Advances in Clinical Pharmacogenomics and Prevention of Severe Cutaneous Adverse Drug Reactions in the Era of Precision Medicine

Abstract

Severe cutaneous adverse drug reactions (SCARs), including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but severe life-threatening adverse drug reactions. Although their incidence is rare, the mortality rates are as high as 10% for DRESS, 1–5% for SJS and 25–50% for TEN. Recent studies have suggested that HLA genes are associated with SCARs during treatment with causative medicines. The HLA gene is located on chromosome 6p21.1–21.3 and consists of HLA class I, II and III. Interestingly, HLA-pharmacogenomic markers influence these mechanisms of immunopathogenesis in culprit drug-induced SCARs. However, due to genetic differences at the population level, drug-induced SCARs are varied; thus, the specific pharmacogenomic markers for ethnicity might differ among populations. For instance, the HLA-A*31:01 allele is associated with carbamazepine-induced SCARs in Europeans and Japanese individuals, while the HLA-B*15:02 allele is associated with carbamazepine-induced SJS-TEN among Thais, Han Chinese, Taiwanese and Southeast Asians populations. Such differences pose a major challenge to preventing SCARs. Therefore, knowledge of the pharmacogenomics, mechanisms of immunopathogenesis and ethnic-specific genetic variation related to drug-induced SCARs is needed.