Association of , and Phenytoin-Induced Cutaneous Adverse Drug Reactions in the South Indian Tamil Population.

Phenytoin (PHT) is one of the most commonly reported aromatic anti-epileptic drugs (AEDs) to cause cutaneous adverse reactions (CADRs), particularly severe cutaneous adverse reactions (SCARs). Although human leukocyte antigen is associated with PHT-induced Steven Johnson syndrome/toxic epidermal necrosis (SJS/TEN) in East Asians, the association is much weaker than it is reported for carbamazepine (CBZ). In this study, we investigated the association of pharmacogenetic variants of the HLA B gene and with PHT-CADRs in South Indian epileptic patients. This prospective case-controlled study included 25 PHT-induced CADRs, 30 phenytoin-tolerant patients, and 463 (HLA-B) and 82 () normal-controls from previous studies included for the case and normal-control comparison. Six SCARs cases and 19 mild-moderate reactions were observed among the 25 cases. Pooled data analysis was performed for the and PHT-CADRs associations. The Fisher exact test and multivariate binary logistic regression analysis were used to identify the susceptible alleles associated with PHT-CADRs. Multivariate analysis showed that was significantly associated with overall PHT-CADRs (OR = 12.00, 95% CI 2.759-84.87, = 003). In subgroup analysis, and were found to be associated with PHT-SCARs (OR = 12.45, 95% CI 1.138-136.2, = 0.003) and PHT-maculopapular exanthema (MPE) (OR = 4.041, 95% CI 1.125-15.67, = 0.035), respectively. Pooled data analysis has confirmed the association between /PHT-SCARs (OR = 6.273, 95% CI 2.24-16.69, = <0.001) and PHT-overall CADRs (OR = 2.323, 95% CI 1.22-5.899, = 0.037). In this study, neither the case nor the control groups had any patients with . The risk variables for PHT-SCAR PHT-overall CADRs, and PHT-MPE were found to be and , respectively. These alleles were identified as the risk factors for the first time in the South Indian Tamil population for PHT-CADRs. Further investigation is warranted to establish the clinical relevance of these alleles in this population with larger sample size.