Azathioprine-induced toxoplasma gondii infection in a patient with Crohn's disease with NUDT15 variation

Abstract

Introduction: Azathioprine (AZA) has been widely used for the treatment of various immune-related diseases and has become a mainstay in the treatment of inflammatory bowel disease. However, patients with genetic mutations may experience severe adverse events when treated with azathioprine. Most of the previous literature focused on the TPMP gene-related adverse reactions, herein, we report a case of Crohn's disease patient with nucleoside diphosphate-linked moiety X motif 15 gene (NUDT15) variation and wild-type TPMP gene who developed toxoplasma gondii infection after azathioprine treatment. Patient concerns: A 56-year-old Crohn's disease patient developed toxoplasma gondii infection within 2 months after the administration of azathioprine; however, he had no relevant high-risk factors. Diagnosis: Subsequent genetic testing revealed that the patient was heterozygous for NUDT15. Therefore, it was reasonable to consider that the patient's genetic mutation resulted in reduced tolerance to azathioprine, leading to low immunity and eventually toxoplasma infection. Interventions: AZA was then discontinued; after anti-infection, antipyretic and other supportive treatments were administered, the patient's condition gradually improved. Outcomes: The patient was followed up at 1, 3, and 6 months after discharge; fortunately, he was in good health. Conclusion: We report a case of Crohn's disease in a patient who developed severe pneumonia caused by toxoplasma gondii infection due to the administration of AZA, with normal TPMP gene but NUDT15 gene mutation. This indicates that NUDT15 variation may contribute to severe adverse events in patients treated with azathioprine, and we suggest that NUDT15 genotype be detected before the use of azathioprine in order to provide personalized therapy and reduce side effects.