【作者】 王芳；

【导师】 徐金华； 唐慧；

【作者基本信息】 复旦大学 ， 皮肤性病学， 2009， 硕士

【摘要】 背景:慢性荨麻疹（chronic urticaria,CU）是皮肤科常见疾病之一,它的发作对患者的心情和生活状态都带来了极大的影响,但是目前慢性荨麻疹的病因仍然不是十分明确,据已知的数据显示,慢性荨麻疹中,25%-50%的患者是自身免疫性荨麻疹,是由肥大细胞膜上高亲和力IgE的受体FcεRI上α亚单位的抗体和IgE的抗体导致的,还有30%-40%的患者因找不到明确的发病原因而被认为是慢性特发性荨麻疹。ASST常被用来筛选具有自身抗体的慢性荨麻疹病人,它的灵敏度和特异性在80%左右。有趣的是,在非物理性因素导致的慢性荨麻疹病人中,ASST的阳性率是50%左右,而APST的阳性率达95%,而且有报道说给慢性荨麻疹患者皮下注射肝素或者用华法林治疗慢性荨麻疹都收到了良好的效果。还有一些研究显示,肝素可以抑制皮肤对自体血清的反应并且在体外试验中可以抑制嗜碱性粒细胞释放组胺。所以就有学者研究了慢性荨麻疹和凝血的关系,结果发现,在慢性荨麻疹患者和正常健康对照之间比较,D-二聚体、片段F₁₊₂、FⅦa都有所增高,FⅦa与片段F₁₊₂的表达增高一致,而FⅫa的区别不大,对皮损处皮肤活检示在炎症较重的细胞中有TF的高表达,这个结果提示了在慢性荨麻疹病人中可能有外源性凝血途径的激活。而近几年的研究热点显示,凝血过程中很多因子都与炎症有着千丝万缕的联系。故本课题将对慢性荨麻疹患者是否存在外源性凝血的异常展开初步研究,并讨论凝血因子在慢性荨麻疹的发病机制中的作用。目的:了解慢性荨麻疹患者发病的一般情况和DLQI,检测其PT、APTT、FⅦa、TAT水平和血浆D-二聚体水平,并研究FⅦa和TAT的关系、TAT和血浆D-二聚体的关系,同时分别研究血浆FⅦa水平和TAT水平与疾病症状严重程度的关系,探讨凝血因子在慢性荨麻疹发病中的作用,并为难治性的慢性荨麻疹提供可能的治疗线索。方法:入选30例慢性荨麻疹患者和30例正常人对照,首先调查慢性荨麻疹患者发病的一般情况和DQLI并对其进行症状分级;其次抽取慢性荨麻疹患者组和正常人对照组外周血,用凝固法检测PT、APTT,免疫比浊法检测血浆D-二聚体,ELISA法检测血浆中FⅦa和TAT的水平,并研究FⅦa和TAT的关系、TAT和血浆D-二聚体的关系,同时分别研究血浆FⅦa水平和TAT水平与疾病症状严重程度的关系。结果:30例慢性荨麻疹患者发病的一般情况、DQLI和症状分级见表1、表2和图1。慢性荨麻疹患者和正常人对照PT、APTT、血浆FⅦa水平、血浆TAT水平和血浆D-二聚体的均数比较见表5、表6、表7、表8和表9,从表中可以看出,与正常人相比,慢性荨麻疹患者PT和APTT并无差异（P＞0.05,P＞0.05）;但血浆FⅦa水平显著增高（P＜0.001）,血浆D-二聚体增高（P＜0.05）,血浆TAT水平显著增高（P＜0.001）。慢性荨麻疹患者血浆FⅦa水平和TAT水平存在正相关关系（P＜0.001）,TAT水平和D-二聚体水平亦呈正相关（P＜0.001）;慢性荨麻疹患者血浆FⅦa的水平与慢性荨麻疹症状等级呈正相关（P＜0.05）,但TAT水平和慢性荨麻疹症状等级无相关关系（P＞0.05）。结论:从本研究的分析中可以看出,慢性荨麻疹对患者生活质量有着极大的影响;患者的FⅦa、D-二聚体和TAT水平较正常人对照升高,且血浆FⅦa水平、TAT水平和D-二聚体水平之间的正相关关系证明了慢性荨麻疹患者外源性凝血途径的异常激活;而慢性荨麻疹患者血浆FⅦa的水平与疾病症状等级存在正相关系,但TAT水平和慢性荨麻疹症状等级无相关性,这提示在慢性荨麻疹的发病机制中凝血因子尤其是FⅦa可能起到一定作用。更多还原

【Abstract】 Background:Chronic urticaria（CU） is a common skin disease,whose etiology is not very clear yet.As the data we already know,25%-50%are autoimmune urticaria,which is caused by the autoantibodies against the alpha subunit of the high-affinity IgE receptor on mast cell and autoantibodies against IgE,but other 30%-40%are thought to be idiopathic for no identified causes.Auto serum skin test（ASST） can be carried out to determine these autoantibodies,whose sensitivity and specificity are just about 80%.What is interesting is that in patients with CU caused by physical factors been excluded the positive rate of ASST is about 50%,while the positive rate of APST is to 95%.There were also cases reporting injecting heparin subcutaneously or using warfarin to treat patients with CU got good effect.More studies showed heparin could inhibit reaction of skin to auto serum and inhibit histamine-releasing of basophilic granulocyte in vivo.So some scholars did research of CU and blood coagulation,the results revealed concentrations of plasma D-dimer,FⅦa and F₁₊₂ were higher in patients with CU than in normal controls,but concentration of plasma FⅫa had no difference between patients and controls.There was a positive correlation between plasma FⅦa content and F₁₊₂ content.Biopsies of skin lesion showed expression of TF was higher in cells with severe inflammation.These founds indicated abnormal activation of exogenous coagulation pathway in patients with CU.Recently,the hot research points finds many factors of blood coagulation have complicated relations with inflammation.On this foundation,we did primary research to determine if patients with CU have activation of exogenous blood coagulation pathway and discuss the roles coagulation factors playing in pathogenesis of CU. Objective:To know common sick status and DQLI of patients with CU.To evaluate the role of blood coagulation in the pathogenesis of chronic urticaria by investigating the PT,APTT,concentration of plasma D-dimer, concentration of plasma activated factorⅦin patients with chronic urticaria and evaluate the relationship between concentration of plasma D-dimer and concentration of FⅦa,at the same time,the correlation between concentration of FⅦa and the disease activity and correlation between concentration of TAT and the disease activity are to be confirmed.By doing this,we hope to discover how coagulation parameters act in CU and find possible therapy clues of incurable CU.Methods:Studied 30 patients with CU and 30 normal controls and investigated common sick status and DQLI of patients,whose disease activity was also estimated.Both in the 30 patients and 30 healthy subjects,PT and APTT were measured by coagulation method,plasma D-dimer content was determined by turbidimetric immunoassay,plasma FⅦa content was investigated by ELISA. Four correlations,which are plasma FⅦa and TAT content,TAT and D-dimer content,concentration of FⅦa and disease activity and concentration of TAT and disease activity,were studied.Results:Common sick status,DQLI is showed in chart 1 and chart 2,while picture 1 shows disease activities.The results of PT,APTT,plasma FⅦa,TAT and D-dimer content are in chart（5-9）.Compared with the normal controls, there was no significant difference of PT and APTT in patients with chronic urticaria（P＞0.05,separately）.But the plasma D-dimer content was higher in patients than controls（P＜0.05） and plasma FⅦa content was significant higher in patients than that in controls（P＜0.001）.There was a positive correlation between concentration of FⅦa and TAT（P＜0.001）,the similar correlation also existed between concentration of TAT and D-dimer（P＜0.001）,and the level of FⅦa,but not the level of TAT（P＞0.05） was significantly correlated with the disease activity（P＜0.05）.Conclusion:From analysis of this study,CU does much negative influence to patients’ life quality.And elevated concentrations of plasma FⅦa,D-dimer and TAT and the positive correlations between FⅦa and TAT content,TAT and D-dimer content prove abnormal activation of exogenous blood coagulation. While the fact that concentration of plasma FⅦa and disease activity has positive correlation,which doesn’t exist between plasma TAT content and disease activity,suggests that the activation of blood coagulation may play a part in the pathogenesis of chronic urticaria.Coagulation factors,especially FⅦa,may involve in the pathogenesis of chronic urticaria.更多还原