Azathioprine toxicity during long‐term immunosuppression of generalized myasthenia gravis

Abstract

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.

Long-Term Results of Corticosteroid Therapy in Patients with Myasthenia Gravis

“…Azathioprine has been largely used and has proven to be highly effective either alone or in association with cor ticosteroids [16,17], Unfortunately, immunosuppressive therapy can also be responsible for serious side effects, and MG deteriorations are not uncommon at drug dis continuation [18,19].…”

Myasthenia Gravis – Current Treatment Standards and Emerging Drugs

“…Side effects of azathioprine consist in hepatotoxicity, myelo-suppression, potential carcinogenesis and teratogenesis, rarely alopecia and increased risk of lymphoma after longterm use (Herrllinger 2000). In 10-15% patients, an idiosyncratic allergy with rush, fever, nausea, vomiting and abdominal pain can occur (Hohlfeld 1988, Kissel 1986). …”

Ocular Myasthenia Analysis of Diagnostic and Treatment Options

“…Support for their use also derives from administration for the generalized disease, but these studies are also not robust. Azathioprine was demonstrated to reduce corticosteroid requirements in a randomized, placebo-controlled trial of generalized MG patients (Palace et al 1998), and retrospective analyses support its efficacy in OM patients (Mertens et al 1981;Matell 1987;Hohlfeld et al 1988;Mantegazza et al 1988). The clinician and the patient then need to consider immunosuppressant therapy, and here the evidence base relies on data from the generalized disease and expert opinion.…”