Immunohistochemical Expression of Apoptotic Markers in Drug-Induced Erythema Multiforme,Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Abstract

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered to be severity variants of the same disease, which is almost always associated with drug intake. In contrast, erythema multiforme (EM) is a disorder regarded as only rarely caused by drugs. Keratinocyte apoptosis has been shown to play an important part in the pathogenesis of SJS and TEN, whilst its role in EM remains controversial. To determine the expression of apoptosis-associated molecules Fas, Fas ligand (FasL), Bcl-2 and Bax in the above disorders, an immunohistochemical analysis was performed. We studied both lesional skin from thirty patients having drug-induced EM and 5 cases classified within the SJS/TEN spectrum and normal skin samples. We found a keratinocyte overexpression of Fas antigen, an important molecule mediating apoptosis, not only in SJS and TEN but also in EM. Another noteworthy finding was the strong expression of Bcl-2, a protein known as blocking apoptosis, along the basal layer and in the dermal infiltrate both in SJS/TEN and in EM. Taken together, these findings suggest that Fas-dependent keratinocyte apoptosis may play a part in the pathogenesis of both SJS/TEN and EM. Fas-mediated cell death may be partially suppressed by the Bcl-2 protein.