Biomarkers Bring Precision Closer in CSU Management

Chronic spontaneous urticaria (CSU) is a common but often frustrating condition for both patients and clinicians. Although most treatment algorithms follow a clear stepwise pathway, starting with second-generation H1 antihistamines and escalating to omalizumab when needed, real-world response is highly variable.¹ A recent review published in Frontiers in Allergy brings together current evidence on clinical and laboratory factors that may help predict which patients are likely to respond early to these therapies.²

Who responds to antihistamines?

Second-generation antihistamines remain the foundation of CSU management, yet fewer than half of patients achieve adequate symptom control at standard doses. According to the review, patients with milder disease at baseline tend to do best. Shorter disease duration, lower urticaria activity scores over 7 days, and absence of angioedema are consistently associated with better response.

In contrast, several features signal a higher likelihood of antihistamine resistance. Patients with high disease activity, coexisting inducible urticaria, or long-standing CSU are more likely to require treatment escalation. Laboratory findings support this distinction. Elevated inflammatory markers such as C-reactive protein and IL-6, along with hematologic changes including basopenia, eosinopenia, and increased neutrophil-to-lymphocyte ratio, are more common in nonresponders.

Markers of coagulation activation—particularly elevated D-dimer and fibrinogen—also appear linked to poor antihistamine response, reinforcing the concept that severe CSU reflects systemic inflammation rather than isolated histamine-driven disease. Autoimmune features, including positive autologous serum skin testing or thyroid autoantibodies, further characterize patients who are less likely to benefit from antihistamines alone.

Predicting response to omalizumab

Omalizumab is highly effective for many patients with antihistamine-refractory CSU, but up to one-third experience delayed or incomplete response. The review highlights total serum IgE as the most studied biomarker in this setting. Higher baseline IgE levels are generally associated with faster and more complete responses, while very low IgE levels are linked to reduced efficacy. Early increases in IgE after treatment initiation also appear to predict clinical improvement.

Basophil-related markers offer additional insight. Higher basophil counts and increased FcεRI expression are associated with better outcomes, whereas basopenia, eosinopenia, and elevated basophil activation markers such as CD203c are more often seen in nonresponders. Functional tests, including autologous serum skin tests and basophil activation assays, may identify autoimmune-driven disease that responds more slowly to omalizumab.

Certain clinical factors also influence response. Advanced age, higher body mass index, severe baseline disease, and the presence of autoimmune or inducible urticaria are repeatedly associated with poorer outcomes. On the other hand, reductions in inflammatory mediators such as IL-31 during treatment tend to parallel clinical improvement.

Moving toward personalized CSU care

The review underscores that CSU is not a single disease entity but a collection of overlapping inflammatory and autoimmune endotypes. No single biomarker can reliably predict treatment response, but combining clinical features with laboratory markers may help clinicians identify difficult-to-treat conditions earlier.

While most of these predictors are not yet ready for routine use, they point toward a future in which CSU management is less reactive and more personalized. Earlier recognition of patients unlikely to respond to antihistamines or omalizumab could shorten time to disease control and reduce unnecessary treatment delays.

References

1. Tbakhi B, Ware K, Park HS, Bernstein JS, Bernstein JA. An overview of chronic spontaneous urticaria: diagnosis, management, and treatment. Allergy Asthma Immunol Res. 2025;17(5):531-546. doi:10.4168/aair.2025.17.5.531
2. Calzari P, Favale EM, Cugno M, Asero R, Marzano AV, Ferrucci SM. Predictors of early treatment response to antihistamines and omalizumab in chronic spontaneous urticaria. Front Allergy. Published online January 12, 2026. doi:10.3389/falgy.2025.1728559