HIGH-DOSE INTRAVENOUS GAMMAGLOBULIN FOR KAWASAKI DISEASE
Abstract
The ability of high-dose intravenous gammaglobulin (IVGG) to prevent the coronary artery lesion of Kawasaki disease has been studied in a multicentre controlled trial of IVGG plus aspirin versus aspirin alone, aspirin being the conventional treatment for Kawasaki disease. Patients were allocated at random to aspirin (45 cases) or IVGG (40 cases), there being no significant intergroup differences in age, sex ratio, duration of disease until the start of treatment, or severity. The development of coronary artery dilatation was monitored by two-dimensional echocardiography. Within 29 days of the onset of the disease, this lesion had developed in 19 cases (42%) in the aspirin group and in 6 cases (15%) in the IVGG group. There were no new instances of this lesion: in the period 30-60 days coronary artery dilatation persisted in 14 and 3 cases, respectively. In patients found to have echocardiographic abnormalities selective coronary arteriography was done 30-60 days after onset of Kawasaki disease and the lesion was confirmed in 1 of the 6 cases in the IVGG group and in 11 of the 19 controls. High-dose IVGG seems to reduce the frequency of coronary artery abnormalities in patients with Kawasaki disease.
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Cited by (629)
To analyse the research history, development trends and current status of relevant literature in the field of Kawasaki disease, and to provide the basis for future directions in Kawasaki disease (KD) research.
Literature on Kawasaki disease published between January 1974 and December 2022 was searched for in the Web of Science database, and CiteSpace was used to perform visual analyses.
The search yielded a total of 6950 articles. The number of publications related to Kawasaki disease showed an increasing trend. A collaborative network analysis revealed that the United States, Japan and mainland China were the most influential countries in this field. The University of California system contributed the most publications and the journal with the most publications was Circulation. JW Newburger was an authoritative author in this field. “Coronary artery lesion”, “Intravenous immunoglobulin” (IVIG) and “Risk factor” were three prominent keywords. Keyword bursts changed from “TNF” and “IVIG”, which focused on aetiology and treatment, to “Long term management”, which emphasized the recovery period, and to “Kawasaki-like disease” and “Multisystem inflammatory syndrome” during the novel coronavirus pandemic. Trends of highly cited references indicated that landmark articles in different periods focused on Kawasaki disease guidelines, gene polymorphisms and multisystem inflammatory syndrome caused by the novel coronavirus.
The aetiology of Kawasaki disease remains unclear, but viral infection is likely to play an important role. The combination of evolving sequencing technologies, large-scale epidemiological investigations and prospective cohort studies is likely to be important in exploring Kawasaki disease and improving its prognosis in future.
Multisystem Inflammatory Syndrome in Children and Kawasaki Disease: A Spectrum of Postinfectious Hyperinflammatory Disease
2023, Rheumatic Disease Clinics of North AmericaAdult and childhood vasculitis
2023, Handbook of Clinical NeurologyVasculitis refers to heterogeneous clinicopathologic disorders that share the histopathology of inflammation of blood vessels. Unrecognized and therefore untreated, vasculitis of the nervous system leads to pervasive injury and disability, making this a disorder of paramount importance to all clinicians. There has been remarkable progress in the pathogenesis, diagnosis, and treatment of primary CNS and PNS vasculitides, predicated on achievement in primary systemic forms. Primary neurological vasculitides can be diagnosed with assurance after intensive evaluation that incudes tissue confirmation whenever possible. Clinicians must choose from among the available immune modulating, suppressive, and targeted immunotherapies to induce and maintain remission status and prevent relapse, unfortunately without the benefit of RCTs, and tempered by the recognition of anticipated medication side effects.
It may be said that efforts to define a disease are attempts to understand the very concept of the disease. This has been especially evident in systemic and neurological disorders associated with vasculitis. For the past 100 years, since the first description of granulomatous angiitis of the brain, the CNS vasculitides have captured the attention of generations of clinical investigators around the globe to reach a better understanding of vasculitides involving the central and peripheral nervous system. Since that time it has become increasingly evident that this will necessitate an international collaborative effort.
Kawasaki disease (KD) is a kind of vasculitis predominantly afflicting children younger than five. Although intravenous immunoglobulin (IVIG) has been regarded as the first-line therapy, there are some children unresponsive to it, resulting in higher risk of coronary artery aneurysms (CAA), the most severe complication of KD. Pyroptosis is an inflammatory apoptosis, which resembles the traits of IVIG-resistance. Therefore, our research aims to find relationships between KD with IVIG-resistance and pyroptosis, and provide the underlying mechanisms of IVIG-resistance.
The transcriptome data of three datasets were downloaded from Gene Expression Omnibus (GEO) database. CIBERSORTx and WGCNA were combined to identify the coexpression gene network correlated with the up-regulated immune cells in KD, using differentially expressed genes (DEGs) overlapped in GSE68004 and GSE73461. The key genes in hub module were intersected with pyroptosis-related genes (PRGs). Then KD patients were divided into subgroups according to the expression of remaining genes, along with the construction of risk score (RS) based on the least absolute shrinkage and selection operator (LASSO) regression analysis. Besides, we explored the clinical value of RS between IVIG-responsive and -resistant KD patients in GSE16797. In addition, the biological pathways between subgroups were evaluated using Gene Set Variation Analysis (GSVA).
A total of 4246 DEGs and three immune cells, including Monocytes, M0 macrophage, and neutrophils, were analyzed with P < 0.05 between KD and healthy controls (HCs). The lightcyan module was the hub module based on WGCNA, and only NLRC4, CASP1, CASP4, GSDMD, IL1B and PYCARD in the hub module were overlapped with PRGs. Then KD patients in GSE68004 were stratified into two clusters on the basis of the expression levels of six genes. RS was built with five out of six genes (exclude PYCARD) according to the LASSO analysis, which could differentiate C1 from C2, IVIG-responsive from -resistant KD patients. Besides, the high-risk group (C1) tended to be with increased levels of inflammation, immune responses and infiltration of neutrophils according to the analysis of GSVA and CIBERSORTx.
We built a pyroptosis-related RS to evaluate the degree of pyroptosis and infiltrating immune cells in subgroups of KD, and associated it with the responsiveness to IVIG, which might help us to further understand the pathological process during IVIG-nonresponse.
Cost-effectiveness analysis of infliximab for the treatment of Kawasaki disease refractory to the initial treatment: A retrospective cohort study
2022, Journal of CardiologyCitation Excerpt :However, CAA can be prevented by suppressing inflammation early in acute phase treatment. Initiation of intravenous immunoglobulin (IVIG) (2 g/kg) within 10 days of fever onset has been confirmed to reduce the risk of CAA by approximately 20% (from 25% to <5%) [4–8]. High-dose IVIG (2 g/kg) or combination with steroid therapy as 1st line treatment has reduced rates of cardiac sequelae in Japan [9].
Infliximab (IFX) treatment is approved in Japan for health insurance coverage in patients with Kawasaki disease (KD). This study aimed to compare the cost-effectiveness of IFX and other therapeutic strategies for KD refractory to initial treatment, including intravenous immunoglobulin (IVIG), steroids, immunosuppressants, and plasma exchange therapy.
This multicenter, retrospective cohort study utilized data from the public medical insurance system of Japan. The target population included those who received treatment for KD between April 2012 and March 2019. Eligibility criteria were as follows: 1) initial onset of KD, 2) age < 15 years at onset, and 3) administration of 3rd line treatment if the 1st line treatment was IVIG alone or 2nd line treatment if the 1st line treatment was a combination of IVIG and steroids, in accordance with Japanese guidelines (2012). Those with KD-related cardiovascular complications before admission and those with congenital cardiac disease were excluded. The primary outcome was cost-effectiveness, which was calculated based on the number of admission events per annum divided by medical expenses per annum (times/10,000 US dollars). The Wilcoxon test was applied to analyze the difference in cost-effectiveness between patients who had received IFX and those who had not.
Among 1267 patients with KD, 25 received IFX treatment, while 206 received another treatment after the disease was designated refractory to initial treatment. The frequency of steroid use during initial IVIG treatment (a predictor of severity) was higher in the non-IFX group than in the IFX group (70.4% vs. 32.0%, p < 0.001) but became comparable after propensity-score matching. Our analysis indicated that IFX was more cost-effective than other treatments [1.04 (0.86, 1.34) vs. 1.38 (1.03, 1.79) (times/10,000 US dollars), p = 0.006].
IFX treatment may be more cost-effective than non-IFX treatment for patients with KD that is refractory to initial treatment.
Management of COVID-19-associated multisystem inflammatory syndrome in children: A comprehensive literature review
2021, Progress in Pediatric CardiologyThe prevalence and severity of COVID-19 are greatly reduced in children, yet some pediatric patients develop a syndrome resembling Kawasaki Disease (KD), termed Multisystem Inflammatory Syndrome in Children (MIS-C). With an estimated incidence of 2/100,000 children, MIS-C is relatively rare but can be fatal. Clinical features can include fever, hyperinflammatory state, gastrointestinal symptoms, myocardial dysfunction, and shock. The pathogenesis of MIS-C, although yet to be completely elucidated, appears to be distinct from KD in terms of epidemiology, severity, and biochemical signature.
Although efficacy of treatments for MIS-C have largely not yet been investigated, we aim to conduct a comprehensive literature search of numerous medical databases (AMED, EBM Reviews, Embase, Healthstar, MEDLINE, ERIC, and Cochrane) to highlight treatments used around the world, their rationale, and outcomes to better inform guidelines in the future. Using the findings, an approach to MIS-C management will be outlined.
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MIS-C appears to be a SARS-CoV-2 related post-infection phenomenon that is distinct from Kawasaki disease.
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Although outcomes are largely favorable, there is significant variation in MIS-C treatment. Most management regimens reported to date mirror that of KD; however, targeted therapy based on specific MIS-C phenotypes may have the potential to improve outcomes.
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We recommend close monitoring by a multidisciplinary team, symptomatic treatment (e.g., intravenous immunoglobulin for KD-like symptoms, steroids/immunotherapy for multisystem inflammation), and long-term follow-up.
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Further research is required to evaluate the effectiveness of current MIS-C treatments and to determine more refined therapies.
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