Pathogenesis and recent therapeutic trends in Stevens-Johnson syndrome and toxic epidermal necrolysis.

OBJECTIVE: To review the current pathophysiologic mechanisms and recent therapeutic trends in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

DATA SOURCES: A MEDLINE search for SJS and TEN in combination with Fas, Fas ligand (FasL), cytotoxic T cells, intravenous immunoglobulin, and cyclosporine for articles published in English during 1966 to 2006.

STUDY SELECTION: Information was derived from original research articles and reviews published in peer-reviewed journals.

RESULTS: The hallmark of SJS and TEN is epidermal cell apoptosis, which may be mediated through keratinocyte Fas-FasL interaction or through cytotoxic T-cell release of perforin and granzyme B. Whereas systemic corticosteroid therapy showed contradictory results, intravenous immunoglobulin (IVIG) and cyclosporine have shown promising outcomes. IVIG contains anti-Fas antibodies that can abrogate apoptosis when preincubated with keratinocytes. Most studies on IVIG in SJS and TEN reported improvement in arresting disease progression and reduction in time to skin healing. Because of variations among studies, the findings cannot be optimally compared. In general, mortality varied from 0% to 12% in studies that supported the use of IVIG and 25% to 41.7% in those that did not demonstrate a beneficial effect. Cyclosporine inhibits CD8 activation and thus may reduce epidermal destruction. Relatively few case reports and 1 case series have been published regarding the use of cyclosporine in SJS and TEN. In general, cyclosporine was associated with a significant improvement in time to disease arrest and to complete reepithelization, with no reported fatalities.

CONCLUSIONS: Both IVIG and cyclosporine have been associated with enhanced healing and better survival through inhibition of apoptosis. Multicenter, randomized, placebo-controlled trials using a standardized design are needed to validate these findings.