Immunoregulatory effector cells in drug-induced toxic epidermal necrolysis

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 387+ monocytes and macrophages), UCLHI (mainly CD45R0+ T-memory lymphocytes), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFalpha). 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 XIIIa+ dendrocytes were abundant and plump in the dermis, although Mac 387+ macrophages were the most numerous inflammatory cells in the epidermis. Their numbers greatly exceeded those of CD45R0+ T lymphocytes and cells showing immunoreactivity for either IL-6 or TNFalpha. In the epidermis, IL-6+ cells were significantly less numerous than TNFalpha+ cells. No quantitative difference was found between IL-6+ and CD45R0+ cell populations. Correlations were observed between either the numbers of TNFalpha+ cells or Mac 387+ macrophages and CD45R0+ lymphocytes. In the dermis, a significant correlation was also present between the numbers of Mac 387+ and factor XIIIa+ cells. These findings highlight the complex interactions between the inflammatory cells that mediate epidermal damage in skin with TEN. The high density of factor XIIIa+ dendrocytes and Mac 387+ macrophages in lesional skin assigns these cellular populations a prominent role in the pathomechanism of TEN. Despite a lower cell density, CD45RO+ T-memory lymphocytes likely participate in TNFalpha- and IL-6-regulated processes in the epidermis of TEN. TNFalpha seems to be a major cytokine involved in TEN, although a less prominent role can be ascribed to IL-6.