Bradykinin-mediated Angioedema

  • B. Floccard
  • E. Hautin
  • B. Allaouchiche
Part of the Annual Update in Intensive Care and Emergency Medicine book series (AUICEM, volume 2012)


Angioedema is a clinical syndrome characterized by transient and recurrent episodes of subcutaneous or mucosal edema that are referred to as attacks. These episodes of swelling can affect the skin, airways or digestive tract. Depending on the location, the attacks can be severe and potentially life-threatening [1]. This syndrome, which has various causes, is associated with excessive levels of bradykinin and is not an allergic reaction [2]. Although misunderstood and rare, this disease can be encountered by any intensive care unit (ICU) physician [3]. Reports from international consensus conferences have been published and specific molecules have been developed in recent years for the treatment of acute attacks [4, 5]. The aim of this article is to present the current protocols used for the emergency management of acute attacks. Pediatric cases will not be discussed because of the lack of new studies [6, 7]. Additionally, short-term prophylaxis to protect against attacks during a procedure or personal event (e.g., endoscopy, dental care, surgery and stressful everyday events) will not be discussed here [4, 5].


Allergy Clin Immunol Fabry Disease Tranexamic Acid Laryngeal Edema Hereditary Angioedema 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Zuraw BL (2008) Clinical practice. Hereditary angioedema. N Engl J Med 359: 1027–1036PubMedCrossRefGoogle Scholar
  2. 2.
    Kaplan AP, Greaves MW (2005) Angioedema. J Am Acad Dermatol 53: 373–388PubMedCrossRefGoogle Scholar
  3. 3.
    Levy JH, Freiberger DJ, Roback J (2010) Hereditary angioedema: current and emerging treatment options. Anesth Analg 110: 1271–1280PubMedCrossRefGoogle Scholar
  4. 4.
    Bowen T, Cicardi M, Farkas H, Bork K, et al (2010) 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol 6: 24PubMedCrossRefGoogle Scholar
  5. 5.
    Bowen T (2011) Hereditary angioedema: beyond international consensus — circa December 2010 — The Canadian Society of Allergy and Clinical Immunology Dr. David McCourtie Lecture. Allergy Asthma Clin Immunol 7: 1PubMedCrossRefGoogle Scholar
  6. 6.
    Farkas H, Varga L, Szeplaki G, Visy B, Harmat G, Bowen T (2007) Management of hereditary angioedema in pediatric patients. Pediatrics 120: e713–722PubMedCrossRefGoogle Scholar
  7. 7.
    Farkas H (2010) Pediatric hereditary angioedema due to C1-inhibitor deficiency. Allergy Asthma Clin Immunol 6: 18PubMedCrossRefGoogle Scholar
  8. 8.
    Agostoni A, Aygoren-Pursun E, Binkley KE, et al (2004) Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol 114: S51–131CrossRefGoogle Scholar
  9. 9.
    Zuraw BL (2008) Hereditary angiodema: a current state-of-the-art review, IV: short-and long-term treatment of hereditary angioedema: out with the old and in with the new? Ann Allergy Asthma Immunol 100: S13–18CrossRefGoogle Scholar
  10. 10.
    Agostoni A, Cicardi M (1992) Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients. Medicine 71: 206–215PubMedCrossRefGoogle Scholar
  11. 11.
    Bork K, Siedlecki K, Bosch S, Schopf RE, Kreuz W (2000) Asphyxiation by laryngeal edema in patients with hereditary angioedema. Mayo Clinic proceedings 75: 349–354PubMedCrossRefGoogle Scholar
  12. 12.
    Bork K, Hardt J, Schicketanz KH, Ressel N (2003) Clinical studies of sudden upper airway obstruction in patients with hereditary angioedema due to C1 esterase inhibitor deficiency. Arch Intern Med 163: 1229–1235PubMedCrossRefGoogle Scholar
  13. 13.
    Bork K, Staubach P, Eckardt AJ, Hardt J (2006) Symptoms, course, and complications of abdominal attacks in hereditary angioedema due to C1 inhibitor deficiency. Am J Gastroenterol 101: 619–627PubMedCrossRefGoogle Scholar
  14. 14.
    Nzeako UC (2010) Diagnosis and management of angioedema with abdominal involvement: a gastroenterology perspective. World J Gastroenterol 16: 4913–4921PubMedCrossRefGoogle Scholar
  15. 15.
    Guichon C, Floccard B, Coppere B, et al (2011) One hypovolaemic shock…two kinin pathway abnormalities. Intensive Care Med 37: 1227–1228PubMedCrossRefGoogle Scholar
  16. 16.
    Bork K, Hardt J, Staubach-Renz P, Witzke G (2011) Risk of laryngeal edema and facial swellings after tooth extraction in patients with hereditary angioedema with and without prophylaxis with C1 inhibitor concentrate: a retrospective study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 112: 58–64PubMedCrossRefGoogle Scholar
  17. 17.
    Maurer M, Bader M, Bas M, et al (2011) New topics in bradykinin research. Allergy Aug 66: 1397–1406CrossRefGoogle Scholar
  18. 18.
    Davis AE 3rd (2005) The pathophysiology of hereditary angioedema. Clin Immunol 114: 3–9PubMedCrossRefGoogle Scholar
  19. 19.
    Bas M, Adams V, Suvorava T, Niehues T, Hoffmann TK, Kojda G (2007) Nonallergic angioedema: role of bradykinin. Allergy 62: 842–856PubMedCrossRefGoogle Scholar
  20. 20.
    Kaplan A (2011) Bradykinin and the pathogenesis of hereditary angiodema. World Allergy Organiz J 4: 73–75CrossRefGoogle Scholar
  21. 21.
    Floccard B, Crozon J, Rimmele T, et al (2011) Management of bradykinin-mediated angioedema. Ann Fr Anesth Reanim 30: 578–588PubMedCrossRefGoogle Scholar
  22. 22.
    Bossi F, Fischetti F, Regoli D, et al (2009) Novel pathogenic mechanism and therapeutic approaches to angioedema associated with C1 inhibitor deficiency. J Allergy Clin Immunol 124: 1303–1310PubMedCrossRefGoogle Scholar
  23. 23.
    Cugno M, Nussberger J, Cicardi M, Agostoni A (2003) Bradykinin and the pathophysiology of angioedema. Int Immunopharmacol 3: 311–317PubMedCrossRefGoogle Scholar
  24. 24.
    Cicardi M, Zanichelli A (2010) Angioedema due to C1 inhibitor deficiency in 2010. Intern Emerg Med 5: 481–486PubMedCrossRefGoogle Scholar
  25. 25.
    Cicardi M, Zanichelli A (2010) Acquired angioedema. Allergy Asthma Clin Immunol 6: 14PubMedCrossRefGoogle Scholar
  26. 26.
    Davis AE, 3rd, Lu F, Mejia P (2010) C1 inhibitor, a multi-functional serine protease inhibitor. Thromb Haemost 104: 886–893PubMedCrossRefGoogle Scholar
  27. 27.
    Bork K, Wulff K, Hardt J, Witzke G, Staubach P (2009) Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features, trigger factors, and therapy. J Allergy Clinical Immunol 124: 129–134CrossRefGoogle Scholar
  28. 28.
    Bouillet L (2010) Hereditary angioedema in women. Allergy Asthma Clin Immunol 6: 17PubMedCrossRefGoogle Scholar
  29. 29.
    Cugno M, Castelli R, Cicardi M (2008) Angioedema due to acquired C1-inhibitor deficiency: a bridging condition between autoimmunity and lymphoproliferation. Autoimmunity Rev 8: 156–159CrossRefGoogle Scholar
  30. 30.
    Brown NJ, Byiers S, Carr D, Maldonado M, Warner BA (2009) Dipeptidyl peptidase-IV inhibitor use associated with increased risk of ACE inhibitor-associated angioedema. Hypertension 54: 516–523PubMedCrossRefGoogle Scholar
  31. 31.
    Hoover T, Lippmann M, Grouzmann E, Marceau F, Herscu P (2010) Angiotensin converting enzyme inhibitor induced angio-oedema: a review of the pathophysiology and risk factors. Clin Exp Allergy 40: 50–61PubMedGoogle Scholar
  32. 32.
    Miller DR, Oliveria SA, Berlowitz DR, Fincke BG, Stang P, Lillienfeld DE (2008) Angioedema incidence in US veterans initiating angiotensin-converting enzyme inhibitors. Hypertension 51: 1624–1630PubMedCrossRefGoogle Scholar
  33. 33.
    Tai S, Mascaro M, Goldstein NA (2010) Angioedema: a review of 367 episodes presenting to three tertiary care hospitals. Ann Otol, Rhinol Laryngol 119: 836–841Google Scholar
  34. 34.
    Morgan BP (2010) Hereditary angioedema-therapies Old and new. N Engl J Med 363: 581–583PubMedCrossRefGoogle Scholar
  35. 35.
    Blankart CR, Stargardt T, Schreyogg J (2011) Availability of and access to orphan drugs: an international comparison of pharmaceutical treatments for pulmonary arterial hypertension, Fabry disease, hereditary angioedema and chronic myeloid leukaemia. PharmacoEconomics 29: 63–82PubMedCrossRefGoogle Scholar
  36. 36.
    De Serres J, Groner A, Lindner J (2003) Safety and efficacy of pasteurized C1 inhibitor concentrate (Berinert P) in hereditary angioedema: a review. Transfus Apher Sci 29: 247–254PubMedCrossRefGoogle Scholar
  37. 37.
    Longhurst HJ (2005) Emergency treatment of acute attacks in hereditary angioedema due to C1 inhibitor deficiency: what is the evidence? Int J Clin Pract 59: 594–599PubMedCrossRefGoogle Scholar
  38. 38.
    Farkas H, Jakab L, Temesszentandrasi G, et al (2007) Hereditary angioedema: a decade of human C1-inhibitor concentrate therapy. J Allergy Clin Immunol 120: 941–947PubMedCrossRefGoogle Scholar
  39. 39.
    Cicardi M, Zingale L, Zanichelli A, Deliliers DL (2007) Established and new treatments for hereditary angioedema: An update. Mol Immunol 44: 3858–3861PubMedCrossRefGoogle Scholar
  40. 40.
    Craig TJ, Levy RJ, Wasserman RL, et al (2009) Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol 124: 801–808PubMedCrossRefGoogle Scholar
  41. 41.
    Craig TJ, Bewtra AK, Bahna SL, et al (2011) C1 esterase inhibitor concentrate in 1085 Hereditary Angioedema attacks — final results of the I.M.P.A.C.T.2 study. Allergy 66: 1604–1611PubMedCrossRefGoogle Scholar
  42. 42.
    Bork K, Frank J, Grundt B, Schlattmann P, Nussberger J, Kreuz W (2007) Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant). J Allergy Clin Immunol 119: 1497–1503PubMedCrossRefGoogle Scholar
  43. 43.
    Cicardi M, Banerji A, Bracho F, et al (2010) Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med 363: 532–541PubMedCrossRefGoogle Scholar
  44. 44.
    Longhurst H (2008) Rhucin, a recombinant C1 inhibitor for the treatment of hereditary angioedema and cerebral ischemia. Curr Opin Investig Drugs 9: 310–323PubMedGoogle Scholar
  45. 45.
    Zuraw BL, Busse PJ, White M, et al (2010) Nanofiltered c1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med 363: 513–522PubMedCrossRefGoogle Scholar
  46. 46.
    Cicardi M, Levy RJ, McNeil DL, et al (2010) Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med 363: 523–531PubMedCrossRefGoogle Scholar
  47. 47.
    Craig TJ, Wasserman RL, Levy RJ, et al (2010) prospective study of rapid relief provided by C1 esterase inhibitor in emergency treatment of acute laryngeal attacks in hereditary angioedema. J Clin Immunol 30: 823–829PubMedCrossRefGoogle Scholar
  48. 48.
    Jensen NF, Weiler JM (1998) C1 esterase inhibitor deficiency, airway compromise, and anesthesia. Anesth Analg 87: 480–488PubMedGoogle Scholar
  49. 49.
    Wilson DA, Bork K, Shea EP, Rentz AM, Blaustein MB, Pullman WE (2010) Economic costs associated with acute attacks and long-term management of hereditary angioedema. Ann Allergy Asthma Immunol 104: 314–320PubMedCrossRefGoogle Scholar
  50. 50.
    Floccard B, Crozon J, Coppere B, Bouillet L, Allaouchiche B (2010) Angio-oedème à bradykinine. In: Leone M (ed) Maladies Rares en Réanimation. Springer, Paris, pp 236–274Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • B. Floccard
  • E. Hautin
  • B. Allaouchiche

There are no affiliations available

Personalised recommendations