Both Extrinsic and Intrinsic Atopy in Chronic Spontaneous Urticaria Patients Indicate a Favorable Response to Omalizumab Treatment

Background: Chronic spontaneous urticaria (CSU), a debilitating condition, is often treated with omalizumab for antihistamine-refractory cases. Atopy subtypes (extrinsic/intrinsic) may influence CSU clinical features and treatment responses, but remain understudied. Objective: To assess the clinical relevance of atopy subtypes in CSU and their link to omalizumab response. Methods: Retrospective analysis of 210 omalizumab-treated CSU patients assessed through allergen-specific immunoglobulin E (IgE), total IgE, personal/family history, and atopic signs. Groups: nonatopic, extrinsic, or intrinsic atopic. Treatment response, onset speed, and safety profiles were evaluated. Results: Atopy prevalence was 70% (extrinsic: 50.5%, intrinsic: 19.5%). Extrinsic atopic patients showed higher personal/family urticaria history and annular/semi-annular wheals. Nonatopic patients were older, with more red plaques/patches and higher IgG-anti-thyroid microsome (IgG-anti-TM) positivity. Atopy predicted a favorable omalizumab response. Omalizumab response rates were superior in extrinsic (97.2%) and intrinsic (95.1%) groups versus nonatopic (77.8%, P < 0.001). Nonatopic patients experienced faster symptom relief (28.6% ≤24 hours vs 9.7–20.5%, P = 0.012). Adverse events were more frequent in atopic subgroups (18.9–22.0% vs 4.8%, P = 0.020). Low total IgE (<40 IU/mL) correlated with reduced group responses. Conclusion: Both extrinsic and intrinsic atopy predict better omalizumab responses in CSU. Intrinsic atopic CSU, often neglected, requires further study for personalized approaches. Comprehensive atopy evaluation improves therapeutic stratification in CSU.