Induction of acantholysis in organ explant culture by penicillamine and captopril.

Pemphigus is an autoimmune disease proved to be mediated by IgG autoantibodies. Skin lesions clinically and histologically identical to pemphigus may occur in patients receiving penicillamine and captopril, but some of these patients lack circulating or tissue-bound autoantibodies. Therefore, we examined the ability of these drugs to produce acantholysis directly in organ explant culture. Human skin explants were prepared from split-thickness graft skin from adults and from neonatal foreskins. Explants were cultured in media containing 0.1 to 200 mmol/L of penicillamine or captopril; parallel drug-free control cultures were also prepared. Acantholysis occurred in all split-thickness graft skin cultures incubated for 72 hours with at least 20 mmol/L of penicillamine and at 24 to 48 hours in those incubated with at least 10 mmol/L of captopril. Acantholysis occurred less frequently in foreskin cultures, being present in 1 (8%) of 12 of those exposed to at least 20 mmol/L of penicillamine and 3 (12%) of 25 of those exposed to at least 10 mmol/L of captopril. None of the parallel drug-free control cultures developed acantholysis. Subcorneal acantholysis, resembling that seen in pemphigus foliaceus, and suprabasilar acantholysis, resembling that seen in pemphigus vulgaris, were induced in vitro. Our results indicate that both drugs can act as ligands and produce acantholysis in organ explant culture in the absence of autoantibody. This ligand-induced acantholysis may also be responsible for induction of the disease in vivo in those patients who lack demonstrable autoantibodies.

Cutaneous pathology following etoposide therapy.

Etoposide (VP-16) is a semisynthetic podophyllotoxin derivative that is active against a number of solid and hematologic malignancies. Previously reported cutaneous complications include Stevens-Johnson syndrome and radiation recall. We report 4 cases of cutaneous eruptions with distinctive histopathologic changes following etoposide therapy. Diffuse erythematous macules and papules developed 5-9 days after initiation of etoposide therapy and resolved spontaneously within 3 weeks. Histologic examination revealed epidermal maturation disturbances with scattered markedly enlarged individual keratinocytes. These cells had pale cytoplasms and fragmented, haphazardly dispersed nuclear chromatin in a starburst pattern ("starburst cells"). Many keratinocytes showed notable nuclear enlargement with multiple prominent nucleoli. In addition, numerous dyskeratotic cells and basilar mitotic figures in metaphase were present. Some of these changes have been described in condylomata acuminata treated with topical applications of podophyllin, a compound structurally related to etoposide. Starburst cells have not been reported in cutaneous eruptions produced by other chemotherapeutic agents. These cells may represent abnormal mitotic arrest secondary to podophyllin and its related compounds.