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Azathioprine (AZA)-induced leukopenia is a common but life-threatening complication of inflammatory bowel disease. Recent studies have found an association between leukopenia and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) mutation in the Asian population. A 26-year-old Caucasian woman with Crohn’s disease presented with severe neutropenia after initiating AZA treatment. While genetic testing did not detect any thiopurine S‐methyltransferase (TPMT) mutations, sequencing of NUDT15 showed R139C homozygous mutation. The absolute neutrophil count normalised following discontinuation of AZA treatment and initiation of granulocyte-colony stimulation factor administration. NUDT15 R139C mutation can be used as a predictive factor for AZA-induced leukopenia in both European and Asian populations. The association between TPMT mutations and AZA-induced leukopenia is well established. However, TPMT mutations are less common among Asian patients than among Caucasian patients. The correlation between single-nucleotide mutations in NUDT15 and leukopenia during thiopurine administration was recently demonstrated. The variant allele frequency of NUDT15 is 10–20% in Asians in contrast to 0.4% in Caucasians. Recent studies have showed that AZA treatment of patients with homozygous mutations should be avoided. Moreover, further research is needed to determine the optimal dosage for patients with heterozygous mutations. Some studies have suggested that pre-treatment genotyping can reduce myelosuppression, the number of outpatient visits, and healthcare-associated costs. NUDT15 variant R139C is a strong predictor of thiopurine-induced neutropenia to a greater extent in individuals of Asian descent than in those of Caucasian descent. Therefore, it is recommended to perform NUDT15 genotyping before initiating AZA treatment.

A rare case of Azathioprine-induced leukopenia in an European woman