Generalized urticaria with use of diphencyprone in the treatment of warts

Journal of Drugs in Dermatology, May, 2007 by Brittney L. Culp, Michael J. Wells

Abstract

Generalized urticaria is an adverse and serious side effect of diphencyprone. We report a case in order to advise of the possibility of associated type I hypersensitivity reaction (urticaria), which could progress to a more severe or life-threatening adverse reaction.

Introduction

Contact allergens are a subcategory of topical immunotherapy agents used for the treatment of various dermatoses. After sensitization, these drugs, which include diphencyprone, squaric acid dibutyl ester, and dinitrochlorobenzene, induce an allergic contact dermatitis with continued intermittent application. (1) We report a rare complication of generalized urticaria that accompanied the use of diphencyprone.

Case Report

A 15-year-old Caucasian female presented with 10 verrucae ranging from 3 to 18 mm on both hands, which had persisted for 10 years. Previous treatment included over-the-counter salicylic acid plaster, liquid nitrogen, and cantharidin without significant improvement. We then sensitized the patient with 1% diphencyprone in acetone in a 1-[cm.sup.2] area on the right, medial, upper arm. The 0.1% diphencyprone was then applied to each wart. The sensitized and treated areas were covered, and the patient was instructed to keep them covered for 24 to 48 hours. Upon follow-up, the patient appeared with a 35-mm eczematous plaque with slightly yellow crusting on the sensitization site, and 0.1% diphencyprone treatment was repeated to the sites of verrucae only. Within 2 weeks, the patient reported pain and swelling only at the location of the re-treated verrucae.

Over-the-counter oral diphenhydramine HC1 and naproxen sodium were used without any relief. Clinically, crusted eczematous plaques surrounding bullae at sites of treatment were noted (Figure 1). We encouraged continued use of nonsteroidal anti-inflammatory agents (NSAIDs) and prescribed cephalexin. Five days later, the patient presented to the emergency room with a worsening urticarial eruption that was spreading over the arms, legs, and back. The patient was given oral diphenhydramine HCl, oral famotidine, and solumedrol by intramuscular injection. When we saw the patient, she complained of urticaria (Figure 2a) affecting the posterior arms and forearms accompanied by a marked dermatographism on the dorsal surface of the right, upper arm (Figure 2b). Crusted, red plaques surrounded the previously treated warts. She denied any dyspnea, dizziness, or mucosal swelling. Fexofenadine, hydroxyzine HC1, and triamcinolone 0.1% cream were prescribed. The patient's mother noted much improvement with the use of NSAIDs and fexofenadine. Within 3 weeks, the urticaria had resolved with discontinuation of diphenhydramine treatment.

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Discussion

Generalized urticaria has been listed as an uncommon adverse affect elicited by contact allergens. While most literature relates the urticaria reaction to diphencyprone treatment for alopecia areata, there are a small number of reports of such a reaction with lower dosages used in viral wart treatment. (2,3) NSAIDs can cause acute urticaria; however, we do not feel this was the cause of our female patient's urticaria as the urticaria improved while the use of NSAIDs was continued. We must also consider that the urticaria could be due to an allergic reaction to cephalexin. However, we have previously witnessed a similar reaction to the same agent used to treat verrucae in an adolescent male. In this case, the urticarial eruption occurred without any administration of antibiotics. His first eruption of urticaria was mild and resolved rapidly, but the second occurrence, following re-treatment with diphencyprone, was more lasting and associated with transient, mild wheezing due to bronchospasms. Diphencyprone use was discontinued and the urticaria resolved. Complications with contact allergens also include localized contact eczema, regional lymphadenopathy, vitiligo, (4) leukoderma, erythema multiforme, (5) and contact urticaria. Many of these complications have been related to the dosage amount in other reviews. (6) We were unable to find any published reports of more severe reactions such as angioedema, bronchospasms, or anaphylaxis associated with the use of these agents, but we are concerned about this possibility as noted by the male patient described.

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References

1. Lin A. Topical immunotherapy. In: Comprehensive Dermatologic Drug Therapy. Wolverton S, ed. United States: W B Saunders Co; 2001:607-630.

2. Lane PR, Hogan DJ. Diphencyprone. J Am Acad of Dermatol. 1988; 19:364-365.

3. Short KA, Higgins EM. Urticaria as a side-effect of diphencyprone therapy for resistant viral warts. Br J Dermatol. 2005;152:583-585.

4. Hatzis J, Gourgiotou K, et al. Vitiligo is a reaction to topical treatment with diphenycprone. Dermatologica. 1988;177:137-138.

5. Perret CM, Steijlen PM, Zaun H, Happle R. Erythema multiforme-like eruptions: a rare side effect of topical immunotherapy with diphenylcyclopropenone. Dermatologica. 1990;180:5-7.