Patients in Japan with hereditary angioedema (HAE) experience a heavy burden of illness in the physical, social, psychosocial, and economic domains, which is associated with reduced health-related quality of life (HRQoL), according to findings from a patient-reported outcome (PRO) survey published in Intractable & Rare Diseases Research.

HAE is a rare, potentially life-threatening disorder linked with spontaneous and recurrent edema in various parts of the body, including the laryngeal region and certain internal organs. The severity and frequency of attacks can vary between patients and over an individual patient’s lifetime. HAE episodes are often unpredictable, painful, and disfiguring, and may cause considerable temporary disability.

Recognizing that delayed diagnosis and treatment of HAE may increase the risks associated with the disease, the researchers of the present study sought to understand the burden of illness among patients with HAE in Japan, both prior to and following their diagnosis, via a PRO survey.

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Between July 2016 and November 2016, a PRO survey was distributed to 121 individuals with HAE via a Japanese HAE patient organization, with the results subsequently evaluated in 2017. Individuals without a confirmed HAE diagnosis and those under 20 years of age were excluded from the study.

Following exclusions, 57.9% (70 of 121) of patients returned the survey. Of the 70 respondents, 55 (78.6%) were female and 15 (21.4%) were male. The average patient age was 44.9±18.8 years (range, 8-84 years).

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Participants were divided into segmented subgroups according to the frequency of their HAE attacks and their impact on HRQoL over the previous year:

  • High-attack group: ≥20 attacks per year; 27.1% (19 of 70) of participants
  • Low-attack group: 1 to 19 attacks per year; 41.4% (29 of 70) of participants
  • No-attack group: history of attacks but no episodes in the previous year; 10.0% (7 of 70) of participants
  • Asymptomatic group: no attacks reported; 10.0% (7 of 70) of participants
  • Unclassified group: individuals who did not indicate the number of attacks that they experienced in 1 year; 11.4% (8 of 70) of participants.

Although 78.6% of the respondents were female, women comprised 94.7% (18 of 19) of individuals in the high-attack group. Additionally, male respondents were overrepresented slightly in the low-attack and asymptomatic groups (24.1% [7 of 29] and 28.6% [2 of 7] of participants, respectively), and they were overrepresented more extensively in the no-attack group (42.9% [3 of 7] of participants).

Participants reported a high utilization of medical resources for routine care of HAE, with 25.7% (18 of 70) of survey respondents visiting a medical center on at least a monthly basis, which included 7.1% (5 of 70) of participants reporting weekly visits. Further, 47.1% (33 of 70) of respondents went to their regular hospital or clinic once every 2 to 3 months. Overall, 42.1% (8 of 19) of those in the high-attack group reported the use of routine care weekly or twice monthly.

The utilization of emergency services and procedures was also often reported among the participants, especially those in the high-attack group. Use of emergency services included requesting an ambulance for HAE symptoms and undergoing a tracheotomy or laparotomy. The economic burden of HAE—both direct and indirect medical costs—was highest prior to diagnosis but continued to be perceived as substantial following an HAE diagnosis.

Disruption of work and school life was also reported, with 45% of respondents indicating they missed 10 or more days of work or education annually. Further, 60% of participants reported that HAE impacted their daily activities.

The authors concluded, “As the burden of disease in these domains was shown to be even higher before than after diagnosis, we can conclude that early diagnosis is a necessary condition to reduce the lifetime burden of this disease.”


Yamamoto B, Honda D, Ohsawa I, et al. Burden of illness seen in hereditary angioedema in Japanese patients: results from a patient reported outcome survey. Intractable Rare Dis Res. 2023;12(1):35-44. doi:10.5582/irdr.2022.01130