Azathioprine hypersensitivity-like reactions : a case report and a review of the literature

Azathioprine is used in a variety of dermatological conditions. However, because of its side-effect profile, azathioprine is limited for use in patients with severe disease. An unpredictable, rare and potentially fatal side-effect of azathioprine is the development of a hypersensitivity reaction, often consisting of fever, hypotension and oliguria. We describe a 17-year-old patient with leucocytoclastic vasculitis who was placed on azathioprine; within 15 days of start of therapy, she developed a fever. Azathioprine was discontinued and an evaluation for sepsis was undertaken; all cultures were negative and the fever abated. Azathioprine was restarted 5 days later. After a single dose, fever, nausea and vomiting, diarrhoea, hypotension, tachycardia and oliguria developed and the patient was admitted to an intensive care unit. Azathioprine was discontinued and investigations revealed no sign of an infection. All the above signs and symptoms abated within 24 h and the patient was discharged from hospital in 7 days. A review of 28 case reports in the literature of azathioprine-induced hypersensitivity reactions suggest that most commonly a fever and gastrointestinal symptoms occurred on initial presentation. In addition, a maculopapular rash, urticaria, vasculitis, erythema multiforme or erythema nodosum may occur. Hepatotoxicity and nephritis have also been reported. The aetiology of the reaction is unknown but sudden onset of fever and hypotension suggests that this reaction may be due to cytokine or mediator release induced by azathioprine. As azathioprine is metabolized to 6-MP, rechallenges to both should be avoided in patients who experienced an azathioprine hypersensitivity-like reaction.