Epidermal calprotectin in drug-induced toxic epidermal necrolysis

Calcium ions (Ca++) in excess alter cell viability. Their potential role in drug-induced toxic epidermal necrolysis (TEN) was investigated. Thirteen T EN patients were biopsied at the site of early bullous lesions and on clini cally normal-looking skin at least 2 cm distant from blisters. Immunohistoc hemistry was applied using the mouse monoclonal antibody Mac 387 recognizin g the cytosolic protein complex L1 (calprotectin). The L1 antigen is a calc ium-binding protein expressed by human granulocytes, monocytes-macrophages and injured epidermis, but not by normal epidermis and other cells harboure d in the skin. The majority (8/13) of TEN samples from apparently non-invol ved skin expressed the L1 antigen in a patch-like pattern inside the epider mis where inflammatory cells were scant or absent. As assessed by computeri zed image analysis of TEN bullous skin, the intensity of the L1 expression in the epidermis was not statistically correlated with the amount of the in filtrating inflammatory cells (Mac 387+ macrophages, UCLH1+ T lymphocytes a nd Factor XIIIa+ dendrocytes) present in the dermis and in the epidermis. S uch findings suggest a key role for keratinocytes in the production of the L1 calcium-binding complex. As the L1 complex formation is a calcium-depend ent process, one of the first biological events in TEN could be a dramatic increase in keratinocytes intracellular Ca++ concentration following damage by the involved drug metabolites. The ultimate toxic cell dysregulation wo uld result from the disturbance in the intracellular Ca++ homeostasis.