【作者】 胡景伟；

【导师】 周忠蜀； 蔡哲；

【作者基本信息】 中国协和医科大学 ， 儿科学， 2010， 博士

【摘要】 背景：近年来,国内外关于糖皮质激素(GCs)治疗川崎病(KD)的研究逐渐增多,但所得到的结果不尽一致,究竟其有效性和安全性如何尚不完全清楚。目的：1.评价GCs治疗KD的有效性。2.评价GCs治疗KD的安全性。方法：以川崎病、激素、糖皮质激素、皮质类固醇激素、肾上腺皮质激素、地塞米松、强的松、氢化可的松、强的松龙和甲基强的松龙为检索词,在全文范围检索14种电子文摘及全文数据库,手工检索3种日文杂志,收集GCs治疗KD的随机对照试验或半随机对照试验。判定指标：①主要指标：冠状动脉病变(CAL)包括冠状动脉扩张和冠状动脉瘤发生率；②次要指标：治疗后发热持续时间、C-反应蛋白(CRP)、红细胞沉降率(ESR)、治疗失败率和不良反应发生率。由两位研究者独立纳入试验、提取数据和评价质量,对所纳入的试验进行系统评价。应用RevMan 5.0.23.0软件进行分析,对于二分变量使用优势比,对于连续性变量使用加权平均差值,二者的可信区间均规定为95%。分析前先进行异质性检验,若无异质性,采用Mental-Haenszel法应用固定效应模型进行分析。如试验存在异质性,采用随机效应模型进行分析。在总体分析的基础上,根据KD类型和治疗方案的不同,分以下3种情况进行分组分析：GCs治疗初治KD、GCs辅助IVIG治疗初治KD和GCs治疗IVIG无反应型KD的试验。发表偏倚采用漏斗图分析。结果：1.共纳入15个试验(14篇文章),患者1105例,其中GCs治疗组547例,对照组558例。6项为单独应用GCs治疗KD的试验,5项试验为GCs辅助IVIG与单独应用IVIG治疗KD的比较,4项试验对GCs在IVIG无反应型KD的治疗进行研究。2.详细描述随机方法者6篇,3篇报告失访与退出,两篇采用意向性治疗分析,采用分配隐藏和盲法的试验仅1篇。Jadad评分3-5分4篇,1-2分10篇。3.总体分析显示GCs组治疗后1个月内CAL发生率低于对照组(p<0.05)；分组分析显示,GCs组与对照组CAL发生率差异均无统计学意义(p>0.05)。4.总体分析与分组分析均显示,GCs组与对照组治疗1个月以后CAL发生率差异无统计学意义(p>0.05)。5.总体分析显示GCs组发热持续时间明显短于对照组(p<0.05)。分组分析显示,GCs治疗初治KD的试验中两组发热时间无差异(p>0.05),其余两种情况下GCs组发热持续时间均明显短于对照组(p<>0.05)。6.总体分析与分组分析均显示,GCs组治疗3天后发热患者少于对照组(p<0.05)。7.总体分析与分组分析均显示,GCs组治疗失败率低于对照组(p<0.05)。8.总体分析显示治疗2周后GCs组ESR水平低于对照组(p<0.05),分组分析显示除GCs治疗IVIG无反应型KD的试验外,其余两种情况下GCs组ESR水平低于对照组(p<0.05)。9.总体分析与分组分析均显示,GCs组治疗1周后CRP水平低于对照组(p<0.05)。10.总体分析与分组分析均显示,GCs组与对照组不良反应发生率无差异(p>0.05)。11.敏感性分析显示,GCs组与对照组比较,治疗1个月以内CAL发生率、治疗1个月后CAL发生率和不良反应发生率差异无统计学意义(p>0.05)。GCs组发热持续时间短于对照组(p<0.05),治疗失败率低于对照组(p<0.05)；12.漏斗图中散点分布稍欠对称,提示存在发表偏倚。结论：1.本研究显示,目前没有证据支持GCs能够降低KD患者发生CAL的风险。2.在IVIG治疗的基础上,GCs能够进一步缩短KD患者发热时间,明显降低CRP及ESR水平,减少治疗失败的患者数量。3.GCs不会增加KD患者发生CAL和其他不良反应的风险。目的：1.探讨川崎病(KD)并发冠状动脉病变(CAL)的临床特点；2.观察大剂量静脉免疫球蛋白(IVIG)治疗对KD患者冠状动脉及实验室检查的影响；3.分析不完全KD(IKD)的临床特征。方法：以我科收治的57例KD患者为病例组,同期住院治疗24例非感染患者作为对照组,对临床资料、实验室检查和随访结果进行回顾性分析。结果：1.KD组与对照组年龄和性别比较差异无统计学意义(P＞0.05)。2.52例KD患者行超声心动图检查,冠状动脉正常(NCAL)者32例,CAL者20例,包括冠状动脉扩张(CAD)16例,冠状动脉瘤(CAA)4例。CAL组口腔粘膜病变及肛周皮肤脱屑的发生率低于NCAL组(p<0.05)；发热时间、白细胞(WBC)、C-反应蛋白(CRP)及天门冬氨酸氨基转移酶(AST)高于NCAL组(p<0.05)；在CAD患者中,左冠状动脉(LCA)脉病变的发生率高于右冠状动脉(RCA)(P<0.01)。3.IVIG治疗后6-18天复查超声心动图,CAD患者左、右冠状动脉直径均明显缩小(p<0.05)；CAA患者冠状动脉内径变化不明显(p>0.05)。4.治疗前KD组WBC和中性粒细胞比例(N%)高于对照组(p<0.05),淋巴细胞比例(L%)低于对照组(p<0.05),血小板(PLT)与对照组比较差异无统计学意义(p>0.05)；IVIG治疗后WBC、N%与L%与对照组比较差异无统计学意义(p>0.05),PLT则明显升高(p<0.05)。与治疗前比较,治疗后KD组的WBC和N%明显降低,L%明显升高,差异有统计学意义(p<0.05),PLT明显升高(p<0.05),CRP于治疗1周内明显降低,红细胞沉降率(ESR)于治疗后2周明显降低(p<0.05)。5.57例KD)患者中,诊断为典型KD(CKD)41例,不完全型KD(IKD)16例。CKD组发热时间短于IKD组(p<0.05),IKD组结膜充血、手足硬肿和口腔黏膜病变的发生率低于CKD组(p<0.05)；IKD组与CKD组比较,血液学及心电图检查结果无差异(p>0.05),CAL和IVIG无反应型KD的发生率较高(p<0.05)。6.33例KD患者进行随访,18例NCAL者无新发病变,13例CAD患者冠状动脉直径恢复正常,1例CAA冠状动脉直径增加,1例CAA病变明显减轻。结论：1.本组资料显示,热程长、血WBC、CRP及AST升高是KD患者并发CAL的危险因素,而性别、年龄和PLT与CAL无关。2.大剂量IVIG治疗急性期KD使扩张的冠状动脉直径明显缩小,WBC、N%、L%、CRP和ESR恢复正常,但PLT不受IVIG影响逐渐升高。3.IKD临床症状隐匿,实验室检查结果与CKD类似,但发生CAL的风险高于CKD,并且对IVIG治疗不敏感。更多还原

【Abstract】 Background In recent years, the number of researches which treat Kawasaki disease (KD) with glucocorticoids (GCs) is gradually increasing, but the results obtained are controversial, the efficacy and safety of the treatment are not fully understood.Objectives1. Evaluate the efficacy of GCs with regard to the prevalence of coronary artery lesion (CAL), duration of fever, changes in blood and biochemical tests.2. Evaluate the safety of GCs in the treatment of Kawasaki disease, particularly in the inducement of CAL, compared with intravenous immunoglobulin(IVIG), aspirin and other drugs.Methods Kawasaki disease, steroids, glucocorticoids, corticosteroids, adreno-corticotropic hormone, dexamethasone, prednisone, hydrocortisone, prednisolone, and methylprednisolone are used as the search terms in the full-text field from 14 electronic databases, hand searched three kinds of Japanese magazines, the randomized controlled trials (RCT) or quasi-randomized controlled trials that describe the use of GCs for the treatment of Kawasaki disease in children were sought. The outcome measures included:1, primary outcome:the incidence of CAL, including coronary artery dilation and coronary artery aneurysms; 2, secondary outcome:the duration of fever after treatment, blood and biochemical test results such as C-reactive protein(CRP) and erythrocyte sedimentation rate (ESR), response to treatment, and adverse effects. Data on methodological quality and trial information was extracted by two researchers separately. Cochrane review methodology was used for assessing trial quality and effectiveness. Each dichotomous outcome will be measured in terms of odds risk, continuous outcomes will be shown as weighted mean differences and combined for meta-analysis with RevMan5.0.23.0 software. Fixed-effect approach will be used unless there is significant heterogeneity, in which case results will be confirmed using a random-effects statistical model. We also performed sensitivity analysis on results to look at the possible contribution of differences in methodological quality, the outcomes were pooled statistically too. Funnel plot was used to analysis the publication bias.Results1.1105 cases in 15 trails were included, of which 547 cases in GCs therapy group and 558 cases in control group. In 6 trials, GCs was used to treat Kawasaki disease alone, GCs in addition to IVIG treatment on Kawasaki disease with IVIG alone were compared in 5 trials,4 tests evaluated the effect of GCs in IVIG unresponsive Kawasaki disease.2.6 articles describe the random method,3 papers report withdrawals and drop-outs, two research use intention to treat analysis, only one study use allocation concealment and blinding in the test. Jadad score 3-5 points in 4 papers,1-2 points in 10 papers. 3. General analysis showed that the incidence of CAL in GCs group is lower than control group within 1 month after treatment (p<0.05); subgroup analysis showed that the incidence of CAL is not different between GCs group and control group (p>0.05).4. The incidence of CAL is not different between GCs group and control group 1 month after treatment (p>0.05).5. General analysis showed that the fever duration in GCs group is shorter than control group (p<0.05). Subgroup analysis showed that in the patients who was initially treated by GCs alone, the difference is not significant (p>0.05). But in the other patients, fever time is significantly shorter in GCs group (p<0.05).6.3 days after treatment, the fever patients in GCs group is less than control group (p<0.05).7. Treatment failure rate in GCs group is less than control group (p<0.05).8. General analysis shows, in GCs group, the level of ESR after 2 weeks of treatment lower than control group (p<0.05), subgroup analysis get the same result except in IVIG resistant KD patirnt.9. After 1 week of treatment, the level of CRP in GCs group is lower than control group (p<0.05).10. The adverse events in two groups is not different (p>0.05).11. Excluded the low-quality trials which Jada score less than 3, the incidence of adverse effect and CAL in GCs group are not different from control group (p>0.05); fever duration is significantly shorter than the control group (p<0.05); treatment failure rate lower than control group (p<0.05).12. The funnel plot analysis suggests that publication bias exists.Conclusions1. This study shows that there is no evidence to support the GCs can reduce the CAL risk of patients with KD.2. In KD patients, GCs in addition to IVIG can reduce fever duration, decrease CRP and ESR levels, and reduce treatment failure rate further.3. GCs can not increase the risk of CAL in KD patients. Objectives1. To study the clinic features of coronary artery lesion (CAL) in Kawasaki disease (KD).2. To observe the changes of laboratory examination and coronary artery induced by intravenous immunoglobulin (IVIG) on patients with KD.3. To investigate the clinical features of incomplete Kawasaki disease (IKD). Methods The clinic information, laboratory examination and follow-up results of 57 KD patients and control group of 24 non-infectious patients were analyzed retrospectively.Results1. There is no significant difference in gender and age between KD and control group (p>0.05).2. Echocardiography was performed in 52 patients,30 in non-coronary artery lesion group (NCAL),22 in CAL group. The frequency of perianal skin desquamation, and lesions of lips and oral cavity are less than CAL group (p<0.05). The time of fever, the level of white blood cells(WBC), C-reactive protein(CRP), and aspartate aminotransferase(AST)in CAL group are significantly higher than NCAL group (p <0.05), in patients with coronary artery dilation (CAD), left coronary artery (LCA) is more susceptive to dilation than right coronary artery (RCA) (p<0.01).3. In CAD patients, the diameter of LCA and RCA were significantly recovery 6 to 18 days after IVIG treatment (p<0.05), while that of CAA patients did not change significantly (p>0.05).4. Before treatment, WBC and the proportion of neutrophil (N%) in KD group were higher than controls(p<0.05), while the proportion of lymphocytes(L%) was lower than control group(p<0.05). In KD group, after IVIG treatment, WBC and N% decreased significantly, L% and PLT increased significantly(p<0.05), CRP was significantly decreased 1 week after treatment, erythrocyte sedimentation rate (ESR) was significantly decreased 2 weeks after treatment (p<0.05).5.41 of 57 KD patients were classic Kawasaki disease (CKD),16 of them were incomplete Kawasaki disease (IKD). In IKD group, the fever duration is longer than CKD group, the frequency of conjunctival congestion, indurative edema of palms and soles, and changes of lips and oral cavity are less than CKD group (p<0.05). The incidence of CAL and IVIG resistance in IKD group is higher than CKD group (p<0.05).6.33 KD patients were followed up, no new impairment occurred in 18 NCAL cases, the dilated coronary artery in 13 patients with CAD regressed completely,1 coronary artery aneurysms (CAA) lesion deteriorated,1 CAA lesion was reduced.Conclusions1. Long duration of fever, high value of WBC, CRP, and AST are the risk factors of CAL secondary to KD. 2. IVIG is an effective agent in the treatment of KD, WBC, N%, L%, CRP and ESR returned to normal, but the platelet increased gradually.3. Although IKD don’t fulfill the Classic diagnostic criteria of KD, the risk of CAL is higher than CKD. Moreover, IKD is not sensitive to IVIG, so the doctors should pay more attention to it.更多还原