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ACE Inhibitor–Induced Angioedema

Abstract

Much has been written about hereditary angioedema (HAE) in recent literature; however, the prevalence of angiotensin-converting enzyme inhibitor–induced angioedema (ACEiIA) far exceeds that of HAE. Similarly, multiple therapies have been developed for HAE, yet no definitive therapy is available for ACEiIA. In this article, we discuss the mechanism, prevalence, pathophysiology, and management of ACEiIA, with focus on newer therapies recently approved for HAE and how they may be effective for ACEiIA.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Vleeming W, van Amsterdam JGC, Stricker BHC, de Wildt DJ. ACE inhibitor-induced angioedema. Incidence, prevention and management. Drug Saf. 1998;18(3):171–88.

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Scheirey CD, Scholz FJ, Shortsleeve MJ, Katz DS. Angiotensin-converting enzyme inhibitor-induced small-bowel angioedema: clinical and imaging findings in 20 patients. AJR Am J Roentgenol. 2011;197(2):393–8.

    PubMed  Article  Google Scholar 

  3. 3.

    •• Caballero T, Baeza ML, Cabañas R, Campos A, Cimbollek S, Gómez-Traseira C, González-Quevedo T, Guilarte M, Jurado-Palomo GJ, Larco JI, López-Serrano MC, López-Trascasa M, Marcos C, Muñoz-Caro JM, Pedrosa M, Prior N, Rubio M, Sala-Cunill A; Spanish Study Group on Bradykinin-Induced Angioedema. Consensus statement on the diagnosis, management, and treatment of angioedema mediated by bradykinin. Part I. Classification, epidemiology, pathophysiology, genetics, clinical symptoms, and diagnosis. J Investig Allergol Clin Immunol. 2011;21(5):333–47. This paper summarizes consensus reached after extensive peer discussions regarding bradykinin-induced angioedema in recent times.

    PubMed  CAS  Google Scholar 

  4. 4.

    Lin RY, Shaili NS. Increasing hospitalizations due to angioedema in the United States. Annals Allergy Asthma Immunol. 2008;101(2):185–92.

    Article  Google Scholar 

  5. 5.

    Papadopoulou-Alataki E. Upper airway considerations in hereditary angioedema. Curr Opin Allergy Clin Immunol. 2010;10(1):20–5.

    PubMed  Article  Google Scholar 

  6. 6.

    CDC. Health, United States, 2008. Hyattsville, MD: National Center for Health Statistics; 2008.

  7. 7.

    Ma J, Lee KV, Stafford RS. Changes in antihypertensive prescribing during US outpatient visits for uncomplicated hypertension between 1993 and 2004. Hypertension. 2006;48:846–52.

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    • Quan M Case study. ACE inhibitor-induced angioedema. Clin Cornerstone –Jan 2009; 9 Suppl 3. This study outlines the important characteristics of ACEiIA.

  9. 9.

    Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy: a review of the literature and pathophysiology. Ann Intern Med. 1992;117(3):234–42.

    PubMed  CAS  Google Scholar 

  10. 10.

    Brown NJ, Ray WA, Snowden M, Griffin MR. Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema. Clin Pharmacol Ther. 1996;60:8–13.

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Banerji A, Clark S, Blanda M, LoVecchio F, Snyder B, Camargo CA, et al. Multicenter study of patients with angiotensin-converting enzyme inhibitor-induced angioedema who present to the emergency department. Ann Allergy Asthma Immunol. 2008;100(4):327–32.

    PubMed  Article  Google Scholar 

  12. 12.

    BaijuMalde, Jane Regalado, Paul A. Greenberger Investigation of angioedema associated with the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Original Research Article. Annals of Allergy, Asthma & Immunology, Volume 98, Issue 1, Jan 2007,57-63.

  13. 13.

    •• 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 Jan;40(1):50–61. Epub 2009 Jul 29. This article reviews the risk factors for ACEiIA.

    PubMed  CAS  Google Scholar 

  14. 14.

    Kostis JB, Kostis JB, Kim HJ, Rusnak J, Casale T, Kaplan A, Corren J, et al. Incidence and characteristics of angioedema associated with enalapril. Arch Intern Med. 2005;165:1637–42.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Duerr M, Glander P, Diekmann F, Dragun D, Neumayer HH, Budde K. Increased incidence of angioedema with ACE inhibitors in combination with mTOR inhibitors in kidney transplant recipients. Clin J Am Soc Nephrol. 2010;5(4):703–8. Epub 2010 Jan 21.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Goodfriend T, Elliot M, Catt K. Angiotensin receptors and their antagonists. N Engl J Med. 1996;334:1649–55.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Ju H, Venema VJ, Liang H, Harris MB, Zou R, Venema RC. Bradykinin activates the Janus-activated kinase/signal transducers and activators of transcription (JAK/STAT) pathway in vascular endothelial cells: localization of JAK/STAT signaling proteins in plasmalemmalcaveolae. Biochem J. 2000;351:257–64.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Bae SW, Kim HS, Cha YN, Park YS, Jo SA, Jo I. Rapid increase in endothelial nitric oxide production by bradykinin is mediated by protein kinase A signaling pathway. Biochem Biophys Res Commun. 2003;306:981–7.

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Adam A, Cugno M, Molinaro G, Perez M, Lepage Y, Agostoni A. Aminopeptidase P in individuals with a history of angio-oedema on ACE inhibitors. Lancet. 2002;59(9323):2088–9.

    Article  Google Scholar 

  20. 20.

    Bas M, Adams V, Suvorava T, Niehues T, Hoffmann TK, Kodja G. Nonallergic angioedema: role of bradykinin. Allergy. 2007;62:842–56.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Haymore BR, Yoon J, Mikita CP, Klote MM, DeZee KJ. Risk of angioedema with angiotensin receptor blockers in patients with prior angioedema associated with angiotensin-converting enzyme inhibitors: a meta-analysis. Original Research Article Annals of Allergy, Asthma & Immunology. 2008;101(5):495–9.

    Article  Google Scholar 

  22. 22.

    Byrd JB, Woodard-Grice A, Stone E, Lucisano A, Schaefer H, Yu C, et al. Brown NJ Association of angiotensin-converting enzyme inhibitor associated angioedema with transplant and immunosuppressant use. Allergy. 2010;65(11):1381–7.

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Woodard-Grice AV, Lucisano AC, Byrd JB, Stone ER, Simmons WH, Brown NJ. Sex-dependent and race-dependent association of XPNPEP2 C-2399A polymorphism with angiotensin-converting enzyme inhibitor-associated angioedema. Pharmacogenet Genomics. 2010;20(9):532–6.

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Nzeako U, Frigas E, Tremaine W. Hereditary angioedema: a broad review for clinicians. Arch Intern Med. 2001;161:2417–29.

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Van Dellen RG, Maddox DE, Dutta EJ. Masqueraders of angioedema and urticaria. Ann Allergy Asthma Immunol. 2002;88(1):10–5.

    PubMed  Article  Google Scholar 

  26. 26.

    Warrier MR, Copilevitz CA, Dykewicz MS, Slavin RG. Fresh frozen plasma in the treatment of resistant angiotensin-converting enzyme inhibitor angioedema. Ann Allergy Asthma Immunol. 2004;92(5):573–5.

    PubMed  Article  Google Scholar 

  27. 27.

    •• Bas M, Greve J, Stelter K, Bier H, Stark T, Hoffmann TK, Kojda. Therapeutic efficacy of icatibant in angioedema induced by angiotensin-converting enzyme inhibitors: a case series. Ann Emerg Med. 2010 Sep;56(3):278–82. This unique trial studied icatibant as a promising therapy for ACEiIA.

    PubMed  Article  Google Scholar 

  28. 28.

    Waytes AT, Rosen FS, Frank MM. Treatment of hereditary angioedema with a vapor-heated C1 inhibitor concentrate. N Engl J Med. 1996;334(25):1630–4.

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Nielsen EW, Gramstad S. Angioedema from angiotensin-converting enzyme (ACE) inhibitor treated with complement 1 (C1) inhibitor concentrate. Acta Anaesthesiol Scand. 2006;50:120–2.

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Hurst M, Empson M: Oral angioedema secondary to ACE inhibitors, a frequently overlooked association: A case report and review. Journal of the New Zealand Medical Association; April 2006, Vol 119, No 1232.

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Disclosure

Dr. Craig has received research grant support from GlaxoSmithKline, Genentech, Novartis, Boehringer Ingelheim, Dyax Corp., CSL Behring, ViroPharma, Shire, and Pharming Group NV; has served as a consultant for Merck & Co., Novartis, CSL Behring, ViroPharma, Shire, and Dyax Corp.; has served as a speaker for ViroPharma, CSL Behring, and Dyax Corp.; has served on boards for the American Academy of Allergy, Asthma and Immunology, American College of Allergy, Asthma and Immunology, ALA-PA, and the Joint Council of Allergy, Asthma and Immunology; and has received salary support from the Vietnam Education Foundation.

Dr. Vasekar reported no potential conflicts of interest relevant to this article.

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Correspondence to Timothy J. Craig.

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Vasekar, M., Craig, T.J. ACE Inhibitor–Induced Angioedema. Curr Allergy Asthma Rep 12, 72–78 (2012). https://doi.org/10.1007/s11882-011-0238-z

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Keywords

  • Angioedema
  • ACEi–induced angioedema
  • Hereditary angioedema
  • Angiotensin-converting enzyme inhibitor
  • Icatibant
  • Ecallantide