutaneous infection due to defects in the innate immune system—not only because of compromise to the skin barrier but also because of defects in pattern recognition receptors and decreased amounts of antimicrobial peptides.3,4

In the case of cutaneous warts, HPV evades detection by the immune system through different mechanisms that involve both innate and adaptive immunity. Infection by HPV is not cytolytic, which refers to its ability to replicate and assemble within the keratinocyte without causing cell death.5 This crucial feature prevents an inflammatory response that may otherwise signal the immune system of the virus.6 Early viral proteins produced by HPV inhibit interferon secretion, an important antiviral mediator. Furthermore, evasion of the innate immune system leads to a delay in the activation of adaptive immunity, together enabling persistence of the HPV infection.5

eczema, warts

Why cimetidine works. Similar to injection treatments, such as intralesional interferon alpha and bleomycin, and topical agents, such as imiquimod and cantharidin, oral cimetidine stimulates an immunologic response to HPV.1 Cimetidine is an antagonist of type 2 histamine receptors. In addition to reducing acid secretion, research has shown it has immunomodulatory properties. Cimetidine exerts its effects on cutaneous warts by enhancing the cell-mediated immune response, necessary in the treatment of viral pathogens.7,8 Its influence on the immune system through these mechanisms theoretically is ideal to help eliminate the HPV infection.

This child was prescribed high-dose cimetidine, 40 mg/kg/d divided in 3 doses. At follow-up 3 months later, all the warts had resolved. 

Although the improvement in the lesions was remarkable in this case (A versus B), how effective cimetidine is in the treatment of warts is still a question.9 Open-label trials showing high complete response rates are confounded by the significant rate of spontaneous resolution of warts.1,3,9 Randomized trials comparing cimetidine treatment with placebo or active treatment have shown a lack of benefit; however, the results were complicated by inadequate dosing in some studies and lack of power analysis in others.9 Such an inexpensive, convenient, and low-risk treatment for a common condition in childhood merits additional investigation.