Abstract
BACKGROUND: Chronic spontaneous urticaria (CSU) exhibits heterogeneous disease activity patterns, suggesting underlying biological variability. Active Helicobacter (H.) pylori infection has been proposed as a potential contributor to inflammatory amplification in CSU. The aim of the study was to evaluate whether active H. pylori infection identifies a distinct activity-linked clinical phenotype in CSU and to examine its relationship with symptom intensity and quality-of-life impact. METHODS: In the retrospective observational study, 245 adults with CSU underwent stool antigen testing for active H. pylori infection. Disease activity was assessed using the daily Urticaria Activity Score (UAS; range 0-6). Gradient analysis across UAS levels, phenotype feature enrichment, correlation with antigen burden, and multivariable modeling were performed. External quality-of-life impact was also evaluated. RESULTS: Active H. pylori infection was detected in 64.9% of patients and was strongly associated with amplified disease activity. A graded increase in infection prevalence was observed across UAS categories, and antigen burden correlated positively with UAS (ρ = 0.540; P < 0.001). Infected patients demonstrated enrichment of severe pruritus, very high wheal counts, and angioedema. After adjustment for age, sex, and disease duration, infection remained independently associated with high disease activity (P < 0.001). Although overall quality-of-life impairment was modest, disease activity showed a weak positive correlation with external impact (P = 0.046). CONCLUSIONS: Active H. pylori infection may represent a marker of an activity-linked inflammatory phenotype in CSU characterized by severity gradient and phenotype clustering. While causality cannot be inferred, these findings support further prospective studies to determine whether infection-targeted strategies influence disease trajectory.