Incomplete Kawasaki disease with coronary artery involvement

We report four patients with Kawasaki disease in whom characteristic coronary artery abnormalities developed after illnesses that did not meet diagnostic criteria. An additional patient lacked a history of acute manifestations of Kawasaki disease, but severe Kawasaki-like arterial changes were noted at autopsy. Fever was present in four of the five patients, in three lasting from 7 to 14 days. Despite manifestation of few classic acute clinical features of Kawasaki disease, three of four patients had desquamation of the fingers and toes 10 to 14 days after onset of illness, and the fifth had desquamation several months prior to death. These patients were seen over a 2-year period during which 22 other children were seen with Kawasaki disease with coronary artery abnormalities. Thus, strict adherence to currently accepted criteria for diagnosis of Kawasaki disease may lead to failure to recognize incomplete forms of this illness, with potential sequelae of myocardial infarction or sudden death. This finding suggests that children with prolonged unexplained febrile illnesses, especially those associated with subsequent peripheral desquamation, should undergo echocardiography 3 to 4 weeks after onset of the illness. This practice would help to identify those patients with illnesses characterized by incomplete diagnostic criteria but in whom significant coronary abnormalities develop.     

Afebrile Kawasaki disease with coronary artery dilatation

Herein we describe the cases of two afebrile patients who were thought to have Kawasaki disease (KD). Patient 1 was a 7‐month‐old‐Japanese girl. She presented with bulbar conjunctival injection, diarrhea, skin erythema, and redness around the bacillus Calmette–Guerin (BCG) inoculation site. Thirteen days after the first symptoms, ultrasonic cardiogram (UCG) showed dilatations of the bilateral coronary arteries (CA). The dilatations had completely resolved 5 months later. Patient 2 was a 13‐month‐old Japanese boy. He first presented with bulbar conjunctival injection and redness around the BCG inoculation site. Twenty‐two days after the first symptoms, UCG indicated bilateral and peripheral CA dilatations. The mild dilatations of the proximal CA remained. Although fever is the principal symptom of KD, some incomplete KD patients may be afebrile. Although it is difficult to diagnose these patients as having KD, redness at the BCG inoculation site may be a clue to the diagnosis.     

Predictive risk factors for coronary artery abnormalities in Kawasaki disease

Clinical characteristics to predict the development of coronary artery abnormalities (CAA) in Kawasaki disease (KD) were assessed by reviewing medical records of patients diagnosed with KD at Korea University Medical Center from March 2001 to February 2005. Of the 285 patients diagnosed with KD, 19 developed CAA (6.7%). Compared with the CAA(−) group, the CAA(+) group had a longer duration of fever after intravenous gamma-globulin (IVGG) injection (2.4±2.9 vs. 1.5±1.2 days, p=0.008) and higher C-reactive protein (CRP)(12.3±7.8 vs. 8.7±7.1 mg/dL, p=0.038). In particular, the CAA(+) group tended to have more than 7 days of fever before IVGG and more than 3 days of fever after IVGG (26.3 vs. 5.3%, p<0.001; 26.3 vs. 6.4%, p=0.002). When the IVGG responsiveness was defined by the presence of defervescence within 3 days after IVGG, IVGG-non-responders showed a higher incidence of CAA (22.7 vs. 5.3%, p=0.002). Non-responders had a longer duration of fever after IVGG (5.5±1.9 vs. 1.2±0.6 days, p<0.001) and a significantly increased CRP, AST, ALT and total bilirubin. Multivariate regression analysis for CAA showed that the only factor significantly associated with the development of CAA was total fever that lasted for longer than 8 days (OR=4.052, 95% CI=1.151–14.263, p=0.0293). Conclusively, the most important predictor of CAA in KD is total duration of fever longer than 8 days. Early identification of IVGG non-responders and active therapeutic intervention for fever in KD cases might decrease the incidence of CAA.     

Advances in Kawasaki disease bypass surgery for coronary artery obstructions

Coronary bypass surgery for the sequelae of Kawasaki disease is effective in improving cardiac function during exercise and probably in preventing sudden deaths and myocardial infarction in children, although surgical efficacy was initially questioned because the disease is inflammatory vasculitis in origin. The operation utilizing the pedicled arterial grafts is now established as a reliable treatment for severe inflammatory coronary obstructive disease due to Kawasaki disease (Kitamura Operation). Results of the surgery and long-term follow up are quite satisfactory up to 20 years. The postoperative quality of life is also markedly improved allowing over 85% of children with surgery to take full exercise at school, although all of them were prohibited from exercise before operation.The pedicted internal thoracic artery graft is not only excellent in its long-term patency but also is capable of growing with the child and meeting the perfusion demand of the myocardium. Thus, it is an ideal graft material for coronary artery reconstruction in children. Use of bilateral internal thoracic arteries is also safe in growing children. Moreover, right gastroepiploic artery grafts are useful in children with distal coronary artery lesions. The use of vein grafts should be avoided in children, because the patency rate is significantly poorer than arterial grafts. The benefits of surgical treatment for severe coronary artery lesions due to Kawasaki disease have now been recognized not only in Japan but all over the world.     

川崎病并发冠状动脉病变研究进展

川崎病是一种原因未明的急性全身血管炎性疾病,其主要并发症为冠状动脉病变,包括冠状动脉扩张、冠状动脉瘤形成等,且急性期过后冠状动脉损害持续存在.近年来研究表明,基因多态性、中性粒细胞、单核细胞、细胞因子等多种因素共同参与了冠状动脉病变的形成,长期抗凝药物的使用可降低冠状动脉损害.     

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.     

A multicenter prospective randomized trial of corticosteroids in primary therapy for Kawasaki disease: clinical course and coronary artery outcome

OBJECTIVE: To investigate the role of corticosteroids in the initial treatment of Kawasaki disease (KD). STUDY DESIGN: Between September 2000 and March 2005, we randomly assigned 178 KD patients from 12 hospitals to either an intravenous immunoglobulin (IVIG) group (n = 88; 1 g/kg for 2 consecutive days) or an IVIG plus corticosteroid (IVIG+PSL) group (n = 90). The primary endpoint was coronary artery abnormality (CAA) before a 1-month echocardiographic assessment. Secondary endpoints included duration of fever, time to normalization of serum C-reactive protein (CRP), and initial treatment failure requiring additional therapy. Analyses were based on intention to treat. RESULTS: Baseline characteristics of groups were similar. Fewer IVIG+PSL patients than IVIG patients had a CAA before 1 month (2.2% vs 11.4%; P = .017). The duration of fever was shorter (P < .001) and CRP decreased more rapidly in the IVIG+PSL group than in the IVIG group (P = .001). Moreover, initial treatment failure was less frequent (5.6% vs 18.2%; P = .010) in the IVIG+PSL group. All patients assigned to the IVIG+PSL group completed treatment without major side effects. CONCLUSIONS: A combination of corticosteroids and IVIG improved clinical course and coronary artery outcome without causing untoward effects in children with acute KD.     

Fatal Kawasaki disease caused by early occlusive coronary artery disease

In Kawasaki disease severe coronary artery narrowing may develop at an early stage despite treatment with gammaglobulin and in the absence of prominent aneurysm formation or thrombosis. Vaso-occlusive disease may not be clinically or echocardiographically apparent until very severe.     

川崎病丙种球蛋白耐药及冠状动脉损伤早期预测指标的研究进展

川崎病是急性全身性血管炎综合征,主要影响冠状动脉.该病的长期预后取决于冠状动脉病变程度.早期应用大剂量静脉丙种球蛋白可以减少冠状动脉病变,丙种球蛋白耐药者冠状动脉病变风险大,早期预测丙种球蛋白耐药及冠脉损伤、及时采取措施对改善预后意义重大.该文对川崎病丙种球蛋白耐药及冠状动脉损伤的预测指标作一介绍.     

Cardiovascular complications in Kawasaki disease: coronary artery lumen and long-term consequences

Kawasaki disease (KD) is an acute vasculitis syndrome in infants and young children which affects small- and medium-sized arteries, particularly the coronary arteries. It has replaced rheumatic fever as the most common cause of acquired heart disease in children. In this article, we review the spectrum of the cardiovascular complications, the natural history or fate of coronary aneurysms and long-term issues, the impact on cardiovascular and overall mortality, and the issues in coronary artery disease in the adulthood, from our experience based on 2117 patients over the past 30 years.     

川崎病患儿并发冠状动脉病变的危险因素分析

目的：探讨川崎病(KD)并发冠状动脉病变(CAL)的危险因素。方法：收集2006年1月至2012年1月间诊断为KD的527例患儿的临床资料,对15个可能与CAL发生有关的因素进行单因素和多因素logistic回归分析。结果：单因素分析显示,患儿年龄、性别、KD类型、大剂量丙种球蛋白（IVIG）治疗起始时间、对IVIG治疗的反应、使用糖皮质激素、发热持续时间及C反应蛋白等因素在合并和未合并CAL两组患儿中差异有统计学意义（P8岁、男性、非典型KD、IVIG治疗开始于发热后10 d 以上、对IVIG治疗无反应、发热持续时间>10 d为CAL发生的独立危险因素（OR分别为2.076、1.890、1.972、1.426、3.251、2.301、1.694,均P8岁）、男性、非典型KD、IVIG治疗起始时间较晚、对IVIG治疗无反应、发热持续时间较长是CAL发生的独立危险因素。     

A sibship with recurrent Kawasaki disease and coronary artery lesion

Although epidemiologic studies of Kawasaki disease suggest an infectious etiology, the cause of this mysterious disease remains unclear. We describe the occurrence of five episodes of Kawasaki disease over a six-year period in three siblings. Two of the three children experienced recurrent Kawasaki disease and developed coronary artery lesions, which included giant coronary artery aneurysms in the youngest child. The non-contemporaneous occurrence of the disease in these three children emphasizes the importance of a genetic basis and/or environmental factors in the etiology of Kawasaki disease.     

Guidelines for catheter intervention in coronary artery lesion in Kawasaki disease

The Research Committee of Ministry of Health, Labour and Welfare 'Study of treatment and long-term management in Kawasaki disease' reported the guidelines for catheter intervention in coronary artery lesion in Kawasaki disease in this paper. The contents include: (i) background and natural history of coronary artery lesion in Kawasaki disease; (ii) indication of catheter intervention; (iii) types of procedure, and their indication and care; (iv) institute and backup system; (v) the management after procedure, evaluation and follow up; and (vi) prospects, especially in relation to bypass surgery.     

Kawasaki disease: effect of treatment on coronary artery involvement.

Ninety-two patients with Kawasaki disease were treated with five different types of drug therapy: a steroid preparation (prednisolone), aspirin, an antibiotic, a combination of steroid plus aspirin, and a combination of steroid plus warfarin. One or two months after the onset of the disease, coronary angiography demonstrated coronary aneurysms in 20% of cases treated with an antibiotic alone, 64.7% of cases in the steroid-treated group, and 11% of those in the aspirin-treated group. These findings suggest that the steroid might act adversely to cause a progression of coronary lesions of the disease. The aspirin-treated group did not have a significantly lower incidence of coronary lesions compared with the group treated with an antibiotic alone. But in view of the fact that the direct cause of sudden death of the disease is thrombotic occlusion of a coronary artery, aspirin might act as the effective means for prevention of sudden death due to Kawasaki disease.     

Six principal symptoms and coronary artery sequelae in Kawasaki disease

Background:  The relationship between coronary artery sequelae due to Kawasaki disease and the six principal symptoms associated with the latter are still unknown.
Methods:  Among the 16 952 patients reported in the 17th nationwide survey on Kawasaki disease, 14 068 were found to have definite and typical cases with five or six principal symptoms. The proportions of coronary artery aneurysms including dilatation of the artery were compared between the patient group with six symptoms and that with five.
Results:  Percentages for those with all six symptoms (7223) were 4.7% for coronary dilatations (i.e. small aneurysms), 1.7% for coronary aneurysms (i.e. middle-sized aneurysms), and 0.42% for giant coronary aneurysms (i.e. large aneurysms) 1 month after onset, whereas for those with five symptoms (6845), the corresponding percentages were 4.1%, 1.4%, and 0.22%, respectively. For overall observation, the odds ratios were 1.44, 1.28, and 1.70 for the three types of aneurysm, respectively. For male patients, all the odds ratios were >1.0, and some were significant. In contrast, odds ratios <1.0 were observed among those with six symptoms in some subgroups among female patients despite the lack of significance.
Conclusions:  Because odds ratios were elevated – especially for male patients with Kawasaki disease – with all six principal symptoms, patients with the six symptoms are more problematic for coronary sequelae among the definite cases, although there was not a specific symptom for the sequelae.     

川崎病患儿血管内皮素改变与心血管损害的关系探讨

对2004年6月至2004年12月我院收治的34例川崎病患儿进行ET-1检测,并同时结合心脏彩超、心肌酶谱、肌钙蛋白I进行分析,探讨ET-1在川崎病患儿中的改变及与     

川崎病并发冠状动脉病变的病因及其发病机制

川崎病是一种以全身中小血管炎为主要病理改变的急性发热性出疹性小儿疾病.该病的长期预后决定于其心血管并发症,尤其是冠状动脉病变(coronary artery lesion,CAL)程度.川崎病并发的CAL临床治疗非常棘手.目前研究显示CAL的发生与超抗原、巨细胞病毒、RNA病毒等特殊病原体感染相关,一些共刺激分子、细胞因子、趋化因子、金属基质蛋白酶、三磷酸肌醇激酶等基因多态性也参与CAL发生;对川崎病动物模型及川崎病死亡患儿的冠状动脉研究发现,免疫系统异常活化、免疫细胞浸润冠状动脉致冠状动脉内皮细胞功能紊乱、细胞基质降解是CAL发病的关键步骤.该文就川崎病并发CAL的病因及其发病机制研究进展进行综述.     

感染因素对川崎病及其冠状动脉病变的影响

目的 探讨感染因素对川崎病(KD)及其冠状动脉病变的影响。 方法 回顾性收集首都医科大学附属北京儿童医院2005年1月至2014年12月出院诊断中包含KD的病历,截取人口学信息、临床发现、急性期和后遗症期超声心动图发现、转归,对每份病历重新行典型KD、不完全KD、IVIG抵抗、冠状动脉病变及其程度和合并感染的甄别。分为KD感染组、KD非感染组分析组间临床发现的差异,分为冠状动脉病变组、非冠状动脉病变组分析感染因素的差异。 结果 2 331例KD患儿进入分析。KD合并感染的发生率为57.1% (1 331/2 331),KD并发冠状动脉病变的发生率为36.0%(840/2 331)。KD感染组与KD非感染组年龄、发热天数及不完全KD比例差异有统计学意义(P均<0.05);冠状动脉病变组与非冠状动脉病变组肺炎支原体感染及消化系统感染伴发腹泻比例差异有统计学意义(P均<0.05)。 结论 合并感染的KD患儿年龄多<1岁,易表现为不完全KD,合并肺炎支原体感染及消化系统感染伴发腹泻的KD患儿易发生冠状动脉病变。     

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.