The first Aotearoa New Zealand case of NUDT15-variant-related thiopurine-induced myelotoxicity.

A 37-year-old Han Chinese man, with a history of severe ulcerative colitis with incomplete response to oral glucocorticoids, was commenced on azathioprine [AZA] 200mg once a day. His pre-treatment thiopurine S-methyltransferase [TPMT] levels were in the normal range. Eleven days later he developed symptoms of stomatitis and gingivitis. Chinese herbal medications were taken in an attempt to treat these symptoms. He presented to the emergency department with this, with normal vital signs. A full blood count five days post-onset of symptoms showed pancytopenia with an absolute neutrophil count [ANC] of 0.0x10(9)/l, C-reactive protein was 120 mg/L. Initial chest radiograph, urinalysis and peripheral blood cultures were unremarkable and he was commenced on broad spectrum antibiotics and granulocyte colony stimulating factor [G-CSF]. He remained an inpatient under the gastroenterology team for 16 days and developed infectious complications of herpes simplex stomatitis, oral candidiasis, dental abscess, and scalp abscess. On day 16 his ANC recovered to 1.0x10(9)/L and was discharged from the hospital. He underwent nudix hydrolase 15 [NUDT15] genotyping and was found to have homozygosity for the variant NUDT15:c.415C>T. This case demonstrates the importance of pre-treatment testing for NUDT15 genetic variants, to predict the risk of severe leucopaenia, particularly in a patient of East Asian ethnicity.