[Epidermal necrolysis: mechanisms of keratinocyte apoptosis].
Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute and severe adverse reaction to drugs, characterized by the widespread destruction of the epithelium of the skin and mucous membranes. This destruction by massive apoptosis leads to a clinical pattern of epidermal necrolysis resembling second degree burns, with sheets of necrotic epidermis detached from the underlying dermis. The mechanisms of acute and extensive destruction of the skin are not yet fully understood. At the onset of the reaction blisters develop from the fluid that accumulates between the dead epidermis and the dermis. High concentrations of mononuclear cells are present in this blister fluid, principally CD8 T-lymphocytes that may exhibit a drug specific MHC class I restricted cytotoxicity against autologous cells. The intervention of soluble mediators such as TNFalpha, perforin/granzyme, or Fas-Ligand may be necessary for amplifying the apoptosis of keratinocytes. A strong association between epidermal necrolysis to certain drugs and rare HLA-B genotypes suggests that direct interaction between these drugs and HLA-B molecules may initiate a reaction resembling the acute rejection of allogeneic epidermis.
Roujeau
Jean-Claude
JC
Service de Dermatologie et Inserm U.659, Hôpital Henri Mondor, Université Paris XII, Faculté de Médecine, 8, rue du Général Sarrail, 94010 Créteil Cedex, France. jean-claude.roujeau@hmn.ap-hop-paris.fr
Gélard
Kristel
K
Bensussan
Armand
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053222:Fas Ligand Protein; D015235:HLA-B Antigens / Q000276:immunology; D006801:Humans; D015603:Keratinocytes / Q000276:immunology / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000502:physiology; D013262:Stevens-Johnson Syndrome / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D048069:Tumor Necrosis Factors / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015235:HLA-B Antigens; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D019014:fas Receptor