Coronary risk factors in Kawasaki disease treated with additional gammaglobulin

Aims: To assess the hypothesis that an additional intravenous gammaglobulin (IVGG) infusion, if administered early, may prevent coronary artery lesions (CAL) in patients with Kawasaki disease (KD) who do not respond to initial IVGG therapy. Methods: Forty four KD patients (17 with CAL and 27 without CAL), treated with additional IVGG because of persistent or recrudescent fever after initial IVGG therapy, were studied. Main outcome measures were the presence of CAL by echocardiography and the number of febrile days before and after start of additional IVGG infusion (pre- and post-additional IVGG). Results: In univariate analyses, risk factors for CAL were the number of febrile days pre-additional IVGG, the number of febrile days post-additional IVGG, the number of days that initial IVGG was divided over, the white blood cell count pre- and post-additional IVGG, and the C reactive protein concentration pre-additional IVGG. In a multivariate analysis, the only independent risk factor was the number of febrile days pre-additional IVGG (⩾10 days; odds ratio 7.86; 95% CI 1.44 to 42.8; p = 0.02). Conclusions: Among KD patients with persistent or recrudescent fever after initial IVGG therapy, administration of additional IVGG before the first 10 febrile days was associated with a decreased prevalence of CAL, when compared with the prevalence in those who were retreated later. An additional IVGG infusion, if administered early, may prevent CAL in initial IVGG non-responders.     

High-dose gammaglobulin therapy for Kawasaki disease

To evaluate the effectiveness of gammaglobulin in decreasing the incidence of coronary artery lesions in Kawasaki disease, a randomized controlled study in 136 patients was conducted using high doses of gammaglobulin 400 mg/kg/d for 3 days plus aspirin 30 mg/kg/d (gammaglobulin group) and aspirin alone at the same dosage (aspirin group). The total febrile period and the duration of fever after treatment were significantly shorter in the gammaglobulin group than in the aspirin group (P less than 0.001). The incidence of coronary artery lesions and of coronary artery aneurysms was significantly lower in the gammaglobulin group than in the aspirin group up to 30 days after the onset of Kawasaki disease (P less than 0.01 and P less than 0.05, respectively). In 16 of 69 patients given gammaglobulin, fever persisted for longer than 3 days, and there was a higher incidence of coronary artery lesions among them. The effectiveness of high doses of gammaglobulin in preventing coronary artery lesions has been demonstrated, but the indications and the optimal dose of gammaglobulin remain to be determined.     

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.     

Time interval of measles vaccination in patients with Kawasaki disease treated with additional intravenous immune globulin

A standard treatment with a dose of 2 g/kg of intravenous immune globulin (IVIG) is sometimes ineffective in some patients with Kawasaki disease (KD), who are commonly treated with additional IVIG. An interval of 6 to 7 months in Japan and 11 months in the United States is recommended before vaccination against measles after IVIG treatment for KD, but it is not known how long after treatment with additional IVIG. We studied the persistence of measles antibody titers in six episodes of KD in five patients without history of measles infection or vaccination, 4 to 28 months of age, after additional infusion of IVIG. The total dose was 4 g/kg in five episodes and 6 g/kg in one episode. Enzyme immunoassay antibody titers against measles were still positive (400) in all patients tested 3 months after additional infusion of IVIG and positive in one patient and equivocal (200 and <400) in three patients after 6 months, but negative (<200) in all after 9 months following infusion. Neutralization test antibody titers against measles were still positive (1:4) in all patients 3 months after additional infusion of IVIG, but only one after 6 months, and negative (<1:4) in all after 9 months following infusion. Conclusion: we suggest that an appropriate interval between infusion of 4 g/kg of intravenous immune globulin and measles vaccination be 9 months. The 11-month interval recommended in the United States for 2 g/kg may be longer than necessary.Abbreviations EIA enzyme immunoassay - HI hemagglutination inhibition - IVIG intravenous immune globulin - KD Kawasaki disease - NT neutralization test     

Meta-analysis of risk factors associated with atherosclerosis in patients with Kawasaki disease

Background

Kawasaki disease (KD) has now become the leading cause of acquired heart disease among children in developed countries. This study investigated whether patients with KD have an increased risk of atherosclerosis.

Methods

Electronic databases, including PubMed, Embase and Springer link, were searched through June 1, 2015, for eligible studies. Studies were included when they met the following criteria: 1) an observational study focusing on evaluating the risk factors for atherosclerosis in patients with KD; 2) KD was diagnosed clinically according to the Japan Kawasaki Disease Research Committee or American Heart Association’s diagnostic criteria; 3) the study subjects were KD patients without coronary heart disease or related cardiovascular disease (KD group) and non-KD patients as control (control group), and 4) investigation of important atherosclerosis risk factors, total cholesterol (TC), low-density lipoprotein cholesterol (LDL), triglycerides (TG), systolic blood pressure (SBP), and flowmediated dilatation (FMD). The methodological quality of the included studies was evaluated using the Newcastle- Ottawa Scale. Mean difference (MD) and relative risk (RR) and corresponding 95% confidence intervals (CI) were used to calculate the pooled results.

Results

Sixteen studies were included with a total of 870 patients, including 421 KD patients and 449 non-KD controls. Differences in TG and SBP between KD patients and controls were not significant; in contrast, TC and LDL levels were significantly higher in KD patients than the controls, whereas FMD in the KD patients was significantly lower.

Conclusions

KD patients may have an increased risk of developing atherosclerosis.

     

Pulse methylprednisolone with gammaglobulin as an initial treatment for acute Kawasaki disease

Approximately 15–20% of patients with Kawasaki disease (KD) are not responsive to high-dose intravenous gammaglobulin (IVIG). We have previously reported a predictive method for identifying IVIG-non-responsive patients (high-risk KD patients). We determined the safety and effectiveness of pulse methylprednisolone with high-dose IVIG (mPSL+IVIG) as a primary treatment for high-risk KD patients. Sixty-two high-risk KD patients were treated with pulse methylprednisolone 30 mg/kg over 2 h, followed by IVIG 2 g/kg over 24 h (mPSL+IVIG group) and were compared with a historical control group of 32 high-risk patients treated with IVIG 2 g/kg alone at the participating hospitals before this study was opened (IVIG group). High-risk patients were identified with at least two of three predictors (C-reactive protein ≥7 mg/dL, total bilirubin ≥0.9 mg/dL or aspartate aminotransferase ≥200 IU/L). Sixty-six percent (95% confidence interval [CI] 54–78%) of patients had a prompt defervescence in the mPSL+IVIG group compared with 44% (95% CI 26–62%) for the IVIG group (p = 0.048). Coronary artery lesions were observed in 24.2% (95% CI 13.2–35.2%) and 46.9% (95% CI 28.6–65.2%) of patients in the mPSL+IVIG and IVIG groups, respectively (p = 0.025). This is the first report showing that mPSL+IVIG is effective and safe as a primary treatment for high-risk KD patients.     

Risk factors associated with the need for additional intravenous gamma-globulin therapy for Kawasaki disease

Aim: To investigate the characteristics of patients with Kawasaki disease who needed intravenous gamma-globulin (IVGG) re-treatment. Methods: Using the database of the 17th nationwide survey in Japan, a total 11 366 patients were identified and analysed (1855 re-treatment patients and 9511 responders). Results: Multivariate logistic regression analysis showed that male sex (odds ratio (OR) 1.26; 95% CI 1.14-1.40), complete cases (OR 1.39; 95% CI 1.07-1.80), recurrence (OR 1.47; 95% CI 1.15-1.88), IVGG treatment within 4 d of illness (OR 2.05; 95% CI 1.84-2.27), daily dose of initial IVGG less than 1000 mg/Kg (OR 0.54; 95% CI 0.48-0.61), exanthema (OR 2.03; 95% CI 1.62-2.56), lips and oral lesions (OR 1.57; 95% CI 1.24-1.98), peripheral extremities changes (OR 1.85; 95% CI 1.54-2.22), and cervical lymphadenopathy (OR 1.89; 95% CI 1.66-2.16) were independent risk factors associated with the need for IVGG re-treatment.

Conclusion: Male sex, recurrence, and treatment with IVGG at a dose of 1000 mg/d or less within 4 d of illness onset are independent risk factors associated with the need for IVGG re-treatment.     

Coronary artery changes in patients with Kawasaki disease

Kawasaki disease (KD) is an acute, self-limiting, systemic vasculitis of unknown aetiology, which most commonly occurs in children aged 6 mo to 5 y, with a peak incidence at 9-11 mo. The inflammatory process preferentially involves the coronary arteries, potentially resulting in coronary arteritis, aneurysmal lesions, arterial thrombotic occlusion and sudden death. Kawasaki disease is the most common cause of acquired coronary vessel abnormalities in children. The cause of KD is not known, but evidence is presented for an inflammatory response and a genetic predisposition. The diagnostic tests are not yet defined, but treatment with immunoglobulin and aspirin is effective at reducing the risk of cardiac complications from 25% to 4.7% in the UK. Sequelae may occur, either acutely with myocardial, endocardial or pericardial inflammation, or many years after the original illness. There may be abnormalities of myocardial blood flow as assessed by MRI, radio-nucleide studies or echo Doppler. Such abnormalities of coronary arteries may require ongoing medication, interventional catheterization or even cardiac surgery. In the future, we hope to have more accurate diagnostic tests or prophylaxis against the disease, in addition to improved means of determining the susceptibility to or presence of long-term complications.     

Coronary artery changes in patients with Kawasaki disease

Kawasaki disease (KD) is an acute, self-limiting, systemic vasculitis of unknown aetiology, which most commonly occurs in children aged 6 mo to 5 y, with a peak incidence at 9–11 mo. The inflammatory process preferentially involves the coronary arteries, potentially resulting in coronary arteritis, aneurysmal lesions, arterial thrombotic occlusion and sudden death. Kawasaki disease is the most common cause of acquired coronary vessel abnormalities in children. The cause of KD is not known, but evidence is presented for an inflammatory response and a genetic predisposition. The diagnostic tests are not yet defined, but treatment with immunoglobulin and aspirin is effective at reducing the risk of cardiac complications from 25% to 4.7% in the UK. Sequelae may occur, either acutely with myocardial, endocardial or pericardial inflammation, or many years after the original illness. There may be abnormalities of myocardial blood flow as assessed by MRI, radio-nucleide studies or echo Doppler. Such abnormalities of coronary arteries may require ongoing medication, interventional catheterization or even cardiac surgery.
Conclusion : In the future, we hope to have more accurate diagnostic tests or prophylaxis against the disease, in addition to improved means of determining the susceptibility to or presence of long-term complications.     

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??Abstract?? Objective To analyze the characteristics and risk factors of coronary artery lesions ??CAL?? in Kawasaki disease ??KD?? based on the clinical grading. Methods The clinical records of 1253 KD patients admitted to Children’s Hospital of Fudan university from January 2000 to June 2011 were analyzed retrospectively. Results ??1??Coronary arterial lesions occurred in 304 cases with the incidence of 24.3% in KD patients. According to the clinical grading of CAL of KD?? among 304 CAL patients?? 32 cases ??10.5%?? were grade II??251 cases ??82.6%?? were grade ?? 13 cases ??4.3%?? were grade ????and 8 cases??2.6%?? were grade V?? with the prevalence in KD patients of 2.6%??20.0%??1.0%??and 0.64% respectively. ??2??In all CAL patients?? single?? double?? three and four coronary branch lesions accounted for 42.4%?? 29.3%??16.1% and 12.2% respectively. The lesions of left main trunk??left anterior descending branch??left circumflex branch and right coronary artery accounted for 43.5 %??18.6%??6.8 % and 31.1% of all the branches involved respectively. ??3??The results of single factor analysis and multivariate logistic regression analysis showed that incomplete KD and elevated C reactive protein ????100 mg/L?? were the risk factors of grade ?? CAL?? while male sex?? age younger than 1 year?? duration of fever over 10 days?? incomplete KD and low serum albumin ????30 g/L?? were the risk factors of Grade ????CAL. Conclusions ??1??Grade III CAL is the most common type in KD patients, accounting for 82.6% of CAL. ??2??About 57.6% CAL occurs in two and abovetwo branches of coronary arteries. ??3??The most frequently involved branch is left main trunk, followed by right coronary artery??left anterior descending branch and circumflex branch. ??4??Being male?? age??1 year old?? incomplete KD?? long-lasting fever ????10 d?? and low serum albumin ????30 g/L?? are the independent risk factors of grade ????CAL.     

Coronary artery calcification in Kawasaki disease

To evaluate the angiographic features of coronary lesions in Kawasaki disease with coronary artery calcification, cinefluoroscopy and cineangiography were retrospectively reviewed in 116 patients who had undergone coronary angiography between 1982 and 1989. Angiographic abnormalities of coronary arteries were demonstrated in 55 of the 116 patients. In 5 (9.1%) of the 55 patients, 9 with calcification were identified by cinefluoroscopy and chest x-ray. Eight of the 9 calcified lesions showed a circular or ring-shape configuration. Coronary angiography revealed a total occlusion of the right coronary artery with collateral circulation from the distal left coronary artery in 2 patients and a severe stenosis of the right coronary artery in 2 patients, in whom anticoagulant therapy had not been continued during the follow-up periods. The remaining patient in whom anticoagulant therapy had been continued had bilateral aneurysms but no significant stenosis. These results indicate that a ringshape calcification on chest x-ray in a patient with a history or Kawasaki disease may suggest an involvement by coronary artery stenosis even when anticoagulant drugs had been given. Therefore, coronary angiography should be performed to evaluate the stenotic lesions if this type of calcification is found by routine radiographic examination.     

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.     

再发川崎病的临床特点及相关危险因素分析

目的探讨川崎病(KD)再发的临床特点及相关危险因素。方法回顾分析2010-2018年间收治的再发性KD患儿的临床特点及危险因素。结果研究期间共收治2 112例初发KD患儿,其中35例再发,再发率1.66%。35例再发KD患儿首次发病后KD再发的中位时间为13.5(4～69)月。与初发患儿相比,再发患儿的发热时间缩短,四肢硬肿比例较低,C反应蛋白升高,血清钾降低,差异均有统计学意义(P0.05)。35例再发KD患儿中,11例初发时有冠状动脉病变(CAL),8例在再发时亦出现CAL。Logistic回归分析显示,支原体感染和CD19~+CD23~+淋巴细胞亚群比例升高是KD再发的独立危险因素(P0.05)。以再发风险评分绘制ROC曲线,曲线下面积为0.84(95%CI:0.76～0.91),最佳临界值为1.24时,其敏感性和特异性分别为0.83和0.70。结论 KD发生后至少应随访2年,支原体感染和CD19~+CD23~+淋巴细胞亚群升高可作为KD再发的预测指标。初发KD发生CAL者再发时更易发生CAL。     

Resistant Kawasaki disease treated with anti-CD20

We report the case of a 6-year-old boy who had Kawasaki disease resistant to intravenous immunoglobulin and systemic steroids. Because of an uncontrolled disease course, with significant lesions of the coronary arteries, anti-CD20 treatment was used. Rapid clinical, biological, and cardiac improvement was observed. The patient tolerated the treatment well.     

Coronary risk factors in schoolchildren.

Death rates from coronary heart disease (CHD) in Northern Ireland are among the highest in the world. However, no data have been available to test the hypothesis that the high prevalence of CHD is reflected by the risk status of the childhood population. A randomly selected 2% population sample of 1015 children aged 12 and 15 years was studied to obtain baseline information on blood pressure, lipid profile, cigarette smoking, family history, physical activity, cardiorespiratory fitness, and dietary fat intake. Using available criteria thresholds, 15-23% displayed increased blood pressure, 12-25% had unfavourable lipid profiles, and 18-34% were overfat. In 15 year old children, 16-21% admitted being regular smokers, 26-34% displayed poor cardiorespiratory fitness, and 24-29% reported little physical activity in the previous week. Dietary analysis revealed relatively low polyunsaturated to saturated fatty acid ratios and high mean fat intakes, accounting for approximately 40% total daily energy. Despite the exclusion of family history from the analysis, 16% of the older children exhibited three or more risk factors. These results justify major concern about the level of potential coronary risk in Northern Ireland schoolchildren. Broadly based primary prevention strategies aimed at children are essential if future adult CHD mortality is to be reduced.     

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。     

Clinical features of recurrent Kawasaki disease and its risk factors

The clinical features and risk factors for recurrence of Kawasaki disease (KD) remain unclear. In order to summarize clinical features of recurrent KD and identify risk factors associated with recurrence, we conducted a retrospective review of the medical records of consecutive cases of KD from January 2002 to December 2010. Demographic, clinical, laboratory, and echocardiographic data were analyzed. The maximum coronary artery Z score normalized against body surface area was assessed using coronary artery diameters. At the first onset of recurrent KD, children had longer durations of fever before intravenous immunoglobulin (IVIG) treatment and higher levels of alanine aminotransferase, serum aspartate aminotransferase (AST), and lower hemoglobin levels than those with a single episode of KD. Multivariate logistic regression analysis showed that long durations of fever before IVIG treatment, high AST levels, and reduced hemoglobin levels were significantly associated with recurrent KD. Ten of the 22 recurrent KD children had coronary artery complications during the first onset episode, and six (60 %) of these also had coronary artery complications during the recurrence. Children with longer durations of fever, lower hemoglobin levels, and higher AST levels may be at increased risk for KD and coronary artery complications are more likely to occur in children with recurrent KD if they were present during the first episode.