Patients diagnosed with Kawasaki disease before the fifth day of illness have a higher risk of coronary artery aneurysm

BACKGROUND: A fever lasting for at least 5 days is an essential characteristic of the original diagnostic criteria of Kawasaki disease (KD). However, it is not difficult for an experienced physician to confirm the diagnosis of KD before the fifth day of fever. The aim of this study is to investigate the effect of intravenous gamma globulin therapy (IVGG) in KD initiated before the fifth day of illness. METHODS: A total of 125 patients treated with IVGGwere divided into group A (IVGG was initiated before the fifth day of illness, n= 46) and group B (IVGG was initiated at the fifth day or after, n= 79). Patients' characteristics,laboratory findings, treatments and outcomes were compared between the groups. RESULTS: White blood cell count value, C-reactive protein and Harada's score showed no difference between the groups. A significantly higher average value of alanine aminotransferase(ALT) was observed in group A. Although the treatments were identical in both groups, the average duration of fever from the initial day of IVGG in group A was significantly longer than in group B. The incidence of aneurysm in group A was significantly higher than that in group B. Stepwise regression analysis using aneurysm as a dependent variable revealed that group A and ALT were significant. CONCLUSIONS: Patients diagnosed with KD before the fifth day of illness showed a poor response to IVGG. This observation might be related to high ALT values. Further examination concerning the modification of treatment in such patients is necessary.     

Current issues in Kawasaki disease

The most important clinical aspect of Kawasaki disease is the cardiovascular problems. This article reports on the cardiovascular spectrum in acute Kawasaki disease, analysis of myocardial infarction and fatal cases, a follow-up study on the natural history of coronary artery lesions, long-term cardiovascular problems including premature atherosclerosis, problems in the adult cardiology and the treatment of acute Kawasaki disease. The etiology and pathogenesis of this disease are still unknown. Current hypotheses and leading studies on the etiology and the pathogenesis of Kawasaki disease are also reviewed.     

Incidence and clinical features of incomplete Kawasaki disease

During the nine-year period from 1983 to 1991, a total of 242 patients (142 males and 100 females) presenting with Kawasaki disease were seen at one hospital. Among them, 25 (10%) patients demonstrated incomplete Kawasaki disease and 17 of these 25 (68%) lacked two of the six principal symptoms of Kawasaki disease, with the most frequently missing symptoms being cervical lymphadenopathy and polymorphous exanthema. The typical laboratory features of Kawasaki disease, such as elevated erythrocyte sedimentation rate, leukocytosis, anemia, positive C-reactive protein and thrombocytosis were also seen in the incomplete cases. None of the 25 patients underwent iv gamma-globulin therapy while in 1 (4%), transient dilatation of the coronary artery was recognized. Incomplete Kawasaki disease may therefore be characterized by a less frequent association of rash, cervical lymphadenopathy and coronary involvement.     

川崎病患儿血红蛋白及血钾变化与冠状动脉病变的关系研究

川崎病(Kawasaki disease,KD)又称皮肤粘膜淋巴结综合征(mucocutaneous lymphnode syndrome,MCLS),是一种以全身血管炎性病变为主的儿童急性发热出疹性疾病,主要病理改变为全身性非特异性血管炎,可引起多脏器受累,以心血管病变最为严重,多侵犯冠状动脉[1],川崎病的早期诊治具有十分重要的意义。本研究通过观察川崎病患儿治疗前后血红蛋白和血钾的变化,结合冠状动脉受累情况,探讨血红蛋白和血钾在川崎病并发冠状动脉病变中的意义。1对象与方法1.1对象2000年1月～2004年1月我科收治川崎病急性期(≤11d)住院患儿50例,均符合第3届国际川崎病…     

Hemodynamic factors of thrombus formation in coronary aneurysms associated with Kawasaki disease

BACKGROUND: We studied the mechanism of thrombus formation in coronary aneurysms based on rheological findings. METHODS: We studied 43 coronary aneurysms in 33 patients with Kawasaki disease (mean (+/- SD) age 6.1 +/- 4.3 years). These lesions were divided into three groups on the basis of maximum diameter: (i) small (group S); (ii) medium sized (group M); and (iii) large (group L) aneurysms. Using a Doppler flow guidewire and a pressure-monitoring guidewire, we measured coronary flow velocity and perfusion pressure inside aneurysms and in adjacent normal-looking vessels. We calculated the average peak velocity (APV) index, the mean coronary perfusion pressure (P) index and shear index. RESULTS: The APV index and shear index decreased significantly (p < 0.005) as the aneurysm size increased (APV index in groups S, M and L was 0.893 +/- 0.149, 0.573 +/- 0.242 and 0.128 +/- 0.131, respectively; shear index in groups S, M and L was 0.750 +/- 0.149, 0.328 +/- 0.153 and 0.020 +/- 0.028, respectively). However, coronary perfusion pressure showed no relationship to aneurysm size and was not significantly different from that in adjacent normal-looking vessels. CONCLUSIONS: The results of the present study suggest that the stagnation of flow and the reduction of shear stress in coronary aneurysms could initiate thrombus formation.     

Intravenous immunoglobulin preparation type: Association with outcomes for patients with acute Kawasaki disease

Manlhiot C, Yeung RSM, Chahal N, McCrindle BW. Intravenous immunoglobulin preparation type: Association with outcomes for patients with acute Kawasaki disease.
Pediatr Allergy Immunol 2010: 21: 515–521.
© 2010 John Wiley & Sons A/S To determine whether two different intravenous immunoglobulin (IVIG) preparations were equally efficacious in the treatment of Kawasaki disease (KD). Single centre retrospective review of all patients treated with IVIG for KD between January 1990 and April 2007. Comparison of IVIG (dose 2 g/kg) from two commercial preparations; Iveegam^® stabilized with sugar (lyophilized, 5 g/ml glucose, pH 6.4–7.2, IgA 10 μg/ml, 5% IgG/ml) and Gamimune^® stabilized through acidification (no sugar, pH 4.0–4.5, IgA 270 μg/ml, 5% 1990–1999, 10% 1999–2007 IgG/ml). Propensity‐adjusted differences in duration of fever after treatment initiation, frequency of retreatment with IVIG, hospital stay and maximum coronary artery z‐score. A total of 954 patients were included, 862 (90%) were treated with Iveegam^® and 92 (10%) were treated with Gamimune^®. Patients’ demographic, clinical and laboratory characteristics were similar between the two groups. In propensity‐adjusted models, Iveegam^® was found to be associated with higher probability of non‐response to IVIG (12% vs. 5%, p = 0.05) and longer median duration of fever after IVIG [1 (1–27) vs. 1 (1–8) days, p = 0.02] than Gamimune^®. Nevertheless, Gamimune^® was found to be associated with longer median duration of hospital stay [5 (2–49) vs. 4 (2–76) days, p < 0.0001] and higher median maximum coronary artery z‐score both at the end of the acute phase (+1.4 vs. +0.8, p < 0.0001) and 6–8 weeks after the acute phase (+0.7 vs. +0.4, p < 0.0001). IVIG preparations with lower IgA content and stabilized with glucose appear to be associated with improved coronary artery outcomes for patients with KD.     

Estimation of myocardial damage in Kawasaki disease using antimyosin antibody

In a retrospective study, 121 children with Kawasaki disease (KD) were investigated to determine (i) the incidence of myocardial damage using the antimyosin antibody (AMA) titer; (ii) the differences in the electrocardiograms between the AMA-positive and -negative patients; and (iii) the effect of treatment with intravenous gamma globulin (IVGG) on the AMA. Comparisons were made with 117 normal children (controls). Patients with KD showed a significantly higher mean AMA titer and more patients were positive for AMA than the controls. The AMA titer in the KD group was not related to the presence of coronary artery lesions. Electrocardiograms obtained during the acute and the convalescent stage of KD revealed that patients positive for AMA had a significantly lower voltage of T wave in lead V6 at week four than at week two of illness, whereas patients negative for AMA showed no T wave change after week two. The group treated with IVGG showed a significantly lower AMA titer than that not given IVGG. These observations suggest that myocardial damage occurs in some patients with KD which is unrelated to the presence of coronary artery lesions and that the treatment with IVGG reduces the AMA titer in patients with KD.     

川崎病并发巨大冠状动脉瘤急性期临床特征与危险因素分析

目的以川崎病(KD)并发巨大冠状动脉瘤(GCAA)的病例对照研究,分析KD急性期的临床特征,并探讨并发GCAA的危险因素。方法选取2001年5月至2009年5月在广州市妇女儿童医疗中心儿童医院住院的KD并发GCAA患儿为GCAA组;选取同期KD并发中小冠状动脉瘤(CAA)患儿为对照组。对两组患儿的临床特征进行比较,对可能影响GCAA发生的因素进行单因素分析,并进行多因素Logistic逐步回归分析。结果GCAA组纳入22例,其中男19例,女3例,发病年龄3个月至10岁,平均(2.9±2.8)岁。中小CAA组纳入65例,其中男51例,女14例。Pearson χ2检验结果提示,年龄≤6个月或≥5岁、发热时间>14 d、延误诊断、确诊前单独使用糖皮质激素、Hb降低、ESR升高和ALB降低与GCAA发生相关(P均<0.05)。多因素Logistic逐步回归分析提示,延误诊断（OR＝2.998,95%CI：1.004～8.950,P=0.047),确诊前单独使用糖皮质激素（OR＝6.556,95%CI：1.561～28.542,P=0.010),ESR≥100 mm·h-1(OR＝3.591,95%CI：1.164～11.079,P=0.026)为发生GCAA的独立危险因素。结论延误诊断、确诊前单独使用糖皮质激素和ESR≥100 mm·h-1为KD并发GCAA的独立危险因素。     

川崎病丙种球蛋白治疗策略与心脏损害及冠状动脉病变的相关性研究(1998-2008上海地区调查报告)(英文)

目的 川崎病(Kawasaki disease,KD)是一种病因未明的全身血管炎性综合征,伴冠状动脉病变(coronary artery lesion,CAL);大剂量静脉注射丙种球蛋白(intravenous immunoglobulin,IVIG)治疗KD的临床疗效肯定,但目前IVIG的用法和用量尚存在争议.该研究主要为评价不同IVIG方法治疗.KD的效果,探讨最佳治疗方案.方法 由上海市儿科心血管学组制定统一的KD调查表,发放到上海提供儿科服务的50家医院.回顾性分析1998-2008年上海地区住院KD患者的临床资料.共收集完全符合要求的KD患者资料表格1682例,其中男性1064例(63.3%),女性618例(36.7%);发病年龄(2.57±2.33)岁(0.1～18.8岁).治疗KD的IVIG方案包括1 g/ks×1次、2 g/kg×1次、0.4～0.5 g/kg×5次、1 g/kg×2次、2 g/kg×2次及其他.采用SAS 6.12统计软件包进行统计分析,计数资料采用X2检验计算;计量资料数据以X-±s表示,采用t检验.结果 在KD病程的5～10 d应用IVIG有助于最大化降低KD患者的CAL发生率;所有IVIG的KD患者中,应用方案1g/kg×2次治疗者心脏损害、冠脉病变的发生率均为最低,差异有统计学意义(P<0.05).结论 在KD病程5～10 d以IVIG 1g/kg×2次的剂量,有助于最大化降低KD患者的CAL发生率.     

Neutrophilic involvement in the damage to coronary arteries in acute stage of Kawasaki disease

BACKGROUND: There has been no morphological evidence that polymorphonuclear leukocytes (PMNL) infiltrate the coronary arterial lesions of acute Kawasaki disease (KD) patients, although clinical data indicate the activation of PMNL. METHODS: The experimental materials consisted of eight autopsy patients who died during the acute phase of KD. Duration of the illness ranged from 6 to 32 days. The tissues were fixed and embedded in paraffin. Hematoxylin and eosin, elastica van Gieson and azan-Mallory stainings were performed for routine histological examination. In addition, antibodies to CD3, CD20, CD68 and neutrophil elastase were used for immunohistochemistry to identify infiltrating cells in arterial lesions. RESULTS: The inflammatory cells that appeared in the coronary arterial lesions were mainly composed of macrophages in all patients. In addition, numerous neutrophils were also identified in the coronary arterial lesions of the patients who died 10 days after the onset of KD. Neutrophilic infiltration reached a peak earlier than the peaks of CD68+ macrophages, CD3+ T lymphocytes and CD20+ B lymphocytes. CONCLUSIONS: These results suggest that neutrophils are involved in the damage occurring to coronary arteries in the early stage of KD. Vasodilation might occur as a result of injury to vascular walls caused by neutrophils, as well as macrophages.     

Absence of hypercoagulability in acute Kawasaki disease

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis syndrome with the striking feature of cardiovascular involvement. Endothelial cell (EC) damage has been suggested to predispose individuals to the development of coronary vascular disorders. When EC are perturbed, prethrombotic complications ensue. The purpose of this study was to examine the clinical relevance of EC activation and hypercoagulability in the pathogenesis of KD and to determine if plasma levels of these markers are correlated with the development of coronary aneurysms. METHODS: EC function and coagulation status were assessed in 52 patients with acute KD, 20 febrile control subjects, and 20 healthy control subjects. Biological markers of EC and hypercoagulability were measured and included thrombomodulin, tissue factor, tissue factor pathway inhibitor, von Willebrand factor (vWF), coagulation factor VII (FVII), activated factor VII, prothrombin fragment 1 + 2 (F1 + 2), and D-dimer. RESULTS: Transient dilatation of coronary arteries was the most common complication (55.8%), and coronary aneurysm was noted in five patients (9.6%). Levels of vWF, FVII, F1 + 2 and D-dimer were higher in acute KD patients compared with healthy controls but not febrile controls. Markers of EC and hypercoagulability were not different between patients with cardiac complications and those without cardiac complications. Biological and immunological assays did not demonstrate the prethrombotic state in acute KD. CONCLUSIONS: Our results suggest that hypercoagulability does not occur during the acute stage of KD. Markers of EC damage and hypercoagulability are not predictive of coronary aneurysms in KD.     

川崎病冠状动脉损害相关危险因素分析

目的探讨川崎病(KD)并发冠状动脉损害(CAL)的相关危险因素。方法回顾性分析110 例KD患儿的临床资料,根据超声心动图检查结果分为冠脉损害组(CAL组)40例,无冠脉损害组(NCAL组)70例,进行统计分析。结果 110例KD患儿的中位发病年龄为1.58(0.92～3.00)岁,其中男67例、女43例。CAL组和NCAL组间年龄分布、不典型KD、静脉用丙种球蛋白(IVIG)前发热持续时间6天比例差异均有统计学意义(P0.05)。CAL组患儿C反应蛋白(CRP)、白细胞(WBC)、白介素-6(IL-6)、N 端脑钠肽前体(NT-proBNP)水平均明显高于NCAL组,差异均有统计学意义(P0.05)。IVIG使用前发热持续时间、WBC、IL-6、NT-proBNP预测KD患儿并发CAL的受试者工作特征曲线(ROC)下面积(AUC)分别为0.97、0.69、0.76和0.87;最佳临界值分别为6.5天、19.85×10~9/L、92.19 pg/mL和1 122.5 pg/mL,预测KD并发CAL的灵敏度分别为84.6%、46.2%、100%和100%,特异度分别为91.4%、91.4%、57.1%和71.4%。结论年龄3岁,IVIG前发热持续时间6.5天,不典型KD,以及WBC、IL-6和NT-proBNP明显升高,是KD发生CAL的危险因素。     

547例川崎病临床分析及伴冠脉病变高危因素探讨

目的 总结川崎病(Kawasaki disease,KD)的临床特征,探讨KD临床表现与预后的关系,了解KD并发冠状动脉病变(coronary artery lesion,CAL)的危险因素.方法 同顾性分析1990年1月至2006年10月间547例住院KD患儿的临床资料,比较典型与不典型KD的临床特征,并探讨KD并发冠状动脉病变的高危因素.结果 547例中典型KD 434例,不典型KD 113例,不典型KD CAL发生牢较高(P＜0.05);除肛周脱屑外,其他临床症状发生少,出现晚(P＜0.05).547例KD中并发CAL 103例(18.82%),相关因素分析显示发病年龄、性别、血沉、血小板、C-反应蛋白与CAL发生率有密切关系.结论 不典型KD的CAL发生率较高,肛周脱屑较其他临床症状出现早,可以作为早期诊断线索之一;3岁以下的男孩及血沉、血小板、C-反应蛋白明显升高是CAL的高危因素.     

Effect of intravenous immunoglobulin on inhibiting peripheral blood lymphocyte apoptosis in acute Kawasaki disease

This study aimed to explore the therapeutic mechanism of intravenous immunoglobulin (IVIG) for Kawasaki disease (KD). Peripheral blood lymphocytes (PBLs) obtained from 26 children with KD and 20 age-matched healthy children were stimulated with anti-CD3 monoclonal antibody (mAb), and the percentage of apoptotic cells and DNA fragmentation were assayed at 0, 12, 24, 48 and 72 h in vitro. The patients were divided into two groups: one treated with aspirin combined with IVIG (n = 16) and one treated with aspirin alone (n = 10). PBLs were stimulated by phytohaemagglutinin to evaluate the lymphocyte proliferative response. Compared with normal controls, the apoptotic cell percentage and the DNA fragmentation were markedly decreased (p < 0.001) and delayed in PBLs from KD patients. After IVIG treatment, the decreased percentage of apoptotic cell and delayed DNA fragmentation were restored to the state of the normal controls, accompanied by a fast clinical remission compared with the aspirin-alone group. The lymphocyte proliferative response was also decreased 3-5 d after IVIG therapy (p < 0.001). Conclusion: The results suggest that decreased PBL apoptosis may be involved in the pathogenesis of KD. The therapeutic mechanism of IVIG in KD may be partially due to the reversal of the inhibited lymphocyte apoptosis, and may have implications for other autoimmune diseases with inefficient lymphocyte apoptosis.     

Successful pregnancy after coronary artery bypass grafting for Kawasaki disease

Abstract A 13-year-old girl with a history of Kawasaki disease underwent coronary artery bypass grafting because of angina pectoris due to a giant coronary artery aneurysm on the left main trunk artery. Nine years after the operation, the patient had an uneventful pregnancy followed by a normal vaginal delivery. This is the first case of a successful pregnancy after coronary artery bypass grafting for Kawasaki coronary artery disease.