Clinical Significance of IL‐4 and IL‐21 Concurrent Elevation in Predicting Disease Activity Score and Antihistamine Treatment Response in Chronic Spontaneous Urticaria

Abstract To investigate the predictive value of interleukin (IL)‐4 and IL‐21 levels in assessing disease activity score and antihistamine treatment response in chronic spontaneous urticaria (CSU) patients. One hundred and twenty CSU patients treated at our hospital between January 2023 and January 2025 were retrospectively selected as the study group. Eighty healthy individuals undergoing routine physical examinations during the same period were included as the control group. Serum IL‐4 and IL‐21 levels, and the proportion of peripheral blood follicular helper T (Tfh) cells within CD4 + T cells were retrieved from the hospital information system. Based on the Urticaria Activity Score over 7 days (UAS7), CSU patients were divided into three subgroups: mild (UAS7 < 16, n = 43), moderate (UAS7 16‐27, n = 52), and severe (UAS7 ≥ 28, n = 25). All patients received standard antihistamine therapy for 4 weeks. According to treatment response, patients were categorized into four groups: complete remission, marked improvement, partial remission, and no response. The correlations of IL‐4, IL‐21, and Tfh cell levels with disease severity were analyzed, and their predictive value for CSU diagnosis and antihistamine treatment response was evaluated. IL‐4 and IL‐21 are co‐upregulated in CSU patients, and their levels increase with disease activity and are positively correlated with UAS7 score (r = .603, 0.314, P < .001). These biomarkers have a certain reference value for diagnosis and severity assessment of CSU. Baseline levels of IL‐4 and IL‐21 may serve as predictive biomarkers for antihistamine treatment response, providing a potential reference for individualized treatment strategies.