Generalized pustular eruptions associated with oral terbinafine.

An active 62-year-old man with noninsulin-dependent diabetes and chronic tinea pedis and tinea unguium developed a painless neurotrophic foot ulcer. His medical history was significant for mild hypercholesterolemia, chronic obstructive pulmonary disease, and long-term tobacco and alcohol use. Oral medications were Glyburide, Glucophage, Zestoretic, gemfibrozil, and aspirin, all of which had been administered daily for at least 8 months. There was no personal or family history of skin disease. After the ulcer failed to respond to conventional therapy, including wound care, debridement, and oral antibiotics, oral terbinafine was prescribed, 250 mg/day, for dermatophytosis-impaired wound healing. After 44 days of terbinafine therapy, the patient developed a generalized, erythematous, maculopapular, pruritic eruption accompanied by fatigue and chills. He denied cough, arthralgias, dizziness, hematuria, or exposure to anyone ill. Despite instructions to stop taking the medication, the patient erroneously continued to take terbinafine. One week later, he was referred to our institution. Physical examination revealed a nontoxic appearing middle-aged man with diffuse, confluent, erythematous plaques studded with pustules, lakes of pus, and crusted erosions and a fever of 38.9 °C ( Figs 1 and 2). Palms, soles, and mucous membranes were unaffected, and the groin was relatively spared. Toenails exhibited yellow–white discoloration, subungual debris, and onychauxis. Fingernails were normal. Lymphadenopathy was absent. A 1.3 cm by 1.7 cm superficial, painless ulcer without significant undermining was present on the left sole over the first metatarsophalangeal joint. There was decreased sensation from the toes to the midleg. Pedal pulses were palpable. Figure 1. Extensive pustular eruption of acute onset involving the trunk and extremities Download figure to PowerPoint Figure 2. Erythematous plaques, pustules, lakes of pus, and crusted erosions Download figure to PowerPoint Laboratory analyses revealed elevated white blood cell count (10.7 × 103 μL) with 11% eosinophils. Electrolytes, renal, thyroid, and liver function tests, urinalysis, and sedimentation rate were normal. A skin biopsy specimen showed an intraepidermal, spongiotic, vesiculopustular dermatitis with a superficial, perivascular, mixed inflammatory cell infiltrate of lymphocytes, neutrophils, and scattered eosinophils ( Figs 3 and 4). A periodic acid–Schiff stain was negative for fungi. Figure 3. Vesiculopustular dermatitis with diffuse superficial perivascular infiltrate (original magnification, ×10) Download figure to PowerPoint Figure 4. Subcorneal neutrophilic pustule, perivascular infiltrate of mononuclear cells, neutrophils, and occasional eosinophils (original magnification, ×40) Download figure to PowerPoint Terbinafine was stopped, but all other medications were continued. Hydrotherapy, twice-daily triamcinolone ointment, and a prednisone taper from 60 mg to 0 mg over 3 weeks were initiated. In 4 days, there was complete resolution of the fever and pustulosis and a significant reduction of the erythema. At 40 days, mildly pruritic, erythematous plaques persisted on the trunk and extremities. The temporal relationship strongly suggested terbinafine as the inciting agent in this patient. Oral provocation test was not performed due to unacceptable patient risk.