Evaluating renal disease in pediatric-onset anti-neutrophil cytoplasmic antibody-associated vasculitis: disease course, outcomes, and predictors of outcome.

Objectives: We aimed to study the disease course, outcomes, and predictors of outcome in pediatric-onset anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affecting the kidneys.

Methods: Patients eligible for this study had a diagnosis of granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or ANCA positive pauci-immune glomerulonephritis, were ≤ 18 years at diagnosis, had renal disease defined by biopsy or dialysis dependence, and had clinical data at diagnosis and either 12- or 24-months. Ambispective data from the ARChiVE/PedVas Registry was used.

Predictive utility of ANCA positivity and antigen specificity in the assessment of kidney disease in paediatric-onset small vessel vasculitis.

Objectives: The objective of this study is to evaluate whether anti-neutrophil cytoplasmic antibody (ANCA) seropositivity and antigen specificity at diagnosis have predictive utility in paediatric-onset small vessel vasculitis.

Methods: Children and adolescents with small vessel vasculitis (n=406) stratified according to the absence (n=41) or presence of ANCA for myeloperoxidase (MPO) (n=129) and proteinase-3 (PR3) (n=236) were compared for overall and kidney-specific disease activity at diagnosis and outcomes between 1 and 2 years using retrospective clinical data from the ARChiVe/Paediatric Vasculitis Initiative registry to fit generalised linear models.

Results: Overall disease activity at diagnosis was higher in PR3-ANCA and MPO-ANCA-seropositive individuals compared with ANCA-negative vasculitis.

Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels.

Chronic primary systemic vasculitis (PSV) comprises a group of heterogeneous diseases that are broadly classified by affected blood vessel size, clinical traits and the presence (or absence) of anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3) and myeloperoxidase (MPO). In small vessel vasculitis (SVV), ANCA are not present in all patients, and they are rarely detected in patients with vasculitis involving medium (MVV) and large (LVV) blood vessels. Some studies have demonstrated that lysosome-associated membrane protein-2 (LAMP-2/CD107b) is a target of ANCA in SVV, but its presence and prognostic value in childhood MVV and LVV is not known.

A decade of progress in juvenile idiopathic arthritis treatments and outcomes in Canada: results from ReACCh-Out and the CAPRI registry.

Objective: To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing 2005-2010 and 2017-2021 inception cohorts.

Methods: Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan-Meier survival analysis and multivariable Cox regression.

Development and validation of the Kids Disability Screen for children with juvenile idiopathic arthritis: results from the CAPRI Registry.

Objective: The aim of this study was to develop and validate a brief disability screen for children with JIA, the Kids Disability Screen (KDS).

Methods: A total of 216 children enrolled in the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry in 2017-2018 formed a development cohort, and 220 children enrolled in 2019-2020 formed a validation cohort. At every clinic visit, parents answered two questions derived from the Childhood Health Assessment Questionnaire (CHAQ): 'Is it hard for your child to run and play BECAUSE OF ARTHRITIS?' ('Hard' 0-10), and 'Does your child usually need help from you or another person BECAUSE OF ARTHRITIS?' ('Help', 0-10).

Wide variation in glucocorticoid dosing in paediatric ANCA-associated vasculitis with renal disease: a paediatric vasculitis initiative study.

Objectives: High-dose glucocorticoids for remission-induction of ANCA-associated vasculitis are recommended and commonly used in adults, but recent studies suggest lower glucocorticoid doses can reduce toxicity without reducing efficacy. No paediatric-specific data exists to inform optimal glucocorticoid dosing in paediatric ANCA-associated vasculitis (pAAV). Our objectives were to describe glucocorticoid use in pAAV-related renal disease, and to explore associations between glucocorticoid dose, baseline patient characteristics and 12-month outcomes.

Impact of the COVID-19 pandemic on juvenile idiopathic arthritis presentation and research recruitment: results from the CAPRI registry.

Objective: The COVID-19 pandemic has disrupted healthcare delivery and clinical research worldwide, with data from areas most affected demonstrating an impact on rheumatology care. This study aimed to characterize the impact of the pandemic on the initial presentation of JIA and JIA-related research in Canada.

Methods: Data collected from the Canadian Alliance of Pediatric Rheumatology Investigators JIA Registry from the year pre-pandemic (11 March 2019 to 10 March 2020) was compared with data collected during the first year of the pandemic (11 March 2020 to 10 March 2021).

Children with systemic autoinflammatory diseases have multiple, mixed ethnicities that reflect regional ethnic diversity.

Objectives: To evaluate the ethnic diversity of children with a systemic autoinflammatory disease (SAID) in a multi-ethnic Canadian province.

Methods: Self-reported ethnicity of 149 children and adolescents with a SAID in British Columbia, Canada, was analysed for ethnic representation among individual patients, across the cohort, within particular SAIDs, and compared to provincial census data on ethnic diversity.

Results: Half of reported cases had a diagnosis of either PFAPA (23.

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.

Clinical and psychosocial stress factors are associated with decline in physical activity over time in children with juvenile idiopathic arthritis.

Background: Physical activity (PA) patterns in children with juvenile idiopathic arthritis (JIA) over time are not well described. The aim of this study was to describe associations of physical activity (PA) with disease activity, function, pain, and psychosocial stress in the 2 years following diagnosis in an inception cohort of children with juvenile idiopathic arthritis (JIA).

Methods: In 82 children with newly diagnosed JIA, PA levels, prospectively determined at enrollment, 12 and 24 months using the Physical Activity Questionnaire for Children (PAQ-C) and Adolescents (PAQ-A) raw scores, were evaluated in relation to disease activity as reflected by arthritis activity (Juvenile Arthritis Disease Activity Score (JADAS-71)), function, pain, and psychosocial stresses using a linear mixed model approach.

Different Disease Endotypes in Phenotypically Similar Vasculitides Affecting Small-to-Medium Sized Blood Vessels.

Chronic primary vasculitis describes a group of complex and rare diseases that are characterized by blood vessel inflammation. Classification of vasculitis subtypes is based predominantly on the size of the involved vessels and clinical phenotype. There is a recognized need to improve classification, especially for small-to-medium sized vessel vasculitides, that, ideally, is based on the underlying biology with a view to informing treatment.

Consensus Treatment Plans for Severe Pediatric Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Objective: There is no standardized approach to the treatment of pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Because of the rarity of pediatric AAV, randomized trials have not been feasible. The present study of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) was undertaken to establish consensus treatment plans (CTPs) for severe pediatric AAV to enable the future study of comparative effectiveness and safety.

Soluble Low-density Lipoprotein Receptor-related Protein 1 in Juvenile Idiopathic Arthritis.

Objectives: This study aimed to expand knowledge about soluble low-density lipoprotein receptor-related protein 1 (sLRP1) in juvenile idiopathic arthritis (JIA) by determining associations of sLRP1 levels in nonsystemic JIA patients with clinical and inflammatory biomarker indicators of disease activity.

Methods: Plasma sLRP1 and 44 inflammation-related biomarkers were measured at enrollment and 6 months later in a cohort of 96 newly diagnosed Canadian patients with nonsystemic JIA. Relationships between sLRP1 levels and indicators of disease activity and biomarker levels were analyzed at both visits.

Kawasaki disease recognition and treatment.

If a child presents to my office with several days of fever and a few features of Kawasaki disease (KD) but does not meet the diagnostic criteria, could they still have KD and is treatment needed? Presentations of KD have a range of clinical signs and symptoms. With the lack of a criterion standard test, the diagnosis of KD relies on syndrome recognition and a high index of suspicion in cases where KD does not present classically. It is still possible to have KD even if not all of the criteria are met, and these children are referred to as having incomplete forms of KD.

Long-term outcomes and disease course of children with juvenile idiopathic arthritis in the ReACCh-Out cohort: a two-centre experience.

Objective: To assess long-term outcomes of children with JIA diagnosed in the biologic era.

Methods: Chart review of patients prospectively enrolled in the Research in Arthritis in Canadian Children Emphasizing Outcomes inception cohort at two Canadian centres. Inactive disease and remission were defined according to Wallace criteria.

Associations of clinical and inflammatory biomarker clusters with juvenile idiopathic arthritis categories.

Objective: To identify discrete clusters comprising clinical features and inflammatory biomarkers in children with JIA and to determine cluster alignment with JIA categories.

Methods: A Canadian prospective inception cohort comprising 150 children with JIA was evaluated at baseline (visit 1) and after six months (visit 2). Data included clinical manifestations and inflammation-related biomarkers.

Clinical and associated inflammatory biomarker features predictive of short-term outcomes in non-systemic juvenile idiopathic arthritis.

Objective: To identify early predictors of disease activity at 18 months in JIA using clinical and biomarker profiling.

Methods: Clinical and biomarker data were collected at JIA diagnosis in a prospective longitudinal inception cohort of 82 children with non-systemic JIA, and their ability to predict an active joint count of 0, a physician global assessment of disease activity of ≤1 cm, and inactive disease by Wallace 2004 criteria 18 months later was assessed. Correlation-based feature selection and ReliefF were used to shortlist predictors and random forest models were trained to predict outcomes.

Complexity in unclassified auto-inflammatory disease: a case report illustrating the potential for disease arising from the allelic burden of multiple variants.

Background: Despite recent advances in the diagnosis and understanding of many autoinflammatory diseases, there are still a great number of patients with phenotypes that do not fit any clinically- and/or genetically-defined disorders.

Case Presentation: We describe a fourteen-year-old boy who presented at two and a half years of age with recurrent febrile episodes. Over the course of the disease, the episodes increased in frequency and severity, with new signs and symptoms continuing to appear.

Real-World Effectiveness of Common Treatment Strategies for Juvenile Idiopathic Arthritis: Results From a Canadian Cohort.

Objective: Undervaluing the effectiveness of conventional treatments may lead to overtreatment with biologic medications in children with juvenile idiopathic arthritis (JIA). Using data from a nationwide inception cohort and strict methods to control bias, the aim of our study was to estimate the real-world effectiveness of simple JIA treatment strategies recommended in current guidelines.

Methods: Children with JIA who were recruited at 16 Canadian centers from 2005 to 2010 were followed for up to 5 years.

Identification of Novel Adenosine Deaminase 2 Gene Variants and Varied Clinical Phenotype in Pediatric Vasculitis.

Objective: Individuals with deficiency of adenosine deaminase 2 (DADA2), a recently recognized autosomal recessive disease, present with various systemic vascular and inflammatory manifestations, often with young age at disease onset or with early onset of recurrent strokes. Their clinical features and histologic findings overlap with those of childhood-onset polyarteritis nodosa (PAN), a primary "idiopathic" systemic vasculitis. Despite similar clinical presentation, individuals with DADA2 may respond better to biologic therapy than to traditional immunosuppression.

Innate Control of Tissue-Reparative Human Regulatory T Cells.

Regulatory T cell (Treg) therapy is a potential curative approach for a variety of immune-mediated conditions, including autoimmunity and transplantation, in which there is pathological tissue damage. In mice, IL-33R (ST2)-expressing Tregs mediate tissue repair by producing the growth factor amphiregulin, but whether similar tissue-reparative Tregs exist in humans remains unclear. We show that human Tregs in blood and multiple tissue types produced amphiregulin, but this was neither a unique feature of Tregs nor selectively upregulated in tissues.

Predicting Which Children with Juvenile Idiopathic Arthritis Will Not Attain Early Remission with Conventional Treatment: Results from the ReACCh-Out Cohort.

Objective: To estimate the probability of early remission with conventional treatment for each child with juvenile idiopathic arthritis (JIA). Children with a low chance of remission may be candidates for initial treatment with biologics or triple disease-modifying antirheumatic drugs (DMARD).

Methods: We used data from 1074 subjects in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort.

Prospective Determination of the Incidence and Risk Factors of New-Onset Uveitis in Juvenile Idiopathic Arthritis: The Research in Arthritis in Canadian Children Emphasizing Outcomes Cohort.

Objective: Identification of the incidence of juvenile idiopathic arthritis (JIA)-associated uveitis and its risk factors is essential to optimize early detection. Data from the Research in Arthritis in Canadian Children Emphasizing Outcomes inception cohort were used to estimate the annual incidence of new-onset uveitis following JIA diagnosis and to identify associated risk factors.

Methods: Data were reported every 6 months for 2 years, then yearly to 5 years.