This study showed that distinct genetic markers were associated with phenotype-specific PHT-induced SCARs. Non-genetic factor, omeprazole co-medication, was strongly associated with PHT-induced DRESS/DHS in addition to variants in HLA-B and CYP2C genes. Combined markers may be better predictors for PHT-induced SCARs.

To develop a pre‐emptive genetic test that comprises multiple predisposing alleles for the prevention of phenytoin‐related severe cutaneous adverse reactions (SCARs), three sets of patients with phenytoin‐SCAR and drug‐tolerant controls from Taiwan, Thailand, and Japan, were enrolled for this study. In addition to cytochrome P450 (CYP)2C9*3, we found that HLA‐B*13:01, HLA‐B*15:02, and HLA‐B*51:01 were significantly associated with phenytoin hypersensitivity with distinct phenotypic specificities. Strikingly, we showed an increase in predictive sensitivity of concurrently testing CYP2C9*3/HLA‐B*13:01/HLA‐B*15:02/HLA‐B*51:01 from 30.5–71.9% for selecting the individuals with the risk of developing phenytoin‐SCAR in Taiwanese cohorts, accompanied by a specificity of 77.7% (combined sensitivity, 64.7%; specificity, 71.9% for three Asian populations). Meta‐analysis of the four combined risk alleles showed significant associations with phenytoin‐SCAR in three Asian populations. In conclusion, combining the assessment of risk alleles of HLA and CYP2C9 potentiated the usefulness of predictive genetic tests to prevent phenytoin hypersensitivity in Asians.

This is the first report of successful deferasirox administration, using graded challenge and treating through, in a patient with mild immediate hypersensitivity reaction. Beginning with drug graded challenges could indicate the eliciting dose and reaction severity which are important for the management plan in the next step. This approach could be a safe shortcut in a stable patient with a mild reaction and a long avoidance period.