CH50 as a Clinically Useful Biomarker of Disease Activity and Antihistamine Resistance in Chronic Spontaneous Urticaria: An Observational Ambispective Single‐Center Study

ABSTRACT Background Chronic spontaneous urticaria (CSU) is frequently refractory to guideline‐based therapy, highlighting the need for predictive biomarkers. Dysregulation of the complement system has been implicated in CSU severity, but global complement activity has not been systematically evaluated. Objective The aim of this study was to assess the total hemolytic complement (CH50) assay as a biomarker for disease activity and predictor of treatment response in CSU. Methods This observational, ambispective, single‐center study included 180 CSU patients and 45 healthy controls. CH50 levels were measured and correlated with clinical and immunological markers. Response to second‐generation antihistamines and omalizumab at 3, 6, and 12 months was evaluated. Results CH50 levels were significantly higher in CSU patients than in controls ( p < 0.001) and were associated with more active and prolonged disease. CH50 correlated with Weekly Urticaria Activity Scores (UAS7) ( ρ = 0.30, p < 0.0001), Urticaria Control Test (UCT) scores ( ρ = −0.25, p < 0.001), longer disease duration ( ρ = 0.28, p = 0.0002), D‐dimer ( ρ = 0.31, p < 0.001), and immunoglobulin G (IgG) anti‐thyroid peroxidase (anti‐TPO) ( ρ = 0.21, p < 0.005). Higher CH50 levels were linked to antihistamine resistance ( p < 0.001), with superior predictive accuracy (area under the curve AUC = 0.87) over D‐dimer, C4, and UAS7. CH50 was also an independent predictor of antihistamine resistance (odds ratio OR 1.13, 95% confidence interval CI 1.09–1.18). No association was observed with omalizumab response. Conclusion CH50 is a novel and promising biomarker for antihistamine resistance in CSU, outperforming previously described markers. Its low cost and accessibility support integration into CSU stratification and endotype‐driven therapeutic algorithms, pending validation in multicenter cohorts. image