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

Vesna Trajkova; Natasa Teovska Mitrevska; Emek Kocatürk; Daria Fomina; Hristina Breshkovska; Daniela Buklioska Ilievska; Irena Dimitrovska; Ana Ristovska Dimitrovska; Ivana Tusheva; Sofija Peshova; Kristina Trpcheva Stojkov

doi:10.37349/eaa.2025.1009101

Exploration of Asthma & Allergy ›› 2025, Vol. 3 ›› Issue (1) :1009101 DOI: 10.37349/eaa.2025.1009101

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

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¹ Dermatology Department, General Hospital 8th September, 1000 Skopje, North Macedonia

² Higher Medical School, University St. Kliment Ohridski, 7000 Bitola, North Macedonia

³ Dermatology Department, Remedica Hospital, 1000 Skopje, North Macedonia

⁴ Faculty of Dental Medicine, International Balkan University, 1000 Skopje, North Macedonia

⁵ Department of Dermatology, Faculty of Medicine, Bahcesehir University, 34353 Istanbul, Türkiye

⁶ Institute of Allergology, Charité-Universitätsmedizin, 12203 Berlin, Germany

⁷ Moscow Research and Clinical Center of Allergy and Immunology, City Clinical Hospital 52, Moscow 123182, Russian Federation

⁸ Department of Clinical Immunology and Allergology, I.M. Sechenov First Moscow State Medical University, Moscow 119991, Russian Federation

⁹ Department of Pulmonology, Astana Medical University, Astana 010000, Kazakhstan

¹⁰ University Clinic of Dermatology, SS Cyril and Methodius University, 1000 Skopje, North Macedonia

¹¹ Department of Pulmonology and Allergology, General Hospital 8th September, 1000 Skopje, North Macedonia

¹² Faculty of Medical Sciences, Goce Delcev University, 2000 Stip, North Macedonia

^*Vesna Trajkova, Dermatology Department, General Hospital 8th September, 1000 Skopje, North Macedonia.vesna.dojcinovska@gmail.com

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Abstract

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.

Keywords

chronic spontaneous urticaria / angioedema / autoimmunity / ASST

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Vesna Trajkova, Natasa Teovska Mitrevska, Emek Kocatürk, Daria Fomina, Hristina Breshkovska, Daniela Buklioska Ilievska, Irena Dimitrovska, Ana Ristovska Dimitrovska, Ivana Tusheva, Sofija Peshova, Kristina Trpcheva Stojkov. Clinical and autoimmune characteristics associated with angioedema in patients with chronic spontaneous urticaria. Exploration of Asthma & Allergy, 2025, 3 (1) : 1009101 DOI:10.37349/eaa.2025.1009101

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