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.

The Alarmin Triad-IL-25, IL-33, and TSLP-Serum Levels and Their Clinical Implications in Chronic Spontaneous Urticaria.

This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI). We analyzed serum levels of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) in 50 CSU patients, comparing these to 38 healthy controls. The study examined the relationship between alarmin levels and clinical outcomes, including disease severity and QoL. Elevated levels of IL-33 and TSLP in CSU patients (p < 0.0001) highlight their potential role in CSU pathogenesis. Although IL-25 showed higher levels in CSU patients, this did not reach statistical significance (p = 0.0823). Crucially, IL-33's correlation with both UAS7 and DLQI scores underscores its potential as a biomarker for CSU diagnosis and severity assessment. Of the alarmins analyzed, IL-33 emerges as particularly significant for further exploration as a diagnostic and prognostic biomarker in CSU. Its substantial correlation with disease severity and impact on QoL makes it a compelling candidate for future research, potentially serving as a target for therapeutic interventions. Given these findings, IL-33 deserves additional investigation to confirm its role and effectiveness as a biomarker and therapeutic target in CSU.

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

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

IL-31-Pruritus Interleukin: Serum Values and Clinical Impact in Chronic Spontaneous Urticaria-A Romanian Retrospective Study.

(1) Background: This study aimed to evaluate the implications of interleukin-31 (IL-31) in the pathogenesis of chronic spontaneous urticaria (CSU) and to assess the differences that occur between its serum values compared to controls. Additionally, the serum IL-31 levels were measured alongside other clinical and paraclinical parameters that were identified in the patients to understand its immunological importance in this skin disease and to determine if it could potentially serve as a therapeutic target in CSU in the future. (2) Methods: The serum levels of IL-31 were estimated in 50 patients diagnosed with CSU according to the accepted international guidelines. Additionally, 38 controls who had not experienced any episodes of urticaria during their lifetime were included. (3) Results: Significantly elevated serum IL-31 levels were observed in CSU patients compared to the controls (p < 0.0001). Although no direct correlations were found between IL-31 and inflammatory markers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)), eosinophils, or total immunoglobulins E (IgE), significant differences in IL-31 levels were identified based on CSU severity, quality of life impact, itch intensity, and response to histamine H1 receptor antagonists (H1 antihistamines) (p < 0.05 for all). (4) Conclusions: Our findings underscore that IL-31 is not directly associated with general inflammation, eosinophilic response, or atopy in CSU. Nevertheless, its expression is influenced by key disease characteristics: severity, pruritus, and H1 antihistamine response. This investigation provides essential insights into CSU pathogenesis, potentially leading to novel therapeutic interventions. An enhanced understanding of these mechanisms is crucial due to the limitations of current treatment modalities in terms of fully managing CSU symptoms.

Comparing four immunosuppressive agents for chronic spontaneous urticaria-A network meta-analysis.

BACKGROUND: Immunosuppression is an integral part of treating chronic spontaneous urticaria (CSU), but there is no literature to evaluate the efficacy of multiple immunosuppressive agents. OBJECTIVE: The comparison of the efficacy, safety, and incidence of adverse effects of four immunosuppressive medicines (tripterygium glycosides, methotrexate, cyclosporine A, and azathioprine) in combination with antihistamines in treating CSU provides a clinical reference and evidence-based medicine for treating CSU. METHODS: PUBMED, The Cochrane Library, EMBASE, WANFANG, CNKI, CBM, and clinical trial registration platform were searched to collect relevant randomized controlled trials (RCT) and cohort studies of four immunosuppressive medicines combined with antihistamines for treating CSU. The primary outcomes were the efficacy of weekly urticaria activity score 7 (UAS7) and adverse effects. RESULTS: This study pooled data from seven randomized clinical trials with 410 participants. The standardized mean differences for change in UAS7 were 0.10 (95% confidence interval (CI), 0.01 to 0.68) for cyclosporine A plus antihistamine; 0.03 (95% CI, 0.00 to 0.23) for azathioprine plus antihistamine; 0.52 (95% CI, 0.32 to 0.85) for tripterygium glycosides plus antihistamine; and 1.54 (95% CI, 0.64 to 3.67) for methotrexate plus antihistamine. There were no significant differences in side effects between these medicines in the limited number of trials and clinical samples. CONCLUSION: Our results indicate that cyclosporine A combined with antihistamine resulted in greater improvements regarding the UAS7 in CSU patients and that tripterygium glycosides are also effective in treating CSU.

Consecutive injections of low-dose interleukin-2 improve symptoms and disease control in patients with chronic spontaneous urticaria.

PURPOSE: To describe the effectiveness and tolerability of low-dose interleukin (IL)-2 in treating patients with chronic spontaneous urticaria (CSU) refractory to H1-antihistamines. METHODS: This retrospective study included CSU patients who received treatment with at least one cycle of IL-2, injected intramuscularly at a dose of 1.0 million international units daily for 7 consecutive days, after failing treatment with H1-antihistamines. Patients were followed up for ≥12 weeks. RESULTS: Of the 15 patients, 7 (46.7%) and 11 (73.3%) achieved complete response at Week 2 and Week 12, respectively. The mean change of urticaria control test (UCT) and weekly urticaria activity score (UAS7) from baseline was 6.6 (95% CI, 4.2 to 8.9) and - 16.9 (95% CI, -24.0 to -9.8), respectively, at Week 12. Local injection-site reactions were the most common adverse events. No serious adverse events were reported. CONCLUSION: Low-dose IL-2 treatment improves symptoms and disease control for CSU patients refractory to H1-antihistamines.

Factors Associated With Refractoriness to an Up to Fourfold Dosage of Antihistamines in Isolated Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disease and has a significant impact on patients' quality of life. The aim of treatment is complete symptom control. AIM: To identify potential factors associated with antihistamine-refractory isolated CSU and to determine the factors that predict response to second-generation H1 antihistamines at dosages from one- to fourfold. METHODS: We conducted a retrospective cohort study, which included adult patients diagnosed with isolated CSU and had complete symptom control. Clinical and laboratory findings were compared between the patients who were responsive to second-generation H1 antihistamines (< fourfold) and those who were refractory to a fourfold dose. Clinical and laboratory data were compared by dosage in the antihistamine-responsive group. RESULTS: There were 182 isolated CSU patients who met the study criteria, of whom 150 (82.4%) were responsive to treatment with up to a fourfold dose of second-generation H1 antihistamines, while 32 (17.6%) were refractory. In univariate analysis, age at onset, body mass index, baseline Urticaria Activity Score-7 (UAS7), white blood cell count, total neutrophil count, neutrophil-lymphocyte ratio, platelet count, and new generation antihistamines were significantly higher in the antihistamine-refractory group. According to multivariate analysis, baseline UAS7 was the only independent factor associated with antihistamine-refractory isolated CSU (odds ratio 1.14, 95% CI 1.01-1.28, P = .03). In the antihistamine-responsive group, white blood cell count tended to predict response to antihistamine treatment (P < .001, 0.04, 0.34 between onefold and twofold, twofold and threefold, and threefold and fourfold, respectively). CONCLUSION: Baseline UAS7 was an independent factor associated with antihistamine-refractory isolated CSU.

Chronic Spontaneous Urticaria: An Etiopathogenic Study.

Importance: Exact etiopathogenesis of chronic spontaneous urticaria (CSU) remains elusive. Infections, pseudoallergens, autoimmunity, and contact sensitization are various postulated factors. Few studies are available measuring cytokine levels in CSU. Objectives: The aim was to study various etiological factors of CSU and levels of IL-6 and IFN-ϒ in cases and controls, and correlation between various etiologies with the levels of the abovementioned interleukins in the cases. Design: Case-control study performed over 2 years with no follow-up of the participants. Setting: It was a referral-center-based study. Participants: Sixty patients of CSU and equal age and sex-matched healthy controls were recruited on the basis of convenience sampling. Exposures: Biochemical and hematological investigations with hepatitis serology, thyroid function tests, anti-thyroid antibodies, and levels IL-6 and IFN-ϒ were performed in all cases and controls. All cases were subjected to ASST. Cases with all above negative tests were patch-tested with Indian standard series. Urticaria activity score (UAS7) was calculated for all the cases and repeated in patients with positive etiological factor after 3 weeks (improvement after allergen or drug avoidance, treatment of infection). Outcomes: To study the various etiological factors (food, infection, autoimmunity, autoreactivity, and contact sensitization) and the levels of IL-6 and IFN- γ in patients of chronic spontaneous urticaria. Results: Etiology was ascertained in 75% of patients (autoimmunity: 50%, contact sensitization: 21.67%, food and drug allergy: 1.67% each). Mean values of the interleukins and anti-thyroid antibodies were significantly higher in cases versus controls. Levels of IFN-ϒ were significantly elevated in patients with higher UAS7 scores. Conclusion: Antithyroid antibodies, ASST, and patch testing are important tools and should be considered in patients of CSU after a thorough history and history-based workup. Elevated levels of IL-6 and IFN- ϒ in cases suggest that both Th1 and Th2 type of immune responses are implicated in pathogenesis of CSU.

Ayurveda panchakarma treatment success in a case of chronic spontaneous urticaria non-responding to conventional medicine-A case study.

This is a case study of a 34-year-old male patient of Chronic Spontaneous Urticaria (CSU) with severe generalised itching and rashes all over the body since 17 years. The patient has no significant relief with conventional antihistamine therapies, AST (Autologous serum therapy) and Omalizumab (OMA). He was clinically assessed and managed with Ayurvedic Panchakarma procedures like Snehapana(therapeutic administration of unctuous formulation like ghee, oil), Vamana, Virechana and internal medication in line of Seethapitta Chikitsa. The patient was asked to monitor hives and itching daily for one week using a validated weekly Urticaria Activity Score (UAS7) at the baseline, after Vamana, after Virechana and after follow up. The Quality of life was assessed at the baseline and after follow-up using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL). The assessment showed complete remission in disease activity and improvement in Quality of life as per the scores. The hematological and biochemical investigations reflect the safety and efficacy of Ayurveda in management of CSU.

The impact of COVID-19 pandemic on the management of patients with chronic urticaria: An observational two-center study from Turkey.

The Coronavirus Disease 2019 (COVID-19) outbreak significantly affected the clinical practice in hospitals and the management of many diseases. The aim of this study was to evaluate the effect of pandemic-related factors on the severity and course of chronic urticaria (CU). A total of 194 CU patients who were on regular follow-up, were enrolled in the study. The disease activity was assessed by means of the weekly urticaria activity score (UAS7) and urticaria control test (UCT). Patients were divided into two subgroups according to their disease aggravation as "aggravated" and "non-aggravated". Two groups were compared in terms of demographic, clinical, COVID-19-associated parameters, and parameters related with the effect of COVID-19 pandemic on CU management. The omalizumab use was statistically higher (P = .017), and the systemic corticosteroid use was statistically lower (P = .025) in the "aggravated" group. Adherence to quarantine was significantly lower in the "aggravated" group (P = .027). 173 patients (89.2%) were unable to contact a dermatologist during the pandemic. Among 186 patients who received treatment for CU before the pandemic, 48 (25.8%) did not continue the existing treatment during the pandemic. CU aggravated in one patient with COVID-19 and remained stable in the other. This study showed that CU patients, especially those on omalizumab therapy, had difficulties in attending medical care and even in the maintenance of their existing therapies during the pandemic. Creating novel follow-up and treatment models as well as the increased use of teledermatology might be beneficial in the management of this life-disturbing condition.

Socio-economic burden and resource utilisation in Italian patients with chronic urticaria: 2-year data from the AWARE study.

INTRODUCTION: In Italy, the real-world evidence on the extent of adherence to guidelines and the benefits of recommended therapeutic medications and their impact on the quality of life (QoL) of H1-antihistamines (H1-AH) refractory chronic urticaria (CU) patients is limited. METHODS: AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) was a global prospective, non-interventional study of CU in real-world setting which included patients aged ≥18 years with a medically confirmed diagnosed of CU present for more than 2 months. In this study, the disease characteristics, pharmacological treatments and patient-reported outcomes (PROs) are reported. RESULTS: In total, 159 patients from 24 study centres in Italy completed the study. At baseline, 221 (89.5%) and 8 (3.2%) patients had chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), respectively, while 18 (7.3%) patients had concomitant CSU and CIndU. For CSU patients, mean dermatology life quality index and CU quality of life questionnaire scores reduced to 3.0 ± 4.9 and 14.6 ± 18.6 at Month 24 from baseline scores of 7.5 ± 6.6 and 33.2 ± 19.5, respectively, indicating an improvement in QoL. This was reflected in their work-life as work productivity impairment reduced considerably after 2 years. Only 71.9% CSU patients had a prior treatment, while during the study, 96.8% of the patients were treated with a medication. At baseline, only 52.9% CSU patients reported nonsedating H1-antihistamines as first-line of treatment in prior medication, this increased to 89.6% during current medication. CONCLUSION: This study shows that CSU has a considerable socio-economic burden and an improvement in QoL can be achieved in CSU patients if an appropriate therapeutic path is followed.

Improving of psychological status and inflammatory biomarkers during omalizumab for chronic spontaneous urticaria.

BACKGROUND: Depression and anxiety are the most common psychiatric comorbidities in chronic spontaneous urticaria (CSU). Omalizumab is a monoclonal antibody approved for CSU treatment. We evaluated the prevalence of anxiety and depression in CSU patients before and after treatment with omalizumab. MATERIALS & METHODS: A total of 30 patients were enrolled in the study: 15 patients affected by CSU and treated with omalizumab and the other 15 healthy subjects did not receive any systemic therapy. All patients were evaluated using Hospital Anxiety and Depression Scale, CRP and erythrocyte sedimentation rate, at baseline and after 6 months. RESULTS: The omalizumab group after 6 months of therapy had a decrease of all the scores and biomarkers. CONCLUSION: Omalizumab allowed an improvement of urticaria and mental comorbidities.

Chronic urticaria treatment patterns and changes in quality of life: AWARE study 2-year results.

BACKGROUND: A Worldwide Antihistamine-Refractory Chronic Urticaria (CU) patient Evaluation (AWARE) is a non-interventional, multicenter study including patients from Europe, Central and Latin America, Asia-Pacific, and the Middle East. AWARE describes real-world evidence for CU, including clinical characteristics, treatment patterns and the impact on quality of life. METHODS: Over the 2-year study, therapy changes, angioedema occurrence, and patient-reported outcomes (PROs) were recorded over 9 visits, including dermatology life quality index (DLQI) and 7-day urticaria activity score (UAS7). Data were stratified into subgroups: chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU), or CSU + CIndU. RESULTS: Out of 4838 patients analyzed, 9.9% were receiving no treatment for their CU symptoms at baseline, and 20.4% were receiving first-line non-sedating H1-antihistamine at approved doses. The predominant baseline therapy was up-dosed non-sedating H1-antihistamines (25.5%). By Visit 2, omalizumab was the overall most commonly used therapy (29.6%), increasing to 30.1% by the end of the study. Baseline DLQI scores for patients with CSU, CIndU and CSU + CIndU were 8.3, 7.6 and 9.1, respectively; scores decreased over the study for CSU and CSU + CIndU patients, but fluctuated for CIndU patients. Baseline angioedema occurrence was higher in CSU and CSU + CIndU patients, reported in 45.4% and 45.5% of patients, respectively, compared to 17.0% in CIndU patients. By the final visit, angioedema had decreased to 11.9% and 11.2% for CSU and CSU + CIndU, respectively, and 9.6% for CIndU. CONCLUSION: CU patients are undertreated at baseline; after entering the AWARE study, more patients received appropriate treatment. However, over two thirds are not escalated to third-line treatments.

Is vitamin D concentration an indicator of the severity of atopic dermatitis and chronic spontaneous urticaria in adults?

Atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) are common chronic and recurrent dermatoses. The role of vitamin D in the immunological processes, including the development of inflammation, has been the subject of numerous studies. The feasible measurement of vitamin D serum concentration and possibly supplementation necessitates the assessment of its impact on the clinical severity of mentioned diseases. AIM: The aim of the study was to determine the relationship between blood serum vitamin D concentration and the severity of clinical symptoms in the group of adults suffering from AD or CSU. MATERIALS AND METHODS: The study was conducted in 2018 on groups of patients suffering from AD or CSU. Serum vitamin D concentration was determined by electrochemiluminescence assay. Student's t-test was adopted to compare vitamin D levels between groups. Spearman's rank correlation coefficient was used to assess the correlation between vitamin D concentration and the severity of AD (according to the SCORAD scale) and CSU (according to the UAS 7 scale). RESULTS: There was not found any statistically significant relationship between the severity of skin lesions scores in the course of AD and CSU and serum vitamin D concentration.

Clinical characteristics and management of chronic spontaneous urticaria in patients refractory to H1-Antihistamines in Asia, Middle-East and Africa: Results from the AWARE-AMAC study.

BACKGROUND: Chronic urticaria (CU) is a condition characterized by recurrent itchy hives and/or angioedema for ≥6 weeks. Most of the data about CU come from western countries with very little information available about CU in Asia, Africa, and the Middle East. METHODS: AWARE-AMAC is a 24-month prospective, observational, real-world, non-interventional study in patients aged ≥18 years from Asia, the Middle East, and Africa (AMAC) with CU refractory to H1-antihistamines (H1-AH). The main objective was to describe the real-world experience with CU, including clinical characteristics, presence of angioedema, treatment patterns (shifts between treatment classes and changes within a treatment class), investigator-assessed disease control, and the impact on quality of life. Subgroups of interest were type of CU at Baseline and treatment class (based on 2013 urticaria guidelines). There were no mandatory visits and diagnostic/monitoring procedures additional to routine practice, except the patient diary (7-day Urticaria Activity Score) and patient reported outcome assessments. RESULTS: The focus of the current manuscript is on patients with chronic spontaneous urticaria (CSU), who formed 98% of the sample. Patients were predominantly female (69.6% female, mean age ± SD 39.8 ± 13.29 years). Time since current diagnosis (Mean ± SD) was 28.6 ± 49.06 months. Amongst patients with CSU, 31.0% had comorbid chronic inducible urticaria (CINDU) and 46.4% had a history of angioedema. 91.9% received H1-AH therapy (±other treatments). The most frequently prescribed treatment classes at Baseline were any/combination of medications, not classified under the other 7 treatment classes, named "Others" (30.5%) followed by, omalizumab (OMA; 23.6%) and second-generation H1-AH monotherapy (sgAH; 15.1%). At Month 12, the most prescribed treatment classes (>15%) for patients were OMA (23.5%) and "Other" (21.3%); 19.7% received "No drug". At Month 24, OMA (22.5%), and "Other" (17.9%) were most frequently prescribed; 28.6% received "No drug". Overall, 79.5% of patients had some type of change in treatment. Over the study period, improvement in self-reported QoL increased, which was mirrored by better disease control. CONCLUSION: In AMAC countries, the non-recommended "Other" treatment class played a major role in the initial management of CU patients. High usage of H1-AH (±other treatments) and OMA was observed. Treatment changes were observed in a majority of patients. Treatment escalation from sgAH was mostly via OMA. Improvement of disease control and QoL was achieved during the study period. TRIAL REGISTRATION: Observational study (NA).

Learnings from real-life experience of using omalizumab for chronic urticaria in Latin America.

BACKGROUND: Updated urticaria guidelines recommend that patients should be assessed for disease activity, severity, control, and quality of life at baseline and follow up. Regarding treatment, guidelines consider second generation antihistamines as the cornerstone in therapy for chronic urticaria (CU), while other drugs, such as omalizumab, are conceived as second-line alternatives. In regards to omalizumab, despite advances in the management of CU, there are still open questions about timing, dosing, and objective measures for clinical response. This study was designed to portray the use of patient-reported outcomes (PROs) in chronic urticaria management, as well as the effectiveness and treatment patterns of omalizumab in CU, as seen in a real-life setting in Latin America. METHODS: This is a retrospective observational study, involving 72 Latin American patients with chronic urticaria treated with omalizumab. Patient reported outcomes and treatment patterns, response, quality of life improvement and discontinuation were analyzed. RESULTS: From the 72 patients, 91.7% (n = 66) were assessed through PROs, where urticaria control test (UCT) was the most used (79.2%; n = 57). Overall, 80.0% (n = 44) responded to omalizumab at some point of the treatment. Omalizumab 300 mg was associated with earlier response compared to lower doses. Regardless of dosage, most patients assessed with CU-Q2oL improved quality of life (80.8%; n = 21). With respect to omalizumab discontinuation, 20.8% (n = 15) patients interrupted omalizumab before the 3rd month of treatment (p = .000). CONCLUSIONS: The present study highlights how the use of PROs and omalizumab in Latin America differ from guidelines' recommendations and clinical trials. Even though most patients were initiated under omalizumab 300 mg, most of them finished with lower doses. Regardless of dosage, most patients responded to omalizumab and improved quality of life at some point during treatment. However, such features were seen earlier with omalizumab 300 mg. Regarding treatment discontinuation, one-fifth of patients interrupted omalizumab before the third month.

Omalizumab normalizes the gene expression signature of lesional skin in patients with chronic spontaneous urticaria: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Omalizumab, a humanized recombinant monoclonal anti-IgE antibody, proved to be effective in patients with chronic spontaneous urticaria (CSU), including severe and treatment-refractory CSU. Here, we report omalizumab's effect on gene expression in skin biopsies from CSU patients enrolled in a double-blind, placebo-controlled study. METHODS: Chronic spontaneous urticaria patients (18-75 years) were randomized to either 300 mg omalizumab (n = 20) or placebo (n = 10) administered s.c. every 4 weeks for 12 weeks (NCT01599637). Lesional and nonlesional skin biopsies were collected from the same area of consenting patients and assessed at baseline and on Day 85 compared with skin biopsies from the same area of 10 untreated healthy volunteers (HVs). Gene expression data were generated using Affymetrix HG-U133Plus2.0 microarrays. Statistical analyses were performed using R packages. RESULTS: At baseline, 63 transcripts were differentially expressed between lesional and nonlesional skin. Two-thirds of these lesional signatures were also differentially expressed between lesional and HV skin. Upon treatment with omalizumab, >75% of lesional signatures changed to reflect nonlesional skin expression levels (different vs placebo, P < 0.01). Transcripts upregulated in lesional skin (vs nonlesional and/or HV skin) suggested increased mast cell/leukocyte infiltration (FCER1G, C3AR1, CD93, S100A8, and S100A9), increased oxidative stress, vascularization (CYR61), and skin repair events (KRT6A, KRT16). Lesional signatures were not modulated by treatment in nonresponders (defined based on UAS7 longitudinal changes ≥16). CONCLUSION: Omalizumab, in treatment responders, reverted transcriptional signatures associated with CSU lesion phenotype to reflect nonlesional/HV expression levels; this is consistent with observed omalizumab-mediated clinical improvement observed in patients with CSU.

Omalizumab in Chronic Spontaneous Urticaria Refractory to Conventional Therapy: An Italian Retrospective Clinical Analysis with Suggestions for Long-Term Maintenance Strategies.

INTRODUCTION: Omalizumab is indicated for the treatment of patients affected by chronic spontaneous urticaria (CSU) refractory to antihistamines. The aim of this study was to assess the efficacy, safety, and recurrence of symptoms in a real-life experience of omalizumab as an add-on therapy for H1-antihistamine-refractory CSU patients (refractory CSU). METHODS: A retrospective review of the clinical records of all refractory CSU treated with omalizumab at our dermatology center from June 2014 to April 2017 was performed. Patients previously treated with second-generation antihistamines at a fourfold increased dose without clinical responses at 4 weeks of treatment were selected. Omalizumab was administered at a single dosage of 300 mg every 4 weeks for 6 months. Disease severity was assessed using the 7-day Urticaria Activity Score (UAS7). RESULTS: Eighteen patients (14 women; mean age 51 years, range 25-74) were enrolled. Mean UAS7 at baseline was 27.3 (range 15-38). Symptoms improved in all patients at 4 weeks (UAS7 = 16.1, range 0-36). Treatment was completed in 17 patients (94.4%), and among these, a complete response (UAS7 = 0) was registered in 10 patients (58.8%). Adverse events included thrombocytopenia in 1 patient (5.6%) at 16 weeks; therapy was suspended after 20 weeks and the complication was resolved, resulting in a freedom from major adverse events of 94.4%. Symptom recurrence occurred in 3 patients (17.6%) at 4, 5, and 7 months from the end of the primary therapy. Retreatment with omalizumab was successful without any adverse effects. Mean follow-up was 9.5 months (range 1-28). CONCLUSION: Add-on omalizumab therapy for refractory CSU in a real-life setting seems to be effective and safe with a relatively low incidence of symptom recurrence. Further research should investigate personalized omalizumab treatment dosages and administration intervals, and the identification of biomarkers for future treatment algorithms.

[Chronic urticaria - new views on diagnosis and treatment of disease]. / Chronická koprivka - nové pohledy na diagnostiku a lécbu onemocnení.

Interest in chronic urticaria has grown in recent years, largely owing to the advent of new modes treatment especially in the form of the biologic preparation omalizumab. New scientific and clinical findings have not only facilitated a more comprehensive view of the disease but have streamlined the classification and diagnostic approach as well. Diagnostics are no longer burdened by cumbersome and lengthy investigative procedures into the etiology of urticaria, but are much more rapid and targeted bringing about more timely relief of the patient's symptoms. According to recent data, the impact of the illness onto the quality of life of the patient, especially in those with more severe forms of urticaria, can be quite devastating both physically and psychologically compared to other chronic diseases (e.g. coronary artery disease, etc.).

Relación entre el Nivel de Vitamina D y Urticaria Crónica Espontánea

Antecedentes: Se ha incrementado la evidencia que demuestra la conexión entre la diferencia/insuficiencia de Vitamina D con aumento de la incidencia, severidad y actividad de trastornos inmunes-inflamatorios. La urticaria crónica es un trastorno de la piel caracterizado por ronchas recurrentes durante más de 6 semanas, y se divide en espontánea o inducible por estímulos físicos. El objetivo principal del siguiente trabajo fue estudiar la relación que pueden tener los niveles de Vitamina D en suero de pacientes con diagnóstico de urticaria crónica espontánea (UCE) que asisten al Servicio de Alergia e Inmunología del Hospital Nacional de Clínicas y compararlos con un grupo control de pacientes sin urticaria. Material y Métodos: Es un estudio descriptivo, prospectivo en donde se estudiaron 27 pacientes con diagnóstico de urticaria crónica espontánea. Luego de confeccionar Historia Clínica compatible con el diagnóstico, se les otorgó un test (UAS7) para evaluar la gravedad de la enfermedad, se realizaron prubeas cutáneas con aeroalergénos y alimentos, se realizó test intradérmico de suero autólogo, laboratorio que incluía además el hemograma, el perfil tiroideo y hepático, serología para virus (Hepatitis B y C, VDRL y HIV), se dosaron niveles de Ig A, G, M, E, y de Vitamina D (D2+D3) a todos los pacientes para luego analizar los resultados y comparar con un grupo control de 16 adultos sanos. Resultados: Hubo diferencias significativas entre los valores séricos de Vitamina D del grupo con urticaria crónica con respecto al control p<0,0001. Conclusión: Este estudio encontró que los pacientes con UCE tienen valores séricos disminuidos de Vitamina D. Son necesarios más estudios acerca del rol de la Vitamina D en la patogénesis de la Urticaria Crónica.

Evidence demostrates the connection between vitamin D deficiency/insufficiency with increased incidence, severity and activity of immune-inflammatory disorders. Chronic urticaria is a skin disorder characterized by recurring hives for mores than 6 weeks, and is divided into spontaneous or inducible by physical stimuli. The main objective of this study was to study the relationship that serum vitamin D levels may have in patients diagnosed with Spontaneous Chronic Urticaria (SCU) who attend the Allergy and Immunology Service of the National Hospital of Clinics and compare them with a control group of patients without urticaria. Materla and Methods: This is a prospective descriptive study in which 27 patients with chronic urticaria spontaneously diagnosed were studied. After making clinical history compatible with the diagnosis, they were given a test (UAS7) to evaluate the severity of the disease. In adition to the hemogram, the thyroid and hepatic profile, serology for virus (Hepatitis B, C, VDRL and VIH), serum levels of immunoglobulins A, G, M, E and vitamin D (D2+D3) to all patients and then analyzed the results and compared with a control group of 16 healthy adults. Results: There were significant differences between serum vitamin D levels in the group with chronic urticaria compared to the control group (p<0,0001) Conclusion: This study found that patients with SCU have decreased serum vitamin D values. More studies are needed about the role of vitamin D in the pathogenesis of UC.