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.

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).

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.

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.

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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.

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.

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.

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.

Efficacy and safety of Xiaofeng powder in the treatment of chronic urticaria: A systematic review and meta-analysis.

BACKGROUND: Chronic urticaria is a group of skin diseases characterized by pruritus and/or vascular oedema and belongs to the category of "addictive rash" in Traditional Chinese Medicine, and its aetiology is closely related to wind evil. Antihistamines are often used in treatment. Although they have certain effects, they also easily cause disease recurrence. Xiaofeng powder treats this disease has a significant effect in improving the disease state and reducing the recurrence rate. However, there is a lack of evidencebased research. This study to systematically evaluate the clinical efficacy of modified Xiaofeng powder in the treatment of chronic urticaria (CU). METHODS: Computer searches of Chinese databases such as China National Knowledge Infrastructure, China Scientific Journal Database, China Biomedical Literature Database, and WanFang Date and foreign databases such as PubMed and the Web of Science were performed. We retrieved published clinical randomized controlled trials of Xiaofeng powder in the treatment of CU from the establishment of the databases to November 2023. The data were extracted from clinical trials that met the inclusion criteria of this study, and the quality was evaluated through the Cochrane Handbook of Systematic Reviews 5.1.0. Finally, a meta-analysis was performed using RevMan 5.3 statistical software. RESULTS: A total of 11 randomized controlled trials involving 1076 patients were included. The cure rate odds ratio (OR) and 95% confidence interval (CI; shown in brackets) were 2.11 [1.45, 3.07]; the total effective rate OR and CI were 2.42 [1.60, 3.68]; the recurrence rate OR and CI were 0.22 [0.15, 0.34]; the adverse reaction rate OR and CI were 0.23 [0.12, 0.45]; and the mean weighted mean difference (MD) and 95% CI (shown in brackets) of itching degree, wind mass size, wind mass number and wind mass duration in symptom and sign integrals were -0.70 [-0.73, 0.67], -0.64 [-0.96, 0.31], , -0.72 [-1.23, 0.22], and -0.68 [-1.13, 0.23], , respectively. CONCLUSION: The clinical efficacy of modified Xiaofeng powder in the treatment of CU is better than that of antihistamine drugs, with lower adverse reaction and recurrence rates and higher safety. However, the quality of clinical research included is relatively low, and findings need to be confirmed by high-quality research.

Immunopathogenesis of urticaria: a clinical perspective on histamine and cytokine involvement.

BACKGROUND: Urticaria is a clinical condition characterized by the appearance of wheals (hives), angioedema, or both. Over the last several decades, a better understanding of the mechanisms at play in the immunopathogenesis of urticaria has underscored the existence of numerous urticaria subtypes. Separating the different kinds of urticaria explicitly helps find the best detection method for the management of this skin disorder. Subtypes of urticaria also include both spontaneous and physical types. The conventional ones include spontaneous urticaria, constituting both acute and chronic urticaria. Therefore, a broad and effective therapy is essential for the diagnosis and treatment of urticaria. METHODS: To understand the immunopathogenesis of urticaria, various databases, including PubMed, Scopus, and Web of Science, were used to retrieve original articles and reviews related to urticaria. While information on several clinical trials were obtained from clinicaltrials.gov database. RESULTS: This article highlights the immunopathogenesis involved in the intricate interaction between cellular infiltration, immune reactions, coagulation cascades, and autoantibodies that underlie urticaria's pathophysiology. CONCLUSION: The recent progress in understanding urticaria can help to understand the intricate characteristics in the immunopathogenesis of urticaria and could play a beneficial role in the management of urticaria.

Impact of Chronic Spontaneous or Inducible Urticaria on Occupational Activity.

The impact of chronic urticaria on work has been scarcely reported, whereas its peak incidence is between the ages of 20 and 40. The aim of this study was to assess the occupational impact of chronic urticaria and its treatment, by combining objective and patient-reported data. A monocentric observational study was performed using questionnaires over a 1-year period from 2021 to 2022 in chronic urticaria patients who were in a period of professional activity and agreed to participate. Of the 88 patients included, 55.7% assessed the occupational impact of their chronic urticaria as significant, and even more severe when chronic urticaria was poorly controlled. Some 86% of patients had symptoms at work, in a third of cases aggravated by work. However, occupational physical factors were not associated with an aggravation of inducible chronic urticaria. A total of 20% reported treatment-related adverse effects affecting their work. Despite low absenteeism, presenteeism and reduced productivity were important (> 20%). Six patients (6.8%) had difficulties keeping their work. For 72.7% of the patients, the occupational physician was not informed. The occupational impact of chronic urticaria should be discussed during consultations, particularly when it is insufficiently controlled. The occupational physician should be informed in order to support patients' professional project.

Urticaria Pigmentosa Without Pruritus.

Mastocytosis is a group of disorders characterized by the pathologic accumulation of mast cells in various tissues. One example of mastocytosis is urticaria pigmentosa, which presents with mastocytomas that can cause hives and, when irritated, pruritus. To our knowledge, we are describing the first case of urticaria pigmentosa without pruritus. The patient had a positive Darier's sign, stated that they never felt itchy, and denied ever using a topical steroid or antihistamine. Although our patient declined additional testing, patients like this may benefit from a detailed evaluation of their sensory system through both quantitative sensory testing and genetic analysis. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.7558e.

The relationship between sleep quality and chronotype differences and urticaria severity in patients with chronic spontaneous urticaria.

INTRODUCTION: Chronic spontaneous urticaria (CSU) is characterized by persistent or recurrent pruritic lesions that last more than 6 weeks. Patients with CSU may experience sleep disturbances, particularly due to itching. Biological rhythms (chronotypes) are categorized as morningness, intermediate, and eveningness types. This study evaluates the relationship between sleep quality, chronotype, and disease severity in CSU patients. METHODS: The study included 53 CSU patients and 50 healthy controls. A sociodemographic data form was completed, and the disease severity was determined utilizing the Urticaria Activity Score over 7 days (UAS7). The Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), and Pittsburgh Sleep Quality Index (PSQI) scales as well as the Morningness-Eveningness Scale (MEQ) were applied to the participants. RESULTS: The CSU group had a significantly higher body mass index (BMI) than that of the healthy control group. In terms of sleep and chronotype scales, compared to the control group, the CSU group had higher ISI scores as well as subscale scores on the PSQI subscales, with the exception of habitual sleep efficiency and total PSQI scores. There was no difference between MEQ scores. In the correlation analysis, the UAS7 and PSQI total scores were found to be correlated, whereas in the logistic regression analysis the estimated relative risk of BMI and PSQI total score for CSU was found to be 1.13 and 1.45, respectively. CONCLUSIONS: When dealing with CSU patients, it is necessary to conduct a sleep quality assessment as part of a holistic evaluation.

Bumble bee microbiota shows temporal succession and increase of lactic acid bacteria when exposed to outdoor environments.

Question: The large earth bumble bee (Bombus terrestris) maintains a social core gut-microbiota, similar as known from the honey bee, which plays an important role for host health and resistance. Experiments under laboratory conditions with commercial hives are limited to vertically transmitted microbes and neglect influences of environmental factors or external acquisition of microbes. Various environmental and landscape-level factors may have an impact on the gut-microbiota of pollinating insects, with consequences for pollinator health and fitness in agroecosystems. Still, it is not fully clear whether access to different flower diversities will have a significant influence on the bumble bee microbiota. Here, we tested in a semi-field experiment if the bumble bee microbiota changes over time when exposed to different flower diversities within outdoor flight cages. We used commercial hives to distinguish between vertically and horizontally transmitted bacteria, respectively from the nest environment or the exposed outside environment. Result: The sequential sampling of foraging workers over a period of 35 days indicated a temporal progression of the bumble bee microbiota when placed outside. The microbiota increased in diversity and changed in composition and variability over time. We observed a major increase in relative abundance of the families Lactobacillaceae, Bifidobacteriaceae and Weeksellaceae. In contrast, major core-taxa like Snodgrassella and Gilliamella declined in their relative abundance over time. The genus Lactobacillus showed a high diversity and strain specific turnover, so that only specific ASVs showed an increase over time, while others had a more erratic occurrence pattern. Exposure to different flower diversities had no significant influence on the progression of the bumble bee microbiota. Conclusion: The bumble bee microbiota showed a dynamic temporal succession with distinct compositional changes and diversification over time when placed outdoor. The exposure of bumble bees to environmental conditions, or environmental microbes, increases dissimilarity and changes the gut-community composition. This shows the importance of environmental influences on the temporal dynamic and progression of the bumble bee microbiota.