Search Results (289)

Background and Objectives: Symptomatic dermographism (SD) is the most common type of physical urticaria; however, data on its clinical characteristics and factors associated with disease severity remain limited. This study aimed to evaluate clinical features, triggering factors, associated conditions, and factors associated with disease severity in patients with SD. Materials and Methods: This cross-sectional study included 174 patients followed at a tertiary dermatology center. Data were collected using a structured questionnaire. Disease severity was categorized as severe versus non-severe using a non-validated, patient-reported classification. Factors associated with severe disease were analyzed using univariate and multivariable logistic regression models. Results: The median age was 33.0 years (IQR 27.0–40.2), and 57.4% of patients were female. Severe disease was present in 36.8% of cases. In multivariable analysis, male sex was independently associated with lower odds of severe disease (adjusted OR 0.40, 95% CI 0.20–0.82; p = 0.01). Angioedema and psychological stress were associated with disease severity in univariate analyses but not after adjustment. Persistent symptoms were more frequently reported among patients with severe disease. Conclusions: Male sex was associated with lower disease severity in this cohort. However, given the cross-sectional design and the use of a non-validated severity assessment, these findings should be interpreted as exploratory and hypothesis-generating, and do not support clinical risk stratification or causal inference. Full article

Cross-reactivity among nonsteroidal anti-inflammatory drugs (NSAIDs) creates a significant clinical difficulty, especially in patients with NSAID hypersensitivity. These reactions are based on cyclooxygenase-1 (COX-1) inhibition and non-immunoglobulin E (IgE)-mediated reactions. COX-1 inhibition leads to dysregulation of arachidonic acid metabolism, with decreased prostaglandin synthesis and increased leukotriene production. Clinically, cross-intolerant reactions manifest in different phenotypes, including NSAID-exacerbated respiratory disease (NERD), NSAID-induced urticaria/angioedema (NIUA), and NSAID-exacerbated cutaneous disease (NECD). In contrast, true allergic reactions—such as single-NSAID-induced urticaria/angioedema and anaphylaxis (SNIUAA) and single-NSAID-induced delayed hypersensitivity reactions (SNIDHR)—are immunologically mediated and drug-specific. These phenotypes differ in underlying conditions, clinical manifestations, and patterns of NSAID tolerance. Paracetamol is generally considered a safer alternative due to its weak COX-1 inhibition; however, reactions may still occur, particularly at higher doses. Selective COX-2 inhibitors are usually better tolerated, however their safety should be confirmed, preferably through controlled drug provocation testing due to sporadic reactions in cross-intolerant patients. Understanding the distinction between pharmacologically mediated cross-intolerance and true allergic reactions is essential for accurate diagnosis, risk stratification, and therapeutic decision-making. This review summarizes current evidence on the mechanisms underlying NSAID hypersensitivity, analyzes the tolerability of paracetamol and alternative analgesics, and discusses practical management strategies to reduce the risk of adverse reactions. Full article

Background: The interaction between coagulation pathways, inflammatory markers, and hematological parameters has not been sufficiently clarified in patients with chronic angioedema (AE) and urticaria. This study aimed to validate previously observed associations and to further explore their relationship with clinical disease control. Methods: In this cross-sectional validation study, 102 participants were enrolled and stratified into three groups: isolated AE (n = 33), AE associated with urticaria (AE/Urt; n = 34), and healthy controls (n = 35). Serum levels of coagulation factors (D-dimer, fibrinogen, factor VII), inflammatory markers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]), and complete blood count parameters were analyzed. Disease control was assessed using the Angioedema Control Test (AECT). Appropriate non-parametric statistical tests were applied. Results: Only D-dimer values differed significantly between groups and were higher in patients with AE/Urt than in controls. At the same time, D-dimers were significantly more often elevated in both AE groups than in healthy individuals. Additionally, CRP values in both AE groups were significantly more often elevated than in controls, with significantly higher values in both AE groups (in both groups 85%) than in controls (57%). Coagulation markers and CRP demonstrated a positive correlation with age (r = 0.268–0.392; p ≤ 0.007), with fibrinogen of all coagulation markers showing the strongest age dependency (r = 0.334; p = 0.001). Gender-related differences in coagulation parameters were not statistically significant, although elevated fibrinogen levels were more common in male participants (p = 0.030). Disease control did not correlate linearly with any inflammatory markers, coagulation factor, age or gender. Conclusions: The findings support a contributory role of coagulation pathway activation and systemic inflammation in the pathophysiology of chronic angioedema and urticaria. These mechanisms may influence clinical disease expression and could represent potential targets for improved diagnostic stratification and therapeutic approaches. However, the interpretation of the present results should be approached with caution in light of several important study limitations, including demographic heterogeneity between the study groups and the relatively limited sample size. Full article

Background and Clinical Significance: Angiotensin-converting enzyme inhibitors (ACE-Is) are commonly used for treatment of hypertension and are well known among primary care specialists. ACE-I-induced angioedema is a rare, yet possible side effect. It should not be taken lightly, as it can be life-threatening. It is characterized by erythematous or skin-coloured, self-limiting, localized, non-pitting swelling of the submucosal and/or subcutaneous layers of tissue. Usually, it develops in the first year of using the medication, although it can also start several years after using it. Herein, we describe a late-onset ACE-I-induced angioedema, which developed 7 years after using the ACE-I. This case report depicts the challenges of diagnosing ACE-I-induced angioedema, especially if it is late-onset. It highlights the importance of actively asking patients questions about possible side effects of medication even several years after using it and the patients themselves not having any complaints. Case Presentation: We present a 61-year-old Caucasian male with recurring swelling of the lips, tongue and an uncomfortable feeling in the throat, which started 7 years after using an ACE-I: perindopril. There was no airway obstruction or urticaria in any of the episodes. Hereditary angioedema was ruled out by blood analysis. Based on the clinical presentation, images and blood analysis, it was diagnosed as late-onset ACE-I-induced angioedema. After discontinuing the ACE-I, there were two more episodes of angioedema reported, which were a lot milder in symptoms and lasted a shorter time period. Since then, there have been no other episodes of angioedema. Conclusions: It is important to keep in mind angioedema as a possible side effect for patients on ACE-Is. Patients should be regularly and actively questioned about side effects, even if the medication has been started several years ago and no complaints are brought up by the patient. Full article

Background/Objectives: Chronic urticaria (CU) is a heterogeneous inflammatory disorder generally attributed to mast cell activation. However, emerging evidence suggests that metabolic reprogramming and systemic immune dysregulation also contribute to the disease pathophysiology. This study aimed to investigate the interplay between epithelial barrier integrity, innate immune regulation, metabolic activity, and mast cell effector mechanisms in CU. Methods: Forty CU patients and 40 healthy controls were evaluated. Clinical parameters included disease severity, disease subtype, antihistamine response, IgE levels, anti-TPO status, gastrointestinal symptoms, and angioedema. Serum levels of histamine, intestinal fatty acid-binding protein (IFABP), soluble CD14 (sCD14), diamine oxidase (DAO), D-lactic acid, endotoxin, zonulin, calprotectin, and related ratios were measured. Disease activity and control were assessed using the UAS7 and UCT scores. Results: CU patients exhibited significantly higher DAO (p = 0.003) and lactic acid (p = 0.004) levels compared to controls, whereas other markers showed no significant differences. In anti-TPO-positive patients, sCD14 levels were reduced (p = 0.024), while histamine/sCD14 (p = 0.005), lactic acid/sCD14 (p = 0.014), IFABP/sCD14 (p = 0.008), and zonulin/sCD14 (p = 0.027) were significantly elevated, suggesting relative amplification of metabolic and barrier-related signals under impaired innate immune regulation. Severe anti-TPO-positive patients exhibited lower sCD14 (p = 0.022) and NLR (p = 0.013) but higher UAS7 (p = 0.032), histamine (p = 0.011), calprotectin (p = 0.041), and CD14-normalized ratios, including histamine (p = 0.003), IFABP (p = 0.028), lactic acid (p = 0.019), zonulin (p = 0.029), and calprotectin (p = 0.011) compared with severe anti-TPO-negative patients, indicating a mast cell-dominant and metabolically active inflammatory phenotype. The lactic acid/DAO ratio was significantly lower in controlled versus uncontrolled CU (p = 0.013) and showed discriminatory potential for disease control. Patients with angioedema had higher CRP (p = 0.038) and UAS7 scores (p < 0.001). Conclusions: CU exhibits marked immunometabolic heterogeneity. Elevated DAO and lactic acid indicate increased histamine turnover and metabolic activation, whereas altered sCD14-normalized biomarker profiles reveal immune dysregulation in anti-TPO-positive patients. Severe CU with features suggestive of thyroid autoimmunity manifests as a mast cell-dominant, metabolically active phenotype with relative suppression of innate immune modulators, contrasting with alternative pathways in other CU phenotypes. The lactic acid/DAO ratio may serve as a candidate biomarker of disease control. These results underscore the importance of phenotype-tailored therapeutic strategies in CU. 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

Background: Urticaria, particularly chronic urticaria (CU), is a highly prevalent inflammatory skin disorder characterized by recurrent wheals and/or angioedema with a fluctuating and unpredictable course that significantly impairs quality of life and requires long-term monitoring. Despite established therapeutic guidelines, disease control remains suboptimal in a considerable proportion of patients. Telemedicine has emerged as a promising adjunctive strategy for chronic disease management. This review aims to critically evaluate the role, applications, benefits, and limitations of telemedicine and digital health interventions in urticaria management. Methods: A scoping review of the literature was conducted focusing on studies addressing telemedicine, digital patient-reported outcomes, mobile health applications, and remote monitoring strategies in urticaria. Evidence from pandemic and post-pandemic telemedicine models was also analyzed to identify transferable approaches. Results: Telemedicine demonstrates significant potential in urticaria management by enabling structured symptom monitoring, facilitating remote follow-up during therapeutic escalation (including biologic therapies), improving patient empowerment and adherence, and reducing healthcare utilization and indirect costs. Digital tools such as electronic diaries and validated PRO-based applications support continuous disease assessment. However, telemedicine cannot replace direct clinical examination, and limitations include diagnostic uncertainty, digital inequalities, data privacy concerns, and lack of large disease specific trials. Conclusions: Telemedicine represents a valuable complementary and integrative model for urticaria care, particularly suited for chronic disease monitoring. Hybrid care pathways combining remote and in-person management appear to be the most effective and sustainable strategy. Further high-quality urticaria-specific studies and standardized digital frameworks are required to optimize its clinical implementation. Full article

Background/Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most consumed drugs worldwide and the main cause of drug hypersensitivity reactions (HSRs). The most common NSAID-HSR class is cross-hypersensitivity (CR), with patients reacting to NSAIDs from different chemical groups without specific immunological recognition, with NSAID-induced acute urticaria/angioedema (NIUA) being the most frequent clinical phenotype. Although CR-HSRs are triggered by arachidonic acid (AA) alterations following cyclooxygenase (COX)-1 inhibition and cysteinyl-leukotrienes synthesis by 5-lypoxygenase (5-LO), current evidence supports the participation of additional mechanisms. As COX-1 and 5-LO head oxidative pathways, it is conceivable that enzymes participating in antioxidant control are involved in these mechanisms. In addition, as the CR-HSR susceptibility seems to be influenced by genetic factors, the possibility of genetic variants playing a role in such enzymes should not be excluded. Methods: In this observational case–control study, we analysed for the first time in NIUA the overall genetic variability in key antioxidant defence enzymes genes, including catalase (CAT), glutathione peroxidase (GPX)-1 and 3, and superoxide dismutase (SOD)-1. We selected a set of tagging single nucleotide polymorphisms (tSNPs) in these genes using data from Europeans in the 1000 Genomes Project. Two independent Spanish populations (discovery and replication) of NIUA patients and NSAID-tolerant individuals were included. Results: Twenty-six tSNPs were genotyped in the discovery population, with three that were significantly associated with NIUA: rs3448 (GPX-1), rs3792798 (GPX-3), and rs10432782 (SOD-1). They were then genotyped in the replication group, with rs3792798 being protective and rs10432782 being associated with an increased NIUA risk. Conclusions: Our results suggest that a role for antioxidant enzyme polymorphisms in NIUA is required. Nevertheless, further research is needed to replicate our findings in other populations and their meaning at the molecular level and to investigate the role of such variants in other CR-HSR-induced phenotypes. 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

Urticaria is a mast cell-mediated disorder commonly encountered in women of reproductive age, making its interaction with pregnancy clinically relevant. Gestation induces profound hormonal and immunologic adaptations—including shifts between Th1/Th17 and Th2/Treg responses and sustained exposure to sex steroids and placental hormones—that can modulate mast cell reactivity. As a result, chronic urticaria (CU) shows heterogeneous behavior during pregnancy: approximately half of patients improve, one third worsen, and the remainder remain stable. Pregnancy also presents several urticaria-like dermatoses, notably polymorphic eruption of pregnancy (PEP/PUPPP), atopic eruption of pregnancy (AEP) and pemphigoid gestationis (PG), as well as rare hormone-induced hypersensitivity reactions. Additionally, systemic disorders such as intrahepatic cholestasis of pregnancy (ICP), chronic kidney disease–associated pruritus and urticarial vasculitis may mimic urticaria but differ markedly in prognosis, maternal–fetal risk and management. Given this complexity, accurate diagnosis requires integration of temporal pattern, lesion morphology and duration, distribution, systemic features and targeted investigations, as outlined in the diagnostic algorithm proposed. Most pregnancy-specific eruptions are benign, whereas PG, ICP and urticarial vasculitis warrant prompt recognition due to potential fetal implications. Management of CU in pregnancy generally follows standard guidelines, with second-generation H1-antihistamines as first-line therapy and omalizumab reserved for severe refractory cases. Full article

Eosinophilic esophagitis (EoE) is a chronic, food-driven inflammatory disorder of the esophagus in which repeated exposure to dietary antigens plays a central role, yet identification of clinically relevant food triggers remains largely empirical. In this retrospective, single-center study, molecular IgE sensitization profiles were descriptively characterized in adult patients with EoE (n = 22) and compared with an allergic control group with chronic urticaria (CU; n = 29) using component-resolved diagnostics. IgE sensitization was common in both cohorts and predominantly reflected inhalant-related, cross-reactive components, particularly PR-10 proteins (63.6% in EoE vs. 37.9% in CU). In contrast, sensitization to structurally stable food allergen components, including lipid transfer proteins and plant storage proteins, was observed in a subset of patients with EoE (31.8%) and was not detected in the control group (0%; p = 0.0015). These food-derived components are characterized by resistance to thermal processing and gastrointestinal digestion and may reflect patterns of sustained dietary exposure rather than acute IgE-mediated reactions. Consistent with previous observations, component-resolved diagnostics showed limited utility for the direct identification of trigger foods in eosinophilic esophagitis. Accordingly, the observed molecular sensitization patterns should be interpreted as descriptive and hypothesis-generating signals rather than as indicators of pathogenic mechanisms or clinical decision-making tools. The findings highlight the importance of considering molecular properties of food allergen components when interpreting sensitization profiles in chronic, non-IgE-mediated inflammatory diseases and underscore the need for prospective studies integrating standardized clinical and dietary outcomes. 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