Urticaria Research Articles

Chronic Spontaneous Urticaria Severity in Association with the Severity of Anxiety and Depression among Egyptian Patients

Abstract Background Urticaria is a condition characterized by the development of wheals (hives), angioedema, or both. Chronic urticaria (CU) is defined as the presence of urticaria for a period exceeding 6 weeks, assuming symptoms for most days of the week. It is divided into chronic inducible urticarias and chronic spontaneous urticaria (CSU), previously termed chronic idiopathic urticaria. The latter designation emphasizes that patients can experience urticaria independent of any exogenous stimulus even if one can define circumstances that may worsen symptoms. Approximately 40% of patients with chronic spontaneous urticaria report accompanying episodes of angioedema, whereas 10% have angioedema as their primary manifestation. In most cases, it is a self-limiting disorder, persisting for 2 to 5 years in most cases, although 20% of patients suffer for more than 5 years. Objective To assess the severity of CSU; screen CSU patients for psychiatric illnesses i.e. Anxiety and Depression and to assess the severity of Anxiety and Depression in patients with CSU. Patients and Methods This was a cross-sectional analytical study that was conducted at allergy clinic Ain-Shams University Hospitals on 300 patients with chronic urticarial, Study Period was 6 months. Results Our study revealed that, there were statically significant Positive correlation Between UAS score and GHQ (Anxiety) score, GHQ (Depression) score, BDI score and HAS score. In this study, there was highly statistically significant difference between HAS level and UAS level. There was highly statistically significant difference between BDI level and UAS level. Conclusion Our data show that patients with CSU experience high rates of anxiety and depression. CSU disease activity affects the severity of depression. CSU patients with high disease activity should be explored for comorbid depression. Females were more likely than men to have CUS and more affected by anxiety and depression than males.

Sleep quality in patients with chronic spontaneous urticaria and relation with Orexin-A, leptin, and ghrelin.

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.

Chronic spontaneous urticaria: diagnosis, treatment, and management

Chronic spontaneous urticaria (CSU) is a disabling condition in which recurrent wheals, with or without angioedema, occur for over 6 weeks. CSU occurs in up to 1% of the general population at any time and, on average, lasts 2–5 years in duration. Standard therapy for CSU includes second-generation antihistamines and omalizumab. However, 25%–50% of patients are refractory to these treatments. CSU profoundly impairs patients’ quality of life and has a substantial societal impact, including significant health care costs and decreased work productivity. These factors underscore the importance of health care providers to be familiar with the diagnosis and management of this condition. This article reviews the epidemiology, pathogenesis, aggravating factors, clinical manifestations, diagnostic assessment, and treatment of CSU.

What can be learned from real-world data about chronic spontaneous urticaria?

Background: Chronic spontaneous urticaria (CSU) is a common disease with complex pathogenesis. Patients' clinical characteristics and responses to treatment vary. Objective: We aimed to investigate the role of data obtained from routinely recommended tests in predicting the response to omalizumab, the only biologic agent approved for treatment, and in defining the clinical characteristics of the patients. Methods: A retrospective study of patients who started omalizumab treatment for CSU between 2015 and 2022 at the Department of Dermatology, Pamukkale University, was conducted. Response criteria were based on the urticaria control test, and patients with a urticaria control test score <12 at 6 months were considered treatment non-responders. Eosinophil and basophil counts, neutrophil-lymphocyte ratio (NLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and total immunoglobulin E (IgE) levels of the patients were evaluated before treatment and at the sixth month of treatment. Results: A total of 23.1% of the patients were unresponsive to omalizumab. The response rate to the omalizumab treatment of the patients with a total IgE level ≤ 30 IU/L (n = 4 [5.7%]) was significantly lower than patients with total IgE level > 30 IU/L (n = 66 [94.3%]) (p = 0.015). The mean ± standard deviation SIRI levels were significantly higher in non-responders versus responders (1.53 ± 1.03 versus 1.15 ± 7.76; p = 0.026). Eosinophil counts positively correlated with basophil counts (r = 587; p < 0.001) and IgE levels (r = 0.290; p = 0.005) but a negative correlation was found with levels of NLR (r = -0.475; p < 0.001), SIRI (r = -0.259; p = 0.013), and SII (r = -0.285; p = 0.006). NLR levels were lower in CSU patients with atopy, than in those without atopy (1.9 ± 0.9 vs 2.9 ± 2.1, p = 0.022). Conclusion: We suggest that eosinopenia and high NLR levels are linked to autoimmune CSU. Predicting a poor response to omalizumab seems possible with total IgE levels < 30 IU/L and high SIRI levels.

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

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

Tuning fluorescence of fexofenadine by switching OFF intramolecular photoinduced electron transfer: Application to development of one-step green and high throughput microwell spectrofluorimetric assay for analysis of tablets and plasma.

Fexofenadine (FEX) is a non-sedating antihistamine commonly used for the treatment of allergic conditions such as seasonal rhinitis and chronic idiopathic urticaria. This study describes the tuning "ON" the intrinsic fluorescence of FEX by switching "OFF" its intramolecular photoinduced electron transfer (PET) through the protonation of the piperidinyl nitrogen atom using sulfuric acid. The resulting fluorescence was utilized as a basis for the development of a highly sensitive microwell spectrofluorimetric assay (MW-SFA) for the one-step determination of FEX in pharmaceutical tablets and plasma. The linear range of the assay was 10-500 ng ml-1, and its limit of quantitation was 25.9ng ml-1. The proposed MW-SFA was successfully applied to analyze FEX in pharmaceutical tablets and plasma samples, demonstrating good accuracy and precision. The greenness of the assay was confirmed using three metric assessment tools. In conclusion, the MW-SFA is a straightforward, single-step analysis that requires no experimental adjustments. It offers high sensitivity, efficient sample processing, and environmental sustainability. This assay is highly recommended for pharmaceutical quality control and clinical lab use, particularly for measuring FEX levels.

A highly sensitive spectrofluorimetric method for the determination of bilastine in human plasma: Application of content uniformity testing.

Bilastine, a new second generation antihistaminic drug, has been widely used for relieving symptoms of allergic rhinitis and urticaria without a sedative effect. A simple, cost-effective, and highly sensitive fluorimetric method was developed for the estimation of bilastine in human plasma, in addition to its pure state and tablets. The suggested method depended on binary complex formation of eosin with bilastine in a buffered medium at pH 4.2. The formed complex resulted in quantitative quenching of eosin emission at 538 nm after excitation at 335 nm. This method demonstrates a broad range of linearity, spanning from 200 to 1000 ng/mL, and exhibits exceptional sensitivity, with a limit of detection and quantitation of 30.85 and 93.48 ng/mL, respectively. In addition, this spectrofluorimetric method may be employed to determine the amount of bilastine in human plasma and tablets with satisfactory accuracy and excellent precision. Furthermore, the content uniformity of bilastine in commercially available tablets was successfully tested by this approach. Compared with the reference method, there were no significant variations in terms of precision or accuracy. In conclusion, the proposed protocol is highly recommended to quantitatively estimate bilastine in different quality control settings.

Knockdown of miR-155 alleviates skin damage in rats with chronic spontaneous urticaria by modulating the JAK/STAT signaling pathway

ObjectiveThe aim of this study was to investigate the role and mechanisms of miR-155 in chronic spontaneous urticaria (CSU).MethodsThe expression level of miR-155 in the skin tissues of patients with CSU and experimental rats were detected by RT-qPCR, followed by the measurement of the histamine release rate in the serum through the histamine release test. Besides, hematoxylin & eosin staining was used to observe the pathological changes of the skin tissues; Corresponding detection kits and flow cytometry to measure the changes of immunoglobulins, inflammatory cytokines and T cell subsets in the serum of rats in each group; and western blot to check the expression level of proteins related to JAK/STAT signaling pathway in the skin tissues.ResultsKnockdown of miR-155 reduced the number and duration of pruritus, alleviated the skin damage, and decreased the number of eosinophils in CSU rats. Moreover, knockdown of miR-155 elevated the serum levels of IgG and IgM, decreased the levels of IgA and inflammatory cytokines, and reduced the proportion of CD4 + and CD4 + CD25 + T cells, as well as the CD4+/CD8 + ratio in CSU rats. However, Tyr705 intervention could reverse the effects of knockdown of miR-155 on CSU model rats. Furthermore, we found that knockdown of miR-155 significantly reduced the protein expression of IRF-9, as well as the P-JAK2/JAK2 and P-STAT3/STAT3 ratios in the skin tissues of CSU rats.ConclusionKnockdown of miR-155 can alleviate skin damage and inflammatory responses and relieve autoimmunity in CSU rats by inhibiting the JAK/STAT3 signaling pathway.

Do Cytokines Play a Role in Chronic Spontaneous Urticaria in Childhood? IL-17 One of Them?

Do Cytokines Play a Role in Chronic Spontaneous Urticaria in Childhood? IL-17 One of Them?

P040 A prospective study to assess the association of serological markers (interleukins 17, 31 and 33) with disease severity and response to antihistamines in paediatric chronic spontaneous urticaria

P040 A prospective study to assess the association of serological markers (interleukins 17, 31 and 33) with disease severity and response to antihistamines in paediatric chronic spontaneous urticaria

CD14 Efficacy of narrowband ultraviolet B phototherapy vs. low-dose oral ciclosporin as second-line management in antihistamine-refractory chronic spontaneous urticaria: a noninferiority, randomized study

CD14 Efficacy of narrowband ultraviolet B phototherapy vs. low-dose oral ciclosporin as second-line management in antihistamine-refractory chronic spontaneous urticaria: a noninferiority, randomized study

Cyclosporine for the treatment of chronic spontaneous urticaria refractory to antihistamines and omalizumab: a case series

Cyclosporine for the treatment of chronic spontaneous urticaria refractory to antihistamines and omalizumab: a case series

Clinico-Epidemiologic Profile and Response to Levocetirizine in Chronic Spontaneous Urticaria: A Retrospective Cohort Study from a Tertiary Care Center in North India.

Comprehensive long-term follow-up data regarding chronic spontaneous urticaria (CSU) among general populations, especially from the Indian subcontinent is scanty. The aim of the study were to analyze the clinico-epidemiological profile, comorbidities of CSU patients, and factors affecting patient response to various doses of levocetirizine. In this retrospective cohort study, complete history regarding demographic profile, clinical examination, investigations, treatment given, and follow-up details of all CSU patients attending urticaria clinic between 2010 and 2019 were analyzed. These were considered variables to determine the factors playing a role in response to various doses of levocetirizine. Totally, 1104 files of CSU were analyzed. The male-to-female ratio was 1:1.5 with a mean age of 33.03 ± 14.33 years. Thyroid dysfunction and atopy were seen in 142 (12.8%) and 184 (16.7%) patients, respectively. Vitamin D deficiency and high serum immunoglobulin E (IgE) levels were seen in 461 (41.7%) and 340 (30.7%) patients, respectively. Immunosuppressives were required at some point in 196 (17.7%) patients. Patients with higher levels of serum IgE and D-dimer (P < 0.05) were found to require frequent updosing of levocetirizine, while age, sex, duration of illness, presence of angioedema, co-morbidities, identifiable precipitating factors, presence of diurnal variation, family history, and vitamin D deficiency were found to not have an effect on levocetirizine dosing. Ours is a large single-center study exemplifying the biomarkers including baseline serum IgE and D-dimer levels, which could identify a CSU patient who could warrant a higher dose of antihistamine/antihistamine refractory urticaria.

Mas-Related G-Protein Coupled Receptor-X2 and Chemokine (C-C Motif) Ligand 2 Correlate With Disease Activity Among Treatment-Naïve Chinese Patients With Chronic Spontaneous Urticaria.

Mas-Related G-Protein Coupled Receptor-X2 and Chemokine (C-C Motif) Ligand 2 Correlate With Disease Activity Among Treatment-Naïve Chinese Patients With Chronic Spontaneous Urticaria.

Эффективность и безопасность применения эбастина у больных хронической спонтанной крапивницей

Эффективность и безопасность применения эбастина у больных хронической спонтанной крапивницей

Basophil and eosinophil recruitment to skin lesions is linked to features of autoimmune chronic spontaneous urticaria including basopenia

Basophil and eosinophil recruitment to skin lesions is linked to features of autoimmune chronic spontaneous urticaria including basopenia

A Retrospective Analysis of Cases of Chronic Spontaneous Urticaria on Treatment with Oral Tofacitinib

A Retrospective Analysis of Cases of Chronic Spontaneous Urticaria on Treatment with Oral Tofacitinib

Treatment options in refractory chronic spontaneous urticaria.

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.

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

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

Unveiling Treatment Response Predictors in Predominant Subtypes of Chronic Inducible Urticaria.

Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria (CU), which requires specific triggers to occur. Despite their common occurrence, treatment response rates and predictors of treatment responses are largely lacking in the literature. This study evaluates antihistamine (AH) and omalizumab response rates in the most common CIndU subtypes and examines whether certain features can predict treatment responses. We retrospectively analyzed CU patients with at least one CIndU subtype and performed comparisons between subgroups, in a total of 423 patients (70% CIndU, 30% chronic spontaneous urticaria [CSU] plus CIndU). The treatment response rates in CIndU were 51.6%, 51.5%, and 86.5% with standard-dose second-generation H1-antihistamines (sgAHs), updosed/combined sgAH, and omalizumab, respectively. Overall AH response was higher in CIndU than CSU plus CIndU (78.3% vs. 62%, p = 0.002) and in symptomatic dermographism (SD) and cold urticaria (ColdU) than cholinergic urticaria (ChoU) (83.2% vs. 78.3 vs. 60.9%, p = 0.04). AH-refractory patients had a longer disease duration (45.2 ± 56.7 months vs. 37 ± 51.9 months, p = 0.04), more angioedema, accompanying CSU, mixed CIndU subtypes (37.5% vs. 21.1%, p = 0.003; 45.1% vs. 27.1%, p = 0.002; 8.8% vs. 2.4%, p = 0.014), and lower baseline urticaria control test scores (5.86 ± 3.3 vs. 8.6 ± 3.6, p &lt; 0.001) than AH-responsive patients. CIndU exhibits a good response to both AHs and omalizumab. Notably, the response to AHs is more pronounced in SD and ColdU compared to ChoU. Disease duration, angioedema, accompanying CSU, mixed CIndU, and lower baseline UCT scores may be used to predict AH treatment outcome in CIndU.