Introduction
Chronic spontaneous urticaria (CSU) is a mast cell-mediated skin condition defined by the presence of wheals, angioedema, or both, persisting for more than 6 weeks without an identifiable cause [1, 2]. It is more common in women, typically begins between the ages of 20 and 40, and may have either autoimmune or idiopathic origins [3]. In CSU, mast cell and basophil degranulation results in the release of histamine and other proinflammatory mediators, which increase vascular permeability and cause oedema and pruritus [3, 4].
Urticarial vasculitis (UV) is a less common skin disorder characterized by more persistent lesions than classic urticaria and histopathological findings of leukocytoclastic vasculitis [5]. Clinically, the wheals often last longer than 24 h and may leave behind hyperpigmentation or purpura upon resolution. In addition to histamine-mediated symptoms, vascular inflammation contributes to the clinical presentation.
Omalizumab is an effective and well-tolerated treatment option approved for patients aged 12 and older with CSU who are unresponsive to high-dose second-generation H1-antihistamines [6]. This monoclonal antibody binds to circulating free immunoglobulin E (IgE), preventing its attachment to FcεRI receptors on mast cells. Thus, in addition to blocking allergic responses, omalizumab may also exert immunomodulatory effects on inflammatory and coagulation pathways [7, 8]. Although omalizumab has shown beneficial effects in some UV patients, their underlying immunologic response patterns may differ from those observed in CSU [9].
In recent years, as seen in rheumatoid arthritis, psoriasis, and other systemic inflammatory diseases, certain systemic hematologic inflammation markers have gained attention in assessing disease activity in CSU. Parameters such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-monocyte ratio (NMR), mean platelet volume (MPV), red cell distribution width (RDW), and C-reactive protein (CRP) have been proposed as markers of inflammation [7, 10–13]. As these markers can be obtained easily through routine and low-cost tests like complete blood count (CBC), they represent potentially valuable tools for monitoring treatment response in clinical practice [11].
Observed changes in these hematologic inflammation markers following omalizumab therapy suggest that the drug may influence inflammatory processes beyond IgE neutralization alone.
Aim
In this study, we aimed to evaluate the effects of omalizumab on various inflammatory parameters in patients diagnosed with CSU and UV, as well as to investigate the interrelationships among these parameters and their potential role in monitoring disease activity.
Material and methods
Study design and ethical approval
This retrospective observational study was conducted at a tertiary dermatology centre by reviewing the medical records of patients who initiated omalizumab treatment between June 2022 and June 2024. Ethical approval was obtained from the relevant institutional ethics committee (approval number 2024/627).
Patient selection
The study included patients aged 18–80 years who were diagnosed with CSU or UV, received omalizumab treatment for at least 3 months, and had CBC and CRP data available both before treatment and at the third month of treatment. Patients with any additional chronic inflammatory or autoimmune disease, active infection, or coexisting systemic dermatologic disorder other than CSU or UV were excluded from the study.
Data collection and parameters
Demographic information (including age and sex), clinical characteristics (such as the diagnosis of CSU or UV and the presence of angioedema), and relevant laboratory parameters were systematically collected from patient records. The CBC results included leukocyte, neutrophil, lymphocyte, monocyte, platelet, eosinophil, basophil, MPV, and RDW. CRP was assessed as a biochemical marker of inflammation. The NLR, PLR, LMR, and NMR were calculated using standard formulas.
Statistical analysis
All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS), version 21.0. Continuous variables were expressed as mean ± standard deviation (SD), and categorical variables were summarised as frequencies and percentages. The Student’s t-test was used to compare means between two groups, while the paired sample t-test was applied to assess changes before and after treatment. Associations between categorical variables were analysed using the chi-square (c2) test. To evaluate the direction and strength of linear relationships between continuous variables, Pearson correlation analysis was performed. Correlation coefficients were reported as r, and a p-value of < 0.05 was considered statistically significant.
Results
Sociodemographic findings
A total of 80 patients who received omalizumab treatment were included in the study. Among them, 67 (83.8%) patients were diagnosed with chronic spontaneous urticaria, and 13 (16.2%) patients with urticarial vasculitis. The mean age was 39.94 ±12.10 years in the CSU group and 45.54 ±12.52 years in the UV group, with no statistically significant difference between the groups (p = 0.133). The CSU group included 50 (74.6%) women and 17 (25.4%) men, while the UV group comprised 11 (84.6%) women and 2 (15.4%) men; the difference in sex distribution was not statistically significant (p = 0.723). Angioedema was present in 34.3% of the CSU group and 38.5% of the UV group, with no statistically significant difference (p = 0.776). However, disease duration was significantly longer in CSU patients (5.52 ±5.84 years) compared to those in the UV group (2.62 ±1.89 years) (p = 0.002).
Findings in the CSU group
Among the 67 patients with CSU, comparison of laboratory parameters before and after 12 weeks of omalizumab treatment revealed the following statistically significant changes:
A decrease in neutrophil count (p = 0.001),
An increase in lymphocyte count (p < 0.001),
A reduction in the neutrophil-to-lymphocyte ratio (p < 0.001),
A reduction in the platelet-to-lymphocyte ratio (p < 0.001),
A decrease in the neutrophil-to-monocyte ratio (p = 0.007),
A reduction in CRP levels (p = 0.025).
No statistically significant changes were observed in leukocyte, monocyte, platelet, eosinophil, basophil, MPV, RDW, or LMR (p > 0.05) (Table 1).
Table 1
Changes in inflammatory parameters before and after 12 weeks of omalizumab treatment in patients with chronic spontaneous urticaria (n = 67)
Findings in the UV group
Among the 13 patients diagnosed with UV, only the NLR showed a statistically significant decrease following 12 weeks of omalizumab treatment (from 2.14 ±0.61 to 1.78 ±0.45; p = 0.046). Although CRP levels also decreased, the change did not reach statistical significance (p = 0.097). No significant differences were observed in other parameters, including neutrophil, lymphocyte, monocyte, platelet, eosinophil, basophil, PLR, NMR, LMR, MPV, and RDW (p > 0.05) (Table 2).
Table 2
Changes in inflammatory parameters before and after 12 weeks of omalizumab treatment in patients with UV (n = 13)
Between-group comparisons
Baseline CRP levels were higher in the UV group (7.57 ±6.27 mg/dl) compared to the CSU group (5.03 ±8.37 mg/dl), although the difference was not statistically significant (p = 0.303). Following treatment, CRP levels significantly decreased in the CSU group (p = 0.025), but not in the UV group (p = 0.097). The NLR showed a statistically significant reduction in both groups: p < 0.001 for CSU and p = 0.046 for UV.
Correlation findings
In the CSU group, a significant positive correlation was found between baseline NLR and CRP levels (r > 0.3, p < 0.05). CRP also correlated positively with leukocyte count, neutrophil count, NMR, and LMR. Post-treatment analyses revealed that NLR was positively correlated with neutrophil count, PLR, and NMR, and negatively correlated with LMR. RDW showed a positive correlation with both NLR and PLR. In the UV group, CRP was positively correlated with leukocyte, neutrophil, lymphocyte, and NMR values.
Discussion
Omalizumab is a monoclonal anti-IgE antibody that exerts effects not only on IgE-mediated allergic mechanisms but also on systemic inflammation. In this study, the effects of omalizumab treatment on various inflammatory parameters were retrospectively evaluated in patients diagnosed with chronic spontaneous urticaria and urticarial vasculitis. Our findings particularly emphasize that omalizumab may influence multiple components of the systemic inflammatory response, especially in the CSU group. Given that omalizumab may modulate not only IgE-related allergic pathways but also inflammatory and coagulation processes, it appears to have broad-spectrum therapeutic potential [7, 8, 10, 14, 15].
CRP is a well-established and widely used marker of systemic inflammation. In patients with CSU, elevated CRP levels have been shown to correlate with disease activity and are significantly higher than in healthy controls, as demonstrated in several studies [12, 16]. Kolkhir et al. reported that approximately one-third of patients had CRP levels ≥ 5 mg/l, which was also associated with a reduced quality of life [12]. Similarly, Acer et al. observed a significant reduction in CRP levels following omalizumab treatment [7].
In our study, a statistically significant decrease in CRP levels was found in the CSU group after omalizumab therapy (p = 0.025), supporting the impact of the treatment on the systemic inflammatory response. In the UV group, although baseline CRP levels were higher (mean: 7.57 ±6.27 mg/l), the post-treatment decrease did not reach statistical significance (p = 0.628). These findings suggest that the anti-inflammatory effect of omalizumab may be more pronounced in CSU patients. However, the sensitivity of CRP as a distinguishing biomarker between disease subgroups may be limited, and it may not be sufficient as a standalone indicator for clinical decision-making.
The NLR has been recognized as a systemic marker of inflammation in various diseases associated with inflammatory processes [17]. In CSU, a significant reduction in NLR following omalizumab treatment has been observed, consistent with previous studies [7, 18]. This decline was accompanied by an increase in lymphocyte count and a decrease in neutrophil count, reflecting the potential of omalizumab to modulate the inflammatory cellular balance. Elevated NLR levels have been linked to more severe vascular wall involvement – such as fibrinoid necrosis, leukocytoclasia, and endothelial injury – in vasculitic conditions [19]. In our study, the significant reduction in neutrophil levels in CSU patients supports the suppressive effect of omalizumab on neutrophil-mediated inflammation [20].
Furthermore, a significant positive correlation was identified between baseline CRP and NLR levels in CSU patients in our study. This suggests that both markers may serve as parallel indicators of the systemic inflammation, often rising concurrently during inflammatory exacerbations. As NLR reflects the cellular component – being elevated due to neutrophilia and/or lymphopenia – and CRP reflects the humoral biochemical response, their simultaneous increase indicates activation of both arms of the inflammatory response. Therefore, the observed correlation implies that combining CRP and NLR may provide a more comprehensive assessment of inflammatory activity in CSU patients.
In the UV group, a statistically significant reduction in NLR was also detected (p = 0.046). While this finding implies that omalizumab may help reduce the inflammatory burden in UV, the absence of significant changes in other parameters suggests that its overall effect might be more limited in this subgroup.
The PLR and NMR are also recognized as systemic inflammatory markers in various inflammatory conditions [11, 19, 21–23]. In CSU patients, significant reductions in both ratios were observed following omalizumab treatment, suggesting that inflammation is modulated at multiple cellular levels. The simultaneous decreases in PLR, NMR, and CRP support the notion that omalizumab suppresses inflammation at both biochemical and cellular levels [10].
In contrast, no statistically significant changes in PLR or NMR were observed in UV patients. This difference may reflect fundamental pathophysiological differences between CSU and UV.
In our study, the CSU group exhibited a significant post-treatment increase in lymphocyte count, along with significant decreases in neutrophil count, NLR, PLR, NMR, and CRP levels. In contrast, no significant changes were observed in parameters such as MPV, RDW, or LMR. Among patients with UV, only the NLR demonstrated a statistically significant reduction. Although CRP levels declined, the decrease did not reach statistical significance.
Correlation analysis in CSU patients revealed a positive association between pre-treatment NLR and CRP levels. CRP also correlated positively with leukocyte and neutrophil counts, as well as with NMR and LMR. Following treatment, NLR was positively correlated with neutrophils, PLR, and NMR, and negatively correlated with LMR, suggesting a potential modulatory effect of omalizumab on neutrophil-lymphocyte dynamics. Additionally, the positive correlation between RDW and both NLR and PLR may indicate that erythrocyte morphology is influenced by systemic inflammation.
Platelet count and MPV are associated not only with inflammation but also with cardiovascular diseases and thrombotic risk [24, 25]. Studies investigating MPV levels in patients with CSU have produced inconsistent results [26–28]. For instance, Kolkhir et al. reported significantly higher CRP and MPV levels in CSU patients compared to healthy controls [13]. In the present study, however, no significant change in MPV was observed following omalizumab treatment (p = 0.861), in line with the heterogeneous data reported in the literature.
The reduction in peripheral blood basophil counts in CSU may be attributed to the migration of these cells into tissues. Some studies have reported an increase in circulating basophil levels following omalizumab therapy [29]; however, in our study, this change did not reach statistical significance. These findings suggest that basophils may have limited utility as sensitive biomarkers for monitoring treatment response.
UV is characterized histopathologically by vasculitic changes, and its underlying immune mechanisms differ from those observed in CSU. This immunological divergence may explain the relatively limited effectiveness of omalizumab in UV patients. The positive correlations between CRP, neutrophil count, and NMR in the UV group suggest that systemic inflammation persists across multiple cellular components. Accordingly, while CSU patients tend to exhibit a more predictable and robust response to omalizumab, UV may involve a more complex and heterogeneous immunoinflammatory profile.
In patients with CSU, significant improvements were observed in low-cost inflammatory biomarkers such as NLR, PLR, NMR, and CRP following omalizumab treatment [13]. These parameters may serve as accessible and objective tools to complement existing clinical scoring systems for monitoring treatment response [2, 7, 10, 11].
The primary strength of this study is its use of real-world data. However, several limitations should be acknowledged, including the relatively small sample size – particularly in the UV subgroup – and the lack of clinical scoring assessments due to the retrospective study design. Future prospective studies with larger cohorts are needed to validate and expand upon these findings.
Conclusions
This retrospective study shows that omalizumab exerts clear anti-inflammatory effects in CSU and more limited effects in UV. In CSU, treatment led to significant reductions in neutrophil count, NLR, PLR, NMR, and CRP, together with an increase in lymphocyte count, indicating suppression of systemic inflammation beyond IgE-mediated pathways. By contrast, in UV only NLR decreased significantly, while other parameters, including CRP, showed no statistical change, likely reflecting the disease’s distinct immunopathology and the limited sample size. No significant alterations were observed in RDW, MPV, LMR, basophils, or eosinophils, suggesting that these markers are less useful for monitoring treatment response. Improvements in low-cost and easily accessible markers such as NLR, PLR, NMR, and CRP highlight their potential as adjunctive tools for evaluating therapeutic outcomes in CSU. Further prospective studies with larger cohorts and longer follow-ups are needed to confirm these findings and clarify omalizumab’s role in UV.
