Top

International Journal of Emergency Medicine

Published in:

Open Access 01-12-2012 | Review

Emerging concepts in the diagnosis and treatment of patients with undifferentiated angioedema

Authors: Jonathan A Bernstein, Joseph Moellman

Published in: International Journal of Emergency Medicine | Issue 1/2012

Abstract

Angioedema is a sudden, transient swelling of well-demarcated areas of the dermis, subcutaneous tissue, mucosa, and submucosal tissues that can occur with or without urticaria. Up to 25% of people in the US will experience an episode of urticaria or angioedema during their lifetime, and many will present to the emergency department with an acute attack. Most cases of angioedema are attributable to the vasoactive mediators histamine and bradykinin. Histamine-mediated (allergic) angioedema occurs through a type I hypersensitivity reaction, whereas bradykinin-mediated (non-allergic) angioedema is iatrogenic or hereditary in origin.

Although their clinical presentations bear similarities, the treatment algorithm for histamine-mediated angioedema differs significantly from that for bradykinin-mediated angioedema. Corticosteroids, and epinephrine are effective in the management of histamine-mediated angioedema but are ineffective in the management of bradykinin-mediated angioedema. Recent advancements in the understanding of angioedema have yielded pharmacologic treatment options for hereditary angioedema, a rare hereditary form of bradykinin-mediated angioedema. These novel therapies include a kallikrein inhibitor (ecallantide) and a bradykinin β2 receptor antagonist (icatibant). The physician’s ability to distinguish between these types of angioedema is critical in optimizing outcomes in the acute care setting with appropriate treatment. This article reviews the pathophysiologic mechanisms, clinical presentations, and diagnostic laboratory evaluation of angioedema, along with acute management strategies for attacks.

Available only for authorised users

Bas M, Adams V, Suvorava T, Niehues T, Hoffmann TK, Kojda G: Nonallergic angioedema: role of bradykinin. Allergy 2007,62(8):842–856. 10.1111/j.1398-9995.2007.01427.xPubMedCrossRef

Brown SG: Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol 2004,114(2):371–376. 10.1016/j.jaci.2004.04.029PubMedCrossRef

Winters M: Clinical practice guideline: initial evaluation and management of patients presenting with acute urticaria or angioedema. American Academy of Emergency Medicine Web site. http://www.aaem.org/em-resources/position-statements/2006/clinical-practice-guidelines. Updated July 10, 2006. Accessed September 14, 2012

Kaplan AP, Ausiello DA: Anaphylaxis. In Cecil Medicine. 23rd edition. Edited by: Goldman L. Saunders, Philadelphia; 2008:1450–1452.

Kaplan AP, Greaves MW: Angioedema. J Am Acad Dermatol 2005,53(3):373–388. 10.1016/j.jaad.2004.09.032PubMedCrossRef

Flattery MP, Sica DA: Angiotensin-converting enzyme inhibitor-related angioedema: recognition and treatment. Prog Cardiovasc Nurs 2007,22(Winter):47–51.PubMedCrossRef

Weldon D: Differential diagnosis of angioedema. Immunol Allergy Clin North Am. 2006,26(4):603–613. 10.1016/j.iac.2006.09.006PubMedCrossRef

Frigas E, Park MA: Acute urticaria and angioedema: diagnostic and treatment considerations. Am J Clin Dermatol 2009,10(4):239–250. 10.2165/00128071-200910040-00004PubMedCrossRef

Greenberger PA: Anaphylactic and anaphylactoid causes of angioedema. Immunol Allergy Clin North Am 2006,26(4):753–767. 10.1016/j.iac.2006.09.002PubMedCrossRef

10.

Bork K: Diagnosis and treatment of hereditary angioedema with normal C1 inhibitor. Allergy, Asthma Clin Immunol 2010,6(1):15. 10.1186/1710-1492-6-15CrossRef

11.

Durham SR: Allergic inflammation: cellular aspects. Allergy 1999,54(suppl 56):18–20.PubMedCrossRef

12.

Nzeako UC, Frigas E, Tremaine WJ: Hereditary angioedema: a broad review for clinicians. Arch Intern Med 2001,161(20):2417–2429. 10.1001/archinte.161.20.2417PubMedCrossRef

13.

Epstein TG, Bernstein JA: Current and emerging management options for hereditary angioedema in the US. Drugs 2008,68(18):2561–2573. 10.2165/0003495-200868180-00003PubMedCrossRef

14.

Papadopoulou-Alataki E: Upper airway considerations in hereditary angioedema. Curr Opin Allergy Clin Immunol 2010,10(1):20–25. 10.1097/ACI.0b013e328334f629PubMedCrossRef

15.

Jessup M, Brozena S: Heart failure. N Engl J Med 2003,348(20):2007–2018. 10.1056/NEJMra021498PubMedCrossRef

16.

Casas JP, Chua W, Loukogeorgakis S, et al.: Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet 2005,366(9502):2026–2033. 10.1016/S0140-6736(05)67814-2PubMedCrossRef

17.

Sánchez-Borges M, González-Aveledo LA: Angiotensin-converting enzyme inhibitors and angioedema. Allergy Asthma Immunol Res 2010, 2: 195–198. 10.4168/aair.2010.2.3.195PubMedCentralPubMedCrossRef

18.

Donaldson VH, Bernstein DI, Wagner CJ, Mitchell BH, Scinto J, Bernstein IL: Angioneurotic edema with acquired C1- inhibitor deficiency and autoantibody to C1- inhibitor: response to plasmapheresis and cytotoxic therapy. J Lab Clin Med 1992,119(4):397–406.PubMed

19.

Bork K, Meng G, Staubach P, Hardt J: Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med 2006,119(3):267–274. 10.1016/j.amjmed.2005.09.064PubMedCrossRef

20.

Zuraw BL: Clinical practice. Hereditary angioedema. N Engl J Med 2008,359(10):1027–1036. 10.1056/NEJMcp0803977PubMedCrossRef

21.

Temiño VM, Peebles RS: The spectrum and treatment of angioedema. Am J Med 2008, 121: 282–286. 10.1016/j.amjmed.2007.09.024PubMedCrossRef

22.

Hill MD, Barber PA, Takahashi J, Demchuk AM, Feasby TE, Buchan AM: Anaphylactoid reactions and angioedema during alteplase treatment of acute ischemic stroke. CMAJ 2000,162(9):1281–1284.PubMedCentralPubMed

23.

Gompels MM, Lock RJ, Abinun M, et al.: C1 inhibitor deficiency: consensus document. Clin Exp Immunol 2005,139(3):379–394. 10.1111/j.1365-2249.2005.02726.xPubMedCentralPubMedCrossRef

24.

Bowen T, Cicardi M, Farkas H, et al.: 2010 international consensus algorithim for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol 2010,6(24):1–13.

25.

Oswalt ML, Kemp SF: Anaphylaxis: office management and prevention. Immunol Allergy Clin North Am 2007,27(2):177–191. 10.1016/j.iac.2007.03.004PubMedCrossRef

26.

Lin RY, Curry A, Pesola GR, et al.: Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 and H2 antagonists. Ann Emerg Med 2000,36(5):462–468.PubMedCrossRef

27.

Bernstein JA: Evaluation of ecallantide for the acute treatment of angiotensin converting enzyme inhibitor induced angioedema (ACE). ClinicalTrials.gov Website. . December 18, 2009. Updated August 17, 2010. Verified March 2012. Accessed September 15, 2012 http://clinicaltrials.gov/ct2/show/NCT01036659?term=ecallantide+ACE+inhibitor&rank=1

28.

Technische Universität M: A Melioration of Angiotensin Converting Enzyme Inhibitor Induced Angioedema Study. ClinicalTrials.gov Website. . Last updated December 22, 2011. Accessed September 15, 2012 http://clinicaltrials.gov/ct2/show/NCT01154361?term=icatibant+ACE+inhibitor&rank=1

29.

Perez DV, Infante S, Marco G, Zubeldia JM, Marañon G: Angioedema induced by angiotensin-converting enzyme inhibitors: two cases of successful treatment with a novel B2 bradykinin antagonist [AAAAI Abstract]. J Allergy Clin Immunol 2011,27(2):AB105.

30.

Schmidt PW, Hirschl MH, Trautinger F: Case letter: treatment of angiotensin-converting enzyme inhibitor-related angioedema with the bradykinin B2 receptor antagonist icatibant. J Am Acad Dermatol 2010,63(5):913–914. 10.1016/j.jaad.2010.03.023PubMedCrossRef

31.

Bas M, Greve J, Stelter K: Therapeutic efficacy of icatibant in angioedema induced by angiotensin-converting enzyme inhibitors: a case series. Ann Emerg Med 2010,56(3):278–282. 10.1016/j.annemergmed.2010.03.032PubMedCrossRef

32.

Berinert [package insert] CSL Behring LLC, Kankakee; 2009.

33.

Kalbitor [package insert] Dyax Corp, Cambridge; 2009.

34.

Firazyr [package insert] Shire Orphan Therapies, Lexington, MA; 2011.

35.

Zuraw B: HAE therapies: past present and future. Allergy Asthma Clin Immunol 2010,6(1):23. 10.1186/1710-1492-6-23PubMedCentralPubMedCrossRef

36.

Amicar [package insert] Xanodyne Pharmaceuticals, Inc, Newport; 2008.

37.

Bernstein JA: Hereditary angioedema: a current state-of-the-art review, VIII: current status of emerging therapies. Ann Allergy Asthma Immunol 2008,100(1 Suppl 2):S41–6.PubMedCrossRef

38.

Banerji A: Current treatment of hereditary angioedema: an update on clinical studies. Allergy Asthma Proc 2010,31(5):398–406. 10.2500/aap.2010.31.3387PubMedCrossRef

39.

Lunn M, Banta E: Ecallantide for the treatment of hereditary angiodema in adults. Clin Med Insights Cardiol 2011, 5: 49–54.PubMedCentralPubMedCrossRef

40.

Cruden NLM, Newby DE: Therapeutic potential of icatibant (HOE-140, JE-049). Expert Opin Pharmacother 2008,9(13):2383–90. 10.1517/14656566.9.13.2383PubMedCrossRef

41.

Cicardi M, Banerji A, Bracho F, et al.: Icatibant, a novel bradykinin B2 receptor antagonist, is effective in the treatment of acute attacks in patients with hereditary angioedema. N Engl J Med 2010,363(6):532–41. 10.1056/NEJMoa0906393PubMedCrossRef

42.

Lumry WR, Li HH, Levy RJ, et al.: Randomized placebo-controlled trial of the bradykinin B2 receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial. Ann Allergy Asthma Immunol 2011,107(6):529–537. 10.1016/j.anai.2011.08.015PubMedCrossRef

43.

Bowen T, Cicardi M, Bork K, et al.: Hereditary angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Ann Allergy Asthma Immunol 2008,100(1 Suppl 2):S30–40.PubMedCrossRef

Title: Emerging concepts in the diagnosis and treatment of patients with undifferentiated angioedema
Authors: Jonathan A Bernstein
Joseph Moellman
Publication date: 01-12-2012
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Emergency Medicine / Issue 1/2012
Print ISSN: 1865-1372
Electronic ISSN: 1865-1380
DOI: https://doi.org/10.1186/1865-1380-5-39

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Emerging concepts in the diagnosis and treatment of patients with undifferentiated angioedema

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2012

Is there a relationship between wound infections and laceration closure times?

Analysis of traumatic injuries presenting to a referral hospital emergency department in Moshi, Tanzania

Subgaleal coiling of the proximal and distal components of a ventriculoperitoneal shunt

National inventory of emergency departments in Singapore

The livelihoods of Haitian health-care providers after the january 2010 earthquake: a pilot study of the economic and quality-of-life impact of emergency relief

Survey of preferred guideline attributes: what helps to make guidelines more useful for emergency health practitioners?