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Azathioprine toxicity during long-term immunosuppression of generalized myasthenia gravis

From the Department of Neurology (Drs. Hohlfeld, Michels, Heininger, and Toyka), University of Düsseldorf, and the Department of Neurology (Dr. Besinger), Technische Universitát, Munich, West Germany.

In this uncontrolled study, 104 patients with generalized myasthenia gravis treated with azathioprine for a median period of 29 months (range, 1 month to 12 years) were surveyed for possible adverse reactions. These occurred in 36 patients (35%) in the following order of frequency: hematologic (18%), gastrointestinal (13%), infectious diseases (13%), and elevation of liver enzymes (6%). No allergic skin reactions were observed. Azathioprine had to be discontinued temporarily in a total of 11 patients (11%) because of possible side effects. The cause of death in the nine patients who died during the period of observation (up to 12 years) was related to myasthenic crisis in two patients. In five patients, a malignant tumor was diagnosed (two carcinoma of the prostate, one ovarian carcinoma, one bronchial carcinoma, and one renal lymphoma) after 2. 5 years, 6 months, 3 months, 5 years, and 6 years of treatment, respectively. A causal relationship seems unlikely in the first four cases, but cannot be excluded in the one case of late lymphoma.

Address correspondence and reprint requests to Dr. Toyka, Neurologische Universitätsklinik, Moorenstr. 5, 4000 Düsseldorf 1, West Germany.

Received December 8, 1986. Accepted for publication in final form May 18, 1987.

Supported in part by Deutsche Forschungsgemeinschaft, To 61, 1 and SFB 200, B5. R. H. is recipient of a Heisenberg Fellowship from the Deutsche Forschungs-gemeinschaft.

Presented in part at the VIIth International Conference on Myasthenia Gravis, New York, NY, March 1986.

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