Drug-induced epidermal necrolysis: Important new piece to end the puzzle.

In 1956, Alan Lyell reported, under the denomination of toxic epidermal necrolysis, the cases of 4 patients with acute necrosis and detachment of the superficial layers of the skin and mucous membrane. Over the years, it became obvious that StevensJohnson syndrome, which is also characterized by blisters affecting the skin and mucous membrane, was close to toxic epidermal necrolysis, and these 2 conditions are now considered severity variants of an identical process differing only in the extent of body surface involved. Therefore it seems preferable to use a single designation encompassing Stevens-Johnson syndrome, toxic epidermal necrolysis, and overlapping forms: epidermal necrolysis or exanthematic necrolysis (EN). EN is rare, with about 1.5 to 2 cases per million inhabitants per year in most countries but about 3 times more cases in Taiwan. It is life-threatening, with an overall death rate close to 30% and ranging from 10% to 15% for Stevens-Johnson syndrome and 40% to 50% for toxic epidermal necrolysis.Most, but not all, cases (60% to 80%) are clearly related to an adverse drug reaction. For several decades, the physiopathology of ENwas considered a mystery. Pathology slides showed a totally necrotic epidermis above a ‘‘silent’’ dermis, without significant cellular infiltrate, vascular lesions, or immune deposits and fitting with none of the usual pathways of tissue destruction through inflammatory processes. In the past 30 years, knowledge has improved slowly, with acceleration in the last years. The larger part of these recent advances was provided by the Taiwanese team authoring an article in the present issue of the Journal. Important pieces of information were initially obtained by studying the skin blister fluid. T lymphocytes were actually found abundantly in these fluids, comprising mostly CD8 T cells and natural killer T cells. CD8 T cells extracted from the lesions were demonstrated to have classic cytotoxic functions: lysis of autologous lymphocytes or keratinocytes in an MHC class I–restricted and medication-dependent manner. Further investigations focused on the cytokines present in blister fluids, especially those inducing apoptosis. TNF-a, soluble Fas ligand,

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