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

Background: Hereditary angioedema is a rare bradykinin-mediated disorder characterized by recurrent, unpredictable swelling attacks that can substantially impair quality of life. Objective: The objectives were to describe attack triggers reported during the previous 4 weeks, compare the clinical impact of emotional and physical and/or organic triggers on attack outcomes, Angioedema Control Test (AECT) based disease control, and quality of life; and, secondarily, to examine the associations of the attack burden with the AECT and Angioedema Quality of Life (AE-QoL) Questionnaire scores. Methods: This single-center retrospective cross-sectional study included 50 adults with type I or type II hereditary angioedema followed up between January 2019 and October 2025. Data extracted from medical records included the number of attacks during the preceding 4 weeks, characteristics of the most severe attack, trigger category, disease control assessed by the AECT, and quality of life assessed by the AE-QoL Questionnaire. Triggers were grouped as emotional (stress/sadness) or physical/organic (trauma, infection, physical exertion, hormonal/metabolic). Results: The median age was 40.5 years, 54% of the patients were women, the median diagnostic delay was 16.5 years, and 82% had a positive family history of hereditary angioedema. Emotional stress was the most commonly reported trigger of the most severe attack (60%). No significant differences were observed between emotional and physical/organic trigger groups in attack frequency, duration or severity of the most severe attack, emergency department visits, AECT-based disease control, or quality-of-life scores (all p > 0.05). Attack frequency was negatively correlated with AECT-based disease control (r = -0.631; p < 0.001) and positively correlated with quality-of-life impairment (r = 0.428; p = 0.002), with the strongest association in the fear/shame domain (r = 0.500; p < 0.001). AECT-based disease control was strongly inversely correlated with quality-of-life impairment (r = -0.734; p < 0.001). Conclusion: Emotional stress was the most frequently reported trigger of recent hereditary angioedema attacks. Although clinical outcomes did not differ according to trigger type, a higher attack frequency was associated with poorer AECT-based disease control and worse quality of life.