Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin.
Toxic epidermal necrolysis (TEN, Lyell's syndrome) is a severe adverse drug reaction in which keratinocytes die and large sections of epidermis separate from the dermis. Keratinocytes normally express the death receptor Fas (CD95); those from TEN patients were found to express lytically active Fas ligand (FasL). Antibodies present in pooled human intravenous immunoglobulins (IVIG) blocked Fas-mediated keratinocyte death in vitro. In a pilot study, 10 consecutive individuals with clinically and histologically confirmed TEN were treated with IVIG; disease progression was rapidly reversed and the outcome was favorable in all cases. Thus, Fas-FasL interactions are directly involved in the epidermal necrolysis of TEN, and IVIG may be an effective treatment.
Department of Dermatology, Geneva University Medical School, CH-1211 Geneva 4, Switzerland.
I
I
Viard
P
P
Wehrli
R
R
Bullani
P
P
Schneider
N
N
Holler
D
D
Salomon
T
T
Hunziker
J H
JH
Saurat
J
J
Tschopp
L E
LE
French
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019138:Antibodies, Blocking / Q000276:immunology / Q000627:therapeutic use; D017209:Apoptosis; D002648:Child; D020405:Dermis / Q000473:pathology; D018450:Disease Progression; D004817:Epidermis / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D019169:Jurkat Cells; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D010865:Pilot Projects; D013262:Stevens-Johnson Syndrome / Q000473:pathology / Q000628:therapy*; D019014:fas Receptor / Q000276:immunology / Q000502:physiology*
D019138:Antibodies, Blocking; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016756:Immunoglobulins, Intravenous; D008562:Membrane Glycoproteins; D019014:fas Receptor