Kawasaki disease: an evidence based approach to diagnosis, treatment, and proposals for future research
TL;DR: A clinical guideline for the diagnosis and treatment of Kawasaki disease in the UK based on the best available evidence to date is proposed, and areas of practice where evidence is anecdotal or based on retrospective data are highlighted.
Abstract: This article proposes a clinical guideline for the diagnosis and treatment of Kawasaki disease in the UK based on the best available evidence to date, and highlights areas of practice where evidence is anecdotal or based on retrospective data. Future research as proposed by the London Kawasaki Disease Research Group is outlined, and clinicians are invited to prospectively enrol their suspected cases into this collaborative research project.
Citations
More filters
TL;DR: Recent advances in the understanding of KD pathogenesis and therapeutics are summarized, and an approach for managing KD patients in the UK in the light of these advances is provided.
Abstract: Kawasaki disease (KD) is an acute self-limiting inflammatory disorder, associated with vasculitis, affecting predominantly medium-sized arteries, particularly the coronary arteries. In developed countries KD is the commonest cause of acquired heart disease in childhood. The aetiology of KD remains unknown, and it is currently believed that one or more as yet unidentified infectious agents induce an intense inflammatory host response in genetically susceptible individuals. Genetic studies have identified several susceptibility genes for KD and its sequelae in different ethnic populations, including FCGR2A, CD40, ITPKC, FAM167A-BLK and CASP3, as well as genes influencing response to intravenous immunoglobulin (IVIG) and aneurysm formation such as FCGR3B, and transforming growth factor (TGF) β pathway genes. IVIG and aspirin are effective therapeutically, but recent clinical trials and meta-analyses have demonstrated that the addition of corticosteroids to IVIG is beneficial for the prevention of coronary artery aneurysms (CAA) in severe cases with highest risk of IVIG resistance. Outside of Japan, however, clinical scores to predict IVIG resistance perform suboptimally. Furthermore, the evidence base does not provide clear guidance on which corticosteroid regimen is most effective. Other therapies, including anti-TNFα, could also have a role for IVIG-resistant KD. Irrespective of these caveats, it is clear that therapy that reduces inflammation in acute KD, improves outcome. This paper summarises recent advances in the understanding of KD pathogenesis and therapeutics, and provides an approach for managing KD patients in the UK in the light of these advances.
224 citations
Cites background from "Kawasaki disease: an evidence based..."
...[6] [7] [8] [9] In view of the frequency and severity of coronary artery complications, there has been intense interest in treatments to reduce the risk of CAA. 6 [10] [11] [12] [13] [14] KD is also potentially an important cause of long-term cardiac disease in adult life....
[...]
...9 Immunisation with all vaccines should be deferred for at least 3 months following an episode of KD treated with IVIG, mainly due to the potential lack of effectiveness of live vaccines following IVIG 75 and due to the potential for any vaccine to induce potentially detrimental immune activation during the convalescent phase of KD....
[...]
...9 If thrombosis does occur, thrombolytic therapy may be indicated, but expert advice must be sought....
[...]
TL;DR: Evaluated randomised controlled trials of intravenous immunoglobulin to treat Kawasaki disease in children showed a significant decrease in new coronary artery abnormalities (CAAs) in favour of IVIG, and children fulfilling the diagnostic criteria for Kaw Osaka disease should be treated with IVIG within 10 days of onset of symptoms.
Abstract: Background Kawasaki disease is the most common cause of acquired heart disease in children in developed countries. The coronary arteries supplying the heart can be damaged in Kawasaki disease. The principal advantage of timely diagnosis is the potential to prevent this complication with early treatment. Intravenous immunoglobulin (IVIG) is widely used for this purpose. Objectives The objective of this review was to evaluate the effectiveness of IVIG in treating, and preventing cardiac consequences, of Kawasaki disease in children. Search strategy Electronic searches of the Cochrane Peripheral Vascular Disease Group Specialised Register, CENTRAL, MEDLINE, EMBASE, and CINAHL were performed (last searched April 2003). We also searched references from relevant articles and contacted authors where necessary. In addition we contacted experts in the field for unpublished works. Selection criteria Randomised controlled trials of intravenous immunoglobulin to treat Kawasaki disease were eligible for inclusion. Data collection and analysis Fifty-nine trials were identified in the initial search. On careful inspection only sixteen of these met all the inclusion criteria. Trials were data extracted and assessed for quality by at least two reviewers. Data were combined for meta-analysis using relative risk ratios for dichotomous data or weighted mean difference for continuous data. A random effects statistical model was used. Main results The meta-analysis of IVIG versus placebo, including all children, showed a significant decrease in new coronary artery abnormalities (CAAs) in favour of IVIG, at thirty days RR (95% CI) = 0.74 (0.61 to 0.90). No statistically significant difference was found thereafter. A subgroup analysis excluding children with CAAs at enrollment also found a significant reduction of new CAAs in children receiving IVIG RR (95%) = 0.67 (0.46 to 1.00). There was a trend towards benefit from IVIG at sixty days (p=0.06). Results of dose comparisons showed a decrease in the number of new CAAs with increased dose. The meta-analysis of 400 mg/kg/day for five days versus 2 gm/kg in a single dose showed statistically significant reduction in CAAs at thirty days RR (95%) = 4.47 (1.55 to 12.86). This comparison also showed a significant reduction in duration of fever with the higher dose. There was no statistically significant difference noted between different preparations of IVIG. There was no statistically significant difference of adverse effects in any group. Reviewer's conclusions Children fulfilling the diagnostic criteria for Kawasaki disease should be treated with IVIG (2 gm/kg single dose) within 10 days of onset of symptoms.
222 citations
TL;DR: The epidemiology of KD has been extensively investigated in many populations and provides much of the supporting evidence for the consensus regarding etiology, and these epidemiological data are reviewed here, in the context of the etiopathogenesis.
173 citations
Cites background from "Kawasaki disease: an evidence based..."
...These children may present a diagnostic challenge 6 and the lack of a specific diagnostic test may delay treatment and thus worsen prognosis....
[...]
...The consensus view supports the concept of a genetically-susceptible host in KD 6, 83 and there is growing realisation that immunogenetic studies may reveal much about the disease and improve diagnosis, treatment and prognosis....
[...]
Journal Article•
TL;DR: The findings highlight the need to improve early diagnosis and initiation of targeted therapy, thereby reducing treatment-related toxicity and comorbidities in patients with systemic vasculitis.
Abstract: There has been a considerable improvement in the survival of patients with systemic vasculitis since the introduction of immunosuppressive therapy and improved diagnostic tools to allow earlier diagnosis. We review the published literature on current risk of mortality in patients with small vessel antineutrophil cytoplasm antibody- (ANCA) associated vasculitis including Wegener's granulomatosis (survival rate of approximately 75% at 5 years), microscopic polyangiitis (survival rate of 45% to 75% at 5 years), Churg-Strauss syndrome (survival rate of 68% to 100% at 5 years), and Henoch-Schonlein purpura (survival rate of 75% in adult-onset, greater in childhood onset); medium vessel vasculitis including polyarteritis nodosa (survival rate of 75% to 80% at 5 years), Kawasaki disease (survival rate of greater than 99% at 5 years); large vessel vasculitis including giant cell arteritis (survival rate equivalent to the age-matched population), and Takayasu arteritis (survival of 70% to 93% at 5 years). Mortality rates are falling as a result of more effective intervention but remain elevated substantially in severe disease. Early deaths are usually attributable to active vasculitis with multiorgan failure or infection, or both. The incidence of late deaths may be increased by long-term effects of therapy and development of comorbidities. These findings highlight the need to improve early diagnosis and initiation of targeted therapy, thereby reducing treatment-related toxicity and comorbidities.
168 citations
TL;DR: In this paper, the authors use molecular dynamics simulation results to discuss in a semi-quantitative manner different aspects of such segregation: how it varies within a homologous ionic liquid family, the influence of the nature of the ions in the morphology of the segregated domains; and the interactions of those domains with molecular solutes or solvents.
Abstract: The concept that ionic liquids are nano-segregated fluids has allowed the rationalization at a molecular level of many of their complex and unusual properties, either as pure substances or as solvents. In this work we will use molecular dynamics simulation results to discuss in a semi-quantitative manner different aspects of such segregation: how it varies within a homologous ionic liquid family; the influence of the nature of the ions in the morphology of the segregated domains; and the interactions of those domains with molecular solutes or solvents.
146 citations
References
More filters
Journal Article•
1,259 citations
TL;DR: Examination of morphological, immunological, and functional characteristics of MPs derived from human umbilical vein endothelial cells stimulated by TNF provides evidence that endothelial-derived MPs are detectable in normal human blood and are increased in patients with a coagulation abnormality characterized by the presence of lupus anticoagulant.
Abstract: Microparticles (MPs) resulting from vesiculation of platelets and other blood cells have been extensively documented in vitro and have been found in increased numbers in several vascular diseases, but little is known about MPs of endothelial origin. The aim of this study was to analyze morphological, immunological, and functional characteristics of MPs derived from human umbilical vein endothelial cells (HUVECs) stimulated by TNF, and to investigate whether these MPs are detectable in healthy individuals and in patients with a prothrombotic coagulation abnormality. Electron microscopy evidenced bleb formation on the membrane of TNF-stimulated HUVECs, leading to increased numbers of MPs released in the supernatant. These endothelial microparticles (EMPs) expressed the same antigenic determinants as the corresponding cell surface, both in resting and activated conditions. MPs derived from TNF-stimulated cells induced coagulation in vitro, via a tissue factor/factor VII–dependent pathway. The expression of E-selectin, ICAM-1, αvβ3, and PECAM-1 suggests that MPs have an adhesion potential in addition to their procoagulant activity. In patients, labeling with αvβ3 was selected to discriminate EMPs from those of other origins. We provide evidence that endothelial-derived MPs are detectable in normal human blood and are increased in patients with a coagulation abnormality characterized by the presence of lupus anticoagulant. Thus, MPs can be induced by TNF in vitro, and may participate in vivo in the dissemination of proadhesive and procoagulant activities in thrombotic disorders.
734 citations
TL;DR: The incidence of CAA both at 30 and 60 days was significantly lower in low-IVig than in ASA and in high-IVIG than in low -IVIG groups, but this was noted at 30 days and not at 60 days.
Abstract: Objective. Varying observations have been made concerning the use of aspirin (ASA) and/or intravenous immunoglobulin (IVIG) in the prevention of coronary artery aneurysm (CAA) in children with Kawasaki disease. A meta-analysis of published articles on the subject was conducted to evaluate the reported efficacy of these therapies. Methods. All published studies in all languages from 1967 through 1993 obtained from MEDLINE and EMBASE were considered, and a defined set of inclusion and exclusion criteria selected the studies for analysis. These studies were grouped based on whether the children in the studies received: (1) ASA alone, (2) low IVIG (≤1 g/kg) and ASA, (3) high IVIG (>1 g/kg) and ASA, (4) single IVIG (>1 g/kg) and ASA, (5) high IVIG and low ASA (≤80 mg/kg), or (6) high IVIG and high ASA (> 80mg/kg). Studies that satisfied the test for homogeneity were subjected to further analysis. The best estimate of the true proportion of CAA as well as the 95% confidence interval for each group were calculated at 30 and 60 days. Hypothesis testing was conducted to determine the statistical significance of the calculated difference in each compared treatment group. Results. The best estimate of true proportion of CAA and the 95% confidence interval in each group at 30 and 60 days were: (1) ASA group, 30 days, 22.8% (20.6%, 25%); 60 days, 17.1% (13.6%, 20.7%); (2) low-IVIG group, 30 days, 17.3% (14.3%, 20.2%); 60 days, 11.1% (8.7%, 13.6%); (3) high-IVIG group, 30 days, 10.3% (8.3%, 12.3%); 60 days, 4.4% (2.8%, 6%); (4) single-IVIG group, 30 days, 2.3% (0.5%, 4.2%); 60 days, 2.4% (0.5%, 4.2%); (5) high-IVIG-low-ASA group, 30 days, 13% (9%, 17%); 60 days, 4.8% (2.3%, 7.4%); and (6) high-IVIG-high-ASA group, 30 days, 9.1% (6.9%, 11.4%); 60 days, 4% (2%, 6.1%). Conclusion. The incidence of CAA both at 30 and 60 days was significantly lower in low-IVIG than in ASA and in high-IVIG than in low-IVIG groups. Also, the incidence was lower in the single-IVIG than in the high-IVIG group, but this was noted at 30 days and not at 60 days. There was no statistically significant difference in the incidence of CAA both at 30 and 60 days between the high-IWIG-low-ASA and high-IVIG-high-ASA groups.
361 citations
TL;DR: The findings suggest that the steroid might act adversely to cause a progression of coronary lesions of the disease, and aspirin might act as the effective means for prevention of sudden death due to Kawasaki disease.
Abstract: Ninety-two patients with Kawasaki disease were treated with five different types of drug therapy: a steroid preparation (prednisolone), aspirin, an antibiotic, a combination of steroid plus aspirin, and a combination of steroid plus warfarin. One or two months after the onset of the disease, coronary angiography demonstrated coronary aneurysms in 20% of cases treated with an antibiotic alone, 64.7% of cases in the steroid-treated group, and 11% of those in the aspirin-treated group. These findings suggest that the steroid might act adversely to cause a progression of coronary lesions of the disease. The aspirin-treated group did not have a significantly lower incidence of coronary lesions compared with the group treated with an antibiotic alone. But in view of the fact that the direct cause of sudden death of the disease is thrombotic occlusion of a coronary artery, aspirin might act as the effective means for prevention of sudden death due to Kawasaki disease.
350 citations