Jump to main content

Symptoms of Hereditary
Angioedema

Woman drinking coffee.

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 attacks can occur throughout the body.1-3

Graphic showing where HAE attacks can occur in the body: face, larynx, gastrointestinal tract, genitals, and extremities.

Skin/subcutaneous tissue

  • Typically affects the face, extremities, and genitals2,4
  • According to a survey of 158 patients, facial swelling can extend to laryngeal edema2
Travel bag icon.

Attacks to the extremities can prohibit patients from completing daily tasks and may cause patients to miss days of work.5

Example without an HAE attack
Woman's face without an HAE attack.
Example during an HAE attack
Woman's swollen face during an HAE attack.

Gastrointestinal (GI) tract and digestive system

  • In a survey of 445 patients, abdominal attacks were the most commonly reported6
  • May present with mild to severe abdominal pain accompanied by vomiting and/or diarrhea4
  • Based on a survey of 23 patients, untreated abdominal attacks may require, on average, between 24 and 50 hours of bed rest7
  • Often are described as cramping or pain in the abdomen and may be the only sign of HAE for years, before more visible swelling attacks present8
  • GI attacks can involve the oropharynx, small intestine, and colon. Although very rare, involvement of the liver and pancreas has been reported based on a review of 8 case reports published from 1992 to 2019 (hepatic changes, n=1 case report, pancreatitis, n=8 case reports).8
Stethoscope icon.

The nonspecific nature of GI tract HAE attacks can be difficult to attribute to HAE, contributing to delays in diagnosis or misdiagnosis.8

Example without an HAE attack
Woman's abdomen without an HAE attack.
Example during an HAE attack
Woman's swollen abdomen during an HAE attack.

Upper airway, including
larynx and oropharynx

  • Attacks of the larynx can become fatal if left unmanaged4
  • In the past, untreated laryngeal attacks resulted in mortality rates of up to 30%4
  • In a survey of 209 patients, 50% of patients experienced at least 1 laryngeal episode during their lifetime2
Bar graph icon.

Those with undiagnosed HAE are at higher risk for mortality due to lack of proper intervention.2

Example without an HAE attack
Upper airway without an HAE attack.
Example during an HAE attack
Swollen upper airway during an HAE attack.

Hereditary angioedema attack triggers

Some triggers have been identified and may include9,10:

Person in distress icon.

Stress

Bandage icon.

Physical trauma, surgery, or a dental procedure

Thermometer icon.

Infection

Female icon.

Hormonal influence

Machine icon.

Mechanical pressure

Prodromal symptoms are common.

Some prodromes experienced by HAE patients before an attack include10-12:

  • 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.11

Circle showing 96% of patients experience prodrome.
96%
of patients

From a survey of 46 patients, 44 (96%) of the patients reported experiencing some sort of prodromal symptom before an HAE attack.11

Differentiating HAE from other angioedema

It is important to differentiate HAE from other forms of angioedema because the approach to treatment is quite different.13

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 days13,14
  • Can migrate to other parts of the body during a single attack4,15
  • Do not respond to antihistamines, corticosteroids, or epinephrine5
  • May be exacerbated by exogenous estrogens and ACE inhibitors5

References:

  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. 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.
  5. 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
  6. 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. doi:10.1016/j.anai.2020.02.018
  7. 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.
  8. 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
  9. Craig T. Triggers and short-term prophylaxis in patients with hereditary angioedema. Allergy Asthma Proc. 2020;41(Suppl 1):S30-S34. doi:10.2500/aap.2020.41.200065
  10. 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
  11. 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.
  12. Lang DM, Aberer W, Bernstein JA, et al. International consensus on hereditary and acquired angioedema. Ann Allergy Asthma Immunol. 2012;109(6):395-402.
  13. 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
  14. Banerji A. The burden of illness in patients with hereditary angioedema. Ann Allergy Asthma Immunol. 2013;111(5):329-336.
  15. Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008;359(10):1027-1036