Induction of Acantholysis in Organ Explant Culture by Penicillamine and Captopril

Abstract

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.

Pemphigus vulgaris: environmental factors. Occupational, behavioral, medical, and qualitative food frequency questionnaire

“…5,6 Other observations indicate that certain drugs have the potential to induce and possibly sustain pemphigus, and these are supported by laboratory studies in organ explant cultures. 7,8 Certain environmental factors also induce acantholysis in vitro. 9 The phenomenon of antigenic diversi®cation or epitope spreading occurs in pemphigus.…”

In vitro tannin acantholysis

“…The minimal concentrations required by tannic acid to provoke in vitro acantholysis (0.1–2.0 m m ) were notably lower than those required by other acantholytic agents, such as penicillamine and captopril (10–20 m m ) 9,10 . Therefore, the tannin acantholytic potential is at least tenfold greater than that of the drugs tested previously.…”

“…The experimental model described in the present study has previously been utilized to investigate the local direct effects of certain drugs on skin explants. 6–10 In the present study, it was employed to assess the effects of tannic acid following suggestions of a possible role of tannins in pemphigus, and their well‐known multiple modes of action 1,3 , 4 . Tannic acid showed a generic toxic effect on skin tissue cultures, as denoted by (i) intracellular edema of keratinocytes (vacuolar degeneration) with areas of reticular degeneration; (ii) edema of the papillary dermis (dermal microvacuolization); (iii) intraepidermal and rare subepidermal detachments; (iv) collagen fragmentation; and (v) necrosis at the highest concentrations.…”

Lesion topography in two cases of nifedipine‐related pemphigus

“…The most common culprits of drug-induced pemphigus contain an active thiol group, such as penicillamine and captopril [3], and lesion distribution most often corresponds to that seen in pemphigus foliaceus with the histologic pattern of subcorneal acantholysis. The most common culprits of drug-induced pemphigus contain an active thiol group, such as penicillamine and captopril [3], and lesion distribution most often corresponds to that seen in pemphigus foliaceus with the histologic pattern of subcorneal acantholysis.…”