Medline ® Abstract for Reference 63

PURPOSE OF REVIEW: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe adverse drug reactions. Once thought to be idiosyncratic and unpredictable, there has been significant progress made in the understanding of the pathomechanism and pharmacogenetics of such reactions. These advances together with their clinical implications will be elaborated in this review.

RECENT FINDINGS: It is now known that the human leukocyte antigen (HLA) association in SJS/TEN is more than just a genetic marker and has a functional role as well. This reaction is mediated by cytotoxic T lymphocytes (CTLs) in an HLA-restricted fashion. Certain drugs may bind directly to the HLA complex and facilitate the development of self-reactivity due to drug-modified HLA-peptide repertoire. The role of the drug-specific T cells and their T-cell receptors has also been clarified. Downstream cytotoxic signals have been elucidated with granulysin, a cytotoxic protein produced by CTLs or natural killer cells deemed to be the key mediator in the reaction.

SUMMARY: Pharmacogenetic screening of HLA alleles prior to drug initiation has already been shown useful in the prevention of such reactions. The other advances in the disease mechanism will form the basis for better preventive and therapeutic strategies.