Bone marrow inhibition induced by azathioprine in a patient without mutation in the thiopurine S-methyltransferase pathogenic site: A case report

Abstract

BACKGROUND

Azathioprine (AZA) and its close analog 6-mercaptopurine are thiopurines widely used in the treatment of patients with cancer, organ transplantation, and autoimmune or inflammatory diseases, including systemic lupus erythematosus. Bone marrow inhibition is a common side effect of AZA, and severe bone marrow inhibition is related to decreased thiopurine S-methyltransferase (TPMT) activity.

CASE SUMMARY

We herein report a patient with proliferative lupus nephritis who was using AZA for maintenance therapy, had no common TPMT pathogenic site mutations, and exhibited severe bone marrow inhibition on the 15^th day after oral administration.

CONCLUSION

This report alerts physicians to the fact that even though the TPMT gene has no common pathogenic site mutation, severe myelosuppression may also occur.

Keywords: Azathioprine; Thiopurine S-methyltransferase; Bone marrow inhibition; Lupus nephritis; Case report

Core Tip: Thiopurine S-methyltransferase (TPMT) gene polymorphism testing alone cannot fully predict the occurrence of azathioprine (AZA) adverse reactions such as bone marrow inhibition and alopecia. According to the literature mentioned above, nucleoside diphosphate-linked moiety X motif 15 (NUDT 15) and inosine triphosphate pyrophosphatase (ITPA) gene polymorphism tests should also be performed to predict the occurrence of AZA adverse reactions and further guide initial medication. On the other hand, AZA should be used with caution, and whole blood examination and liver and kidney function should be closely monitored during the entire treatment with AZA regardless of the status of TPMT, NUDT 15, and ITPA single nucleotide polymorphisms.