川崎病诊治进展

川崎病的病因及发病机制至今未明.其病因可能与感染、遗传易感及超免疫反应有关,发病机制与免疫反应、细胞因子及炎性介质、血管内皮功能紊乱、血小板活化、易感基因多态性等有关.联合应用丙种球蛋白和阿司匹林是川崎病的首选治疗方案.对于糖皮质激素的使用临床尚有争议,严重冠状动脉病变可采用外科及介入治疗.     

Intravenous γ-Globulin Treatment in Kawasaki Disease

A multicenter randomized controlled study was carried out to assess the effectiveness of different, doses and kinds of γ-globulin in Kawasaki disease. Gamma globulin lowered the incidence of coronary artery abnormalities. The effect of γ-globulin was dose dependent. The intact type was more effective than the pepsin treated type. To establish the indications for γ-globulin, a study was made of patients who received neither γ-globulin nor indomethacin and who, within nine days of onset of illness, satisfied at least four of the following criteria: (1) WBC: more than 12,000/mm; (2) platelet count: less than 35×10⁴γmm; (3) CRP: more than 3 +; (4) Hct: less than 35%; (5) albumin: less than 3.5 g/dl (6) age: 12 months or less; (7) male sex. This prospective study is continuing. Of 143 children, 73.4% received γ-globulin, and only two demonstrated small dilatations of the coronary arteries in children who did not receive γ-globulin. These guidelines seem satisfactory to establish the indications for γ-globulin in Kawasaki disease.     

Dobutamine Stress Echocardiography in the Evaluation of Young Patients with Kawasaki Disease

There has been no consistent approach to the follow-up of Kawasaki disease patients for remote coronary perfusion abnormalities. Dobutamine stress echocardiography (DSE) has become a standard method for evaluation of perfusion abnormalities in adults with coronary artery disease. In addition, DSE has been used with success in some pediatric patients. The purposes of this study were to evaluate safety and accuracy of DSE in the follow-up of patients with Kawasaki disease, to evaluate whether DSE adds any additional value to the resting echocardiogram, and to determine the association of DSE results with American Heart Association (AHA) risk level categories. DSE was performed 1 month to 13 years after acute Kawasaki disease in 47 patients (range, 3.8–22.6 years; 33 males and 16 females). Patients were stratified according to AHA risk level categories (I–V). Ischemia was defined as a new or worsening regional wall motion abnormality or >1 mm ST segment depression on the electrocardiogram during DSE. In 45/47 patients, DSE was completed successfully (i.e., achievement of target heart rate or development of ischemia). No patients in risk levels lower than V (i.e., patients without coronary artery stenoses) had positive DSE, whereas 2/4 (50%) in the risk level V category had positive DSE, both of whom had coronary occlusion >50% confirmed by angiography. Of the 2 AHA risk level V patients with negative DSE, 1 had extensive collateralization and the other had coronary obstruction <50%. DSE is a safe and feasible method for the evaluation of children with Kawasaki disease. DSE provides a confirmatory benefit and may be a useful screening alternative to cardiac catheterization during follow-up. Patients in AHA risk levels I–IV are unlikely to have dobutamine-induced coronary perfusion abnormalities. Patients in the risk level V category may or may not have positive DSE depending on the degree of both coronary obstruction and collateralization.     

血清心脏肌钙蛋白I在儿童川崎病中的诊断价值

目的：探讨静脉注射免疫球蛋白(IVIG)在川崎病(KD) 治疗前后血清心肌肌钙蛋白I(cTnI)浓度变化的临床意义。方法：检测 KD组 (n=58) 及对照组 (n=23) 患儿血清 cTnI、肌酸激酶(CK)、乳酸脱氢酶( LDH)与谷草转氨酶(GOT)的浓度。结果：KD组血清cTnI浓度为(0.62±1.08) μg/L,明显高于对照组(0.06±0.06) μg/L,两者差异有显著性意义(P0.05)。IVIG治疗后cTnI浓度为(0.08±0.15) μg/L,明显低于治疗前(0.62±1.08) μg/L,差异有显著性意义(P0.05)。结论：cTnI是一项早期诊断 KD患儿急性心肌损伤的有价值的方法,可为早期静脉注射免疫球蛋白减少心血管病变提供依据,并可作为 IVIG疗效观察指标。     

Kawasaki Disease and Epstein-Barr Virus

We report the results of virological (serological and molecular biological) studies of Epstein-Barr virus (EBV) in patients with Kawasaki disease (KD). Forty-nine (86%) of 57 Kawasaki disease patients and 15 (68%) of 22 patients with recurrent Kawasaki disease had serological evidence of primary Epstein-Barr virus infection during the first month after the onset of their disease based on the results of a sensitive method of detecting antibody to viral capsid antigen (VCA). The serological response to EBV was significantly low and transient. EBV sequences were identified directly in peripheral blood mononuclear cell (PBMC) DNA samples from 23 (56%) of 41 KD patients within 2 weeks after onset by means of the polymerase chain reaction (PCR). EBV sequences were also detected in 10 (83%) of 12 repeatedly tested KD patients within 3 months after onset. In contrast, only 7 (18%) of 40 control DNA samples were PCR-positive. These virological studies indicate that an unusual EBV-cell interaction may occur in KD.     

Anticardiolipin Response in Kawasaki Disease

ABSTRACT. Antibodies against cardiolipin are formed in many different infectious diseases, and high levels are associated with susceptibility to thrombosis, especially in patients with systemic lupus erythematosus. In view of the postulated infectious etiology of Kawasaki disease and its association with thrombosis, we have studied the occurrence of anticardiolipin antibodies in this disease. Serial serum specimens from 36 patients were tested, using a solid-phase enzyme immunoassay. A change of at least 0.3 optical density units between two consecutive specimens for at least one immunoglobulin class was observed in 47% of cases. Peak levels occurred one to two weeks after the onset of symptoms. Four patients developed coronary artery aneurysms, and they all showed a clear anticardiolipin response. Anticardiolipin antibodies might be one factor contributing to coagulation abnormalities in patients with Kawasaki disease.     

Kawasaki Disease update

Kawasaki Disease is rapidly becoming the most common cause of acquired heart disease in children in both the developed and developing world. Its etiology remains a mystery but important progress has been made in characterizing the features of the arterial wall and myocardial pathology and long-term clinical consequences. New treatments aimed at modifying the host immune response are currently under study. The genetic influence on susceptibility and disease outcome is an area of active research.     

Kawasaki Disease and Agranulocytosis

Kawasaki disease associated with agranulocytosis was observed in a one-year-old girl. The agranulocytic state continued for a month, and granulocyte transfusions were required. We discuss the relation between agranulocytosis and drugs, viral infections, Kawasaki disease, etc. The systemic vasculitis of Kawasaki disease seems to be the cause of the bone marrow disturbance.     

Clinical Characteristics of Hemophagocytic Lymphohistiocytosis Related to Kawasaki Disease

It is difficult to predict the prognosis or clinical course of secondary hemophagocytic lymphohistiocytosis (HLH) due to the various underlying causes. The authors analyzed the clinical and laboratory findings and outcomes in patients with HLH who had initially been diagnosed with Kawasaki disease (KD), and evaluated the clinical significance of each factor. Among the 21 patients with HLH, 5 had initially been diagnosed with KD and 16 had other etiologies. A comparative analysis was performed for fever duration, presence of cytopenia, serum ferritin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride, fibrinogen, hyponatremia, reactivation, and survival rate in those HLH patients associated with KD (group I) and other causes (group II). In patients in group I, a higher level of reactivation (20%), a lower survival rate (P = .001), higher AST (P = .031) and ferritin (P = .005), and frequent hyponatremia (P = .000) were found compared to patients in group II. Interestingly, patients in group I was older than the average of age of most KD patients. A high index of suspicion on the progression from KD to HLH would be mandatory when the KD patients show elevated AST and ferritin and the presence of hyponatremia, and especially so if the patient is of older age.     

Kawasaki Disease: Update on Diagnosis, Treatment, and a Still Controversial Etiology

Diagnosis of Kawasaki syndrome still relies solely on clinical criteria because the etiology is unknown. However, the function and structure of different bacterial superantigens as potential pathogens are discussed. In this regard, the recent determination of the crystal structure of the toxic shock syndrome toxin-1 superantigen complexed with major histocompatibility complex class II suggests potential implications for the controversial findings concerning a role of those superantigens in Kawasaki disease. Although a specific therapy is not available, coronary complications can be significantly reduced with the help of intravenous immunoglobulin therapy combined with oral aspirin.     

川崎病临床表现与早期诊断的探讨

目的：探讨建立一种早期诊断川崎病(KD)的诊断指标的可能性。方法：参照KD现行诊断标准,统计分析69例KD患儿各种临床表现出现的时间及发生率。结果：本病早期发热、唇红和或干裂、皮疹、眼结膜充血的发生率分别为100%,92.8%,84%,81%;肛周皮肤潮红和/或脱皮96%出现在起病8 d内,卡介苗接种疤痕(卡疤)反应常在起病3 d内出现。结论：KD患儿发热、皮肤粘膜改变是主要临床表现,当出现发热、唇红干裂、眼结膜充血的“川崎面容”时即应高度怀疑KD的可能。肛周皮损及“卡疤”反应具有早期诊断的价值。     

Epidemiology of Kawasaki Disease in Japan

Three nation-wide epidemiological surveys, three case control studies and a few other epidemioligical studies on mucocutaneous lymph node syndrome have been conducted in Japan since 1970. The principal epidemiological features of the disease are (1) total numbers reported as of June 1974 being 6,537, (2) prevailing throughout the country without north-south or urban-rural differences, (3) steady increases after 1968 without distinct seasonal variation, (4) peak age at 6–11 months in male and 12–17 months in female, (5) male/female ratio in incidence: 1. 5/1, that of fatal cases 4/1, (6) family and area clustering, (7) previous history of pharyngitis and allergic reactions, (8) no specific characteristics in weight at birth, birth order, immunization history, artificial feeding, (9) temporal curves of incidence consistent with the production of certain medicines.     

静脉注射丙种球蛋白无反应型川崎病治疗进展

川崎病(KD)是一种病因未明、以全身血管炎性病变为主要病理改变的儿童急性发热性疾病。KD常累及冠状动脉,若未及时治疗,患儿可发生冠脉损伤(CAL)。目前急性期KD标准治疗方案为静脉用丙种球蛋白(IVIG)联合口服阿司匹林,但仍有10%~20%的患儿对IVIG无反应,并且这部分患儿发生CAL的风险增高。文献报道有多种IVIG无反应型KD的治疗方法,如二次IVIG治疗、糖皮质激素、英夫利昔单抗、免疫抑制剂和血浆置换等,然而具体治疗方案仍无定论。文章综述IVIG无反应型KD的治疗。     

Conjunctival Biopsy in Patients with Kawasaki Disease

Kawasaki disease (KD) is an acute vasculitis of infants and young children that is associated with bilateral nonexudative conjunctivitis during the acute illness. Epidemiologic evidence has suggested an infectious cause but the etiology of KD remains unknown. We examined conjunctival biopsy specimens from seven patients with typical KD to characterize the pathologic changes during the acute disease. Light microscopic examination revealed nonspecific, mild inflammatory changes that included vascular dilatation, infiltration with scattered lymphocytes, increased numbers of plasma cells in the conjunctival stroma, and increased prominence of goblet cells in the epithelium. No pathogens were identified by special stains for bacteria and rickettsiae, nor were viral particles seen by electron microscopy. We conclude that the conjunctivitis of acute KD is characterized by vascular dilatation with a mild mononuclear cell response with no pathognomonic features. The conjunctiva can be readily sampled in these patients and biopsy may prove useful in selected patients to exclude other clinical entities in the differential diagnosis.     

与川崎病相关的基因多态性研究进展

川崎病(KD)的病因不清,目前仍倾向于感染因素,但大量的流行病学资料显示KD的发病具有一定的遗传背景。为此,通过检索和分析了近几年与KD相关的基因多态性的论文,现对血管紧张素转换酶基因多态性、一氧化氮合酶基因多态性、细胞因子基因多态性等问题作一综述。     

Treatment of Kawasaki Disease using the Intravenous Aspirin Anti-inflammatory Effect of Salicylate

Serum salicylate concentrations were measured in 60 patients with acute phase Kawasaki disease (KD), who were treated with intravenous aspirin (IVASP), to evaluate its antiinflammatory effect in the treatment of KD. Patients with serum salicylate concentrations ± 150μg/ml showed shorter durations of fever (7.1 ± 2.0 vs 10.4 ± 6.6 days; P < 0.05), shorter durations of positive serum C-reactive protein (14.6 ± 4.5 vs 22.3 ± 10.6 days; P < 0.01) and lower incidences of coronary arterial involvements (0/10 vs 6/24; P < 0.05) than did patients with serum salicylate concentrations < 150μg/ml. Significant linear correlations were recognized between daily IVASP dosage and serum salicylate concentrations ( r = 0.73; P < 0.01), and between serum salicylate concentrations and serum free salicylate concentrations ( r = 0.82; P < 0.01). These correlations did not differ between the presence and absence of coronary arterial involvements. Based on these findings we concluded that a beneficial anti-inflammatory effect in the treatment of KD is achieved when the serum salicylate concentration is 150μg/ml, and that such concentrations could be achieved by increasing the daily IVASP dosage to 100 mg/kg per day or more.     

Serum Sodium Levels in Patients with Kawasaki Disease

The purpose of this study was to assess the hypothesis that lower serum sodium levels are associated with cardiovascular sequelae in patients with Kawasaki disease (KD). We used the database of the 16th nationwide survey of KD in Japan. We investigated the distribution of serum sodium levels and the relationship between serum sodium levels and cardiovascular sequelae. Of the reported cases, serum sodium levels were reported in 13,569 patients (89%). The proportion of patients with serum sodium levels 130 mEq/L or less, was greater in complete cases than in incomplete cases. The proportion of patients with serum sodium levels 130 mEq/L or less was increased with age. The largest proportion of patients with serum sodium levels 130 mEq/L or less was found in the category of 3–5 days since onset of illness. A serum sodium of level 135 mEq/L or less was an independent risk factor for cardiovascular sequelae (odds ratio, 1.79, 95% confidence interval, 1.42–2.26). Among patients with KD, there are significant differences in serum sodium levels between diagnostic categories, age, and days since the onset of illness. The sodium level may be a simple predictor of cardiovascular sequelae.     

川崎病患儿抗心磷脂抗体检测的意义

目的：检测川崎病(KD)患儿血清中抗心磷脂抗体(ACA),探讨ACA与KD血管损害的关系。方法：55例急性期KD患儿,采用ELISA方法检测血中ACA-IgG,IgM和IgA三种亚型。结果：55例急性期KD患儿血清ACA-IgG阳性31例,ACA-IgM阳性13例。急性期KD组ACA-IgG,IgM阳性率比对照组显著增高(P<0.01);治疗后ACA-IgG阳性率仍高于对照组(P<0.05),而ACA-IgG阳性或阴性两组的临床表现比较差异均无显著性(P>0.05),但6例伴有血栓形成者有5例ACA-IgG阳性。结论：ACA-IgG是KD常见的抗体,ACA-IgG阳性与KD血栓性血管损害关系密切,但对病情判断无作用。