Relation of thiopurine S-methyltransferase genotype and phenotype (serum enzyme level) with azathioprine-related toxicity in a sample of Egyptian patients with immunobullous diseases

Background Azathioprine (AZA) is a commonly used steroid-sparing agent to treat various inflammatory conditions, including immunobullous diseases. Objective To evaluate thiopurine S-methyltransferase (TPMT) enzyme level by enzyme-linked immunosorbent assay and TPMT genotype by PCR, and to assess the correlation between TPMT enzyme level and genotype with AZA-related toxicity in Egyptian patients with immunobullous diseases. Patients and methods This was a prospective observational cohort study that included 69 patients with immunobullous diseases. Serum TPMT enzyme level was assessed using enzyme-linked immunosorbent assay for phenotyping, while common inactivating alleles (TPMT*2, TPMT*3 A, and TPMT*3C) were identified through allele-specific-PCR and PCR-restriction fragment length polymorphism genotyping. After initiating AZA therapy, patients were followed for adverse drug reactions, with evaluations conducted at baseline, 1 month, and 3 months. Results Of the 56 patients who completed the study, 28.6% developed AZA-related toxicity. Incidence of cytopenias increased from 4.5% at 1 month to 7.1% at 3 months, while hepatotoxicity rose from 16.4 to 23.2% over the same period. TPMT testing revealed that 72.5% had normal enzyme levels, 24.6% had low levels, and 2.8% had high levels, with only wild-type TPMT*2, TPMT*3A, and TPMT*3C variants identified. Conclusion TPMT enzyme level and genotyping were not reliable predictors of AZA-related toxicity. Emphasizing the importance of close clinical and laboratory monitoring of patients after initiation of AZA.