A NEW study has produced the first comprehensive estimate of the prevalence of hereditary angioedema (HAE), a rare but potentially life-threatening genetic condition characterised by episodes of swelling in the skin and mucous membranes. HAE can severely impact quality of life and, in some cases, lead to fatal airway obstruction if not treated promptly.
Historically, HAE caused by C1-inhibitor deficiency (HAE-C1INH) was considered extremely rare, with prevalence estimates ranging from 1.1 to 2.0 per 100,000 people. A less common form, HAE with normal C1-inhibitor (HAE-nl-C1INH), has only recently been recognised, with even lower prevalence figures. However, this study found overall HAE prevalence in the US to be significantly higher, ranging from 2.43 to 2.67 per 100,000 using claims-based data, and 1.84 to 2.13 per 100,000 based on expert-reviewed patient records.
These findings suggest that previous estimates may have underrepresented the true HAE population by excluding HAE-nl-C1INH or patients with atypical presentation. Researchers used a proxy algorithm to identify cases within large insurance claims databases, overcoming the lack of specific diagnostic codes in earlier ICD systems. Sensitivity analyses also helped adjust for underrepresented populations, such as older adults on Medicare.
The study highlights the growing role of real-world data in understanding rare diseases and calls for adoption of ICD-11, which includes dedicated HAE codes, to further improve accuracy. With eight HAE-specific therapies approved since 2008 and increased disease awareness efforts, diagnoses are rising. This in turn makes insurance claims databases a more reliable source for tracking HAE prevalence.
While the study acknowledges some limitations, such as gaps in data from Medicaid recipients and the uninsured, it marks a major step forward in quantifying the burden of HAE in the US. These prevalence figures will help guide future research, support development of new treatments, and ensure better access to care for patients living with this serious condition.
Reference
Castaldo AJ et al. Establishing a hereditary angioedema prevalence for the United States using a large administrative claims database. Ann Allergy Asthma Immunol. 2025;DOI:10.1016/j.anai.2025.05.018.
