Distinct Clinical and Laboratory Profiles in Chronic Spontaneous Urticaria Requiring High-Intensity Treatment

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.

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.

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 immunoglobulin G (IgG) levels (all p < 0.05).

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.