Spontaneous Urticaria Patients Research Articles

Disease burden and physical activity in patients with chronic spontaneous urticaria

BACKGROUND: Сhronic spontaneous urticaria is a disease characterized by itchy wheals and/or angioedema on the skin over a period of 6 weeks or longer. Сhronic spontaneous urticaria is characterized by a significant disease burden for patients, their families, healthcare system and a society. Some aspects of сhronic spontaneous urticaria burden. Including the disease impact on physical activity and sport engagement, have not been well characterized.
 AIM: to evaluate the сhronic spontaneous urticaria impact on patients quality of life and physical activity of patients, and to assess the correlation between the level of physical activity and a UCT control/severity.
 MATERIALS AND METHODS: The study included 31 сhronic spontaneous urticaria patients, who underwent history taking and a survey using international questionnaires: UAS7 (Urticaria Activity Score for 7 days), UCT (Urticaria Control Test), DLQI (Dermatology Life Quality Index) и GPAQ (Global Physical Activity Questionnaire) developed by the World Health Organization (WHO).
 RESULTS: According to the GPAQ results, the physical activity level below that recommended by WHO was noted in five (16.1%) patients (MET-minutes/week 600). The moderate level of physical activity was reported in 17 (54.8%) patients, and the high level ― 9 (29%). Median sedentary time in сhronic spontaneous urticaria patients was 420 [300480] min/day, that exceeds the WHO recommendations. The DLQI assessment suggests that 16 (51.6%) сhronic spontaneous urticaria patients had difficulties in their sport activities. Four (12.9%) patients had very strong impact of сhronic spontaneous urticaria on their sport activities. Noteworthy, five patients had to stop their regular physical activity because of сhronic spontaneous urticaria severity. Based on the UCT data, uncontrolled сhronic spontaneous urticaria was reported in 23 of 31 (74.2%) patients, who also had a significantly lower quality of life compared to those with a well-controlled disease.
 CONCLUSIONS: Сhronic spontaneous urticaria may negatively affect patients quality of life, including their physical activity. A sedentary lifestyle (below the WHO recommendations) was noted in 16.1% patients. In further studies, the optimized recommendations for physical activity in сhronic spontaneous urticaria patients should consider their disease control/severity, their fitness level and patients preferences.

Omalizumab normalizes the gene expression signature of lesional skin in patients with chronic spontaneous urticaria: A randomized, double‐blind, placebo‐controlled study

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. Chronic spontaneous urticaria patients (18-75years) were randomized to either 300mg omalizumab (n=20) or placebo (n=10) administered s.c. every 4weeks for 12weeks (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. 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). 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.

166 Assessment of Chronic Spontaneous Urticaria by Serum-Induced TNF & ALPHA; and MMP-9 Release

BackgroundPrevious studies from our group have demonstrated that IgE-mediated basophil activation leads to release of TNFα that in turn can induce matrix metallo-proteinase-9 (MMP-9) release from monocytes. We wished to investigate if serum from chronic spontaneous urticaria-patients with auto-antibodies against IgE/IgE-receptor could induce TNFα and MMP-9 release from donor PBMCs, and if release levels could be used to assess severity and activity of chronic spontaneous urticaria (CSU).MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from whole blood from healthy donors and basophils isolated with MACS Basophil Isolation Kit to 97 to 99% purity. Cells were pulsed 1 hour with or without anti-IgE or with sera from CSU-patients/healthy controls and incubated for a total of 21 h before protein analysis of supernatants. MMP-9 and TNFα in supernatants were measured with commercial ELISAs (R & D), and histamine release determined with HR-test from RefLab ApS.ResultsStimulations with serum-pools demonstrated that CSU-serum, in contrast to healthy controls, was able to induce TNFα-release from isolated basophils. 10 sera from healthy controls and 22 sera from CSU-patients were tested for serum-induced histamine, TNFα and MMP-9 release. The CSU sera were grouped by reaction/no reaction in the autologous skin serum test (ASST), each group consisting of 11 sera. Nine of the 22 CSU-sera were found positive in the HR-test, 6 sera from ASST+ and 3 from ASST- patients. Sera from ASST+ and ASST- patients were observed to induce highly significant MMP-9 and TNFα release from donor PBMCs when compared to sera from healthy controls (P < 0.001). Urticaria assessment score (UAS) did not appear to correlate with release levels for histamine, TNFα or MMP-9 in either group but in the ASST+ group, the ASST score appeared to be positive correlated to histamine and TNFα release and to a smaller degree to MMP-9 release.ConclusionsWe have shown for the first time that serum from CSU-patients, in contrast to serum from healthy controls, can induce TNFα release from isolated basophils, as well as TNFα and MMP-9 from donor PBMCS. Release levels appeared to be positive correlated to ASST reaction in ASST+ patients but not to disease severity for CSU patients in general.