Angiotensin-Converting Enzyme Inhibitor-Induced Non-allergic Perioral Angioedema: A Case-Based Scoping Review

Abstract

Patients with angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema (ACEIIA) may visit family physicians. The aim of this article was to describe a case of delayed-onset ACEIIA and to present a concise scoping review. Using a case report and a scoping review study design, we report a case of ACEIIA, with clinically confirmed diagnosis. The symptoms resolved after replacing the offending ACEI with another antihypertensive agent. After excluding other causes of perioral swelling and discontinuation of ACEI, the patient was symptom-free within a few days thereafter. Based on this case presentation, we performed a meta-narrative scoping review including up-todate diagnosis and management of ACEIIA, based on published data in English, French, and German from inception to April 1, 2021. Patients with angioedema of unknown origin should be cautiously examined to rule out oral diseases, including allergy to dental materials and drug-induced angioedema. Clinicopathological aspects and current treatment guidelines for ACEI-associated angioedema are also presented.

Keywords: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Oral Medicine; Review.

Figure. 1.

Clinical picture of the patient. The patient gave written consent for publication of his clinical data and image.

Figure. 2.

Mechanism of histamine- versus bradykinin-mediated angioedema [2,8-10,22,23]. TXA, tranexamic acid; HMWK, high-molecularweight kininogen; C1-INH, C1 esterase inhibitor; ACEIs, angiotensin-converting enzyme inhibitors; ACE, angiotensin-converting enzyme; NEP, neutral endopeptidase; APP, aminopeptidase; DPP-IV, dipeptidyl peptidase IV; , activation; , inhibition.

Figure. 3.

The 2019 French guideline on laboratory investigation of bradykininmediated angioedema according to the French National Centre of Reference for Angioedema (“Centre de Référence National des Angiœdèmes”; CREAK) [22]. HAE, hereditary angioedema. ^*C1 esterase inhibitor (C1-INH) measurement in patients on C1-INH or danazol therapy requires “drug-pause” interval 1 and 4 weeks before the test, respectively. ^† The test should be repeated, if the result shows 50%–60% of normal values.

Figure. 4.

The 2019 emergency care algorithm for treatment of adult drug-induced non-allergic angioedema patients with acute airway compromise proposed by the University Hospital of Ulm, Germany [20]. Drug regime 1: Prednisolon 250–1,000 mg i.v. + dimetindene 4–8 mg i.v. + ranitidine 50 mg i.v. + adrenaline 0.2–0.5 mg i.m.; Drug regime 2: C1 esterase inhibitor (C1-INH) concentrate Berinert 20 IU/kg i.v. or Icatibant 30 mg s.c. SaO₂, oxygen saturation; ACEIs, angiotensinconverting enzyme inhibitors; ICU, intensive care unit; IMC, intermediate medical care ward; i.v., intravenous; i.m., intramuscular; s.c., subcutaneous.