Severe myelosuppression and alopecia after thiopurine initiation in a patient with NUDT15 deficiency

Abstract

Thiopurines are a class of immunosuppressant and antineoplastic agents. They are widely used in the treatment of inflammatory bowel disease, haematological malignancies and autoimmune diseases, but can cause significant toxicity. Inherited gene mutations are now recognized as independent risk factors for severe adverse drug reactions to thiopurines even at 10-fold dose reductions. We present a case of thiopurine toxicity resulting in severe myelosuppression, hepatotoxicity and alopecia in an individual with homozygous *3/*3 loss-of-function alleles in the NUDT15 gene. Our case highlights important differences in gene mutation frequencies between races that can help guide pharmacogenomic testing.