Angioedema associated with ACE inhibitors

• This side effect occurs in approximately 0.1 to 0.7% of users (1) with an increased risk in elderly individuals, females, and the African American population with a prior history of cutaneous drug eruptions, allergy reactions, and patients on immunomodulatory agents (2)
  
  
• The mechanism underlying the angio-oedema is likely to be the increased availability of bradykinin; this effect may also aggravate the angio-oedema associated with HAE. Angio-oedema associated with angiotensin receptor blockers has been reported infrequently and hence their use in individuals with ACE inhibitor-related angio-oedema has been questioned but is not contra-indicated (3)
  
  
• this side effect most commonly affects the face and mucous membranes, lips, tongue and larynx (3)
  
  
• in general, symptoms are mild and short-lived and this side effect occur within hours, or, at most weeks, after starting ACE inhibitor therapy - it reverses within hours of stopping treatment with the ACE inhibitor
  • however note that episodes of angio-oedema may persist for a few months after withdrawal of the ACE inhibitor without undermining the validity of the drug-related diagnosis
  • individuals of Afro-Caribbean origin are at increased risk of ACE inhibitor-induced angio-oedema and as these drugs are less effective in such individuals, an alternative antihypertensive may be prudent (2)
  • antihistamines, corticosteroids and adrenaline are often used to treat these individuals although the efficacy of such treatment remains undetermined. C1 inhibitor concentrate is not beneficial in patients with acute angio-oedema associated with ACE inhibitors. Icatibant is a specific antagonist of bradykinin B2 that can be used to treat angioedema and when compared to conventional steroid and antihistamine therapy, it shows comparable relief after a single dose (4)
  • individuals who do not improve even after several months of stopping the ACE inhibitor, probably have idiopathic angio-oedema and are coincidentally taking an ACE inhibitor (1)
    • there are no routine investigations to distinguish responders from non-responders to ACE inhibitor withdrawal
    • if the ACE inhibitor is responsible but is not withdrawn, the attacks may become more frequent and severe. ACE inhibitors are contra-indicated in subjects with a history of chronic angio-oedema, and alternative drugs should be used

Reference:

1. Ameer M. et al. Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Case Report With a Review of Management Options. Cureus. 2023 Jun; 15(6): e40320.

2. Kostis WJ et al. ACE inhibitor-induced angioedema: a review. Curr Hypertens Rep. 2018;20:55.

3. Maurer M, Magerl M. Differences and similarities in the mechanisms and clinical expression of bradykinin-mediated vs. mast cell-mediated angioedema. Clin Rev Allergy Immunol. 2021;61:40–49.

4. Yuen TY, Goh MS. A case report of ACE inhibitor induced angioedema and review of management options. Proc UCLA Healthcare. 2017;21