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Item Metadata only Can Synthetic Data Allow for Smaller Sample Sizes in Chronic Urticaria Research?(2025-08-01) Gutsche A.; Salameh P.; Jahandideh S.S.; Roodsaz M.; Kutan S.; Salehzadeh-Yazdi A.; Kocatürk E.; Gregoriou S.; Thomsen S.F.; Kulthanan K.; Tuchinda P.; Dissemond J.; Kasperska-Zajac A.; Zajac M.; Zamłyński M.; van Doorn M.; Parisi C.A.S.; Peter J.G.; Day C.; McDougall C.; Makris M.; Fomina D.; Kovalkova E.; Streliaev N.; Andrenova G.; Lebedkina M.; Khoskhkui M.; Aliabadi M.M.; Bauer A.; Kiefer L.; Muñoz M.; Weller K.; Kolkhir P.; Metz M.; Gutsche A.; Mahidol UniversityBackground: Robust data are essential for clinical and epidemiological research, yet in chronic spontaneous urticaria (CSU), certain patient groups, such as the elderly or comorbid patients, are often underrepresented. In clinical trials, strict inclusion and exclusion criteria frequently limit recruitment, making it difficult to achieve sufficient statistical power. Similarly, real-world observational studies may lack sufficient sample sizes for robust analysis. To address these limitations, we generated synthetic patient data that reflect these groups’ clinical characteristics and variability. This approach enables more comprehensive analyses, facilitates hypothesis testing in otherwise inaccessible populations, and supports the generation of evidence where traditional data sources are insufficient. Methods: A tree-based decision model was applied to generate synthetic data based on an existing set of real-world data (RWD) from the Chronic Urticaria Registry (CURE). Descriptive characteristics and association strength between relevant RWD variables and their synthetic counterparts were analyzed as indicators of replication accuracy, providing insight into how closely the synthetic data aligns with the RWD. Finally, we determined the minimum sample size required to generate high-quality synthetic data. Results: The algorithm produced extensive synthetic data records, closely mirroring patient demographics and disease clinical characteristics. Smaller subgroups of the data were equally replicated and followed the same distribution as RWD. Known associations and correlations between disease-specific factors (disease control) and risk factors (age) yielded similar results, with no significant difference (p > 0.05). The lowest threshold at which synthetic data could be generated while maintaining high accuracy in RWD was identified to be 25%, enabling a fourfold increase in the synthetic population. Conclusion: Synthetic data could replicate RWD with reasonable accuracy for patients with CSU down to 25% of the original population size. This method has the potential to extend small patient subgroups in clinical and epidemiological research.Item Metadata only Baricitinib treatment rapidly improves the four signs of atopic dermatitis assessed by Eczema Area and Severity Index (EASI) clinical subscores(2023-01-01) Wollenberg A.; Simon D.; Kulthanan K.; Figueras-Nart I.; Misery L.; Tangsirisap N.; Spina L.; Lu N.; Grond S.; Eyerich K.; Mahidol Universityand sustained control of skin inflammation, and that rapid reductions in itch translate into early disruption of the itch-scratch cycle.Item Metadata only Potential Therapeutic Approaches for Chronic Urticaria: Beyond H1-Antihistamines and Biologics(2023-08-01) Zuberbier T.; Peter J.; Staubach P.; Chularojanamontri L.; Kulthanan K.; Mahidol UniversityChronic urticaria is a disease that can significantly impact a patient's quality of life and ability to function. There are effective treatment options, such as nonsedating antihistamines or biologics, but some patients do not respond to these therapies, or the therapies are not available or affordable to all patients. This review aims to summarize potential treatment strategies for patients (1) who do not respond to antihistamines and (2) cannot readily access or do not respond to biologics. The review emphasizes the importance of sound clinical practice, including correct diagnosis of chronic urticaria phenotypes, treatment of associated comorbidities, and consideration of add-on pharmacological and nonpharmacological approaches. Although some treatments may lack high-quality evidence, they may still be justifiable in certain cases, provided that there is shared decision-making, regular reassessment, and early recognition of adverse events.Item Metadata only Basophil FCER1A and PTAFR Gene Expression Profiles Correlate With Disease Severity in Chronic Spontaneous Urticaria(2026-04-01) Soetanto K.M.; Sripatumtong C.; Paringkarn T.; Angkoolpakdeekul N.; Kulthanan K.; Srinoulprasert Y.; Soetanto K.M.; Mahidol UniversityBackground: Chronic Spontaneous Urticaria (CSU) is a debilitating skin condition characterized by recurrent wheals and pruritus, significantly impacting quality of life. Molecular mechanisms underlying different severity phenotypes are not fully understood. This study aimed to investigate the expression of FCER1A and PTAFR genes in basophils implicated in CSU pathogenesis from CSU patients with varying disease severities. Methods: We recruited 45 CSU patients, stratified into mild (n = 15), moderate (n = 15), and severe (n = 15) groups, and 15 healthy controls. Basophils were isolated from peripheral blood, and the relative mRNA expression of FCER1A and PTAFR genes was quantified using real-time PCR. Results: CSU patients exhibited significantly higher expression levels of FCER1A and PTAFR genes compared to healthy controls. FCER1A expression was significantly elevated in all CSU groups compared to controls and was higher in moderate and severe groups than in the mild group. PAFR expression was also significantly higher in moderate and severe CSU. Correlation analysis revealed that both FCER1A and PTAFR mRNA expression levels positively correlate with CSU severity. Conclusion: The expression of FCER1A and PTAFR genes in basophils correlates significantly with CSU severity, suggesting their potential as both prognostic and severity biomarkers. These findings highlight key molecular pathways that could be targeted for therapeutic intervention. Early detection of elevated gene expression could facilitate timely, targeted treatments, potentially reducing the progression to severe disease in CSU patients.Item Metadata only Chronic urticaria: unmet needs, emerging drugs, and new perspectives on personalised treatment(2024-01-01) Zuberbier T.; Ensina L.F.; Giménez-Arnau A.; Grattan C.; Kocatürk E.; Kulthanan K.; Kolkhir P.; Maurer M.; Zuberbier T.; Mahidol UniversityChronic urticaria is a common and debilitating mast cell-driven skin disease presenting with itchy wheals, angio-oedema, or both. Chronic urticaria is classified as spontaneous (without definite triggers) and inducible (with definite and subtype-specific triggers; eg, cold or pressure). Current management guidelines recommend step-up administration of second-generation H1-antihistamines to four-fold the approved dose, followed by omalizumab and ciclosporin. However, in many patients, chronic urticaria does not respond to this linear approach due to heterogeneous underlying mechanisms. A personalised endotype-based approach is emerging based on the identification of autoantibodies and other drivers of urticaria pathogenesis. Over the past decade, clinical trials have presented promising options for targeted treatment of chronic urticaria with the potential for disease modification, including Bruton's tyrosine kinase inhibitors, anti-cytokine therapies, and mast cell depletion. This Therapeutics article focuses on the evidence for these novel drugs and their role in addressing an unmet need for personalised management of patients with chronic urticaria.Item Metadata only Urticaria(2022-12-01) Kolkhir P.; Giménez-Arnau A.M.; Kulthanan K.; Peter J.; Metz M.; Maurer M.; Mahidol UniversityUrticaria is an inflammatory skin disorder that affects up to 20% of the world population at some point during their life. It presents with wheals, angioedema or both due to activation and degranulation of skin mast cells and the release of histamine and other mediators. Most cases of urticaria are acute urticaria, which lasts ≤6 weeks and can be associated with infections or intake of drugs or foods. Chronic urticaria (CU) is either spontaneous or inducible, lasts >6 weeks and persists for >1 year in most patients. CU greatly affects patient quality of life, and is linked to psychiatric comorbidities and high healthcare costs. In contrast to chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) has definite and subtype-specific triggers that induce signs and symptoms. The pathogenesis of CSU consists of several interlinked events involving autoantibodies, complement and coagulation. The diagnosis of urticaria is clinical, but several tests can be performed to exclude differential diagnoses and identify underlying causes in CSU or triggers in CIndU. Current urticaria treatment aims at complete response, with a stepwise approach using second-generation H1 antihistamines, omalizumab and cyclosporine. Novel treatment approaches centre on targeting mediators, signalling pathways and receptors of mast cells and other immune cells. Further research should focus on defining disease endotypes and their biomarkers, identifying new treatment targets and developing improved therapies.Item Metadata only Blue Wheals and Blue Angioedema Induced by Blue Dyes: A Systematic Review(2023-01-01) Kulthanan K.; Tuchinda P.; Eimpunth S.; Chuthapisith S.; Rushatamukayanunt P.; Limphoka P.; Panjapakkul W.; Pochanapan O.; Maurer M.; Mahidol UniversityBackground: Blue wheals and blue angioedema, the adverse reactions to blue dye injections with or without anaphylaxis, are poorly defined. Objective: The objective is to review the characteristics (ie, sex and age at onset, interval between blue dye injection and symptom onset, clinical manifestations, duration of blue wheals or angioedema), natural courses, and treatments of blue dye adverse reactions. Methods: A review of the articles published through July 2021 was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. Results: Across 523 patients (175 studies) with any adverse reactions to blue dye injections, wheals, angioedema, or both occurred in 193 patients (36.9%). Of these 193 patients, 68 patients (35.2%) developed blue wheals or angioedema, 118 (61.1%) had ordinary wheals or angioedema (nonbluish), and 7 had both (3.6%). We reviewed 169 patients with available data (99 with ordinary lesions and 70 with blue lesions). Patent blue violet had the highest rate of inducing blue wheals or angioedema (odds ratio 4.9). Almost half of the patients with blue wheals or angioedema developed systemic symptoms; and of those with systemic symptoms, all except 1 progressed to anaphylaxis. On-demand treatments with antihistamines, corticosteroids, and epinephrine were commonly used and effective. Conclusions: Using blue dyes can lead to blue wheals or angioedema and systemic reactions. In patients with a history of a severe allergic reaction to a blue dye, repeat administration of a blue dye should be used only after carefully weighing all the risks and benefits.Item Metadata only A Systematic Review of Aquagenic Urticaria—Subgroups and Treatment Options(2022-08-01) Rujitharanawong C.; Kulthanan K.; Tuchinda P.; Chularojanamontri L.; Metz M.; Maurer M.; Mahidol UniversityBackground: Aquagenic urticaria (AquaU) is a rare variant of chronic inducible urticaria where wheals occur after skin contact with water. Information on clinical manifestations and treatment outcomes is limited, which makes the management of AquaU challenging. Objective: To systematically review disease features and relevant triggers of AquaU and patients’ response to treatment. Methods: Related articles were searched by use of the terms “aquagenic urticaria” and “aquagenic angioedema” until June 2021 and reviewed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. Results: A total of 77 patients with AquaU were investigated in 59 studies including 47 case reports and 12 case series. AquaU predominantly presented in women (47 patients, 61%), and the mean age of onset of the disease was 19.6 ± 10.8 years (range: 0-54 years). Wheals commonly occurred in localized areas and regardless of the water temperature. Based on the reviewed evidence, AquaU can be classified as familial AquaU (FAquaU, 18.2%) and acquired AquaU (AAquaU, 81.8%). Although many treatments were used in both subtypes of AquaU, the use of second-generation H1 antihistamines (2ndAH1) was reported most often to achieve marked improvement in both subtypes. The use of topical therapies in AquaU, which most commonly use hydrophobic vehicles, is poorly documented and of controversial efficiency. Conclusions: AquaU is proposed to be classified into 2 subtypes, FAquaU and the more common AAquaU. Treatment with a 2ndAH1 is recommended as the first-line treatment for both types of AquaU. Further studies are required to fill knowledge gaps.Item Metadata only Food-Dependent Exercise-Induced Wheals/Angioedema, Anaphylaxis, or Both: A Systematic Review of Phenotypes(2023-01-01) Kulthanan K.; Ungprasert P.; Jirapongsananuruk O.; Rujitharanawong C.; Munprom K.; Trakanwittayarak S.; Pochanapan O.; Panjapakkul W.; Maurer M.; Mahidol UniversityBackground: Food-dependent exercise-induced allergic reactions can manifest with wheals, angioedema, and anaphylaxis, alone or in combination. Objective: To systematically review the clinical manifestation, culprit foods and exercise, augmenting factors, comorbidities, and treatment options of each phenotype. Methods: Using predefined search terms, we assessed and analyzed the relevant literature until June 2021. Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations were applied to this systematic review. Results: A total of 231 studies with 722 patients were included. The most common phenotype was anaphylaxis with wheals, angioedema, or both, reported in 80% of patients. This was associated with a higher number of anaphylactic episodes, augmenting factors, and use of on-demand antihistamine compared with the least common phenotype, anaphylaxis without wheals or angioedema, reported in 4% of patients. Anaphylaxis with wheals/angioedema was also associated with distinct characteristics compared with stand-alone wheals, angioedema, or both, in 17% of patients. Patients with anaphylaxis were older at the time of disease onset, less often had a history of atopy, showed more positive results in response to food and exercise provocation tests, had a more restricted spectrum of culprit foods, and more often used on-demand epinephrine. Conclusions: The three phenotypes of allergic reactions to food and exercise differ in clinical characteristics, triggers, and response to treatment. Knowledge of these differences may help with patient education and counseling as well as disease management.Item Metadata only Food-Dependent Exercise-Induced Wheals, Angioedema, and Anaphylaxis: A Systematic Review(2022-09-01) Kulthanan K.; Ungprasert P.; Jirapongsananuruk O.; Rujitharanawong C.; Munprom K.; Trakanwittayarak S.; Pochanapan O.; Panjapakkul W.; Maurer M.; Mahidol UniversityBackground: Food-dependent exercise-induced wheals, angioedema, and anaphylaxis remain insufficiently characterized. Objective: We systematically reviewed the literature on clinical manifestations, laboratory investigations, culprit foods, triggering exercise, comorbidities, and treatment outcomes. Methods: Using predefined search terms and Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) recommendations, we searched 3 electronic databases to identify relevant literature published before July 2021. Results: Of 722 patients (median age 25 years; 55.4% male) from 231 studies (43 cohort studies, 15 cases series, and 173 case reports), 79.6% and 3.7% had anaphylaxis with and without wheals and/or angioedema, respectively. The remaining 16.6% had wheals and/or angioedema without anaphylaxis. The duration from eating to exercising and from exercising to symptom onset ranged from 5 minutes to 6 hours (median 1 hour) and from 5 minutes to 5 hours (median 30 minutes), respectively, and virtually all patients exercised within 4 hours after eating and developed symptoms within 1 hour after exercising. Wheat was the most common culprit food. Running was the most common trigger exercise. Most patients were atopic, and 1 in 3 had a history of urticaria. Aspirin and wheat-based products were the most frequent augmenting factors. On-demand antihistamines, corticosteroids, and epinephrine were commonly used and reported to be effective. Patients who stopped eating culprit foods before exercise no longer developed food-dependent exercise-induced allergic reactions. Conclusions: Food-dependent exercise-induced allergic reactions are heterogeneous in their clinical manifestations, triggers, and response to treatment. Patients benefit from avoidance of culprit foods before exercise, which highlights the need for allergological diagnostic workup and guidance.