Coronary risk factors in acute Kawasaki disease: Correlation of serum immunoglobulin levels with coronary complications

Abstract Background To determine the usefulness of the IgG z-score (age and sex-standardized serum IgG level) before intravenous gamma globulin therapy (1VGG) in predicting the occurrence or severity of coronary complications in Kawasaki disease (KD).
Methods A case-control study of clinical and laboratory findings with 88 children in the early stage of acute KD who received IVGG (100 or 200 mg/kg for2–5 days) therapy. Of these, 20 cases had persistent coronary arterial lesions (small aneurysm, moderate aneurysm or large aneurysm persisting more than 1 month). The controls comprised 68 children with no coronary aneurysms or transient small aneurysm only observed within 1 month after the onset of KD. The association between serum levels of immunoglobulin G (IgG), IgM, IgA as well as other coronary risk factors previously reported and the occurrence of the coronary arterial lesions was evaluated using logistic regression analysis.
Results: After adjustment for age, gender, total IVGG dose before the 9th illness day and other traditional coronary risk factors, the odds ratio for the persistent coronary aneurysm associated with lower serum IgG r-score (<-0.7485 v.v & -0.7485). was 30.3 (95% confidence interval, 3.8–243.2). Furthermore, the serum IgG z-score was inversely correlated with the severity of the coronary arterial lesion.
Conclusions: The IgG z-score before IVGG therapy in the early stage of KD provides useful information on the risk factors for persistent coronary aneurysm and is a novel, additional indicator for therapy to prevent the coronary complications in acute KD.     

冠状动脉造影追踪观察川崎病引起的巨大冠状动脉瘤

目的 探讨川崎病(KD)导致的巨大冠状动脉瘤(GCAA)的中远期变化特点,为此类儿童进入青少年期后心血管意外事件的防治提供依据.方法 采用冠状动脉造影(CAG)、超声心动图及心电图检查对12例急性期合并GCAA的KD患儿[男10例,女2例;发病年龄1～10(4.05±2.50)岁]进行2～10年追踪观察,分析该组患儿冠状动脉损害的变化特点.结果 本组患儿除2例急性期超声心动图诊断为单发右冠状动脉巨大瘤外,其余10例均为双侧多发冠状动脉瘤.随访CAG发现8例出现右冠状动脉节段性狭窄,其中右冠状动脉闭塞并桥样新生血管形成3例,多节段局域性狭窄4例,右冠状动脉全程编织样损害(血栓性闭塞并簇状新生血管)1例.本组9例冠状动脉瘤经治疗后仍有不同程度的存在,其中4例左前降支瘤远端血流充盈明显减慢.仅1例患儿(1/12) CAG见双侧冠状动脉瘤回缩至轻度扩张,未见狭窄及其他改变.本组12例患儿随访2 ～ 10年,均无自觉症状,活动未受限.静息心电图1例发现病理Q波,其余11例结果正常.静息心电图正常的11例患儿行药物负荷心电图检查仅1例出现多导联S-T段下移及T波低平;与同期CAG比较,超声心动图检出12例患儿冠状动脉近段形态改变,5例发现可疑室壁运动异常,但对观察冠状动脉中、远段狭窄欠敏感;对4例冠状动脉闭塞并新生血管形成的病例,超声观察均未能提示.结论 KD引起的GCAA损害可在急性期后长期存在.表现为GCAA持续存在、回缩、冠状动脉闭塞、局部狭窄及血管再形成等.本病缺乏临床表现,常规心电图及超声心动图对KD后遗症期冠状动脉形态及功能损害检查欠敏感,CAG对本病的追踪观察有重要价值.     

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.     

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.     

A fatal case of ruptured giant coronary artery aneurysm

A 5-year-old Japanese boy died because of a ruptured left coronary artery aneurysm (CAA). He was diagnosed as having Kawasaki disease (KD) on the 5th day from onset, with all of the principal signs. On the 7th day of illness, bilateral CAAs were already found via echocardiography, and he was treated with intravenous (IV) gamma globulin and oral ASA. However, the fever persisted and the CAA progressed rapidly. Echocardiography on the 12th illness day showed a giant (18-mm) left anterior descending (LAD) artery aneurysm. Oral propranolol and nifedipine were administered, in conjunction with warfarin/aspirin anti-coagulation therapy. On the 13th day of illness, cardiac arrest developed abruptly, and, despite cardiopulmonary resuscitation (CPR), the patient remained unresponsive and died one hour later. The final pathological diagnosis was a ruptured LAD artery aneurysm and cardiac tamponade. Microscopic investigation of the ruptured vascular wall revealed marked neutrophilic infiltration, with fewer macrophages and lymphocytes. CAA ruptures are a very rare, but fatal, complication of KD. Based on a review of previous reports on CAA ruptures, we consider it useful to distinguish aneurysms which rapidly dilate and continue to expand beyond a diameter of 10 mm with ongoing vasculitis (these CAAs can be termed “super-giant”) from the more common giant CAAs limited to a diameter of 8 or 9 mm, because a decision must be made as to whether to start intensive care or to intervene surgically, in order to ensure the survival of patients with such a potentially critical complication.     

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.     

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.     

Strict management of a pregnant patient with giant coronary artery aneurysm due to Kawasaki disease

Coronary artery aneurysms (CAA) may occur in Kawasaki disease (KD). Patients with giant CAA (diameter >8 mm), in particular, have higher risk of myocardial infarction. Previous reports have demonstrated the necessity of anticoagulation therapy in such cases. The management of patients with KD complicated by giant CAA later in life, however, remains controversial. Here, we describe the strict management in the case of a 28‐year‐old pregnant Japanese woman with KD with giant CAA (diameter, 11 mm). Instead of warfarin, the patient was given low‐dose aspirin and i.v. unfractionated heparin during pregnancy to prevent thrombosis in the giant CAA. At 38 weeks of gestation, she had spontaneous delivery of a healthy baby. No thrombotic or bleeding complications were observed. The strict anticoagulation therapy resulted in successful pregnancy and delivery without any adverse events.     

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.     

An apparent case of undiagnosed donor Kawasaki disease manifesting as coronary artery aneurysm in a pediatric heart transplant recipient

We present a case of coronary ectasia and LAD coronary artery aneurysm with angiographic characteristics of Kawasaki disease in a three‐yr‐old girl two‐yr status post‐orthotopic heart transplant. Coronary anomalies were noted during initial screening coronary angiography two yr after transplant. Subsequent review of the donor echocardiogram revealed that the LMCA had been mildly dilated prior to transplant. In the absence of any symptoms consistent with Kawasaki disease in the transplant recipient, this appears to be a case of Kawasaki disease in the organ donor manifesting with coronary anomalies in the transplant recipient. The patient has done well clinically, and repeat coronary angiography has revealed partial regression of coronary anomalies. Given multiple reports in the literature of persistent abnormalities of coronary artery morphology and function after Kawasaki disease, close monitoring is warranted, with consideration of potential coronary protective medical therapies.     

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。     

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。     

川崎病合并多发体循环动脉病变1例报告并文献复习

目的报告1例川崎病(Kawasaki disease,KD)合并多发体循环动脉病变并复习文献,以提高对该病的认识和临床诊疗水平。方法根据患儿的症状、体征、心脏超声及体动脉B超等检查结果进行诊断,并结合文献资料进行分析。结果女孩,5个月,诊断川崎病合并双侧冠状动脉瘤,符合静脉注射丙种球蛋白(intra-venous immunoglobulin,IVIG)无反应性川崎病诊断标准,体循环动脉B超提示存在多发体动脉病变。结论川崎病合并多发体循环动脉病变较罕见,应提高认识,及时诊断并长期随诊监测病情变化。     

Prevalence of coronary artery abnormality in incomplete Kawasaki disease

BACKGROUND: The aim of the present study was to determine the prevalence of coronary artery abnormality (CAA) and other clinical features in patients with incomplete Kawasaki disease (iKD) using the data from the 17th Japanese nationwide survey of KD. METHODS: iKD was defined as the presence of four or fewer of the principal symptoms of the Japanese diagnostic guidelines, regardless of whether the patient had CAA. A total of 15,857 cases were analyzed. RESULTS: Among 15,857 cases, 83.9% of patients had five to six principal symptoms (complete KD: cKD), and 16.1% had iKD. The prevalence of CAA in cKD was 14.2%, and 18.4% in iKD. The prevalence of CAA in patients with four principal symptoms was 18.1%, which was higher than in cKD cases (14.2%). Although the reliability of the data has some limitations, the prevalence of CAA among patients with one to three symptoms was 19.3%. Among all CAA patients, 14% had four symptoms, and 6% had only one to three symptoms. CONCLUSION: Incomplete KD should not be equated with mild KD. Patients with four principal symptoms were comparable to cKD with respect to CAA occurrence. In patients with one to three symptoms also, especially in those under 1 year and older than 4 years of age, other significant symptoms and laboratory findings of the guidelines are very important in making a correct and early diagnosis of iKD so as to prevent CAA.