Urticaria Activity Score Research Articles

Comparison of long term efficacy and cost-effectiveness of omalizumab in 150 mg and 300 mg doses in patients with chronic spontaneous urticaria

BackgroundChronic 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. ObjectivesThe 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. Methods108 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. ResultsThere 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. Study limitationsRetroactive 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. ConclusionSince 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.

Changes of vitamin D, Th17/Treg related cytokines and their correlations with disease activity in chronic spontaneous urticaria

AimsTo investigate levels of 25-hydroxyvitamin-D (25HVD), interleukin-17 (IL-17), IL-27, IL-35, and transforming growth factor β1 (TGF-β1) in chronic spontaneous urticaria (CSU) patients and their correlations with disease activity.MethodsAn observational, case-control study was conducted. Eighty-one CSU patients and fifty-eight healthy individuals were recruited into two groups. Serum levels of 25HVD, IL-17, IL-27, IL-35, TGF-β1 were determined via enzyme-linked immunosorbent assay (ELISA). Disease activity of CSU was assessed using urticaria activity score (UAS).ResultsSerum level of 25HVD was significantly lower in CSU group compared to control group (P < 0.001). Serum levels of IL-17 (P < 0.001), IL-27 (P < 0.001), TGF-β1 (P = 0.01) were significantly higher in CSU group than those in control group. In CSU group, the level of 25HVD was negatively associated with IgE (P < 0.01) and positively correlated with IL-35 (P < 0.01). In addition, serum level of IL-17 was negatively correlated with disease activity among female patients (P < 0.05).ConclusionDeficiency of 25HVD is associated with development of CSU, the underlying mechanism might be related with IL-35. Likewise, IL-17, IL-27, IL-35, and TGF-β1 might also contribute to development of CSU.

Validity, reliability and responsiveness of digital visual analogue scales for chronic spontaneous urticaria monitoring: A CRUSE® mobile health study.

CRUSE® is an app that allows patients with chronic spontaneous urticaria (CSU) to monitor their daily disease activity through the use of visual analogue scales (VASs). We aimed to determine the concurrent validity, reliability, responsiveness and minimal important difference (MID) of CRUSE® VASs. We evaluated the properties of three daily VASs: VAS for how much patients were affected by their CSU ('VAS urticaria'), VAS for the impact of urticaria on work/school productivity ('VAS productivity') and the VAS of EQ-5D. Concurrent validity was assessed by measuring the association between each VAS and the Urticaria Activity Score (UAS). Intra-rater reliability was determined based on the data of users providing multiple daily questionnaires within the same day. Test-retest reliability and responsiveness (ability to change), respectively, were tested in clinically stable and clinically unstable users. MIDs were determined using distribution-based methods. We included 5938 patients (67,380 days). Concurrent validity was high, with VAS urticaria being more strongly associated with the UAS score than the remaining VASs. Intra-rater reliability was also high, with intraclass correlation coefficients (ICC) being above 0.950 for all VASs. Moderate-high test-retest reliability and responsiveness were observed, with reliability ICC being highest for VAS EQ-5D and responsiveness being highest for VAS urticaria. The MID for VAS urticaria was 17 (out of 100) units, compared to 15 units for VAS productivity and 11 units for VAS EQ-5D. Daily VASs for CSU available in the CRUSE® app display high concurrent validity and intra-rater reliability and moderate-high test-retest reliability and responsiveness.

Decoding the variability in clinical and laboratory profiles of Chronic Inducible Urticaria vs. Chronic Spontaneous Urticaria - a retrospective study from a tertiary care center.

Chronic inducible urticaria (CIndU) is characterized by wheals and/or angioedema for longer than 6 weeks induced by specific triggers. The data regarding epidemiology of CIndU is scarce with limited available literature on urticaria severity, investigations, and treatment responses in CIndU compared to CSU. We performed a retrospective chart review of all CIndU patients(cases) enrolled in our Urticaria clinic, past seven years between January 2017 to December 2023. Equal number of CSU patients enrolled during study period were taken as controls. Patients with absence of weals and both CSU and CIndU were excluded from the study. Urticaria severity was assessed by Urticaria activity score over 7 days (UAS7). Statistical analyses were performed using SPSS V29 with P < 0.05 as significant. Out of all records screened, 222 CIndU (cases) and 226 CSU (controls) were eligible based on complete availability of data. Both groups were comparable in terms of age and gender with slight female preponderance. Mean UAS7 at baseline was comparable(p = 0.619) between two groups [(11.49 ± 10.37 in CIndU vs. 10.9 ± 12.2 in CSU)]. The mean CRP (mg/dl) levels for CIndU vs. CSU patients was 2.8 ± 4.2 vs. 6.9 ± 11.2 (p < 0.001). Serum D-dimer levels (mg/dl) were also significant between cases(167 ± 220) and controls(265 ± 452) (p = 0.020). The quality of life assessed by CU-QOL score was 9.39 ± 9.5 in CIndU vs. 16 ± 14.8 in CSU (p < 0.001). 80% of CIndU patients and 52% of CSU patients required updosing of antihistamines upto 4 times and the difference was statistically significant between two groups(p = < 0.001). The mean time taken to achieve remission i.e. UAS7 = 0 (T0) was 60 ± 42 days amongst CIndU while it was shorter in CSU (27.77 ± 27 days) (p < 0.001).Amongst all CIndU cases, commonest subtypes were symptomatic dermographism (SD) (39.5%) followed by cholinergic urticaria(4.2%) and cold urticaria(1.8%). Our study underscores the distinct clinical and laboratory profiles between CIndU and CSU patients. CIndU patients exhibit poorer response to standard antihistamine doses, requiring more frequent updosing and longer treatment duration. The time to attain remission as assessed by UAS7 score was also longer in CIndU patients than CSU patients (mean difference of 33 days). Further research is warranted to elucidate the underlying mechanisms and explore targeted treatment approaches for CIndU.

The prevalence of patients suffering from chronic spontaneous urticaria, in whom omalizumab cannot be stopped even after six years.

Omalizumab (OMA) was the first FDA-approved biological drug for severe chronic spontaneous urticaria (CSU), and until today is the only beneficial and truly safe one. The objectives were: To assess the prevalence of CSU patients in whom OMA cannot be stopped over time. We also asked if biomarkers (e.g., anti-TPO antibodies and total IgE) could assist in anticipating this issue. We used our prospective registry of 93 patients, which included CSU disease duration, the onset of OMA treatment, Urticaria Activity Score (UAS7) during follow-up, co-morbidities, serum IgE levels and the presence of anti-TPO antibodies. Finally, we assessed the response to OMA during a period of six years. Out of the 93 treated CSU patients, OMA was stopped in ten patients after six months being defined as failures. In another ten patients, OMA was discontinued after 2-4 years of therapy, achieving a remission. Seventy-three patients are still treated between 2 and 6 years, having different degrees of response. Of these, in thirty-eight (52%) patients, we could not stop OMA even after six years due to CSU relapses. The prevalence of lower serum IgE levels and anti-TPO antibody positivity was significantly higher in CSU patients in whom OMA could not be stopped. This is the first study where OMA-treated CSU patients were followed up to six years. In half of them, long-term therapy of six years is still required.

A study on serum zonulin in chronic spontaneous urticaria patients

hronic spontaneous urticaria (CSU) is a widespread disease with a complicated heterogenous pathophysiology. Increased intestinal permeability i.e., leaky gut has been linked to the pathology of many diseases. Zonulin was recently used as a marker for leaky guts. This study aimed to assess the relation between serum zonulin level and CSU and its possible relationship with disease activity. This was a comparative cross-sectional study, which included 97 CSU adult patients and 87 apparently healthy controls. CSU patients had significant lower zonulin level than controls (p&lt;0.001). The median of serum zonulin level was equal to 2.93 ng/ml with interquartile range (IQR) (1.40-4.19) in the CSU group and of 3.92 ng/ml with IQR (2.97-4.69) in the control group. We found a positive correlation between serum zonulin and C-reactive protein with Pearson correlation coefficient of 0.2, (p=0.04). No significant correlation was found between serum zonulin level and urticaria activity score 7 or total immunoglobulin E level. In conclusion, this study found that serum zonulin level is lower in CSU patients than in controls which could be attributed to food restriction, severity of the CSU disease and/or drug intake in the CSU cases.

Validation of the Cholinergic Urticaria Activity Score (CholUAS)

BackgroundIn cholinergic urticaria (CholU), itchy wheal and flare-type skin reactions are triggered by sweat-inducing activities. The CholU activity score, CholUAS, is used to assess disease activity, but has not yet been validated.The aim of the study was to validate the CholUAS, develop an English version, and provide instructions for scoring. MethodsCognitive debriefing of CholUAS was performed. CholU patients (n =75) used the CholUAS on 7 consecutive days, underwent provocation testing, and completed additional anchor instrument questionnaires including global evaluation tools and established quality of life instruments. A scoring protocol for the calculation of the weekly CholUAS, the CholUAS7, was developed. The CholUAS7 was tested for validity, reliability, and influencing factors. An English version of the CholUAS was developed. ResultsThe final CholUAS contains 3 questions that are used for scoring as well as one global question. The weekly CholUAS, CholUAS7, showed excellent test-retest reliability and good correlations with anchor instruments. Statistical analysis showed no significant influence of age or duration of disease on CholUAS7 results. ConclusionThe validated CholUAS is ready for use in clinical trials and routine clinical practice.

Minimal clinically important difference for acupuncture for patients with chronic spontaneous urticaria: secondary analysis from a multicentre randomised controlled trial in China.

To evaluate the minimal clinically important difference (MCID) value for acupuncture treatment in chronic spontaneous urticaria (CSU), providing guidance for its application in CSU management. Secondary analysis of data from a multicentre randomised controlled trial. Three tertiary hospitals across three cities in China. 103 CSU patients (78.7% female) with an average age of 39.97 years. Participants received acupuncture treatment for 4 weeks in the original study. MCID and minimal detectable change (MDC) for the Urticaria Activity Score over 7 days (UAS7) in acupuncture treatment of CSU. Convergent validity assessed by intraclass correlation coefficient (ICC). Responsiveness evaluated through Spearman correlation between UAS7 improvements and anchor tools (physician's and patient's assessments). MDC calculated using SE of measurement of changes in UAS7 scores. MCID estimated using distribution-based and anchor-based methods. The ICC for UAS7 was 0.86. Improvements in UAS7 scores were significantly correlated with patient (r=0.44, p<0.01) and physician (r=0.85, p<0.01) assessments of CSU activity shifts. The MDC for UAS7 was 5.08. The MCID for acupuncture treatment in CSU was 8.3. This study provides the first MCID value for acupuncture treatment in CSU. These findings contribute to the understanding of acupuncture's effects in treating CSU and may inform future research and clinical practice in the management of this condition. ChiCTR1900022994.

Efficacy and safety of switching to bilastine, an H1-antihistamine, in patients with refractory chronic spontaneous urticaria (H1-SWITCH): a multicenter, open-label, randomized, parallel-group comparative study.

For treating patients with refractory chronic spontaneous urticaria (CSU) resistant to standard doses of 2nd generation H1-antihistamines (H1AH) the International and Japanese guidelines recommend increasing H1AH dose. The latter also recommends switching to a different H1AH. This study explored if the efficacy of the standard dose of bilastine 20 mg is non-inferior to that of double-dose of H1AH in patients with refractory CSU. This phase IV, multicenter, open-label, randomized, parallel-group trial evaluated the efficacy and safety of switching treatment to bilastine compared to treatment with a 2-fold dose of H1AH in patients with CSU refractory to standard dose H1AH. The primary endpoint was the mean total symptom score (TSS) at Day 5-7 after the start of administration. Treatment efficacy and safety were evaluated in 128 patients (bilastine, n=64; 2-fold dose of H1AH, n=64). The mean TSS at Day 5-7 after the start of administration was smaller than the non-inferiority margin of 0.8, demonstrating non-inferiority of the bilastine switching group to the double-dose H1AH group (0.17 (95% CI -0.32, 0.67)). No difference in Japanese version of Epworth Sleepiness Scale (JESS), DLQI, and urticaria activity score over 7 consecutive days (UAS7) was observed between the two groups. There were no serious adverse events in either group. H1AH-related adverse events occurred in 5 subjects (8 cases) and 2 subjects (3 cases) in the double-dose H1AH and bilastine groups, respectively. Switching treatment to bilastine demonstrated non-inferiority to a double-dose of H1AH in terms of efficacy in patients with CSU refractory to standard dose H1AH with a favorable safety profile. https://jrct.niph.go.jp/latest-detail/jRCTs051180105, identifier jRCTs051180105.

Clinical and Immunological Features of Bronchial Asthma Comorbid Chronic Urticaria: A Retrospective Study.

Asthma and chronic urticaria (CU) are two high prevalent diseases and often coexist. The underlying relationship and potential immunological mechanism between the two diseases are still unclear. The objective of this study was to investigate the clinical and immunological feature of asthma comorbid with CU. A retrospective study was conducted. Fifty patients with asthma comorbid CU, 50 patients with asthma, and 50 patients with CU alone were included. Age and sex of the patients enrolled were matched. Data of demographic characteristics, clinical manifestations including disease severity (frequency of symptoms, age of onset, disease duration, symptom score, complication with allergic rhinitis) as well as serum immunological index including total IgE (tIgE), allergen-specific IgE (sIgE), and food-specific IgG4 (FS-IgG4), were collected and analyzed. No significant differences in the frequency of symptoms, age of onset, and disease duration were found among the three groups. The score of asthma control test (ACT) in patients with asthma comorbid CU was significantly lower than that of asthma (p = 0.005); however, compared with patients with CU, the 7-day urticaria activity score (UAS7) of patients with asthma comorbid CU did not show obvious differences. Immunological index showed that the positive rates of tIgE, house dust mite (HDM)-sIgE, and FS-IgG4 were different among the three groups (p &lt; 0.05). Patients with asthma comorbid CU had the highest rate of positive tIgE, moderate and severe positive sIgE to HDM. Egg-specific IgG4 (egg-sIgG4) had the highest positive rate in all groups. Patients of asthma comorbid CU obtained the highest rate of severe positive of egg-sIgG4. Our results demonstrated that patients with asthma comorbid CU have lower control level of asthma symptoms, higher tIgE and HDM-sIgE level, and highest rate of severe positive egg-sIgG4. These results indicate that comorbidity of CU in asthma obviously increases the severity of allergens.

Jujube Oxymel for the Treatment of Chronic Spontaneous Urticaria: Efficacy and Safety

Background: 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. Materials and Methods: 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). Results: 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 &lt; 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). Conclusion: 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.

In chronic spontaneous urticaria, increased Galectin-9 expression on basophils and eosinophils is linked to high disease activity, endotype-specific markers, and response to omalizumab treatment.

Galectin-9 (Gal-9) has been implicated in allergic and autoimmune diseases, but its role and relevance in chronic spontaneous urticaria (CSU) are unclear. To characterize the role and relevance of Gal-9 in the pathogenesis of CSU. We assessed 60 CSU patients for their expression of Gal-9 on circulating eosinophils and basophils as well as T cell expression of the Gal-9 receptor TIM-3, compared them with 26 healthy controls (HCs), and explored possible links with disease features including disease activity (urticaria activity score, UAS), total IgE, basophil activation test (BAT), and response to omalizumab treatment. We also investigated potential drivers of Gal-9 expression by eosinophils and basophils. Our CSU patients had markedly increased rates of circulating Gal-9+ eosinophils and basophils and high numbers of lesional Gal-9+ cells. High rates of blood Gal-9+ eosinophils/basophils were linked to high disease activity, IgE levels, and BAT negativity. Serum levels of TNF-α were positively correlated with circulating Gal-9+ eosinophils/basophils, and TNF-α markedly upregulated Gal-9 on eosinophils. CSU patients who responded to omalizumab treatment had more Gal-9+ eosinophils/basophils than non-responders, and omalizumab reduced blood levels of Gal-9+ eosinophils/basophils in responders. Gal-9+ eosinophils/basophils were negatively correlated with TIM-3+TH17 cells. Our findings demonstrate a previously unrecognized involvement of the Gal-9/TIM-3 pathway in the pathogenesis CSU and call for studies that explore its relevance.

Dupilumab Reduces Urticaria Activity, Itch, and Hives in Patients with Chronic Spontaneous Urticaria Regardless of Baseline Serum Immunoglobulin E Levels.

In chronic spontaneous urticaria (CSU), interleukin (IL)-4 and IL-13 may promote mast cell activation directly via IL-4 receptor expression, or indirectly via upregulated immunoglobulin E (IgE) production. Dupilumab significantly improved CSU signs and symptoms in the phase 3, randomized, placebo-controlled LIBERTY-CSU CUPID Study A. This analysis explores the impact of dupilumab on CSU signs and symptoms and serum IgE levels in patients from LIBERTY-CSU CUPID Study A with serum total IgE above and below 100IU/mL at baseline. Patients with H1-antihistamine-refractory CSU received dupilumab (n = 70) or placebo (n = 68) for 24 weeks. Efficacy endpoints were change from baseline to weeks 12 and 24 in serum total IgE levels, Itch Severity Score over 7 days (ISS7), Urticaria Activity Score over 7 days (UAS7), and Hives Severity Score over 7days (HSS7) in dupilumab- or placebo-treated patients with serum total IgE above and below 100IU/mL at baseline. Dupilumab treatment significantly reduced median (interquartile range) IgE levels at week 12 [dupilumab: -31.9% (-41.9; -22.6); placebo: -6.3% (-21.3; 14.9)] and week 24 [dupilumab: -48.2% (-56.8; - 39.5); placebo: - 6.3% (-34.5; 14.8)]. Similar IgE reductions relative to baseline were observed in dupilumab-treated patients regardless of baseline IgE level. Dupilumab treatment improved ISS7, UAS7, and HSS7 over 12 and 24 weeks, regardless of baseline serum IgE level (interaction p ≥ 0.59 for all treatment by subgroup comparisons), with weak correlations (r < 0.2) observed between IgE level changes and ISS7, UAS7, and HSS7 outcomes. Dupilumab significantly improved CSU signs and symptoms and reduced serum IgE, regardless of baseline IgE levels. In the current analysis, baseline total IgE had no predictive value as a dupilumab treatment response biomarker in CSU. Downregulation of IgE, a key mediator of mast cell activation and histamine release, may at least partially explain the effectiveness of dupilumab in reducing CSU signs and symptoms. ClinicalTrials.gov Identifier: NCT04180488.

Autologous Serum Therapy in Recalcitrant Chronic Spontaneous Urticaria: Experience from Three Dermatology Clinics in Malaysia

Abstract Autohemotherapy is a commonly used treatment for recalcitrant chronic urticaria in some countries. Herein we report our experience using autologous serum therapy in eight patients with recalcitrant chronic spontaneous urticaria. Autologous serum therapy was initiated weekly for nine weeks followed by every fortnightly. Urticaria Activity Score (UAS) 7, Dermatology Life Quality Index (DLQI), and reduction of antihistamine usage were used to assess the treatment response. Eight patients (age range: 25–76 years old; four females and four males) had one to ten years of duration of recalcitrant chronic spontaneous urticaria. All failed to respond to high doses of second-generation antihistamines and five to immune-modulating agents. Three did not respond to omalizumab. At week nine, the reduction of UAS7 ranged from 76.2% to 100%. There was more than an 80% improvement in DLQI in all patients. The number of wheals seemed to be reduced first followed by pruritus. Three patients had stopped antihistamines by week eight of treatment. No adverse events were reported in all eight patients. Autologous serum therapy may serve as an alternative treatment for recalcitrant chronic spontaneous urticaria. Apart from the practicality, which requires frequent clinic visits, venipuncture, and centrifugation, it is cheap and effective with minimal adverse events.

The efficacy of autologous serum therapy in chronic spontaneous urticaria: A systematic literature review and meta-analysis

Chronic spontaneous urticaria (CSU) is an autoimmune disease characterised by urtica lesions and/or angioedema accompanying an itching sensation, recurring for at least six weeks without any specific trigger. Autologous serum therapy (AST) is an adjuvant therapy for CSU that is resistant to H1 antihistamines. This therapy is an economical option in developing countries. There were a few studies discussing the role of AST in CSU. This systematic review and meta-analysis were conducted to evaluate the efficacy of AST based on urticaria activity scores (UAS or UAS7) and urticaria total severity scores (TSS) so that clinicians can consider them. Data were searched systematically in Cochrane, PubMed, Google Scholar, Willey, and EMBASE from 2000 to March 2023. Data analysis using Excel 2010 (Microsoft Corp) and MedCalc version 20.218. There were 14 studies: 4 randomised controlled trials (RCT), 9 prospective, and 1 cross-sectional. The average improvement in UAS and TSS scores at the end of therapy was 42.24% and 41.24%. Results of subgroup analysis of AST administration in the group autologous serum skin test (ASST) positive and ASST negative based on the end of therapy UAS score (p=0.18). Results of subgroup analysis of AST administration in the positive ASST and negative ASST groups based on the TSS score at the end of therapy (p=&lt;0.001). Results of subgroup analysis of AST administration versus placebo based on TSS score (p=0.861). Based on subgroup analysis, autologous serum therapy improves TSS scores in CSU patients (ASST positive). However, AST is not significantly different from placebo.

Peripheral blood T-cell modulation by omalizumab in chronic urticaria patients.

Chronic spontaneous urticaria (CSU) is a highly prevalent and difficult to manage cutaneous disease characterized by the presence of recurrent urticaria, angioedema, or both, for a period of 6 weeks or longer. One of the biological treatments used for patients with CSU with an autoimmune background and bad control of the disease is omalizumab, an anti-IgE monoclonal antibody. The understanding of the mechanism of action of this biological drug in CSU along with the identification of potential biomarkers of clinical response can be helpful in the personalized management of the disease. The purpose of this study was to analyze the effect of omalizumab on peripheral blood lymphocyte subpopulations in patients with CSU in order to identify potential biomarkers of treatment response. We analyzed 71 patients with CSU [33 under omalizumab and 38 under non-immunomodulatory drugs (treated with antihistamines; NID)] and 50 healthy controls. An exhaustive immunophenotyping of whole blood T-cell subpopulations, including naïve, central memory, effector memory, effector cells, Th1, Th2, and Th17 was performed by multiparametric flow cytometry. Moreover, in CSU patients, we analyzed markers of inflammation (ESR, DD, CRP), atopy (prick test, IgE quantification), and autoimmunity (anti-thyroid antibodies and indirect basophil activation test).To evaluate the clinical activity, the Urticaria Activity Score 7 (UAS 7) test was used. In patients with CSU under treatment with omalizumab, there was a significant decrease in the percentage of naïve and an increase in the percentage of central memory CD4 T cells as well as a decrease in the percentage of naïve and increase in the percentage of effector CD8 T-cell subsets. Moreover, patients under treatment with omalizumab had higher percentages of Th1 and Th2 cells than patients under treatment with NID. The immune monitoring of T-cell subpopulations in patients with CSU starting omalizumab, may be a useful strategy to analyze treatment response in the clinical practice.

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.

Efficacy and Mechanism of Acupoint Catgut Embedding in the Treatment of Chronic Spontaneous Urticaria: Protocol for a Randomized Double-Blind Placebo-Controlled Trial.

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.

The relationship between serum transglutaminase-2 levels and the severity of chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is an immunological disease that is depicted by high prevalence and eminent burden for patients and society that is attributable to the arbitrary nature of symptoms and inconsistent tools for assessment of activity and severity. Transglutaminase-2 (TG2) is a posttranslational enzyme that is pervasively expressed in many cells and tissue types including mast cells. It has various biological functions, and its role in allergic disorders has been highlighted and delineated through several postulated mechanisms. This case–control study aimed at determining the relationship between serum levels TG2 and severity of CSU. To the best of our knowledge, this is the first study in Egypt to determine the relationship between serum TG2 and severity of CSU. We enrolled 60 adult patients with confirmed diagnosis of CSU. According to urticaria activity score (UAS), patients were categorized into three groups [20 with mild disease; UAS = 0, 20 with moderate disease; UAS = 1–3, 20 with severe disease; UAS = 4–6]. Another 20 healthy individuals (age and gender matched) served as a control group. All patients were subjected to detailed medical history, clinical examination, complete blood count with differential, serum total IgE, CRP, ESR, TSH, ANA, liver and renal function tests. Serum level of TG2 was done by quantitative ELISA for all enrolled patients and controls. Serum TG2 is significantly higher in patients group compared to control group (P value < 0.001). Serum TG2 levels were significantly higher in patients with severe disease compared to patients with moderate or mild disease. This is illustrated by the significant positive correlation between serum TG2 and UAS (r 0.814 and P value 0.000). Moreover, serum TG2 accurately classified CSU patients into mild, moderate and severe subgroups: as regards differentiation between mild and moderate cases (sensitivity 70%, specificity 80%, PPV 77.8, NPV 72.7) and as for the differentiation between moderate and severe cases (sensitivity 95%, specificity 90%, PPV 90.5, NPV 94.7). Serum TG2 may have a pivotal role as a marker of severity in patients with CSU.

Serum Concentration of IL-5 Receptor (IL-5R) and Associations with Disease Severity in Patients with Chronic Spontaneous Urticaria (CSU) and Atopic Dermatitis (AD).

The immunological pathogenesis of atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) has not been fully elucidated yet. The aim of our research was to assess the serum concentration of interleukin-5 receptor (IL-5R) in relation to the disease activity and pruritus intensity in adult patients with AD and CSU. This pilot study included 45 participants (15 patients with AD, 15 patients with CSU, and 15 healthy controls). Blood samples were taken to examine the serum levels of IL-5R using the enzyme-linked immunosorbent assay (ELISA) test. The Scoring Atopic Dermatitis (SCORAD) index, the Urticaria Activity Score (UAS7), and the Visual Analogue Scale (VAS) were used to assess the disease activity and the pruritus intensity, respectively. Obtained results revealed that the IL-5R concentration was significantly higher in patients with CSU than in patients with AD and in the controls (p = 0.038). There was a positive correlation between the IL-5R level and the SCORAD index in patients with AD (r = -0.9, p = 0.047), which was not found for the CSU activity by UAS7 and with the pruritus severity by VAS in both examined groups of patients. Our findings underscore higher serum levels of IL-5R among CSU and AD patients, which may highlight its functional role in the pathogenesis of these diseases. In contrast, IL-5R might not be fully useful in reflecting the severity of symptoms. Although our results are promising, this study should be conducted on a larger cohort of patients.