Severe megaloblastic anaemia associated with abnormal azathioprine metabolism

Severe anaemia is a rare, unexplained, side effect of azathioprine therapy. We report here such a case associated with a previously unreported abnormality in azathioprine metabolism. A 57 year old man on azathioprine therapy, for a presumed collagen vascular disease, developed severe megaloblastic anaemia. This resolved on cessation of azathioprine treatment. A very high concentration of an azathioprine metabolite, 6-thioguanine nucleotide, was found in the patient's red blood cells and this was confirmed by subsequent rechallenge with a single dose of 50 mg azathioprine.