Identification of key genes and molecular mechanisms of chronic urticaria based on bioinformatics.

Chronic urticaria (CU) is characterized by persistent skin hives, redness, and itching, enhanced by immune dysregulation and inflammation. Our main objective is identifying key genes and molecular mechanisms of chronic urticaria based on bioinformatics. We used the Gene Expression Omnibus (GEO) database and retrieved two GEO datasets, GSE57178 and GSE72540. The raw data were extracted, pre-processed, and analyzed using the GEO2R tool to identify the differentially expressed genes (DEGs). The samples were divided into two groups: healthy samples and CU samples. We defined cut-off values of log2 fold change ≥1 and p < .05. Analyses were performed in the Kyoto Encyclopaedia of Genes and Genomes (KEGG), the Database for Annotation, Visualization and Integrated Discovery (DAVID), Metascape, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and CIBERSOFT databases. We obtained 1613 differentially expressed genes. There were 114 overlapping genes in both datasets, out of which 102 genes were up-regulated while 12 were down-regulated. The biological processes included activation of myeloid leukocytes, response to inflammations, and response to organic substances. Moreover, the KEGG pathways of CU were enriched in the Nuclear Factor-Kappa B (NF-kB) signaling pathway, Tumor Necrosis Factor (TNF) signaling pathway, and Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway. We identified 27 hub genes that were implicated in the pathogenesis of CU, such as interleukin-6 (IL-6), Prostaglandin-endoperoxide synthase 2 (PTGS2), and intercellular adhesion molecule-1 (ICAM1). The complex interplay between immune responses, inflammatory pathways, cytokine networks, and specific genes enhances CU. Understanding these mechanisms paves the way for potential interventions to mitigate symptoms and improve the quality of life of CU patients.

The Correlation between Serum Vitamin D and Total IgE Levels and Chronic Spontaneous Urticaria among Chinese Population: A Retrospective Study.

Objective: This study aims to investigate the relationship between serum vitamin D, total IgE levels and chronic spontaneous urticaria (CSU). Methods: We collected data from 101 patients with chronic spontaneous urticaria (experimental group) and 115 healthy normal subjects (control group) in the same period of physical examination. Results: The results showed that the number of deficient and absolute deficient 25-hydroxyvitamin D in the experimental group was significantly lower than in the control group (P < 0.05). Pearson correlation analysis showed that the activity score of CSU patients was negatively correlated with serum vitamin D (r = -0.2278, P = 0.0220) and positively correlated with IgE (r = 0.2078, P = 0.0380). It was observed that serum vitamin D in CSU patients was negatively correlated with their activity (r = -0.2278, P = 0.0220) and positively correlated with age (r = 0.2675, P = 0.0069). The Point-biserial correlation analysis revealed that gender was positively correlated with serum vitamin D (Pearson correlation coefficient = 0.286, P = 0.004) and UAS score (Pearson correlation coefficient = 0.273, P = 0.006). Ordinal logistic regression analysis showed that only serum vitamin D was correlated to activity scores (P = 0.008). In addition to activity scores, age (P = 0.005) and gender (P = 0.04) were correlated to serum vitamin D. Conclusion: The activity score of CSU patients was negatively correlated with serum vitamin D and positively correlated with IgE. Serum vitamin D in CSU patients was negatively correlated with activity score and disease duration and positively correlated with age and gender.

Social Media and Urticaria - A Data Audit of Facebook®, LinkedIn®, and Twitter® Posts.

Introduction: Urticaria is a common debilitating dermatological disorder impairing a patient's quality of life. Such patients are increasingly using socialmedia to manage their health and interact with peers, particularly during the ongoing COVID-19 pandemic. Objectives: To explore and analyse the quality of urticaria related social-media information available to patients. Materials and Methods: An in-depth data audit of the three most commonly used social networks viz. Facebook®, LinkedIn®, and Twitter® were done on a single day, as posts may change or lose relevance over time. The word "urticaria" was searched on three social media, and the first 100 posts in each were further analysed. The post-creator was either categorised as "individual" or "group", and non-English posts were excluded. All types of posts have been analysed, including text, images, video, and website links. We also collected the comments/replies, share/re-tweet, and likes on the posts. Results: Among the total 300 social-media posts, the highest number of "individual" posts was on LinkedIn® followed by Twitter® and Facebook® (χ2 = 82.86, P < 0.0001). Regarding thematic content, most Facebook® posts discussed disease symptoms, followed by the promotion of journal or blog posts, and discussion about causative and triggering agents. LinkedIn® was primarily used for the promotion of journal articles or blog posts, followed by educational webinars and urticaria treatment stories. Twitter® users mostly interacted with peers about their urticaria symptoms and perceived etiologic and triggering factors. Regarding the type of post, images were maximally shared on Facebook®, while video/video links and web links were highest on LinkedIn® (χ2 = 21.59, P < 0.0001). Conclusion: The overall quality of urticaria related information on these 3 social media platforms is satisfactory for patients. Dermatologists may consider utilising social media to further educate such patients and improve the overall treatment outcome. The use of such networking channels will continue to grow, as communication remains crucial for urticaria management.

Identification of pyruvic and maleic acid as potential markers for disease activity and prognosis in chronic urticaria.

BACKGROUND: Population-based studies have highlighted the link between chronic urticaria (CU) and metabolic syndrome, and metabolic alterations have been revealed in CU. However, to our knowledge, a comprehensive metabolomics study on a large cohort of CU patients has not been reported. OBJECTIVE: To explore the underlying metabolic subtypes and novel metabolite biomarkers for CU diagnosis and therapy. METHODS: Plasma samples from 80 CU patients and 82 healthy controls (HCs) were collected for metabolomics quantification and performed bioinformatics analysis. Another independent cohort consisting of 144 CU patients was studied to validate the findings. Bone marrow-derived mast cells (BMMCs) and IgE-induced passive cutaneous anaphylaxis (PCA) mice were utilized for in vitro and in vivo experiments, respectively. RESULTS: We observed clear metabolomics difference between CU and HC. Meanwhile, differential metabolites N6-acetyl-l-lysine, L-aspartate, maleic acid and pyruvic acid were used to respectively construct random forest classifiers, and achieved AUCs greater than 0.85, suggesting their potential as diagnostic biomarkers of CU. More importantly, by exploring the underlying metabolic subtypes of CU, we found that the low abundance of pyruvic acid and maleic acid was significantly related to the activity of CU, poor efficacy of second-generation H1-antihistamines (sgAHs), and short relapse-free time. The results were validated in the independent cohort. Moreover, supplementation with pyruvate or maleate could significantly attenuate IgE-mediated mast cells activation in vitro and in vivo. CONCLUSIONS: The combination of plasma pyruvic acid and maleic acid may be effective biomarkers for predicting the disease activity, therapeutic efficacy as well as prognosis for CU patients.

Disparities in chronic spontaneous urticaria: Eligibility for drug reimbursement associated with clinical outcomes.

Background: Chronic spontaneous urticaria (CSU) is an immunologic condition with an estimated prevalence of 0.1%. For CSU that is poorly controlled despite the use of antihistamines, omalizumab is the only treatment approved and recommended by international guidelines. Objective: Our aim was to outline the impact of treatment accessibility on CSU outcomes in the real world. Methods: Serial data on adult patients with CSU receiving care for at least 6 months at a dedicated, immunologist-led urticaria clinic at Grantham Hospital in Hong Kong between 2018 and 2023 were analyzed. Patients' clinicodemographic data, drug eligibility status (eligible for reimbursement or not), treatment step, and disease activity (weekly Urticaria Activity Score [UAS7]) were collected and compared according to drug eligibility status. Results: This study included 238 patients, 80 (33.6%) of whom were eligible for reimbursement and 158 of whom were not. No significant clinicodemographic differences, including disease activity, were found at baseline. At latest follow-up, significantly more patients in the eligible group were receiving omalizumab (28.7% vs 5.7% [P < .001]), which is equivalent to a multivariate odds ratio of 9.35 (95% CI = 3.689-23.703 [P < .001]). The discrepancy persisted even in patients with moderate-to-severe CSU whose UAS7 was 16 or higher (40.6% [13 of 32] vs 10.2% [6 of 59]; P < .001). In addition, there was significantly less dose reduction (<300 mg every 4 weeks) in the eligible omalizumab users (4.3% vs 44.4% [P = .015]). Clinically, significantly greater improvements in UAS7 were reported by the eligible group (median change -8.0 vs -5.0 [P = .021]). Conclusion: Patterns of management varied largely among patients with different drug eligibility statuses and led to disparities in health outcomes. More efforts to secure equitable access to guideline-based CSU care are warranted.

Predicting responses to omalizumab in antihistamine-refractory chronic urticaria: A real-world longitudinal study.

Background: Treating chronic urticaria (CU) that is unresponsive to H1-antihistamines (H1AHs) is challenging, and the real-world effectiveness of omalizumab remains unclear. Objective: Our aim was to evaluate the real-world effectiveness of omalizumab, optimal response assessment timing, and predictive factors. Methods: Initially, 5535 patients with CU who were receiving at least 20 mg of loratadine daily for at least 6 months (January 2007-August 2021) were screened. Ultimately, 386 patients who had been receiving omalizumab add-on treatment for >6 months were followed-up for more than 2 years. Predictors of treatment response to omalizumab add-on therapy for patients with antihistamine-refractory CU were identified by using a generalized linear model. Results: In our retrospective cohort, omalizumab treatment showed cumulative response rates of 55.2% at 3 months, 71.0% at 6 months, and 81.4% at 9 months for patients with H1AH-refractory CU. Analysis of longitudinal responses to omalizumab treatment revealed 3 distinct clusters: favorable (cluster 1 [n = 158]), intermediate (cluster 2 [n =1 43]), and poor responses (cluster 3 [n = 85]). Subjects were categorized on the basis of whether they had achieved a complete response within 3 months; 213 early responders, 117 late responders, and 56 nonresponders were identified. The initial dose of omalizumab differed significantly among the 3 clusters. Low total IgE level (<40 kU/L) predicted nonresponse (odds ratio [OR] = 3.10 [P = .018]). Early responders were associated with a higher initial omalizumab dose (≥300 mg) (OR = 2.07 [P = .016]), higher basophil counts (OR = 2.0 [P = .014]), total IgE levels exceeding 798 kU/L (OR = 0.37 [P = .047]), and lower platelet-to-lymphocyte ratio (OR = 0.50 [P = .050]). Conclusion: Real-world data reveal 3 distinct clusters for response to omalizumab treatment; confirm low serum total IgE level (<40 kU/L) as a predictor of nonresponse; and identify potential biomarkers, including IgE level, basophil count, and PLR, for early responders.

Different doses and courses of omalizumab for patients with chronic spontaneous urticaria: A systematic review with meta-analysis and trial sequential analysis.

Background: The stability, efficacy, and safety of omalizumab at different doses and regimens for chronic spontaneous urticaria (CSU) are yet to be studied. Objective: A systematic review (SR) with meta-analysis (MA) and trial sequential analysis (TSA) was performed to assess the efficacy and safety of omalizumab in CSU. Methods: Randomised controlled trials (RCTs) of administering omalizumab versus placebo for CSU were searched. Random-effects MAs were performed using planned subgroup analyses. TSA was performed to control for the risk of random errors and assess the stability of our MA results. Publication bias was visually assessed using a contour-enhanced funnel plot and the trim-and-fill method. The quality of RCTs was assessed using the Cochrane Risk of Bias Tool 2. Results: Twelve studies met the inclusion criteria. Omalizumab had remarkable effects on the patient percentage of the weekly urticaria activity score is zero (UAS = 0) [RR 4.64, 95% CI (3.38, 6.37)], percentage of no angioedema-burdened days [MD 3.15, 95% CI (0.10, 6.19], patient percentage of UAS ≤6 [RR 3.05, 95% CI (2.46, 3.78)], and patient percentage of the weekly itch severity score minimally important difference (ISS7 MID) [RR 1.50, 95% CI (1.36, 1.66)]. Omalizumab was well tolerated across studies [RR 0.98, 95% CI (0.90, 1.08)]. TSA confirmed the above results, except for "the percentage of no angioedema-burdened day". Conclusion: Among the different doses and courses assessed, omalizumab (300 mg, 12 weeks) can be recommended as an effective treatment for patients with CSU. However, whether omalizumab improves angioedema requires further investigation. The clinical management of angioedema accompanying CSU requires further attention.

Anisakis simplex and urticaria. What we know about its real incidence and management in dermatological settings?

Acute or chronic infections have been described among causes of chronic urticaria (CU). Anisakidosis is a human disease caused by the ingestion of larval nematodes of the family Anisakidae. The infestation is acquired by eating raw seafood or undercooked fish and squid. There are considerable variations in the frequency of underlying causes in the different studies and in different countries, such as differences in diets and the prevalence of infections. Anisakis simplex has been recognized as a trigger of both acute and CU manifestations. However, there is still a lack of evidence about its management and treatment in dermatology. We, therefore, reviewed some biologic properties of Anisakis simplex in order to understand the relationship between its biology and the mechanism it uses to establish chronic dermatological conditions such as urticaria and cause late complications. In addition, we herein report some concerns about the effectiveness of systemic treatment in preventing complications and management in dermatological settings.

Efficacy and Safety of Systemic Corticosteroids for Urticaria: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Short courses of adjunctive systemic corticosteroids are commonly used to treat acute urticaria and chronic urticaria flares (both with or without mast cell-mediated angioedema), but their benefits and harms are unclear. OBJECTIVE: To evaluate the efficacy and safety of treating acute urticaria or chronic urticaria flares with versus without systemic corticosteroids. METHODS: We searched MEDLINE, EMBASE, CENTRAL, CNKI, VIP, Wanfang, and CBM databases from inception to July 8, 2023 for randomized controlled trials of treating urticaria with versus without systemic corticosteroids. Paired reviewers independently screened records, extracted data, and appraised risk of bias with the Cochrane 2.0 tool. We did random effects meta-analyses of urticaria activity, itch severity and adverse events. We assessed certainty of the evidence using the GRADE approach. RESULTS: We identified 12 randomized trials enrolling 944 patients. For patients with low or moderate probability (17.5% to 64%) to improve with antihistamines alone, add-on systemic corticosteroids likely improve urticaria activity by a 14% to 15% absolute difference (odds ratio [OR] 2.17, 95%CI 1.43-3.31; Number needed to treat [NNT] 7; Moderate certainty). Among patients with a high chance (95.8%) for urticaria to improve with antihistamines alone, add-on systemic corticosteroids likely improved urticaria activity by a 2.2% absolute difference (NNT, 45; Moderate certainty). Corticosteroids may improve itch severity (OR, 2.44; 95%CI 0.87-6.83; Risk difference, 9%; NNT, 11; Low certainty). Systemic corticosteroids also likely increase adverse events (OR, 2.76; 95%CI 1.00-7.62; Risk difference, 15%; number needed to harm [NNH], 9; Moderate certainty). CONCLUSION: Systemic corticosteroids for acute urticaria or chronic urticaria exacerbations likely improve urticaria, depending on antihistamine-responsiveness, but also likely increase adverse effects in approximately 15% more.

Patient-Reported Outcome Measures in Atopic Dermatitis and Chronic Urticaria are Underused in Clinical Practice.

BACKGROUND: Patient-reported outcome measures (PROMs) are validated and standardized tools that complement physician evaluations and guide treatment decisions. PROMs are crucial for monitoring atopic dermatitis (AD) and chronic urticaria (CU) in clinical practice, but there are unmet needs and knowledge gaps regarding their use in clinical practice. OBJECTIVE: We investigated the global real-world use of AD and CU PROMs in allergology and dermatology clinics as well as their associated local and regional networks. METHODS: Across 72 specialized allergy and dermatology centers and their local and regional networks, 2,534 physicians in 73 countries completed a 53-item questionnaire on the use of PROMs for AD and CU. RESULTS: Of 2,534 physicians, 1,308 were aware of PROMs. Of these, 14% and 15% used PROMs for AD and CU, respectively. Half of physicians who use PROMs do so only "rarely" or "sometimes". AD and CU PROM usage is associated with being female, younger, and a dermatologist. POSCORAD and UAS were the most utilized PROMs for AD and CU, respectively. Monitoring disease control and activity are the main drivers of the use of PROMs. Time constraints were the primary obstacle to using PROMs, followed by the impression that patients dislike PROMs. AD and CU PROM users would like training in selecting the proper PROM. CONCLUSION: Even though PROMs offer several benefits, their use in routine practice is suboptimal, and physicians perceive barriers to their use. It is essential to attain higher levels of PROM implementation in accordance with national and international standards.

Biomarkers to predict therapeutic response in chronic spontaneous urticaria: a review.

Chronic spontaneous urticaria (CSU) is a relatively common dermatological disorder characterized by sudden and unpredictable onset of pruritic wheals and/or angioedema, for more than six weeks. It is a mast cell-mediated histaminergic disorder, considerably worsening patients' quality of life. Current treatment options include anti-histamines, omalizumab and cyclosporine, in a step-wise algorithmic approach, aimed at complete symptom control. Patients do not respond uniformly to these therapeutic options due to phenotypic and endotypic heterogeneity, and often remain uncontrolled/poorly controlled. Recent research is focused on identifying certain biomarkers to predict therapeutic response and facilitate patient-targeted personalized treatment, for maximum benefit. The current article summarizes various biomarkers explored to date, and also elaborates their role in predicting therapeutic response to anti-histamines, omalizumab and cyclosporine, in CSU patients. High disease activity, elevated CRP/ESR and elevated D-dimer are the most important predictors of non/poor-response to antihistamines. Low and very low baseline IgE, elevated CRP/ESR, ASST+, BAT/BHRA+, basopenia, eosinopenia, and elevated D-dimer are predictors of poor and good response to omalizumab and cyclosporine, respectively. Additionally, normal or slightly elevated baseline IgE and FceR1 overexpression are predictors of a faster response with omalizumab. However, none of these predictors have so far been completely validated and are not yet recommended for routine use. Thus, large-scale prospective studies are needed to confirm these predictive biomarkers and identify new ones to achieve the goal of personalized medicine for CSU.

Does chronic urticaria affect quality of sleep and quality of life?

Background: Urticaria affects a wide range of daily activities and social relationships. It has a severe impact on quality of life (QOL) and causes psychological problems. Objective: was to assess the impact of chronic urticaria (CU) on quality of sleep, the levels of depression, anxiety, QOL and their interaction with each other and their relation to disease related factors. Patients and methods: The study included 25 patients with CU and 25 healthy controls. Urticaria Activity Score (UAS) was used for objective evaluation of the intensity of urticaria. Patients completed a 10-cm visual analogue score (VAS) indicating the overall severity of their itching over the previous 2 weeks. The Dermatology Life Quality Index (DLQI) was used to evaluate patients' QOL. Patients were also assessed for anxiety and depression with the Hospital Anxiety and Depression Scale (HADS). Pittsburgh Sleep Quality Index (PSQI) was used for evaluation of sleep quality and sleep disturbances. Results: In our CU patients the mean of UAS7 score was 39.72 ± 2.76 and the mean of VAS score was 28 ± 1.34. The mean of DLQI score was 24.8 ± 4.37 indicating severe impact of QOL. CU patients had higher total HADS score when compared to controls; 72% of the patients had depression and 92% had anxiety. By using PSQI, CU patients had significantly longer sleep latency onset, shorter total sleep duration, lower sleep efficiency and higher PSQI scores compared to controls. Conclusion: CU highly affects the QOL of patients and is associated with higher levels of anxiety, depression and poor sleep quality.

Chronic spontaneous urticaria preceded by localized insulin reactions: case report.

Chronic spontaneous urticaria presents with wheals and/or angioedema for >6 weeks without any specific triggers. The incidence of chronic spontaneous urticaria is increased in patients with comorbid autoimmune conditions. Here, we present a case of chronic spontaneous urticaria in a 9-year-old with type 1 diabetes and autoimmune thyroid disease who first presented with insulin pump site reactions concerning an insulin-related allergy. The patient was successfully treated with antihistamines and later immunosuppression with resumption of insulin pump therapy and remission of chronic spontaneous urticaria symptoms 18 months after onset.

Leukotriene receptor antagonists as adjuvant therapy of antihistamines in chronic urticaria: a systematic review and meta-analysis.

Certain guidelines recommend a second-generation H1-antihistamine (AH) as first-line treatment for patients with chronic urticaria (CU). However, some patients show insufficient response to a standard dose of this therapy and might benefit from adding leukotriene receptor antagonists (LTA). Therefore, we aimed to perform a systematic review and meta-analysis comparing LTA plus antihistamines with antihistamines alone. We performed a systematic review and meta-analysis, searching PubMed, EMBASE, and Cochrane Central for randomized clinical trial (RCT) data comparing LTA plus AH treatment to AH alone in patients with CU. Statistical analysis was performed using R Studio 4.3.2. Heterogeneity was assessed with I2 statistics. Three studies comprising 234 patients with urticaria were included. The mean age was 37.23 years in the leukotriene antagonist + antihistamines (LTA + AH) group and 39.14 years in the antihistamines (AH) group. Follow-up ranged from 2 to 18 months between studies. There was no statistically significant difference between groups in terms of TSS level (SMD: -74.82; 95% CI: -222.66 to 73.02; P = 0.32; I2 = 98%), neither in terms of pruritus (MD: -0.07; 95% CI: -0.42 to 0.28; P = 0.70; I2 = 74%). After sensitivity analysis, with the systematic exclusion of each study from the grouped estimates, the result for TSS level did not change. These findings suggest that leukotriene receptor antagonists with antihistamines do not have better outcomes than antihistamines alone regarding TSS and pruritus in patients with CU.

Lin-CD117+CD34+FcεRI+ progenitor cells are increased in chronic spontaneous urticaria and predict clinical responsiveness to anti-IgE therapy.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common, debilitating skin disorder characterized by recurring episodes of raised, itchy and sometimes painful wheals lasting longer than 6 weeks. CSU is mediated by mast cells which are absent from peripheral blood. However, lineage-CD34hiCD117int/hiFcεRI+ cells in blood have previously been shown to represent a mast cell precursor. METHODS: We enumerated FcεRI-, FcεRI+ and FcεRIhi lineage-CD34+CD117+ cells using flow cytometry in blood of patients with CSU (n = 55), including 12 patients receiving omalizumab and 43 not receiving omalizumab (n = 43). Twenty-two control samples were studied. Disease control and patient response to omalizumab was evaluated using the urticaria control test. We performed single-cell RNA sequencing (scRNA-Seq) on lineage-CD34hiCD117hi blood cells from a subset of patients with CSU (n = 8) and healthy controls (n = 4). RESULTS: CSU patients had more lineage-CD34+CD117+FcεRI+ blood cells than controls. Lineage-CD34+CD117+FcεRI+ cells were significantly higher in patients with CSU who had an objective clinical response to omalizumab when compared to patients who had poor disease control 90 days after initiation of omalizumab. scRNA-Seq revealed that lineage-CD34+CD117+FcεRI+ cells contained both lymphoid and myeloid progenitor lineages, with omalizumab responsive patients having proportionally more myeloid progenitors. The myeloid progenitor lineage contained small numbers of true mast cell precursors along with more immature FcεRI- and FcεRI+ myeloid progenitors. CONCLUSION: Increased blood CD34+CD117+FcεRI+ cells may reflect enhanced bone marrow egress in the setting of CSU. High expression of these cells strongly predicts better clinical responses to the anti-IgE therapy, omalizumab.

Predicting the Speed of Response to Omalizumab in Chronic Spontaneous Urticaria.

INTRODUCTION: Two distinct chronic spontaneous urticaria (CSU) endotypes, IgE-mediated autoallergic and IgG-mediated autoimmune, were defined based on the response patterns to omalizumab. However, the coexistence of IgE and IgG autoantibodies in a subset of patients might complicate the prediction of the treatment outcomes. This study aimed to evaluate the effectiveness and safety of omalizumab in CSU patients, focusing on the factors predicting the response patterns. METHODS: This was a retrospective cross-sectional single-center study investigating CSU patients treated with omalizumab for at least 6 months between September 2015 and February 2023. Patients were evaluated regarding demographics, clinical findings, baseline laboratory parameters, treatment outcomes, and side effects. Early and late responders were defined depending on the time for response, within or after 3 months, respectively. RESULTS: Among 82 patients, 75 (91.5%) responded to omalizumab during the first 6 months, classified as early (n = 51) and late responders (n = 24). The IgG anti-thyroid peroxidase (anti-TPO)/total IgE ratio was an independent predictor for determining the speed of response (p < 0.05). Of 29 patients who discontinued omalizumab, 19 (65.5%) experienced relapse with a good response to retreatment (n = 18/19, 94.7%). Early responders relapsed more frequently than late responders (77.3% vs. 28.6%) (p < 0.05). Only mild side effects were observed in a minority of patients (n = 8/82, 9.8%). CONCLUSION: Omalizumab is an effective and safe treatment in CSU. The IgG anti-TPO/total IgE ratio seems a valuable tool to predict the early and late responders, the former having a higher possibility of relapse upon drug withdrawal.