Urticária Crônica Espontânea: abordagem clínico-laboratorial e manejo terapêutico / Chronic Spontaneous Urticaria: clinical-laboratory approach and therapeutic management

Contexto: Urticária crônica caracteriza-se pela presença de urticas e/ou angioedema, com tempo de evolução superior a 6 semanas. Classifica- se em urticária crônica espontânea (UCE), com causas conhecidas ou não conhecidas e urticária crônica induzida (UCI). Objetivo: Esta revisão de UCE visa abordar os aspectos clínico-laboratoriais e indicações terapêuticas, de acordo com as diretrizes brasileira e internacional. Métodos: para esta revisão de UCE foi realizada pesquisa nas bases de dados PubMed, Embase, Google Acadêmico e Web of Science. Resultados: Foram incluídos artigos em inglês publicados entre 2018 e 2024, de acordo com sua relevância. Discussão: A patogênese da UCE engloba mecanismos imunológicos do tipo I e IIb. O diagnóstico da afecção é clínico, podendo ser realizados exames laboratoriais complementares, incluindo hemograma, VHS, D-dímero, PCR, anticorpos anti-peroxidase tireoidiana e IgE total. O diagnóstico diferencial da UCE apresenta diversas condições clínicas com morfologia semelhante à UCE. O tratamento indicado da UCE envolve medidas como suspensão de eventuais fatores desencadeantes e abordagem farmacológica, com utilização de anti-histamínicos não-sedantes, omalizumabe e uso eventual de ciclosporina. Conclusões: O impacto da UCE para os pacientes e para o sistema de saúde é de extrema relevância e avanços nas pesquisas permitirão um tratamento individualizado, com melhores perspectivas em relação à terapêutica e qualidade de vida dos pacientes.

A Prospective Randomized Non-Blinded Study of Safety and Efficacy of Bilastine Up-Dosing (40 mg) Versus Combination of Bilastine 20 mg With Levocetirizine 5 mg in the Treatment of Chronic Spontaneous Urticaria.

Introduction: Chronic spontaneous urticaria (CSU) is the most commonly diagnosed skin condition in dermatology outpatient departments. Second-generation antihistamines are shown to be effective in the control of CSU. As per the guidelines, a combination of antihistamines is less recommended due to the lack of synergistic effect, though used widely. Exploring effective treatment options are crucial, given the challenges posed by CSU. Aims and Objectives: To assess the safety and efficacy of Bilastine up-dosing versus combination of 20 mg Bilastine with 5 mg Levocetirizine in the treatment of CSU. Materials and Methods: This prospective randomized non-blinded comparative trial involved 62 patients, with 32 in group A and 30 in group B. Group A received Tablet Bilastine 20 mg bd, while Group B received a combination of Tablet Bilastine 20 mg and Tablet Levocetirizine 5 mg. Urticarial Activity Score 7 was performed at baseline and follow-up visits (every 2 weeks for 6 weeks). Results: Both groups had a higher number of male patients in the 20-30 years age group. Angioedema was present in 15.6% of group A and 23.3% in group B. After 6 weeks, both the groups showed a significant improvement in UAS 7 scores (P value <0.05). Group A demonstrated a remarkable reduction in UAS 7 from 19.4% to 0.03% with minimal side effects. Conclusion: Bilastine up-dosing proved to be efficient, secure, and well tolerated when compared to the combined dose of Levocetirizine 5 mg and Bilastine 20 mg, suggesting that up-dosing of Bilastine could be a valuable addition to the current medication arsenal with the minimal side effects.

Urticaria multiforme in Asian children.

AIM: Urticaria multiforme is an uncommon presentation of acute urticaria. It most commonly affects children and most often occurs secondary to an underlying viral infection. We performed a retrospective review of a cohort of Asian children with urticaria multiforme and reviewed the literature on the condition. METHODS: We retrospectively reviewed the clinical notes of children and adolescents less than 16 years of age, diagnosed with urticaria multiforme at our tertiary paediatric hospital between January 2017 and December 2022. Data collected and analysed included age, gender, initial diagnosis, antecedent symptoms, recent immunisations and medications, results of diagnostic tests, treatment and outcome. RESULTS: A total of 20 children were identified, with median age of diagnosis of 1.9 years, with most patients (79%) 7 years of age or younger. Viral infections were the commonest triggers. The most common referring diagnoses were erythema multiforme and Stevens-Johnson syndrome. Common antecedent or concomitant symptoms were fever and upper respiratory symptoms. Blood investigations were generally unremarkable except for mildly increased white cell counts and other markers of infection. Outcomes were good in all patients, with resolution of symptoms within 6 weeks without sequelae. CONCLUSION: Urticaria multiforme is an uncommon presentation of acute urticaria. Despite its striking appearance, it is generally a benign, self-limiting condition. Extensive investigations are usually not required and management is largely supportive.

Assessment of ELR, PLR, NLR and BLR Ratios during Omalizumab Treatment of Chronic Spontaneous Urticaria.

Background: There is a need for searching for biomarkers indicating patients who will benefit the most from treatment with omalizumab for chronic spontaneous urticaria (CSU). The aim of this study was to assess whether the eosinophil/neutrophil/platelet/basophil-to-lymphocyte ratio (ELR, NLR, PLR, BLR) may predict the response to omalizumab treatment of chronic spontaneous urticaria. Methods: A retrospective data analysis of CSU patients treated s-c with 300 mg of omalizumab every four weeks under the drug program was carried out. NLR, ELR, PLR and BLR, DLQI, UAS-7, CRP, anti-TPO and tIgE were assessed before (V0) and after three (V3) and six months (V6) of treatment. Results: Among 52 patients with CSU, 21 were responders, 24 were partially responders and 6 were non-responders to treatment with 300 mg omalizumab every four weeks. An amount of 18 patients had features of type I autoallergic CSU (CSUaiTI) and 34 patients had autoimmunity type IIb CSU with mast cell-directed activating autoantibodies (CSUaiTIIb). NLR, ELR, PLR and BLR indices did not change during a six-month-course of biological treatment. Initial values of ELR and BLR were significantly correlated with the initial tIgE level and anti-TPO/IgE ratio. Initial values of NLR, ELR and BLR were significantly correlated with initial CRP. Comparisons between type I autoallergic CSU (CSUaiTI) and autoimmunity type IIb CSU (CSUaiTIIb) revealed that the absolute number and percentage of eosinophils, basophils, BLR and tIgE were significantly higher in type CSUaiTI and anti-TPO and anti-TPO/IgE were significantly lower in type CSUaiTI. Conclusions: NLR, ELR, PLR and BLR do not change significantly during six months of omalizumab treatment and do not appear to be useful in predicting its efficacy.

Fibromyalgia and Skin Disorders: A Systematic Review.

Background: Fibromyalgia is a complex multifaceted syndrome primarily characterised by chronic musculoskeletal pain, fatigue, and functional symptoms. Although FM is known to be associated with several comorbidities, the aim of this systematic review was to comprehensively examine the available evidence regarding the relationship between FM and dermatological manifestations. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and MedLine and Web of Science (WOS) databases were searched up to June 2023. After removing duplicate records, 21 articles were deemed eligible for inclusion in the qualitative synthesis. Results: Overall, the included studies revealed an increased frequency of FM among patients with cutaneous diseases, including psoriasis, chronic urticaria, contact allergy, acneiform disorders, hidradenitis suppurativa, and vitiligo. Additionally, the presence of comorbid FM may intensify skin conditions, which has a negative impact on quality of life and vice versa. Conclusions: Although the causal mechanisms of FM are still far from being understood, this systematic review suggests a relationship between FM and skin disorders. However, further research is encouraged in this area.

Validation and correlations of the Angioedema Activity Score (AAS), Angioedema Quality of Life (AE-QoL) questionnaire, and Angioedema Control Test (AECT) in Chinese patients with angioedema.

Background: The impact of recurrent angioedema can be severely debilitating and remains difficult to quantify. Several standardized patient-reported outcome measures (PROMs), including the Angioedema Activity Score (AAS), Angioedema Quality of Life (AE-QoL) questionnaire, and Angioedema Control Test (AECT), have been developed and translated into different languages. However, these PROMs have yet to be validated in Chinese individuals, and their correlations in the Chinese population remain unknown. Objective: Our aim was to validate the Chinese versions of the AAS, AE-QoL questionnaire, and AECT and assess their intercorrelations. Methods: A prospective cohort of 118 Chinese patients with recurrent angioedema at the Angioedema and Urticaria Centre of Reference and Excellence in Hong Kong completed the traditional Chinese versions of the AAS, AE-QoL questionnaire, and AECT. We analyzed the reliability and validity of these PROMs and their correlations with each other as well as with generic PROMs. Results: The Chinese AAS, AE-QoL questionnaire, and AECT demonstrated excellent internal consistency (Cronbach α = 0.920, 0.976, and 0.832, respectively; McDonald ω = 0.972, 0.977, and 0.901, respectively). Confirmatory factor analysis for the AE-QoL questionnaire showed an acceptable fit with the 4-dimensional model (comparative fit index = 0.869; Tucker-Lewis index = 0.842). The AECT showed significant correlations with both the AAS and AE-QoL questionnaire (ρ = -0.750 and -0.456 respectively [both P < .05]). The AE-QoL questionnaire was moderately correlated with certain domains of generic PROMs such as the Work Productivity and Activity Impairment Questionnaire: General Health, version 2.0, and the Short Form 12-Item Health Survey, version 2 (all ρ < 0.60). Conclusion: The Chinese AE-QoL questionnaire, AAS, and AECT are valid and reliable tools for use with Chinese patients. More validated tools should be made available to improve patient care and research for all patients with angioedema globally.

Exploring the Bidirectional Effects of Gut Microbiota and Short-Chain Fatty Acids on Urticaria Subtypes Through Mendelian Randomization and Mediation Analysis.

Background: Emerging evidence links gut microbiota and their by-products, notably short-chain fatty acids (SCFAs), to urticaria. This study employs multiple Mendelian Randomization (MR) analyses to unravel the complex interactions among gut microbiota, SCFAs, and different subtypes of urticaria, aiming to elucidate the underlying mechanisms and enhance future clinical research. Methods: We analyzed published genome-wide association study (GWAS) summary statistics to identify associations between gut microbiota and three common subtypes of urticaria: spontaneous, dermatographic, and temperature-triggered. Initial two-sample and reverse MR analyses explored the causality in these relationships. Subsequent multivariate MR analyses investigated the role of SCFAs in modulating these interactions, with multiple sensitivity analyses to ensure robustness. Findings: Specific taxa were differently associated with various urticaria subtypes. From microbiota to urticaria: one taxon was negatively associated with dermatographic urticaria; seven taxa were negatively associated and four positively associated with temperature-triggered urticaria; four taxa were negatively associated and six positively associated with spontaneous urticaria. Conversely, from urticaria to microbiota: five taxa were negatively associated with dermatographic urticaria; four were negatively and two positively associated with temperature-triggered urticaria; and two were negatively associated with spontaneous urticaria. These associations were observed at a nominal significance level (P < 0.05). After applying Bonferroni correction for multiple testing, these associations did not reach statistical significance. The observed trends, however, provide insights into potential microbiota-urticaria interactions. Multivariate MR analyses elucidated the role of SCFAs, particularly acetate, which plays a crucial role in modulating immune response. Adjusting for acetate revealed direct effects of Actinobacteria, Bifidobacteriales, and Bifidobacteriaceae on spontaneous urticaria, with corresponding mediation effects of -22%, -24.9%, and -24.9% respectively. Similarly, adjustments for Alcaligenaceae and Betaproteobacteria indicated significant negative effects of acetate on dermatographic and spontaneous urticaria, with mediation effects of -21.7% and -23.7%, respectively. Conclusion: This study confirms the interconnected roles of gut microbiota, SCFAs, and urticaria. It highlights SCFAs' potential mediating role in influencing urticaria through microbiota, providing insights for future therapeutic strategies.

The potential of Bruton's tyrosine kinase (BTK) inhibitors in the pharmacotherapeutic management of immune and dermatological disease.

INTRODUCTION: The review article explores the evolving role of Bruton's tyrosine kinase (BTK) inhibitors in immune-mediated dermatological conditions, addressing significant gaps in current treatment approaches. AREAS COVERED: The review comprehensively discusses the mechanisms of action of BTK inhibitors, including irreversible and reversible inhibitors. Clinical applications of BTK inhibitors in dermatological diseases such as pemphigus, chronic spontaneous urticaria (CSU), hidradenitis suppurativa (HS), systemic lupus erythematosus (SLE), and atopic dermatitis are explored, highlighting recent advancements and ongoing clinical trials. Potential advantages of BTK inhibitors over existing therapies and challenges in translating preclinical findings to clinical outcomes are discussed. EXPERT OPINION/COMMENTARY: BTK inhibitors represent a promising therapeutic avenue for immune-mediated dermatological conditions, offering oral administration, targeted pathway inhibition, and a favorable safety profile compared to biologic therapies. Ongoing research and clinical trials hold the potential to address unmet needs and reshape the therapeutic landscape in dermatology.

Our manuscript explores how a new class of medications called Bruton tyrosine kinase (BTK) inhibitors could revolutionize the treatment of skin conditions caused by the immune system. These conditions, like chronic spontaneous urticaria (CSU), pemphigus, and systemic lupus erythematosus (SLE), often lack effective treatments. BTK inhibitors work by targeting specific pathways in the immune system, offering hope for patients with these challenging conditions.We reviewed clinical trials and research studies to understand how BTK inhibitors could benefit patients. One significant advantage of BTK inhibitors is their ability to provide targeted therapy, meaning they can specifically block the faulty immune responses driving these conditions without affecting the entire immune system. This targeted approach could lead to fewer side effects compared to current treatments, such as corticosteroids or immunosuppressants, which can have widespread effects on the body.Overall, BTK inhibitors represent a promising new approach to treating immune-mediated skin conditions. With further research and development, they could offer safer and more effective alternatives to current treatments, improving the lives of patients worldwide.

Cold urticaria in tropics: A clinico-epidemiological study from North India.

Background Cold urticaria (ColdU) is classified as a subtype of chronic inducible urticaria characterised by recurring pruritic wheals and/or angioedema upon exposure to cold stimuli. However, very limited data is available on ColdU specifically among Indians. Objectives The aim of this study was to describe the clinico-epidemiological characteristics and treatment response in North Indian patients diagnosed with ColdU. Materials and Methods The clinical records of patients diagnosed with ColdU past 5 years (January 2018 to December 2022) were retrospectively reviewed. Data including patient demographics, clinical manifestations, comorbidities, laboratory findings, and treatment response were collected and analysed. Results Among the 1780 urticaria patients included in our study, only 15 cases of cold-induced urticaria were identified. ColdU was classified as typical in all but three patients. The mean age of affected individuals was 36 ± 18 years (20-65 years) and eight patients (53.3%) were males. Mean disease duration at presentation was 18 ± 27 months (3 months-4 years). Two patients experienced cold-induced angioedema and one patient had hypotensive episodes following cold exposure. Twelve patients demonstrated positive results in the ice cube provocation test. Of 15, only 6 (40%) achieved complete control of symptoms with standard dosing of second generation anti-histamines while six patients (40%) required titration to higher doses and three patients (20%) were initiated on cyclosporine therapy, resulting in remission. Limitations Retrospective study design and possibility of selection bias. Conclusion Due to India's predominantly tropical climate, ColdU prevails at lower levels compared to the western regions. ColdU is likely underdiagnosed in India, possibly dismissed as chronic spontaneous urticaria. The management of ColdU involves a combination of protective measures against cold exposure and the use of anti-histamines to control disease activity. This retrospective study provides valuable insights into the clinico-epidemiological characteristics and treatment response of north Indian patients with ColdU.

Efficacy and safety of combinations of H1 antihistamines in the treatment of urticaria: A scoping review.

The efficacy and safety of combining H1 antihistamines (AHs) for treating urticaria are currently unclear. This scoping review aims to provide a comprehensive overview of the evidence regarding the efficacy and safety of H1 AH combinations in the management of urticaria up to May 2023. The search encompassed databases such as PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and the China Biological Medicine Database. The inclusion criteria comprised randomised controlled trials (RCTs), non-randomised trials (NRTs), case reports, and case series focusing on urticaria treatment. Initially screening 12,887 studies, this review ultimately selected 109 studies involving 11,435 patients. These studies documented 43 different combination treatments across 11 types of urticaria. In comparison to monotherapy, combination therapy exhibited superior efficacy in 94 studies that reported treatment efficacy. Regarding adverse drug reactions (ADRs), 67 studies disclosed ADR incidences, with combination therapy showing lower ADR rates in 32 studies. Additionally, 7 studies reported similar ADR rates between combination therapy and monotherapy with AHs. Common ADRs included symptoms such as drowsiness, nausea, fatigue, dry mouth, dizziness, and headache, while less frequent side effects encompassed hypotension, otitis media, polyuria, rhinorrhoea, abnormal liver function, and rash. ADR rates ranged from 0% to 21% in the treatment group, and from 0.5% to 75% in the control group. Importantly, patients generally tolerated these ADRs well, with symptoms resolving upon discontinuation of treatment. The study's findings suggest that combining AHs leads to enhanced efficacy and reduced safety risks compared to monotherapy in the context of urticaria treatment. These results advocate for considering combination therapy as a viable option in clinical practice, especially for chronic urticaria cases. Nonetheless, caution is advised, and close monitoring for potential ADRs is crucial during treatment.

Acute urticaria and cardiovascular diseases.

BACKGROUND: Acute urticaria (AU), characterized by sudden skin wheals, has been associated with various triggers. While chronic urticaria's cardiovascular comorbidities have been studied, AU's associations remain largely unexplored. OBJECTIVE: This study aimed to identify prevalent cardiovascular comorbidities in AU patients and assess their clinical significance. METHODS: A retrospective cohort study used data from Leumit Health Services, matching AU patients with controls. Demographic, clinical, and laboratory data were analyzed. Statistical analyses included Fisher's Exact Test and Mann-Whitney U test. RESULTS: The AU group (72,851 individuals) showed no sex/ethnic distribution differences from controls (291,404 individuals). Systolic blood pressure, weight, BMI, glucose, hemoglobin A1c, C-reactive protein, eosinophil counts, total IgE levels were higher in AU (p < 0.001). Several cardiovascular comorbidities showed significant associations with AU, including valvular heart diseases (aortic regurgitation, mitral regurgitation, and pulmonary valve stenosis), cardiac arrhythmias (atrial fibrillation and others), deep vein thrombosis, diseases of capillaries, peripheral artery disease, cerebrovascular disease, coronary artery disease, and inflammatory heart diseases (pericarditis, heart failure, and hypertension) (p < 0.05). Medications, including antihistamines and glucocorticoids, were more prevalent in the AU group (p < 0.001). CONCLUSION: This study's findings underscore the importance of recognizing cardiovascular comorbidities in AU patients and considering their implications for management. The observed associations provide insight into potential shared mechanisms between AU and cardiovascular diseases, though further research is needed to validate and expand upon these findings.

Translation and cross-cultural adaptation of the Nordic Occupational Skin Symptoms Questionnaire to Brazilian Portuguese.

Introduction: Occupational skin diseases are a frequently self-reported condition in industrialized countries. However, there are few developed and standardized self-report instruments to screen the population at risk for occupational dermatological diseases. Objectives: Translation and cross-cultural adaptation of the long and short versions of The Nordic Occupational Skin Symptoms Questionnaire into Brazilian Portuguese. Methods: The process of translation and cross-cultural adaptation of the questionnaire was developed following the good practice recommendations of the International Society for Pharmacoeconomics and Outcomes Research. Results: After translation into Brazilian Portuguese, the first reconciled version of the questionnaire was evaluated in a first round of interviews with 28 individuals, including patients with dermatological disease and healthy people. In the first meeting of the study review group, changes were made to 43 questions (75.4%) (e.g., inclusion of definition of terms, reformulation of instructions, and changes to alternative words or synonyms). In the second meeting of the study review group, there were modifications in three questions, creation of the second consensus version in Brazilian Portuguese, and then the back-translation of this version. After the second round of cognitive interviews, which took place with 10 patients, we had the third review group meeting (no modification was made) and definition of the final version of the questionnaire. Conclusions: The short and long versions of the Nordic Occupational Skin Symptoms Questionnaire questionnaire are available in Brazilian Portuguese.

Introdução: As doenças ocupacionais de pele são uma condição frequentemente autorrelatada em países industrializados. No entanto, existem poucos instrumentos de autorrelato desenvolvidos e padronizados para triagem da população de risco para doenças ocupacionais de pele. Objetivos: Tradução e Adaptação Transcultural da versão longa e curta do Nordic Occupational Skin Symptoms Questionnaire para o português brasileiro. Métodos: O processo de tradução e adaptação transcultural do questionário foi desenvolvido seguindo as boas práticas recomendadas pela International Society for Pharmacoeconomics and Outcomes Research. Resultados: Após a tradução para o português brasileiro, a primeira versão conciliada do questionário foi avaliada em uma primeira rodada de entrevistas com 28 indivíduos entre pacientes com doença dermatológica e pessoas saudáveis. Na primeira reunião do grupo de revisão do estudo, foram feitas alterações em 43 questões (75,4%) (por exemplo, inclusão de definição de termos, reformulação de instruções e alteração para palavras alternativas ou sinônimos). Na segunda reunião do grupo de revisão do estudo, houve modificações em três questões, criação da segunda versão de consenso em português brasileiro e, posteriormente, a retrotradução desta versão. Após a segunda rodada de entrevistas cognitivas, que ocorreram com 10 pacientes, tivemos a terceira reunião do grupo de revisão (não houve modificação) e definição da versão final do questionário. Conclusões: As versões curta e longa do questionário Nordic Occupational Skin Symptoms Questionnaire estão disponíveis em português brasileiro.

Integrating network toxicology and molecular docking to explore the toxicity of the environmental pollutant butyl hydroxyanisole: An example of induction of chronic urticaria.

The study aimed to comprehensively investigate environmental pollutants' potential toxicity and underlying molecular mechanisms, focusing on chronic urticaria (CU) induced by butylated hydroxyanisole (BHA) exposure, further drawing public awareness regarding the potential risks of environmental pollutants, applying ChEMBL, STITCH, and SwissTargetPrediction databases to predict the targets of BHA, CTD, GeneCards, and OMIM databases to collect the relevant targets of CU. Ultimately, we identified 81 potential targets of BHA-induced CU and extracted 31 core targets, including TNF, SRC, CASP3, BCL2, IL2, and MMP9. GO and KEGG enrichment analyses revealed that these core targets were predominantly involved in cancer signaling, estrogen and endocrine resistance pathways. Furthermore, molecular docking confirmed the ability of BHA to bind with core targets. The onset and development of CU may result from BHA by affecting multiple immune signaling pathways. Our study elucidated the molecular mechanisms of BHA toxicity and its role in CU induction, providing the basis for preventing and treating chronic urticaria associated with environmental BHA exposure.

Patient Reported Outcome Measures in Chronic Spontaneous Urticaria, Angioedema and Atopic Dermatitis.

Reducing the burden of disease for patients and families requires being able to measure health status changes related to disease severity, control, and response to treatment over time. Patient reported outcomes are patient perceptions of their health status. Such perceptions are critical to decision-making. Some patient reported outcome measures (PROMs) are extensive and often intended to be used only for detailed research assessments. Many PROMs, however, form critical components of valid, reliable, and responsive assessments in clinical research and routine clinical practice. The smallest score change in a PROM that would lead to different decision-making by patients is called the minimally important difference (MID). Using PROMs may also offer advantages over general questions or unvalidated tools. With the innovation of technology, the ability to chronicle disease symptoms using communication technology (mobile phone apps) has become increasingly available. Collection of real-world data in this capacity will be very useful for identifying more precise phenotypes/endotypes necessary for investigation of tailored therapies for chronic spontaneous and inducible urticaria, angioedema and atopic dermatitis. Here we provide an overview of PROMs that have been developed for the assessment of disease severity, control, and quality of life and that have been validated for the use of adults and children with these skin disorders.

Combining dipyridamole and cilostazol with up-dosing antihistamines improves outcomes in chronic spontaneous urticaria with high D-dimer levels: A randomized controlled trial.

In a double-blind, randomized controlled trial, we investigated the effectiveness of adding antiplatelet drugs to up-dosing antihistamines for the treatment of chronic spontaneous urticaria (CSU) in patients with elevated D-dimer levels who had an inadequate response to conventional antihistamine doses. Twenty patients with Urticaria Activity Score over 7 days (UAS7) ≥16 and D-dimer >500 ng/mL were randomized to receive either antiplatelet therapy (cilostazol 150 mg/day + dipyridamole 50 mg/day) with antihistamine (desloratadine 20 mg/day) or antihistamine alone for 4 weeks. The antiplatelet group demonstrated a greater decrease in UAS7 compared to the control group (28.10 to 8.90 vs. 22.90 to 16.40, p < 0.001 vs. p = 0.054). Both groups experienced improved quality of life (DLQI), but the improvement was greater in the antiplatelet group (p = 0.046). D-dimer levels decreased only in the antiplatelet group (1133.67 ng/mL to 581.89 ng/mL, p = 0.013) with no significant change observed in the control group. This suggests that combining dipyridamole and cilostazol with up-dosing antihistamines may be more effective for CSU patients with high D-dimer levels compared to up-dosing antihistamines alone. This could be due to a reduction in platelet activation, as evidenced by the decrease in D-dimer levels observed in the antiplatelet group.

A comprehensive analysis on the safety of two biologics dupilumab and omalizumab.

Dupilumab was approved for the treatment of several dermatologic immune-mediated inflammatory diseases, such as atopic dermatitis and bullous pemphigoid; whereas omalizumab is the first biological agent which was approved to treat chronic spontaneous urticaria. None of the published meta-analyses has provided the sufficient data regarding the safety of these two biologics, especially regarding their potential serious adverse events (SAEs). The aim of this study was, to comprehensively evaluate the safety of the two biologics dupilumab and omalizumab. In this study, we included 32 randomized trials, and performed meta-analyses on 113 types of SAEs regarding dupilumab and 61 types of SAEs regarding omalizumab. We identified that: (1) use of dupilumab was significantly associated with the lower incidence of atopic dermatitis, while use of omalizumab was significantly associated with the lower incidence of asthma; and (2) use of dupilumab was not significantly associated with the incidences of 112 other kinds of SAEs including various infectious diseases, while use of omalizumab was not significantly associated with the incidences of 60 other kinds of SAEs including various infectious diseases. This meta-analysis for the first time assessed the association between use of dupilumab or omalizumab and incidences of various SAEs, and identified that neither dupilumab use nor omalizumab use was associated with the increased risks of any SAEs including various infectious diseases. These findings further confirm the general safety of the two biologics dupilumab and omalizumab. This informs clinicians that there is no need to worry too much about the safety issues of these two biologics.

Omalizumab in Chronic Spontaneous Urticaria: A Real-World Study on Effectiveness, Safety and Predictors of Treatment Outcome.

Background: Although omalizumab has shown success in treating chronic spontaneous urticaria (CSU) patients unresponsive to antihistamines, the exact mechanism of action and predictive markers of response remain unclear. Purpose: The aim of this study was to examine the correlation between baseline levels of biomarkers and clinical parameters with omalizumab response and response rate in patients with CSU. Methods: This retrospective study included 82 adult CSU patients who received omalizumab 300mg every 4 weeks for 16 weeks between January 2022 and December 2023. Treatment response was assessed using UAS7 and DLQI scores at baseline and weeks 4, 8, 12, and 16. Responders were defined as patients achieving UAS7 < 7, with early and late responders categorized based on response within or after 4 weeks, respectively. Baseline clinical features and laboratory biomarkers were compared between responders and non-responders. Results: The overall response rate was 71.95% (59/82), with 23 early responders and 36 late responders. Responders had significantly lower baseline UAS7 (median: 28 vs 35, P < 0.01), DLQI (median: 8 vs 15, P < 0.001), and IL-17 levels (median: 0.53 vs 1.26 pg/mL, P < 0.001) compared to non-responders. Baseline UAS7 > 31, DLQI > 9.5, and IL-17 > 0.775 pg/mL predicted non-response with sensitivities of 78.26%, 100%, and 78.26%, and specificities of 67.8%, 59.32%, and 72.88%, respectively. ASST positivity and comorbid allergic diseases were associated with early response (P < 0.05). Adverse events were reported in 6.09% of patients, including mild injection site reactions and transient urticaria exacerbation, not requiring treatment discontinuation. Conclusion: This study suggests that omalizumab is an effective and safe treatment option for antihistamine-refractory CSU. Baseline UAS7, DLQI, ASST status, serum total IgE levels, and IL-17 may serve as potential predictors of omalizumab response. Notably, ASST positivity and comorbid allergic diseases were associated with an early response to treatment. These findings highlight the importance of considering individual patient characteristics when predicting the likelihood and timing of response to omalizumab in CSU.

Severity of papular urticaria in children is associated with specific IgG4 anti-salivary gland antigens from Aedes aegypti.

Summary: Background. Papular Urticaria (PU) is a cutaneous hypersensitivity disorder triggered by hematophagous arthropod bites. Despite being a common condition, especially in tropical environments, many knowledge gaps are observed for this disease. The main objective of this study was to investigate the patterns of humoral immune response to mosquito antigens in children with PU and establish a correlation between this response and the severity of clinical symptoms. Methods. An analytical cross-sectional observational study was carried out. Clinical and sociodemographic data and children's blood samples were collected to measure the specific antibodies from: 1. A. aegypti salivary gland antigens; 2. A. aegypti whole body antigens (both produced in the laboratory of the Center for Health Sciences at the Federal University of Rio de Janeiro). A PU severity score based on clinical data is proposed to correlate disease severity with antibody reactivity signatures. Results. According to the clinical data, 58.9% of children received high severity scores. A significant statistical correlation was found between patients with high PU severity score and the development of symptoms before the age of two (p = 0.0326) and high IgG4 anti-salivary gland antigens concentration (p less than 0.05). Conclusion. It is suggested that PU severity in children is associated with a high concentration of IgG4 anti-salivary gland antigens from Aedes aegypti. Further studies are recommended to deepen the understanding of the mechanisms involved.