ENOrphanet Journal of Rare Diseases | A Multinational Survey on the Burden of Disease in Patients with Hereditary Angioedema
Date: February 22, 2026
Classification: Frontiers
Recommend:
This study, through a multinational survey covering 13 countries, reveals significant disease burden in patients with hereditary angioedema, including frequent attacks, impaired quality of life, poor disease control, and reduced work productivity, and finds that most patients are not receiving guideline-recommended first-line long-term prophylactic treatment.
Literature Overview
The article titled 'Burden of disease in adult patients with hereditary angioedema: results from a multinational survey,' published in the journal *Orphanet Journal of Rare Diseases*, reviews and summarizes demographic and clinical characteristics and patient-reported outcomes from 260 adult patients with hereditary angioedema (HAE) across Argentina, Brazil, Colombia, Croatia, Denmark, Germany, Hungary, Ireland, Norway, Poland, Portugal, Romania, and Sweden. Using a web-based cross-sectional survey, the study assessed multidimensional burdens including disease control, health-related quality of life, mental health, and work productivity. Results show that patients frequently experience HAE attacks, have poor disease control, suffer significantly impaired quality of life, and most are not receiving first-line long-term prophylaxis recommended by international guidelines. This study provides important real-world data to understand the burden of HAE.Background Knowledge
Hereditary angioedema (HAE) is a rare autosomal dominant disorder primarily caused by mutations in the C1 inhibitor (C1INH) gene, leading to functional or quantitative deficiency of C1INH (HAE-C1INH), with a minority having normal C1INH (HAE-nC1INH). The disease is characterized by recurrent episodes of subcutaneous or submucosal edema affecting the skin, abdomen, and upper airway, with laryngeal edema potentially leading to fatal asphyxiation. Although modern therapies such as C1INH concentrates, lanadelumab, and berotralstat are recommended as first-line long-term prophylaxis (LTP) by international guidelines, global access remains limited. Patients often rely on less effective and less safe second-line treatments like danazol or tranexamic acid due to delayed diagnosis, limited treatment options, or reimbursement barriers. Previous studies have shown HAE significantly impacts patients’ quality of life, mental health, and economic status, but most research has focused on high-income countries. This study expands geographical coverage by including several previously understudied countries, filling a gap in multinational burden data and highlighting the urgent need to improve treatment accessibility.
Methods and Experiment
This was a non-interventional, cross-sectional, web-based multinational survey enrolling adult HAE patients from 13 countries. Participants were required to: self-report a physician diagnosis of HAE, have experienced at least one HAE attack or prodromal symptom in the past year, and have used HAE-related medication within the past two years. Data were collected via standardized questionnaires covering demographics, clinical characteristics, and validated patient-reported outcome (PRO) instruments: the Angioedema Control Test (AECT) for disease control; the Angioedema Quality of Life (AE-QoL) for health-related quality of life (HRQoL); SF-12 v2 for general health; the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression; and the Work Productivity and Activity Impairment: General Health (WPAI:GH) for work productivity loss. Descriptive statistics were used for analysis, with continuous variables presented as mean ± standard deviation and categorical variables as n (%).Key Findings and Insights
Implications and Outlook
This study is the first to systematically assess the multidimensional burden of HAE in several previously understudied countries, revealing that even in nations where modern therapies are available, most patients are not receiving guideline-recommended first-line LTP. This highlights a gap between treatment accessibility, reimbursement policies, and clinical practice. The findings emphasize that HAE not only causes frequent physical symptoms but also significantly affects mental health and daily functioning, particularly due to the ongoing anxiety and shame associated with unpredictable attacks. Future efforts should promote broader patient education, increase awareness of modern treatment options, and advocate for improved drug access policies. Additionally, the study supports incorporating patient-reported outcomes (PROs) into routine HAE management to enable individualized treatment goals.
Conclusion
This multinational survey of 260 adult HAE patients from 13 countries comprehensively reveals the multifaceted burden of the disease. Results show patients experience over 20 HAE attacks annually on average, have poor disease control, significantly reduced quality of life, and substantial work productivity loss and psychological distress. Although more than half of patients use long-term prophylaxis, only about one-third receive first-line therapies recommended by international guidelines, indicating major barriers to treatment access globally. Disease burden is closely linked to attack frequency—more frequent attacks correlate with poorer perceived control and lower quality of life. Notably, even patients without recent attacks still experience reduced quality of life, likely due to psychological stress from disease unpredictability. These findings underscore the urgency of improving HAE patient management, including enhancing access to first-line prophylactic treatments, strengthening patient education to align treatment expectations, and integrating patient-reported outcomes into clinical decision-making. This study provides crucial evidence to inform more effective HAE management strategies and health policies.
