Cardiovascular

Determining the clinical impact of attack triggers in patients with hereditary angioedema.

TL;DR

Emotional stress was the most frequently reported trigger of recent hereditary angioedema attacks, and although clinical outcomes did not differ according to trigger type, higher attack frequency was associated with poorer disease control and worse quality of life.

Key Findings

Emotional stress was the most commonly reported trigger of the most severe hereditary angioedema attack.

  • 60% of patients reported emotional stress (stress/sadness) as the trigger for their most severe attack
  • Triggers were categorized as emotional (stress/sadness) or physical/organic (trauma, infection, physical exertion, hormonal/metabolic)
  • Study included 50 adults with type I or type II hereditary angioedema followed between January 2019 and October 2025
  • Data were collected from a single-center retrospective cross-sectional study

No significant differences were observed between emotional and physical/organic trigger groups across multiple clinical outcome measures.

  • No significant differences were found in attack frequency, duration, or severity of the most severe attack between trigger groups
  • Emergency department visits did not differ significantly between trigger groups
  • AECT-based disease control and quality-of-life scores also did not differ between groups
  • All comparisons yielded p > 0.05

Attack frequency was negatively correlated with AECT-based disease control.

  • Correlation coefficient r = -0.631, p < 0.001
  • This indicates that patients with more frequent attacks had worse disease control as measured by the Angioedema Control Test (AECT)
  • The AECT assessed disease control based on attacks during the preceding 4 weeks

Attack frequency was positively correlated with quality-of-life impairment, with the strongest association in the fear/shame domain.

  • Overall correlation between attack frequency and quality-of-life impairment: r = 0.428, p = 0.002
  • Strongest domain-specific association was in the fear/shame domain: r = 0.500, p < 0.001
  • Quality of life was assessed using the Angioedema Quality of Life (AE-QoL) Questionnaire

AECT-based disease control was strongly inversely correlated with quality-of-life impairment.

  • Correlation coefficient r = -0.734, p < 0.001
  • This was described as a strong inverse correlation, indicating that better disease control was associated with less quality-of-life impairment
  • Both the AECT and AE-QoL Questionnaire were used to assess these outcomes

The study population had a notably long diagnostic delay and a high rate of positive family history.

  • Median diagnostic delay was 16.5 years
  • 82% of patients had a positive family history of hereditary angioedema
  • Median age of the cohort was 40.5 years
  • 54% of patients were women
  • The cohort comprised 50 adults with type I or type II hereditary angioedema

What This Means

This research examined what triggers attacks in people with hereditary angioedema (HAE), a rare condition that causes unpredictable, recurring episodes of swelling. The study looked at 50 adult patients and found that emotional stress — such as anxiety or sadness — was the most commonly reported trigger for the most severe recent attacks, cited by 60% of participants. Interestingly, despite emotional triggers being so common, the type of trigger (emotional versus physical causes like injury or infection) did not make a statistically significant difference in how bad attacks were, how long they lasted, how often patients needed emergency care, or how well the disease was controlled. The study also found important links between how often attacks occurred and patients' overall wellbeing. Patients who experienced more frequent attacks had worse scores on a standardized disease control test and reported a lower quality of life. The strongest impact on quality of life was seen in the 'fear and shame' domain, suggesting that the emotional burden of living with unpredictable attacks is particularly significant. Better disease control, as measured by the Angioedema Control Test, was strongly associated with better quality of life. This research suggests that reducing attack frequency — regardless of what is triggering the attacks — may be a key goal for improving both disease control and quality of life in HAE patients. The finding that emotional stress is the leading reported trigger also highlights the potential importance of psychological support as part of comprehensive HAE management. The notably long average diagnostic delay of 16.5 years underscores the ongoing challenge of timely recognition of this rare condition.

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Citation

Aslan Savas S, Colkesen F, Gerek M, Ergun U, Harman E, Kolak S, et al.. (2026). Determining the clinical impact of attack triggers in patients with hereditary angioedema.. Allergy and asthma proceedings. https://doi.org/10.2500/aap.2026.47.260043