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Symptoms & Presentation of
Hereditary Angioedema

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Hereditary angioedema (HAE) attacks are usually unpredictable and can be life-threatening. HAE attacks typically cause swelling of the skin/subcutaneous tissues, gastrointestinal tract, and upper airway, including larynx and oropharynx, some of which may be painful and functionally disabling. Almost all patients experience recurrent abdominal pain related to HAE.1-3

HAE can be triggered due to hormonal changes.4

Angioedema presentation throughout the body

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To better understand the impact HAE has on patients, use the Disease Burden Tool.

Hereditary angioedema attack triggers

HAE attacks can occur without warning. Here are some triggers that people with HAE have recognized5,10,11:

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Physical trauma, surgery, or a dental procedure

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Hormonal influence

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Mechanical pressure

Attack triggers for women with HAE may include menstruation, ovulation, pregnancy, and the use of estrogen-containing contraceptives. Nearly ⅓ of women have increased numbers of HAE attacks during or after menopause.6

Prodromal HAE symptoms are common.12

Some prodromes experienced by HAE patients before an attack include 12-14:

  • Tingling sensation
  • Erythema marginatum: a mild, nonpruritic rash
  • Fatigue and malaise
  • Nausea
  • Muscle aches
  • Neurologic symptoms

The most commonly reported prodrome is unusual fatigue and malaise. In a survey of 46 patients, 29 patients reported having unusual fatigue before their most recent HAE attack, and 26 reported unusual fatigue before most or all of their previous attacks.12

Circle showing 96% of patients experience prodromal HAE symptoms.
of patients

From a survey of 46 patients, 44 (96%) of the patients reported experiencing some sort of prodromal symptom before an HAE attack.12

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The severity and frequency of HAE attacks may be different for each patient, and past attacks do not predict the severity of future attacks. Untreated HAE attacks can grow in severity, may take longer to resolve-and in the case of laryngeal attacks can be fatal.6,15

Differentiating HAE from other angioedema

It is important to differentiate HAE from other forms of angioedema because the approach to treatment is quite different.16

HAE attacks:

  • Can occur without warning1,2
  • Develop swelling slower, over 12 to 36 hours, then plateau, and resolve, on average, over 2 to 5 days if left untreated15,16
  • Can migrate to other parts of the body during a single attack5,17
  • Do not respond to antihistamines, corticosteroids, or epinephrine6
  • May be exacerbated by exogenous estrogens and ACE inhibitors6
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  1. Longhurst HJ, Bork K. Hereditary angioedema: causes, manifestations and treatment. Br J Hosp Med (Lond). 2006;67(12):654-657.
  2. 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.
  3. Cicardi M, Aberer W, Banerji A, et al. Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy. 2014;69(5):602-616. doi:10.1111/all.12380
  4. Craig T, Riedl M, Dykewicz MS, et al. When is prophylaxis for hereditary angioedema necessary? Ann Allergy Asthma Immunol. 2009;102(5):366-372. doi:10.1016/S1081-1206(10)60506-6
  5. Agostoni A, Aygören-Pürsün E, Binkley KE, et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004;114(Suppl 3):S51-S131.
  6. Busse PJ, Christiansen SC, Riedl MA, et al. US HAEA Medical Advisory Board 2020 guidelines for the management of hereditary angioedema. J Allergy Clin Immunol Pract. 2021;9(1):132-150. doi:10.1016/j.jaip.2020.08.046
  7. Banerji A, Davis KH, Brown TM, et al. Patient-reported burden of hereditary angioedema: findings from a patient survey in the United States. Ann Allergy Asthma Immunol. 2020;124(6):600-607.
  8. Bork K, Staubach P, Eckardt AJ, Hardt J. Symptoms, course, and complications of abdominal attacks in hereditary angioedema due to C1 inhibitor deficiency. Am J Gastroenterol. 2006;101(3):619-627.
  9. Mormile I, Cocchiaro A, Bova M, et al. Gastrointestinal manifestations of angioedema: a potential area of misdiagnosis. Eur J Gastroenterol Hepatol. 2021;33(6):787-793. doi:10.1097/MEG.0000000000001848
  10. Nielsen EW, Gran JT, Straume B, Mellbye OJ, Johansen HT, Mollnes TE. Hereditary angio-oedema: new clinical observations and autoimmune screening, complement and kallikrein-kinin analyses. J Intern Med. 1996;239(2):119-130.
  11. Bork K, Barnstedt SE. Laryngeal edema and death from asphyxiation after tooth extraction in four patients with hereditary angioedema. J Am Dent Assoc. 2003;134(8):1088-1094.
  12. Prematta MJ, Kemp JG, Gibbs JG, Mende C, Rhoads C, Craig TJ. Frequency, timing, and type of prodromal symptoms associated with hereditary angioedema attacks. Allergy Asthma Proc. 2009;30(5):506-511.
  13. Azmy V, Brooks JP, Hsu FI. Clinical presentation of hereditary angioedema. Allergy Asthma Proc. 2020;41(Suppl 1):S18-S21. doi:10.2500/aap.2020.41.200065
  14. Lang DM, Aberer W, Bernstein JA, et al. International consensus on hereditary and acquired angioedema. Ann Allergy Asthma Immunol. 2012;109(6):395-402.
  15. Banerji A. The burden of illness in patients with hereditary angioedema. Ann Allergy Asthma Immunol. 2013;111(5):329-336.
  16. Manning ME. Hereditary angioedema: differential diagnosis, diagnostic tests, and family screening. Allergy Asthma Proc. 2020;41(Suppl 1):S22-S25. doi:10.2500/aap.2020.41.200062
  17. Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008;359(10):1027-1036