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Angioedema Differential Diagnoses

  • Author: Huamin Henry Li, MD, PhD, CPI; Chief Editor: Michael A Kaliner, MD  more...
 
Updated: Jul 28, 2016
 
 

Diagnostic Considerations

Special consideration should be given to those who experience angioedema without urticaria. In such cases, hereditary and acquired angioedema (AAE) must be differentiated.[14]

When angioedema is associated with urticaria, the diagnostic algorithm is almost identical to that of urticaria patients. For recurrent angioedema without urticaria, it is strongly recommended to rule out hereditary angioedema (HAE), angiotensin-converting enzyme inhibitor induced angioedema (ACEI-AAE, or AIIA), and acquired C1 esterase inhibitor deficiency angioedema (C1-INH-AAE).[49]

Except for ACEI-AAE (or AIIA), C1-INH-AAE, and different types of HAE, a significant proportion of angioedema can be adequately controlled with daily doses of nonsedating antihistamines.[14] Therefore, for angioedema without urticaria, and once C1 INH deficiency and ACEI-AAE are ruled out, empirical treatment with high doses of a second generation antihistamine (up to 4 times more than the conventional dose) can help further categorize the patients (histaminergic vs. nonhistaminergic).

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Huamin Henry Li, MD, PhD, CPI Director of Chevy Chase Clinical Research, Institute for Asthma and Allergy; Assistant Professor, George Washington University Hospital; Clinical Faculty, Johns Hopkins Asthma and Allergy Center, Johns Hopkins Hospital

Huamin Henry Li, MD, PhD, CPI is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, Joint Council of Allergy, Asthma and Immunology, MedChi The Maryland State Medical Society

Disclosure: Received consulting fee from Dyax for consulting; Received consulting fee from Pharming/Salix for consulting; Received consulting fee from CSL Behring for consulting; Received honoraria from Viropharma/Shire for speaking and teaching; Received consulting fee from Viropharma/Shire for consulting; Received honoraria from Dyax for speaking and teaching.

Chief Editor

Michael A Kaliner, MD Clinical Professor of Medicine, George Washington University School of Medicine; Medical Director, Institute for Asthma and Allergy

Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, Association of American Physicians

Disclosure: Nothing to disclose.

Acknowledgements

Stephen C Dreskin, MD, PhD Professor of Medicine, Departments of Internal Medicine, Director of Allergy, Asthma, and Immunology Practice, University of Colorado Health Sciences Center

Stephen C Dreskin, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association for the Advancement of Science, American Association of Immunologists, American College of Allergy, Asthma and Immunology, Clinical Immunology Society, and Joint Council of Allergy, Asthma and Immunology

Disclosure: Genentech Consulting fee Consulting; American Health Insurance Plans Consulting fee Consulting; Johns Hopkins School of Public Health Consulting fee Consulting; Array BioPharma Consulting fee Consulting

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
  1. Wakisaka M, Shuto M, Abe H, et al. Computed tomography of the gastrointestinal manifestation of hereditary angioedema. Radiat Med. 2008 Dec. 26(10):618-21. [Medline].

  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 Aug. 197(2):393-8. [Medline].

  3. Kaplan AP. Urticaria and angioedema. Adkinson Jr, NF. Middleton's Allergy: Principle and Practice. 7th ed. Mosby; 2009. 1061-81.

  4. Nakamura S, Nagao A, Kishino M, Konishi H, Shiratori K. Education and Imaging. Gastrointestinal: angioedema of the small bowel. J Gastroenterol Hepatol. 2008 Jul. 23(7 Pt 1):1158. [Medline].

  5. Raman SP, Lehnert BE, Pruthi S. Unusual radiographic appearance of drug-induced pharyngeal angioedema and differential considerations. AJNR Am J Neuroradiol. 2009 Jan. 30(1):77-8. [Medline].

  6. Donati M. De medica historia mirabili. Mantuae, per Fr. Osanam. 1586.

  7. Milton JL. On giant urticaria. Edinburgh Med J. 1876. 22:513-26.

  8. Quincke H. Uber Akutes Umschreibenes H Autodem. Monatusschr Pract Dermatol. 1882. 129-31.

  9. Osler W. Hereditary angio-neurotic edema. Am J Med Sci. 1888. 95:362-7.

  10. Adhikari SP, Schneider JI. An unusual cause of abdominal pain and hypotension: angioedema of the bowel. J Emerg Med. 2009 Jan. 36(1):23-5. [Medline].

  11. Kaplan AP. Angioedema. World Allergy Organ J. 2008 Jun. 1(6):103-13. [Medline].

  12. Rye Rasmussen EH, Bindslev-Jensen C, Bygum A. Angioedema--assessment and treatment. Tidsskr Nor Laegeforen. 2012 Nov 12. 132(21):2391-5. [Medline].

  13. Marx J, Hockberger R, Walls R. Urticaria and angioedema. Rosen's Emergency Medicine. 7th ed. Mosby; 2009. [Full Text].

  14. Mansi M, Zanichelli A, Coerezza A, Suffritti C, Wu MA, Vacchini R, et al. Presentation, diagnosis and treatment of angioedema without wheals: a retrospective analysis of a cohort of 1058 patients. J Intern Med. 2014 Sep 4. [Medline].

  15. [Guideline] Cicardi M, Aberer W, Banerji A, Bas M, Bernstein JA, Bork K, et al. Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy. 2014 May. 69(5):602-16. [Medline].

  16. Oschatz C, Maas C, Lecher B, Jansen T, Björkqvist J, Tradler T, et al. Mast cells increase vascular permeability by heparin-initiated bradykinin formation in vivo. Immunity. 2011 Feb 25. 34(2):258-68. [Medline].

  17. Asero R, Bavbek S, Blanca M, Blanca-Lopez N, Cortellini G, Nizankowska-Mogilnicka E, et al. Clinical management of patients with a history of urticaria/angioedema induced by multiple NSAIDs: an expert panel review. Int Arch Allergy Immunol. 2013. 160(2):126-33. [Medline].

  18. Fonacier LS, Dreskin SC, Leung DY. Allergic skin diseases. J Allergy Clin Immunol. 2010 Feb. 125(2 Suppl 2):S138-49. [Medline].

  19. Bas M, Adams V, Suvorava T, Niehues T, Hoffmann TK, Kojda G. Nonallergic angioedema: role of bradykinin. Allergy. 2007 Aug. 62(8):842-56. [Medline].

  20. Cugno M, Marzano AV, Asero R, Tedeschi A. Activation of blood coagulation in chronic urticaria: pathophysiological and clinical implications. Intern Emerg Med. 2010 Apr. 5(2):97-101. [Medline].

  21. Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4. 359(10):1027-36. [Medline].

  22. Champion RH, Roberts SO, Carpenter RG, Roger JH. Urticaria and angio-oedema. A review of 554 patients. Br J Dermatol. 1969 Aug. 81(8):588-97. [Medline].

  23. Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012 May 4. 18(5):693-704. [Medline]. [Full Text].

  24. Frigas E, Nzeako UC. Angioedema. Pathogenesis, differential diagnosis, and treatment. Clin Rev Allergy Immunol. 2002 Oct. 23(2):217-31. [Medline].

  25. Banerji A, Sheffer AL. The spectrum of chronic angioedema. Allergy Asthma Proc. 2009 Jan-Feb. 30(1):11-6. [Medline].

  26. Cugno M, Zanichelli A, Foieni F, Caccia S, Cicardi M. C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress. Trends Mol Med. 2009 Feb. 15(2):69-78. [Medline].

  27. Kaplan AP, Greaves M. Pathogenesis of chronic urticaria. Clin Exp Allergy. 2009 Jun. 39(6):777-87. [Medline].

  28. Zingale LC, Castelli R, Zanichelli A, Cicardi M. Acquired deficiency of the inhibitor of the first complement component: presentation, diagnosis, course, and conventional management. Immunol Allergy Clin North Am. 2006 Nov. 26(4):669-90. [Medline].

  29. Byrd JB, Adam A, Brown NJ. Angiotensin-converting enzyme inhibitor-associated angioedema. Immunol Allergy Clin North Am. 2006 Nov. 26(4):725-37. [Medline].

  30. Bork K, Barnstedt SE, Koch P, Traupe H. Hereditary angioedema with normal C1-inhibitor activity in women. Lancet. 2000 Jul 15. 356(9225):213-7. [Medline].

  31. Bowen T, Cicardi M, Bork K, Zuraw B, Frank M, Ritchie B, 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 Jan. 100(1 Suppl 2):S30-40. [Medline].

  32. Dewald G, Bork K. Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun. 2006 May 19. 343(4):1286-9. [Medline].

  33. Bork K, Gül D, Dewald G. Hereditary angio-oedema with normal C1 inhibitor in a family with affected women and men. Br J Dermatol. 2006 Mar. 154(3):542-5. [Medline].

  34. Craig TJ, Levy RJ, Wasserman RL, et al. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol. 2009 Oct. 124(4):801-8. [Medline].

  35. Bossi F, Fischetti F, Regoli D, et al. Novel pathogenic mechanism and therapeutic approaches to angioedema associated with C1 inhibitor deficiency. J Allergy Clin Immunol. 2009 Dec. 124(6):1303-10.e4. [Medline]. [Full Text].

  36. Banerji A, Weller PF, Sheikh J. Cytokine-associated angioedema syndromes including episodic angioedema with eosinophilia (Gleich's Syndrome). Immunol Allergy Clin North Am. 2006 Nov. 26(4):769-81. [Medline].

  37. Ferreli C, Pinna AL, Atzori L, Aste N. Eosinophilic cellulitis (Well's syndrome): a new case description. J Eur Acad Dermatol Venereol. 1999 Jul. 13(1):41-5. [Medline].

  38. Brown AF, McKinnon D, Chu K. Emergency department anaphylaxis: A review of 142 patients in a single year. J Allergy Clin Immunol. 2001 Nov. 108(5):861-6. [Medline].

  39. Yang MS, Lee SH, Kim TW, et al. Epidemiologic and clinical features of anaphylaxis in Korea. Ann Allergy Asthma Immunol. 2008 Jan. 100(1):31-6. [Medline].

  40. Kalmár L, Hegedüs T, Farkas H, Nagy M, Tordai A. HAEdb: a novel interactive, locus-specific mutation database for the C1 inhibitor gene. Hum Mutat. 2005 Jan. 25(1):1-5. [Medline].

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

  42. Frigas E, Park M. Idiopathic recurrent angioedema. Immunol Allergy Clin North Am. 2006 Nov. 26(4):739-51. [Medline].

  43. Hentges F, Hilger C, Kohnen M, Gilson G. Angioedema and estrogen-dependent angioedema with activation of the contact system. J Allergy Clin Immunol. 2009 Jan. 123(1):262-4. [Medline].

  44. Cichon S, Martin L, Hennies HC, et al. Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III. Am J Hum Genet. 2006 Dec. 79(6):1098-104. [Medline]. [Full Text].

  45. Gleich GJ, Leiferman KM. The hypereosinophilic syndromes: current concepts and treatments. Br J Haematol. 2009 May. 145(3):271-85. [Medline].

  46. Morgan M, Khan DA. Therapeutic alternatives for chronic urticaria: an evidence-based review, Part 2. Ann Allergy Asthma Immunol. 2008 Jun. 100(6):517-26; quiz 526-8, 544. [Medline].

  47. Bouillet L, Longhurst H, Boccon-Gibod I, Bork K, Bucher C, Bygum A, et al. Disease expression in women with hereditary angioedema. Am J Obstet Gynecol. 2008 Nov. 199(5):484.e1-4. [Medline].

  48. Sánchez-Borges M, Asero R, Ansotegui IJ, Baiardini I, Bernstein JA, Canonica GW, et al. Diagnosis and treatment of urticaria and angioedema: a worldwide perspective. World Allergy Organ J. 2012 Nov. 5(11):125-47. [Medline].

  49. Joint Taskforce on Practice Parameters Website. Available at http://www.allergyparameters.org/. Accessed: June 5, 2013.

  50. Joint Taskforce on Practice Parameters. Angioedema practice parameters: 2013 update. J Allergy Clin Immunol. [in press] June 2013.

  51. Cugno M, Zanichelli A, Bellatorre AG, Griffini S, Cicardi M. Plasma biomarkers of acute attacks in patients with angioedema due to C1-inhibitor deficiency. Allergy. 2009 Feb. 64(2):254-7. [Medline].

  52. Lang DM, Aberer W, Bernstein JA, Chng HH, Grumach AS, Hide M, et al. International consensus on hereditary and acquired angioedema. Ann Allergy Asthma Immunol. 2012 Dec. 109(6):395-402. [Medline].

  53. Powell RJ, Leech SC, Till S, Huber PA, Nasser SM, Clark AT. BSACI guideline for the management of chronic urticaria and angioedema. Clin Exp Allergy. 2015 Mar. 45(3):547-65. [Medline].

  54. Craig T, Pürsün EA, Bork K, Bowen T, Boysen H, Farkas H, et al. WAO Guideline for the Management of Hereditary Angioedema. World Allergy Organ J. 2012 Dec. 5(12):182-199. [Medline].

  55. Zuberbier T, Asero R, Bindslev-Jensen C, Walter Canonica G, Church MK, Giménez-Arnau A, et al. EAACI/GA(2)LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy. 2009 Oct. 64(10):1417-26. [Medline].

  56. Ferrer M, Sastre J, Jáuregui I, Dávila I, Montoro J, del Cuvillo A, et al. Effect of antihistamine up-dosing in chronic urticaria. J Investig Allergol Clin Immunol. 2011. 21 Suppl 3:34-9. [Medline].

  57. Handa S, Dogra S, Kumar B. Comparative efficacy of cetirizine and fexofenadine in the treatment of chronic idiopathic urticaria. J Dermatolog Treat. 2004 Jan. 15(1):55-7. [Medline].

  58. Potter PC, Kapp A, Maurer M, Guillet G, Jian AM, Hauptmann P, et al. Comparison of the efficacy of levocetirizine 5 mg and desloratadine 5 mg in chronic idiopathic urticaria patients. Allergy. 2009 Apr. 64(4):596-604. [Medline].

  59. Curran MP, Scott LJ, Perry CM. Cetirizine: a review of its use in allergic disorders. Drugs. 2004. 64(5):523-61. [Medline].

  60. Hindmarch I, Johnson S, Meadows R, Kirkpatrick T, Shamsi Z. The acute and sub-chronic effects of levocetirizine, cetirizine, loratadine, promethazine and placebo on cognitive function, psychomotor performance, and weal and flare. Curr Med Res Opin. 2001. 17(4):241-55. [Medline].

  61. Asero R, Tedeschi A, Lorini M. Leukotriene receptor antagonists in chronic urticaria. Allergy. 2001 May. 56(5):456-7. [Medline].

  62. Maurer M, Rosén K, Hsieh HJ, Saini S, Grattan C, Gimenéz-Arnau A, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013 Mar 7. 368(10):924-35. [Medline].

  63. Spector SL, Tan RA. Advances in allergic skin disease: omalizumab is a promising therapy for urticaria and angioedema. J Allergy Clin Immunol. 2009 Jan. 123(1):273-4. [Medline].

  64. Song CH, Stern S, Giruparajah M, Berlin N, Sussman GL. Long-term efficacy of fixed-dose omalizumab for patients with severe chronic spontaneous urticaria. Ann Allergy Asthma Immunol. 2013 Feb. 110(2):113-7. [Medline].

  65. Zuraw BL et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. Aug 2010. 363:513-22.

  66. Riedl MA, Hurewitz DS, Levy R, Busse PJ, Fitts D, Kalfus I. Nanofiltered C1 esterase inhibitor (human) for the treatment of acute attacks of hereditary angioedema: an open-label trial. Ann Allergy Asthma Immunol. 2012 Jan. 108(1):49-53. [Medline].

  67. Cicardi M et al. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. Aug 2010. 363:523-31.

  68. Cicardi M, et al. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010 Aug 5. 363(6):532-41. [Medline].

  69. US Food and Drug Administration. FDA approves Firazyr to treat acute attacks of hereditary angioedema. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm269616.htm. Accessed: January 3, 2013.

  70. [Guideline] Cicardi M, Bork K, Caballero T, Craig T, Li HH, Longhurst H, et al. Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy. 2012 Feb. 67(2):147-57. [Medline].

  71. [Guideline] Caballero T, Farkas H, Bouillet L, Bowen T, Gompel A, Fagerberg C, et al. International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency. J Allergy Clin Immunol. 2012 Feb. 129(2):308-20. [Medline].

  72. Simons FE, Sussman GL, Simons KJ. Effect of the H2-antagonist cimetidine on the pharmacokinetics and pharmacodynamics of the H1-antagonists hydroxyzine and cetirizine in patients with chronic urticaria. J Allergy Clin Immunol. 1995 Mar. 95(3):685-93. [Medline].

  73. Paul E, Bödeker RH. Treatment of chronic urticaria with terfenadine and ranitidine. A randomized double-blind study in 45 patients. Eur J Clin Pharmacol. 1986. 31(3):277-80. [Medline].

  74. Sharpe GR, Shuster S. In dermographic urticaria H2 receptor antagonists have a small but therapeutically irrelevant additional effect compared with H1 antagonists alone. Br J Dermatol. 1993 Nov. 129(5):575-9. [Medline].

  75. Fedorowicz Z, van Zuuren EJ, Hu N. Histamine H2-receptor antagonists for urticaria. Cochrane Database Syst Rev. 2012 Mar 14. 3:CD008596. [Medline].

  76. Trojan TD, Khan DA. Calcineurin inhibitors in chronic urticaria. Curr Opin Allergy Clin Immunol. 2012 Aug. 12(4):412-20. [Medline].

 
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Photographic documentation of swelling.
Bradykinin production and metabolism.
Classification of angioedema without urticaria based on clinical or etiopathologic features. AAE = acquired angioedema; ACEI = angiotensin-converting enzyme inhibitors; HAE = hereditary angioedema; Specific triggers = food, drug, insect bite, environmental allergen, or other physical stimulus. Based on data from Zingale LC, Beltrami L, Zanichelli A, et al. Angioedema without urticaria: a large clinical survey. CMAJ. Oct 24 2006; 175(9): 1065–70.
Angioedema secondary to angiotensin-converting enzyme (ACE) inhibitors.
Types of angioedema.
Pathways for production of prostaglandins and leukotrine from mobilized arachidonic acid.
 
 
 
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