Factors relating to the cardiac sequelae of Kawasaki disease one month after initial onset

This study aimed to determine the risk factors related to the presence of cardiac sequelae 1 mo after initial onset and to examine the preventive effect of the early administration of high-dose gamma-globulin (GG) on cardiac sequelae in patients with Kawasaki disease. Patients treated with high-dose GG of 2000 +/- 100 mg kg(-1) were selected as subjects from the 15th nation-wide survey in Japan. Univariate and logistic multiple variable analyses were used to test the effects of background variables such as age and gender, variables relating to laboratory findings such as the percentage of neutrophil leucocytes, and variables relating to the GG treatment on the presence of cardiac sequelae. The odds ratios were significantly higher for males (1.48), those younger than 1 y of age (1.71), recurrent cases (2.42), and those with a low haematocrit (<32.5%) (1.45) and high percentage of neutrophil leucocytes (>68%) (1.63). The odds ratio was low for those who started GG administration in less than 6 d from onset between the patients with and without cardiac sequelae. The odds ratio for the duration of GG treatment was not significantly different between those with and without cardiac sequelae. Conclusion: Patients who received early administration of GG, less than 6 d from onset of the disease, had a lower risk than those received GG more than 6 d from the onset. The percentage of neutrophil leucocytes and the haematocrit level are useful indicators in predicting the development of cardiac sequelae.     

Effects of Gamma-Globulin on the Cardiac Sequelae of Kawasaki Disease

Our aim was to delineate the effect of various factors, such as sex, age, serum albumin levels, and the timing of gamma-globulin (GG) therapy, on cardiac sequelae of Kawasaki disease. The patients with Kawasaki disease who were reported at the 1995–1996 nationwide survey and received 2000 mg/kg at specified hospitals were selected as the subjects of the study. A total of 2221 patients actually received the basic dose. The relationships of the GG therapy with the cardiac sequelae, sex, age, timing of GG administration (the date of initiation and duration of the regimen following disease onset), and serum albumin levels were examined by using logistic regression analysis. The odds ratios for the cardiac sequelae in patients with Kawasaki disease were high in males (1.63), in those under the age of 1 year (1.54), and in those with a serum albumin level <3.2 g/dl (2.64). The odds ratio was low in those who received GG before day 8 of the illness (0.69) or in those for whom the administration period was for 2 days or less (0.67). To prevent cardiac sequelae of Kawasaki disease it is desirable that GG therapy be started as soon as possible and completed within 2 days.     

Use of Intravenous γ-Globulin for Kawasaki Disease: Effects on Cardiac Sequelae

The administration of intravenous γ-globulin (IVGG) for Kawasaki disease was investigated throughout Japan in 1993 by obtaining information from pediatric departments in 2652 hospitals that had more than 100 beds. Of 11,221 reported patients, 8958 patients (79.8%) received IVGG treatment. Of all the patients to whom IVGG was administered, the most common total dose was 1000 mg/kg (36.3%) followed by 2000 mg/kg (16.9%) and 1200 mg/kg (16.8%). The treatment was started in 53.8% by day 5 of the illness and in 83.7% by day 7. The proportion of those with cardiac sequelae was higher among patients administered >2000 mg/kg or in those started on IVGG on day 9 of their illness or later. The possible reasons are (1) those who were more severely affected were treated with high-dose IVGG earlier; or (2) IVGG does not effectively prevent cardiac sequelae. We concluded that there is a risk of unfavorable effects with IVGG regarding cardiac sequelae when the IVGG dose is >2000 mg/kg or if IVGG is started on day 9 or later. We believe that only a randomized controlled trial, undertaken prospectively, can adequately address the question of the optimal use of IVGG.     

Cardiac sequelae of Kawasaki disease in Japan over 10 years

To observe the secular trend of a proportion of Kawasaki disease patients with cardiac sequelae in Japan, we analyzed patients with Kawasaki disease reported to nationwide surveys of the disease during 10.5 years from July 1982 to December 1992. Of 69 382 patients reported to the surveys, 10 596 (15.3%) were reported to have cardiac sequelae such as dilatation or stenosis of coronary arteries, myocardial infarction or valvar lesions, 1 month or more after onset. The percentage of cardiac sequelae was particularly high in males, infants younger than 1 year and children older than 5 years of age. The overall prevalence declined steadily over the observed period. However, the percentage for children older than 5 years of age did not decrease, whether treated with intravenous gamma globulin or untreated. As a consequence of the increased number of patients treated with intravenous gamma globulin, the proportion of Kawasaki disease patients with cardiac sequelae decreased annually. However, the proportion of children older than 5 years of age did not decrease.     

Intravenous γ-Globulin for Kawasaki Disease

We studied the effect of γ-globulin (IVGG) and aspirin (ASA) on the development of the coronary artery lesions (CAL) of Kawasaki disease (KD) in three different protocols. Within 29 days of the onset of KD the echocardiographic evidence of CAL had developed in 39–42% of the patients in the ASA group, but only in 13.7–20.8% of the patients treated with IVGG (200 or 400 mgγkgX5). In long-term follow-up observation of CAL of these patients the evidence of CAL in both the ASA and the IVGG group regressed gradually; however, the residual rate of CAL was significantly low in the IVGG group at all times up to 24 months after onset. These facts suggest that when using IVGG for KD, we should select a dose of intact γ-globulin, 1,000 mgγkg or more in total, to prevent the occurrence of CAL. We have demonstrated not only a significant reduction in the occurrence of CAL in patients treated with IVGG but a reduction in the residual rate of CAL for two years as compared with those treated by ASA.     

A multicenter collaborative study on the risk factors of cardiac sequelae due to Kawasaki disease: a one-year follow-up study

Objective: To measure the prevalence of cardiac sequelae 1 y after the onset of Kawasaki disease and determine the risk factors associated with these cardiac sequelae. Material and methods: 1594 patients who initially visited one of the 87 target hospitals in 1996 for Kawasaki disease participated. Selection of the target hospitals was based on a nationwide survey. The patients were followed‐up and information concerning cardiac sequelae occurring within 1 y of onset was obtained by mail survey. Results: The prevalence of cardiac sequelae 1 mo after onset was 10.2% and decreased to 4.2% in 1 y. The prevalence was higher among males than females and higher in patients less than 1 y and 5 ys or older than in 1–4 year‐olds. Of the patients with cardiac sequelae at 1 mo, the sequelae disappeared in 60.7% after 1 y. Analysis revealed low serum albumin as a risk factor related to the occurrence of cardiac sequelae 1 y after onset. Of the 1594 patients, 10 had giant anuerysms and 3 had a fatal outcome. Conclusions: Approximately 60% of cardiac sequelae due to Kawasaki disease that developed within 1 mo after onset disappeared in 1 y. The odds ratio was significantly higher among patients with a low serum albumin level 1 y after onset.     

Recurrent Kawasaki disease

Summary This case report describes a boy who had Kawasaki disease (KD) at age 12 months and had a recurrence one year later. The coronary arteries were normal following the initial episode; however, during the second episode he developed coronary aneurysms. Gallium-67 radionuclide imaging, echocardiography, and angiography were used to diagnose the coronary abnormalities.This work was supported in part by grant RR-00188 from the General Clinical Research Branch of the National Institutes of Health, Bethesda, Maryland.     

Kawasaki disease with severe cardiac sequelae: lessons from recent New Zealand experience

OBJECTIVES: To review recent cases of Kawasaki disease (KD) with significant cardiac sequelae in New Zealand. It is known that intravenous immunoglobulin (IVIG) reduces the risk of coronary artery aneurysm formation if given within 8-10 days of onset of KD. METHODS: Retrospective review of medical course, criteria for KD, laboratory and cardiac findings for six children identified with KD and significant coronary artery sequelae. RESULTS: There was delay in diagnosis of KD in three of the six children. Three cases were atypical by extremes of age (2 months, 10 years, 14 years). By definition all six children had significant coronary artery involvement. One patient had a thrombus detected in a coronary aneurysm 3 weeks after KD. One patient underwent coronary artery bypass grafting for unstable angina 2 years after KD. One patient developed coronary artery aneurysms after an initial 'toxic shock' type illness evolving to KD. Three patients died, one due to rupture of a coronary artery aneurysm, two from rapid early coronary artery obstruction occurring at three and 4 months after initial KD. CONCLUSIONS: Kawasaki disease remains an important cause of mortality and morbidity for children. Diagnostic delay beyond 8 days reduces the chances of successful IVIG therapy in KD. Current studies supported by the Paediatric Surveillance Unit should establish the epidemiology of KD in New Zealand.     

Pelviureteric junction obstruction as sequelae of Kawasaki disease

We present a 7-year-old boy who was admitted with a history of cough for a week, neck pain with associated swelling for 4 days, fever, and vague periumbilical pain. He was diagnosed with Kawasaki disease, and subsequently developed vasculitis of the ureter and stricture of the ureteric lumen at the level of the pelviureteric junction.     

Leukotriene B4 and Kawasaki Disease

The role of LTB4 in Kawasaki disease as a chemo-attractant and immunomodulator is reviewed through our own experience and reports by other invenstigators. In our experiment using 19 patients, we measured calcium ionophore-stimulated LTB4 synthesis in PMNs obtained in three different stages of the illness (acute, convalescent and recovered phases). LTB4 synthesis was significantly increased in the convalescent phase of the illness. Other investigators showed increased serum-LTB4 concentration in acute as well as convalescent phases, suggesting that LTB4 participated in the inflammatory process of Kawasaki disease as an inflammatory mediator and immunomodulator. However, no difference was found in LTB4 synthetic activity in PMNs in any phases of the illness between the patients with and without coronary lesions, which indicated that LTB4 was not a parameter of coronary aneurysm formation. Therapeutic use of high-dose γ-globulin showed a tendency to decreased LTB4 synthesis in PMNs, although it is not conclusive.     

Effect of Intravenous γ-Globulin on Neutrophil Function in Kawasaki Disease

The effect of intravenous γ-globulin (IVGG) on the neutrophil count and neutrophil chemiluminescence (CL) of patients with Kawasaki Disease (KD) was investigated. Forty patients with KD were enrolled in the study. Ten patients were treated with 100 mg/kg/day of γ-globulin for five days (GG 100 group) and 14 patients were treated with 400 mg/kg/day of γ-globulin (GG 400 group) for five days. These patients also took aspirin. Sixteen patients were treated with aspirin alone (ASA group). The neutrophil counts were significantly lower in the GG 400 and GG 100 groups than in the ASA group, three days, and one and two weeks after the start of treatment. Neutrophil CL of the GG 400 and GG 100 groups was significantly lower than in the ASA group one and two weeks after the start of treatment. In the in vitro study, γ-globulin had a dose-dependent suppressive effect on the neutrophil CL in the early stage. Albumin had similar effects. The suppressive effect of γ-globulin on CL was not specific. These findings suggest that IVGG is effective in reducing the production of active oxygen which is considered responsible for the vascular damage in the early stage of KD.     

Coronary arteriovenous fistulae mimicking cardiovascular sequelae of Kawasaki disease

Summary A case of coronary artery dilatation in childhood, initially attributed to Kawasaki disease, was determined by careful serial echocardiography to be the result of congenital coronary arteriovenous fistulae.     

Aerobic exercise function of patients with persistent coronary artery aneurysms secondary to Kawasaki disease

Nine patients with persistent coronary artery aneurysms 1.7–14.0 years after an episode of Kawasaki disease underwent progressive bicycle ergometry with expiratory gas analysis. Two of the patients had aneurysms complicated by angiographically documented coronary artery stenosis. Results of the exercise tests were compared to those obtained from a group of age- and gender-matched normal control subjects. The Kawasaki disease patients did not differ significantly from the control subjects with regard to peak oxygen consumption (81 ± 7% versus 79 ± 12% predicted), peak workload (75 ± 13% versus 77 ± 9% predicted), anaerobic threshold (21.9 ± 6.5 versus 18.9 ± 4.0 ml/kg per minute) or oxygen pulse (96 ± 7% versus 90 ± 14% predicted). None of the patients developed significant ST segment changes or rhythm disturbances during exercise. The exercise function of the patients with coronary artery stenosis did not differ from that of patients without stenosis. It was concluded that the aerobic exercise function of patients with persistent coronary artery aneurysms after an episode of Kawasaki disease appears to be well preserved. Kawasaki disease patients with significant coronary artery pathology are not accurately identified by a single assessment of aerobic exercise function.     

Serum and urine Helicobacter pylori antibody titer after intravenous γ-globulin treatment for Kawasaki disease and its clearance

BACKGROUND: It is not clear the effect of gamma-globulin therapy on results of enzyme-linked immunosorbent assays (ELISA) based on serum and urine for detection of Helicobacter pylori (H. pylori) antibodies, although the therapy can cause false-positive results in those assays. METHODS: To examine the effect of intravenous gamma-globulin (IVIG) treatment on the results of ELISA based on serum and urine, levels of H. pylori IgG were measured in the serum and urine before and after IVIG therapy in 18 children with Kawasaki disease (KD) uninfected with H. pylori. RESULTS: The serum and urine H. pylori IgG levels decreased time-dependently after the IVIG therapy and there were significant differences (P < 0.01) in the levels prior to therapy and at 7 days and 1 month after the therapy. The significant difference in the H. pylori IgG levels prior to therapy and 3 months after the therapy was observed in the serum but not in the urine. CONCLUSION: The results suggest that gamma-globulin administration can cause false-positive results in ELISA based both on serum and urine for detection of H. pylori antibodies, and that the H. pylori antibodies cleared much more quickly from the urine than from the serum.     

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川崎病是导致儿童后天性心脏病的主要原因.川崎病并发冠状动脉损害及巨大冠状动脉瘤等心血管后遗症给儿童的身心健康造成很大影响.日本循环学会(JCS)联合日本心脏外科学会(JSCS)2020年7月共同发布了《川崎病心血管后遗症的诊断和管理指南(JCS/JSCS 2020)》,系统介绍了川崎病心血管后遗症的诊疗和管理新进展.该...     

Circulating Cardiac Troponin I Levels in Kawasaki Disease

In addition to the vascular findings of Kawasaki disease (KD), clinical, electrocardiographic, and/or echocardiographic signs of myocarditis are recognizable in the acute phase of KD in many patients. The mechanism of myocarditis and an association with the development of subsequent coronary artery abnormalities in KD is unknown. Previous studies of serum cardiac troponin I (cTnI) measurements in pediatric populations have suggested a possible utility of measurements in diagnosis and follow-up of KD. We designed a retrospective study to evaluate cTnI measurements during acute KD and to assess the predictive value of cTnI measurements in acute KD for the subsequent development of coronary artery abnormalities. Twenty-nine children were studied. Group 1 consisted of 15 KD patients who developed coronary artery abnormalities as detected by transthoracic echocardiographic evaluation. Group 2 consisted of 14 KD patients with persistently normal coronary artery findings on echocardiograms. A control group consisted of 11 children, none of whom were known to have had clinical findings of KD or myocarditis. The mean cTnI values for all three groups were lower than the values suggestive of cardiac damage: group 1 = 0.11 ± 0.16 ng/ml, group 2 = 0.15 ± 0.34 ng/ml, and control = 0.04 ± 0.08 ng/ml. The current study demonstrates that there is no significant elevation of cTnI in KD patients. Additionally, there is no correlation between cTnI measurements and the finding of myocarditis, as reflected by decreased cardiac function, or the subsequent development of coronary artery abnormalities.     

Coronary risks after high-dose γ-globulin in children with Kawasaki disease

OBJECTIVES: The goals of the present study were to develop a predictive coronary risk scoring system after intravenous gamma-globulin (IVGG) therapy of any dose for the different preparations currently used in the treatment of children with Kawasaki disease and to determine the predictive value of the system. The previously reported scoring systems were based on treatment with high-dose IVGG therapy at limited doses and were determined using investigative methods. METHODS: Four hundred and fifty-one patients were randomized into one of three groups and received either i.v. polyethylene glycol-treated human immunoglobulin at a dose of either 200 (n = 147) or 400 mg/kg per day (n = 152) or freeze-dried sulfonated human immunoglobulin at 200 mg/kg per day (n = 152) for 5 consecutive days. We documented 31 cases of coronary abnormalities (CA). Univariate and multivariate logistic regression was performed using 49 clinical variables and the resulting predictive model was validated. RESULTS: The duration of fever (odds (I day)/odds (- 5 days)= 0.158; 95% confidence interval (CI) 0.0385-0.648), hemoglobin (odds (Q1 = 10.3)/odds (Q3 = 11.6) = 3.97; 95% CI 1.92-8.20), IgG (odds (Q1 = 1,900)/odds (Q3=2,658)=2.72, 95% CI 1.18-6.25) and IgA (odds (Q1 =72)/odds (Q3= 160) = 0.415; 95% CI 0.253-0.680) levels after completion of gamma-globulin infusion were independent predictors. The model is quasi-cross validated and has acceptable sensitivity and selectivity. The estimated risk and observed occurrence of CA coincide. CONCLUSIONS: Determinants of the risk of CA after IVGG therapy are a longer duration of fever, a lower IgG level, a higher IgA level and a lower hemoglobin level after IVGG infusion. This model is applicable for IVGG doses from 1 to 2 g/kg and for at least two different gamma-globulin preparations.