Objective To investigate the role of Staphylococcus aureus enterotoxin B (SEB) in non-IgE mediated activation of mast cells (MCs) by in vitro co-culture of laboratory of allergic disease 2 (LAD2) cells and SEB.Methods The LAD2 cells were incubated with SEB at different concentrations of 0.01,0.1,1,10 and 100 μg/ml,A23187 positive control and negative control separately for 30 minutes.Then,effects of SEB on the morphology of MCs were observed by using a light microscope,and culture supernatants of the above incubation systems were collected.The concentration of tryptase released from MCs was analyzed by enzymatic activity assay,and the level of histamine was detected by enzyme-linked immunosorbent assay (ELISA).Results After 30-minute co-culture of LAD2 cells and SEB,MCs showed larger size,obscure boundaries,increased number of protuberances on the cell surface and decreased refractivity,with a radial burr fin-like appearance.After 30-minute co-culture of LAD2 cells and SEB at different concentrations of 0.01,0.1,1,10 and 100 μg/ml,the concentrations of tryptase in the culture supematants were 4.116 ± 0.651,5.344 ± 0.874,3.806 ± 0.459,1.309 ± 0.247,0.310 ± 0.199 ng/ml respectively.Additionally,the tryptase levels were significantly higher in the 0.01-,0.1-,1-μg/ml SEB groups than in the negative control group(1.538 ± 0.490,all P ＜ 0.05),and gradually decreased along with the increase of SEB concentrations.The histamine levels in the 0.01-,0.1-,1-,10-and 100-μg/ml SEB groups were 242.409 ± 63.915,522.491 ± 73.466,550.926 ± 84.466,334.397 ± 33.640,226.527 ± 5.678 ng/ml respectively.In the 0.01-,0.1-,1-μg/ml SEB groups,the levels of histamine released from MCs were gradually increased along with the increase of SEB concentrations,and were significantly higher than those in the negative control group (146.436 ± 3.100,all P ＜ 0.05).However,with the continued increase of SEB concentrations,the histamine levels gradually decreased.Conclusion SEB can directly activate MCs by a non-IgE mediated mechanism,followed by morphologic changes of MCs and release of tryptase and histamine.

Chronic spontaneous urticaria (CSU) is characterized by recurrent wheals with severe itching, and greatly affects the life quality of patients. The European guideline on chronic urticaria recommends the anti-IgE monoclonal antibody omalizumab as the only third-line therapy for patients with CSU whose condition can not be controlled by high doses of antihistamines. Although a lot of researches have shown that omalizumab is effective and safe for the treatment of CSU, its therapeutic mechanisms have not yet been fully elucidated. This review summarizes therapeutic mechanisms of omalizumab in the treatment of CSU, and indices for predicting and monitoring its clinical efficacy.

Objective To investigate the role of mast cells in Staphylococcus aureus enterotoxin B (SEB)-induced atopic dermatitis (AD)-like skin inflammation in BALB/c mice.Methods A total of 24 BALB/c mice were randomly and equally divided into 4 groups to be topically treated with ovalbumin (OVA group),SEB (SEB group),OVA + SEB (OVA + SEB group) and sodium chloride physiological solution (control group) respectively,so as to establish mouse models of epicutaneously induced AD-like skin inflammation.The AD-like skin lesions were evaluated by clinical observation and eczema area and severity index (EASI).Biopsy specimens were obtained from lesional skin of mice and then subjected to toluidine blue staining and immunohistochemical staining to count the mast cells,observe the morphology and distribution of mast cells,and calculate the percentage of degranulated mast cells.Results After 7-week treatment,the OVA group,SEB group and OVA + SEB group all showed severer local skin inflammation,higher EASI scores and denser infiltration of inflammatory cells compared with the control group.Moreover,the OVA + SEB group showed significantly severer local skin inflammation,skin lesions and degree of infiltration of inflammatory cells compared with the OVA group and SEB group (all P ＜ 0.05).The number of mast cells in the dermis of AD-like skin lesions per high-power field (× 400) was significantly higher in the OVA group (median [quartile range]:10.625 [3.675]),SEB group (11.000 [4.163]) and OVA + SEB group (13.875 [8.813]) than that in the control group (5.925 [2.088],all P ＜ 0.05).The SEB group (71.083％ ± 14.519％) and OVA + SEB group (58.767％ ±.16.978％) both showed significantly higher percentage of degranulated mast cells compared with the OVA group (24.050％ ± 11.161％,both P ＜ 0.05) and control group (23.617％ ± 8.132％,both P ＜ 0.05).Bivariate correlation analysis showed that the number of mast cells in the skin lesions was positively linearly correlated with the EASI scores (P ＜ 0.05).Conclusions Epicutaneous application of SEB can induce AD-like skin lesions in mice,and can exacerbate the severity of OVA-induced AD-like skin lesions.Mast cell proliferation,activation/degranulation and tryptase release may participate in the inflammation.

Objective:To evaluate clinical efficacy and safety of omalizumab in the treatment of symptomatic dermographism by analyzing real-world data.Methods:Clinical data were collected from patients with symptomatic dermographism who completed 16-week treatment with omalizumab in Department of Dermatology, Peking University First Hospital from February 2018 to May 2021, and retrospectively analyzed. The analysis was done by comparing data obtained before and after the treatment, including critical friction thresholds (CFTs) , pruritus scores in a provocation test, as well as urticaria control test (UCT) , dermatology life quality index (DLQI) and chronic urticaria quality of life questionnaire (CU-Q2oL) scores. Adverse events reported by patients during the treatment were recorded. Wilcoxon signed-rank test was applied for the analysis of clinical data before and after the treatment.Results:A total of 27 patients with symptomatic dermographism who completed 16 weeks of omalizumab treatment were included. At baseline, the CFTs of all the 27 patients were 4, and their UCT, DLQI and CU-Q2oL scores were 7.0 (5.0, 8.0) , 9.0 (6.0, 10.0) , 63.0 (50.0, 72.0) points respectively. At week 4, the CFTs decreased from 4 to 0 in 9 patients (33.3%) , the UCT scores increased to 14.0 (12.0, 16.0) points ( Z = 4.548, P<0.05) , and the DLQI and CU-Q2oL scores decreased to 2.0 (0.0, 2.0) and 32.0 (25.0, 41.0) points respectively in the 27 patients ( Z = 4.513, 4.433, respectively, both P<0.05) . At week 6, the UCT scores increased to 15.0 (14.0, 16.0) points, and the DLQI and CU-Q2oL scores decreased to 0.0 (0.0, 1.0) and 25.0 (23.0, 30.0) points respectively in the 27 patients. No drug-related serious adverse events were reported during the treatment. Conclusion:Omalizumab can effectively improve the symptoms of symptomatic dermographism and patients′ quality of life with a good safety profile.

The etiology and pathogenesis of chronic urticaria are complex. The main traditional treatment is oral antihistamines. With the progressive development in the biomedical field, targeted therapy has gradually become a new treatment option. Anti-immunoglobulin E monoclonal antibodies (omalizumab) can rapidly improve patients′ condition and enhance their quality of life during the treatment of chronic urticaria, and its clinical efficacy and safety have been gradually confirmed in clinical practice. This article summarizes and analyzes the current status of clinical diagnosis and treatment of chronic urticaria, discusses some common problems and corresponding strategies, and provides a reference for clinical management of these patients.

Objective:To evaluate the efficacy and safety of baricitinib in the treatment of moderate-to-severe atopic dermatitis (AD) .Methods:From June 2020 to June 2021, patients with moderate-to-severe AD who were insensitive or intolerant to topical agents were enrolled from Department of Dermatology, Peking University First Hospital. Before treatment, the patients were evaluated by 4 scales, including the Investigator′s Global Assessment (IGA), Eczema Area and Severity Index (EASI), Itch Numeric Rating Scale (NRS), and Dermatology Life Quality Index (DLQI) ; meanwhile, photos of skin lesions were taken, routine blood test was performed, blood biochemical indices and total IgE levels were measured. After exclusion of contraindications, the patients were treated with oral baricitinib at a dose of 2 mg/d for 16 weeks. Regular follow-up was conducted at weeks 1, 2, 4, 8, 12, 16 and 20 after the start of treatment, clinical evaluation was carried out with the above 4 scales, and adverse events were recorded during the treatment.Results:A total of 24 patients were enrolled in the study, and all completed 16-week oral treatment and 20-week follow-up. All the 4 scale scores showed a continuous downward trend within 20 weeks after the start of treatment. At week 20, the patients′ IGA, EASI, NRS, and DLQI scores significantly decreased from 4.13 ± 0.61, 37.59 ± 14.86, 6.83 ± 2.26 and 18.67 ± 8.64 points respectively at baseline to 1.12 ± 0.49, 4.53 ± 3.78, 0.72 ± 0.58 and 1.39 ± 0.85 points respectively ( t = 22.70, 10.55, 10.69, 8.40, respectively, all P < 0.001). During the follow-up period, no serious adverse reactions were observed; 3 patients experienced gastric discomfort at the start of oral treatment, but the symptoms disappeared after the treatment continued; 3 developed acute allergic manifestations (1 case of allergic conjunctivitis, 2 cases of acute urticaria), which resolved rapidly after the use of antihistamines without recurrence. Conclusion:Baricitinib can provide a safer and more effective treatment option for patients with moderate-to-severe AD, especially those who are insensitive or intolerant to topical agents and need systemic treatments.

The pathogenesis of rosacea has not been fully elucidated. It is currently believed that genetic factors, local skin immune imbalance, neuroimmune and neurovascular dysfunction, skin barrier function abnormalities, microbiota imbalance, etc., are all involved in the occurrence and development of rosacea. This review summarizes research progress in the pathophysiological pathogenesis of rosacea.

Objective:To investigate clinical application of critical temperature threshold (CTT) measurement by using a temperature tester in the diagnosis of cold contact urticaria, and to explore relationships of CTTs with disease activity, disease control condition and quality of life in patients with cold contact urticaria.Methods:A total of 20 patients with cold contact urticaria were collected from Department of Dermatology, Peking University First Hospital from October 2017 to March 2019. Disease activity was assessed by the patients themselves at the first visit; the CTT was measured, and dermatology life quality index (DLQI) was evaluated by the patients themselves at the first visit and subsequent 2 follow-up visits. At the second follow-up visit, disease control condition was evaluated in the patients. Spearman correlation analysis was used to analyze correlations of CTTs with disease activity, CTT improvement and disease control condition. Friedman test was used to compare the improvement of CTTs and DLQI during treatment, and Bonferroni multiple test was used for multiple comparisons.Results:Based on the patients′ self-assessed disease activity, there were 3 patients with mild cold contact urticaria, 8 with moderate cold contact urticaria, and 9 with severe cold contact urticaria, and the disease activity was positively correlated with CTTs ( r s = 0.573, P = 0.008) . Clinician assessment of disease control condition showed 3 patients with poor disease control, 6 with fair disease control and 9 with good disease control, and the disease control condition was positively correlated with the improvement of CTTs ( r s = 0.516, P = 0.020) . The CTTs were (20.10 ± 4.67) ℃, (10.75 ± 5.30) ℃, and 5.50 (4.00, 10.75) ℃ (expressed as median[ P25, P75]) at the first visit and 2 follow-up visits respectively, and significantly differed among different visits ( χ2 = 34.16, P < 0.001) ; meanwhile, the DLQI scores were 19.75 ± 3.81, 8.45 ± 6.27, 0.50 (0, 9.00) (expressed as median[ P25, P75]) respectively, and there was a significant difference among different visits ( χ2 = 35.23, P < 0.001) ; the CTT and DLQI were significantly lower at the 2 follow-up visits than at the first visit (all P < 0.001) . Conclusion:CTTs can reflect disease activity in patients with cold contact urticaria, and are correlated with the quality of life and disease control condition.

Chronic spontaneous urticaria (CSU) greatly affects the quality of life of patients. Currently, no sensitive and convenient biomarkers are available to assess the severity of CSU and efficacy of drug therapies. It is particularly important to apply patient-reported outcome assessment tools with good reliability and validity in daily management of CSU, such as urticaria activity score, urticaria control test and chronic urticaria quality of life questionnaire. This review outlines the existing CSU assessment tools, analyzes their strengths, limitations and clinical application, aiming to establish a CSU clinical scoring system, and to facilitate personalized treatment and efficacy evaluation.

Objective:To retrospectively evaluate efficacy and safety of omalizumab in the treatment of chronic spontaneous urticaria (CSU) , as well as recurrence after its withdrawal.Methods:Clinical data on patients with CSU, who received omalizumab treatment in Peking University First Hospital from February 2018 to January 2021, were collected and analyzed retrospectively. Through outpatient follow-up, urticaria control test (UCT) and dermatology life quality index (DLQI) were recorded to assess disease severity, and adverse events and recurrence after omalizumab withdrawal were monitored. Comparisons of normally distributed measurement data between groups were carried out using t test or analysis of variance, comparisons of non-normally distributed measurement data between groups using Mann-Whitney U test, Wilcoxon signed-rank test or Kruskal-Wallis H test, and comparisons of enumeration data between groups using chi-square test or Fisher′s exact test. Results:A total of 59 patients with CSU were included and treated with omalizumab for at least 3 months, of whom, 45 were treated for more than 6 months, and 15 for more than 12 months. After the start of omalizumab treatment, UCT scores increased from 3.0 (1.0, 6.0) points at baseline to 11.0 (3.0, 14.0) points at 1 month and 15.0 (12.0, 16.0) points at 3 months (both P < 0.05) ; DLQI scores decreased from 16.0 (12.0, 20.0) points at baseline to 7.0 (1.0, 13.0) points at 1 month and 1.0 (0.0, 4.0) points at 3 months (both P < 0.05) . The proportion of patients achieving partial or complete disease control increased from 0 at baseline to 44.1% at 1 month, 78.0% at 3 months, and 88.9% at 6 months. The proportion of patients whose quality of life was severely or extremely severely affected by CSU decreased from 84.7% at baseline to 30.5% at 1 month, 15.3% at 3 months, and 4.4% at 6 months. The disease duration was significantly shorter in the complete response group and partial response group than in the non-response group ( t = -2.894, -2.511, P = 0.011, 0.036, respectively) ; the treatment duration was significantly longer in the complete response group than in the partial response group and non-response group ( t = 2.479, 2.677, P = 0.039, 0.022, respectively) . Compared with the rapid response group, the slow response group showed higher DLQI scores ( Z = -2.622, P = 0.009) and lower UCT scores ( Z = -2.746, P = 0.006) at baseline. Nineteen patients withdrew omalizumab after complete control of CSU, of whom 13 (68.4%) experienced relapse 7.0 (5.0, 8.0) weeks after the withdrawal, and showed significantly higher UCT scores at relapse than at baseline ( Z = 3.172, P = 0.001) . The disease duration was significantly longer in the recurrence group than in the non-recurrence group ( Z = -2.635, P = 0.007) . After recurrence, 5 patients restarted omalizumab treatment, and all of them regained partial or complete disease control. The adverse events reported during the treatment were all mild to moderate. Conclusions:Omalizumab can effectively and safely control symptoms of CSU and improve the quality of life of patients with CSU. However, recurrence frequently occurs after omalizumab withdrawal, and reinitiating omalizumab treatment after recurrence is still effective.