gms | German Medical Science

Objective: Azathioprine is an immunosuppressive drug effective in post transplantation therapy, remission of inflammatory bowel disease (IBD) and other autoimmune diseases. Pancreatitis is a rare adverse effect (≥ 1/1000, <1/100) and occurs mainly in patients with IBD. In this case report we present an azathioprine-induced pancreatitis in a patient with myasthenia gravis proven by positive rechallenge and integrate results from a PubMed and FDA adverse event reporting system (FAERS) based review.

Methods: Patient data were collected in the Berlin Case-Control Surveillance Study for adverse drug reactions (FAKOS). Literature based review was performed with PubMed on azathioprine-induced pancreatitis. The research in the FAERS database included azathioprine-induced pancreatitis in the years 2012 until 2014.

Results: A 32-year-old woman with myasthenia gravis was treated with azathioprine for 3 weeks when she was admitted with acute gastroenteritis, abdominal pain and elevated lipase (>4-fold above the upper limit of normal (ULN), 297 U/l). Seven days after the withdrawal of azathioprine and initiation of a glucocorticoid therapy the lipase level decreased (83 U/l). As the drug-induced etiology of the lipase increase in the first event was uncertain and in order to medicate adequately the myasthenia gravis the therapy was restarted with azathioprine. A re-exposure with a single dose of azathioprine provoked abdominal pain and ultrasonic examination demonstrated an edematous pancreas. Blood examination showed leukocytosis, an elevation of pancreatic amylase (> 5-fold above ULN, 316 U/l) and lipase (> 20-fold above ULN, 1716 U/l). Seven days later enzyme levels declined (amylase < 54U/l, lipase 186 U/l) and the pancreas morphology was normalized. According to the WHO criteria, the presented positive rechallenge implicates a certain causality of the azathioprine-induced pancreatitis. Between 2012 and 2014, three cases of azathioprine-associated pancreatitis were listed in the FAERS database: two patients with IBD and one patient with a lung disorder. PubMed research retrieved case reports and case series mostly in IBD but not in myasthenia gravis.

Conclusion: Azathioprine-induced pancreatitis is a rare adverse effect and the pathomechanism is unknown. An earlier publication showed a different safety profile of azathioprine in various diseases with a higher incidence of pancreatitis in IBD [1]. Nevertheless, Crohn’s disease was identified as independent risk factor for thiopurine treatment induced adverse events [2]. Our case report emphasizes the general association between azathioprine intake and pancreatitis.