Cytokines predict coronary aneurysm formation in Kawasaki disease patients

In this study, we measured serially the serum levels of cytokines including interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R) and tumour necrosis factor (TNF-) in 60 patients with Kawasaki disease (KD) and evaluated the clinical significance of these cytokines in predicting coronary aneurysm formation. Of the 60 patients, 12 were complicated with coronary aneurysm. Blood samples were collected within the 1st week after onset of fever, then once a week for the 1st month, and once a month for another 5 months. The serum levels of IL-6, IL-8, sIL-2R and TNF were measured using an ELISA or RIA method. Our results show that the changes in serum IL-6 and IL-8 were faster than those of sIL-2R and TNF. Within the 1st week, the serum levels of IL-6 and IL-8 were significantly higher in the patients with than in those without coronary aneurysm (P<0.001). In addition, the serum levels of IL-6 and IL-8 obtained in the 1st week were highly correlated (P<0.001) with those of C-reactive protein and erythrocyte sedimentation rate, and the serum levels of sIL-2R and TNF were also increased at the 1st week reaching the highest level in the 2nd week. In the 2nd week, the serum levels of sIL-2R and TNF were significantly higher in the patients with than in those without coronary aneurysm (P<0.05). These findings suggest that the serum levels of IL-6 and IL-8 obtained in the 1st week may serve as useful parameters in predicting coronary aneurysm formation in KD patients.     

标准治疗方案联合糖皮质激素对川崎病冠状动脉瘤发生率影响的Meta分析

目的评价标准治疗方案+糖皮质激素对川崎病(KD)冠状动脉瘤(CAA)发生率的影响。方法制定原始文献的纳入标准及检索策略,检索Medline、EMBASE、Cochrane图书馆、万方数据库、中国期刊全文数据库和中国维普数据库,检索时间均从建库至2010年6月。纳入标准治疗方案(大剂量IVIG+阿司匹林)+糖皮质激素对KD CAA发生率影响的相关文献。依据KD诊断标准、研究设计、冠状动脉影像学随访时间和冠状动脉检查是否采用盲法进行文献质量评价。计数资料采用相对危险度(RR)及其95%CI表示;计量资料采用加权均数差(WMD)及其95%CI表示。采用Stata11.0软件进行Meta分析。结果 7篇文献进入Meta分析,均为英文文献,其中4篇为RCT文献,3篇为回顾性对照研究。文献质量评价结果显示,评分2分3篇,5分1篇,6分3篇。Meta分析结果显示,标准治疗方案+糖皮质激素可显著降低CAA的发生率(RR=0.34,95%CI:0.13~0.89)。由于纳入文献间存在显著的异质性,进行亚组分析,显示研究设计(RCT和非RCT)、样本量(100和100)、糖皮质激素的类型(泼尼松龙和其他)是异质性产生的原因。RCT研究及样本量100文献的Meta分析结果显示,标准治疗方案+糖皮质激素未能显著降低CAA的发生率(RR分别为0.79和0.73,95%CI分别为0.43~1.43和0.42~1.28)。标准治疗方案+糖皮质激素可显著降低IVIG再治疗率(RR=0.48,95%CI:0.32~0.72),显著减少发热天数(WMD=-1.66d,95%CI:-2.58~-0.73d),对不良反应事件发生率无显著影响(RR=0.87,95%CI:0.35~2.16)。结论现有证据提示标准治疗方案+糖皮质激素未能显著降低CAA的发生率,可减少IVIG再治疗率和发热天数。     

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.     

儿童川崎病致巨大冠状动脉瘤伴血栓形成一例

患儿女,9岁10个月。因巨大冠状动脉(简称冠脉)瘤1年余入我院。患儿于13个月前无明显诱因而发热,体温达39~40℃,双眼结膜及咽部充血,2 d后左颈部淋巴结肿大,约1·5 cm×1·0 cm大小,并有触痛。于发热第6天出现口唇潮红、杨梅舌、手足硬性水肿,转诊上级医院,诊断为“川崎病(Kawasak i d isease,KD)”。行二维超声心动图(2-d im ensional echocard iography,2DE)检查示“巨大冠脉瘤(coronary arterial aneurysm,CAA)”,即予大剂量静脉免疫球蛋白(intravenous immunoglobu lin,IVIG,40 g/d,共用2 d)及阿司匹林治疗。约于病程第8天热退,第9…     

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.     

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.     

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.     

川崎病合并巨大冠状动脉瘤101例中长期随访

目的总结分析川崎病合并巨大冠状动脉瘤(GCAA)患儿的临床特点及中长期预后。方法回顾性队列研究。自首都医科大学附属北京儿童医院2004年建立的川崎病冠状动脉瘤随诊患儿队列中选择符合标准的101例GCAA患儿进行总结。GCAA诊断标准为冠状动脉瘤内径≥8.0 mm,患儿均完成定期随诊。随访终点为患儿最后一次随诊或死亡时间。组间比较采用t检验或χ²检验。结果101例符合纳入标准GCAA患儿入选研究对象,其中男82例(81.2%)、女19例(18.8%);发病年龄2.5(1.0,4.5)岁,随访时间4.5(2.7,7.5)年,最长19年。患儿常规接受阿司匹林、华法林治疗,严重者另加氯吡格雷。截至随访终点,13例(12.9%)患儿出现心脏增大,11例(10.9%)合并心功能不全,13例(12.9%)发生心肌梗死,2例(2.0%)接受冠状动脉搭桥术,6例(5.9%)死亡。受累冠状动脉共170支,位于左侧主干24支(14.1%),左回旋支10支(5.9%),左前降支57支(33.5%),右侧冠状动脉中段78支(45.9%),右侧冠状动脉远段1支(0.6%)。11例(10.9%)患儿GCAA内径回缩至4.0 mm及以下;受累的170支冠状动脉中,28支(16.5%)冠状动脉内径回缩到4.0 mm及以下。左侧、右侧GCAA回缩情况差异无统计学意义[18.7%(17/91)比13.9%(11/79),χ²=2.473,P=0.116]。单侧GCAA与双侧GCAA患儿回缩情况差异无统计学意义[16.1%(9/56)比4.4%(2/45),χ²=2.381,P=0.123]。结论川崎病GCAA以右冠状动脉中段、左冠状动脉前降支最常见,患儿心血管事件发生率及病死率较高,预后欠佳。     

AST-to-ALT ratio and coronary artery lesions among patients with Kawasaki disease

Background The aim of this study was to explore the associations between the aspartate aminotransferase-to-alanine ami-notransferase ratio (AST/ALT) and coronar...     

川崎病伴冠状动脉瘤、休克和多脏器功能损伤一例

患儿男,11岁9个月。因“发热、咳嗽7d,加重2d”入院。7d前无明显诱因出现发热,体温：38℃-39℃,伴咳嗽,予抗感染输液等治疗,仍时有高热,腹痛、腹胀,呕吐胃内容物。2d前病情加重,出现血压下降,神志不清,纳差,尿少。体检：体温38．8℃,脉搏128次／min,呼吸40次／min,血压61／28mmHg（1mmHg=0．133kPa）。神志不清,精神极度萎靡,气促,全身见密集充血性斑丘疹。浅表淋巴结未触及肿大。双眼球结膜充血,唇红、皲裂出血,杨梅舌。颈抵抗,双肺可闻及中、小水泡音。     

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.