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.

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.

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.

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.

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.

[Approved therapies and their effects on the main symptoms of urticaria : When symptom control of itchy wheals is not adequate-does updosing help?] / Zugelassene Therapien und ihre Wirkung auf die Leitsymptome der Urtikaria : Hilfreiche Therapieoptionen, wenn juckende Quaddeln nicht weichen ­ Viel hilft viel?

International guidelines for the treatment of chronic spontaneous urticaria support the updosing of second-generation antihistamines to four times of the approved dose when adequate symptom control cannot be achieved with the standard dosage. However, this recommendation is primarily based on expert opinions, and there is a lack of large, well-designed, double-blind clinical trials. Most the existing trials provide insufficient data, and due to the heterogeneity of the conducted trials on antihistamine effects (definition of control, design, quality, lack of an active comparator, no placebo arm, small sample size, outcomes) and their short duration, comparative analysis is challenging. However, it can be concluded that the use of modern second-generation antihistamines is both effective and safe based on the available data and our own long-term experiences in the specialized outpatient clinic of a university dermatology department, even though increased dosages (up to fourfold as per the current international guidelines) may be necessary for symptom control. Another therapeutic option for refractory symptoms in chronic spontaneous urticaria is subcutaneous administration of omalizumab at a dosage of 300 mg at 4­week intervals as a very safe and effective treatment.

Sustained control of recalcitrant chronic spontaneous urticaria after initiation of inflammatory airway diseases treatment: two case reports.

BACKGROUND: Current classification of chronic urticaria is primarily based on clinical presentation of skin manifestations. Hence, therapeutic treatment is primarily aimed locally for immediate symptom relief. We reason that limiting therapeutic strategies to the skin pathology might be inadequate since cellular activation and inflammation might be triggered remotely. CASE PRESENTATION: In this series two patients had exhausted all current treatments for recalcitrant urticaria but remained symptomatic. The first case was 26-year-old Caucasian female and the second was 63-year-old African American female. Both cases had frequent breakthrough urticaria requiring frequent pulsating courses of prednisone to control urticaria despite treatment with omalizumab and antihistamines. When inflammatory airway disease was discovered and managed with inhaled corticosteroid, urticaria is controlled much faster without the need of high dose immunosuppression over several years of observation. Coincidentally, autoimmune thyroiditis and anti-immunogobulin-E immunoglobulin-G titers dropped significantly in one case with sustained inhaled corticosteroid therapy. CONCLUSIONS: We suggest a novel approach of controlling remote epithelial site inflammation in these two cases that resulted in sustained-control of urticaria symptoms without the need for systemic corticosteroids or immunosuppressant. The changes of autoimmune antibodies might be the consequences of tolerance breaking from chronic lower airway inflammation as observed in other epithelial inflammatory condition like in celiac disease and rheumatoid arthritis.

Risk calculator of the clinical response to antihistamines in chronic urticaria: Development and internal validation.

Early detection of CSU patients with low probability of a clinical response with antihistamines could undergo prompt initiation of therapeutic alternatives. The aim of the study was to develop and internally validate a model for predicting the clinical response to antihistamines in adult patients with chronic spontaneous urticaria (CSU), who consult allergology and dermatology care centers. A cohort of CSU patients, recruited from four participating centers, were followed up for 12 months. Fifteen candidate variables were selected to be included in the multivariate model and then internal validation was done with bootstrap analysis with 1000 simulations. The outcome variable, clinical response to antihistamines, was evaluated with the UAS (Urticaria Activity Score) scale for seven days: "No response to antihistamines" was defined as UAS7 ≥7 points after at least one month with a maximum dose of antihistamines, while "Response to antiH1" was defined as UAS7 ≤6 points for at least three months with the use of antiH1. A total of 790 patients were included. Among the different models analyzed, the model that included age, angioedema, anxiety/depression, time with the disease, NSAIDs (Non-steroidal anti-inflammatory drugs) intolerance, and UAS7 baseline was considered the one with the best performance (accuracy 0.675, HL 0.87, AUC 0.727). The internal validation analyses demonstrated good consistency of the model. In conclusion, this prediction model identifies the probability of response to antihistamines in patients with chronic spontaneous urticaria. The model could be useful for a personalized therapeutic approach according to individual patient risk.

Evaluation of Pharmacological Treatments for Acute Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness and safety of pharmacological treatments for acute urticaria remain unclear. OBJECTIVE: To systematically review and meta-analyze the efficacy and safety of pharmacological treatments for acute urticaria in emergency department (ED) and non-ED settings. METHODS: We searched electronic databases and gray literature up to July 8, 2023, without language restrictions. Randomized clinical trials (RCTs) relating to pharmacological interventions in patients with acute urticaria, regardless of age, were eligible for inclusion. The relevant outcomes of interest were the treatment efficacy and safety profiles. The results are presented as standardized mean differences (SMDs) or odds ratios (ORs). RESULTS: We identified 8 RCTs comprising 680 patients. Regarding the ED setting (2 trials, n = 118), intramuscular first-generation H1-antihistamine (fgAH) was more efficacious in decreasing pruritus symptoms (SMD, -0.38; 95% confidence interval [CI], -0.75 to -0.02) but had higher sedative effects than H2-blockers. With comparable pruritus symptom improvement (2 trials, n = 295), intravenous second-generation H1-antihistamine (sgAH) had favorable clinical outcomes compared with intravenous fgAH in the ED setting with a lower risk of return to any ED/clinic (OR, 0.31; 95% CI, 0.12-0.83) and lower risk of any adverse event (OR, 0.24; 95% CI, 0.09-0.63). The efficacy of adjunctive therapy with a short course of systemic glucocorticosteroids in ED and non-ED settings remains unclear. No serious concerns regarding the safety profiles were observed in any of the treatment comparisons. CONCLUSIONS: H1-antihistamine is a crucial and effective component of acute urticaria treatment, and intravenous sgAH is preferred as an initial treatment option.

Solar Urticaria: An Ambispective Study in a Long-term Follow-up Cohort with Emphasis on Therapeutic Predictors and Outcomes.

Solar urticaria is a rare photodermatosis with several unknown pathogenic, clinical and therapeutic aspects. This study analysed the clinical and therapeutic features of a long-term follow-up solar urticaria cohort, with a focus on omalizumab management and outcomes, and characterized omalizumab response with the use of the high-affinity immunoglobulin E (IgE) receptor (FcεRI) and the Urticaria Control Test. An observational, unicentric, ambispective study was conducted from 2007 to 2023. Solar urticaria was diagnosed in 41 patients with a median follow-up of 60 months. Thirteen patients were prescribed omalizumab, with a median treatment time of 48 months. A significant decrease in FcεRI baseline levels and subsequent median increase in Urticaria Control Test was evidenced after omalizumab prescription in all patients. Drug survival at 48 months was at 88.9%. Omalizumab stepping-down protocol led to sustained omalizumab discontinuation in only 1 patient. Median basal Urticaria Control Test was lower (p < 0.01) in patients who were prescribed omalizumab and in patients without remission. This study contributes to our knowledge of omalizumab outcomes in real-life clinical practice and highlights the pathogenic importance of IgE-mediated pathways in solar urticaria, where FcεRI emerges as a possible biomarker of omalizumab response.

Immediate Reaction to Propranolol: An Extremely Rare but Important Condition. A Case Report.

INTRODUCTION: Beta-blockers involve a group of drugs widely used nowadays. Propranolol was the first beta-blocker available in the market. It is the most prescribed first-generation betablocker and is commonly used. Beta-blocker allergy is extremely unusual. Only an isolated case of an urticaria reaction to propranolol has been published in 1975. CASE PRESENTATION: We present a 44-year-old man. In 2016, he was treated with a daily dose of 5 mg of propranolol prescribed for a diagnosis of essential tremor. On the third day of medical treatment, he experienced an episode of generalized urticaria directly related to the administration of propranolol. He continued with his habitual treatment and he had no other urticaria episodes. A drug provocation test was carried out with gradually increasing doses of the culprit drug. Thirty minutes after a total cumulative dose of 5 mg, the patient had several hives on the chest, abdominal region and arms. Two weeks later, a new drug provocation test was performed to bisoprolol as an alternative beta-blocker, with good tolerance. CONCLUSION: We describe a new case of urticaria secondary to propranolol, presenting as an immediate hypersensitivity reaction. Bisoprolol has been succesfully proved to be a safe option. Bisoprolol is a second-generation beta-blocker, it is available and commercialized worldwide, which makes it a good alternative.

Safety of omalizumab in chronic urticaria during pregnancy: a real-life study.

BACKGROUND: Managing a pregnant patient with chronic spontaneous urticaria (CSU) is often challenging. Recent data have shown that most CSU treatments in pregnant patients are second-generation H1 antihistamines (sgAHs), while data on the safety of omalizumab are scant. OBJECTIVES: To evaluate, in a routine clinical practice setting, the efficacy and safety of omalizumab in patients with severe CSU refractory to sgAHs who either became pregnant during treatment or who started the drug during pregnancy. METHODS: We conducted a retrospective study of women aged ≥ 18 years who were pregnant, who received one or more doses of omalizumab at any time during their pregnancy or who were taking omalizumab at the time of, or in the 8 weeks before, conception. RESULTS: Twenty-nine pregnant patients were evaluated: 23 (79%) conceived a child while taking omalizumab (group A), while 6 (21%) started omalizumab treatment during pregnancy (group B). Among patients in group A, we observed 23 births (21 liveborn singletons and 1 liveborn twin pair) and 1 miscarriage. Fifteen (65%) patients discontinued omalizumab after confirming their pregnancy, while eight (35%) were exposed to omalizumab during their entire pregnancy. In group B, omalizumab was introduced at a mean (SD) 10.83 (3.60) weeks' gestation and all patients were exposed to it until the end of pregnancy. In this group, there were seven liveborn infants (five singletons and one twin pair). No adverse events, pregnancy complications or congenital anomalies in newborns were recorded in either group. CONCLUSIONS: Omalizumab for CSU treatment before and during pregnancy does not appear to have negative effects on maternal or fetal outcomes.

Severe acute urticaria is associated with elevated plasma levels of D-dimer.

Evaluation of the disease severity of acute urticaria (AU) is essential for adequate treatment of patients. However, there are no reliable biomarkers for such an evaluation. In our department, we observed patients with severe AU having elevated plasma D-dimer levels. Thus, the objective of this study was to investigate the elevated D-dimer levels in patients with severe AU in more detail. One hundred and thirty-nine hospital patients diagnosed with severe AU were enrolled. Clinical laboratory data were collected from electronic medical records. One hundred and seventeen of the patients presented with elevated plasma D-dimer levels. Compared to the normal group, the elevated group had a significantly higher proportion of patients who were female, younger, febrile, and had a shorter prehospital time (P < 0.05). Univariate regression analysis showed that neutrophil percentage, C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels increased as D-dimer levels increased, while prehospital time showed the opposite trend. Multiple regression analysis was used to estimate the simultaneous effects of CRP and LDH on D-dimer levels. Patients who responded to additional antibiotic treatment had higher levels of D-dimer. The group with highly elevated D-dimer levels required a higher maximum dose of daily glucocorticoids (GCs) to control the symptoms of AU. In conclusion, patients with severe AU might have elevated plasma D-dimer levels, which are positively correlated with CRP and LDH levels. Patients with severe AU with dramatically elevated D-dimer levels might need a higher dose of daily GCs and antibiotics to relieve symptoms. D-dimer may be a reasonable marker to evaluate the severity of AU and guide treatment.

Mast cell silencing: A novel therapeutic approach for urticaria and other mast cell-mediated diseases.

Chronic urticaria (CU) is a mast cell (MC)-dependent disease with limited therapeutic options. Current management strategies are directed at inhibiting IgE-mediated activation of MCs and antagonizing effects of released mediators. Due to the complexity and heterogeneity of CU and other MC diseases and mechanisms of MC activation-including multiple activating receptors and ligands, diverse signaling pathways, and a menagerie of mediators-strategies of MC depletion or MC silencing (i.e., inhibition of MC activation via binding of inhibitory receptors) have been developed to overcome limitations of singularly targeted agents. MC silencers, such as agonist monoclonal antibodies that engage inhibitory receptors (e.g., sialic acid-binding immunoglobulin-like lectin8 -[Siglec-8] [lirentelimab/AK002], Siglec-6 [AK006], and CD200R [LY3454738]), have reached preclinical and clinical stages of development. In this review, we (1) describe the role of MCs in the pathogenesis of CU, highlighting similarities with other MC diseases in disease mechanisms and response to treatment; (2) explore current therapeutic strategies, categorized by nonspecific immunosuppression, targeted inhibition of MC activation or mediators, and targeted modulation of MC activity; and (3) introduce the concept of MC silencing as an emerging strategy that could selectively block activation of MCs without eliciting or exacerbating on- or off-target, immunosuppressive adverse effects.

Dual biologics therapy in a patient with severe asthma and chronic urticaria: a case report and review of the literature.

INTRODUCTION: The data on the use of dual biologics are scant, but a topic of current interest. CASE STUDY: In this report, the treatment regimen of a patient with two T helper 2 pathway-related comorbidities, severe asthma, and chronic spontaneous urticaria, was presented. RESULTS: Both urticaria and asthma symptoms of the patient could not be controlled entirely with monotherapy while both diseases could be controlled after omalizumab-mepolizumab dual treatment. No adverse events were observed after 6 months of dual biologics use. CONCLUSION: This report supports other publications in the literature involving the use of dual biologics and provides a summary of the literature.