Clinical and autoimmune characteristics associated with angioedema in patients with chronic spontaneous urticaria

Aim: Angioedema is a common but often underestimated manifestation of chronic spontaneous urticaria (CSU). Its presence may indicate higher disease severity, longer duration, and autoimmune involvement. This study aims to assess the clinical relevance and associations of angioedema in CSU patients with disease severity and duration, treatment response to H1-antihistamines, correlation with autoimmune status, and autologous serum skin test (ASST) positivity. Methods: A prospective study was conducted at the Dermatology Department, General Hospital 8th September, Skopje, North Macedonia, from December 2021 to November 2022, including 230 CSU patients. Disease activity was assessed using the Urticaria Activity Score over 7 days (UAS7), and severity was categorized accordingly. Response to H1-antihistamines was defined as achieving UAS7 < 7 for several months. Angioedema was recorded as a symptom regardless of localization. Autoimmune status was based on autoimmune disease history and/or autoantibody (AAb) detection. The ASST was performed, classifying patients as ASST-positive (ASST⁺) or ASST-negative (ASST⁻). Results: Angioedema was observed in 70% of CSU patients, all with accompanying wheals. It was significantly more common in severe CSU than in moderate (82.02% vs. 65.38%, p = 0.026), mild (82.02% vs. 65.96%, p = 0.036), and well-controlled disease (82.02% vs. 45.45%, p = 0.0004). Patients with a positive autoimmune status more often had angioedema than those with a negative status (75.17% vs. 61.18%, p = 0.025). CSU showed longer duration in patients with angioedema (p = 0.000012), with no association to good antihistamine response (p = 0.55). Conclusions: Angioedema in CSU is associated with higher disease activity, autoimmune status, and prolonged disease duration but not with differences in antihistamine response. Its presence marks a more severe phenotype, emphasizing the need for careful monitoring and individualized management.