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. 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.

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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

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