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Diagnosis

When diagnosing HAE, a combination of factors should be considered, including symptoms, family history and laboratory testing.1

Testing for C1-INH deficiency or dysfunction

Patients suspected of having Type I or Type II HAE are assessed for blood levels of C1-INH function, C1-INH protein, and C4. Using complement testing, a patient’s peripheral blood test will show low C4 levels, in addition to low C1-INH activity or levels. If any of the levels are abnormally low, the tests should be repeated to confirm the diagnosis.1

Delays in diagnosis

HAE is often misdiagnosed, even among patients with a family history:2

  • In a real-world registry study of patients with Type I or Type II HAE, almost half of patients had initially received one or more misdiagnoses (185/418)2
  • Patients who received a misdiagnosis experienced a mean diagnostic delay of 15 years2
  • In general, misdiagnosis can result in increased health resource use, including unnecessary abdominal surgeries and increased risk of death from laryngeal attacks3-5

 

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spotblock image Good to know

  1. Genetic testing increases diagnostic reliability in children. It may be helpful if the mutation of the parent is known, or if biochemical measurements are inconclusive.1,6
  2. Around 25% of HAE cases are due to spontaneous mutations.7

Other types of angioedema

Different types of angioedema that are not hereditary also exist. These can cause symptoms of oedema and pain that are similar to those seen with HAE.8,9

 

    • Acquired deficiency of C1-INH8,9-11
    • Linked to various conditions that produce autoantibodies to C1-INH8,9-11
    • Linked to an underlying condition of white blood cells, which is usually mild, but tests should be done to exclude more serious conditions such as lymphoma8,9-11

Acquired angioedema

  • Acquired deficiency of C1-INH8,9-11
  • Linked to various conditions that produce autoantibodies to C1-INH8,9-11
  • Linked to an underlying condition of white blood cells, which is usually mild, but tests should be done to exclude more serious conditions such as lymphoma8,9-11

Idiopathic angioedema

  • Typically occurs with urticaria and is often chronic and relapsing8,9

Acute allergic angioedema

  • Caused by an allergic reaction to food, medication, insect venom or rubber latex8,9
  • Typically occurs with urticaria 1-2 hours after exposure8,9

Non-allergic or drug-induced angioedema

  • Caused by a reaction to medications, such as angiotensin-converting enzyme (ACE) inhibitors8,9
  • Symptoms may occur days to months after first exposure8,9

References: 

  1. Maurer M, et al. Allergy 2018;73(8):1575–96.
  2. Zanichelli A, et al. Ann Allergy Asthma Immunol 2016;117(4):394–8.
  3. Longhurst H, et al. Clin Rev Allerg Immunol 2016;51(2):230–9.
  4. Patel N, et al. Case Reports Immunol 2015;2015:925861.
  5. Bork K, et al. J Allergy Clin Immunol 2012;130(3):692–7.
  6. Cicardi M, et al. Allergy 2014;69(5):602–16.
  7. Bernstein JA. Am J Manag Care 2018;24(14 Suppl):S292–8.
  8. Angioedema News. Available from: https://angioedemanews.com/angioedema-types/ Accessed August 2021.
  9. DermNet NZ. Available from: https://www.dermnetnz.org/topics/angioedema/##targetText=Angioedema Accessed August 2021.
  10. Angioedema News. Available from: https://angioedemanews.com/acquired-angioedema/ Accessed August 2021.
  11. HAE UK. Available from https://www.haeuk.org/what-is-hae/types-of-hae/ Accessed August 2021.
Job code: C-ANPROM/UK//2467 Date of preparation: August 2021