Urticaria Research Articles

564 - Conjunctivitis adverse events in dupilumab clinical trials

Abstract Introduction Dupilumab inhibits signaling of IL-4 and IL-13, key drivers of Type 2 inflammatory diseases such as atopic dermatitis (AD), asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), prurigo nodularis (PN), and Chronic Spontaneous Urticaria (CSU).1,2 Adults with AD have a significant and disease severity-dependent increased risk of developing ocular surface diseases, including conjunctivitis and keratitis, compared with the general population.3 In randomized placebo-controlled trials of dupilumab in patients with moderate-to-severe AD, more conjunctivitis events were reported in patients who received dupilumab treatment than in placebo-treated patients.4,5 Objective This analysis reviewed the incidence, severity, and resolution of conjunctivitis adverse events (AEs) in patients from clinical trials evaluating dupilumab in AD, asthma, CRSwNP, EoE, PN, and CSU. Methods “Conjunctivitis” refers to the group of MedDRA Preferred Terms (PTs) that include the term ‘conjunctivitis’, namely conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, adenoviral conjunctivitis, and atopic keratoconjunctivitis. All cases of conjunctivitis were included regardless of etiology (including blepharoconjunctivitis, which was coded as the MedDRA PT conjunctivitis, and excluding blepharitis in the absence of conjunctivitis. This analysis excludes events of keratitis. Randomized, double-blinded, placebo-controlled trials included in this analysis were: Liberty AD Solo 1, Liberty AD Solo 2, Liberty AD Chronos, LIBERTY AD ADOL, LIBERTY AD PEDS, LIBERTY AD PRESCHOOL Part B (AD); Liberty Asthma Quest, Liberty Asthma Venture (asthma); Liberty NP Sinus-24, Liberty NP Sinus-52 (CRSwNP); Liberty EoE Treet (EoE); Liberty PN Prime, Liberty-PN Prime2 (PN); and Liberty-CSU Cupid Part A (CSU). Results Overall conjunctivitis incidence was higher in patients receiving dupilumab vs placebo in all randomized AD trials, with 7.9% to 19.4% of adult dupilumab-treated patients and 4.8% to 14.8% of dupilumab-treated patients aged 6 months to <18 years experiencing conjunctivitis events. In contrast, conjunctivitis rates were <5% and similar between dupilumab and placebo in the asthma, CRSwNP, EoE, PN, and CSU trials. Most conjunctivitis cases observed in adult patients with AD receiving dupilumab treatment were mild to moderate in severity, with severe conjunctivitis being reported at rates of ≤0.6%. A majority of all conjunctivitis cases in dupilumab-treated adults with AD were resolved during the treatment period. Conclusions Overall conjunctivitis events were more frequent in dupilumab-treated vs placebo-receiving patients in AD trials across ages, whereas rates were low and similar between dupilumab and placebo groups in the asthma, CRSwNP, EoE, PN, and CSU trials. Most conjunctivitis cases observed in adult patients with AD receiving dupilumab treatment were mild to moderate in severity and resolved by the end of the study period. Current evidence suggests that conjunctivitis associated with dupilumab occurs predominantly in patients with AD. It is possible that pre-existing ocular disorders and a dupilumab–AD disease-specific interaction may be responsible for this increased incidence in dupilumab-treated patients with AD.

Atopy in chronic urticaria: an important yet overlooked issue.

Chronic urticaria (CU) is one of the most common dermatological diseases and has a significant impact on the quality of life of patients. However, the pathogenesis of this disease remains unclear. Autoimmunity in chronic spontaneous urticaria (CSU) has received considerable attention and has been studied previously. Atopy is an important characteristic of CU; however, it has not been fully recognized. Atopy predisposes individuals to immune responses to allergens, leading to type 2 inflammation and immunoglobulin E (IgE) overproduction. Compared with healthy individuals, patients with CU have a higher proportion of atopy, and an atopic background is correlated with the clinical characteristics of CU. The total IgE levels in patients with CU is significantly higher than those in healthy individuals. Although its level is not higher than that in classic allergic diseases, it is closely related to CU. Exogenous allergens, auto-allergens, and specific IgEs, which are closely related to atopy, have been reported, and their roles in CU pathogenesis are also being studied. Local and systemic atopic inflammation is present in patients with CU. This review summarizes the current knowledge regarding atopy and CU, speculating that there are CU subtypes, such as atopic CSU or atopic chronic inducible urticaria (CIndU) and that atopy may be involved in the pathogenesis of CU. These findings provide a new perspective for a comprehensive understanding of the clinical features of CU and further research regarding its pathogenesis.

Mapping the intellectual structure of the research of omalizumab in chronic spontaneous urticaria: A bibliometric analysis

BackgroundGuidelines for treating Chronic Spontaneous Urticaria (CSU) recommend using the IgE-targeted biologic Omalizumab in patients with antihistamine-refractory disease. ObjectiveTo present a bibliometric review of publications related to Omalizumab and CSU over the past two decades. MethodsPublications that are relevant from 2003 to 2022 were extracted from the Science Citation Index-Expanded (SCI-EXPANDED) in the Web of Science Core Collection (WoSCC) database as of January 8, 2023. We utilized CiteSpace (version 6.1.R3), VOSviewer (version 1.6.18), and the R package (version 4.2.1) to analyze and visualize the data. The R package bibliometrix (version 4.2.1) was also used. ResultsBetween 2003 and 2022, a total of 566 articles were published. Since 2014, there has been a rapid increase in publication outputs. According to the collaboration network, the most influential country/institute/scholar was the USA, Charité Universitätsmedizin Berlin, and Maurer Marcus, respectively. The study identified the Journal of Allergy and Clinical Immunology: In Practice as the most productive journal and the Journal of Allergy and Clinical Immunology as the most co-cited journal. The analysis of keywords revealed that high-frequency terms such as angioedema, IgE, treatment, anti-IgE, asthma, and atopic dermatitis were present. Moreover, recent studies in this area have mainly concentrated on biomarkers, Dupilumab, and COVID-19. ConclusionThere has been a growing interest in the use of Omalizumab in CSU in recent years. The current trending topics in this research are the identification of biomarkers and the development of new monoclonal antibodies for the treatment of CSU.

An Open-Label, Investigator-Initiated, Single-Centre Pilot Study to Determine the Safety and Efficacy of Tofacitinib in Resistant Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is a distressing skin condition characterized by the recurrent appearance of itchy hives. A subset of CSU patients remains resistant to conventional treatment with high-dose antihistamines. Tofacitinib, a Janus kinase inhibitor, has shown promise in various inflammatory skin diseases. We aimed to evaluate the efficacy of oral tofacitinib in patients with CSU resistant to antihistamines. This study examined data retrospectively from seven patients who were diagnosed with CSU and were treated with tofacitinib for at least six months. These patients initially exhibited resistance to treatment with four-fold up-dosed antihistamines. One of the patients was already on omalizumab, and another was tried on cyclosporine. The patients were administered oral tofacitinib at a dosage of 5 mg twice daily for six months. Patients were followed up monthly for disease control and side effects. The response to treatment was evaluated using the urticaria activity score over 7 days (UAS7) and urticaria control test (UCT). Paired t-tests were conducted to determine the statistical significance of the results using SPSS version 25 software. Six out of the seven patients demonstrated a significant improvement in both UAS7 and UCT scores after six months of treatment with oral tofacitinib. The mean UAS7 score decreased from 24.86 at baseline to 3.83 at the study endpoint (P < 0.0001). Similarly, the mean UCT score increased from 0.57 at baseline to 14 at the study endpoint (P < 0.0001). The standard deviations for both measures were 4.85 and 0.98 at baseline and 3.1 and 3.1 at the study endpoint for UAS7 and UCT, respectively. In this six-month follow-up study, oral tofacitinib demonstrated significant efficacy in treating CSU patients' resistant to high-dose antihistamines. Most patients experienced a remarkable reduction in urticaria activity and an improvement in disease control. These findings suggest that tofacitinib holds promise as a potential therapeutic option for this challenging subset of CSU patients. However, larger, randomized controlled trials are warranted to further investigate the long-term safety and effectiveness of tofacitinib in this population.

A global perspective on stepping down chronic spontaneous urticaria treatment: Results of the Urticaria Centers of Reference and Excellence SDown-CSU study.

Although there have been significant advances in the treatment of chronic spontaneous urticaria (CSU) in recent years, there remains a lack of clear guidance on when and how to step down treatment in responders. This study aims to investigate stepping down approaches of different steps of CSU treatment from a global perspective. "Stepping down chronic spontaneous urticaria treatment" (SDown-CSU) is an international, multicenter, observational, cross-sectional, survey-based study of the Urticaria Centers of Reference and Excellence (UCARE) network. The questionnaire included 48 questions completed by physicians in the UCARE network. Surveys completed by 103 physicians from 81 UCAREs and 34 countries were analyzed. Seventy-eight percent of the participants responded that they had a national urticaria management guideline written by their professional societies and 28% responded that they had to operate under a regulatory guideline proposed by central health funding organizations. Seventy-two and 58.7% of these national recommendations do not contain any detailed information on when and/or how CSU treatment should be discontinued. There was a lack of detailed information on antihistamines and cyclosporine in particular. A predefined maximum duration was generally not applicable to omalizumab and cyclosporine (81% and 82%, respectively). Nearly all UCAREs step down omalizumab within 6months from the first controlled status and 42% discontinue cyclosporine after 6months regardless of the control status. The findings from the SDown-CSU study clearly highlight a global need for guidance on the process of stepping down treatment in CSU. Additionally, the study offers a step-down algorithm applicable to all stages of CSU treatment.

The Role Of Serum Biomarkers In Predicting Response To Omalizumab Therapy In Patients With Chronic Spontaneous Urticaria

The Role Of Serum Biomarkers In Predicting Response To Omalizumab Therapy In Patients With Chronic Spontaneous Urticaria

Patient Characteristics and Comorbidities Among US Veterans With Chronic Spontaneous Urticaria (CSU): Data From the Veterans Health Administration (VHA)

Patient Characteristics and Comorbidities Among US Veterans With Chronic Spontaneous Urticaria (CSU): Data From the Veterans Health Administration (VHA)

Study of effectiveness of methotrexate oral pulse in refractory chronic urticaria

Objectives: Chronic urticaria (CU) is an unexplained problem that needs to be addressed, and since patients also experience the morbidity associated with irritable itch, they must take a significant quantum of antihistamines. Autoantibodies in the blood cause recurrent flare-ups in autoreactive urticaria when the symptoms are more noticeable. As a result, the need for an adjuvant drug to lessen the weight of pills is felt. The aim of this study was to find out the effectiveness of oral methotrexate (MTX) pulse with antihistamines in chronic refractory urticaria. Material and Methods: This was the present longitudinal intervention. The study lasted six months and was carried out at the Department of Dermatology in a hospital with tertiary care status. Fifty patients of chronic spontaneous urticaria have been selected by simple random sampling. All subjects have been given Oral Methotrexate, 15 mg once weekly along with folic acid. Besides, MTX all cases have been given oral desloratadine 5 mg twice daily. Results: Most patients have seen a significant decline in urticaria activity score 7 (UAS7) and dermatological life quality index. The baseline mean UAS7 reduced significantly from 30.16 ± 8.65 to 1.24 ± 2.24 with a statistically significant P &lt; 0.01. No serious side effects were seen except mildly raised liver transaminases in seven patients. Conclusion: When standard second-generation antihistamines are insufficient at treating chronic uncontrolled urticaria, MTX is a very safe, well-tolerated, and economical treatment option.

Dupilumab Improves Urticaria-Specific Quality of Life in Patients with Chronic Spontaneous Urticaria Uncontrolled by H1 Antihistamines

Dupilumab Improves Urticaria-Specific Quality of Life in Patients with Chronic Spontaneous Urticaria Uncontrolled by H1 Antihistamines

Remibrutinib monotherapy reduced rescue medication in chronic spontaneous urticaria patients: Findings from a Phase 2b extension study

Remibrutinib monotherapy reduced rescue medication in chronic spontaneous urticaria patients: Findings from a Phase 2b extension study

Management of severe chronic spontaneous urticaria with omalizumab

Management of severe chronic spontaneous urticaria with omalizumab

The Efficacy and Safety of High Dose (10 mg) of Desloratadine (Dazit® 10) in the Treatment of Chronic Spontaneous Urticaria in India: A Phase III, Multicentric, Open-Label, Single-Arm Study.

Chronic spontaneous urticaria (CSU) is a debilitating affliction that affects diverse quality of life (QoL) parameters such as sleep, self-esteem, and daily activities. Second-generation antihistamines, such as desloratadine, are more effective and safer in managing CSU. Desloratadine is a nonsedating, potent, and highly selective H1 receptor antagonist. At its daily dose of 5 mg, almost half of CSU patients do not show symptomatic improvement. European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Network (GA2LEN)/European Dermatology Forum (EDF) (EuroGuiDerm)/Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI) guidelines recommend increasing the dosage to up to four times in such nonresponsive patients. However, there is insufficient clinical evidence in Indian settings. We evaluated the efficacy and safety of 10 mg desloratadine (OD) in 256 nonresponsive patients with moderate to severe CSU. The primary outcome was the change in Urticaria Activity Score (UAS7) from baseline to four weeks. Additionally, change in Chronic Urticaria Quality of Life (CU-Q2oL) scores during the course of treatment was also evaluated. The mean UAS7 scores showed a significant reduction from 31.9 ± 4.8 at baseline to 18.2 ± 8.1 at the end of the study (p < 0.0001). The use of a higher dose of desloratadine also decreased the CU-Q2oL scores significantly from 59.8 ± 14.7 at baseline to 35.4 ± 10 at four weeks (p < 0.0001). The incidence of adverse events (AEs) possibly linked to the drug was low (1.6%), and no serious adverse events were reported. Results indicated improvements in the disease severity as well as its positive impact on participants' QoL. This study confirms the efficacy and safety of daily use of a twofold dose of desloratadine in nonresponsive moderate to severe CSU patients.

The comparative burden of chronic spontaneous urticaria, atopic dermatitis and psoriasis in five European countries

AbstractBackgroundSkin diseases can have a significant impact on the physical, psychological and social well‐being of patients. Quantification of the burden of chronic spontaneous urticaria (CSU) compared to other dermatological conditions is limited.ObjectivesTo evaluate the comparative humanistic and economic burden of CSU, atopic dermatitis (AD), and psoriasis (PSO) in five European countries (EU5).MethodsThis cross‐sectional analysis compared data from adult respondents with a physician diagnosis of CSU, AD and PSO from the 2020 National Health and Wellness Survey in EU5 (France, Germany, Italy, Spain and the United Kingdom). Outcomes included Short Form (SF)‐12v2 [mental (MCS) and physical component (PCS) summary scores], SF‐6D, EQ‐5D, EQ‐Visual Analogue Scale (VAS), Dermatology Life Quality Index (DLQI), General Anxiety Disorder‐7 (GAD‐7), Patient Health Questionnaire‐9 (PHQ‐9), Work Productivity and Activity Impairment (WPAI) and healthcare resource utilization (HRU). Multivariable analyses comparing CSU to AD and PSO, respectively, were conducted for each outcome.ResultsThis analysis included 379 CSU, 788 AD and 2,636 PSO patients. Adjusted MCS and PCS scores were lower among CSU patients than AD (MCS, p = 0.006; PCS, p &lt; 0.001) and PSO (p &lt; 0.001 for all). SF‐6D and EQ‐5D scores were consistently lower among CSU patients versus AD and PSO (p &lt; 0.001 for all), whereas the EQ VAS was lower in CSU cohort versus PSO cohort (p = 0.003). Higher DLQI scores were reported in the CSU cohort versus AD and PSO (p &lt; 0.001 for both) and the proportion of patients with anxiety and depression, respectively, (GAD‐7 and PHQ‐9 scores ≥5) was greater among the CSU cohort versus AD and PSO (p &lt; 0.001 for all). Finally, higher HRUs and worse WPAI scores (p &lt; 0.005) were observed in the CSU cohort relative to AD and PSO cohort.ConclusionsCSU is associated with significantly worse health‐related quality of life, more mental comorbidities, negative impact on patients' daily lives and the ability to work, ultimately leading to higher HRU compared with AD and PSO.

Circulating basophils in patients with type IIb autoimmune chronic spontaneous urticaria have a lower histamine content

AbstractBackgroundPatients suffering from chronic spontaneous urticaria (CSU) are typically classified as type I or type IIb autoimmune CSU, but further patient stratification is hindered by the lack of biomarkers.ObjectivesWe investigated whether the histamine content of individual basophils differ between patient subtypes in CSU to evaluate its potential as a biomarker.MethodsA total of 101 patients diagnosed with CSU were included in the study. The histamine content per circulating basophil was derived from the basophil count in peripheral blood and levels of total cellular blood histamine. These measures, together with results from the serum‐induced basophil histamine release assay (s‐BHRA), were correlated to information on demographics, clinical characteristics, patient reported outcomes and laboratory analyses.ResultsThe histamine content per basophil was significantly different between s‐BHRA positive and ‐negative patients (0.175 vs. 1.40 pg/cell, p &lt; 0.001) and showed a significant negative correlation to the degree of basophil activation in s‐BHRA (ρ = −0.209, p = 0.036). Furthermore, the amount of histamine in individual basophils was found to be significantly correlated with levels of total cellular blood histamine (ρ = 0.376, p &lt; 0.001), eosinophil counts (ρ = 0.205, p = 0.040), levels of thyroid stimulating hormone (ρ = −0.246, p = 0.014) and titre of antibodies against thyroid peroxidase (ρ = −0.216, p = 0.031) and thyroglobulin (ρ = −0.203, p = 0.044).ConclusionsLow content of intracellular histamine in circulating basophils is associated with known markers of type IIb autoimmune CSU. Further studies are required to assess whether the amount of histamine in basophils can be used to monitor or predict response to treatment in patients.

Beyond skincare routines: Follow your gut to healthy skin – A review of the interplay between gut microbiome and skin

The gut microbiome, comprising trillions of microorganisms with diverse genetic material, plays a pivotal role in human health. Its impact on immunity, metabolism, and even psychological well-being has garnered significant attention. This review delves into the evolution of microbiome research, highlighting historic breakthroughs and modern revelations. The gut microbiota’s influence extends beyond digestion, impacting immune system development, hormone regulation, and maintenance of protective barriers. Disturbances in this balance, known as dysbiosis, can disrupt immune responses, fostering harmful bacteria over beneficial ones. Dysbiosis has been linked to various diseases, motivating exploration of the gut-skin axis. Research suggests that the gut microbiome significantly influences dermatological conditions. Imbalances can contribute to skin diseases like atopic dermatitis and psoriasis. Short-chain fatty acids produced by gut bacteria have anti-inflammatory effects and maintain skin health. Gut dysbiosis can lead to systemic inflammation, affecting skin physiology. Ultraviolet (UV) damage and skin aging are also affected by the gut microbiome. Studies reveal that certain Lactobacillus strains, ingested orally, possess anti-inflammatory properties, mitigating UV-induced skin aging. Moreover, supplementation with specific bacteria enhances skin elasticity and hydration. Conditions such as rosacea, hidradenitis suppurativa, and chronic spontaneous urticaria have been linked to gut dysbiosis. Research indicates a potential for treatments that target the gut microbiome, such as fecal microbiota transplantation and probiotics, to alleviate dermatological disorders. In conclusion, the gut microbiome exerts a profound influence on skin health and diseases. Its intricate interactions with the immune system, systemic inflammation, and barrier maintenance underscore its significance. Harnessing these insights could lead to innovative therapies for various skin conditions, paving the way for enhanced well-being.

Management of Atopy with Dupilumab and Omalizumab in CADINS Disease.

The caspase activation and recruitment domain 11 (CARD11) gene encodes a scaffold protein required for lymphocyte antigen receptor signaling. Dominant-negative, loss-of-function (LOF) pathogenic variants in CARD11 result in CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease. Patients with CADINS suffer with severe atopic manifestations including atopic dermatitis, food allergy, and chronic spontaneous urticaria in addition to recurrent infections and autoimmunity. We assessed the response of dupilumab in five patients and omalizumab in one patient with CADINS for the treatment of severe atopic symptoms. CARD11 mutations were validated for pathogenicity using a T cell transfection assay to assess the impact on activation-induced signaling to NF-κB. Three children and three adults with dominant-negative CARD11 LOF mutations were included. All developed atopic disease in infancy or early childhood. In five patients, atopic dermatitis was severe and recalcitrant to standard topical and systemic medications; one adult suffered from chronic spontaneous urticaria. Subcutaneous dupilumab was initiated to treat atopic dermatitis and omalizumab to treat chronic spontaneous urticaria. All six patients had rapid and sustained improvement in atopic symptoms with no complications during the follow-up period. Previous medications used to treat atopy were able to be decreased or discontinued. In conclusion, treatment with dupilumab and omalizumab for severe, refractory atopic disease in patients with CADINS appears to be effective and well tolerated in patients with CADINS with severe atopy.

Comparison of Study Designs for Primary Phase III Trials for Omalizumab Versus Dupilumab for Patients With Chronic Spontaneous Urticaria

Introduction&#x0D; Omalizumab is currently the only biologic approved and recommended as second-line treatment for patients with chronic spontaneous urticaria (CSU). However, clinical trial programs are underway for other biologic treatments such as dupilumab. Given head-to-head trials will not be conducted, consideration of study design may be important.&#x0D; Methods&#x0D; Comparison of participants, interventions, outcomes, and results for phase III primary efficacy clinical trials for omalizumab versus dupilumab for patients with CSU. The omalizumab trials were ASTERIA I/II (NCT01287117 and NCT01292473) and the dupilumab trial was LIBERTY-CSU CUPID (NCT04180488) that consisted of Study A, B, and C.&#x0D; Results&#x0D; Participants in ASTERIA I/II were 12 to 75 years with a diagnosis of CSU refractory to H1 antihistamines. Participants in LIBERTY-CSU CUPID were 6 to 80 years (Study A and C) or 12 to 80 years (Study B) with a diagnosis of CSU refractory to H1 antihistamines, and Urticaria Activity Score (UAS)7≥16 and Itch Severity Score (ISS)7≥8 during the 7 days before randomization; Study A and C included participants who were omalizumab naïve and Study B included intolerant or incomplete responders to omalizumab. For ASTERIA I and II, the interventions were placebo or omalizumab (75mg, 150mg, 300mg) every 4 weeks for 24 and 12 weeks, respectively. For LIBERY-CSU CUPID, the interventions were placebo or dupilumab (200mg or 300mg, weight based) every 2 weeks for 24 weeks. The primary efficacy outcome for ASTERIA I/II was change from baseline in ISS7 at Week 12. The primary efficacy outcome for LIBERTY-CSU CUPID was change from baseline in ISS7 at Week 24. For the ASTERIA I primary outcome, the change from baseline in ISS7 at Week 12 was -3.6 for placebo and -6.5, -6.7, and ‑9.4 for omalizumab 75mg, 150mg, and 300mg, respectively. For the ASTERIA II primary outcome, the change from baseline in ISS7 at Week 12 was -5.1 for placebo and ‑5.9, ‑8.1, and ‑9.8 for omalizumab 75mg, 150mg, and 300mg, respectively. For the LIBERTY-CSU CUPID Study A primary outcome, the change from baseline in ISS7 at Week 24 was ‑6.0 for placebo and -10.2 for dupilumab. The LIBERTY-CSU CUPID Study B was stopped due to futility based on a pre-specified interim analysis.&#x0D; Conclusion&#x0D; Comparing study designs for primary clinical trials for omalizumab and dupilumab for patients with CSU will aid in the comparative analysis and clinical evaluation of final trial results.&#x0D; Funding: ASTERIA I/II were funded by Genentech Inc. and Novartis Pharma AG.

Oral tofacitinib in refractory chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is a skin condition marked by the emergence of wheals on their own that persist for six weeks or more. CSU is quite common, affecting up to 1% of the population, and has a serious detrimental effect on a patient's health and quality of life. Antihistamines (AH) are currently the backbone of treatment for chronic urticaria (CU), however up to 40% of patients do not respond to even large (four-fold) daily dosages of AH. Tofacitinib is a small-molecule that inhibits intracellular signalling of several important cytokines involved in the inflammatory cascade and blocks JAK1/3. While there are reports of tofacitinib's positive effects in patients with mast cell activation disorder, there are none in those with urticaria. The aim of our study is to assess the efficacy of oral tofacitinib in refractory chronic spontaneous urticaria. 5 cases of refractory CSU between the age group of 20 to 40 years were included in our study and they were followed up for 6 months. The patients were started on oral tofacitinib 5mg twice a day. On every weekly follow-up, we used clinical assessment, urticaria activity score and urticaria control test to evaluate the treatment response The usage of oral tofacitinib significantly improves the clinical picture in refractory CSU. Although more research is required to determine Tofacitinib's effectiveness in CSU, our study raises the possibility that it could represent a novel therapeutic option for individuals with refractory CSU.

A prospective observational study correlating possible novel biomarkers with disease severity and antihistamine response in chronic spontaneous urticaria.

Role of complement fraction 5a (C5a), interleukin (IL)-9, and apolipoprotein (apo) A-IV as biomarkers of disease severity and antihistamine response in chronic spontaneous urticaria (CSU) remains elusive. To identify the role of C5a, IL-9, and apo A-IV as potential biomarkers in predicting disease severity and antihistamine response in CSU patients. This was a prospective observational study of 95 patients and 42 controls. Serum analysis of C5a, IL-9, and apo A-IV was done using enyzme linked immunosorbent assay kits. Also, serum IgE and anti-thyroid peroxidase (TPO) levels were assessed in all patients. All patients were started on oral levocetirizine 5 mg at baseline and dose was titrated upwards to maximum of 20 mg based on response. Patients were categorized into antihistamine responders or nonresponders as per their disease response. Serological markers, serum IgE, and anti-TPO were correlated with baseline disease severity and antihistamine response. C5a levels were significantly higher in cases as compared to controls (P = 0.004). Significantly higher IL-9 levels were observed in antihistamine responders than nonresponders (P = 0.008). Baseline urticaria severity demonstrated a statistically significant positive and negative correlations with IL-9 (ρ = 0.277, P = 0.007) and apo A-IV (ρ = -0.271, P = 0.008) levels, respectively. Levels of serum IgE (P = 0.031) and anti-TPO (P = 0.039) were significantly higher in antihistamine nonresponders compared to responders. IL-9 and apo A-IV might be potential novel biomarkers to predict urticaria severity. Higher IL-9 might be a predictor of antihistamine response. Elevated anti-TPO and serum IgE might predict poor antihistamine response.

Evaluation of Pediatric Chronic Urticaria with Emphasis on Clinical and Laboratory Characteristics and Treatment Response to Omalizumab: A Real-Life Experience from a Tertiary Allergy Center.

Pediatric data on the clinical and etiologic features, treatment response, and use of omalizumab for chronic urticaria (CU) are quite limited. The aim of this study was to evaluate the clinical and demographic characteristics, laboratory findings, and response to treatment of CU in children. Children with a diagnosis of CU between 2019 and 2023 were included in the study. Information on demographic characteristics, clinical features, laboratory tests, provocation tests for inducible urticaria, urticaria activity scores (UAS7), and treatment responses were obtained from patients' medical records. A total of 150 children (50.7% male) with CU were enrolled in the study. A total of 14 (9.3%) patients had autoimmune diseases of which 11 (7.3%) had autoimmune thyroiditis. Overall, 97 (64.7%) patients had chronic spontaneous urticaria (CSU) and 53 (35.3%) had chronic inducible urticaria. A total of 16 patients who remained symptomatic despite high-dose antihistamines were treated with omalizumab, with a good response in 13 (81.3%) and a partial response in 3 (18.7%) patients. CSU accounts for the majority of pediatric CU, with the etiology being in part related to an autoimmune background. This study provides an overview of CU in children and demonstrates the safety and efficacy of treatment with omalizumab.