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Background: Non‐sedating H1‐antihistamines (nsAH) are the most commonly used treatment for chronic spontaneous urticaria (CSU). Many patients use them as on‐demand (OD) therapy rather than a maintenance treatment. Here, we compared OD versus daily maintenance treatment with the nsAH rupatadine, assessed the efficacy of rupatadine updosing, and investigated potential long‐term disease‐modifying effects. Methods: This multicenter, randomized study consisted of 2 weeks of screening, 8 weeks of double‐blind treatment, and 6 weeks of treatment‐free follow‐up (OD allowed). Adult patients were randomized to 10 mg rupatadine OD or 10 mg rupatadine daily. At Week 4, if patients did not have a complete response, they switched from 10 to 20 mg rupatadine daily or underwent sham updosing (patients on 10 mg rupatadine OD). The primary aim was to compare CSU disease activity at the end of follow‐up between daily versus OD. Additionally, we assessed the efficacy of rupatadine updosing. Major outcomes were disease activity, CSU‐related quality of life (QoL), and disease control. Results: At Week 4, disease activity and QoL significantly improved in daily versus OD‐treated patients. Updosing of rupatadine did not improve the mean disease activity, but the number of complete responders increased during updosing from 5% to 22%. At the end of follow‐up, the disease activity of patients treated OD versus daily was not significantly different. Conclusions: Daily rupatadine treatment significantly improved CSU disease activity and QoL during treatment versus OD treatment but not after discontinuation of rupatadine, indicating the benefits of a daily maintenance nsAH schedule. [ABSTRACT FROM AUTHOR]

Background: Systemic allergic reactions to vaccines are very rare. In this study we assessed the management and outcome of suspected SARS‐CoV‐2 vaccine hypersensitivity. Methods: Totally, 334 individuals underwent an allergy work up regarding SARS‐CoV‐2 vaccination (group A: 115 individuals suspected to be at increased risk for vaccine‐related reactions before vaccination and group B: 219 patients with reactions after COVID vaccination). The large majority of the SPT/IDT with the vaccines were negative; however, we identified in 14.1% (n = 47) a possible sensitization to the SARS‐CoV‐2 vaccine and/or its ingredients defined as one positive skin test. Of the 219 individuals (group B) who experienced symptoms suspicious for a hypersensitivity reaction after vaccination, 214 were reported after the first vaccination with a mRNA vaccine (157 mRNA (Comirnaty®, 38 Spikevax®) and 18 with a vector vaccine (Vaxzevria®), 5 cases were after the second vaccination. Results: The symptom profile in group B was as follows: skin symptoms occurred in 115 cases (n = 59 angioedema, n = 50 generalized urticaria and n = 23 erythema/flush. Seventy individuals had cardiovascular, 53 respiratory and 17 gastrointestinal symptoms. Of the overall 334 individuals, 78 patients tolerated (re)‐vaccination (out of skin test positive/negative 7/19 from group A and 17/35 from group B). Conclusion: Proven IgE‐mediated hypersensitivity to SARS‐CoV‐2 vaccines is extremely rare and not increased in comparison with reported hypersensitivity to other vaccines. The value of skin tests is unclear and nonspecific reactions, in particular when intradermal testing is applied, should be considered. [ABSTRACT FROM AUTHOR]

Background: Omalizumab, a humanized recombinant monoclonal anti‐IgE antibody, proved to be effective in patients with chronic spontaneous urticaria (CSU), including severe and treatment‐refractory CSU. Here, we report omalizumab's effect on gene expression in skin biopsies from CSU patients enrolled in a double‐blind, placebo‐controlled study. Methods: Chronic spontaneous urticaria patients (18‐75 years) were randomized to either 300 mg omalizumab (n = 20) or placebo (n = 10) administered s.c. every 4 weeks for 12 weeks (NCT01599637). Lesional and nonlesional skin biopsies were collected from the same area of consenting patients and assessed at baseline and on Day 85 compared with skin biopsies from the same area of 10 untreated healthy volunteers (HVs). Gene expression data were generated using Affymetrix HG‐U133Plus2.0 microarrays. Statistical analyses were performed using R packages. Results: At baseline, 63 transcripts were differentially expressed between lesional and nonlesional skin. Two‐thirds of these lesional signatures were also differentially expressed between lesional and HV skin. Upon treatment with omalizumab, >75% of lesional signatures changed to reflect nonlesional skin expression levels (different vs placebo, P < 0.01). Transcripts upregulated in lesional skin (vs nonlesional and/or HV skin) suggested increased mast cell/leukocyte infiltration (FCER1G, C3AR1, CD93, S100A8, and S100A9), increased oxidative stress, vascularization (CYR61), and skin repair events (KRT6A, KRT16). Lesional signatures were not modulated by treatment in nonresponders (defined based on UAS7 longitudinal changes ≥16). Conclusion: Omalizumab, in treatment responders, reverted transcriptional signatures associated with CSU lesion phenotype to reflect nonlesional/HV expression levels; this is consistent with observed omalizumab‐mediated clinical improvement observed in patients with CSU. The gene expression of the lesional skin of patients with chronic spontaneous urticaria shows a distinct signature when compared to their nonlesional skin and the skin of healthy volunteers. The pattern of gene expression in the lesional skin of omalizumab‐treated patients are different than before treatment, but not in their nonlesional skin. In treatment responders, omalizumab treatment shows reverted transcriptional signatures associated with CSU lesion phenotype to reflect nonlesional/healthy volunteer expression levels consistent with observed clinical improvement. [ABSTRACT FROM AUTHOR]