Over diagnosis of bradykinin angioedema in patients treated with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers

Marie Douillard; Zineb Deheb; Agathe Bozon; Nadia Raison-Peyron; Olivier Dereure; Lionel Moulis; Angèle Soria; Aurélie Du-Thanh

doi:10.1016/j.waojou.2023.100809

Over diagnosis of bradykinin angioedema in patients treated with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers

World Allergy Organ J. 2023 Aug 19;16(8):100809. doi: 10.1016/j.waojou.2023.100809. eCollection 2023 Aug.

Authors

Marie Douillard¹, Zineb Deheb², Agathe Bozon¹, Nadia Raison-Peyron¹, Olivier Dereure¹, Lionel Moulis³, Angèle Soria^{2

4}, Aurélie Du-Thanh¹

Affiliations

¹ Department of Dermatology, St Eloi Hospital, 34000, Montpellier, France.
² Médecine Sorbonne Université, Service de Dermatologie et Allergologie, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
³ Clinical and Epidemiological Research Unit, CHU, Montpellier, 34000, France.
⁴ Cimi-Paris, INSERM 1135, Paris, France.

Abstract

Background: Bradykinin angioedemas are a potentially serious side effect of angiotensin-converting enzyme inhibitors (ACEI) and more controversially of angiotensin II receptor blockers (ARB). Their challenging diagnosis is based on the absence of any recurrence after more than 6 months of drug discontinuation; otherwise mast-cell driven angioedemas as a differential diagnosis must be considered.

Objective: The aim of this study was to determine the prevalence of recurrent angioedema in patients referred for ACEI/ARB-induced bradykinin angioedema, after more than 6 months of drug discontinuation.

Methods: We included ACEI/ARB-treated patients referred for angioedema(s) without hives and unresponsive to antihistamines, after they discontinued ACEI/ARB for at least 6 months. Any C1-inhibitor deficiency was excluded. The primary endpoint was the prevalence of patients with recurrent angioedema after more than 6 months of drug discontinuation and/or developing hives during follow-up. The secondary endpoint was the identification of epidemiological factors associated with any final diagnosis.

Results: Thirty-eight of 93 patients (41%) with a suspicion of ACEI/ARB-induced bradykinin angioedema still had recurrent angioedema (n = 27) or developed hives (n = 2) or both (n = 9) after 6 months of drug discontinuation. Good response to icatibant and facial but not oral localization were predictive for the final diagnosis of ACEI/ARB-induced bradykinin angioedema and mast-cell driven angioedema, respectively.

Conclusion: In patients referred for acquired angioedema without wheals occurring during ACEI/ARB therapy, 59% finally had a diagnosis of ACEI/ARB-induced bradykinin angioedema whereas 41% were rather diagnosed with mast-cell driven angioedema. The overdiagnosis of ACEI/ARB-induced bradykinin angioedema may deteriorate the management of severe cardiovascular conditions.

Keywords: Angioedema; Angiotensin converting enzyme inhibitors; Bradykinin; Mast-cell; Urticaria.