enalapril and Pemphigus

To identify patients examined in the Mayo Clinic Department of Dermatology whose pemphigus was attributable to an angiotensin-converting enzyme inhibitor and to compare these cases with previously reported cases of drug-induced pemphigus.. A retrospective review of medical records revealed two cases of captopril-induced pemphigus and one of enalapril-induced pemphigus. Our patients had substantially increased circulating IgG autoantibodies to intercellular substance, as detected on monkey esophagus substrate.. Our findings contrast those of other reports of drug-induced pemphigus in which circulating autoantibodies are implied to be low or absent.

Topics: Aged; Autoantibodies; Captopril; Enalapril; Female; Humans; Male; Middle Aged; Pemphigus; Retrospective Studies; Skin

Traditionally, drugs that are capable of inducing pemphigus are divided into two main groups according to their chemical structure, in particular, the existence of a sulfhydryl group in their molecule. Thus, two groups are formed: (1) drugs containing a sulfhydryl radical (thiol drugs or SH drugs) and (2) nonthiol or other drugs. Much emphasis has been put on the role of the sulfhydryl group in the pathogenesis of drug-induced pemphigus. The effects of this group have been extensively studied, and a logical paradigm on the mode of its action has been created. However, no attempt has been made to search for other biochemical radicals which might have an influence on the activation/triggering of this disease. The aim of the present report is to draw attention to a chemical group common to the molecule of several drugs that have been associated with the induction of pemphigus. Careful analysis of the chemical structure of nonthiol drugs known to induce pemphigus revealed that several of them share an active amide group in their molecule. We believe that this group might be responsible for the induction of the disease; thus, a third group of drugs capable of triggering pemphigus can be formed, namely drugs containing an active amide group. Several drugs of this group are discussed.

Topics: Amides; Cephalosporins; Enalapril; Humans; Pemphigus; Penicillins; Sulfhydryl Compounds

Pemphigus lesions appeared in a 58-year-old man who was taking captopril for his hypertension. Drug withdrawal resulted in complete remission of the eruption. The subsequent use of enalapril as an antihypertensive agent caused a recurrence of pemphigus lesions along with onset of itching and dermographism. Intercellular antibodies were not found. Discontinuance of enalapril therapy had no effect on the clinical course. Steroid treatment was needed to resolve the eruption. Recently repeated immunofluorescent studies disclosed intercellular IgG antibodies in the serum at a low titer. Pemphigus induction could be initially related to the thiol acantholytic property of captopril. Subsequent production of intercellular antibodies and drug-activation of the kinin system could be responsible for relapsing.

Topics: Anti-Inflammatory Agents; Captopril; Enalapril; Humans; Male; Middle Aged; Pemphigus; Pregnenediones; Recurrence

Pemphigus foliaceus is a blistering autoimmune disease related to the production of autoantibodies against desmoglein 1. We present a patient with psoriasis and pemphigus foliaceus aggravated by enalapril and amlodipine intake, with successful response of both conditions to adalimumab therapy.. El pénfigo foliáceo es una enfermedad autoinmune ampollosa debida a la producción de autoanticuerpos frente a la desmogleína 1. Presentamos el caso de un paciente con psoriasis y pénfigo foliáceo agravado por enalapril y amlodipino, con buena respuesta de ambas patologías a la terapia con adalimumab.Pemphigus foliaceus is a blistering autoimmune disease related to the production of autoantibodies against desmoglein 1. We present a patient with psoriasis and pemphigus foliaceus aggravated by enalapril and amlodipine intake, with successful response of both conditions to adalimumab therapy.. El pénfigo foliáceo es una enfermedad autoinmune ampollosa debida a la producción de autoanticuerpos frente a la desmogleína 1. Presentamos el caso de un paciente con psoriasis y pénfigo foliáceo agravado por enalapril y amlodipino, con buena respuesta de ambas patologías a la terapia con adalimumab.

Topics: Adalimumab; Amlodipine; Anti-Inflammatory Agents; Antihypertensive Agents; Enalapril; Humans; Male; Middle Aged; Pemphigus; Psoriasis

Captopril is an angiotensin-converting enzyme inhibitor with sulphydryl groups in its chemical structure. It is commonly used as an antihypertensive drug. The occurrence of pemphigus vulgaris has repeatedly been reported in patients receiving captopril. The capacity of captopril and pemphigus serum to induce acantholysis, in vivo or in vitro, has been demonstrated experimentally.. To show that captopril and pemphigus serum, acting by a biochemical and immunological mechanism, respectively, trigger apoptosis.. Human keratinocyte cells were treated with 15 mmol L-1 captopril or with pemphigus serum. DNA was extracted and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling method was used to detect apoptosis.. DNA fragmentation occurred after 72 h of treatment. Increased expression of p53, c-myc and inducible nitric oxide (NO) synthase (iNOS) mRNA were observed by polymerase chain reaction (PCR) in the treated cells compared with the untreated ones. The increase in iNOS gene expression was associated with overproduction of NO. Moreover, the addition of 1 mmol L-1N-monomethyl-L-arginine, a structural analogue of arginine, reduced nitrite levels by about 70% in cells treated with captopril or pemphigus serum. Western blot analysis revealed an overexpression of heat shock protein 70 (hsp70) in cells treated with captopril or pemphigus serum. Finally, total inhibition of the keratinocyte transglutaminase gene was shown by PCR analysis in the same samples, compared with control cells.. These data demonstrate the involvement of apoptosis in keratinocytes treated with captopril or pemphigus serum, with induction of the iNOS gene and hsp70 in the cascade of events leading to programmed cell death.

Topics: Angiotensin-Converting Enzyme Inhibitors; Apoptosis; Autoantibodies; Blotting, Western; Captopril; Cells, Cultured; Culture Media, Conditioned; Cytoskeleton; DNA Fragmentation; Dose-Response Relationship, Drug; Enalapril; Enzyme Activation; HSP70 Heat-Shock Proteins; Humans; Keratinocytes; Microscopy, Fluorescence; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitrites; Pemphigus; Proto-Oncogene Proteins c-myc; Reverse Transcriptase Polymerase Chain Reaction; Transglutaminases; Tumor Suppressor Protein p53

Topics: Administration, Topical; Aged; Betamethasone; Enalapril; Follow-Up Studies; Humans; Hypertension; Male; Pemphigus; Psoriasis; Risk Assessment; Severity of Illness Index; Treatment Outcome

Topics: Antihypertensive Agents; Child; Enalapril; Humans; Hypertension; Male; Oral Ulcer; Pemphigus; Severity of Illness Index

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

Topics: Enalapril; Esophageal Diseases; Humans; Laryngeal Diseases; Male; Middle Aged; Pemphigus

Pemphigus vegetans, a rare form of pemphigus vulgaris, consists of vegetating plaques localized to flexural areas. Two types, the Neumann and the Hallopeau type, are recognized with their own characteristics.. Three patients with pemphigus vegetans were examined, two with Hallopeau type and one with Neumann type. The microscopic and immunofluorescence findings were recorded.. Two remarkable features were present. In one case pemphigus vegetans was possibly induced by the use of enalapril. Only in three previous cases has enalapril been described in relation to pemphigus. A second case was associated with a malignant lung tumor, a phenomenon which could not be traced in the literature.. Two types of pemphigus vegetans must be distinguished. Induction of pemphigus (also vegetans) is an accepted side effect of captopril. The effect of enalapril on pemphigus is still in debate. To the best of our knowledge, this is the first time that a patient with pemphigus vegetans and a simultaneously occurring internal malignancy is described.

Topics: Aged; Atenolol; Carcinoma, Squamous Cell; Enalapril; Eosinophils; Female; Humans; Lung Neoplasms; Lymphocytes; Male; Middle Aged; Mouth Diseases; Pemphigus

Topics: Enalapril; Female; Humans; Immunoglobulin G; Middle Aged; Pemphigus