Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Aug 19;16(8):100809.
doi: 10.1016/j.waojou.2023.100809. eCollection 2023 Aug.

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

Marie Douillard  1 , Zineb Deheb  2 , Agathe Bozon  1 , Nadia Raison-Peyron  1 , Olivier Dereure  1 , Lionel Moulis  3 , Angèle Soria  2   4 , Aurélie Du-Thanh  1
Affiliations

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

Marie Douillard et al. World Allergy Organ J. .

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.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Flow chart of the study. ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor blockers; N, number. ∗discontinuation of ACEI/ARB and complete follow-up over 6 months ∗∗according to the classification by Cicardi et al. also considered as mast-cell driven angioedema
Fig. 2
Fig. 2
Classification of acquired angioedema without wheals, adapted from Cicardi et al.. ACEI, angiotensin-converting inhibitors; C1–INH, C1-inhibitor; CSU, chronic spontaneous urticaria; y.o, years-old. ∗others drugs such as angiotensin II receptor blockers, gliptins, etc. are also believed to be involved. Blue blocks represent mast-cell driven entities, gray blocks represent bradykinin mediated entities
Fig. 3
Fig. 3
Differential diagnoses of angioedema without wheals occurring during ACEI/ARB therapy. ACEI, angiotensin-converting inhibitors; ARB, angiotensin II receptor blockers; OMA, omalizumab; AH, antihistamines; pdC1-INH, plasma derived C1-inhibitor. ∗according to the classification of acquired angioedema by Cicardi et al. those angioedema are believed to be mast-cell driven. Grey blocks represent entities that are not currently supported by the literature
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Hoover T., Lippmann M., Grouzmann E., Marceau F., Herscu P. Angiotensin converting enzyme inhibitor induced angio-oedema: a review of the pathophysiology and risk factors. Clin Exp Allergy. 2010;40(1):50–61. - PubMed
    1. Banerji A., Blumenthal K.G., Lai K.H., Zhou L. Epidemiology and incidence of ACE inhibitor angioedema utilizing a large electronic health record. J Allergy Clin Immunol Pract. 2017;5(3):744–749. - PMC - PubMed
    1. Ames M.K., Atkins C.E., Pitt B. The renin-angiotensin-aldosterone system and its suppression. J Vet Intern Med. 2019 Mar;33(2):363–382. - PMC - PubMed
    1. Dicpinigaitis P.V. Angiotensin-converting enzyme inhibitor-induced cough: ACCP evidence-based clinical practice guidelines. Chest. 2006 Jan 1;129(1, Supplement):169S–173S. - PubMed
    1. Caldeira D., David C., Sampaio C. Tolerability of angiotensin-receptor blockers in patients with intolerance to angiotensin-converting enzyme inhibitors. Am J Cardiovasc Drugs. 2012 Aug 1;12(4):263–277. - PubMed

LinkOut - more resources