Drug-induced toxic epidermal necrolysis (TEN) and acute cutaneous graft-versus-host reaction (GVHR) under immunopreventive therapy share some histopathological resemblance. So far, there are no serum biomarkers and no immunohistochemical criteria distinguishing with confidence and specificity the skin lesions of TEN and GVHR. Both diseases present as an inflammatory cell-poor necrotic reaction of the epidermis. This report compares three sets of 15 immunostaining patterns found in TEN, GVHR, and partial thickness thermal burns (PTTB), respectively. Three series of 17 skin biopsies were scrutinized. Irrespective of the distinct causal pathobiology of TEN and GVHR, similar secondary effector cells were recruited in lesional skin. Burns were less enriched in cells of the monocyte-macrophage disease. These cells likely exert deleterious effects in TEN and GVHR and cannot be simply regarded as passive bystanders. These life-threatening conditions are probably nursed, at least in part, by macrophages. 1. Introduction Toxic epidermal necrolysis (TEN), formerly called under its eponym Lyell’s syndrome, is a severe cutaneous adverse reaction (SCAR) to drugs [1]. Conceptually, both TEN and the Stevens-Johnson syndrome (SJS) are likely part of the same continuum of clinical presentations [2–6], and they are regarded to be likely distinct from erythema multiforme [7–9]. The precise TEN pathomechanism remains unclear [1, 5, 10–12]. Some toxic metabolites and/or cytotoxic inflammatory cells induce epithelial apoptosis and necrosis [5, 13–15]. Cytotoxic lymphocytes, regulatory T cells (Treg), macrophages, and dermal dendrocytes (DD) are likely involved, and they probably represent more than passive bystanders [16–20]. Graft-versus-host reaction (GVHR), both in its acute and chronic stages, is responsible for both potentially severe morbidity and mortality [21, 22]. GVHR remains quite frequent in susceptible groups of patients as about half of recipients of allogeneic hematopoietic cell transplantation (HCT) develop GVHR [23–25]. This condition results from a complex and intricate pathobiology sustained by interactions between the donor and host innate and adaptive immune responses. A number of lymphocyte subsets (naive, memory, Treg, Th1, Th17, NK,？…) are involved, as well as eosinophils, mesenchymal stem cells and the monocyte-macrophage lineage including Factor XIIIa+ DD [26–30]. There is an overlap in a series of histopathological signs between early GVHR and various other posttransplantation diseases including some viral exanthems, immune reconstitution rash, and
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