Genetic associations of human leukocyte antigen alleles in cutaneous delayed drug hypersensitivity reactions: An updated review

• DOI: 10.4103/ds.ds-d-23-00082
• Publication Date: 2023-12-29T19:00:07Z
• Authors: Chun-Bing Chen; Chih-Chun Lee; Chuang-Wei Wang; Wei-Kai Hung; Wen-Hung Chung
• Keywords: Abacavir; Toxic Epidermal Necrolysis; Pharmacogenomics

Abstract Cutaneous delayed drug hypersensitivity reactions (DHRs) are common iatrogenic events with potentially life-threatening consequences. Delayed DHRs encompass diverse phenotypes and can be classified by their distinct T-cell responses to antigens. Interaction between the immune receptors, human leukocyte antigen (HLA) receptor (TCR), complementary antigenic peptide is required for development of DHRs. These idiosyncratic interactions elicited formation drug-protein adducts (hapten hypothesis) or from direct drugs receptors (pharmacological interaction concept, altered repertoire model, TCR model). In addition, viral infections may play a role providing co-stimulatory signals enhancing TCR/HLA expression on T-cells. The associations HLA allele polymorphisms phenotype ethnicityspecific. discovery genetic associated has provided strategy prevent diagnose reactions. Recently, advances in next-generation sequencing technologies, such as incorporation whole-exome whole-genome sequencing, enabled comprehensive detection susceptibility loci. Several have shown clinical utility cost-effectiveness, HLA-B*15:02 (carbamazepine-induced Stevens–Johnson syndrome/toxic epidermal necrolysis Han Chinese), HLA-B*58:01 (allopurinol-induced severe cutaneous adverse HLA-B*57:01 (abacavir Caucasians), HLA-B*13:01 (dapsone-induced reaction eosinophilia systemic symptoms Chinese). Herein, we summarize current knowledge pathogenesis, presentation models,