Kawasaki Disease

The goal of this observational study is to learn about the safety and effects of atorvastatin in treatment of Chinese Kawasaki disease (KD) children complicated with coronary artery abnormalities (CAA) in acute phase. The main questions it aims to answer are: Is atorvastatin safe in Chinese children of acute KD? Does atorvastatin contribute to control the acute inflammation in KD and improve the CAA?

The study investigators are interested in learning more about how drugs, that are given to children by their health care provider, act in the bodies of children and young adults in hopes to find the most safe and effective dose for children. The primary objective of this study is to evaluate the PK of understudied drugs currently being administered to children per SOC as prescribed by their treating provider.

Kawasaki Disease (KD) is one of the most common vasculitides in childhood and represents a leading cause of acquired heart disease in developed countries. Macrophage Activation Syndrome (MAS) is a potentially life threatening hyperinflammatory condition belonging to the spectrum of hemophagocytic lymphohistiocytosis (HLH), and it can complicate various rheumatologic diseases. Awareness of MAS in the context of KD has recently increased, supporting the hypothesis that it is an underdiagnosed complication. The study aims to define the epidemiology, clinical characteristics, management, and therapeutic strategies of MAS in patients with KD, through a multicenter data collection in Europe.

The goal of this observational study is to develop an AI-based early warning system for Kawasaki Disease (KD) using chest X-rays (CXR) in children diagnosed with Kawasaki Disease. The main question\[s\] it aims to answer are: 1. Can AI modeling of CXR features help identify high-risk KD patients earlier than current diagnostic methods? 2. Can the AI system predict the optimal IVIG treatment window and coronary artery risks in KD patients? Participants will: Provide retrospective data on chest X-rays and clinical data (CRP, coronary ultrasound, etc.) Allow analysis of CXR features using deep learning models to extract relevant patterns Have their data incorporated into a federated learning model to ensure privacy and data security

Evaluating the impact of a machine-learning clinical decision support tool on provider practice when evaluating febrile patients with Kawasaki Disease (KD) and non-KD illnesses.

Kawasaki disease (KD) is currently the leading cause of acquired heart diseases in children in developed countries. Cardiac involvement is the main determinant of the long-term prognosis of these patients, as coronary aneurisms (CAAs) may lead to ischemic heart disease and even sudden death. The current standard of care for KD has consistently reduced CAAs frequency from 25-30% to about 5%. Unfortunately, 10-20% of KD patients results resistant to standard treatment leading to a major risk of cardiac complications. Thus, scoring systems have been constructed in order to identify patients likely to be resistant to IVIG and who may benefit from more aggressive initial therapy. Different scoring scales developed by Kobayashi, Egami et Sano had shown a good sensitivity (77-86%) and specificity (67-86%) in predicting IVIG unresponsiveness in Japanese populations. However, their predictive value was not confirmed by subsequent studies in different ethnic populations. Recently, the French Kawanet group have proposed a IVIG unresponsiveness score that provided good sensitivity and acceptable specificity in a non-Asian KD population even if it was not subsequent validated by an external study. In our study population, the achievement of specificity and sensitivity values for both scores consistent with those reported by the original studies (sensitivity 70% and specificity 80% for Kobayashi and sensitivity 77% and specificity 60% for Kawanet), will be considered a success.

Based on a population pharmacokinetic model-based dose optimization study, a 15 mg-equivalent, age-, and bodyweight-adjusted dosing regimen for Chinese children with giant coronary artery aneurysms after Kawasaki disease was proposed. This single-center, single-arm, pilot study aims to evaluate the feasibility of the 15 mg-equivalent dosing regimen within a limited sample size. Patients will be followed for more than 6 months. Clinical outcomes, including coronary artery thrombosis, major adverse cardiovascular events, and bleeding events, will be recorded. Rivaroxaban levels will be measured to assess the robustness of the model-informed dose optimization.

Children living with chronic health conditions face a higher risk of developing cardiovascular diseases than their peers, largely due to the accelerated aging of the heart and blood vessels. Although experts recognize this elevated risk and recommend close monitoring and early intervention, the underlying mechanisms driving this phenomenon remain poorly understood. At present, no effective interventions specifically target its root causes. Recent research shows that both large blood vessels (such as the carotid artery) and small vessels (such as those in the retina) can display early signs of damage decades before clinically apparent heart or vascular disease emerges. This accelerated vascular aging can result from multiple factors - including disease-related processes such as persistent inflammation and metabolic disturbances, treatment-related effects such as chemotherapy or long-term steroid use, and lifestyle changes associated with chronic illness, such as reduced physical activity and altered eating habits. However, it is still unclear how these factors influence the development and progression of vascular changes in children as they grow. Importantly, these changes can be monitored through non-invasive methods, offering a unique opportunity to study at-risk patients many years before overt cardiovascular disease develops. Identifying these early changes may enable us to detect and track individuals at heightened risk well in advance of clinical disease. This study aims to deepen our understanding of the causes of increased cardiovascular risk in children with chronic conditions and to lay the groundwork for earlier, more targeted prevention strategies.

Based on population pharmacokinetic model-based simulation, a 15 mg-equivalent, age-, and bodyweight-adjusted dosing regimen for Chinese children with giant coronary artery aneurysms after acute Kawasaki disease was proposed. This exploratory trial aims to evaluate the feasibility, safety and effectiveness of rivaroxaban compared to warfarin for thromboprophylaxis in children aged over 2 years with giant coronary artery aneurysms after Kawasaki disease

Based on an established Kawasaki disease cohort database, this prospective, single-center, single-arm, observational study will collect clinical data from children aged 2 years and older with giant coronary artery aneurysms after Kawasaki disease who received rivaroxaban treatment. Rivaroxaban plasma concentrations, anti-factor Xa activity levels, and genetic polymorphisms will be measured and analyzed to support the population pharmacokinetic/pharmacodynamic analysis

CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access. Visit sanfordresearch.org/CoRDS to enroll.

Human Endogenous Retroviruses (HERVs) are ancient sequences that became integrated into our DNA during evolutionary processes. The significance of their presence in DNA is still being studied, but HERVs appear to be involved in the regulation of the immune response. The gut microbiota is the set of microorganisms that physiologically colonize the gastrointestinal tract. Progressively increasing attention is being paid to the gut microbiota and its potential role in diseases of various kinds. In particular, it has recently been shown how abnormalities in the microbiota can affect immune regulation by determining the occurrence of certain diseases. One objective of the study is to evaluate whether there is an association between the expression of HERVs and clinical manifestations in pediatric age in patients with various diseases such as Kawasaki Disease, IgA Vasculitis/Schonlein-Henoch's Purpura, SARS-CoV-2 infection, or, finally, febrile virosis. Another objective of the study is to evaluate whether there is an association between the presence of particular types of bacteria in the gut microbiota and clinical manifestations in pediatric age in patients with Kawasaki Disease, IgA Vasculitis/Schonlein-Henoch purpura, SARS-CoV-2 infection or febrile virosis. The results from this may open new perspectives for both the care and therapeutic management of children with these diseases.

This is a multicenter, open-label, randomized, controlled, interventional trial followed by a long-term observational extension period in patients with Kawasaki Disease (KD) to be treated eitherwith endovenous Immunoglobulins (IVIG-standard treatment) versus anakinra Aim of the study: to demonstrate that anakinra is non-inferior to IVIG in KD, in terms of fever control in the acute phase and development of coronary artery dilation/aneurisms (CAA) within one year from the onset.

Kawasaki disease (KD) is the most frequent vasculitis in younger children \<5years, and the first cause of acquired ischemic myocardiopathy in childhood. Exceptionally, KD may cause early death during the acute phase by myocardial infarction, but may compromise the long-term cardiovascular outcome by accelerating atherosclerotic disease. The incidence of KD is high in far-Eastern countries and Hawaii but KD is relatively rare in other regions (10/100000 children \<5years in northern Europe) which makes it difficult to develop research on these rare population. Early recognition and treatment by intravenous immunoglobulins (IVIG) influences the prognosis positively. IVIG are the standard of care and decrease significantly the risk of coronary aneurysms. However, despite a first infusion of IVIG, 20% of KD patients remain febrile and have high risk of coronary vasculitis. Recent Japanese research group assessed additional cyclosporine treatment in first line KD treatment but failed preventing relapse. To date there is no agreement for a more effective second line treatment. Based on the auto-inflammatory pattern of KD, the investigators hypothesize that anti IL-1 blocking agents could bring a rapid and sustained effect on systemic and coronary inflammation in patients with KD. Our hypotheses are: 1. Anakinra treatment may reduce the early and long-term mortality of patients with Kawasaki Disease (KD), by a rapid and sustained effect on vascular inflammation. 2. The safety of anakinra is good, as the drug has a very short half-life, which allows its rapid withdrawal in case of serious adverse event. The use of anakinra is not associated with the risk of contamination by infectious agents, which remain even minimal, a possibility with the use of IVIG.