【作者】 石春蕊；

【导师】 严祥；

【作者基本信息】 兰州大学 ， 内科学， 2011， 博士

【摘要】 背景慢性荨麻疹(chronic urticaria,CU),也被称为慢性自发性荨麻疹(chronic spontaneous urticaria, CSU)被定义为自发风团和/或伴发血管神经性水肿超过6周及以上者,是皮肤科的常见过敏性疾病。它越来越成为世界范围内非常严重的健康问题与负担,并因环境和食品污染及工业化进程不断加快等因素而发病风险激增。其发病率逐年上升,目前全世界人口发病率为0.5-1%。慢性荨麻疹患者症状反复,迁延不愈,严重地影响了患者的睡眠、工作、私人生活和精神状态,降低了患者的生活质量。它直接和间接增加了医疗保健成本,对社会造成不利影响。H1-抗组胺药物治疗是目前的主要治疗方法,但其仅对部分患者有效,大多数的患者病因不明,症状反复,治疗棘手。因此,迫切需要新的治疗策略及其病因学研究。目的本课题拟通过循证医学的方法系统评价过敏原特异性免疫治疗(Allergen specific immunotherapy, SIT)和中药当归饮子治疗慢性荨麻疹的安全性及有效性；同时通过对兰州地区慢性荨麻疹的疾病复发相关因素调查,为兰州地区荨麻疹病因学研究及防治慢性荨麻疹复发提供临床资料及依据。方法计算机检索Cochrane图书馆、Pubmed、Science Citation Index Expanded, EMBASE. CNKI、VIP,手工检索有关引用文献,收集以过敏原特异性免疫治疗和中药当归饮子为干预措施治疗慢性荨麻疹(CU)的随机对照试验(RCT),按Cochrane系统评价方法,评价纳入研究的方法学质量并提取有效数据进行Meta分析。主要结局指标为有效率(包括治愈率、好转率)和生活质量,次要结局指标为复发率和不良反应事件。采用病例对照方法,选择收集兰州地区慢性荨麻疹患者病例222例,同时收集163例非过敏性疾病患者作为对照人群,对两组人群首先进行性别、年龄等基线资料比较。然后对两组人群的饮食习惯,本次发病两周前的进食状况、用药情况、预防接种等信息进行回顾性调查,并采用SPSS13.0软件进行数据统计分析。结果对于过敏原特异性免疫治疗,共纳入14个研究(包括1838例患者),原始文献全部来自中国,无双盲安慰剂对照试验研究。Meta分析结果显示：过敏原特异性免疫治疗与常规治疗(conventional treatment, CT)相比有更高的好转率[OR=2.39,95%CI(1.73,3.30)I2=55%]和治愈率[OR=2.13,95%CI(1.55,2.91)I2=61%]。研究提示治疗后两周过敏原特异性免疫治疗也许可降低慢性荨麻疹的复发率[OR=0.38,95%CI(0.24,0.61)I2=36%]；但是在采用荨麻疹活动评分(UAS)的原始研究与未采用UAS评分的原始研究间合并研究结果存在差异；只有一个研究报道了生活质量评价数据；在不良反应方面,没有研究报道在过敏原特异性免疫治疗中有严重的不良反应。对于中药当归饮子治疗,共纳入11个研究(包括1081例患者),原始文献全部来自中国,无双盲安慰剂对照试验研究。Meta分析结果显示：与常规抗组胺治疗相比中药当归饮子有更高的治愈率[OR=2.36,95%CI(1.80,3.10)I2=22%],好转率[OR=4.56,95%CI(2.65,7.87)I2=0%],在随访治疗后三个月较常规治疗复发率降低[OR=0.43,95%CI(0.22,0.82)I2=0%],没有研究报道中药当归饮子对生活质量评价数据。在不良反应方面,没有研究报道中药当归饮子治疗有严重的不良反应。双录入《兰州地区慢性荨麻疹患者发病相关因素调查表》问卷调查数据,经logistic回归分析显示：兰州地区慢性荨麻疹患者组发病前在进食海鲜(P<0.001)、药物(P<0.002)、失眠(P<0.001)、遇冷(P<0.001)、热(P<0.036)、风(P<0.003)及摩擦(P<0.000)等因素方面与对照组的差异具有统计学意义。结论当前证据表明,IgE介导的过敏反应可能是部分慢性荨麻疹患者的发病原因,与常规抗组胺药物治疗方法相比,过敏原特异性免疫治疗可能对这部分患者有益。但是由于纳入的原始研究文献数量较少,方法学质量偏低,因此现有证据尚不能获得一个肯定的结论,需要有更多病例、更有说服力的数据和高质量的研究来确定该结论。此外,当前证据还表明对比常规抗组胺药物治疗方法,中药当归饮子对慢性荨麻疹有更好的治愈率和好转率,可在治疗后三个月降低复发率。但是同样由于纳入原始研究文献的数量较少,方法学质量偏低,当前证据尚不能得出肯定结论,虽然如此,中药当归饮子的优势值得做进一步的研究,特别是需要严格设计的多中心、大样本、随机、双盲对照试验来支持这一结论。慢性荨麻疹患者在发病前两周进食海鲜、药物、失眠、冷热变化、遇风、摩擦等因素是导致该病复发的危险因素。更多还原

【Abstract】 BACKGROUNDChronic urticaria (CU) also known as chronic spontaneous urticaria (CSU) is a common allergic disease of dermatology, characteristic by reoccurring itching and wheal lasting longer than six weeks, which accompanied by angioedema in40%of patients. It has became a very serious worldwide health problem and burden increasingly. The incidence of CU is increasing year by year because of environmental and food contamination, accelerating by the process of industrialization. By now,0.5-1.0%of the population suffers from CU in the world. CU impact patients’quality of life (QOL) seriously. There are high direct and indirect healthcare costs of this disease due to the large socioeconomic implications of reduction in performance. Although antihistamines as mainstay of treatment for CU can alleviate some symptoms, factors such as capricious course, intermittent attack, poor responsiveness to treatment, and ongoing recurrence trouble both clinicians and patients. Thus, new therapy strategies and etiology research of CU constitute our most urgent problem.OBJECTIVESThe study systematically reviewed allergen specific immunotherapy (SIT) and Chinese angelica decoction (CAD) for CU by meta-analysis, to evaluate the efficacy and safety of SIT and CAD versus conventional treatment (CT) in the treatment of CU. To investigate relapse-related risk factors of patients with urticaria in Lanzhou area, provide clinical evidence and information to the prevention of relapse of this disease.METHODSThe comprehensive search strategies of various electronic databases (MEDLINE, EMBASE, the Cochrane Library, ISI Web of Knowledge, China National Knowledge Infrastructure, CNKI, CBMWeb and Chinese Scientific Journals Full Text Database) were used in this study to evaluate the efficiency and safety of SIT and CAD versus conventional treatment (CT) in patients with CU. In addition, manual searched reference lists from original studies and review articles. Only randomized controlled trials (RCT) included our searching criteria but not limited language. Upon strictly included and excluded standard, the primary outcomes were efficacy and quality of life (QOL) and the secondary outcomes were relapse rate and adverse events (AEs).Case-control study was used to collect the information from222CU cases and163controls that were all Lanzhou dwellers. The information including general social and demographic characteristics, eating habits, diet history, drugs using history, vaccination history, sleep and mental condition, physical stimulation, et al. were investigated retrospectively. Then, SPSS13.0software was used for statistical analysis.RESULTSFourteen studies (1,838patients) were included in systematical review of SIT. Our study demonstrated that SIT seemed to show more clinical efficacy rate (OR2.39;95%CI,1.73to3.30;I2=55%), more complete recovery rate (OR2.13;95%CI,1.55to2.91;I2=61%), and less relapse rate two weeks after treatment (OR0.38;95%CI,0.24to0.61;I2=36%) than CT. However, the pooled results of studies using urticaria activity score (UAS) were different from those of studies using non-UAS. Only one study reported improved QOL and no study reported serious AEs after SIT.Eleven studies (1,081patients) were included in systematical review of CAD. Our study demonstrated that CAD seemed to show more complete recovery rate (OR2.36;95%CI,1.80to3.10; I2=22%), more clinical efficacy rate (OR4.56;95%CI,2.65to7.87; I2=0%), and less relapse rate the third month after treatment (OR0.43;95%CI,0.22to0.82;I2=0%) than CT. No study reported QOL and serious AEs after CAD.After logistic regression analysis, the results of the survey with double entry and validation showed:there were statistically significant different between the case and control group on eating seafood (P<0.001), insomnia (P<0.001), using drugs (P<0.002), and the physical factors, such as hot (P<0.036), cold (P<0.001), wind (P<0.003) and friction (P<0.000).CONCLUSIONSCurrent evidences indicate that IgE-mediated allergy may be causative in a small number of CU patients and specific immunotherapy with these allergens may be beneficial in those patients. However, the number of included studies was small and the quality was low. So, available evidence is not adequate to draw an affirmative conclusion and larger studies of high quality are needed to provide increasingly convincing data and cases.CAD might show better clinical efficacy than CT for CU patients. However, the number of included studies was small and the quality was low. So current evidence is not adequate to draw an affirmative conclusion and larger studies of high quality are needed to provide increasingly convincing data and cases. Nevertheless, the advantages of CAD was considered worthy of further investigation, and the strict design of the multi-center, large sample, randomized, double-blind controlled trials to support this conclusion were extremely needed.The relapse-related risk factors:seafood eating, drugs using, insomnia, physical stimulation such as encountered cold, heat and wind, friction were showed on patients with CU in Lanzhou area, which should be avoided to prevent disease recurrence.更多还原