Cutaneous adverse drug reactions: Stevens-Johnson syndrome and toxic epidermal necrolysis

Abstract

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous reactions caused by drugs or infections and exhibiting widespread epidermal necrosis. SJS/TEN might be a specific immune reaction initiated by cytotoxic T lymphocytes via an HLA-restricted pathway. Recent advances in pharmacogenomic studies have provided evidence for genetic predispositions to SJS/TEN. Toward explaining how drug-specific (immunological) reactions induce adverse drug reactions, several concepts have been proposed: in addition to the hapten concept and the p-i concept, there is the idea that drugs alter the antigen by binding to the HLA pocket. With regard to keratinocyte death, several cell death mediators, such as FasL and granulysin, have been proposed as playing a role in SJS/TEN pathogenesis. If SJS/TEN is simply the most extreme reaction on a spectrum of drug reactions, then regulating the immunological reaction could influence the severity of the adverse drug reaction. A subset of T lymphocytes, including regulatory T cells, also might play a role in SJS/TEN.