Orphanet Journal of Rare Diseases | Multinational Survey of Caregivers for Hereditary Angioedema Patients Reveals Significant Psychological and Life Burden

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This study reveals the significant psychological, occupational, and daily life impacts on family members caring for patients with hereditary angioedema through a multinational survey, highlighting the urgent need for caregiver support.

 

Literature Overview

The article titled 'Burden of hereditary angioedema: results from a multinational survey of caregivers for adult and pediatric patients', published in the Orphanet Journal of Rare Diseases, reviews and summarizes the psychological and quality-of-life burdens experienced by primary caregivers of patients with hereditary angioedema (HAE). Using an online questionnaire conducted across 13 countries in Europe and South America, the study collected self-reported data from 120 caregivers, covering time investment, emotional distress, work impact, and social functioning limitations during caregiving. Results show that caregivers of both pediatric and adult patients face significant physical and mental stress, particularly in the form of persistent concerns about the patient's health and future, sleep disturbances, anxiety, and work absenteeism. The study emphasizes the broad negative impacts of HAE on family caregivers and calls for systematic interventions to support caregivers within disease management. The data provide crucial empirical evidence for understanding the burden of care in rare diseases and suggest that clinical practice should prioritize caregiver mental health.

Background Knowledge

Hereditary angioedema (HAE) is a rare autosomal dominant disorder primarily caused by deficiency or dysfunction of C1 inhibitor (C1INH), characterized by recurrent episodes of skin or submucosal swelling. In severe cases, laryngeal involvement can lead to asphyxiation and be life-threatening. HAE is classified into types I and II associated with C1INH deficiency, and HAE-nC1INH with normal but dysfunctional C1INH. The global prevalence is approximately 1 in 50,000 to 1 in 100,000, with symptoms often beginning in childhood and persisting throughout life. The unpredictable nature of HAE significantly affects patients' quality of life, including absenteeism, anxiety, depression, and social avoidance. Although on-demand treatments for acute attacks (e.g., icatibant, C1INH concentrates) and long-term prophylaxis (e.g., lanadelumab, berotralstat) are available, access to treatment varies geographically. Caring for HAE patients is typically performed by family members, yet the caregiving burden has been largely overlooked in previous studies. Most existing research focuses on patients’ quality of life, with limited systematic assessment of the psychological and social impacts on caregivers. This study fills that gap by revealing the complexity and long-term psychological stress of caring for HAE patients through a multinational survey, providing key evidence for developing comprehensive support strategies.

 

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Research Methods and Experiment

This study was a non-interventional, cross-sectional, web-based multinational survey conducted from July 2022 to February 2023 across 13 countries in Europe and South America. It included 120 primary caregivers (aged 18 or older) of HAE patients, divided into two groups: caregivers of pediatric patients (CoPs, n=54) and caregivers of adult patients (CoAs, n=66). The survey was administered via the online platform Confirmit, covering demographics of caregivers and patients, clinical characteristics, economic burden, and humanitarian burden. The questionnaire included the frequency of HAE attacks in the past six months, treatment use, absenteeism, and the caregiver’s quality of life, emotional state, work impact, and social restrictions. Descriptive statistics were used for data analysis, including mean ± standard deviation and frequency (%). All participants provided informed consent, and the study complied with the Declaration of Helsinki and relevant ethical guidelines.

Key Conclusions and Findings

• In the past six months, caregivers of adult patients reported an average of 13.1 HAE attacks per patient, compared to 5.6 for pediatric patients, indicating significantly higher attack frequency in adults
• Caregivers of pediatric patients provided care for an average of 23.5 days per month, missed an average of 2.6 workdays in the past four weeks, and pediatric patients missed an average of 3.9 school days, highlighting the significant impact of caregiving on work and education
• Approximately 37.0% of pediatric patient caregivers reported that caregiving affected their work, sleep, and household duties, while also limiting time spent with family, partners, and friends
• Over 90% of pediatric patient caregivers expressed ongoing concern for the child’s health, nearly 70% worried about their future, and reported personal sleep issues (24.1%), migraines (22.2%), and anxiety (20.4%)
• Among caregivers of adult patients, 92.4% worried about the patient’s health, 40.9% about their future, 13.6% reported anxiety symptoms, 12.1% had sleep problems, and they missed an average of 0.94 workdays in the past four weeks
• Both groups of caregivers reported insufficient understanding of HAE care needs from schools, employers, family, and friends, reflecting a lack of social support systems
• Nearly half of pediatric patient caregivers also had HAE themselves, indicating familial clustering of the disease and added stress from a dual role

Research Implications and Outlook

This study is the first to systematically assess the psychological and social burden on caregivers of HAE patients in a multinational context, revealing extensive negative impacts of caregiving on personal health, career development, and family relationships. The findings emphasize that HAE affects not only patients but also their family members, particularly in terms of emotional health. Future HAE management should incorporate caregiver support into comprehensive care pathways, including psychological interventions, social service referrals, and workplace support policies. Additionally, increasing public and healthcare provider awareness of HAE care needs can help reduce misunderstanding and discrimination, improving the caregiving environment.

Although this study has a relatively large sample size and broad geographic coverage, limitations remain, such as reliance on self-reported data potentially introducing recall bias, and recruitment primarily through patient advocacy organizations possibly causing selection bias. Future research could adopt longitudinal designs and incorporate standardized psychological assessment tools (e.g., WHO-5, HADS) for more objective measurement of caregiver mental health. Exploring how healthcare policies and social support systems in different countries moderate caregiver burden will help develop more targeted interventions. This study provides methodological reference for research on caregiving burden in rare diseases and calls for enhanced global support systems for families affected by rare diseases.

 

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Conclusion

This study, through a multinational survey covering 13 countries, systematically reveals the significant psychological and life burden experienced by primary caregivers of patients with hereditary angioedema (HAE). Whether caring for pediatric or adult patients, family members commonly face managing frequent disease attacks, extensive caregiving time, and resulting work absenteeism, sleep disturbances, and emotional distress. The study finds that over 90% of caregivers continuously worry about the patient’s health and future, and a significantly higher proportion report anxiety, migraines, and sleep problems compared to the general population. Additionally, insufficient societal understanding of HAE care needs further exacerbates caregivers’ feelings of isolation and stress. These results highlight the necessity of integrating caregiver support into HAE clinical management, including psychological interventions, social service linkages, and policy advocacy. The study provides important empirical evidence on caregiving burden in rare diseases, suggesting that healthcare systems should shift from a 'patient-centered' to a 'family-centered' model to comprehensively improve the well-being of HAE families. Future research should further explore cross-cultural differences and structural support strategies to alleviate the long-term burden on this invisible population.

 

Maureen Watt, Inmaculada Martinez-Saguer, Angela Simon, Mauricio Sarrazola, and Anete S Grumach. Burden of hereditary angioedema: results from a multinational survey of caregivers for adult and pediatric patients. Orphanet Journal of Rare Diseases.