Kinetics and Specificity of Fas Ligand Induction in Toxic Epidermal Necrolysis

Recent advances in the genetics and immunology of Stevens-Johnson syndrome and toxic epidermal necrosis

“…Viard et al reported that FasL distributes on the keratinocyte cell surface, and soluble FasL (sFasL) presented with a high level in the serum of TEN patients. A consistent finding of the increased sFasL expression after the onset of skin damage in TEN has been reported by Chang et al [51]. However, the proposed role of FasL in the induction of keratinocyte apoptosis in SJS/TEN was questioned by other studies.…”

Toxic epidermal necrolysis

“…116,117 The increased serum levels of sFasL observed in TEN patients may be caused by the action of MPs at the keratinocyte cell surface. 114 Consistent with this idea is a clinical observation made by Chang et al 118 Serum levels of sFasL from a 42-year-old male with antibiotic-induced TEN were measured daily. A marked rise in sFasL levels occurred approximately 24 to 48 hours after the onset of major skin damage.…”

“…A marked rise in sFasL levels occurred approximately 24 to 48 hours after the onset of major skin damage. 118 This observation suggests that sFasL does not cause keratinocyte apoptosis, but rather that it is a byproduct of FasL expressed by keratinocytes. Not all investigators have been able to duplicate Viard's model.…”

Severe Drug-Induced Skin Reactions: Clinical Pattern, Diagnostics and Therapy

“…Cytotoxic T cells can initiate apoptosis, exacerbated by the release of perforins, cytokines such as tumor necrosis factor-alpha (TNF-) and FAS-ligand. [Abe, et al, 2003, Chang, et al, 2004, Nassif, et al, 2004a, Nassif, et al, 2002 Recent findings demonstrate that secretory granulysin is a key molecule responsible for the disseminated keratinocyte death in SJS/TEN and highlight a mechanism for cytotoxic T lymphocyte-and natural killer cell-mediated cytotoxicity that does not require direct cellular contact. [Chung, et al, 2008] Granulysin concentrations in the blister fluids were two to four orders of magnitude higher than perforin, granzyme B or soluble FAS-ligand concentrations, therewith being the most highly expressed cytotoxic molecule.…”

“…[Chung, et al, 2008] It is also thought that proteins such as FAS-antigen (CD95) and p55-TNF--receptors promote keratinocyte apoptosis. [Abe, et al, 2003, Chang, et al, 2004, Viard, et al, 1998] In blister fluid obtained from patients with sulfonamide-induced TEN, it has been shown that the lymphocytes were only cytotoxic in the presence of cotrimoxazole or sulfamethoxazole, but not toward hydroxylamine metabolites of sulfamethoxazole. This is the first sign that lesional T lymphocytes exhibit a direct cytotoxic response towards autologous cells without prior re-stimulation.…”