Paraclinics in Chronic Spontaneous Urticaria: Are They Useful as Biomarkers?

Abstract Purpose of review Chronic spontaneous urticaria (CSU) is a heterogeneous mast cell–driven disease with highly variable clinical course and treatment response. Traditional diagnostic approaches are insufficient to capture this complexity, highlighting the need for biomarker-based endotyping. This review aims to critically evaluate the current evidence on paraclinical biomarkers used in CSU, focusing on their role in defining disease endotypes, predicting treatment response, assessing disease severity, and estimating prognosis and remission potential. Recent Findings Recent advances have clarified the immunopathogenic distinction between Type I autoallergic and Type IIb autoimmune CSU, each characterized by distinct biomarker profiles. Elevated total IgE, IgE autoantibodies, and soluble FcεRI are increasingly linked to the autoallergic endotype and favorable response to omalizumab. In contrast, low total IgE, IgG autoantibodies to FcεRI or IgE, eosinopenia, basopenia, elevated CRP, D-dimer, and positivity in functional assays such as the basophil activation test (BAT) or basophil histamine release assay (BHRA) characterize Type IIb autoimmune CSU and predict treatment refractoriness to antihistamines and omalizumab, with better response to immunosuppressive therapies. Emerging functional platforms, including mast cell activation tests, further expand the diagnostic landscape. Summary Paraclinical tests have evolved from ancillary investigations into essential tools for endotype-driven precision medicine in CSU. While no single biomarker is diagnostic in isolation, integrated interpretation of serological, cellular, and functional markers enables more accurate endotyping, improved treatment stratification, and realistic prognostic counseling. Future research should focus on assay standardization, validation of composite biomarkers, and development of practical diagnostic tools—particularly for Type I autoallergic CSU—to facilitate broader implementation of precision medicine approaches in routine clinical practice.