Severe Thiopurine-Induced Myelotoxicity and Hair Loss in Japanese Patients with NUDT15 Gene Variant: A Retrospective Case-Control Study

This study assessed the relationship between thiopurine-susceptible gene polymorphisms and adverse effects in adult Japanese patients with dermatological diseases. It found that the NUDT15 R139C variant was a significant genetic risk factor for azathiopurine (AZA)-induced severe myelotoxicity, including leukocytopenia, thrombocytopenia, agranulocytosis, febrile neutropenia, and rapid total hair loss. Two patients homozygous for NUDT15 R139C developed severe hematotoxicity within 2-4 weeks of AZA intake, while two heterozygous for ITPA 94C>A experienced no adverse events. The study concluded that routine gene screening for the NUDT15 variant is advisable to prevent severe thiopurine-induced adverse events in East-Asian populations.