川崎病患儿并发冠状动脉损伤的危险因素探讨及分析
发布时间：2018-08-17 10:56
【摘要】：研究背景川崎病(Kawasaki diseases,KD),即皮肤黏膜淋巴结综合征(mucocutaneous lymphnode syndrome,MCLS),是一种主要发生在5岁以下婴幼儿的急性发热性出疹性疾病,以全身中小血管炎变为主要病理改变[1]。病因及发病机制仍未完全清楚,目前认为KD是一种免疫介导的血管炎综合征。由于该病可发生严重的心血管病变,越来越引起人们重视。近年来,随着该病发病率的上升,其引起的冠状动脉损伤(coronary artery lesions,CAL)已成为儿童后天性心脏病的首要病因,可能与成年后缺血性心脏病关系密切,未经正规治疗的KD患儿CAL发生率达15%～25%[6]。静脉注射人免疫球蛋白(IVIG)和口服阿司匹林(ASP)的标准治疗后不仅可以明显的缩短热程,缓解临床症状,还可以明显减少CAL的发生率,然而部分患儿在治疗后仍有持续发热,且出现冠状动脉并发症。超声心动图是诊断和评估CAL的最敏感、简便、无创的方法。研究目的本文对山东大学齐鲁医院临床确诊的367例KD患儿的临床资料、相关实验室检测指标及超声心动图检查结果进行回顾性的分析,旨在分析探讨KD并发CAL的危险因素,以便儿科临床医师早期干预,预防及减少CAL的发生率,改善患儿的生活质量及预后。材料与方法1、回顾性分析山东大学齐鲁医院2006年2月-2016年2月确诊KD的住院患儿367例。其中男性257例,女性110例,男女之比为2.34:1;年龄为1个月-11岁,平均年龄为31.59±27.64个月。367例KD的诊断均符合2004年美国心脏病学会(AHA)及美国儿科学会(AAP)联合制定的KD诊疗指南。367例包括典型川崎病(313例)和不典型川崎病(54例)。将此367例KD患儿按年龄分为0～18个月龄组、18个月-3岁组、大于3岁组,分别为162、86、119例,比较3组冠状动脉损害发生率的差异。将此367例KD患儿根据在初始治疗中是否合用糖皮质激素分为两组:一组单独应用人免疫球蛋白(nGCs),另一组应用人免疫球蛋白联合糖皮质激素(Dex 0.1-0.2mg/kg·d,疗程1-3天)(GCs),并应用心脏彩色多普勒超声来评估两组KD患儿冠状动脉损害(CAL)的情况。其中nGCs组218例,GCs组149例。再将此367例根据心脏彩色多普勒超声检查结果分为KD并发冠状动脉损害组(CAL组)和KD未并发冠状动脉损害组(nCAL组)。其中CAL组122例,nCAL组245例。CAL诊断标准采用日本KD研究组提出的标准。2、统计被纳入367例KD患儿的性别、年龄、临床诊断、白细胞计数(WBC)、中性粒细胞比例(N%)、血红蛋白计数(HGB)、血小板计数(PLT)、红细胞沉降率(ESR)、C-反应蛋白(CRP)、谷丙转氨酶(ALT)、乳酸脱氢酶(LDH)、谷草转氨酶(AST)、前白蛋白(PA)、白蛋白(ALB)、球蛋白(GLB)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、甘油三酯(TG)、低密度脂蛋白(LDH-C)、高密度脂蛋白(HDL-C)、总胆固醇(Cho)、血钠(血Na)、纤维蛋白原、血浆D-二聚体(D__Di)、初始治疗是否合用激素及二维心脏彩色多普勒超声测量的冠状动脉内径值等资料,并将其纳入研究对象,分析KD并发冠状动脉病变的危险因素。3、将所收集的367例KD患儿的临床病历资料,采用统计软件SPSS 19.0进行处理,其中计数资料数据以例数(百分率)[n(%)]表示,计数资料组间比较采用x2检验。计量资料用均数土标准差(X土SD)表示,采用独立样本t检验,可信区间取95%,P0.05有统计学意义。对筛选出的有意义的变量分别与冠状动脉内径值进行线性相关性分析,得出各自相关系数及P值,其中P0.05为差异,即有统计学意义。结果1、统计2006-2015年每年KD的总例数、完全性KD、不完全性KD的发病例数,结果如下:2006(6,6,0),2007(15,11,4),2008(19,19,0),2009(17,16,1),2010(25,24,1),2011(30,29,1),2012(41,40,1),2013(50,41,9),2014(68,56,12),2015(81,62,19)。2、统计各个年龄组发病情况,结果显示:0-18个月龄组162例,发生率为44.1%,其中CAL组49例,nCAL组113例,CAL发生率30.2%;18个月-3岁组86例,发生率为23.4%,其中CAL组27例,nCAL组59例,CAL发生率31.4%;3岁以上组119例,发生率为32.4%,其中CAL组46例,nCAL组73例,CAL发生率38.6%。采用x2检验,两两比较得出,P0.05,差异无统计学意义。3、通过统计两组临床诊断得出,典型川崎病313例,其中CAL组112例(35.8%),nCAL组201例(64.2%),不典型川崎病54例,其中CAL组10例(18.5%),nCAL组44例(81.5%)。采用x2检验,P0.05,差异有统计学意义。4、通过统计两组性别得出CAL组122例,其中男90例,占73.7%,女32 "例,占26.3%;nCAL组245例,其中男157例,占64.1%,女88例,占35.9%。利用X2检验,P0.05,性别构成差异有统计学意义。5、相关实验室检测指标中,WBC、PLT、CRP、AST、ALB、Na以上这6个变量在CAL组与nCAL组中差异有统计学意义(P0.05);ESR、ALT、LDH、D_Di以上这4个变量在KD患儿均明显升高,但在CAL组与nCAL组中差异无统计学意义(P0.05);PA、HDL-C在KD患儿均明显下降,但在CAL组与nCAL组中差异无统计学意义(P0.05);N%、HGB、GLB、CK、CK-MB、Cho、TG、LDL-C、Fib在KD患儿中变化不明显,且在CAL组与nCAL组中比较差异无统计学意义。6、通过统计KD患儿在初始治疗过程中是否合用糖皮质激素(GCs)与冠状动脉损害的关系得出,nCAL组(245例)中合用GCs有138例(占56.3%),未合用GCs有107例(占43.7%);CAL组(122例)中合用GCs有80例(占65.6%),未合用GCs有42例(占34.4%),采用x2检验,P0.05,差异无统计学意义。7、对于筛选出的变量进行线性相关分析,其中性别、KD的临床诊断(完全性KD、不完全性KD)不满足正态分布,采用spearman相关分析。WBC、PLT、CRP、AST、ALB、Na满足正态分布,采用pearson相关分析。得出各自的相关系数及P值,P0.05差异有统计学意义。结果显示对所有年龄组KD患儿,KD典型/不典型、WBC、ALB与冠状动脉内径值显著相关;5岁者KD典型/不典型、WBC、ALB与冠状动脉内径值显著相关,≥5岁者WBC、PLT与冠状动脉内径值显著相关。结论1、本组病例研究显示,对所有年龄组KD患儿,典型KD、WBC、ALB为KD合并CAL的危险因素;对5岁年龄组患儿,典型KD、WBC、ALB为KD合并CAL的危险因素;对≥5岁年龄组患儿,WBC、PLT为KD合并CAL的危险因素。2、本组病例研究显示,KD患儿初始治疗合用糖皮质激素并未增加CAL发生率。
[Abstract]:Background Kawasaki disease (KD), or mucocutaneous lymph node syndrome (MCLS), is an acute febrile eruptive disease mainly occurring in infants under 5 years old. The main pathological changes are systemic small and medium-sized vasculitis. D is a kind of immune-mediated vasculitis syndrome. It has attracted more and more attention because of its serious cardiovascular disease. In recent years, with the increasing incidence of the disease, coronary artery lesions (CAL) have become the primary cause of acquired heart disease in children, and may be related to ischemic heart disease in adulthood. The incidence of CAL in children with KD without regular treatment is 15%-25%[6].Standard treatment with intravenous human immunoglobulin (IVIG) and oral aspirin (ASP) can not only significantly shorten the course of fever, alleviate clinical symptoms, but also significantly reduce the incidence of CAL. Coronary artery complications occur. Echocardiography is the most sensitive, simple and noninvasive method for the diagnosis and evaluation of CAL. Objective To retrospectively analyze the clinical data, laboratory test indexes and echocardiographic results of 367 children with KD diagnosed in Qilu Hospital of Shandong University. Materials and Methods 1. 367 hospitalized children with KD diagnosed in Qilu Hospital of Shandong University from February 2006 to February 2016 were retrospectively analyzed. Among them, 257 were males, 110 were females, and the ratio of males to females was 2.34:1. 367 children with KD were divided into 0 to 18 months of age group, 18 months to 3 years of age group, older group. The incidence of coronary artery lesions was compared in 162,86,119 children aged 3 years. The 367 children with KD were divided into two groups according to whether glucocorticoids were used in the initial treatment: one group was given human immunoglobulin alone (nGCs), the other group was given human immunoglobulin combined with glucocorticoids (Dex 0.1-0.2 mg/kg.d, 1-3 days of treatment) (GC). Coronary artery lesions (CAL) were assessed by color Doppler echocardiography (CDUS) in 218 children with KD and 149 children with GCs. The 367 patients were divided into two groups according to the results of CDUS: KD with coronary artery lesions (CAL group) and KD without coronary artery lesions (nCAL group). The diagnostic criteria for CAL were sex, age, clinical diagnosis, white blood cell count (WBC), neutrophil ratio (N%), hemoglobin count (HGB), platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), alanine aminotransferase (ALT), lactate dehydrogenase (L). DH, AST, prealbumin (PA), albumin (ALB), globulin (GLB), creatine kinase (CK), creatine kinase isozyme (CK-MB), triglyceride (TG), low density lipoprotein (LDH-C), high density lipoprotein (HDL-C), total cholesterol (Cho), serum sodium (Na), fibrinogen, plasma D-dimer (D_ Di), whether hormone and two-dimensional treatment are combined or not The data of coronary artery diameter measured by color Doppler echocardiography were included in the study. The risk factors of coronary artery disease complicated by KD were analyzed. 3. The clinical data of 367 KD patients were processed by statistical software SPSS 19.0. The counting data were represented by the number of cases (percentage) [n(%) and counted. Data were compared by x2 test. Measurements were expressed by mean soil standard deviation (X SD). Independent sample t test showed that the confidence interval was 95% and P 0.05 was statistically significant. Linear correlation analysis was conducted between the selected significant variables and the coronary artery diameter, and the correlation coefficients and P values were obtained. P 0.05 was the difference, i.e. P 0.05 was the difference. Results 1. The total number of KD cases, complete KD cases and incomplete KD cases in 2006-2015 were statistically analyzed. The results were as follows: 2006 (6,6,0), 2007 (15,11,4), 2008 (19,19,0), 2009 (17,16,1), 2010 (25,24,1), 2011 (30,29,1), 2012 (41,40,1), 2013 (50,41,9), 2014 (68,56,12), 2015 (81,62,19). The results showed that the incidence of CAL was 34.1% in 162 cases of 0-18 months old group, including 49 cases of CAL group, 113 cases of nCAL group, the incidence of CAL was 30.2%; 86 cases of 18-3 months old group, the incidence of CAL was 23.4%; 27 cases of CAL group, 59 cases of nCAL group, the incidence of CAL was 31.4%; 119 cases of over 3 years old group, the incidence of CAL was 32.4%, 46 cases of CAL group, 73 cases of nCAL group, the incidence of CAL was 38.6%. There were 313 cases of typical Kawasaki disease, including 112 cases in CAL group (35.8%), 201 cases in nCAL group (64.2%) and 54 cases of atypical Kawasaki disease, including 10 cases in CAL group (18.5%) and 44 cases in nCAL group (81.5%). There were 122 cases in CAL group, including 90 males, accounting for 73.7%, 32 females, accounting for 26.3%; 245 cases in nCAL group, including 157 males, accounting for 64.1%, 88 females, accounting for 35.9%. ESR, ALT, LDH, D_Di above the four variables in KD children were significantly increased, but there was no significant difference between the CAL group and nCAL group (P 0.05); PA, HDL-C in KD children were significantly decreased, but there was no significant difference between CAL group and nCAL group (P 0.05); N%, HGB, GLB, CK, CK-MB, Cho, TG, LDL-C, Fib in KD children did not change significantly, and in CAL group and nCAL group and nCAL group. There was no significant difference between the two groups. According to the statistics of the relationship between the use of glucocorticoid (GCs) and coronary artery lesion, 138 (56.3%) of the patients in the nCAL group (245 cases), 107 (43.7%) of the patients in the CAL group (122 cases), 80 (65.6%) of the patients in the CAL group (80 cases) and 42 (42 cases) in the non-use of GC. There was no significant difference between x2 test, P 0.05 and P 0.7. Linear correlation analysis was used to analyze the selected variables. The clinical diagnosis of gender and KD (complete KD, incomplete KD) did not satisfy the normal distribution. WBC, PLT, CRP, AST, ALB and Na met the normal distribution. Pearson correlation analysis was used to obtain their respective phases. The results showed that KD typical / atypical, WBC, ALB and coronary artery diameter were significantly correlated in all age groups; KD typical / atypical, WBC, ALB and coronary artery diameter were significantly correlated in 5-year-olds; WBC, ALB and coronary artery diameter were significantly correlated in over 5-year-olds; WBC, PLT and coronary artery diameter were significantly correlated in over 5-year-olds. The results showed that typical KD, WBC and ALB were risk factors for KD and CAL in all age groups; typical KD, WBC and ALB were risk factors for KD and CAL in 5-year-old children; WBC and PLT were risk factors for KD and CAL in children over 5-year-old children; and WBC and PLT were risk factors for KD and CAL in children over 5-year-old children. Rate of birth.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R725.4
[Abstract]:Background Kawasaki disease (KD), or mucocutaneous lymph node syndrome (MCLS), is an acute febrile eruptive disease mainly occurring in infants under 5 years old. The main pathological changes are systemic small and medium-sized vasculitis. D is a kind of immune-mediated vasculitis syndrome. It has attracted more and more attention because of its serious cardiovascular disease. In recent years, with the increasing incidence of the disease, coronary artery lesions (CAL) have become the primary cause of acquired heart disease in children, and may be related to ischemic heart disease in adulthood. The incidence of CAL in children with KD without regular treatment is 15%-25%[6].Standard treatment with intravenous human immunoglobulin (IVIG) and oral aspirin (ASP) can not only significantly shorten the course of fever, alleviate clinical symptoms, but also significantly reduce the incidence of CAL. Coronary artery complications occur. Echocardiography is the most sensitive, simple and noninvasive method for the diagnosis and evaluation of CAL. Objective To retrospectively analyze the clinical data, laboratory test indexes and echocardiographic results of 367 children with KD diagnosed in Qilu Hospital of Shandong University. Materials and Methods 1. 367 hospitalized children with KD diagnosed in Qilu Hospital of Shandong University from February 2006 to February 2016 were retrospectively analyzed. Among them, 257 were males, 110 were females, and the ratio of males to females was 2.34:1. 367 children with KD were divided into 0 to 18 months of age group, 18 months to 3 years of age group, older group. The incidence of coronary artery lesions was compared in 162,86,119 children aged 3 years. The 367 children with KD were divided into two groups according to whether glucocorticoids were used in the initial treatment: one group was given human immunoglobulin alone (nGCs), the other group was given human immunoglobulin combined with glucocorticoids (Dex 0.1-0.2 mg/kg.d, 1-3 days of treatment) (GC). Coronary artery lesions (CAL) were assessed by color Doppler echocardiography (CDUS) in 218 children with KD and 149 children with GCs. The 367 patients were divided into two groups according to the results of CDUS: KD with coronary artery lesions (CAL group) and KD without coronary artery lesions (nCAL group). The diagnostic criteria for CAL were sex, age, clinical diagnosis, white blood cell count (WBC), neutrophil ratio (N%), hemoglobin count (HGB), platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), alanine aminotransferase (ALT), lactate dehydrogenase (L). DH, AST, prealbumin (PA), albumin (ALB), globulin (GLB), creatine kinase (CK), creatine kinase isozyme (CK-MB), triglyceride (TG), low density lipoprotein (LDH-C), high density lipoprotein (HDL-C), total cholesterol (Cho), serum sodium (Na), fibrinogen, plasma D-dimer (D_ Di), whether hormone and two-dimensional treatment are combined or not The data of coronary artery diameter measured by color Doppler echocardiography were included in the study. The risk factors of coronary artery disease complicated by KD were analyzed. 3. The clinical data of 367 KD patients were processed by statistical software SPSS 19.0. The counting data were represented by the number of cases (percentage) [n(%) and counted. Data were compared by x2 test. Measurements were expressed by mean soil standard deviation (X SD). Independent sample t test showed that the confidence interval was 95% and P 0.05 was statistically significant. Linear correlation analysis was conducted between the selected significant variables and the coronary artery diameter, and the correlation coefficients and P values were obtained. P 0.05 was the difference, i.e. P 0.05 was the difference. Results 1. The total number of KD cases, complete KD cases and incomplete KD cases in 2006-2015 were statistically analyzed. The results were as follows: 2006 (6,6,0), 2007 (15,11,4), 2008 (19,19,0), 2009 (17,16,1), 2010 (25,24,1), 2011 (30,29,1), 2012 (41,40,1), 2013 (50,41,9), 2014 (68,56,12), 2015 (81,62,19). The results showed that the incidence of CAL was 34.1% in 162 cases of 0-18 months old group, including 49 cases of CAL group, 113 cases of nCAL group, the incidence of CAL was 30.2%; 86 cases of 18-3 months old group, the incidence of CAL was 23.4%; 27 cases of CAL group, 59 cases of nCAL group, the incidence of CAL was 31.4%; 119 cases of over 3 years old group, the incidence of CAL was 32.4%, 46 cases of CAL group, 73 cases of nCAL group, the incidence of CAL was 38.6%. There were 313 cases of typical Kawasaki disease, including 112 cases in CAL group (35.8%), 201 cases in nCAL group (64.2%) and 54 cases of atypical Kawasaki disease, including 10 cases in CAL group (18.5%) and 44 cases in nCAL group (81.5%). There were 122 cases in CAL group, including 90 males, accounting for 73.7%, 32 females, accounting for 26.3%; 245 cases in nCAL group, including 157 males, accounting for 64.1%, 88 females, accounting for 35.9%. ESR, ALT, LDH, D_Di above the four variables in KD children were significantly increased, but there was no significant difference between the CAL group and nCAL group (P 0.05); PA, HDL-C in KD children were significantly decreased, but there was no significant difference between CAL group and nCAL group (P 0.05); N%, HGB, GLB, CK, CK-MB, Cho, TG, LDL-C, Fib in KD children did not change significantly, and in CAL group and nCAL group and nCAL group. There was no significant difference between the two groups. According to the statistics of the relationship between the use of glucocorticoid (GCs) and coronary artery lesion, 138 (56.3%) of the patients in the nCAL group (245 cases), 107 (43.7%) of the patients in the CAL group (122 cases), 80 (65.6%) of the patients in the CAL group (80 cases) and 42 (42 cases) in the non-use of GC. There was no significant difference between x2 test, P 0.05 and P 0.7. Linear correlation analysis was used to analyze the selected variables. The clinical diagnosis of gender and KD (complete KD, incomplete KD) did not satisfy the normal distribution. WBC, PLT, CRP, AST, ALB and Na met the normal distribution. Pearson correlation analysis was used to obtain their respective phases. The results showed that KD typical / atypical, WBC, ALB and coronary artery diameter were significantly correlated in all age groups; KD typical / atypical, WBC, ALB and coronary artery diameter were significantly correlated in 5-year-olds; WBC, ALB and coronary artery diameter were significantly correlated in over 5-year-olds; WBC, PLT and coronary artery diameter were significantly correlated in over 5-year-olds. The results showed that typical KD, WBC and ALB were risk factors for KD and CAL in all age groups; typical KD, WBC and ALB were risk factors for KD and CAL in 5-year-old children; WBC and PLT were risk factors for KD and CAL in children over 5-year-old children; and WBC and PLT were risk factors for KD and CAL in children over 5-year-old children. Rate of birth.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R725.4
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