Toxic epidermal necrolysis (TEN) is a rare drug-induced disease for which the pathomechanism remains poorly understood. The effector cells of epidermal injury in TEN were studied by taking skin biopsies of early lesions in 23 TEN patients and by performing immunohistochemical tests using antibodies to factor XIIIa (type I dendrocytes), L1-protein (mainly Mac 387plus;monocytes and macrophages), UCLH1 (mainly CD45R0plus;T-memory lymphocytes), interleukin-6 (IL-6), and tumor necrosis factor-agr; (TNFagr;). Computerized image analysis was used to evaluate the cell density relative to each immunolabeling. A statistical analysis of cellular counts revealed a numeric relation between the cell types in skin with TEN. Factor XIIIaplus;dendrocytes were abundant and plump in the dermis, although Mac 387plus;macrophages were the most numerous inflammatory cells in the epidermis. Their numbers greatly exceeded those of CD45R0plus;T lymphocytes and cells showing immunoreactivity for either IL-6 or TNFagr;. In the epidermis, IL-6plus;cells were significantly less numerous than TNFagr;plus;cells. No quantitative difference was found between IL-6plus;and CD45R0plus;cell populations. Correlations were observed between either the numbers of TNFagr;plus;cells or Mac 387plus;macrophages and CD45R0plus;lymphocytes. In the dermis, a significant correlation was also present between the numbers of Mac 387plus;and factor XIIIaplus;cells. These findings highlight the complex interactions between the inflammatory cells that mediate epidermal damage in skin with TEN. The high density of factor XIIIaplus;dendrocytes and Mac 387plus;macrophages in lesional skin assigns these cellular populations a prominent role in the pathomechanism of TEN. Despite a lower cell density, CD45R0plus;T-memory lymphocytes likely participate in TNFagr;- andagr;-and IL-6ndash;regulated processes in the epidermis of TEN. TNFagr; seems to be a major cytokine involved in TEN, although a less prominent role can be ascribed to IL-6.
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