Unlocking Precision in CSU Management: The Role of Biomarkers
Understanding Chronic Spontaneous Urticaria: Insights into Treatment Response
Chronic spontaneous urticaria (CSU) is a prevalent condition that poses significant challenges for both patients and healthcare providers. While established treatment protocols typically follow a systematic approach, beginning with second-generation H1 antihistamines and advancing to omalizumab when necessary, the effectiveness of these treatments can vary widely among individuals (Source: Tbakhi B et al., Allergy Asthma Immunol Res). A recent review published in Frontiers in Allergy consolidates current findings regarding clinical and laboratory indicators that may assist in predicting early therapeutic responses in patients undergoing treatment for CSU (Source: Calzari P et al., Predictors of early treatment response).
Who Is Likely to Respond to Antihistamines?
Second-generation antihistamines form the cornerstone of CSU management; however, data indicates that less than half of the patients achieve satisfactory symptom control using standard dosages. The review suggests that patients presenting with milder forms of the disease at baseline generally experience better outcomes.
Several factors are consistently linked to improved responses to antihistamines, including:
- Shorter duration of the disease
- Lower urticaria activity scores over a 7-day period
- Absence of angioedema
Conversely, certain characteristics are associated with a higher probability of antihistamine resistance. Patients exhibiting elevated disease activity, those with coexisting inducible urticaria, or those suffering from long-standing CSU are more prone to require escalated treatment.
Laboratory findings reinforce these observations. Elevated inflammatory markers, such as C-reactive protein and IL-6, along with hematologic alterations including basopenia, eosinopenia, and an increased neutrophil-to-lymphocyte ratio, are frequently observed in nonresponders.
Additionally, markers indicative of coagulation activation—especially elevated D-dimer and fibrinogen—seem to correlate with poor responses to antihistamines. This finding supports the notion that severe CSU represents a broader systemic inflammatory condition rather than merely a localized histamine-driven reaction.
Patients exhibiting autoimmune features, such as positive autologous serum skin testing or the presence of thyroid autoantibodies, are further identified as less likely to experience benefits from antihistamines alone.
Predicting Response to Omalizumab
Omalizumab has shown substantial efficacy for many patients with antihistamine-refractory CSU; however, approximately one-third of patients may experience delayed or incomplete therapeutic responses. The review identifies total serum IgE as the most extensively studied biomarker in this context. Generally, higher baseline IgE levels correlate with quicker and more comprehensive responses to treatment, whereas very low IgE levels are associated with diminished efficacy.
Moreover, early increases in IgE levels following the initiation of treatment appear to be predictive of clinical improvement. Insights from basophil-related markers also contribute to understanding treatment outcomes. Elevated basophil counts and increased FcεRI expression are indicative of favorable outcomes, while basopenia, eosinopenia, and heightened levels of basophil activation markers such as CD203c are more frequent in nonresponders.
Functional assays, including autologous serum skin tests and basophil activation tests, may help to identify autoimmune-driven disease, which tends to respond more slowly to omalizumab. Clinical factors also play a crucial role in influencing treatment response.
Factors such as advanced age, elevated body mass index, severe baseline disease, and the presence of autoimmune or inducible urticaria consistently correlate with poorer treatment outcomes. In contrast, reductions in inflammatory mediators like IL-31 during treatment generally align with clinical improvement.
Advancing Toward Personalized Care for CSU
The review emphasizes that CSU should not be viewed as a singular disease entity but rather as a spectrum of overlapping inflammatory and autoimmune endotypes. While no single biomarker currently exists to reliably predict treatment responses, a combination of clinical characteristics and laboratory findings may help clinicians to identify challenging cases earlier.
Although most of these predictive markers are not yet ready for routine clinical application, they signal a future where CSU management can become more personalized and less reactive. Early identification of patients who are unlikely to respond to antihistamines or omalizumab may lead to faster disease control and minimize unnecessary delays in treatment.
Sources
- Tbakhi B, Ware K, Park HS, Bernstein JS, Bernstein JA. An overview of chronic spontaneous urticaria: diagnosis, management, and treatment. Allergy Asthma Immunol Res. doi:10.4168/aair.2025.17.5.531
- 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. Published online January 12, 2026. doi:10.3389/falgy.2025.1728559