Azathioprine-induced neuro-psychiatric disorders

摘要

Neurologic and neuropsychiatric complications are uncommon in the setting of inflammatory bowel disease and even less common as a treatment adverse event. A 38 year old male presented with a ten year history of ileocolonic and perianal Crohn's disease without extra-intestinal manifestation. He underwent ileocolonic resection for small bowel obstruction within the first year of diagnosis without post-operative treatment. He relapsed 7 years later. Reluctant to immunosuppressive medication, he was first treated with steroids, antibiotics as well as alternative treatments that were ineffective with occurrence of a penetrating ileo-colitis 3 years after disease recurrence. Combination therapy with infliximab and azathioprine was initiated. Thiopurine methyltransferase enzyme activity was normal at a level of 28.3 EU. One month later, the patient complained having forgetfulness, confusion, memory loss and communication difficulty, as well as the onset of behavioral disorders such as leaving home at night. Brain magnetic resonance imaging described a generalized atrophy with dilatation of the cortical sulk and ventricles without mass, hemorrhage, acute infarction or abnormal contrast enhancement. There was no finding suggesting demyelinating process. The posterior fossa structures including brainstem and cerebellum were normal as well as those of the skull base and calvarium. A neurologic workup did not find significant findings. Biology did not reveal any azathioprine toxicity on liver enzyme or abnormal white and blood count cells. The patient had no drug illicit consumption. Infiximab was continued, azathioprine was stopped and the neurological symptoms resolved. One month after azathioprine withdrawal, immunosuppressive intake was resumed with 6-mercaptopurine which led to the recurrence of the same neuro-psychiatric disorders without additional neurological findings, that again resolved after 6-mercapturine withdrawal.