Cellular adhesion molecules in chronic urticaria: modulation of serum levels occurs during levocetirizine treatment

BACKGROUND: Some antihistamines are capable of reducing levels of adhesion molecules in wealing tissues of patients with chronic urticaria (CU). OBJECTIVES: To determine if 6 weeks of therapy with levocetirizine 5 mg once daily would also induce any decrease in serum levels of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial leucocyte adhesion molecule-1 (ELAM-1) or P-selectin in subjects with CU and chronic autoimmune urticaria. METHODS: Thirty-six patients with CU (18 with positive and 18 with negative autologous serum skin test) were studied, together with 10 control healthy subjects. All patients received levocetirizine 5 mg daily. Serum soluble cellular adhesion molecule (CAM) levels were determined by immunoenzymatic assay before and after the end of the study period. Disease activity was recorded according to the EAACI/GA(2)LEN/EDF scoring system. RESULTS: After levocetirizine therapy CAM levels decreased in patients with CU, significantly in the cases of ELAM-1 and P-selectin. Patients' clinical scores improved during regular antihistamine therapy. CONCLUSIONS: Levocetirizine 5 mg daily demonstrated a broad anti-inflammatory effect in patients with CU. The significant decrease in serum levels of ELAM-1 and P-selectin might reflect the inhibitory activity on neutrophil rolling and extravasation towards inflamed skin.     

Epidemiology and comorbidities of patients with chronic urticaria in Korea: A nationwide population‐based study

Few population‐based studies have focused on the epidemiology and comorbidities of chronic urticaria (CU) or chronic spontaneous urticaria (CSU). The objective of this study was to obtain information on the epidemiology and comorbidities associated with CU and CSU in Korea. We conducted a cross‐sectional analysis using a national health insurance database. An algorithm based on the International Classification of Diseases, 10th revision, was used for the identification of patients with CU and CSU, and an age–sex adjusted logistic regression model was used to assess the risk of comorbidities in these patients. The average annual prevalence rates of CU and CSU during the 4‐year period between 2010 and 2013 were 3.08% and 1.40%, respectively. The prevalence rates of CU and CSU were higher in women than men (1:1.39 and 1:1.34, respectively) and peaked at 0–9 and 70–79 years, respectively. After adjustment for age and sex, the patients with CU and CSU were found to have a significantly higher prevalence rate of CU/CSU‐related diseases, compared with those without CU (mean adjusted odds ratio, 8.46; 95% confidence interval, 8.10–8.83). Allergic rhinitis, drug allergies, asthma, thyroid diseases and cancers were the most common comorbidities. Stomach, thyroid, liver and prostate cancers were the most prevalent cancers. This study provides large epidemiological data on the prevalence rates of CU and CSU, and their comorbidities, in Korea. Patients with CU and CSU impose a higher burden, in terms of specific comorbidities, than those without CU.     

Increased levels of serum IL‐31 in chronic spontaneous urticaria*

Please cite this paper as: Increased levels of serum IL‐31 in chronic spontaneous urticaria. Experimental Dermatology 2010; 19: 464–466. Abstract: IL‐31 represents a novel cytokine involved in pruritic skin diseases including atopic dermatitis (AD). We, therefore, aimed at investigating IL‐31 levels in chronic spontaneous urticaria (CU). We included 46 patients with CU, 26 non‐atopic skin healthy subjects as negative and 28 patients with AD as positive controls. IL‐31 serum levels were analysed using commercial ELISA kit. IL‐31 serum levels were higher in patients with CU compared to healthy controls (P < 0.001), but lower compared to patients with AD (P < 0.001). There was no difference in IL‐31 serum levels in autologous serum skin test positive or negative CU patients and patients with infectious trigger factors including helicobacter pylori infection. IL‐31 serum levels may play a role in the pathophysiology of CU. This is supported by the finding that not all patients with CU respond to antihistamine treatment but to the treatment with immunosuppressive drugs.     

Blood urokinase plasminogen activator system in chronic urticaria

The evidence gathered has pointed to the fibrinolytic system, which apart from its major role in hemostasis may also be involved in inflammatory and immune processes. To understand better the role of fibrinolysis in urticaria, we measured plasma levels of the urokinase system associated molecules such as urokinase-type plasminogen activator (uPA), its soluble receptor (suPAR; CD87) and an inhibitor, plasminogen activator inhibitor type 1 (PAI-1) activity in chronic urticaria (CU) patients. Plasma was obtained from symptomatic sixteen CU patients (12 females and 4 males) showing positive response to autologous serum skin test (ASST), 28 CU patients with negative ASST (20 females and 8 males) as well as from healthy subjects matched by sex and age. The plasma level of uPA and suPAR antigens, PAI-1 activity did not differ significantly among the three subjects groups. The data obtained suggest that CU patients showing positive response to ASST have plasma profile of the urokinase system-associated proteins, which is not markedly different as compared with CU patients with negative ASST as well as healthy subjects. Our findings have also confirmed the earlier studies, suggesting that systemic fibrinolysis may not be involved in chronic urticaria.This study was supported by a research grant from the Committee for Scientific Research (NN-1-246/03).     

Omalizumab is an effective and rapidly acting therapy in difficult-to-treat chronic urticaria: A retrospective clinical analysis

BackgroundOmalizumab (anti-IgE) therapy is effective and safe in chronic urticaria (CU) in placebo-controlled clinical trials but real life clinical data are scarce.ObjectiveTo better understand the effects of omalizumab in CU patients treated outside of clinical trials.MethodsIn this retrospective clinical analysis, we assessed responder rates, optimal dosage, response to up-/downdosing, time to relief of symptoms, rates of return and time of relapse after omalizumab administration, and safety in 51 CU patients, 20 with chronic spontaneous urticaria (CSU) alone, 21 with different forms of chronic inducible urticaria (CindU) and 10 with both.ResultsOmalizumab treatment led to complete remission in 83% of CSU and 70% of CindU patients. When starting with 150 mg omalizumab 4 weekly, only 2/15 CSU and 7/17 CindU patients required updosing to achieve complete remission. In CSU, 57% of complete responses occurred within week one, all on the first day. Relapses were 2–8 weeks in all but six patients, where they were <4 months. Omalizumab was safe. Efficacy was not correlated to baseline IgE levels.ConclusionClinical experience from more than 1250 injections in 51 patients over four years indicates that omalizumab is a rapidly acting, highly effective and safe drug in CSU and CindU patients. Our observations in a real life clinical setting support the recommendation of current EAACI/GA²LEN/EDF/WAO guideline for the management of urticaria to use omalizumab to treat urticaria patients.     

慢性自发性荨麻疹患者自体血清皮肤试验的免疫学机制及与临床特征和预后的关系

自体血清皮肤试验(ASST)在临床上常用于筛查慢性自发性荨麻疹(CSU)的免疫亚型, 但其免疫学机制、与CSU患者临床特征及预后的关系尚未明确。研究显示, ASST阳性与CSU患者免疫球蛋白G自身抗体升高、嗜酸性粒细胞和嗜碱性粒细胞计数减少、嗜碱性粒细胞CD63表达升高、循环炎症细胞因子水平变化相关, 与患者年龄、病程以及个人或家族史无关, 但可能是慢性荨麻疹病情严重程度的预测指标。ASST阳性患者可能对第二代H1抗组胺药反应不佳, 对奥马珠单抗起效缓慢, 但对环孢素和自体全血/血清注射治疗反应良好。该文综述ASST阳性患者的免疫学和临床特征, 探讨ASST阳性对不同治疗方案疗效的预测作用。     

Factors linked to disease severity and time to remission in patients with chronic spontaneous urticaria

Biomarkers useful for the evaluation and management of patients with chronic spontaneous urticaria (CSU) are not currently available. A review of various clinical and laboratory markers that have been studied to assess their value for determining the severity or predicting the evolution of disease in adult patients with CSU was carried out. A search of the medical literature on PubMed and MEDLINE including the terms urticaria, chronic urticaria, chronic idiopathic urticaria, CSU, severity, prognosis and treatment was performed. Based on our review of the literature, among the clinical markers studied, higher age at onset, being female, long disease duration and aspirin/NSAID hypersensitivity may be linked to both severe CSU and a long time to spontaneous remission. In addition, a positive autologous serum skin test (ASST) may be associated with severe CSU, and comorbidity of inducible urticaria and concomitant recurrent angio‐oedema may be linked to longer CSU duration. Potential biomarkers of CSU severity and/or duration include basophil numbers and susceptibility to activation, inflammatory markers, markers of activation of the extrinsic coagulation pathway, immunoglobulin E and vitamin D. Although the described markers are promising, further studies on representative and well‐characterized patient populations are needed to determine the value of these clinical and biological markers for predicting the severity and course of disease in patients with CSU.     

Serum neopterin levels in spontaneous urticaria and atopic dermatitis

Serum neopterin may be considered a diagnostic marker of the degree of activation of the immune system. This preliminary study was performed to measure serum neopterin levels in patients with acute spontaneous urticaria (ASU), chronic spontaneous urticaria (CSU) and atopic dermatitis (AD). In total, 180 patients [96 men, 84 women; mean age 23.1 years; 41 with spontaneous urticaria (13 ASU and 28 CSU), 48 with AD] and 96 healthy controls were enrolled in the study. Patients with ASU had the highest neopterin levels, and all three groups of patients (ASU, CSU and AD) had higher values than normal subjects. This preliminary study demonstrates that serum neopterin could be a biomarker of immune activation in patients with SU or AD.     

Evaluation of D-dimer serum levels among patients with chronic urticaria,psoriasis and urticarial vasculitis

BACKGROUND

It has been demonstrated that neutrophils, eosinophils and monocytes, under appropriated stimulus, may express tissue factor and therefore, activate the extrinsic pathway of coagulation. We performed a transversal and case-control study of patients with chronic urticaria and patients with psoriasis, in our outpatient clinic to evaluate the production of D-dimer.

OBJECTIVE

To evaluate D-dimer serum levels in patients with chronic urticaria and its possible correlation with disease activity.

PATIENTS AND METHODS

The study was conducted from October 2010 until March 2011. We selected 37 consecutive patients from our Allergy Unit and Psoriasis Unit, and divided them into three groups for statistical analysis: (i) 12 patients with active chronic urticaria (CU); (ii) 10 patients with chronic urticaria under remission and (iii) 15 patients with psoriasis (a disease with skin inflammatory infiltrate constituted by neutrophils, lymphocytes and monocytes). Another five patients with urticarial vasculitis were allocated in our study, but not included in statistical analysis. The serum levels of D-dimer were measured by Enzyme Linked Fluorescent Assay (ELFA), and the result units were given in ng/ml FEU.

RESULTS

Patients with active chronic urticaria had the highest serum levels of D-dimer (p<0.01), when compared to patients with CU under remission and the control group (patients with psoriasis).

CONCLUSIONS

Patients with active chronic urticaria have higher serum levels of D-dimer, when compared to patients with chronic urticaria under remission and patients with psoriasis. We found elevated serum levels of D-dimer among patients with urticarial vasculitis.     

补充维生素D3协同第二代抗组胺药物治疗慢性自发性荨麻疹的临床疗效观察和作用机制研究

目的：评价补充维生素D3（VD3）协同第二代抗组胺药物对控制慢性自发性荨麻疹（CSU）临床症状的疗效。方法：① 90例CSU患者,21例慢性可诱导性荨麻疹(CIndUI)和55例健康自愿者选自武汉大学人民医院皮肤科门诊（2017年10月至2018年10月）;② 受试者进行血清25羟维生素D3［25-(OH)D3］,血浆D-二聚体(D-dimer)、纤维蛋白降解产物（FDP）,血沉（ESR）等实验室检查,并给予荨麻疹活动度评分（UAS7）;③ 分离和体外培养正常人与CSU患者各15例外周血单个核细胞（PBMC）,经1 nM和10 nM 1α,25-(OH)2D3处理后用实时荧光定量PCR技术检测白介素-6(IL-6)和维生素D受体（VDR）mRNA的表达水平;④ VD3严重缺乏（血清浓度<10 ng/mL）的患者补充大剂量(2400 IU/d)VD3,缺乏者(10~20 ng/mL)给予补充小剂量（800 IU/d）VD3,设未补充患者作对照,于6周和12周时再行UAS7评分。结果：与健康对照组相比,CSU患者血清25-(OH)D3水平明显减少,D-dimer、FDP及ESR水平明显增加,且与UAS7评分呈正相关;qPCR结果显示15例CSU患者PBMC IL-6和VDR mRNA表达水平较正常人明显增加;经1α,25-(OH)2D3处理后,IL-6 mRNA表达减少,VDR mRNA表达增加(P<0.05);与未补充组比较,VD3严重缺乏组给予补充大剂量VD3 12周,UAS7评分明显下降(P<0.0001)。结论：补充VD3有助于协同控制CSU的临床症状,可能与其抑制了荨麻疹亚临床炎症有关。     

Autoreaktive Urtikaria und Autoimmunurtikaria

Symptoms in patients with autoreactive urticaria (ArU), a sub-form of chronic urticaria (CU), are caused by circulating histamine-releasing signals. ArU patients are readily identified by the autologous serum skin test, in which they exhibit inflammatory reactions to their serum after intracutaneous injection. CU patients who also exhibit functional autoantibodies against IgE and/or its high affinity receptor Fc(epsilon)RI are thought to suffer from autoimmune urticaria (Aiu). ArU and AiU are pathogenetically and clinically different from other sub-forms of CU.     

慢性自发性荨麻疹患者血清IL-17、IL-23水平的检测及意义

目的:探讨白细胞介素-17(Interlenkin-17,IL-17)、白细胞介素-23(Interleukin-23,IL-23)在慢性自发性荨麻疹患者中的表达及意义。方法:选取慢性自发性荨麻疹患者和健康献血者各30例,用酶联免疫吸附法检测血清中IL-17、IL-23水平,并分析它们与病情、病程之间的关系。结果:慢性自发性荨麻疹患者的血清IL-17水平[(19.3±8.1)pg/mL]、IL-23水平[(28.9±11.1)pg/mL]均高于对照组[(8.6±5.7)pg/mL,(10.9±6.2)pg/mL],组间比较差异有统计学意义(t值分别为5.92、7.72,P值均<0.01)。慢性自发性荨麻疹患者IL-17、IL-23与症状评分呈正相关关系(r=0.89、r=0.75,P值均<0.01),与病程无明显相关性(r=0.23、r=0.24,P值均>0.05),IL-17与IL-23呈正相关关系(r=0.81,P<0.01)。结论:IL-17、IL-23在慢性自发性荨麻疹发病机理中可能起着重要作用。     

178例急性自发性荨麻疹转归为慢性的危险因素回顾性分析

目的：分析影响急性自发性荨麻疹（ASU）转归为慢性自发性荨麻疹（CSU）的危险因素。方法：回顾性分析本院2018年11月至2019年10月178例ASU患者的人口学信息、发病季节、初发病程、自诉可疑过敏原、自体血清皮肤试验（ASST）、7日荨麻疹活动度评分（UAS7）、血常规、血清总IgE测定、治疗药物，Logistic回归分析ASU转归为CSU的危险因素。结果：178例ASU中42例（23.60%）转归为CSU,单因素分析自诉食物过敏（P<0.001）、 ASST试验阳性（P<0.001）、初发病程（P＜0.001）与ASU患者转归为CSU具有相关性；多因素Logistics回归分析示自诉食物过敏（P=0.029）、ASST试验阳性（P=0.043）、初发病程长（P＜0.001）均是影响ASU转归为CSU的独立危险因素。结论：食物过敏、ASST试验阳性、初发病程长是ASU患者转归为CSU的危险因素。     

Chronic idiopathic urticaria: prevalence and clinical course

The purpose of our study was to assess the prevalence and clinical course of patients with chronic idiopathic urticaria (CIU), as well as possible causes or associated findings, laboratory findings and the duration of the disease in patients with chronic urticaria (CU). We retrospectively reviewed the 450 case record forms of patients with CU and/or angioedema who attended the Department of Dermatology, Siriraj Hospital, during the period 2000-2004. Of 450 patients with CU, 337 patients (75%) were diagnosed as CIU. Forty-three patients (9.5%) had physical urticaria, while 17 patients (3.8%) had infectious causes. Other possible causes were food, thyroid diseases, atopy, drugs, dyspepsia and collagen vascular diseases. In eighty-nine percent of patients, no abnormalities were detected at the time of physical examination. The most common abnormal laboratory finding was minimal elevation of the erythrocyte sedimentary rate (42%). In 61 patients, autologous serum skin tests had been done. Fifteen patients (24.5%) had positive results i.e. autoimmune urticaria. Anti-thyroglobulin and anti-microsomal antibodies were positive in 16 % and 12% of CIU patients respectively. After 1 year from the onset of the symptoms, 34.5% of CIU patients were free of symptoms and after 1.2 years from the onset of the symptoms, 56.5% of autoimmune urticaria patients were free of symptoms. The median disease duration of CIU and autoimmune urticaria were 390 days and 450 days respectively. Our study provided an overview of CU and CIU in a large series of Thai patients, based on etiological aspects and clinical courses.     

Systemic inflammatory response and calcification markers in patients with long lasting moderate-severe chronic spontaneous urticaria

Background

Low grade inflammation is associated with both chronic spontaneous urticaria (CSU) and atherosclerosis. Data regarding an association between urticarial inflammation and atherosclerosis and subsequent cardiovascular events are scarce. It has been demonstrated that matrix GLA protein (MGP), a biomarker of arterial calcification, is increased in patients with atherosclerosis.

Objectives

To evaluate circulating levels of markers of arterial calcification and acute phase response (APR) in patients with CSU.

Methods

Concentrations of MGP and IL-6 were measured in venous blood samples of patients with long-lasting moderate-severe CSU.

Results

There were no significant differences in serum MGP concentration between healthy subjects and CU patients. Serum IL-6 concentration was significantly higher in CSU patients as compared with healthy subjects.

Conclusions

The results confirm that CSU is accompanied by a low grade systemic inflammatory state. However, the long lasting urticarial inflammation was not paralleled by an increased circulating level of the calcification marker matrix Gla protein.

     

慢性自发性荨麻疹患者血清白细胞介素9、血小板活化因子水平与总IgE、病情严重程度和病程的相关性研究

【摘要】 目的 探讨慢性自发性荨麻疹（CSU）患者血清白细胞介素（IL）9、血小板活化因子（PAF）水平与血清IgE水平、病情严重程度和病程的相关性。方法 收集河北北方学院附属第一医院皮肤科2018年3月至2019年3月收治的60例活动期CSU,按7日荨麻疹活动评分（UAS7）将其分为轻度组、中度组和重度组;同时将经规范抗组胺治疗28 d后进入疾病静止期的患者纳入CSU静止期组。另选同期30例健康体检者为健康对照。采集各组受试者外周静脉血,使用酶联免疫法检测血清IL-9、PAF水平,选用免疫散射比浊法测定血清总IgE水平。分析CSU患者血清IL-9、PAF水平与血清总IgE水平、UAS7评分和病程之间的相关性。多组间比较采用单因素方差分析,组间两两比较采用LSD-t检验,相关性分析采用Pearson检验。结果 CSU活动期组男28例,女32例,年龄11 ~ 68（34.68 ± 8.62）岁,病程2个月至7年［（1.42 ± 0.41）年］。健康对照组男14例,女16例,年龄10 ~ 70（35.06 ± 7.89）岁。轻、中、重度CSU患者分别有12、26、22例,经规范治疗后22例纳入静止期组。CSU活动期组、CSU静止期组、健康对照组血清IL-9水平（144.34 ± 23.19、109.25 ± 20.77、107.23 ± 19.23 pg/ml）、PAF水平（362.45 ± 51.45、223.18 ± 32.46、221.23 ± 28.38 pg/ml）、总IgE水平（168.12 ± 32.48、24.04 ± 7.04、21.76 ± 5.95 IU/ml）差异均有统计学意义（F = 38.80、148.38、499.12,均P < 0.001）,CSU活动期组IL-9、PAF、总IgE水平均显著高于CSU静止期组与健康对照组（P < 0.05）;CSU静止期组与健康对照组差异均无统计学意义（P > 0.05）。血清IL-9水平、PAF水平与血清总IgE水平、UAS7评分均呈正相关（P < 0.05）,与病程无显著相关性（P > 0.05）。结论 CSU活动期患者血清IL-9、PAF水平均随病情严重程度的增加而明显升高,且与血清总IgE水平具有密切的相关性。     

Serum amyloid A levels in acute and chronic urticaria

Background: Serum amyloid A is an acute-phase protein. There is no available data regarding serum amyloid A levels in patients with acute (AU) and chronic urticaria (CU).Objectives: To investigate the association between serum amyloid A and urticaria.Methods: This was a case-control study of 81 patients who visited our Hospital between June and December 2016 with a diagnosis of urticaria. Eighty healthy controls (HC) who visited for routine health examination and physical checkups were recruited. Serum amyloid A and C-reactive protein levels were measured by automated methods.Results: Serum amyloid A and C-reactive protein levels were significantly higher in AU (Serum amyloid A: 207.1 (6.7-439.0) mg/L; C-reactive protein: 16.0 (0.2-90.0) mg/L) and CU (Serum amyloid A: 6.5 (2.5-35.8) mg/L; C-reactive protein: 1.0 (0.1-16.0) mg/L) compared with HC (Serum amyloid A: 5.04 (2.0-9.1) mg/L; C-reactive protein: 1.2 (0.1-5.6) mg/L), and in AU compared with CU (all P<0.05). There were no differences between the CU and HC group. In CU, Serum amyloid A levels in those with moderate/severe urticaria (median, 16.4 (9.7-35.8) mg/L) were higher than in those with mild urticaria (median, 5.7 (2.5-9.5) mg/L) and HC (all P<0.05). Serum amyloid A and C-reactive protein levels exceeded the normal lab range in 90.7% and 72.1% patients with AU compared with 28.9% and 13.2% patients with CU, respectively. Significant positive correlations were found between serum amyloid A and C-reactive protein (r = 0.562, P < 0.001).Study limitations: There was no comparison between active disease and remission.Conclusion: There was an association between serum amyloid A levels and urticaria. Higher serum amyloid A levels were associated with AU and more severe CU. Serum amyloid A may help to identify CU patients earlier.     

The Relation of Autologous Serum Skin Test and Autologous Plasma Skin Test Result with Various Clinical and Laboratory Findings in Patients with Chronic Spontaneous Urticaria

BackgroundDespite the autologous serum skin test (ASST) and autologous plasma skin test (APST) is widely used test accessing whether a patient with chronic spontaneous urticaria (CSU) has autoreactivity or not, the clinician often encounter difficulty making correlation between the test result and clinical implications.ObjectiveThis study was aimed to find any clinical and laboratory findings related to the ASST and APST response. Agreement and correlation between the two tests was also analyzed.MethodsA retrospective study was conducted on 300 CSU patients who underwent ASST, APST. The subjects were divided into four groups according to the skin test result. Also, the degree of serum and plasma response was recorded.ResultsBoth ASST and APST positive group had shorter duration of the disease, higher incidence of at least one episode of angioedema than negative group. There were no significant differences in the positivity for autoantibodies including antinuclear, ds-DNA, and thyroid-related between the two groups. The predicted positive rate of ASST and APST according to age showed bimodal peak and decreasing pattern according to disease duration. Predicted positivity of both tests declined with increase in total immunoglobuline E (IgE) level. In the correlation study, the two tests showed high correlation coefficients.ConclusionASST and APST positivity may be related to disease duration and severity of CSU. The two tests showed a generally consistent result. Autoreactivity may be gradually lost as disease continues. We suggest the autoreactivity in CSU could arise independently from IgE mediated immune process.     

136例慢性荨麻疹自体血清皮肤试验及实验室检测

目的：分析自体血清皮肤试验（ASST）及部分实验室检查指标与慢性荨麻疹（CSU）临床严重性？的相关性。方法：收集136 例CSU患者的临床资料,并进行ASST、血清总IgE、血浆D-二聚体、甲状腺功能及甲状腺抗体检测。结果：136例患者中总IgE升高37例,ASST阳性54例（39.7%）,其中ASST阳性患者病程45.27±65.67个月,明显长于ASST阴性患者的35.24±42.54个月（P＜0.01）。血浆D-二聚体升高49例（36%）,且与活动度评分（英文全称UAS）成正相关（P＜0.01, r=0.469）。患者抗甲状腺球蛋白抗体阳性24例(17.6%);甲状腺过氧化物酶抗体阳性14例(10.6%)。25例甲状腺功能异常患者中有9例ASST阳性。结论：ASST、血浆D-二聚体与CSU患者病情相关,而血清总IgE水平与病情无关。