Angioedema in the Emergency Department

  • Malcolm W. Greaves
  • Allen P. Kaplan
Part of the Allergy Frontiers book series (ALLERGY, volume 4)

The molecular, and in hereditary forms, the genetic basis of angioedema is becoming better understood, leading to improved management including more focussed emergency room diagnosis and treatment.

It is now possible to distinguish in the laboratory the three subtypes of hereditary angioedema from each other and from acquired C′1 esterase inhibitor deficiency and this is important because of the impact on treatment.

C′1 inhibitor concentrate is established as a safe and effective emergency room treatment for hereditary C′1 inhibitor deficient angioedema, but in the acquired forms, because of increased consumption, it may have to be supplemented by tranexamic acid treatment. Icatibant, a bradykinin antagonist, has now been licensed in Europe for acute attacks of types 1 and 2 hereditary angioedema. Both Icatibant and the kallikrein inhibitor ecallantide are promising treatments for ACE inhibitor angioedema though not yet licensed for this indication.

In all cases of acute angioedema whatever the type or cause, the cornerstones of emergency treatment include securing the airway, establishing an intravenous line and parenteral adrenaline. Admission for 24h observation is also advisable for all but the mildest cases.


Allergy Clin Immunol Tranexamic Acid Chronic Urticaria Chronic Idiopathic Urticaria 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.
    Kaplan AP, Greaves MW. Angioedema. J Am Acad Dermatol. 2005; 53: 373–388.PubMedCrossRefGoogle Scholar
  2. 2.
    Champion RH, Roberts SOB, Carpenter RG, Roger JH. Urticaria and angioedema: a review of 554 patients. Br J Dermatol. 1969; 81: 588–597.PubMedCrossRefGoogle Scholar
  3. 3.
    Kaplan AP, Greaves MW. Angioedema. Current Allergy Clin Immunol. 2006; 19: 104–111.Google Scholar
  4. 4.
    Zuberbier T, Bindslev-Jensen C, Canonica W, et al. EAACI/GA2LEN/EDF guideline: management of urticaria. Allergy. 2006; 61: 321–331.PubMedCrossRefGoogle Scholar
  5. 5.
    Downing A, Jacobsen J, Sorenesen HT, et al. Risk of hospitalisation for angioedema among users of newer Cox – 2 selective inhibitors and other nonsteroid anti-inflammatory drugs. Br J Clin Pharmacol. 2006; 62: 496–501.PubMedCrossRefGoogle Scholar
  6. 6.
    Wakelin SH, White IR. Latex allergy. Clin Exp Dermatol. 1999; 24: 245–248.PubMedCrossRefGoogle Scholar
  7. 7.
    Sabroe RA, Seed PT, Francis DM, et al., Chronic idiopathic urticaria: comparison of clinical features of patients with or without anti-FceR1 or anti-IgE autoantibodies. J Am Acad Dermatol. 1999; 40: 443–450.PubMedCrossRefGoogle Scholar
  8. 8.
    Kozel MA, Mekkes JR, Bossuyt PM, Bos JD. Natural course of physical and chronic urticaria and angioedema in 220 patients. J Am Acad Dermatol. 2001; 45: 387–391.PubMedCrossRefGoogle Scholar
  9. 9.
    Hide M, Francis DM, Grattan C, et al. Autoantibodies against the high-affinity IgE receptor as a cause for histamine release in chronic urticaria. New Engl J Med. 1993; 328: 1599–1604.PubMedCrossRefGoogle Scholar
  10. 10.
    Sabroe RA, Greaves MW. Chronic idiopathic urticaria with functional autoantibodies: 12 years on. Br J Dermatol. 2006; 154: 813–819.PubMedCrossRefGoogle Scholar
  11. 11.
    Greaves MW. Chronic idiopathic urticaria. Curr Opin Allergy Clin Immunol. 2003; 3: 363–368.PubMedCrossRefGoogle Scholar
  12. 12.
    Nimii N, Francis DM, Kermani F, et al. Dermal mast cell activation by autoantibodies against the high affinity IgE receptor in chronic urticaria. J Invest Dermatol. 1996; 106: 1001–1006.CrossRefGoogle Scholar
  13. 13.
    Wedi B, Novacovic V, Koerner M, et al. Chronic urticaria serum induces histamine release, leukotriene and basophil CD 63 surface expression-inhibitory effects of anti-inflammatory drugs. J Allergy Clin Immunol. 2000; 105: 552–560.PubMedCrossRefGoogle Scholar
  14. 14.
    Confino-Cohen R, Aharoni D, Goldberg A, et al. Evidence for aberration of regulation of the p21 Ras pathway in PBMC's of patients with chronic idiopathic urticaria. J Allergy Clin Immunol. 2002; 109: 349–356.PubMedCrossRefGoogle Scholar
  15. 15.
    Black AK. Physical urticaria and cholinergic urticaria. In Greaves MW, Kaplan AP, eds, Urticaria and Angioedema. New York: Marcel Dekker, 2004: 171–214.Google Scholar
  16. 16.
    Wisnieski JJ, Baer AN, Christensen J, et al. Hypocomplementaemic urticarial vasculitis syndrome. Clinical and serologic findings in 8 patients. Medicine (Baltimore) 1995; 74: 24–41.CrossRefGoogle Scholar
  17. 17.
    Osler W. Hereditary angioneurotic edema. Am J Med Sci. 1888; 95: 362–367.CrossRefGoogle Scholar
  18. 18.
    Nussberger J, Cugno M, Amstutz C, et al. Plasma bradykinin in angioedema. Lancet. 1998; 351: 1693–1697.PubMedCrossRefGoogle Scholar
  19. 19.
    Visy B, Fust G, Varga L, et al. Sex hormones in hereditary angioneurotic oedema. Clin Endocrinol. (Oxf) 2004; 60: 508–515.CrossRefGoogle Scholar
  20. 20.
    Yip J, Cunliffe WJ. Hormonally exacerbated Hereditary angioedoema. Australas. J Dermatol. 1992; 33: 35–38.PubMedCrossRefGoogle Scholar
  21. 21.
    Gompels MM, Lock RJ, Morgan JE, et al. A multicentre study of the diagnostic efficiency of serological investigations for C1 inhibitor deficiency. J Clin Pathol. 2002; 55: 145–147.PubMedCrossRefGoogle Scholar
  22. 22.
    Tosi M. Molecular genetics of C'1 inhibitor. Immunobiology 1998; 119: 358–365.Google Scholar
  23. 23.
    Kramer J, Rosen F, Colten H, et al. Transinhibition of C'1 inhibitor synthesis in type I hereditary angioedema. J Clin Immunol. 1993; 91: 1258–1262.Google Scholar
  24. 24.
    Farkas H, Harmat G, Fust G, et al. Clinical management of hereditary angio-oedema in children. Pediatr Allergy Immunol 2002; 13: 153–161.PubMedCrossRefGoogle Scholar
  25. 25.
    Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: the clinical syndrome and its management. Ann Int Med. 1976; 84: 580–593.PubMedGoogle Scholar
  26. 26.
    Farkas H, Harmat G, Fay A, et al. erythema marginatum preceding an acute oedematous attack of hereditary angio-neurotic oedema. Acta Derm Venereol. 2001; 81: 376–377.PubMedCrossRefGoogle Scholar
  27. 27.
    Shah TJ, Knowles WO, Mc Geadt SJ. Hereditary angioedema with recurrent abdominal pain and ascites. J Allergy Clin Immunol. 1995; 96: 259–261.PubMedCrossRefGoogle Scholar
  28. 28.
    Farkas H, Harmat G, Kaposi PN, et al. Ultrasonography in the diagnosis and monitoring of ascites in acute abdominal attacks of hereditary angioneurotic oedema. Eur J Gastroenterol Hepatol. 2001; 13: 1225–1230.PubMedCrossRefGoogle Scholar
  29. 29.
    Bork K, Siedlecki K, Bosch S, Schopf RE, Kreuz, W. Asphyxiation due to laryngeal edema in patients with hereditary angioedema. Mayo Clin Proc. 2000; 75: 349–354.PubMedCrossRefGoogle Scholar
  30. 30.
    Koide M, Shirahama S, Tokura Y, et al. Lupus erythematosus associated with C1 inhibitor deficiency. J Dermatol. 2002; 29: 503–507.PubMedGoogle Scholar
  31. 31.
    Gompels, MM, Lock RJ, Unsworth GJ, et al. Misdiagnosis of hereditary angioedema type 1 and type 2. Br J Dermatol. 2003; 148: 719–723.PubMedCrossRefGoogle Scholar
  32. 32.
    Zuraw BL, Sugimoto S, Curd JG. The value of rocket immunoelectrophoresis for C'4 activation in the evaluation of patients with angioedema or C1-inhibitor deficiency. J Allergy Clin Immunol. 1986; 78: 1115–1120.PubMedCrossRefGoogle Scholar
  33. 33.
    Nielson EW, Johanson HT, Holt J, Mollines TE. C1 inhibitor and diagnosis of HAE in new-borns. Paediatr Res. 1994; 35: 184–187.Google Scholar
  34. 34.
    Warin RP, Cunliffe WJ, Greaves MW, Wallington TB. Recurrent angioedema: familial and oestrogen-induced. Br J Dermatol. 1986; 115: 731–734.PubMedCrossRefGoogle Scholar
  35. 35.
    Bork K, Barnstedt SE, Koch P, Traupe H. Hereditary angioedema with normal C1-inhibitor activity in women. Lancet. 2000; 356: 213–217.PubMedCrossRefGoogle Scholar
  36. 36.
    Martin L, Degenne D, Toutain A, Ponard D, Watier H. Hereditary angioedema type 111: an additional French pedigree with autosomal dominant transmission. J Allergy Clin Immunol. 2001; 107: 747–748.PubMedCrossRefGoogle Scholar
  37. 37.
    Binkley KE, Davis AE. Estrogen-dependent inherited angioedema. Transfus Apheresis Sci. 2003; 29: 215–219.CrossRefGoogle Scholar
  38. 38.
    Dewald G, Bork K. Missense mutations in the coaulation factor XII (Hageman factor) genein hereditary angioedema with normal C′ 1 inhibitor. Biochem. Biophys. Res. Commun. 2006; 343: 1286–1289.PubMedCrossRefGoogle Scholar
  39. 39.
    Schreiber A, Zweiman B, Atkins P, et al. Acquired angioedema with lymphoproliferative disorder: association of C′1 inhibitor deficiency with cellular abnormality. Blood. 1976; 48: 567–580.PubMedGoogle Scholar
  40. 40.
    Geha R, Quinti I, Austen KF, et al. Acquired C′1 inhibitor deficiency associated with anti-idiotypic antibody to monoclonal immunoglobulins. N Engl J Med. 1985; 312: 534–540.PubMedGoogle Scholar
  41. 41.
    Donaldson V, Hess E, McAdams A. Lupus erythematosus-like disease in three unrelated women with hereditary angioneurotic edema. Ann Int Med. 1977; 86: 312–313.PubMedGoogle Scholar
  42. 42.
    Jackson J, Sim R, Whelan A, et al. An IgG autoantibody which inactivates C1-inhibitor. Nature. 1986; 323: 722–724.PubMedCrossRefGoogle Scholar
  43. 43.
    Alsenz, J, Bork K, Loos M. Autoantibody-mediated acquired deficiency of C1 Inhibitor. N Engl J Med. 1987; 316: 1360–1366.PubMedGoogle Scholar
  44. 44.
    Chevailler A, Arlaud G, Ponard D, et al. C1-inhibitor binding monoclonal immunoglobulins in three patients with acquired angioneurotic oedema. J Allergy Clin Immunol. 1996; 97: 998–1008.PubMedCrossRefGoogle Scholar
  45. 45.
    Agah R, Bandi V, Gunturpalli KK. Angioedema: the role ofACE inhibitors and factors associated with poor outcome. Intensive Care Med. 1999; 23: 793–796.CrossRefGoogle Scholar
  46. 46.
    Hedner T, Samuelsson O, Lunde H et al. Angioedema in relation to treatment with angiotensin converting enzyme inhibitors. Brit Med. J. 1992; 304: 941–946.PubMedCrossRefGoogle Scholar
  47. 47.
    Lin RY, Shah SN, Karandish K. Increasing Hospitalisations due to angioedema in the united States. J Allergy Clin Immunol. 2008; Suppl. 1; 121: S99 (abs).CrossRefGoogle Scholar
  48. 48.
    Pigman EC, Scott JL. Angioedema in the emergency department: the impact of angiotensin converting enzyme inhibitors. Am J Emerg Med. 1993; 11: 350–354.PubMedCrossRefGoogle Scholar
  49. 49.
    Schiller PI, Langauer MS, Haefeli WE, et al. Angiotensin-converting enzyme inhibitor induced angioedema: late onset, irregular course and potential role of triggers. Allergy. 1997; 52: 432–435.PubMedCrossRefGoogle Scholar
  50. 50.
    Brown NJ, Snowden M, Griffin MR. Recurrent angiotensin convertase enzyme inhibitor-associated angioedema. J Am Med Assoc. 1997; 278: 232–233.CrossRefGoogle Scholar
  51. 51.
    Greaves MW, Shuster S. Responses of skin blood vessels to bradykinin, histamine and 5-hydroxytryptamine. J Physiol. 1967; 193: 255–267.PubMedGoogle Scholar
  52. 52.
    Nussberger J, Cugno M, Amstutz C, et al. Plasma bradykinin in angioedema. Lancet 1998; 351: 1693–1697.PubMedCrossRefGoogle Scholar
  53. 53.
    Mathews KP, Pan M, Gardner MJ, Hugli T. Familial carboxypeptidase N deficiency. Ann Int Med. 1980; 93: 443–445.PubMedGoogle Scholar
  54. 54.
    Sabroe RA, Black AK. Angiotensin converting enzyme (ACE) inhibitors and angioedema. Br J Dermatol. 1997; 136: 153–158.PubMedCrossRefGoogle Scholar
  55. 55.
    Irons BK, Kumar A. Valsartan-induced angioedema. Ann Pharmacother. 2003; 37: 1024–1027.PubMedCrossRefGoogle Scholar
  56. 56.
    Abdi R, Dong VM, Lee CJ, Ntoso KA. Angiotensin 11 receptor blocker-associated angioedema: on the heels of ACE inhibitor angioedema. Pharmacotherapy. 2002; 22: 1173–1175.PubMedCrossRefGoogle Scholar
  57. 57.
    Tan Y, Hutchinson FN, Jaffa AA. Mechanisms of angiotensin 11-induced expression of B2 kinin receptors. Am J Physiol Heart Circ Physiol. 2004; 286: H926–932.PubMedCrossRefGoogle Scholar
  58. 58.
    Coats AJ. Omipatrilat — the story of Overture and Octave. Int J Cardiol. 2002; 86: 1–4.PubMedCrossRefGoogle Scholar
  59. 59.
    Pickering RJ, Kelly JR, Good RA, Gerwuz H. Replacement therapy in hereditary angioedema: successful treatment of two patients with fresh frozen plasma. Lancet. 1969; 1: 326–330.PubMedCrossRefGoogle Scholar
  60. 60.
    Gompels MM, Lock RJ. C1 inhibitor deficiency: management. Clin Exp Dermatol. 2005; 30: 737–740.PubMedCrossRefGoogle Scholar
  61. 61.
    Waytes TA, Rosen FS, Frank MM. Treatment of hereditary angioedema with a vapor-heated C′1 inhibitor concentrate. N Engl J Med. 1996; 334: 1630–1634.PubMedCrossRefGoogle Scholar
  62. 62.
    Bowen T, Cicardi M, Farkas H, et al. Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema. J Allergy Clin Immunol. 2004; 114: 629–646.PubMedCrossRefGoogle Scholar
  63. 63.
    Bork K, Yasothan U, Kirkpatrick P. Icatibant. Nat Rev Drug Disc 2008; 7: 801–802.CrossRefGoogle Scholar
  64. 64.
    Cugno M, Cicardi M, Agostoni A. Activation of the contact system and fibrinolysis in autoimmune acquired angioedema: a rationale for prophylactic use of tranexamic acid. J Allergy Clin Immunol. 1994; 93: 870–876.PubMedCrossRefGoogle Scholar
  65. 65.
    Oike Y, Ogata Y, Higashi D, et al. Fatal angioedema associated with enalapril. Int Med. 1993; 32: 308–310.CrossRefGoogle Scholar
  66. 66.
    Thompson T, Frable M. Drug-induced life-threatening angioedema revisited. Laryngoscope. 1993; 103: 10–12.PubMedCrossRefGoogle Scholar
  67. 67.
    Orfan, N, Patterson R, Dykewicz M. Severe angioedema related to ACE inhibitors in patients with a history of idiopathic angioedema. JAMA. 1990; 264: 1287–1289.PubMedCrossRefGoogle Scholar
  68. 68.
    Kaplan AP. Clinical practice. Chronic urticaria and angioedema. N Engl J Med. 2002; 346: 175–179.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2009

Authors and Affiliations

  • Malcolm W. Greaves
    • 1
    • 2
  • Allen P. Kaplan
    • 3
  1. 1.London Allergy Clinic, 66New Cavendish St London W1 and Institute of DermatologyLondonUK
  2. 2.Guy's Kings and St Thomas' Schools of Medicine and DentistryUniversity of LondonLondonUK
  3. 3.National Allergy and Urticaria Centres of CharlestonCharlestonUSA

Personalised recommendations