Stevens-Johnson syndrome and toxic epidermal necrolysis.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, but potentially life threatening, diseases characterized by widespread epidermal necrosis, and are predominantly medication-induced. Unfortunately, though they are often associated with long-term debilitating sequelae, there are currently no efficacious pharmaceutical interventions proven through large clinical trials. It has been well established that the epidermal damage in these diseases is due to keratinocyte apoptosis. Although drug-specific T cells are implicated in this process, our understanding of the immunopathology is far from complete. The scenario suggested by today's literature points towards drug-specific CD8+ cytotoxic T cells utilizing perforin/granzyme B trigger keratinocyte apoptosis. Subsequently, there may be an expansion of apoptosis involving the interaction of either membrane-bound or soluble Fas ligand (sFasL) with its receptor Fas. The cellular source of sFasL remains controversial, with both peripheral lymphocytes and keratinocytes themselves as potential candidates. Cytokines produced by T lymphocytes, macrophages or keratinocytes may participate by activating keratinocytes and enhancing their expression of Fas and FasL, or by promoting the skin recruitment of lymphocytes by upregulating adhesion molecules. A better understanding of the underlying immunological mechanisms is required to identify appropriate therapeutic interventions. Finally, clinicians must remain vigilant about drug hypersensitivity to prevent SJS/TEN.
Borchers
Andrea T
AT
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616, United States.
Lee
Jennifer L
JL
Naguwa
Stanley M
SM
Cheema
Gurtej S
GS
Gershwin
M Eric
ME
D000818:Animals; D006801:Humans; D013262:Stevens-Johnson Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology* / Q000401:mortality / Q000473:pathology