Pemphigus and pemphigoid-like effects of nifedipine on in vitro cultured normal human skin explants

Background A variety of drugs have been implicated in the onset and exacerb ation of pemphigus and bullous pemphigoid. The demonstration of biochemical acantholysis in skin explants to various drugs in the absence of autoantib odies, in which the tested drugs evoke a biochemical reaction that leads to desmosomal function lass, may be a valuable adjunct to patient management by confirming the suspicion of drug-related pemphigus or bullous pemphigoid . Objective To determine whether a skin explant model might serve as a possib le in vitro correlate of drug-induced pemphigus and pemphigoid-like effects related to the calcium channel blocker nifedipine. Methods Normal human breast skin obtained from nonpemphigus and nonpemphigo id patients undergoing mastectomy was cultured with nifedipine at final con centrations of 2, 4, and 8 mM. The drug effect on skin explants evidenced b y morphologic changes was evaluated by microscopy by three observers. Results Five out of seven explants cultured with nifedipine at concentratio ns ranging from 2 to 8 mM exhibited obvious morphologic changes of two type s: intraepithelial (or pemphigus-type) splittings and subepithelial (or pem phigoid-type) splittings. Two explants showed no acantholysis and no subepi thelial splittings. Control cultures without polyethylene glycol 200 (PEG) showed no changes. Skin control samples cultured in medium supplemented wit h 10% PEG displayed vacuolar degeneration throughout the entire epidermis, but no sign of cell-cell dyshesion or dermo-epidermal detachment. Conclusions A type of skin susceptibility to nifedipine may be genetically determined, with some nifedipine-treated patients developing an acantholyti c reaction and others a subepidermal bullous eruption.