Stevens–Johnson syndrome due to prophylactic fluconazole in two patients with liver failure

Fluconazole is an antifungal drug used increasingly for the prevention of superficial and systemic fungal infections in immunosuppressed patients. It has been shown that fluconazole prophylaxis prevents colonization and invasive Candida infections in high-risk patients. We present two cases of Steven–Johnson Syndrome (SJS) triggered by fluconazole. Both patients had hepatic impairment and had been placed on fluconazole for candidiasis prophylaxis. Patient 1 was a 40-year-old woman who presented with a 5-day history of a rash and associated high fever, malaise, gritty eyes, dysuria and difficulty in eating. Prednisolone 20 mg once daily had been started 28 days previously for alcoholic hepatitis; fluconazole 100 mg once daily had been started 13 days previously. On physical examination, the patient was found to have confluent targetoid lesions and multiple erosions over the chest, back (Fig. 1a) and arms, extending onto the face and involving approximately 10% of the body surface area. She had oral and vulval erosions, and there was bilateral conjunctival injection. Histological examination of a skin biopsy showed an interface vacuolar dermatitis with necrotic keratinocytes. The extent of skin involvement in association with severe mucositis and the histology was in keeping with a diagnosis of SJS. Fluconazole was identified as the causative agent and was stopped. Patient 2 was a 23-year-old woman with autoimmune hepatitis, who presented with a maculopapular rash, associated with erosions, over the ankles and wrist and across the chest. She had dysuria and her eyes were gritty and painful. She had been started 16 days previously on prednisolone 20 mg once daily to treat her autoimmune hepatitis, and fluconazole 100 mg once daily for prophylaxis against candidiasis. On physical examination, erythematous targetoid lesions were found on the chest and back with a papular, erythematous rash on the arms. Haemorrhagic crusting was seen on the lips, there were erosions within the oral cavity and erythema of the gums (Fig. 2), and there was bilateral conjunctival injection. Erosions were seen on the labia minora. Histological examination of a skin biopsy showed an interface vacuolar dermatitis with necrotic keratinocytes consistent with erythema multiforme (Fig. 3a–b). Based on the biopsy findings and the clinical picture, a diagnosis of SJS was made. Fluconazole was thought to be the most likely trigger, with prednisolone modifying the presentation. In both cases, the patients were taking fluconazole and prednisolone concurrently. There have been reported cases of prednisolone causing SJS but in our patients prednisolone had previously been tolerated without problems and in both cases prednisolone was subsequently used as treatment for SJS. Fluconazole was identified as the most Figure 1 Patient 1. Confluent targetoid lesions across the back with superficial erosions. Viewpoints in dermatology • Correspondence