A recent update of pharmacogenomics in drug-induced severe skin reactions

Drug Metab Pharmacokinet. 2012;27(1):132-41. doi: 10.2133/dmpk.dmpk-11-rv-116. Epub 2011 Nov 1.


In some adverse drug reactions (ADRs), genetic predisposition plays a significant role in pathogenesis, and the skin is the most frequently reported target. These severe cutaneous ADRs include bullous fixed drug eruptions (FDE), acute generalized exanthematous pustulosis (AGEP), drug-induced hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). The putative contribution of individual effector cells in drug hypersensitivity is briefly mentioned. To trigger these drug hypersensitivities, certain class I HLA alleles (e.g., HLA-A and HLA-B alleles) and certain class II HLA alleles (e.g., HLA-DR alleles) have been recently found to be the genetic determinants. One of the best characterized examples mentioned in this article is HLA-B*1502 to determine the incidence of carbamazepine-induced SJS. How drugs are processed and presented by these HLA alleles to activate immune responses has been explained by several hypotheses. Further implication of pharmagenomic findings to prevent drug-induced severe skin reactions can be achieved by pre-screening putative risk HLA alleles before using drugs.

Publication types

  • Review

MeSH terms

  • Acute Generalized Exanthematous Pustulosis / chemically induced
  • Acute Generalized Exanthematous Pustulosis / genetics
  • Acute Generalized Exanthematous Pustulosis / metabolism
  • Acute Generalized Exanthematous Pustulosis / prevention & control
  • Drug Eruptions / genetics*
  • Drug Eruptions / immunology
  • Drug Eruptions / metabolism*
  • Drug Eruptions / prevention & control
  • HLA Antigens / genetics*
  • HLA Antigens / metabolism*
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Pharmacogenetics / methods*
  • Polymorphism, Genetic*
  • Severity of Illness Index
  • Stevens-Johnson Syndrome / chemically induced
  • Stevens-Johnson Syndrome / genetics
  • Stevens-Johnson Syndrome / immunology
  • Stevens-Johnson Syndrome / metabolism
  • Stevens-Johnson Syndrome / prevention & control


  • HLA Antigens