Severe necrotizing cutaneous reaction to topical 5-fluorouracil

Introduction

5-Fluorouracil (5-FU) is a cytotoxic agent that has been used systemically, topically and intralesionally for the treatment of many malignant and pre-malignant conditions. Topical chemotherapy with 5% 5-FU cream has been used as a standard treatment of actinic keratosis, superficial basal cell carcinomas and Bowen′s disease.[1],[2],[3] It has also been used successfully in viral warts prior to curettage.[4] 5-FU is highly specific in action and is believed to be well tolerated by normal skin. We report a case where topically applied 5-FU used for the treatment of warts led to severe localized cutaneous necrosis.

Case Report

A 30-year-old healthy married male presented with severe pain, burning and cozing over his right hand following two applications of 5-FU 5% cream for the treatment of warts. Cutaneous examination revealed lesions of verruca vulgaris surrounded by blackish necrotic skin and an erythematous halo. Dorsum of the hand was diffusely swollen and tender [Figure - 1]. No regional lymphadenopathy was observed and systemic examination was normal. Haemogram, serum biochemistry, chest radiograph, urine and stool examination were within normal limits. He was diagnosed to have a local necrotizing reaction to 5-FU and was treated with a topical corticosteroid cream (betamethasone dipropionate 0.05%) and ciprofloxacin 500-mg twice daily for a week. Necrotic lesions healed in one week′s time leaving behind active lesions of warts which were treated later with electrocautery.

Discussion

Fluorouracil is a phrimidine antimetabolite that produces its toxic destructive effects by interfering with ribonucleic acid and deoxyribonucleic acid synthesis.[5] Its specificity of action relates directly both to the metabolic rate of the cells exposed to it and the extra cellular and intracellular concentration attained.6 In warts, the presence of papilloma virus causes an increase in the rate of division of epidermal cells while 5-FU inhibits cell proliferation and restricts spreading of the virus.[4] Goncalves and Hursthouse have shown extensive use of 5-FU for the therapy of warts.[7],[8]

The inflammatory reaction that occurs in the skin following therapy with topical 5-FU remains a teratment disadvantage. Other side effects reported after topical 5-FU administration include hyperpigmentation, hypopigmentation, allergic contract sensitization, photosensitivity, a tendency to conceal an underlying cancer, onycholysis, onychodystrophy, telangiectasia and hypertrophic scarring.[2]

The selective cytotoxicity of fluorouracil, with a limited inflammatory reaction in grossly normal skin is what makes this therapy unique.[2] The impermeability of normal human skin usually protects it from the toxic effects of topical 5-FU. Although Zelickson et al[9] have demonstrated mild histological and ultramicroscopical changes in 5-FU treated normal skin, only about 6% of 5-FU is absorbed from glabrous skin which is insufficient to induce visible effects.[1] Enhanced absorption of 5-FU i.e. in skin folds, under occlusion and from special sites like scrotum[6] may result in acute dermatitis over normal skin but in our patient none of these factors were present. The severe cutaneous necrosis and intense inflammation of the surrounding normal skin in our patient could be due to allergic contact dermatitis or may be similar to the ′field effect′ of topical 5-FU observed in solar keratosis. Severe cutaneous necrosis to topical 5-FU as occurred in our patient has not been reported to the best of our knowledge.