enalapril and Acantholysis

Enalapril is a widely used antihypertensive drug with a very powerful in vitro acantholytic effect. It has been known to potentially induce pemphigus in genetically predisposed subjects. The action mechanism is complex and still only partially understood. We describe the case of a 66-year-old man, affected with intermediary basal cell carcinoma, in whom the histological examination showed suprabasal acantholytic clefts in the perilesional epidermis. Surprisingly a second biopsy taken from the apparently healthy skin of his back confirmed the presence of acantholytic changes. Clinical signs of pemphigus were absent. The patient's history did not reveal any relevant data but a mild arterial hypertension that had been treated for 1 year with 10 mg enalapril. Taking into account the patient's history (enalapril long-term administration), the absence of any bullous or erosive lesions and the histological findings, a diagnosis was made of in vivo enalapril-induced acantholysis.

Topics: Acantholysis; Aged; Angiotensin-Converting Enzyme Inhibitors; Diagnosis, Differential; Enalapril; Humans; Male

The factors that contribute to a preferential anatomic localization of pemphigus lesions are not well known. In particular, the question arises as to whether certain skin areas may be more acantholysis-prone than others.. To verify whether, in pemphigus patients, a different susceptibility to acantholysis exists among different cutaneous regions, the technique of tissue cultures was used.. Normal human skin explants from two distinct anatomic regions (back and buttocks) of two former pemphigus patients were cultured in vitro in the presence of enalapril (6 mM) or cystamine (10 mM), two substances with a proven biochemical acantholytic effect. After 4 days of culture, the tissues were processed for standard histology.. Diffuse acantholysis, with large intraepidermal splits, was observed in the explants taken from the backs of both subjects and cultured with either enalapril or cystamine. Mild to moderate acantholytic changes were detected in the explants taken from the buttocks of both subjects and cultured with either enalapril or cystamine. No structural changes were seen in the control cultures.. Pemphigus patients present different thresholds of acantholysis in different areas of their bodies. This might explain, at least in part, certain preferential anatomic localizations of pemphigus lesions.

Topics: Acantholysis; Adult; Angiotensin-Converting Enzyme Inhibitors; Back; Buttocks; Culture Techniques; Cystamine; Enalapril; Enzyme Inhibitors; Female; Humans; Pemphigus; Skin

The loss of intercellular cohesion among keratinocytes (acantholysis) may be considered the histologic marker of pemphigus. Many drugs, especially thiol drugs, proved to be able to provoke in vitro acantholysis by biochemical mechanisms interfering with the disulfide and thiol group balance. As to nonthiol drugs, the pathomechanism of acantholysis is still unexplained.. To explain the molecular mechanism of enalapril-induced acantholysis a potential link between transglutaminase (TGase) activity and the effects of this drug was investigated.. TGase activity in extracts from human breast skin cultured in the presence of thiopronine, captopril and enalapril were evaluated in vitro. The acantholytic potential of cystamine, a known TGase inhibitor, was also investigated.. Enalapril, the most powerful acantholytic drug in vitro, was found to inhibit both the purified enzyme and the TGase activity in the extracts from cultured human breast skin explants. Kinetic studies showed that enalapril inhibition was competitive with respect to the amino acceptor substrate and uncompetitive with respect to the amino donor substrate. Moreover, an acantholytic effect of cystamine on explants of normal human skin was shown.. These results suggest that acantholysis and the inhibition of TGase activity could be two related phenomena.

Topics: Acantholysis; Angiotensin-Converting Enzyme Inhibitors; Binding, Competitive; Biochemical Phenomena; Biochemistry; Breast; Captopril; Cell Adhesion; Cells, Cultured; Cystamine; Disulfides; Enalapril; Enzyme Inhibitors; Humans; Keratinocytes; Pemphigus; Skin; Sulfhydryl Compounds; Tiopronin; Transglutaminases

Drugs containing sulfhydryl groups (thiol drugs) (e.g., penicillamine, captopril, thiopronine) can induce pemphigus in vivo and provoke acantholysis in vitro. Enalapril, like captopril, is an angiotensin-converting enzyme (ACE) inhibitor largely used as an antihypertensive drug; it has recently been reported to induce pemphigus, though it is not a thiol drug. In this study we investigated the possible in vitro acantholytic effect of enalapril on normal human skin from donors. The drug induced severe acantholytic changes of keratinocytes and complete suprabasal splitting at one tenth the concentration required by thiol drugs in similar experiments, even after a shorter period of culture. All skin samples from different donors was highly susceptible to the acantholytic effect of enalapril. In our experience, enalapril is the most powerful acantholytic drug in vitro.

Topics: Acantholysis; Captopril; Culture Techniques; Enalapril; Female; Humans; Immunoglobulin G; Penicillamine; Skin; Time Factors; Tiopronin; Tissue Survival