Episode 974: ACE Inhibitor Angioedema

Contributor: Ricky Dhaliwal, MD

Educational Pearls:

• Angioedema in anaphylaxis
  • Histamine and mast cell-mediated pathway
  • Treatment:
    • First line: epinephrine for vasoconstriction and bronchodilation
    • Second line: H1 and H2 antihistamines such as Benadryl and famotidine
• ACE inhibitor-induced angioedema
  • Different pathway from anaphylaxis
    • ACE inhibitor-induced angioedema is mediated by bradykinins
    • Therefore, anaphylaxis medications are not beneficial in patients with ACE inhibitor-induced angioedema
  • Leading cause of drug-induced angioedema in the US
  • Patients most commonly present with swelling of the lips, tongue, or face
  • Treatment:
    • Airway management: varies depending on the severity and progression of the presentation
      • If awake nasointubation is required, LMX is a 5% lidocaine water-soluble solution that provides anesthesia to the oropharynx
    • Medications:
      • Icatibant is a synthetic bradykinin B2-receptor antagonist that can be used in acute treatment
      • Tranexamic acid (TXA) inhibits the plasmin-dependent formation of bradykinin, but the data on this treatment are mixed and limited
      • Fresh frozen plasma (FFP) is thought to degrade high levels of bradykinin with subsequent resolution of angioedema
    • Discontinue ACE inhibitor

References

1. Bork K, Wulff K, Hardt J, Witzke G, Staubach P. Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features, trigger factors, and therapy. J Allergy Clin Immunol. 2009 Jul;124(1):129-34. doi: 10.1016/j.jaci.2009.03.038. Epub 2009 May 27. PMID: 19477491.
2. Bova M, Guilarte M, Sala-Cunill A, Borrelli P, Rizzelli GM, Zanichelli A. Treatment of ACEI-related angioedema with icatibant: a case series. Intern Emerg Med. 2015 Apr;10(3):345-50. doi: 10.1007/s11739-015-1205-9. Epub 2015 Feb 10. PMID: 25666515.
3. Karim MY, Masood A. Fresh-frozen plasma as a treatment for life-threatening ACE-inhibitor angioedema. J Allergy Clin Immunol. 2002 Feb;109(2):370-1. doi: 10.1067/mai.2002.121313. PMID: 11842313.
4. Pathak GN, Truong TM, Chakraborty A, Rao B, Monteleone C. Tranexamic acid for angiotensin-converting enzyme inhibitor-induced angioedema. Clin Exp Emerg Med. 2024 Mar;11(1):94-99. doi: 10.15441/ceem.23.051. Epub 2023 Aug 1. PMID: 37525579; PMCID: PMC11009700.
5. Simons FE. First-aid treatment of anaphylaxis to food: focus on epinephrine. J Allergy Clin Immunol. 2004 May;113(5):837-44. doi: 10.1016/j.jaci.2004.01.769. Erratum in: J Allergy Clin Immunol. 2004 Jun;113(6):1039. Dosage error in article text. PMID: 15131564.

Summarized by Meg Joyce, MS2 | Edited by Meg Joyce & Jorge Chalit, OMS4

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