Clinical Characteristics, Investigations and Treatment in Children with Chronic Urticaria: An Observational Study.

Background and Objectives: The guidelines for chronic urticaria in children contain recommendations that are often based on adult studies. The diagnostic pathway has not been standardized and the effectiveness of anti-H1, omalizumab, montelukast, and systemic glucocorticoids is rarely reported in the pediatric population. There is a wide variation in the rate of remission of chronic urticaria between studies. The aim of this study is to enhance our understanding of pediatric chronic urticaria. Materials and Methods: This study enrolled 37 children with chronic urticaria aged from 0 to 18 years. Demographic parameters, medical history, clinical features, laboratory data and treatment information were collected. Children were treated with the recommended dosage of second-generation H1-antihistamines, which was increased by up to twofold. Omalizumab was added for refractory anti-H1 patients. A three-day course with systemic glucocorticoids was administered for severe exacerbations. Montelukast was administered to some children. Results: Wheals without angioedema were common. Chronic urticaria was spontaneous in 32 children (86.48%), inducible in 2 (5.41%), induced by a parasite in 1 and vasculitic in 2. Treatment of the potential causes of chronic urticaria was of no benefit, except for eradication of Dientamoeba fragilis. Chronic urticaria was resolved within three years in 45.9% of cases. Allergic diseases were present in nine children (24.32%) and autoimmune diseases were present in three (8.11%). All children were treated with anti-H1 at the licensed dose or at a higher dose. A partial or complete response to anti-H1 was observed in 29 (78.38%) patients. Montelukast showed no benefit. All children treated with omalizumab responded. Systemic glucocorticoids were successfully used to treat exacerbations. Conclusions: Our findings indicate that laboratory tests should not be routinely performed in children with chronic urticaria without clinical suspicion. However, comorbidities such as thyroid autoimmune disease and coeliac disease are suggested to be monitored over the chronic urticaria course. These clinical conditions could be diagnosed from the diagnostic framework of chronic urticaria. Increasing the dosage of anti-H1 and omalizumab was effective in children resistant to standard treatment but we still need further studies to generate a standard patient-centered treatment.

Acetylcholinesterase is regulated by exposure of ultraviolet B in skin keratinocytes: A potential inducer of cholinergic urticaria.

Cholinergic urticaria is a dermatological disease characterized by the presence of large patches of red skin and transient hives triggered by factors, such as exercise, sweating, and psychological tension. This skin problem is hypothesized to be attributed to a reduced expression of acetylcholinesterase (AChE), an enzyme responsible for hydrolyzing acetylcholine (ACh). Consequently, ACh is thought to the leak from sympathetic nerves to skin epidermis. The redundant ACh stimulates the mast cells to release histamine, triggering immune responses in skin. Here, the exposure of ultraviolet B in skin suppressed the expression of AChE in keratinocytes, both in in vivo and in vitro models. The decrease of the enzyme was resulted from a declined transcription of ACHE gene mediated by micro-RNAs, that is, miR-132 and miR-212. The levels of miR-132 and miR-212 were markedly induced by exposure to ultraviolet B, which subsequently suppressed the transcriptional rate of ACHE. In the presence of low level of AChE, the overflow ACh caused the pro-inflammatory responses in skin epidermis, including increased secretion of cytokines and COX-2. These findings suggest that ultraviolet B exposure is one of the factors contributing to cholinergic urticaria in skin.

Altered Sweat Composition Due to Changes in Tight Junction Expression of Sweat Glands in Cholinergic Urticaria Patients.

In cholinergic urticaria (CholU), small, itchy wheals are induced by exercise or passive warming and reduced sweating has been reported. Despite the described reduced muscarinic receptor expression, sweat duct obstruction, or sweat allergy, the underlying pathomechanisms are not well understood. To gain further insights, we collected skin biopsies before and after pulse-controlled ergometry and sweat after sauna provocation from CholU patients as well as healthy controls. CholU patients displayed partially severely reduced local sweating, yet total sweat volume was unaltered. However, sweat electrolyte composition was altered, with increased K+ concentration in CholU patients. Formalin-fixed, paraffin-embedded biopsies were stained to explore sweat leakage and tight junction protein expression. Dermcidin staining was not found outside the sweat glands. In the secretory coils of sweat glands, the distribution of claudin-3 and -10b as well as occludin was altered, but the zonula occludens-1 location was unchanged. In all, dermcidin and tight junction protein staining suggests an intact barrier with reduced sweat production capability in CholU patients. For future studies, an ex vivo skin model for quantification of sweat secretion was established, in which sweat secretion could be pharmacologically stimulated or blocked. This ex vivo model will be used to further investigate sweat gland function in CholU patients and decipher the underlying pathomechanism(s).

Navigating the diagnostic maze: A case presentation of C1q vasculitis mimicking hypocomplementemic urticarial vasculitis in a patient with systemic lupus erythematosus.

In rare instances, patients with SLE may exhibit atypical clinical manifestations, such as Hypocomplementemic Urticarial Vasculitis, which can pose diagnostic challenges. Here, we present a case report of a 28-year-old female with a history of SLE with lupus nephritis clase IV who developed HUV-like symptoms, ultimately leading to a diagnosis of C1q Vasculitis. This case underscores the importance of considering C1q Vasculitis in SLE patients presenting with HUV-like features and highlights Rituximab as a promising therapeutic option for managing this rare condition.

Analysis of coagulation factors in angioedema/urticaria: increased values of D-dimer and fibrinogen in isolated angioedema.

INTRODUCTION: Recent research has shown that blood coagulation and the extrinsic coagulation cascade are involved in the pathogenesis of chronic spontaneous urticaria (CSU), but little is known about the coagulation factors in angioedema. METHODS: This study included 58 participants: 29 patients with chronic angioedema (14 with isolated angioedema and 15 with angioedema with wheals) and 29 healthy controls (HCs). We compared the values of coagulation factors in patients with isolated angioedema to those with wheals. Plasma levels of D-dimer, fibrinogen, and factor VII were measured by enzyme-linked immunosorbent assay (ELISA) for all participants. RESULTS: Significantly higher D-dimer (p = 0.016; ε² = 0.381) and fibrinogen (p = 0.044; ε² = 0.331) levels were recorded in patients with angioedema (both groups) than in the HCs, with higher levels for angioedema with wheals. Factor VII and fibrinogen levels did not differ significantly between the groups with angioedema, but coagulation factors were more often elevated in both angioedema groups than in HCs. CONCLUSIONS: One characteristic of angioedema is an elevated blood coagulation potential, which may help produce fibrin and may be important in controlling angioedema attacks.

Research hotspots in urticaria: A bibliometric study of the top 100 most cited articles.

BACKGROUND AND PURPOSE: Urticaria is a prevalent recurrent skin allergic condition. Severe itching significantly impacts patients' quality of life. This paper aims to investigate the development status of urticaria through bibliometric analysis to predict future research hotspots and trends. METHODS: On October 29, 2023, a literature search was conducted in the Web of Science (WOS) database to collect urticaria-related publications. The top 100 most cited articles were charted, and VOSviewer software was utilized for the literature data analysis. A visual analysis was performed on the number of articles, journals, main researchers, keywords, and so on. RESULTS: The research involved 415 authors from 28 countries, published across 25 journals, ranging from 1963 to 2023. Marcus Maurer was the leading author, with the United States being the foremost country in urticaria research. CEH Grattan received the most citations, and The Medical University of South Carolina had the highest number of publications. Key research focuses include epidemiology, pathogenesis, drug therapy, and quality of life assessments. "Anti-high affinity IgE receptor α chain (FcεRIα)," "chronic idiopathic urticaria," "autoantibodies," "histamine-release" emerged as the keywords with the highest prominence. CONCLUSION: The field of urticaria research has attracted substantial attention over the past few decades, witnessing rapid development. This study highlighted the top 100 articles by citation frequency within the urticaria field. Bibliometric analysis revealed a shift in treatment methods from traditional antihistamines to biological agents, with significant emphasis on improving the quality of life in chronic urticaria management. These areas represent the current research focal points and indicate future trends in urticaria research.

Overexposure to ultraviolet radiation in solar urticaria.

A man in his 50s was diagnosed with solar urticaria following monochromated light testing that demonstrated exquisite photosensivity to ultraviolet (UV) A, UV B (UVB) and visible light.Treatment options for this photodermatosis are limited; UVB phototherapy is one modality that can be appropriate in some patients. This is administered at very low doses in a controlled environment to induce skin hardening.1 To self-treat his condition, the patient used a commercial sunbed on two occasions several days apart. He noted an immediate flare of solar urticaria after first use with associated dizziness. Following the second use, he felt generally unwell and was witnessed to lose consciousness and displayed jerky movements of his limbs while a passenger in a car. Investigations including a head MRI and an EEG were normal; an anoxic seizure caused by a flare of solar urticaria was later confirmed.Solar urticaria is a rare photodermatosis that is poorly understood and difficult to treat. The condition has a significant impact on the quality of life of patients. Severe cases can be associated with systemic symptoms that could be life-threatening.

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Histamine receptors are classified into 4 types: H1, H2, H3, and H4, each mediating distinct physiological effects and possessing its corresponding antagonistshat that can be used for the prevention and treatment of various diseases. Among them, H1 antihistamines are the fundamental medications in dermatology and are widely used in many diseases such as urticaria and atopic dermatitis. In recent years, with the emergence of novel antihistamines and the discovery of new potential indications for traditional H1 antihistamines, the clinical application of antihistamines is facing new challenges. Further investigation of the novel mechanism for H1 antihistamines, the use of multiple doses of common drugs and potential indications will furnish vital insights for practical clinical application.

Global, regional, and national levels and trends in burden of urticaria: A systematic analysis for the Global Burden of Disease study 2019.

Background: Urticaria places a significant burden on individuals and society due to its widespread nature. The aim of this study was to evaluate the burden of urticaria in different regions and nations by analysing data from the Global Burden of Disease study 2019 (GBD 2019), with the goal of providing information to health care policymakers. Methods: By utilising data from the GBD 2019 database, this study analysed metrics such as incidence, prevalence, disability-adjusted life years (DALYs), age-standardised rate (ASR), and estimated annual percentage changes (EAPC) globally and across 204 countries and regions. The data was further stratified by age, sex, and sociodemographic index (SDI). Results: In 2019, global incidence cases, prevalence cases, and overall disease burden as measured by DALYs all increased. The distribution of the burden exhibited marked geographical heterogeneity. At the regional level, the burden is highest in Central and Eastern Europe and Central Asia, with the strongest growth in South Asia, compared with a decline in the high-income Asia Pacific. At the country level, Nepal reports the highest burden of urticaria, while Portugal has the lowest. Gender and age analyses showed that the burden of urticaria is higher in females than in males, with urticaria cases declining with age, especially in children, and picking up among the elderly. The study also finds a correlation between the burden of urticaria and the SDI, with the central part of the SDI showing a consistent increasing trend. Conclusion: This study found that the global burden of urticaria has risen from 1990 to 2019. Factors like geographic location, gender, and SDI influenced the urticaria burden. Overall, these results offer a resource to guide public health strategies seeking to reduce the burden of urticaria.

The role of the environment in allergic skin disease.

PURPOSE OF REVIEW: This paper explores how environmental factors influence allergic skin diseases, including atopic dermatitis (AD), contact dermatitis (CD), urticaria, angioedema, and reactions to drugs and insect bites. RECENT FINDINGS: Research indicates a significant impact of environmental elements on allergic skin diseases. High air pollution levels exacerbate symptoms, while climate change contributes to increased skin barrier dysfunction, particularly affecting AD. Allergen prevalence is influenced by climate and pollution. Irritants, like those in detergents and cosmetics, play a major role in CD. Plants also contribute, causing various skin reactions. Understanding the interplay between environmental factors and allergic skin diseases is crucial for effective management. Physicians must address these factors to support patient well-being and promote skin health amidst environmental changes.

Update on Urticaria and Angioedema.

Urticaria and angioedema are caused by immunoglobulin E- and non-immunoglobulin E-mediated release of histamine and other inflammatory mediators from mast cells and basophils. Diagnosis is made clinically, and anaphylaxis must be ruled out if urticaria or angioedema is present. A limited nonspecific laboratory workup should be considered unless elements of the history or physical examination suggest specific underlying conditions. The mainstay of treatment is avoidance of triggers when and if triggers are identified. The first-line pharmacotherapy is second-generation H1 antihistamines, which can be titrated to greater than standard doses.

Biomarkers to predict therapeutic response in chronic spontaneous urticaria: a review.

Chronic spontaneous urticaria (CSU) is a relatively common dermatological disorder characterized by sudden and unpredictable onset of pruritic wheals and/or angioedema, for more than six weeks. It is a mast cell-mediated histaminergic disorder, considerably worsening patients' quality of life. Current treatment options include anti-histamines, omalizumab and cyclosporine, in a step-wise algorithmic approach, aimed at complete symptom control. Patients do not respond uniformly to these therapeutic options due to phenotypic and endotypic heterogeneity, and often remain uncontrolled/poorly controlled. Recent research is focused on identifying certain biomarkers to predict therapeutic response and facilitate patient-targeted personalized treatment, for maximum benefit. The current article summarizes various biomarkers explored to date, and also elaborates their role in predicting therapeutic response to anti-histamines, omalizumab and cyclosporine, in CSU patients. High disease activity, elevated CRP/ESR and elevated D-dimer are the most important predictors of non/poor-response to antihistamines. Low and very low baseline IgE, elevated CRP/ESR, ASST+, BAT/BHRA+, basopenia, eosinopenia, and elevated D-dimer are predictors of poor and good response to omalizumab and cyclosporine, respectively. Additionally, normal or slightly elevated baseline IgE and FceR1 overexpression are predictors of a faster response with omalizumab. However, none of these predictors have so far been completely validated and are not yet recommended for routine use. Thus, large-scale prospective studies are needed to confirm these predictive biomarkers and identify new ones to achieve the goal of personalized medicine for CSU.

Overview of Dermatological Manifestations Associated with the COVID-19 Infection.

COVID-19 is an infectious disease caused by SARS-CoV-2 that is characterized by respiratory symptoms, fever, and chills.[1] While these systemic symptoms are widely known and well understood, there have also been reports of dermatological manifestations in patients with COVID-19. These manifestations include chilblain-like lesions, maculopapular lesions, urticarial lesions, necrosis, and other varicella-like exanthems.[2] The pathogenesis of these lesions are not well understood, but the procoagulant and pro-inflammatory state induced by COVID-19 infections may be contributing to varied cutaneous manifestations.[3] Drug interactions and concurrent hypersensitivity reactions have also been postulated.[4] This review aims to compile and analyze various retrospective studies and case reports to summarize the clinical presentation of dermatological lesions associated with COVID-19 infections and suggest further areas of research.

An overview of a preliminary multicenter retrospective study on food and drug allergies in Moroccan pediatric population.

Introduction: this study aimed to investigate the prevalence and management of food allergies (FA) and drug allergies (DA) in Morocco. Sparse and conflicting epidemiological data exist on the exact prevalence of allergies in the country. The rise in allergies can be attributed to various factors. Methods: the study analyzed data from patients with suspected FA and DA who sought medical attention. Statistical tests were used to analyze the data, percentages were computed for qualitative variables, and for quantitative variables, medians or means accompanied by standard deviations (SD) were calculated. The Chi-square test was employed to assess categorical variables. A p-value < 0.05 was considered statistically significant. Results: Cow's milk was the most reported food allergen (58.2%), followed by egg and nuts (23.4% and 12.1%, respectively). The most affected age group was children under 5 years. Antibiotics were the leading cause of reported drug allergies (44.8%), particularly Beta-lactams. Immediate reactions were commonly associated with antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). Symptoms of FA included acute urticaria, vomiting, anaphylactic shock, and facial edema. Urticaria was the most frequent symptom of DA. Antihistamines and corticosteroids were the main treatments used for both FA and DA. Conclusion: the prevalence of FA and DA in Morocco remains uncertain due to limited data. There is a need for centralized data collection and awareness among clinicians and the general population regarding allergies. The study highlights the importance of proper diagnosis and management of allergies to ensure patient safety. The findings emphasize the necessity of establishing a mandatory center for allergy care in Morocco to improve the understanding and management of allergic conditions.

Increased Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Chronic and Severe Urticaria.

Chronic spontaneous urticaria (CSU) is a disturbing skin condition often severely detrimental to quality of life. Haematological markers of inflammation such as neutrophil-to-lymphocyte and platelet-to-lymphocyte may be used in the assessment of inflammatory skin diseases. Their usefulness in urticaria is unknown. Neutrophil- to-lymphocyte, platelet-to-lymphocyte, and total serum IgE were investigated in urticaria patients: acute spontaneous urticaria (ASU) versus CSU, children versus adults with CSU, and patients with mild-to-moderate versus severe CSU. This retrospective cohort study included patients of all ages diagnosed with urticaria between 2005 and 2020 and blood counts within 30 days of diagnosis. Patients with comorbidities influencing blood cells (infection, surgery, malignancy) were excluded. Neutrophil-to-lymphocyte and platelet-to-lymphocyte were evaluated in patients with ASU vs CSU and mild-to-moderate CSU vs severe CSU (defined by the use of systemic medications or hospitalizations). A total of 13,541 urticaria patients were included in the study. CSU patients (n = 5,021) had higher neutrophil-to-lymphocyte and platelet-to-lymphocyte, as well as serum IgE levels compared with ASU patients (n = 8,520). Adults had higher neutrophil-to-lymphocyte and platelet-to-lymphocyte than children. Severely affected patients (n = 53) had higher neutrophil-to-lymphocyte and platelet-to-lymphocyte compared with mild-to-moderately affected patients (n = 4,968). Patients with higher neutrophil-to-lymphocyte and platelet-to-lymphocyte had higher odds of having CSU rather than ASU and severe urticaria rather mild-to-moderate. In conclusion, neutrophil-to-lymphocyte and platelet-to-lymphocyte are simple and available markers that can be used to predict and assess severe and chronic urticaria.

Clinical Impacts of Omalizumab on the Psychiatric Comorbidities of Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis.

Individuals with chronic spontaneous urticaria (CSU) experience significant sleep disturbances and are at risk of anxiety and depression.

UCOMB-real life data: treatment strategies for chronic urticaria patients with comorbidities.

BACKGROUND: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities. METHODS: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines. RESULTS: Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria. CONCLUSIONS: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.