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Azathioprine toxicity in neuromuscular disease

Department of Neurology, Ohio State University School of Medicine (Drs. Kissel and Mendell), Columbus, OH, and the University of Rochester School of Medicine (Drs. Levy and Griggs), Rochester, NY.

Azathioprine toxicity was examined in 64 consecutively treated patients with various neuromuscular diseases. Reversible leukopenia was seen in 14 patients (22%). Hepatotoxicity developed in six patients (9%), and a systemic reaction characterized by fever, abdominal pain, nausea, vomiting, and anorexia occurred in eight patients (12%). Toxic effects limited the dose of azathioprine in 27 patients (42%) and led to discontinuation of therapy in 13 (20%). Macrocytosis developed in 20% of patients, but did not require an adjustment in the dose. Two patients received allopurinol and azathioprine; both developed reversible leukopenia and macrocytosis. Patients with hematologic and hepatic toxicity, but not those with systemic toxicity, successfully tolerated retreatment with azathioprine. Toxicity was delayed as long as 56 weeks after starting azathioprine in some patients.

Address correspondence and reprint requests to Dr. Kissel, Department of Neurology, Ohio State University School of Medicine, Columbus, OH 43210.

Dr. Kissel is the recipient of a Muscular Dystrophy Association research fellowship.

Accepted for publication May 8, 1985.

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