Itch is an uncomfortable feeling that evokes a desire to scratch. This protective reflex can effectively eliminate parasites that invade the skin. When itchy skin becomes severe or lasts for more than six weeks, it has deleterious effects on both quality of life and productivity. Despite decades of research, the complete molecular and cellular coding of chronic itch remains elusive. This persistent condition often defies treatment, including with antihistamines, and poses a significant societal challenge. Obtaining pathophysiological insights into the generation of chronic itch is essential for understanding its mechanisms and the development of innovative anti-itch medications. In this review we provide a systematic overview of the recent advancement in itch research, alongside the progress made in drug discovery within this field. We have examined the diversity and complexity of the classification and mechanisms underlying the complex sensation of itch. We have also delved into recent advancements in the field of itch mechanism research and how these findings hold potential for the development of new itch treatment medications. But the treatment of clinical itch symptoms still faces significant challenges. Future research needs to continue to delve deeper, not only to discover more itch-related pathways but also to explore how to improve treatment efficacy through multitarget or combination therapy.

The basophil activation test (BAT) is considered to be the best biomarker to predict autoimmune chronic spontaneous urticaria (aiCSU). To date, few studies have investigated the utility of BAT in real-world clinical practice, the role of aiCSU biomarkers in relation to omalizumab therapy and the degree of association between different aiCSU tests.

To analyse the clinical and laboratory features of a prospective cohort with chronic spontaneous urticaria (CSU) according to their BAT status, as well as to study omalizumab efficacy according to aiCSU biomarkers.

A prospective study was conducted from 2010 to 2024 in patients with CSU. BAT alongside other laboratory tests were performed, and clinical and therapeutic features were prospectively collected. Data obtained were compared according to BAT status (positive vs. negative). Furthermore, omalizumab drug survival was typified according to aiCSU biomarkers.

In total, 240 patients were included in the study. Patients who were BAT positive presented more frequently with low IgE levels, higher occurrence of IgG antithyroid peroxidase (anti-TPO) positivity, autologous serum skin test (ASST) positivity, basopenia and eosinopenia. Multivariate logistic regression revealed that ASST [odds ratio (OR) 7.69, 95% confidence interval (CI) 2.81-21.0] and anti-TPO (OR 2.63, 95% CI 1.05-6.61) were associated with BAT positivity. All aiCSU biomarkers (BAT, ASST, combined ASST/BAT positivity and low IgE/anti-TPO+) were associated with significantly shorter omalizumab survival because of treatment failure. In the cohort, both low IgE/anti-TPO+ and ASST were associated with BAT positivity.

The use of BAT in clinical practice delineates a subgroup of patients with specific clinical, laboratory and therapeutic features, including increased omalizumab failure.

Bruton's tyrosine kinase (BTK) is a cytoplasmic signaling protein expressed across a variety of immune cells, terminally differentiated plasma cells, and natural killer cells. Due to the signal potential and targetable nature of BTK, the use of BTK inhibitors (BTKis) has been proposed for the management of several diseases. Currently, the use of BTKis is under investigations for several dermatological conditions such as pemphigus, systemic lupus erythematosus, hidradenitis suppurativa, atopic dermatitis, and chronic spontaneous urticaria (CSU).

The aim of this review is to delve into the use of BTKis in the management of CSU, in order to explore the potential of therapeutic inhibition of BTK in patients with CSU. A thorough analysis of the existing medical literature was conducted across the PubMed, Ovid, Scopus, Embase, and Cochrane Library databases up to 17 August 2024.

BTK use may represent a breakthrough in the management of CSU. Indeed, their use is characterized by oral administration and a favorable mechanism of action that acts on a significant pathogenic pathway rather than a single molecule. However, long-term studies are needed to further investigate safety data, although data from registered trials appear to be reassuring.

The purpose of this study was to evaluate dermatologists' knowledge, attitudes, and practices (KAP) concerning omalizumab therapy for chronic urticaria. We conducted a cross-sectional study in several hospitals in China, mainly in hospitals in Zhejiang Province, during August 1, 2024 - August 15, 2024 using a self-administered KAP questionnaire. Wilcoxon-Mann-Whitney tests and Kruskal-Wallis analysis of variance were performed to compare differences across groups Factors influencing practice were determined through multivariable logistic regression. The study analyzed 354 valid questionnaires. Among the respondents, 248 (70.06%) were aged between 31 and 35 years, and 269 (75.99%) had 5-10 years of experience. The mean scores for knowledge, attitudes, and practices were 5.71 ± 1.39 (possible range: 0-9), 21.39 ± 2.25 (possible range: 5-25), and 19.84 ± 2.53 (possible range: 5-25), respectively. Multivariate logistic regression indicated that a higher attitude score (OR = 1.929, 95% CI: [1.511-2.462], P < 0.001), being male (OR = 3.262, 95% CI: [1.507-7.059], P = 0.003), and awareness of omalizumab (OR = 4.966, 95% CI: [1.466-16.830], P = 0.010) were significantly associated with proactive practice. Dermatologists demonstrated insufficient knowledge, positive attitudes, and proactive practices towards omalizumab therapy for chronic urticaria. Given the identified knowledge gap, there is a pressing need for targeted educational interventions to enhance dermatologists' understanding of omalizumab therapy for chronic urticaria, aiming to improve patient care and outcomes in clinical practice.

Chronic spontaneous urticaria (CSU) is a clinical condition that affects patients quality of life. Omalizumab is preferred in antihistamines resistant CSU cases. Urticaria activity score-7 (UAS-7) is a scale that shows the severity of the disease.

The authors aimed to compare the long-term (60 months) efficacy and side effects of 150 mg and 300 mg doses of omalizumab in patients with CSU.

108 patients followed up at the clinic with the diagnosis of CSU were included. Omalizumab was started in patients who were resistant to conventional CSU treatment. Two groups were formed to receive 150 mg and 300 mg doses of omalizumab. Urticaria activity score (UAS-7), antihistamine usage, time to achieve disease-free stage, relapse after treatment, and side effects of omalizumab treatment were compared in the two groups.

There were no statistically significant differences between the groups regarding basal characteristics and laboratory findings. Average follow-up time was sixty months. UAS-7 scores were similar in the follow-up. There were no adverse events in both groups.

Retroactive design and single-center nature to reach a more significant number of patients. Lack of patients receiving the lowest dose 75 mg and the highest dose 600 mg of omalizumab. Absence of total body mass indexes of all patients. Besides, the use of distinct drugs may contribute to non confident results and is another limitation of this study.

Since there is no significant difference between 150-300 mg omalizumab doses regarding long-term treatment efficacy and side effects in CSU patients, starting treatment with a 150 mg dose may be suitable. In patients who do not respond to 150 mg, the omalizumab dose can be increased to 300 mg. It will prevent unpredictable dose and time-dependent complications and will be a cost-effective approach even in strong economies.

Chronic spontaneous urticaria (CSU) significantly impairs patients' quality of life. Despite advances in diagnosis and therapy, treatment is still unsatisfactory. Telemedicine offers a promising solution to improve treatment. This pilot study assesses the acceptability and utilization of a digital health model for CSU, examines its impact on disease management, and identifies technical challenges.

In this prospective pilot study, CSU patients at a university hospital in Germany were included. Over 12 months, participants interacted with physicians via a telemedicine platform, which was the study-specific intervention. After each three-month digital visit, symptoms and quality of life were assessed using electronic patient reported outcomes (ePROs) and online questionnaires. In the end, patients and doctors rated the overall satisfaction, the user-friendliness of the platform and the technical challenges.

24 patients completed the study. The majority (92%) reported that the digital concept could be a promising alternative to traditional consultations. Analysis from baseline to end of study revealed that disease control remained stable while quality of life improved. All physicians found the digital application reliable and time-saving.

This pilot study demonstrates the feasibility and high acceptance of a digital health model for the management of CSU. Further research with larger cohorts is needed and planned to determine broader applicability.

Chronic spontaneous urticaria (CSU) is a persistent skin condition with no known cause or trigger. The unpredictability of CSU attacks lowers patients' quality of life. NOD-like receptor pyrin domain containing 3 (NLRP3) gene dysregulation can result in numerous immunological and inflammatory diseases.

This case-control study aimed to determine the association between the NLRP3 inflammasome (rs10754558) single nucleotide polymorphism (SNP) and the occurrence, severity and etiology of CSU.

Each study group included 62 participants; all were subjected to CSU severity evaluation by the urticaria activity score (UAS), autologous serum skin testing (ASST) and NLRP3 (rs10754558) genotyping.

The NLRP3 (rs10754558) CG genotype was the most predominant in both study groups, followed by the CC genotype (41.9 %) in the CSU group and the GG genotype (25.8 %) in the control group. Most of the CSU group (66.1 %) had the C allele, compared to most controls (53.2 %) with the G allele. The frequency of NLRP3 (rs10754558) genotypes and alleles did not differ significantly according to the severity of CSU by UAS (P > 0.05). The prevalence of the CC genotype was significantly higher among the ASST-positive CSU patients. The C allele elevated the likelihood of positive ASST in CSU patients by 21 times, suggesting the autoimmune theory of CSU. None of the ASST-positive patients had the GG genotype.

The NLRP3 inflammasome (rs10754558) C allele may be associated with CSU risk but not severity by UAS. It may also be associated with ASST positivity which suggests a connection between the C-allele and the autoimmune notion of CSU.

Biomarkers that could reliably anticipate the effectiveness of antihistamines and omalizumab in treating chronic spontaneous urticaria (CSU) have not been conclusively identified. Our objective was to examine how eosinophilic cationic protein (ECP), tryptase, D-dimer, and total Immunoglobulin E (IgE) impact the response to antihistamine and omalizumab treatments in individuals with CSU.

In this cross-sectional retrospective study, CSU patients that had undergone treatment with either antihistamines or omalizumab for a minimum of 12 weeks between 2015 and 2021 at an Allergy and Immunology Department were analyzed. Several demographic and laboratory parameters including eosinophil counts, mean platelet volüme (MPV), sedimentation, C-reactive protein (CRP), antinuclear antibodies (ANA) and Anti-thyroperoxidase (Anti-TPO) and total IgE, tryptase, ECP and D-dimer were retrived from patient files. The association of these biomarkers with Urticaria Control Test (UCT) and the effect of these biomarkers on treatment response were evaluated. Treatment response was assessed using the UCT, with a score of UCT ≥ 12 indicating a responder and UCT < 12 indicating a non responder.

The patients in the omalizumab group were older, had a longer disease duration and had worse urticaria control (lower baseline UCT scores). 421 patients were treated with antihistamines and 88 patients were treated with omalizumab. ECP was found to be inversely correlated with baseline UCT (p < 0.001 r=-0.268). ECP and D-dimer levels of non-responder patients in the antihistamine group were significantly higher than in responder patients (ECP: 49 ng/mL vs 28.1 ng/mL, p < 0.001) (D-dimer: 0.60 mg/L vs 0.30 mg/L, p < 0.001), while there were no significant difference in terms of tryptase and total IgE. These four biomarkers were similar, in omalizumab responders and non responders.

In this study with CSU, we looked at predictors of responses to treatments. ECP can serve as a marker of poor urticaria control and may predict antihistamine refractoriness along with D-dimer.

Chronic idiopathic urticaria (CIU) is difficult for patients and healthcare professionals to manage owing to its chronic and unpredictable nature. While the exact cause of CIU is unknown, it is suggested that food allergies may contribute to the development of symptoms. To determine the prevalence of food allergy in patients diagnosed with CIU. This systematic review is reported in accordance with PRISMA guidelines. We included all relevant articles published from inception to April 2023 in Scopus, Midline, and Web of Science. The initial search yielded 282 articles, of which only seven were included after applying the inclusion and exclusion criteria. The systematic review included a total of 1551 patients with urticaria. Approximately 25% of patients with food allergies had CIU. The prevalence of a family history of atopy was 37.9% (range, 24.3-53.8%, P = 0.133). There was a significant risk of angioedema in patients with urticaria (P = 0.039). The risk of CIU among patients with food allergies was estimated to be one in every four patients with urticaria, with a similar risk among the adult and pediatric populations. Patients with food allergies and a history of atopy were at higher risk of CIU. Angioedema is a common concomitant manifestation associated with common urticaria. This knowledge is important to identify patients at higher risk of urticaria and implement the necessary management to minimize potential complications and maintain a controlled disease.

Patients' collaboration with healthcare providers, along with their individual dedication to follow medical recommendations, is a crucial component of effective therapy in chronic diseases. If a patient fails to fill their prescription, administers the medication improperly in terms of method and/or dosage, misses follow-up visits, or discontinues the treatment for any reason, these lapses can adversely affect disease management, impairing the effectiveness of symptom relief and prevention of progression and complications. A comparable situation pertains to allergic diseases, which require long-term and consistent treatment to achieve symptom alleviation and control. Research has shown that adherence rates for long-term therapy in chronic diseases have improved marginally over the years and continue to hover at approximately the figure published in a World Health Organization (WHO) report "Adherence to long-term therapies: evidence for action." from 2003, which had stated that only 50% of patients in developed countries follow medical recommendations and that this rate would be even lower in developing countries. Over 20 years later, literature indicated that there has been only a slight improvement on the matter, leaving room for developing and implementing effective solutions to improve medication compliance. Further investigation on this matter is required. Causes for non-adherence classified by the Global Initiative for Asthma in their main report seem to correspond to those of the report by the WHO. Similar dependency might be determined by other allergic diseases as they fit chronic disease criteria, and the issue of non-adherence affects them too. This literature review seeks to compile and synthesize current insights on factors that influence adherence, as well as explore potential methods for monitoring, evaluating, and improving its outcomes in chronic diseases related to the medical field of allergology, such as asthma, allergic rhinitis, allergic conjunctivitis, rhinoconjunctivitis, atopic dermatitis, and urticaria.

Chronic urticaria (CU) is a prevalent dermatologic disease that negatively affects life, current therapies remain suboptimal. Hence, there is an urgent need to identify effective and safe treatment.

Assess the efficacy and safety of compound glycyrrhizin (CG) combined with second-generation nonsedated antihistamine for the treatment of CU.

Nine databases were queried to screen RCTs related. Two reviewers independently assessed the risk of bias using Cochrane Collaboration. Primary objective was the total efficiency rate, while secondary was rate of recurrence, adverse events, and cure. Statistical analyses using Review Manager 5.4 and Stata17.

Twenty-four RCTs were identified. Significant differences were noted in rate of total efficiency (n = 2649, RR = 1.36, 95%CI:1.30-1.43, p < 0.00001), cure (n = 2649, RR = 1.54, 95%CI:1.42-1.66, p < 0.00001) and recurrence (n = 446, RR = 0.34, 95%CI:0.20-0.58, p < 0.00001) between the combination of CG with second-generation non-sedated antihistamine and antihistamine monotherapy. Contrastingly, adverse events rate (n = 2317, RR = 0.76, 95% CI:0.59-0.97, p = 0.03) was comparable between the two groups. Our results indicated that CG combined with second-generation non-sedated antihistamine could significantly mitigate the symptoms in CU compared with antihistamine monotherapy. No serious adverse events were reported.

CG combined with second-generation nonsedated antihistamine is effective for CU. Nevertheless, higher-quality studies are warranted to validate our results.

In this study, the European Academy of Dermatology and Venereology (EADV) Task Forces on Quality of Life and Patient-Oriented Outcomes and Urticaria and Angioedema has examined the Health-Related Quality of Life (HRQoL) measurement in the treatment of urticaria. The Dermatology Life Quality Index was the most frequently used HRQoL instrument in clinical trials on urticaria. Many reports of clinical trials of urticaria gave no exact numeric results related to HRQoL changes, making clear conclusions and comparisons with other studies impossible. The interpretation of HRQoL impairment data is more difficult when assessed by instruments without severity stratification systems. The minimal clinically significant difference (MCID) is a more clinically oriented and relevant parameter than depending on statistically significant changes in HRQoL scores. Therefore, using HRQoL instruments with established MCID data in clinical trials and clinical practice is preferred.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.

To explore the knowledge, attitudes and practices (KAP) of urticaria patients regarding the medication treatment.

A cross-sectional study.

At the Dermatology Department of the First Affiliated Hospital of Kunming Medical University from 15 June 2023 to 12 March 2024.

Urticaria patients.

The primary outcome was KAP of urticaria patients using a self-administered questionnaire. The secondary outcomes were factors associated with KAP.

A total of 497 valid responses were collected. Of these respondents, 333 (67.0%) were female, and 375 (75.5%) lived in urban areas. The median KAP scores were 1.00 [0.00, 3.00] (possible range: 0-8), 23.00 [18.00, 26.00] (possible range: 10-50) and 32.00 [31.00, 36.00] (possible range: 8-40), respectively. Most patients (91.7%) clearly needed to understand the aetiology and treatment process related to urticaria. Less than half (43.5%) of patients believed that their healthcare providers offered comprehensive information about the knowledge and procedures related to urticaria medication. Demographic analysis uncovered substantial variations in knowledge and attitude scores across different education levels, age groups, occupations and residential areas (p<0.001 for all). In contrast, the impact on practice scores was less significant, particularly concerning educational diversity. Multivariate logistic regression analysis revealed that a higher knowledge score (OR=1.17, 95% CI: [1.03 to 1.33], p=0.014) and age between 35-65 years (OR=1.78, 95% CI: [1.16 to 2.74], p=0.009) were independently associated with proactive practices.

Urticaria patients exhibit insufficient knowledge, unfavourable attitudes and proactive practices concerning medication treatment. Enhancing patient education and targeted interventions are essential to improve the knowledge and attitudes towards medication treatment, ultimately promoting better self-management practices among urticaria patients.

Urticaria is characterized by transient itchy symptoms on the skin, usually accompanied by swelling, which is caused by mast cell activation leading to increased vascular permeability and dilation of the dermis. Urticaria involves recurrent activation of mast cells, T cells, eosinophils, and other immune cells around lesioned venules, with complex regulatory systems affecting mast cell functions, potentially contributing to urticaria pathogenesis. The direct causal relationship between immune cells and urticaria is currently unclear. To address this, our study utilized a bidirectional Mendelian randomization analysis, employing instrumental variables (IVs) associated with immune cells and urticaria, to investigate this causal relationship. First, by utilizing Genome-wide Association Study (GWAS) data, we identified 31 immunophenotypes associated with urticaria risk, with 18 increasing and 13 decreasing the risk. Through rigorous criteria, we identified 4 immunophenotypes that have a strong causal relationship with urticaria. Notably, HLA DR+ CD4+AC, CD45 on CD8br, and HLA DR on plasmacytoid dendritic cells were associated with an increased risk, while CD8dim NKT %lymphocyte was identified as a protective factor. Sensitivity analyses, including the MR-Egger intercept test, scatter plots, funnel plots, and leave-one-out analysis, supported the robustness of the findings. Reverse MR analysis suggested an inverse causal effect of urticaria on CD8dim NKT %lymphocyte, reinforcing the potential bidirectional nature of the relationship between urticaria and immune cell phenotypes. Our research substantiates the bidirectional causal relationship between immune cells and urticaria, thus benefiting for urticaria-targeted therapy development.

The European Academy of Dermatology and Venereology (EADV) Task Forces on quality of life (QoL) and patient-oriented outcomes and on urticaria and angioedema recommendations for the assessment of Health-related (HR) QoL in all patients with urticaria in research and practice are as follows: to use the DLQI for adults and the CDLQI for children as dermatology-specific and the CU-Q2oL as a disease-specific HRQoL instruments in urticaria; to use generic instruments to provide comparison of data on urticaria with non-dermatologic diseases, or to compare with healthy volunteers or the general population; to select validated HRQoL instruments with appropriate age limits; to present exact numeric data for HRQoL results; correct title of any HRQoL instrument should be used, along with its correct abbreviation and the reference to its original publication, where possible. The EADV TFs discourage the use of non-validated HRQoL instruments and modified HRQoL instruments that have not undergone standard validation.

Chronic spontaneous urticaria (CSU) is both physically and emotionally stressful, and guideline recommendations are often not optimally implemented in clinical practice. The objective of this study was to provide an overview on the patient journey in CSU and to develop a mathematical model based on solid data.

The journey of CSU patients in Germany was traced through literature review and expert meetings that included medical experts, pharmacists and representatives of patient organizations. The current situation's main challenges in the patient journey (education, collaboration and disease management) were discussed in depth. Then, a probabilistic model was developed in a co-creation approach to simulate the impact of three potential improvement strategies: (1) patient education campaign, (2) medical professional education programme and (3) implementation of a disease management programme (DMP).

Chronic spontaneous urticaria patients are severely burdened by delays in diagnosis and optimal medical care. Our simulation indicates that in Germany, it takes on average of 3.8 years for patients to achieve disease control in Germany. Modelling all three optimization strategies resulted in a reduction to 2.5 years until CSU symptom control. On a population level, the proportion of CSU patients with disease control increased from 44.2% to 58.1%.

In principle, effective CSU medications and a disease-specific guideline are available. However, implementation of recommendations is lagging in practice. The approach of quantitative modelling of the patient journey validates obstacles and shows a clear effect of multiple interventions on the patient journey. The data generated by our simulation can be used to identify strategies for improving patient care. Our approach might helping in understanding and improving the management of patients beyond CSU.

The etiology and pathophysiology of vaccine-associated chronic urticaria (CU) remain unclear, particularly during the coronavirus disease 2019 (COVID-19) pandemic. Thus, this study aimed to comprehensively investigate the global burden and long-term trends of vaccine-associated CU, with a focus on the associated vaccines and the distribution of cases across different age groups and sexes.

Using data from the World Health Organization international pharmacovigilance database (VigiBase), which encompasses reports from 156 countries and territories between 1968 and 2023, we systematically analyzed the global burden and long-term trends in vaccine-associated CU reports (total individual case safety reports = 131,255,418). We estimated the global and regional reports, information component (IC) with IC0.25 using disproportionality analyses, and reporting odds ratio (ROR) with 95% confidence interval (CI) to investigate the potential associations between 27 vaccines and CU.

Among the 3,474 reports of all-cause CU, 1,898 vaccine-associated CU reports were identified between 2010 and 2023. A dramatic surge in vaccine-associated CU reports has been observed since 2020, primarily driven by the COVID-19 mRNA vaccines. The COVID-19 mRNA vaccines were associated with the most CU reports (ROR, 26.52 [95% CI, 24.33-28.90]; IC, 3.18 [IC0.25, 3.10]), followed by papillomavirus (ROR, 4.23 [95% CI, 2.55-7.03]; IC, 1.93 [IC0.25, 1.06]), influenza (ROR, 3.09 [95% CI, 2.16-4.43]; IC, 1.57 [IC0.25, 0.96]), Ad5-vectored COVID-19 (ROR, 2.82 [95% CI, 2.40-3.31]; IC, 1.42 [IC0.25, 1.16]), and zoster vaccines (ROR, 2.28 [95% CI, 1.32-3.93]; IC, 1.12 [IC0.25, 0.18]). These increased risks were particularly pronounced for males and older adults. No fatal outcomes have been reported in vaccine-associated CU.

This study underscores the importance of clinicians considering the potential risk factors associated with vaccine-associated CU, especially in the context of COVID-19-related vaccines. Ongoing pharmacovigilance efforts facilitated by robust reporting systems are required to further validate our findings.

Chronic urticaria is a mast cell (MC)-driven disease characterized by the development of itching wheals and/or angioedema. In the last decades, outstanding progress has been made in defining the mechanisms involved in MC activation, and novel activating and inhibitory receptors expressed in MC surface were identified and characterized. Besides an IgE-mediated activation through high-affinity IgE receptor cross-linking, other activating receptors, including Mas-related G-protein-coupled receptor-X2, C5a receptor, and protease-activated receptors 1 and 2 are responsible for MC activation. This would partly explain the reason some subgroups of chronic spontaneous urticaria (CSU), the most frequent form of urticaria in the general population, do not respond to IgE target therapies, requiring other therapeutic approaches for improving the management of the disease. In this review, we shed some light on the current knowledge of the immunologic and nonimmunologic mechanisms regulating MC activation in CSU, considering the complex inflammatory scenario underlying CSU pathogenesis, and novel potential MC-targeted therapies, including surface receptors and cytoplasmic signaling proteins.

Chronic spontaneous urticaria (CSU) patients sometimes do not respond to second-generation antihistamine, and 10-50% patients do not even respond to four-fold the usual dose of nonsedating H1 antihistamine, which further leads to repeated courses of oral corticosteroids to abate the symptoms. There are third-line agents approved by EAACI guidelines, which include omalizumab and cyclosporine. Certain patients are even resistant to the third-line agents. In this review, various other treatment options will be discussed in patients of refractory CSU.

Recently, we demonstrated azathioprine as a possible third-line option, which was found noninferior to cyclosporine in antihistamine refractory CSU. There have been trials, studies, case series and reports, which suggest other putative options for refractory CSU management.

Studies on the management of refractory CSU are accumulating thereby expanding the armamentarium of dermatologists and allergologist against difficult-to-treat urticaria patients.

Several studies have shown that subcutaneous injections of omalizumab can treat chronic idiopathic/spontaneous urticaria (CIU/CSU) patients by only assessing the efficacy on specific endpoints. This study aimed to quantitatively analyze different doses of omalizumab in CIU/CSU and compare it with ligelizumab.

Literature searches were performed in PubMed, Embase, and Web of Science databases. A model-based meta-analysis (MBMA) was utilized to develop a model incorporating time since the initiation of treatment and dose for omalizumab, with the change from baseline in Urticaria Activity Score (CFB-UAS7) as the primary efficacy endpoint. The time-course and dose-effect relationship throughout the omalizumab treatment period was analyzed, and the findings were compared with those of the investigational ligelizumab.

The model equation for the CFB-UAS7 was established as E = -Emax × time/(ET50 + time) × (b0 + b1 × dose). The estimated values of the model parameters E max ,ET 50 , b 0 , and b 1 were -1.16, 1.26 weeks, -9.90, and -0.0361 mg-1, respectively. At week 12 after the first dose, the model-predicted CFB-UAS7 for 150 mg and 300 mg of omalizumab were -16.0 (95% CI, -17.2 to -14.8) and -21.7 (95% CI, -22.9 to -20.5), respectively. In the PEARL-1 trial, the CFB-UAS7 for 72 mg and 120 mg of ligelizumab were -19.4 (95% CI, -20.7 to -18.1) and -19.3 (95% CI, -20.6 to -18.0), respectively. In the PEARL-2 trial, these values were -19.2 (95% CI, -20.5 to -17.9) and -20.3 (95% CI, -21.6 to -19.0), respectively.

Omalizumab showed a significant dose-dependent effect in the treatment of CSU. Both 72 mg and 120 mg ligelizumab might have the potential to outperform 150 mg (but not 300 mg) omalizumab.

Managing pruritic conditions is essential due to their significant impact on patients' quality of life. Chronic urticaria (CU), characterized by persistent itching and hives, severely affects daily activities and sleep. CU includes chronic inducible urticaria and chronic spontaneous urticaria, with the latter lacking identifiable triggers, making treatment especially challenging. CU is a condition that occurs across all age groups, with a higher prevalence among young adults and middle-aged women. Current antihistamine treatments include first-generation antihistamines, which are associated with sedation, and second-generation antihistamines such as cetirizine and fexofenadine, which cause less sedation but have varying efficacy and safety profiles. Bilastine, a novel second-generation H1-antihistamine, offers advantages due to its potent antihistaminic activity, rapid onset of action, and minimal sedation. This narrative review thoroughly synthesizes the evidence for the efficacy and safety of bilastine in treating CU and other pruritic conditions. By analyzing clinical trials, real-world evidence, and comparative studies, this review aims to provide a comprehensive understanding of the role of bilastine in managing pruritic conditions, emphasizing its pharmacokinetic properties, clinical efficacy, and safety profile compared to other antihistamines.

Chronic spontaneous urticaria (CSU) is a challenging disorder that severely impacts the quality of life. The current study objective was to evaluate the efficacy and safety of jujube oxymel (JO) for treating CSU.

In this randomized double-blind controlled trial, 92 patients (aged 12-65) with CSU were randomly allocated to JO or placebo groups. They received 30cc of each syrup three times daily with 10 mg cetirizine for 28 days, subsequently taking 10 mg cetirizine alone for the next 4 weeks. Outcomes were evaluated using the weekly urticaria activity score (UAS-7) and Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL).

After four weeks, the UAS-7 score mean and standard deviation in the JO group significantly decreased to 10.89 ± 4.87 compared to the placebo group at 15.06 ± 7.55 (P: 0.002). In the follow-up period, JO group participants achieved a score of 10.28 (4.67), while a significant increase occurred in the control group (18.33 ± 6.29) (P = 0.001). On day 28, there was a notable improvement in the quality of life within the JO group (P < 0.05). By the eighth week, both groups experienced an increase in CU-Q2oL score, but the changes in the control group were statistically significant (18.09 (5.96) vs 41.31 (10.34) (P: 0.001).

JO, as part of integrated therapy, exhibited potentially longer-lasting efficacy than cetirizine alone, contributing to enhanced quality of life and increased patient satisfaction due to minimal side effects.

A large proportion of patients with chronic spontaneous urticaria (CSU) are resistant to a standard dose of antihistamine. Acknowledged biomarkers for identifying these patients have not been determined. The neutrophil/lymphocyte ratio (NLR) has been considered as an important indicator of inflammation in chronic diseases.

To explore whether NLR could serve as a biomarker for predicting the response to H1-antihistamine in patients with CSU.

This hospital-based, retrospective study included 109 patients with CSU diagnosed from 2017 to 2020 in our clinic and divided them into two groups by their responses to the 2-week antihistamine therapy of standard-dose: 69 with H1-antihistamine-refractory and 40 with non-H1-antihistamine-refractory CSU. The laboratory test results were collected from the hospital information system and integrated with SPSS software.

Patients refractory to H1-antihistamine had significantly higher median NLR (P = 0.039), age (3 P = 0.021), complement C3 (P = 0.026), presence of elevated WBC (P = 0.026) and elevated monocytes (MONO) (P = 0.045) and significantly lower IgM (P = 0.022). The binary logistic regression model revealed that NLR was significantly associated with H1-antihistamine-refractory of CSU (odds ratio (OR) 1.717, 95% confidence interval (CI) 1.065-2.766, P = 0.026), which was consistent with that after adjusted for potential confounding factors including age, complement C3, presence of elevated WBC and MONO, and IgM (OR 1.681, 95% CI 1.019-2.773, P = 0.042).

Our results showed a strong and significant association between higher NLR and H1-antihistamine resistance in CSU, suggesting that NLR may be a potential biomarker for predicting the response to H1-antihistamine therapy in patients with CSU.

Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (Phe) metabolism, resulting from the deficient activity of phenylalanine hydroxylase that converts Phe to tyrosine in the liver, leading to elevated levels of Phe. Pegvaliase is an innovative and effective enzyme replacement therapy for reducing Phe concentration, but it has been associated with severe drug-induced hypersensitivity adverse events (HAEs). Limited data is available on the management of these HAEs, thus, we aimed to present a case report of a successful management strategy. The patient was a 28-year-old Caucasian male with classical PKU, who was otherwise healthy. Due to poor metabolic control, the pegvaliase treatment was initiated. The titration phase was uneventful, with transient and mild side effects, localized to the injection site. After the patient was on a maintenance dose of pegvaliase and had no reactions to the drug, we discontinued the H1-antihistamine. In the following days, within minutes after receiving the pegvaliase injection, an acute hypersensitivity reaction occurred that required emergency treatment. H1-antihistamine treatment was reintroduced. Four days after the incident he received pegvaliase under medical supervision and did not experience any symptoms. In conclusion, cautious reintroduction of pegvaliase in a hospital setting can be safely performed after HAE due to the discontinuation of H1-antihistamines. HAEs could be successfully mitigated by scheduling daily antihistamines administration closer to the pegvaliase injection. This approach can enable PKU patients to maintain their access to an effective and quality-of-life-improving therapy.

Chronic spontaneous urticaria (CSU) is a debilitating, inflammatory skin condition characterized by infiltrating immune cells. Available treatments are limited to improving the signs and symptoms. There is an unmet need to develop therapies that target disease-driving pathways upstream of mast cell activation to inhibit or delay the progression of CSU and associated comorbidities. Here, we aim to define disease modification due to a treatment intervention and criteria that disease-modifying treatments (DMTs) must meet in CSU. We have defined disease modification in CSU as a favorable treatment-induced change in the underlying pathophysiology and, therefore, the disease course, which is clinically beneficial and enduring. A DMT must fulfil the following criteria: (1) prevents or delays the progression of CSU, (2) induces long-term, therapy-free clinical remission, which is the sustained absence of CSU signs and symptoms without the need for treatment, and (3) affects the underlying mechanism of CSU, as demonstrated by an effect on disease-driving signals and/or a biomarker. DMTs in CSU should slow disease progression, achieve long-lasting disease remission, target disease-driving mechanisms, reduce mast cell-activating IgE autoantibodies, target cytokine profile polarization, and normalize the gut microbiome and barrier. Treating CSU at the immune system level could provide valuable alternatives to pharmacotherapy in CSU management. Specific DMTs in CSU are yet to be developed, but some show potential benefits, such as inhibitors of Bruton's Tyrosine Kinase, IL-4 and IL-13. Future therapies could prevent CSU signs and symptoms, achieve long-term clinical benefits after discontinuing treatment, and prevent associated concomitant disorders.

Cetirizine and Loratadine are the two best-selling second-generation antihistamines for allergic diseases. This study aims to provide a comparative analysis of the differences in adverse drug events (ADEs) between these two medications, which can assist clinicians in making appropriate treatment decisions.

ADE reports related to Cetirizine and Loratadine obtained from the FDA adverse event reporting system (FAERS) database were analyzed using disproportionality analysis and Bayesian analysis to evaluate and compare the ADE signals of both drugs.

A total of 28,051 and 28,073 ADE reports were retrieved from the FAERS database related to Cetirizine and Loratadine, respectively, with both drugs showing a predominance of middle-aged females. Specifically, Loratadine was associated with respiratory symptoms, mainly nasal symptoms such as rhinorrhea (n = 326, ROR 6.75), sneezing (n = 251, ROR 15.24), and nasal congestion (n = 185, ROR 4.25), while Cetirizine did not show this association. Notably, both drugs exhibited strong signals for somnolence in the nervous and psychiatric systems, especially Cetirizine (Cetirizine, n = 2556, ROR 10.52 vs. Loratadine, n = 1200, ROR 7.76). Additionally, Cetirizine itself showed strong signals for attention disturbance (n = 233, ROR 3.3), while Loratadine was associated with nervousness (n = 145, ROR 3.3). Further exploration revealed more severe adverse reactions closely associated with Cetirizine, including hallucinations, aggression, and abnormal behavior. Importantly, Cetirizine was significantly associated with the occurrence of pericarditis (n = 138, ROR 8.13), potentially leading to serious adverse consequences.

Compared to Loratadine, Cetirizine poses a greater potential risk in the nervous and psychiatric systems. Additionally, this study reveals previously underestimated potential cardiac toxicity of Cetirizine; albeit at a relatively low incidence rate, the high signal intensity warrants further attention and exploration. These findings highlight the need for enhanced patient monitoring and therapy optimization when prescribing these medications, ensuring better management of allergic diseases while minimizing risks.

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.

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.

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.

Chronic inducible urticaria (CIndU) is characterized by the appearance of hives (urticaria) and/or angioedema in response to specific triggers or stimuli. For accurate diagnosis, anamnesis-driven specific, and if available, standardized trigger testings, as well as patient reported outcomes, should be applied. The currently recommended treatment algorithm is the same as for chronic spontaneous urticaria but is largely off-label for CIndU. New, and possibly more disease-specific, treatment options are needed for CIndU patients, who are often severely impacted by their disease. Several clinical trials are currently ongoing.

This study focuses on quality of life (QoL) assessment in chronic urticaria, delving into tools, disease-specific measures, and its profound impact. With expanding therapeutic options, understanding QoL becomes crucial. QoL measures often involve comparisons of patient-reported outcomes in addition to quantitative measures of disease control. Emerging tools include the Urticaria Activity and Impact Measure, which may provide a balanced evaluation. In addition to discussions of the various QoL measures, the psychological impact of chronic urticaria are highlighted, covering emotional burden, stress, and psychiatric comorbidities. Finally, the economic impacts reveal escalating health care costs and cost-effectiveness considerations of therapies like omalizumab.

The term "urticaria" was first introduced by William Cullen in the eighteenth century. Urticaria is a common mast cell-mediated cutaneous disease presenting with pruritic wheals, angioedema, or both. It is classified as acute (≤6 weeks) or chronic (>6 weeks) and as spontaneous (no definite triggers) or inducible (definite and subtype-specific triggers). The international urticaria guideline on the definition, classification, diagnosis, and management of urticaria is revised every 4 years. The global network of Urticaria Centers of Reference and Excellence, the biggest and most active consortium of urticaria specialists, offers physicians and patients several research, educational, and digital care initiatives.

Drug-induced skin disease or cutaneous adverse drug reactions (CADRs) are terms that encompass the clinical manifestations of the skin, mucosae and adnexa induced by a drug or its metabolites. The skin is the organ most frequently affected by drug reactions, which may affect up to 10% of hospitalized patients and occur in 1-3% of multimedicated patients. Most CADRs are mild or self-resolving conditions; however, 2-6.7% of could develop into potentially life-threatening conditions. CADRs represent a heterogeneous field and can be diagnostically challenging as they may potentially mimic any dermatosis. Currently, there are between 29-35 different cutaneous drug-reaction patterns reported ranging from mild dermatitis to an extensively burnt patient. The most frequently reported are maculopapular rash, urticaria/angioedema, fixed drug eruption and erythema multiforme. Less common but more severe patterns include erythroderma, drug reaction with eosinophilia and systemic symptoms, and Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum. Almost any drug can induce a CADR, but antibiotics, nonsteroidal anti-inflammatory drugs and antiepileptics are the most frequently involved. Different mechanisms are involved in the pathogenesis of CADRs, although in some cases, these remain still unknown. CADRs could be classified in different ways: (i) type A (augmented) or type B (bizarre); (ii) immediate or delayed; (iii) immune-mediated or nonimmune-mediated; (iv) nonsevere or life-threatening; and (v) by their phenotype, including exanthematous, urticarial, pustular and blistering morphology. Recognizing a specific CADR will mostly depend on the ability of the physician to perform a detailed clinical examination, the proper description of the morphology of the skin lesions and supporting laboratory and/or skin biopsy findings.

There have been reports indicating a correlation between heightened intestinal permeability and many autoimmune and chronic inflammatory disorders. The involvement of autoimmunity is now recognized as a significant factor in the development of chronic spontaneous urticaria (CSU). Zonulin is an important biomarker that regulates tight junction permeability within cells in the gastrointestinal tract, hence facilitating intestinal permeability.

To evaluate the correlation of CSU with intestinal permeability by measuring the serum levels of zonulin in patients diagnosed with CSU.

The study included 60 patients diagnosed with CSU and 64 age- and sex-matched healthy individuals as controls. Levels of serum zonulin were determined using the ELISA method.

Although the serum zonulin value of the patients was higher compared to the controls, the difference did not reach a significant level (24.65±8.49 ng/ml vs. 21.03±7.36 ng/ml, p=0.077). The serum zonulin level had a significant correlation with the urticaria activity score in the CSU group (p=0.013). The results of the current study revealed that serum zonulin values significantly differed between patients with CSU and healthy controls.

This study is important in terms of being the first to investigate the serum zonulin levels in CSU. However, there is a need for further studies with larger patient groups.

Chronic urticaria is an inflammatory skin disorder defined by the presence of evanescent erythematous pruritic wheals, angioedema, or both. While treatment guidelines are continuing to become more clearly defined, there is still a gap in the medical literature surrounding chronic spontaneous urticaria (CSU) treatment in vulnerable populations such as children (aged 0-18 years), pregnant women, and the elderly (aged >65 years). The purpose of this review is to provide an update on CSU in each of these special population categories by defining prevalence, identifying diagnostic considerations, and exploring current and future management options.

Chronic spontaneous urticaria (CSU) is a common chronic inflammatory skin disease that manifests as itching and wheals, seriously affecting quality of life. Clinical observations and previous research trials have shown that acupuncture is safe and effective for the treatment of CSU. However, there are problems, such as a short duration of action and frequent treatment. Compared with traditional acupuncture, acupoint catgut embedding (ACE) has the advantages of a longer effect and higher compliance. Clinical trials are needed to prove its efficacy and mechanism of action.

This trial aims to provide definitive evidence for the treatment of CSU with ACE and explore the mechanism of ACE.

This is a randomized, double-blind, placebo-controlled trial. In this trial, 108 participants aged 18-60 years with a diagnosis of CSU and no history of ACE will be randomly assigned to 2 groups (1:1 ratio) using the Statistical Analysis System: treatment (ACE) and control (sham ACE). The participants and efficacy evaluators will be blinded to the grouping. Both the ACE and sham ACE groups will undergo acupuncture, but the sham ACE group will not receive catgut sutures. Treatment will be performed twice weekly for 8 weeks, with a 1-week run-in period and a 16-week follow-up period. Twenty patients will be randomly selected to undergo functional magnetic resonance imaging before and after the treatment period. The primary outcome will be the urticaria activity score over 7 days (UAS7). We will use R (version 4.0.1; R Project for Statistical Computing) to perform ANOVA and independent samples t tests to compare the differences within and between groups before and after treatment by judging the rejection range based on a significance level of .05.

The study protocol has been approved by the Ethics Committee of Guang'anmen Hospital on September 7, 2022, and has been registered on November 30, 2022. Recruitment began on March 1, 2023. A total of 4-6 participants are expected to be recruited each month. The recruitment is planned to be completed on March 1, 2025, and we expect to publish our results by the winter of 2025. As of November 1, 2023, we have enrolled 25 participants with CSU.

This randomized, double-blind, placebo-controlled trial aims to provide definitive evidence for the treatment of CSU with ACE and explore the mechanism of ACE. We hypothesize that wheals and itching will show greater improvement in participants receiving active therapy than in those receiving sham treatment. The limitations of this study include its single-center trial design, small sample size, and short treatment duration, which may have certain impacts on the research results.

Chinese Clinical Trial Registry ChiCTR2200066274; https://www.chictr.org.cn/showprojEN.html?proj=179056.

DERR1-10.2196/54376.

Chronic spontaneous urticaria (CSU) is a relatively common skin disease associated with hives and angio-oedema. Eosinophils play a role in CSU pathogenesis. Benralizumab, an anti-interleukin-5 receptor-α monoclonal antibody, has been shown to induce nearly complete depletion of eosinophils.

To determine the clinical efficacy and safety of benralizumab in patients with CSU who were symptomatic despite H1 antihistamine treatment.

The 24-week, randomized, double-blind, placebo-controlled, phase IIb portion of the ARROYO trial enrolled adult patients with CSU who were currently on H1 antihistamine treatment. Patients were randomized to one of five treatment groups according to benralizumab dose and regimen for a 24-week treatment period. The primary endpoint was change from baseline in Itch Severity Score (ISS)7 at week 12. The key secondary endpoint was change from baseline in Urticaria Activity Score (UAS)7 at week 12. Additional secondary endpoints included other metrics to assess CSU at week 24, blood eosinophil levels, and pharmacokinetics and immunogenicity assessments. Exploratory subgroup analyses were conducted to explore responses according to demographics, clinical features and biomarkers. Safety was assessed in all treatment groups.

Of 155 patients, 59 were randomized to benralizumab 30 mg, 56 to benralizumab 60 mg and 40 to placebo. Baseline and disease characteristics were consistent with what was expected for patients with CSU. There were no significant differences in change from baseline in ISS7 score at week 12 between benralizumab and placebo [benralizumab 30 mg vs. placebo, least-squares mean difference -1.01, 95% confidence interval (CI) -3.28 to 1.26; benralizumab 60 mg vs. placebo, least-squares mean difference -1.79, 95% CI -4.09 to 0.50] nor in change from baseline in UAS7 score at week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, P = 0.407; benralizumab 60 mg vs. placebo, P = 0.082). Depletion of blood eosinophil levels was observed at week 24 in patients treated with benralizumab. All other secondary endpoints and exploratory/subgroup analyses indicated no significant differences between benralizumab and placebo. Safety results were consistent with the known profile of benralizumab.

Although benralizumab resulted in near-complete depletion of blood eosinophils, there was no clinical benefit over placebo.

The silent information regulator sirtuin 1 (SIRT1) protein is an NAD+-dependent class-III lysine deacetylase that serves as an important post-transcriptional modifier targeting lysine acetylation sites to mediate deacetylation modifications of histones and non-histone proteins. SIRT1 has been reported to be involved in several physiological or pathological processes such as aging, inflammation, immune responses, oxidative stress and allergic diseases. In this review, we summarized the regulatory roles of SIRT1 during allergic disorder progression. Furthermore, we highlight the therapeutic effects of targeting SIRT1 in allergic diseases.

Molecularly targeted therapies, such as monoclonal antibodies (mAbs) and Janus Kinase inhibitors (JAKis), have emerged as essential tools in the treatment of dermatological diseases. These therapies modulate the immune system through specific signaling pathways, providing effective alternatives to traditional systemic immunosuppressive agents. This review aims to provide an updated summary of targeted immune therapies for inflammatory skin diseases, considering their pathophysiology, efficacy, dosage, and safety profiles.

The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was conducted on PubMed over the past 10 years, focusing on randomized clinical trials, case reports, and case series related to targeted immune therapies in dermatology. Eligibility criteria were applied, and data were extracted from each study, including citation data, study design, and results.

We identified 1360 non-duplicate articles with the initial search strategy. Title and abstract review excluded 1150, while a full-text review excluded an additional 50 articles. The review included 143 studies published between 2012 and 2022, highlighting 39 drugs currently under investigation or in use for managing inflammatory skin diseases.

The heterogeneity of summarized information limits this review. Some recommendations originated from data from clinical trials, while others relied on retrospective analyses and small case series. Recommendations will likely be updated as new results emerge.

Targeted therapies have revolutionized the treatment of chronic skin diseases, offering new options for patients unresponsive to standard treatments. Paradoxical reactions are rarely observed. Further studies are needed to fully understand the mechanisms and nature of these therapies. Overall, targeted immune therapies in dermatology represent a promising development, significantly improving the quality of life for patients with chronic inflammatory skin diseases.

Background: Sleep can be affected in patients with chronic spontaneous urticaria (CSU). The mechanisms of sleep regulation remain poorly understood. Orexin-A, a neuroexcitatory peptide, plays a role in coordinating sleep-wake states. Ghrelin and leptin are involved in sleep regulation through the orexin system. Objective: The effects of orexin-A, ghrelin, and leptin on sleep quality in patients with CSU have not been investigated. We aimed to determine the effects of CSU on sleep quality and the association between serum orexin-A, ghrelin, and leptin levels, and sleep quality in patients with CSU. Methods: Thirty-three patients with CSU and 34 sex- and age-matched controls were included in the study. Serum orexin-A, leptin, and ghrelin levels, and the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) scores were measured in patients with CSU and in the controls; also used were the chronic urticaria quality-of-life questionnaire score and the urticaria activity score used for 7 consecutive days. Results: Median (minimum-maximum) orexin-A, leptin, and ghrelin levels in patients were 385 pg/mL (90-495 pg/mL), 3.1 ng/mL (0-21.2 ng/mL), and 701.8 pg/mL (101.9-827.7 pg/mL), respectively. Median serum orexin-A and leptin levels were higher in the patients compared with the controls (p < 0.001 and p = 0.012, respectively), whereas the median serum ghrelin levels were similar to the controls (p = 0.616). The serum orexin-A level was positively correlated with ghrelin (r = 0.298, p = 0.014), PSQI sleep quality (r = 0.356, p = 0.003), and ESS (r = 0.357, p = 0.003). Conclusion: Serum orexin-A is associated with sleep quality in patients with CSU. Further studies are needed to elucidate the role of ghrelin and leptin on sleep quality in patients with CSU.