HAE Diagnosis

Because Hereditary angioedema (HAE) is so rare, an HAE diagnosis may be delayed. On average, there is more than a 10-year delay in diagnosis from the first attack. Some patients have remained undiagnosed for decades. This setback means that patients must live with extremely painful and often debilitating symptoms of an otherwise manageable condition. In particular, those patients with laryngeal attacks are at much greater risk of death without effective treatment.19

Cutaneous HAE attacks are often misdiagnosed as allergic angioedema.19 Cutaneous HAE attacks can be preceded by erythema marginatum (a nonpruritic, serpiginous rash with a map-like pattern) in up to one-third of patients.2

Abdominal HAE symptoms can be mistaken for a number of other conditions, including gastroenteritis, acute appendicitis, bowel obstruction, diverticulitis, and pancreatitis. Patients are often subjected to unnecessary surgery and diagnostic procedures, particularly when severe abdominal pain is the primary complaint.2,19

From a review of a large database, nearly 50% of patients with HAE received 1 or more incorrect diagnoses. In addition, almost half of the patients with a positive family history of HAE received a wrong diagnosis.19

Considering that symptoms often begin during childhood, a delay in diagnosis is likely to significantly disrupt patients’ education and early working life and could account for many of the reported psychological, social, and economic consequences for patients with HAE.19 Even during attack-free periods, HAE has an emotional impact on patients’ quality of life, reinforcing the clinical importance of reducing disease burden.18

Laboratory Testing for HAE Diagnosis

The WAO/EAACI guideline states HAE Type 1 or Type 2 should be suspected when a patient presents with a history of recurrent angioedema attacks, which is further substantiated by evidence ruling out other forms of angioedema. Laboratory testing can then support a diagnosis of HAE Type 1 or Type 2.8

C1-INH quantitative to count the number of C1-INH proteins in the blood

C1-INH functional to measure how well the protein is working

C4 protein level is typically low in confirmed cases of  HAE Type 1 or 224


References

  • [2] Lumry WR. Overview of epidemiology, pathophysiology, and disease progression in hereditary angioedema. Am J Manag Care. 2013;19(7 Suppl):s103-110.
  • [8] Maurer M, Magerl M, Betschel S, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update. Allergy. 2022;77(7):1961-1990.
  • [18] Bygum A, Aygören-Pürsün E, Beusterien K, Hautamaki E, Sisic Z, Wait S, Boysen HB, Caballero T (2015) Burden of illness in hereditary angioedema: a conceptual model. Acta Derm Venereol 95:706–710
  • [19] Zanichelli A, Longhurst HJ, Maurer M, et al. Misdiagnosis trends in patients with hereditary angioedema from the real-world clinical setting. Ann Allergy Asthma Immunol. 2016 Oct;117(4):394-398.
  • [24] US Hereditary Angioedema Association. Comprehensive Table of Angioedema Types.