BackgroundGlobal chronic urticaria (CU) disease experience and management is not well documented. This study descriptively compares these aspects among CU patients residing in Europe (EU) and Central and South America (C/SA).MethodsAWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is a global prospective, non-interventional study of CU in the real-world setting. Patients were ≥ 18 years with a diagnosis of H1-antihistamine-refractory CU for > 2 months. Differences between the EU and C/SA regions in demographic and clinical characteristics, quality of life (QoL), work and activity impairment, pharmacological treatment, and healthcare resource use were examined.ResultsIn total, 4224 patients were included in the analysis (C/SA 492; EU 3732). Rates of untreated patients were greater in the C/SA region (45.1% vs. 31.9%; P < 0.005) and escalation to third-line therapy was rare in both regions. Differences in disease experience emerged, with C/SA patients more commonly experiencing angioedema (C/SA 50.8% vs. EU 46.1%; P = 0.03) or comorbid chronic inducible urticaria (C/SA 30% vs. EU 22%; P < 0.001). Correspondingly, rates of uncontrolled urticaria were higher among C/SA patients (82.8% vs. 77.5%; P = 0.017) and patients in the C/SA region showed significantly greater work and activity impairment (absenteeism: 10.4 ± 19.7 vs. 6.7 ± 19.0, P = 0.004; presenteeism: 30.3 ± 31.9 vs. 24.4 ± 25.8, P = 0.001; work productivity loss: 33.9 ± 33.9 vs. 26.5 ± 27.5, P < 0.001; activity impairment: 37.7 ± 34.7 vs. 32.7 ± 30.1, P = 0.001). However, QoL impairment was greater in the EU region (Dermatology Life Quality Index: C/SA 6.5 ± 5.9 vs. EU 8.3 ± 7.0; P < 0.001). There was a significant difference in use of healthcare resources, including emergency services (39.6% vs. 29.3%; P < 0.001), hospitalization (7.7% vs 21.9%; P < 0.001) general practitioners (31.7% vs 57.3%; P < 0.001), and additional allergists or dermatologists (50.6% vs. 47.3%, P < 0.001), among patients in the C/SA and EU region, respectively. In both regions, patients with a primary diagnosis of CU with angioedema had significantly greater impairment in work and non-work activities and healthcare resource utilization compared to those without angioedema.ConclusionsThis study revealed that CU is a heterogeneous condition with differences in healthcare utilization and outcomes between EU and C/SA. However, overall there is a high unmet need of H1-antihistamine-refractory CU patients, which is associated with high use of healthcare resources, and has a large negative effect on QoL and work productivity.

Summary Most knowledge about dendritic cells (DCs) and regulatory T cells in humans+ cells were found in T-and B-cell areas. The improvement in cell separation, manipulation and expansion techniques, will facilitate the manipulation of donor spleen cells as a part of protocols for induction and maintenance of allograft tolerance or treatment of autoimmune diseases.

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Purpose Eosinophils are frequently found in atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) that release eosinophil peroxidase (EPX) and eosinophil cationic protein (ECP). Continuous exposure to these proteins could trigger an autoimmune response which may contribute to the pathogenesis and severity of skin inflammation. In this study, we investigate the immunoglobulin E (IgE) response against eosinophil proteins in CSU and AD. Methods We recruited patients with severe AD, severe CSU and healthy subjects to explore the presence of IgE autoantibodies and cross-reactivity against EPX, ECP and thyroid peroxidase (TPO). The potential cross-reactive epitopes among the peroxidase family were determined using in silico tools. Results The frequencies of anti-EPX IgE (28.8%) and anti-ECP IgE (26.6%) were higher in the AD group, and anti-TPO IgE was higher in the CSU group (27.2%). In the CSU group, there was a correlation between the anti-EPX IgE and anti-TPO IgE levels ( r = 0.542, P < 0.001); TPO inhibited 42% of IgE binding to EPX, while EPX inhibited 59% of IgE binding to TPO, suggesting a cross-reactivity with EPX as a primary sensitizer. There was greater inhibition when we used a pool of sera CSU and AD, TPO inhibited 52% of IgE binding to EPX, while EPX inhibited 78% of IgE binding to TPO. In silico analysis showed a possible shared epitope in the peroxidase protein family. Conclusions IgE against eosinophil proteins may contribute to chronic inflammation in patients with AD and CSU. Cross-reactivity between EPX and TPO could explain thyroid problems in CSU patients.