Epidermal Necrolysis: 60 Years of Errors and Advances

Y.K. Heng; H.Y. Lee; J.-C. Roujeau

Disclosures

The British Journal of Dermatology. 2015;173(5):1250-1254. 

In This Article

Mediators of Keratinocyte Apoptosis

Various mediators have been proposed previously including tumour necrosis factor (TNF)-α,[19] TNF-related apoptosis inducing ligand (TRAIL),[19] perforin/granzyme,[17,20] Fas-ligand[21] and more recently granulysin.[18]

The Fas-ligand theory was propagated based on two premises. Firstly, activated keratinocytes expressed Fas-ligand. Secondly, when sheets of epidermis from patients with EN were applied to Jurkat cells (a lymphocyte cell line that was very sensitive to apoptosis via Fas-ligand), apoptosis of these Jurkat cells occurred.[21] Although in that same study, human immunoglobulins inhibited the apoptosis of Jurkat cells, both the ability of Fas-ligand to induce keratinocyte apoptosis as well as the effectiveness of human intravenous immunoglobulin (IVIG) to block keratinocyte apoptosis in vitro has never been proven.

Through the work of Chung et al.,[18] it is now known that the key mediator of apoptosis in SJS/TEN is granulysin. It has been demonstrated that granulysin was the most highly expressed cytotoxic molecule with concentrations in blister fluids of two to four orders higher than other mediators previously reported such as perforin, granzyme B and soluble Fas ligand. In addition, granulysin also killed target cells in vitro, depletion of granulysin reduced the cytotoxicity and similar EN blisters were observed when it was injected into the skin of normal mice at concentrations observed in blisters of patients. In that same study, Fas ligand was detected at very low levels.

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