Distinct clinical and laboratory profiles in chronic spontaneous urticaria requiring high-intensity treatment

Introduction Second-generation H1-antihistamines are the first-line therapy for chronic spontaneous urticaria (CSU); however, many patients remain symptomatic despite standard treatment. This study aims to identify the clinical and laboratory characteristics associated with high treatment requirements in patients with CSU. Methods This retrospective cohort study analyzed 6,033 adults with CSU who visited a tertiary hospital in Korea between 2002 and 2020. High-treatment-requirement CSU (HTR-CSU) was defined as requiring treatment with ≥4 H1-antihistamines simultaneously or at least one use of omalizumab. Results Of 6,033 patients, 34.5% were classified as HTR-CSU. Compared with non-HTR patients, HTR-CSU patients had a higher rate of long-term follow-up (≥60 months: 7.9% vs. 3.2%, P < 0.001) and more cholinergic urticaria (2.8% vs. 2.0%, P = 0.045), while angioedema was more common in non-HTR-CSU cases (17.8% vs. 13.0%, P < 0.001). The use of sedative H1-antihistamines, leukotriene receptor antagonists, corticosteroids, H2 blockers, and omalizumab was significantly higher in the HTR-CSU group. Laboratory findings showed elevated white blood cell counts (6.6 vs. 6.4 ×10³/μL), neutrophil count (3.8 vs. 3.6 ×10³/μL), total IgE (155.0 vs. 135.0 IU/mL), C3 (114.3 vs. 111.0 mg/dL), C4 (29.6 vs. 26.9 mg/dL), and D-dimer levels (0.40 vs. 0.34 μg/mL), along with reduced IgG levels (all P < 0.05). Conclusion HTR-CSU is associated with longer disease duration, heavier medication burden, and distinctive laboratory profiles characterized by elevated neutrophil, complement, D-dimer, and IgE levels, as well as decreased IgG levels, suggesting potential differences in immunological mechanisms compared to non-HTR-CSU.