Angioedema: a rare and sometimes delayed side effect of angiotensin-converting enzyme inhibitors

Abstract

The effects of angiotensin converting enzyme (ACE) inhibitors result from the inhibition of the ACE (kininase II) to ultimately influence both the renin-angiotensin system and the degradation of the bradykinin (BK) metabolism. ACE inhibitors block the degradation of BK and substance P by ACE. In addition, an active metabolite of BK (Des-Arg9-BK) is catalysed by kininase I and its degradation is controlled in part by the conversion enzyme. These molecules have been associated with increased plasma extravasation associated with ACE inhibitors. ACE inhibitors are the leading cause of drug-induced Angioedema (AE). Symptoms of AE mainly occur after the first month of treatment by ACE. However, very late onset cases, sometimes after several years of stable therapy, are also described in the literature. It has been observed that patients previously stable under ACE inhibitor will most likely develop AE soon after the addition of another medication, including the combination of aspirin or non-steroid anti-inflammatory drugs with ACE inhibitor which has proved to be the most common cause, accounting for close to 50% of all AE cases related to ACE inhibitors. This side effect of ACE inhibitors, sometimes very late and rare, deserves to be recalled ARTICLE HISTORY

SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung

“…Transcripts encoding C1-Inhibitor were decreased 80-fold in BALF from COVID-19 patients (Table 1), raising the possibilities that contact activation-initiated thrombin generation is locally dysregulated and control of bradykinin production is compromised. Furthermore, the angiotensin converting enzyme (ACE) that degrades bradykinin (Cicardi and Zuraw, 2018;Davin et al, 2019) was downregulated 8-fold in COVID-19 BALF.…”

Common variants near the bradykinin receptor B2gene are associated with angioedema induced by angiotensin-converting-enzyme inhibitor treatment - a genome wide association study

“…The primary target of ACEi is the renin-angiotensin-aldosterone system, which results in decreased production of angiotensin II and leads to decreased aldosterone secretion, decreased vasopressin activity, and the favorable antihypertensive and cardiovascular effects that are seen in this drug class. [42] The mechanism of ACEi-associated angioedema is thought to be related to its role in the kallikrein-kinin system, an antagonistic counterpart to the renin-angiotensin-aldosterone system. Kallikrein is a protease that converts high-molecular-weight kininogens into kinins, primarily bradykinin.…”

Gastrointestinal involvement of primary skin diseases

“…Acquired angio-oedema related to angiotensin-converting enzyme inhibitor is bradykininergic and commonly seen within the first month of exposure, while a late onset, even after years of stable therapy, has been described. 44 In these cases, interaction with other medications such as aspirin, non-steroidal anti-inflammatory drugs and in particular oral contraceptives should be attended. 45 Angio-oedema induced by non-steroidal anti-inflammatory drugs can be IgE-or non-IgE-mediated and is histaminergic with urticaria and itch.…”

“…Hereditary angio‐oedema involves the GI tract more commonly and severely than the acquired form. Acquired angio‐oedema related to angiotensin‐converting enzyme inhibitor is bradykininergic and commonly seen within the first month of exposure, while a late onset, even after years of stable therapy, has been described 44 . In these cases, interaction with other medications such as aspirin, non‐steroidal anti‐inflammatory drugs and in particular oral contraceptives should be attended 45 .…”