Search Results (96)

Background/Objectives: Omalizumab is an effective treatment for antihistamine-refractory chronic urticaria. However, post-injection urticaria exacerbation and related adverse reactions remain inconsistently reported. This scoping review mapped evidence on clinical presentation, timing, mechanisms, management strategies, rechallenge outcomes, treatment discontinuation, and patient outcomes associated with these reactions. Methods: The review followed the Joanna Briggs Institute methodology and was registered prospectively in INPLASY (INPLASY202650060). PubMed, Scopus, and the Directory of Open Access Journals were searched from inception to April 2026. Eligible studies included English-language case reports, case series, observational studies, cohort studies, registry or pharmacovigilance studies, postmarketing surveillance studies, and clinical trials reporting urticaria-related or hypersensitivity-type adverse reactions during omalizumab treatment for chronic urticaria. Data were charted descriptively and synthesized narratively. Results: Seventeen studies published between 2015 and 2026 included 2790 patients with chronic urticaria, 60 of whom experienced urticaria-related adverse reactions, corresponding to a mapped proportion of 2.2%. Clinical phenotypes included transient urticaria exacerbation, urticaria flare or worsening, localized urticarial plaques at the injection area, angioedema, anaphylaxis or anaphylaxis-like reactions, and serum sickness-like reactions. Reactions occurred within minutes to several hours, within 24 h, several days, or up to 1 week after injection or dose escalation. Reactions occurred following the first dose, repeated doses, and dose escalation. Proposed mechanisms included delayed hypersensitivity, possible IgE-mediated delayed-onset anaphylaxis, serum sickness-like reaction, paradoxical worsening, infection-associated flare, excipient-related reactions, and severe underlying CSU exacerbation mimicking anaphylaxis. Management strategies ranged from observation or symptomatic treatment to discontinuation of omalizumab and systemic interventions. Conclusions: Omalizumab-associated urticaria-related adverse reactions were infrequently reported across the mapped evidence but were clinically heterogeneous. Standardized definitions and detailed case reporting are needed to clarify causality, recurrence risk, rechallenge safety, and long-term outcomes. Full article

Background/Objectives: Several novel biologics and small-molecule therapies have emerged for the treatment of antihistamine-refractory chronic spontaneous urticaria (CSU), yet no study has directly compared their speed of response. This study aims to provide indirect evidence on the relative time to meaningful clinical response across approved and investigational therapies using a Bayesian network meta-analysis. Methods: Phase 2 and phase 3 randomized controlled trials reporting UAS7 scores in a graphical format for antihistamine-refractory CSU were included. The primary outcome was the mean time in weeks to minimal clinically important difference (MCID), defined as a UAS7 reduction of 10 points. Data were extracted using WebPlotDigitizer (v4.7) and analyzed via Bayesian random-effects network meta-analysis in MetaInsight (v6.4.0), with placebo as the reference node. Results: All drugs except rilzabrutinib 400 mg daily demonstrated faster mean time to MCID than placebo. Fenebrutinib had the fastest mean time to MCID (0.67–0.76 weeks), and tezepelumab the slowest (5.41–5.65 weeks). Only omalizumab 300 mg every 4 weeks, dupilumab 300 mg every 2 weeks, and ligelizumab 72 mg and 120 mg every 4 weeks achieved statistically significant reductions compared with placebo. All treatments had wide credible intervals reflecting limited direct comparisons. Conclusions: This is the first network meta-analysis comparing time to meaningful symptom control across therapies for antihistamine-refractory CSU. Omalizumab, dupilumab, and ligelizumab demonstrated statistically significant reductions in time to MCID compared with placebo. Head-to-head trials with standardized outcome reporting would enable more definitive comparative conclusions. Full article

Emerging research highlights the complex interplay between the gut microbiome, skin health, and environmental exposures, forming what is now recognized as the gut–skin–exposome axis. This narrative review explores the role of gut microbiome dysbiosis—a disruption in the balance of intestinal microorganisms—in the pathogenesis and progression of various non-communicable inflammatory skin diseases, including acne, atopic dermatitis, psoriasis, rosacea, systemic lupus erythematosus, chronic spontaneous urticaria, hidradenitis suppurativa, and alopecia areata. This review synthesizes mechanistic studies, clinical trials, and Mendelian randomization data to elucidate how altered gut microbial composition contributes to systemic and cutaneous inflammation. Key modifiable factors, such as diet, antibiotics, stress, and sleep, as well as interventions like probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, are discussed for their potential therapeutic value. By integrating clinical insights with microbiome science, this review underscores the importance of a holistic, systems-based approach in managing inflammatory skin diseases, offering clinicians evidence-based strategies to improve patient outcomes through gut microbiome modulation. Full article

Background/Objectives: Chronic spontaneous urticaria (CSU) is characterized by almost daily wheals or angioedema lasting for more than six weeks and not attributable to a defined inducing factor. CSU reportedly affects 1–2% of the general population and may lead to a substantial impairment in patients’ quality of life. Thus, developing methods that enable early diagnosis and assessment of disease activity is a major objective for scientists and clinicians. Methods: A significant proportion of CSU cases appears to be associated with autoimmune mechanisms, which mainly involve IgE autoantibodies (type I CSU), IgG autoantibodies (type IIb CSU), or both (type I and type IIb overlap). To this end, detection of specific IgE and/or IgG autoantibodies in CSU patients using biological or immunochemical assays can offer valuable information and enable further investigation and better management of the disease. Results: This review focuses on and presents various immunochemical assays, mainly ELISAs, for determining specific IgE and/or IgG autoantibodies, along with immunochemical methods for quantifying total IgE levels as an additional biomarker in CSU patients; the development and/or application of these assays has been reported in several papers published in the last decade on CSU. Conclusions: The methods presented have recently been applied and have substantially contributed to CSU diagnosis, endotyping and prediction of response to various treatments. Further validation of the existing immunochemical assays along with the development of reliable assays for novel autoantibodies and/or autoantigens will deepen our understanding of CSU pathogenesis and support the clinical diagnosis and treatment of CSU. Full article

Skin diseases frequently coexist with other disorders, such as metabolic syndrome, diabetes mellitus, depression, psoriatic arthritis, and cardiovascular disease. Altered levels of distinct chemokines, like CCL5/RANTES, CXCL12/SDF-1a, CCL7/MCP-3, CCL2/MCP-1, CXCL1/GROa, and the eotaxin family, contribute to the development and/or exacerbation of inflammation, which is a common feature of numerous skin diseases as well as metabolic syndrome. The pathological and molecular connections between chronic inflammatory skin diseases and metabolic syndrome are increasingly recognized as being driven by shared inflammatory pathways, oxidative stress, and adipokine dysregulation. While systemic inflammation acts as a common thread, the precise mechanisms for some conditions remain partially understood. Nevertheless, the exact pathological and molecular connections between skin diseases (i.e., psoriasis, atopic dermatitis, pemphigus vulgaris, acute and chronic spontaneous urticaria, bullous pemphigoid, squamous cell carcinoma, alopecia areata, systemic sclerosis, discoid lupus erythematosus, diffuse large B-cell lymphoma) and metabolic syndrome are not yet fully understood. This narrative review summarizes the robust association between various chronic inflammatory skin diseases and metabolic syndrome in the context of pro-inflammatory chemokines. Full article

Background/Objectives: Chronic Spontaneous Urticaria (CSU) is a skin disorder marked by recurrent wheals and itching, with or without angioedema, which can greatly affect the quality of life. Vitamin D has been implicated in the pathophysiology of various immune-mediated conditions, including CSU. The connection between vitamin D levels, patients’ perceived symptoms, and life impact remains unexplored. This study aims to elucidate vitamin D levels and their correlation with perceived disease-related burden in individuals with CSU. Methods: PROM-based questionnaires, serum 25(OH)D levels, and BMI were statistically analyzed in high-disease-activity CSU, among hospitalized and outpatients who attended the main tertiary hospital center during a 1-year period. These data were compared with a control group, after obtaining their consent. Results: The study included 104 patients, 74 (71.15%) females, mean age 43.17 ± 18.26 years, and 23 controls, 12 (52.17%) females, mean age 44.61 ± 12.77 years. Levels of 25(OH)D were significantly lower in patients compared to controls and in the hospitalized versus the outpatient group (p < 0.05). Suboptimal 25(OH)D was found in 94.23% of patients (mean level 18.29 ± 6.74 ng/mL) and 82.61% of controls (mean 24.01 ± 7.44 ng/mL). A BMI > 25 kg/m² was found in 71 (68.3%) patients and 11 (47.83%) controls. Age was not significantly correlated with vitamin D levels. A significant positive correlation was found between vitamin D levels and the perceived bothersomeness score of urticarial elements and pruritus. Age was negatively correlated with perceived bothersomeness of pruritus. Irrespective of 25(OH)D levels, perceived bothersomeness of urticarial elements positively correlated with scores for angioedema, pruritus, and the impact of CSU on life and daily activities. Life and daily activities impact scores were also positively correlated with angioedema and pruritus. Conclusions: Suboptimal levels of 25(OH)D were common in CSU patients, especially among hospitalized patients, and were significantly lower compared with controls, suggesting a potential link between low vitamin D status and high disease activity. PROMs did not show a significant association between lower vitamin D levels and worse scores for perceived bothersomeness of urticarial elements, angioedema, pruritus, or impact on life and daily activities. Full article

Chronic urticaria (CU) is a mast cell-driven inflammatory skin disorder characterized by recurrent wheals, angioedema, or both lasting more than six weeks, often resulting in significant impairment of quality of life. Although CU has traditionally been regarded as a predominantly histamine-mediated condition, evidence accumulated over the past decade has redefined chronic spontaneous urticaria (CSU) as a complex immune-mediated disease with marked biological heterogeneity. Distinct pathogenic mechanisms involving autoimmune pathways, dysregulated mast cell activation, and chronic inflammatory networks have been identified, providing a mechanistic basis for disease persistence, variable severity, and therapeutic refractoriness. This review synthesizes current concepts in CSU pathophysiology, with emphasis on mast cell biology, autoimmune endotypes, and inflammatory amplification mechanisms. We further discuss emerging biomarkers with potential relevance for disease stratification and treatment prediction, as well as established and novel therapeutic strategies targeting key pathogenic pathways. By integrating mechanistic insights with clinical implications, this review highlights the transition toward endotype-driven and biomarker-guided management of chronic urticaria. Full article

Having appropriate and meaningful diagnostic procedures is crucial in the approach to patients with chronic spontaneous urticaria (CSU), so we wanted to investigate relationships between CSU patients’ common serum factors and clinical CSU features, and their temporal trends during antihistamine treatment. In this exploratory hypothesis-based study, we assessed disease severity and quality of life (QoL) in, initially, 41 CSU patients using UAS7, daily UAS, UCT, DLQI, and CU-Q2oL. Concurrently, we measured serum complete blood count (CBC), total IgE, thyroid antibodies and hormones, ANA, D-dimer, vitamin D, and the inflammatory molecules CRP, ESR and IL-6. We compared initial (T1) and follow-up findings (T2) (after 3 months of antihistamine therapy). Basophil concentration was the only examined serum factor useful in assessing current CSU severity/daily UAS (sensitivity 78.6%; specificity 63%; p = 0.028). Basopenia was more frequent in patients with moderate/severe CSU than in those with mild disease or remission, as measured by daily UAS (79% vs. 37%; p = 0.020). T4 values showed a significant dependence on CSU duration (r = −0.328; p = 0.036). ESR was the only examined serum factor significantly associated with weekly CSU severity (UAS7) (p = 0.038). Antihistamine treatment significantly reduced CSU activity (recorded by daily UAS and UAS7) and improved QoL (DLQI) (p = 0.006) and disease control/UCT (p = 0.005). After three months of treatment, only the CRP value correlated with CSU control/UCT (p = 0.014). We encourage the use of diagnostics employing basophil counts and clinical indices UAS7, daily UAS, UCT and DLQI for insight into a patient’s CSU clinical condition. Serum factor values did not change during the 3-month treatment period, so it is not useful to measure them repeatedly. Although this study involved a small cohort and has many limitations, these promising results highlight the need for replication with a greater number of CSU patients. Full article

Background and Objectives: Chronic spontaneous urticaria (CSU) significantly affects patients’ quality of life (QoL) and remains challenging to manage, particularly in under-researched regions. This study aimed to assess the clinical burden, disease control, and quality of life among patients with CSU in Kazakhstan and to identify predictors of severe disease activity. Materials and Methods: We conducted a cross-sectional study of 350 patients with CSU attending the Republican Allergy Center in Almaty between December 2024 and June 2025. Patients were classified based on the presence of co-existing chronic inducible urticaria (CIndU), angioedema, or both. Disease activity, control, and QoL were assessed using the Urticaria Activity Score over 7 days (UAS7), Urticaria Control Test (UCT), and Dermatology Life Quality Index (DLQI), respectively. Multivariable logistic regression and correlation analyses were used to identify predictors of severe disease and interrelationships among clinical measures. Results: Among 350 patients (mean age 43.5 ± 14.7 years; 78% female), 46.3% had CSU alone, while 53.7% had associated phenotypes. Severe urticaria (UAS7 ≥ 28) affected 30% of patients. Suboptimal disease control (UCT ≤ 11) was reported in 30%, and 30% experienced strong or very strong QoL impairment (DLQI > 10). Older disease onset (≥60 years; OR = 1.98; 95% CI: 1.02–3.81) and nighttime symptoms (OR = 1.67; 95% CI: 1.02–2.73) were independently associated with severe disease. A strong inverse correlation was observed between UAS7 and UCT (ρ = −0.71), and a positive correlation between UAS7 and DLQI (ρ = 0.66), highlighting the impact of disease activity on control and QoL. Conclusions: CSU imposes a substantial clinical and psychosocial burden in Kazakhstan. One-third of patients experience severe symptoms and impaired QoL despite ongoing treatment. Older age at disease onset and nighttime symptoms may serve as practical indicators of disease severity. These findings highlight the need for improved access to advanced therapies, systematic monitoring using validated tools, and multidisciplinary care strategies in resource-constrained settings. Full article

Small intestinal bacterial overgrowth (SIBO) is an increasingly recognized condition that influences immune responses. It may be linked to atopic disorders such as bronchial asthma (BA), food allergies (FA), chronic spontaneous urticaria (CSU), and mast cell activation syndrome (MCAS). The aim of our study was to perform a structured literature search to assess the possible correlation between SIBO and the presentation of atopic disorders. The prevalence of SIBO was highest in patients with BA (60–100%) and FA (50–87.5%), followed by MCAS (30.9%) and CSU (27.9%). The diagnosis of SIBO was based on lactulose or glucose breath tests. SIBO exacerbated symptoms of atopic diseases, and treating it within BA and MCAS improved the symptoms, in contrast to CSU. The present evidence suggests a possible crosslink between SIBO and atopic manifestations. Bacterial overgrowth appears to trigger the Th2 immune response via the mucosal pathway and low-grade endotoxemia. These result in the increased synthesis of interleukins involved in allergic reactions (IL-4, IL-5, IL-13). Further studies are essential to confirm the clinical significance of this association. The “gut–allergy axis” may offer new therapeutic options and possibly improve quality of life in patients with atopy. Full article

Background: For the majority of chronic spontaneous urticaria (CSU) sufferers, nocturnal itch has a profound effect on quality of life (QoL), as it leads to sleep disturbances. To ensure good sleep quality (SQ), the body must produce an adequate amount of melatonin, which regulates the sleep cycle. Methods: This study examines the levels of salivary melatonin in 38 CSU patients and 38 healthy controls, as well as the relationship between CSU severity, QoL and SQ. The Enzyme-Linked Immunosorbent Assay (ELISA), Dermatology Quality of Life Index (DLQI), and Pittsburgh Sleep Quality Index (PSQI) were used to determine salivary melatonin levels, QoL, and SQ. In addition, the CSU participants were given the Urticaria Activity Score (UAS) and the Urticaria Control Test. Results: The median value of salivary melatonin in CSU patients was lower than that in healthy individuals (0.2 vs. 15.985 pg/mL; p < 0.001). A decreased melatonin level was seen in 90% of CSU patients and 18% of healthy individuals. Individuals with lower melatonin levels were significantly more likely to have CSU compared with those with higher melatonin levels (OR = 37.6; 95% CI 10.0–141.1). Melatonin was linearly related to QoL and sleep quality in the whole sample (r = −0.606 and −0.536; p < 0.001) but not in CSU patients. Impaired QoL in patients correlated with itch intensity and the number of hives (r = 0.740 and 0.646). The severity and activity of CSU are linearly related to impaired QoL and sleep quality (r = −0.606 and −0.536; p < 0.001). Sleep quality acts as the mediator of the association between QoL and salivary melatonin, when controlling for the effect of age and gender (B = −0.347; 95% CI = −0.679 to −0.080). Conclusions: The data suggest that melatonin may be more a non-specific marker of sleep disturbance than the severity of CSU. Sleep quality may act as a mediator linking dermatology-related QoL, circadian dysregulation and reduced melatonin secretion. Full article

Nonsteroidal anti-inflammatory drugs (NSAIDs) can exacerbate urticaria and/or angioedema in up to 30% of patients with chronic urticaria (CU), representing a distinct subtype characterized by heightened inflammation and leukotriene-driven pathophysiology. MicroRNAs (miRNAs) are post-transcriptional regulators that modulate immune and inflammatory responses. This study aimed to identify differentially expressed miRNAs (DEMs) according to NSAID hypersensitivity status and to elucidate their molecular networks in CU. Serum miRNA profiles were analyzed in 14 NSAID-exacerbated CU (NECU) and 16 NSAID-tolerant CU (NTCU) patients using an Affymetrix GeneChip^® miRNA 4.0 Array. DEMs were identified (fold difference > 1.5, p < 0.05), and validated targets were retrieved from the multiMiR database for network construction and Gene Ontology enrichment analyses. NECU patients exhibited a higher frequency of angioedema and systemic corticosteroid use than NTCU patients. Eight DEMs were identified, including upregulated miR-5001-5p, miR-4270, and miR-6869-5p, and downregulated miR-6511b-5p, miR-2277-5p, and miR-378h in NECU. Network integration revealed AGO2-BTG2-LMNB2, NFIC-ZZZ3, and NUFIP2-GLG1 as central clusters, implicating dysregulation of mRNA decay and inflammatory signaling pathways. Reduced miR-6511b-5p expression may derepress BRG1, enhancing chromatin accessibility for inflammatory and leukotriene-synthetic genes. Distinct miRNA signatures differentiate NECU from NTCU, implying a miR-5001-5p/miR-6511b-5p–mRNA decay axis that links impaired post-transcriptional regulation with leukotriene-driven inflammation in CU. These findings highlight candidate miRNAs as potential biomarkers for disease endotyping and therapeutic stratification. Full article

Background: Chronic urticaria (CU) is characterized by recurrent wheals and/or angioedema persisting for more than six weeks. While disease triggers are often unidentified, seasonal and environmental factors may modulate disease activity; however, evidence regarding their clinical impact remains limited. Objective: This study aimed to evaluate the effects of seasonal, meteorological, and pollutant-specific environmental factors on urticaria control using the Urticaria Control Test (UCT), and to compare these effects between chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIU) in relation to inflammatory serum biomarkers. Materials and Methods: This prospective observational study was conducted at the Allergy and Clinical Immunology outpatient clinic of Kirikkale University Faculty of Medicine between 1 June 2023 and 1 April 2024. Patients with CU were classified as CSU or CIU according to international guidelines. Each participant was evaluated during summer and winter seasons. Area-level air pollution data and meteorological parameters were obtained from national monitoring systems. Disease control was assessed using the UCT, and inflammatory biomarkers were analyzed. Results: Urticaria control showed significant seasonal variation, with lower UCT scores during summer and higher scores during winter in both CSU and CIU patients. Among environmental factors, ozone (O₃) was the only pollutant consistently associated with poorer urticaria control, whereas particulate matter and traffic-related pollutants, despite being higher in winter, showed no clinically relevant association. Summer months were characterized by increased inflammatory activity, including elevated leukocyte counts, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and D-dimer levels, particularly in CSU patients. D-dimer emerged as an independent marker associated with poor disease control during summer. Conclusions: CU demonstrates marked seasonal variation, with disease worsening during summer months. Pollutant-specific effects, particularly O₃ exposure, rather than overall air pollution burden, appear to be clinically relevant in urticaria control. Inflammatory and coagulation-related biomarkers may provide additional insight into disease activity. These findings support a season-aware and individualized management approach and highlight the need for future studies incorporating individual-level exposure assessment and biomarker-guided strategies. Full article

Background and Clinical Significance: Urticaria in children is generally self-limiting, and infections are a significant trigger. While anti-IgE therapy (Omalizumab) is approved for chronic spontaneous urticaria (CSU) in adolescents and adults, its role in treating acute urticaria, particularly in children, is not well defined. Case Presentation: We present two pediatric cases of acute urticaria associated with Mycoplasma pneumoniae infection. Both cases were refractory to antihistamines and corticosteroids but showed rapid response with anti-IgE treatment. Conclusions: This is the first case report in the literature of pediatric acute urticaria treated with Omalizumab. These cases suggest a potential role for IgE-mediated pathways in acute urticaria related to Mycoplasma infection and raise the question of broader applications for Omalizumab beyond CSU. Full article

Background: The symptoms of chronic spontaneous urticaria can be exacerbated or even induced by psychological stress. Assessing the severity of symptoms using the recommended Urticaria Control Test is an important diagnostic step before deciding on the type of pharmacological treatment to be used. Due to the possibility of urticaria symptoms affecting patient’s emotional condition, the authors attempted to analyze if the way of coping with stress has an impact on urticaria symptom control as assessed with this questionnaire. Methods: The study included 61 (37 female; 60,6%;) patients with symptoms of chronic spontaneous urticaria without other coexisting diseases. All patients were treated with antihistamines. In the analyzed group of patients, the Urticaria Control Test and the Polish version of Endler and Parker’s Coping Inventory for Stressful Situations questionnaire were conducted. Results: The average score on the Urticaria Control Test in the analyzed group was 8.5 (±3.9) points. In our group, the most common coping style was a mixed style based on emotions and avoidance—32 (53%) respondents. Next, 11 (18%) patients reported an emotion-based style. A task-oriented style of coping with stress was observed in 8 (13%) respondents. In the study group, we found no statistical significance in the correlation between the UCT results and the patient’s coping style. Conclusions: Emotions play a significant role as a stress-coping style in chronic spontaneous urticaria patients. The lack of relation found between the Urticaria Control Test result and the Coping Inventory for Stressful Situations questionnaire confirms the objective usefulness of the Urticaria Control Test in assessing the control of spontaneous urticaria. Full article