Evaluating the time-varying risk of hypertension, cardiac events, and mortality following Kawasaki disease diagnosis.

Background: This study evaluated the risk of hypertension, major adverse cardiac events (MACE), and all-cause mortality in Kawasaki disease (KD) patients up to young adulthood.

Methods: An inception cohort of 1169 KD patients between 1991 and 2008 from a tertiary-level hospital in Ontario, Canada was linked with health administrative data to ascertain outcomes up to 28 years of follow-up. Their risk was compared with 11,690 matched population comparators.

Higher concentrations of vitamin D in Canadian children with juvenile idiopathic arthritis compared to healthy controls are associated with more frequent use of vitamin D supplements and season of birth.

A number of studies have demonstrated that patients with autoimmune disease have lower levels of vitamin D prompting speculation that vitamin D might suppress inflammation and immune responses in children with juvenile idiopathic arthritis (JIA).  The objective of this study was to compare vitamin D levels in children with JIA at disease onset with healthy children. We hypothesized that children and adolescents with JIA have lower vitamin D levels than healthy children and adolescents.

Long-term use and remission of granulomatosis with polyangiitis with the oral C5a receptor inhibitor avacopan.

Granulomatosis with polyangiitis (GPA) is a rare antineutrophil cytoplasm antibody-associated vasculitis. Several therapeutic advances have occurred over the past two decades, but relapse rate remains high and refractory cases are not uncommon. Here, we present the case of a female patient diagnosed with GPA at the age of 9 years with a severe, multirelapsing disease course which failed to adequately respond to conventional therapies.

Is multisystem inflammatory syndrome in children on the Kawasaki syndrome spectrum?

An alarming increase in children presenting with fever, hyperinflammation, and multiorgan dysfunction frequently requiring intensive care has been observed after severe acute respiratory syndrome coronavirus 2 infection. The illness resembles Kawasaki disease (KD), with coronary dilatation and aneurysm occurring in some. However, the cardiovascular manifestations were typically on the severe end of the KD spectrum, with cardiogenic shock a common presentation together with other features.

Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease.

Human actin-related protein 2/3 complex (Arp2/3), required for actin filament branching, has two ARPC1 component isoforms, with ARPC1B prominently expressed in blood cells. Here we show in a child with microthrombocytopenia, eosinophilia and inflammatory disease, a homozygous frameshift mutation in ARPC1B (p.Val91Trpfs*30).

Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications.

Objectives: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases.

Genetic Variation in the SLC8A1 Calcium Signaling Pathway Is Associated With Susceptibility to Kawasaki Disease and Coronary Artery Abnormalities.

Background: Kawasaki disease (KD) is an acute pediatric vasculitis in which host genetics influence both susceptibility to KD and the formation of coronary artery aneurysms. Variants discovered by genome-wide association studies and linkage studies only partially explain the influence of genetics on KD susceptibility.

Methods And Results: To search for additional functional genetic variation, we performed pathway and gene stability analysis on a genome-wide association study data set.

Enhancing translational research in paediatric rheumatology through standardization.

The past decade has seen many successes in translational rheumatology, from dramatic improvements in outcomes brought about by novel biologic therapies, to the discovery of new monogenic inflammatory disorders. Advances in molecular medicine, combined with progress towards precision care, provide an excellent opportunity to accelerate the translation of biological understanding to the bedside. However, although the field of rheumatology is a leader in the standardization of data collection and measures of disease activity, it lags behind in standardization of biological sample collection and assay performance.

Inositol-Triphosphate 3-Kinase C Mediates Inflammasome Activation and Treatment Response in Kawasaki Disease.

Kawasaki disease (KD) is a multisystem vasculitis that predominantly targets the coronary arteries in children. Phenotypic similarities between KD and recurrent fever syndromes point to the potential role of inflammasome activation in KD. Mutations in NLRP3 are associated with recurrent fever/autoinflammatory syndromes.

Variability in Response to Intravenous Immunoglobulin in the Treatment of Kawasaki Disease.

Objectives: To characterize the pattern of temperature response to intravenous immunoglobulin (IVIG) infusion in patients with Kawasaki disease (KD).

Study Design: Patients nonresponsive to IVIG (axillary temperature ≥37.5°C >24 hours after end of IVIG) were identified.

Arterial dissection in childhood Takayasu Arteritis: not as rare as thought.

Background: Arterial vessel wall dissection is a rare, life-threatening and rarely described complication in childhood Takayasu Arteritis (cTA). Prevalence and risk factors for arterial dissection in cTA are unknown. We sought to study the prevalence and analyse risk factors for arterial dissection in cTA.

Kawasaki Disease and Exposure to Fine Particulate Air Pollution.

Objective: To analyze associations of short-term exposure to fine particulate matter (diameter ≤ 2.5 µm [PM2.5]), a measurable component of urban pollution, with the event date of fever onset for patients with Kawasaki disease (KD) residing in 7 metropolitan regions.

Gene Expression Deconvolution for Uncovering Molecular Signatures in Response to Therapy in Juvenile Idiopathic Arthritis.

Gene expression-based signatures help identify pathways relevant to diseases and treatments, but are challenging to construct when there is a diversity of disease mechanisms and treatments in patients with complex diseases. To overcome this challenge, we present a new application of an in silico gene expression deconvolution method, ISOpure-S1, and apply it to identify a common gene expression signature corresponding to response to treatment in 33 juvenile idiopathic arthritis (JIA) patients. Using pre- and post-treatment gene expression profiles only, we found a gene expression signature that significantly correlated with a reduction in the number of joints with active arthritis, a measure of clinical outcome (Spearman rho = 0.

Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's): An ARChiVe Cohort Study.

Objective: To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA).

Methods: The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria.

HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis.

Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata.

The risk and nature of flares in juvenile idiopathic arthritis: results from the ReACCh-Out cohort.

Objective: To describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis (JIA) and to identify clinical features associated with an increased risk of flare.

Methods: We studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment.

Description of active joint count trajectories in juvenile idiopathic arthritis.

Objective: To describe the trajectories of longitudinal joint disease activity in juvenile idiopathic arthritis (JIA), and to examine associations of clinical and laboratory characteristics with the identified trajectories.

Methods: A retrospective cohort study at 2 Canadian centers was performed. The longitudinal trajectories of active joint counts were described in a proof-of-concept study using a latent growth curve analysis.

The biologic basis of clinical heterogeneity in juvenile idiopathic arthritis.

Objective: Childhood arthritis encompasses a heterogeneous family of diseases. Significant variation in clinical presentation remains despite consensus-driven diagnostic classifications. Developments in data analysis provide powerful tools for interrogating large heterogeneous data sets.

The human immune system recognizes neopeptides derived from mitochondrial DNA deletions.

Mutations in mitochondrial (mt) DNA accumulate with age and can result in the generation of neopeptides. Immune surveillance of such neopeptides may allow suboptimal mitochondria to be eliminated, thereby avoiding mt-related diseases, but may also contribute to autoimmunity in susceptible individuals. To date, the direct recognition of neo-mtpeptides by the adaptive immune system has not been demonstrated.

Atorvastatin safety in Kawasaki disease patients with coronary artery aneurysms.

Statins (HMG-CoA reductase inhibitors) may decrease inflammation in postacute Kawasaki disease (KD) complicated by coronary artery aneurysm (CAA) and promote vascular remodeling. There are limited data on their safety in young children. Twenty patients with CAAs after KD (median CAA z-score = +25) were treated with 5/10 mg atorvastatin daily for a median of 2.

Access to biologic therapies in Canada for children with juvenile idiopathic arthritis.

Objective: To compare access to biologic therapies for children with juvenile idiopathic arthritis (JIA) across Canada, and to identify differences in provincial regulations and criteria for access.

Methods: Between June and August 2010, we compiled the provincial guidelines for reimbursement of biologic drugs for children with JIA and conducted a multicenter Canada-wide survey of pediatric rheumatologists to determine their experience with accessing biologic therapies for their patients.

Results: There were significant difficulties accessing biologic treatments other than etanercept and abatacept for children.

Rate, associated factors and outcomes of recurrence of Kawasaki disease in Ontario, Canada.

Background: Previous studies on recurrence of Kawasaki disease (KD) have mostly been limited to Japan, which has an incidence of KD 8-10-fold higher than North America. The aim of the present study was to determine the rate of KD recurrence for patients in Ontario, to identify factors potentially associated with increased odds of recurrence, and to compare the clinical course and outcomes of index and recurrent KD episodes.

Methods: Review was undertaken of all patients with recurrence of KD identified in Ontario, Canada, from 1995 to 2006.

Epidemiology and management of Kawasaki disease.

Kawasaki disease (KD) is an acute systemic vasculitis affecting young children and is rising in incidence worldwide. It is most common in children <5 years of age, males and those of Asian ethnicity. It is an important cause of acquired heart disease in children.