“Two‐step” Pemphigus Induction by Ace‐inhibitors

Abstract

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.

In vivo Enalapril-Induced Acantholysis

“…Enalapril is known to induce pemphigus in some subjects [2, 3, 4]. The acantholytic potential of this drug, a non-thiol antihypertensive ACE inhibitor, has repeatedly been proven in vitro [1, 6, 7].…”

“…It has been known to potentially induce pemphigus in genetically predisposed subjects [2, 3, 4]. The complex and still only partially understood action mechanism seems to be correlated with an inhibitory interference of the drug with keratinocyte-aggregating enzymes [4, 5, 6, 7]. …”

Pemphigus Variant Associated With Penicillin Use

“…12,13 Previous studies suggested that a number of different medications can induce pemphigus variants. These can be categorized into the following 3 main groups: (1) drugs containing a sulfhydryl radical, such as penicillamine 14 or captopril (an angiotensin-converting enzyme inhibitor) 15 ; (2) masked thiols that contain an S molecule and can be converted to a thiol, such as penicillin 16,17 ; and (3) nonthiol or other drugs such as cephalosporins. 18 It has been postulated that, in a case of an abortive form of pemphigus induced by protracted penicillin treatment, the probable trigger was actually penicillamine, which was formed by the metabolic breakdown of the penicillin molecule.…”

“…We examined all purchases of medications that were previously associated with pemphigus 15,16,19,20 during the 6 months before the date that the pemphigus was first diagnosed. These medications included penicillins, cephalosporins, angiotensinconverting enzyme inhibitors, dipyrone, phenobarbiturate, topical anti-inflammatory drugs, and nonsteroidal antiinflammatory medications.…”

Precautions and Suggestions for Pemphigus Patients

“…As mentioned before, these widely prescribed antihypertensive agents (table 3) are capable of inducing pemphigus independently from the thiol group that features their progenitor captopril [17, 18, 19, 20, 21]. In particular, enalapril, a nonthiol drug, which in vitro shows an acantholytic potential tenfold greater than captopril [22], can in vivo induce true pemphigus [19]or even a subclinical form of the disease [23].…”