Although the etiology of Kawasaki disease (KD) is largely unknown, a large body of clinical, epidemiologic, immunologic, pathologic and ultrastructural evidence suggests that an infectious agent ...triggers a cascade that causes the illness. However, this elusive infectious agent remains unidentified at present. Increasingly sensitive molecular methods for identifying microbial nucleic acids and proteins in tissue samples continue to rapidly emerge, and these methods should be utilized in studies on KD etiology as they become available. Identifying the etiology of this enigmatic disease remains the single most important research goal in the field, and accomplishing this goal is the best means to improve diagnosis, treatment and prevention of this potentially fatal childhood disease.
Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acquired heart ...disease in children in developed countries.
To revise the previous American Heart Association guidelines, a multidisciplinary writing group of experts was convened to review and appraise available evidence and practice-based opinion, as well as to provide updated recommendations for diagnosis, treatment of the acute illness, and long-term management. Although the cause remains unknown, discussion sections highlight new insights into the epidemiology, genetics, pathogenesis, pathology, natural history, and long-term outcomes. Prompt diagnosis is essential, and an updated algorithm defines supplemental information to be used to assist the diagnosis when classic clinical criteria are incomplete. Although intravenous immune globulin is the mainstay of initial treatment, the role for additional primary therapy in selected patients is discussed. Approximately 10% to 20% of patients do not respond to initial intravenous immune globulin, and recommendations for additional therapies are provided. Careful initial management of evolving coronary artery abnormalities is essential, necessitating an increased frequency of assessments and escalation of thromboprophylaxis. Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalized as
scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up.
These recommendations provide updated and best evidence-based guidance to healthcare providers who diagnose and manage Kawasaki disease, but clinical decision making should be individualized to specific patient circumstances.
The aim of this article was to review the properties of the various gadolinium-based contrast agents used for CNS imaging along with the clinical evidence and published data that highlight the impact ...these different properties can have on diagnostic performance. In addition, approaches to optimizing image acquisition that take into account the different properties of specific gadolinium-based contrast agents and an extensive review of the safety profiles of the various agents are presented.
Epidemiologic and clinical features of Kawasaki Disease (KD) strongly support an infectious etiology. KD is worldwide, most prominently in Japan, Korea, and Taiwan, reflecting increased genetic ...susceptibility among Asian populations. In Hawaii, KD rates are 20-fold higher in Japanese ethnics than in Caucasians, intermediate in other ethnicities. The age distribution of KD, highest in children < 2 yo, lower in those < 6 months, is compatible with infection by a ubiquitous agent resulting in increasing immunity with age and with transplacental immunity, as with some classic viruses. The primarily winter-spring KD seasonality and well-documented Japanese epidemics with wave-like spread also support an infectious trigger. We hypothesize KD pathogenesis involves an RNA virus that usually causes asymptomatic infection but KD in a subset of genetically predisposed children. CD8 T cells, oligoclonal IgA, and upregulation of cytotoxic T cell and interferon pathway genes in the coronaries in fatal KD also support a viral etiology. Cytoplasmic inclusion bodies in ciliated bronchial epithelium identified by monoclonal antibodies made from oligoclonal IgA heavy chains also supports a viral etiology. Recent availability of "second generation" antibodies from KD peripheral blood plasmablasts may identify a specific viral antigen. Thus, we propose an unidentified ("new") RNA virus infects bronchial epithelium usually causing asymptomatic infection but KD in a subset of genetically predisposed children. The agent persists in inclusion bodies, with intermittent respiratory shedding, entering the bloodstream via macrophages targeting coronaries. Antigen-specific IgA plasma cells and CD8 T cells respond but coronaries can be damaged. IVIG may include antibody against the agent. Post infection, 97-99% of KD patients are immune to the agent, protected against recurrence. The agent can spread either from those with asymptomatic primary infection in winter-spring or from a previously infected contact who intermittently sheds the agent.
Kawasaki disease is recognized as the most common cause of acquired heart disease in children in the developed world. Clinical, epidemiologic, and pathologic evidence supports an infectious agent, ...likely entering through the lung. Pathologic studies proposing an acute coronary arteritis followed by healing fail to account for the complex vasculopathy and clinical course.
Specimens from 32 autopsies, 8 cardiac transplants, and an excised coronary aneurysm were studied by light (n=41) and transmission electron microscopy (n=7). Three characteristic vasculopathic processes were identified in coronary (CA) and non-coronary arteries: acute self-limited necrotizing arteritis (NA), subacute/chronic (SA/C) vasculitis, and luminal myofibroblastic proliferation (LMP). NA is a synchronous neutrophilic process of the endothelium, beginning and ending within the first two weeks of fever onset, and progressively destroying the wall into the adventitia causing saccular aneurysms, which can thrombose or rupture. SA/C vasculitis is an asynchronous process that can commence within the first two weeks onward, starting in the adventitia/perivascular tissue and variably inflaming/damaging the wall during progression to the lumen. Besides fusiform and saccular aneurysms that can thrombose, SA/C vasculitis likely causes the transition of medial and adventitial smooth muscle cells (SMC) into classic myofibroblasts, which combined with their matrix products and inflammation create progressive stenosing luminal lesions (SA/C-LMP). Remote LMP apparently results from circulating factors. Veins, pulmonary arteries, and aorta can develop subclinical SA/C vasculitis and SA/C-LMP, but not NA. The earliest death (day 10) had both CA SA/C vasculitis and SA/C-LMP, and an "eosinophilic-type" myocarditis.
NA is the only self-limiting process of the three, is responsible for the earliest morbidity/mortality, and is consistent with acute viral infection. SA/C vasculitis can begin as early as NA, but can occur/persist for months to years; LMP causes progressive arterial stenosis and thrombosis and is composed of unique SMC-derived pathologic myofibroblasts.
Kawasaki disease (KD) is a vasculitis of young childhood that particularly affects the coronary arteries. Molecular analysis of the oligoclonal IgA response in acute KD led to production of synthetic ...KD antibodies. These antibodies identify intracytoplasmic inclusion bodies in acute KD tissues. Light and electron microscopic studies indicate that the inclusion bodies are consistent with aggregates of viral proteins and RNA. Advances in molecular genetic analysis and completion of the Human Genome Project have sparked a worldwide effort to identify genes associated with KD. A polymorphism of one such gene, ITPKC, a negative regulator of T cell activation, confers susceptibility to KD in Japanese populations and increases the risk of developing coronary artery abnormalities in both Japanese and U.S. children. Identification of the etiologic agent and of genes conferring KD susceptibility are the best means of improving diagnosis and therapy and enabling prevention of this important disorder of childhood.
Sustainability analysts and environmental decision makers often overcome the difficulty of interpreting comprehensive environmental profiles by aggregating the results using multi-criteria decision ...analysis (MCDA) methods. However, the wide variety of methodological approaches to weighting and aggregation introduces subjectivity and often uncertainty. It is important to select an approach that is consistent with the decision maker's information needs, but scant practical guidance is available to environmental managers on how to do this.
In this paper, we aim to clarify the theoretical implications of an analyst's choice of MCDA method. By systematically examining the methodological decisions that must be made by the analyst at each stage of the assessment process, we aim to improve analysts' understanding of the relationship between MCDA theory and practice, and enable them to apply methods that are consistent with a decision maker's needs in any given problem context.
► Forming an overall judgement on environmental preferability can be challenging. ► Methodological choices when aggregating multi-criteria data introduce subjectivity. ► The ubiquitous ‘weighted sum’ operationalises some quite restrictive assumptions. ► We clarify the theoretical implications of methodological choices in MCDA. ► We present a workflow to support choosing a suitable MCDA method.
Kawasaki disease (KD) must be considered in the differential diagnosis of any child with fever for 4 to 5 days and compatible clinical and laboratory features, and in any infant with prolonged fever ...and compatible laboratory features, even in the absence of the classic clinical signs. Prompt therapy is required, because delayed or unrecognized KD can lead to lifelong heart disease or death in previously healthy children. Most children with KD respond to a single 2 g/kg dose of intravenous gammaglobulin with oral aspirin, but a small subset require additional therapies to resolve the clinical illness.
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