Refractory Chronic Spontaneous Urticaria to Conventional Treatment: Challenges and Therapeutic Strategies

Presenter: G. Yánez Lema

Chronic spontaneous urticaria (CSU) is a condition driven by mast cells (immune cells) that causes recurrent hives and/or swelling (angioedema) lasting longer than six weeks. In nearly 10-50% of cases, CSU remains persistent despite management with high-dose second-generation H1-antihistamines (AH1). This case report describes the treatment course of an 8-year-old girl with severe chronic spontaneous urticaria (CSU) that was refractory to multiple therapies. Following an infectious episode, she developed daily, intensely pruritic generalized wheals with a Weekly Urticaria Activity Score (UAS7) of 50. The condition was accompanied by bilateral eyelid angioedema, abdominal pain, and nausea. Initial treatment with cetirizine was increased to four times the standard dose, and short courses of oral corticosteroids were used during episodes of angioedema. Despite these measures, disease activity remained uncontrolled. Baseline investigations showed normal blood counts and inflammatory markers. Laboratory findings included positive antinuclear antibodies (ANA; 1:80), total immunoglobulin E (IgE) of 97 kU/L, and a positive autologous serum test Teste de Ativação de Basófilos (TAB), which translates to Basophil Activation Test (BAT), suggesting an autoimmune form of CSU. Due to persistent symptoms, omalizumab (OMZ) 300 mg every 4 weeks was initiated and continued for 14 months. The patient experienced only a temporary partial response. Given the autoimmune features and family history of autoimmunity, further rheumatologic evaluation was performed, which identified a heterozygous variant of uncertain significance in the RELA gene. The same variant was also detected in the patient’s asymptomatic mother. Cyclosporine therapy (30 mg/day) was started 21 months after disease onset and resulted in complete remission that was maintained for 12 months. However, the disease relapsed 3 months after treatment discontinuation. Dupilumab 300 mg every 2 weeks was subsequently initiated. The patient achieved rapid and sustained clinical remission, and treatment was well tolerated throughout follow-up.

This case highlights the challenges of managing severe pediatric CSU that is refractory to standard therapies. In this patient, dupilumab provided sustained disease control after inadequate response to high-dose antihistamines, omalizumab, and relapse following cyclosporine withdrawal.

Assessment of Serum Substance P Levels in Chronic Spontaneous Urticaria with Predominant Pruritus Refractory to H1-Antihistamines and Omalizumab

Presenter: D. Fomina

Substance P is a neuropeptide involved in mast cell activation and itch regulation, but its significance in chronic spontaneous urticaria is not fully understood. This study evaluated the role of serum Substance P levels (SSPL) in chronic spontaneous urticaria (CSU) and their potential association with disease severity and treatment requirements. A total of 61 participants were included. Patients were categorized into four groups: CSU with incomplete disease control (n=10), CSU with persistent pruritus, defined as an isolated UAS7 elevation driven by pruritus (mean 5.67, SD 4.97) despite H1-antihistamines and/or omalizumab treatment (n=15), CSU with predominant pruritus receiving or requiring psychopharmacotherapy (n=24), and pruritus due to other causes (n=12). Ten healthy individuals served as controls. Among the 49 CSU patients, an SSPL threshold of 18.863 pg/mL was identified as a potential marker of disease severity. This cut-off showed a sensitivity of 94.1% (16/17) and a specificity of 56.3% (18/32) for identifying patients who required omalizumab because of inadequate response to antihistamines (p=0.000565). Patients with persistent pruritus despite treatment (Group 2) had significantly higher SSPL than healthy controls (24.55 [22.24–35.23] vs 15.88 [10.61–25.32] pg/mL; p=0.0213). Similarly, patients with pruritus from causes other than CSU (Group 4) also had higher SSPL than controls (23.85 [18.03–40.05] pg/mL; p=0.0409). No significant differences from controls were observed in patients with incompletely controlled CSU (Group 1: 23.07 [18.97–25.47] pg/mL; p=0.4727) or in those receiving psychopharmacotherapy (Group 3: 17.47 [15.78–21.40] pg/mL; p=0.4384). Among CSU patients, those receiving omalizumab had significantly higher SSPL than patients treated with H1-antihistamines and/or psychopharmacotherapy (23.54 [21.67–30.47] vs 18.32 [15.55–24.23] pg/mL; p=0.00296). SSPL were also significantly higher in omalizumab-treated patients than in healthy controls (p=0.0254). Additional analyses included eosinophil, basophil, leukocyte counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), total immunoglobulin E (IgE), immunoglobulin G anti-thyroid peroxidase (IgG anti-TPO), and immunoglobulin G anti-thyroglobulin (IgG anti-TG). SSPL showed a significant correlation with CRP levels in the overall study population (p=0.0176) and within each study group.

Overall, elevated SSPL were associated with persistent pruritus and pruritus of other causes. High SSPL were detected in patients receiving omalizumab and with elevated CRP. Higher SSPL and elevated CRP may identify patients whose disease remains inadequately controlled due to persistent itch despite treatment.

Comparison of Disease Duration, Remission, and Other Disease-Related Parameters with the Duration of Omalizumab Treatment in Patients with Chronic Spontaneous Urticaria

Presenter: BS. Akyol

Omalizumab is a biologic drug commonly used in patients with chronic spontaneous urticaria (CSU) whose symptoms don't respond to antihistamines, and most patients see improvement with it. This retrospective study evaluated the relationship between omalizumab treatment duration with disease duration, remission, and disease characteristics in patients with antihistamine-resistant CSU. The analysis included 175 patients who received or were receiving omalizumab and were followed at a single clinic between January 2015 and December 2025. Patients were categorized according to omalizumab treatment duration: Group 1 (1–24 months), Group 2 (25–60 months), and Group 3 (>60 months) and disease duration (before omalizumab therapy), remission, and disease-related parameters were compared.. Remission was defined as remaining symptom-free for at least 6 months after discontinuation of omalizumab therapy. No significant differences were observed among the three groups with respect to age, sex, elevated immunoglobulin E (IgE) levels, specific immunoglobulin E (sIgE) positivity, angioedema, atopic diseases, antinuclear antibody (ANA) positivity, thyroid-stimulating hormone (TSH), thyroid disease, anti-thyroid peroxidase (anti-TPO) positivity, low complement C3, low complement C4, tryptase levels, or remission rates. However, significant differences were identified for disease duration, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Therefore, pairwise comparisons (Mann-Whitney U) were performed to identify which groups accounted for these differences. Pairwise analyses showed a significant difference in CRP levels between Groups 1 and 2 (p=0.033). Significant differences in disease duration and ESR were observed between Groups 1 and 3 (disease duration: p=0.001; ESR: p=0.011) and between Groups 2 and 3 (disease duration: p=0.033; ESR: p=0.033). When all three groups were analyzed together, the significant differences in disease duration and ESR were primarily driven by patients in Group 3, who had received omalizumab for more than 60 months. Although the difference was not statistically significant, patients with a shorter disease duration tended to have higher remission rates. The study also found that patients requiring long-term omalizumab treatment had significantly higher ESR levels, suggesting a greater degree of chronic inflammation.

The most notable finding was a positive correlation between disease duration before starting omalizumab and the subsequent duration of omalizumab treatment, indicating that patients with a longer history of CSU may require longer periods of omalizumab therapy.

Alexithymia and Depression in Patients with Chronic Spontaneous Urticaria Treated with Omalizumab

Presenter: GG. Atay

This study evaluated levels of depression and alexithymia in patients with chronic spontaneous urticaria (CSU) receiving omalizumab treatment and examined their relationship with disease activity, disease control, and quality of life. The study included 27 patients with CSU who were receiving omalizumab therapy and a group of healthy controls. Disease activity was assessed using the Urticaria Activity Score over 7 days (UAS7), disease control with the Urticaria Control Test (UCT), and quality of life with the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL). Depression was measured using the Beck Depression Inventory (BDI), while alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20). Patients with CSU had significantly higher levels of both depression and alexithymia compared with healthy controls. The mean BDI score was 12.1 ± 6.8 in patients versus 6.8 ± 6.7 in controls (p=0.003). Similarly, the mean TAS-20 score was significantly higher in patients than in controls (54.4 ± 10.7 vs 40.5 ± 12.2; p<0.001). A significant positive correlation was observed between disease activity and depression severity, with higher UAS7 scores associated with higher BDI scores (r=0.39, p=0.046). However, alexithymia scores were not significantly associated with disease activity, disease control, or quality of life measures (p>0.05).

Overall, despite receiving omalizumab treatment, patients with CSU experienced higher levels of depressive symptoms and alexithymic traits than healthy individuals. Depression was associated with greater disease activity, whereas alexithymia appeared to be independent of clinical disease measures.

Vitamin D Status as a Modifiable Factor in Chronic Spontaneous Urticaria

Presenter: A. Kovchun

Several autoimmune diseases have been associated with low levels of vitamin D. However, supporting data to prove the impact of vitamin D status on the course of chronic spontaneous urticaria (CSU) is limited. This study evaluated the effect of vitamin D supplementation on disease activity and disease control in patients with chronic spontaneous urticaria (CSU). The study included 42 patients with CSU that was refractory to standard-dose antihistamine treatment and 15 healthy controls. Serum 25-hydroxyvitamin D (25[OH]D) levels, Urticaria Activity Score over 7 days (UAS7), and Urticaria Control Test (UCT) scores were assessed at baseline and after 4 weeks. All patients received second-generation antihistamines at four times the standard dose. Patients were divided into three groups: Group A had 25(OH)D levels >20 ng/mL (n=12), Group B had 25(OH)D levels <20 ng/mL (n=15), and Group C had 25(OH)D levels <20 ng/mL (n=15) and additionally received oral cholecalciferol 5,000 IU/day for 4 weeks. Statistical analysis was performed using SPSS version 21. Among the CSU patients, 66.6% were women and 33.4% were men. Baseline serum 25(OH)D levels were significantly lower in patients with CSU than in healthy controls (15.62±2.10 vs 31.58±6.4 ng/mL; p<0.001). There was no significant difference in baseline vitamin D levels between Groups B and C (p=0.21). At baseline, Group A showed significantly lower disease activity and better disease control than Groups B and C, as reflected by lower UAS7 scores and higher UCT scores. After 4 weeks of treatment, significant improvements in both UAS7 and UCT scores were observed in Groups A and C (p<0.05 for all comparisons). In contrast, no significant improvement was seen in Group B. Serum 25(OH)D levels increased significantly only in Group C, the group receiving vitamin D supplementation (p=0.018).

Overall, patients with CSU had lower vitamin D levels than healthy individuals, and vitamin D deficiency was associated with higher disease activity and poorer disease control. Supplementation with cholecalciferol in vitamin D–deficient patients improved both urticaria activity and disease control when added to high-dose antihistamine therapy.

Thyroid Autoantibody Seroconversion in Chronic Spontaneous Urticaria: Insights from Omalizumab Treated Patients

Presenter: R. Oztas

This retrospective study investigated the clinical and laboratory features associated with anti-thyroid peroxidase immunoglobulin G (anti-TPO IgG) seroconversion in patients with chronic spontaneous urticaria (CSU) receiving omalizumab therapy. The analysis included 54 patients who developed anti-TPO IgG seroconversion during follow-up. These patients were compared with age-, sex-, and baseline total immunoglobulin E (IgE)-matched CSU patients who remained anti-TPO negative throughout follow-up. Demographic characteristics, disease duration, treatment patterns, laboratory findings, and disease activity measures were evaluated. Within the seroconversion group, patients were further classified according to their disease control status during the period of anti-TPO positivity. Patients who developed anti-TPO IgG seroconversion had higher disease activity and were more likely to require additional treatment compared with patients who remained anti-TPO negative. Among patients with seroconversion, those who experienced disease flare-ups had higher rates of nonsteroidal anti-inflammatory drug (NSAID) sensitivity, greater antihistamine requirements, more frequent eosinopenia, and significantly lower total IgE levels than those with better disease control. Analysis identified total IgE levels at the time of seroconversion as the only independent predictor of disease control. The timing of seroconversion was also associated with clinical outcomes. Early anti-TPO IgG seroconversion was linked to a greater need for treatment escalation, while late seroconversion was associated with higher baseline total IgE levels.

Overall, anti-TPO IgG seroconversion during omalizumab treatment was associated with higher disease activity, changes in IgE levels, eosinopenia, and increased treatment requirements in a subset of patients with CSU. These findings suggest that the development of thyroid autoimmunity-related antibodies may be associated with changes in disease characteristics and disease control during treatment.

Potential Clinical and Laboratory Biomarkers for Predicting Omalizumab Response in Chronic Spontaneous Urticaria

Presenter: B. Özkan Kırgın

This retrospective study evaluated treatment response to omalizumab (OMA) and potential predictors of response in pediatric patients with chronic spontaneous urticaria (CSU). The study included 28 children treated with OMA at the Ankara Etlik City Hospital Pediatric Immunology and Allergy Clinic between October 2022 and March 2025. Demographic, clinical, and laboratory data were collected from hospital records. Treatment response was assessed at Week 12 using the Urticaria Activity Score (UAS). Patients with a UAS <7 were classified as complete responders, those with a UAS of 7–15 as partial responders, and those with a UAS >15 as non-responders. Responsiveness to OMA was also evaluated using the Outcome and Assessment Information Set Database (OASIS-D) rating system. At Week 12, 53.6% of patients achieved a complete response, 42.9% achieved a partial response, and 3.6% were non-responders. Improvement in OASIS-D scores was observed in 96% of patients. Patients with a younger age at disease onset and diagnosis had significantly higher pre-treatment OASIS-D scores. Complete responders had significantly lower baseline C-reactive protein (CRP) levels and neutrophil-to-lymphocyte ratio (NLR) compared with patients who achieved a partial response or did not respond to treatment (p<0.05). A higher anti-thyroid peroxidase antibody (anti-TPO) to total immunoglobulin E (IgE) ratio was associated with lower rates of complete response; however, this association did not reach statistical significance. In addition, a history of allergic disease was significantly associated with a higher likelihood of achieving a complete response.

Overall, omalizumab was effective in most pediatric patients with CSU. Lower baseline CRP levels and NLR were associated with a greater likelihood of complete response and may serve as potential predictors of treatment success.

EAACI 2026, June 12-15, Istanbul, Türkiye