Clinical relevance of Thiopurine methyl transferase genotype testing for azathioprine in dermatology.

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Polymorphisms in thiopurine methyltransferase (TPMT) are a predominant cause of azathiopurine-induced leukopenia in the Western countries. The exact role of these polymorphisms in Indian population with dermatological disorders is uncertain. We included consecutive patients on Azathioprine who were initiated for dermatological disorders from south India. Three TPMT polymorphisms (c.238 G > C, c.460 G > A, and c.719A > G) were assessed. A comparison of the proportion of adverse events to azathioprine, especially myelosuppression, was performed between those with wild-type genotype and those with TPMT polymorphisms. Of the 123 patients (61 males, mean age 46 years), 65% had autoimmune blistering disorder. Adverse event to azathioprine was noted in 25 (20.3%), of which 16 (13%) had myelosuppression, four (3.2%) each had hepatotoxicity and gastrointestinal intolerance. TPMT polymorphisms were detected amongst 13 (10.7%), of which five had experienced adverse events. The polymorphisms could explain 25% (4 out of 16) of the cases of leucopenia. The odds of developing leukopenia in TPMT polymorphism was not significant (3.63, 95% CI 0.96-13.60, p=0.055). The tested TPMT polymorphisms could not predict the adverse events, particularly the haematological toxicity of azathioprine in dermatological use among the south Indian population.