Behavioural withdrawal during an acute stress test as a marker of psychobiological vulnerability in hereditary angioedema.

Non-completers of the SECPT showed poorer disease control compared to Completers.

• 20 HAE-C1INH patients were enrolled: 15 Completers and 5 Non-completers (early withdrawal).
• Disease control measured via Angioedema Control Test (AECT) scores: Non-completers 10.6 ± 5.5 vs Completers 14.5 ± 2.2 (p ≤ 0.05).
• Non-completers also showed worse Angioedema Quality of Life (AE-QoL) scores.

Non-completers had worse quality of life in the Functioning and Fatigue/Mood domains of the AE-QoL questionnaire.

• Functioning domain scores: Non-completers 8.6 ± 4.3 vs Completers 4.7 ± 1.7 (p ≤ 0.05).
• Fatigue/Mood domain scores: Non-completers 13.6 ± 7.1 vs Completers 10.5 ± 3.5 (p ≤ 0.05).
• Quality of life was measured using the Angioedema Quality of life (AE-QoL) questionnaire.

Non-completers reported significantly higher perceived stress, pain, and unpleasantness during the SECPT.

• Stress ratings: Non-completers 91 ± 8.9 vs Completers 50.5 ± 33.7 (p ≤ 0.05).
• Pain ratings: Non-completers 87.8 ± 12.8 vs Completers 50.1 ± 31.3 (p ≤ 0.05).
• Unpleasantness ratings: Non-completers 83 ± 19.9 vs Completers 49.5 ± 30.5 (p ≤ 0.05).
• Stress appraisal was assessed during the Socially Evaluated Cold Pressor Test (SECPT).

Non-completers displayed an attenuated systolic arterial pressure response during the SECPT compared to Completers.

• Systolic arterial pressure (SAP) during SECPT: Non-completers 128.3 ± 18.0 mmHg vs Completers 148.9 ± 18.3 mmHg (p ≤ 0.05).
• Cardiovascular parameters assessed included heart rate (HR) and systolic/diastolic arterial pressure (SAP/DAP).
• Non-completers showed a blunted cardiovascular stress response relative to Completers.

Non-completers showed higher IL-6 levels and opposite TNF-α trajectories compared to Completers following the SECPT.

• IL-6 levels at 40 minutes after SECPT: Non-completers 3.5 ± 1.1 pg/ml vs Completers 2.2 ± 0.7 pg/ml (p ≤ 0.05).
• TNF-α change from baseline: Non-completers 0.9 ± 1.0 pg/ml vs Completers -0.5 ± 0.9 pg/ml (p ≤ 0.05), indicating opposite trajectories.
• Plasma cytokines assessed included IL-1β, TNF-α, and IL-6.
• Divergent inflammatory profiles between the two groups suggest distinct immunological stress responses.

HAE-C1INH features clinical heterogeneity and stress-triggered attacks, motivating assessment of behavioral tolerance to acute stress as a vulnerability marker.

• Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) is characterized by clinical heterogeneity.
• Stress is recognized as a trigger for angioedema attacks in HAE-C1INH.
• The study aimed to characterize stress response patterns beyond standard clinical descriptors using the SECPT.