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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). We used 36-fold cross-validation and tested nine different mathematical methods to combine the answers and optimize psychometric properties. The results were confirmed in the validation cohort. Results Expressed as the mean of the two answers, KDS best balanced ease of use and psychometric properties, while a LASSO regression model combining the two answers with other patient characteristics [estimated CHAQ [eCHAQ]) had the highest responsiveness. In the validation cohort, 22.7%, 25.9% and 28.6% of patients had a score of 0 at enrolment for the KDS, eCHAQ and CHAQ, respectively. Responsiveness was 0.67, 0.74 and 0.62, respectively. Sensitivity to detect a CHAQ > 0 was 0.90 and specificity 0.56, KDS detecting some disability in 44% of children with a CHAQ = 0. Conclusion This simple KDS has psychometric properties comparable with those of a full CHAQ and may be used at every clinic visit to identify those children who need a full disability assessment.

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. Data from a Canadian cohort of children with new-onset JIA (n= 164, data collection 2007-2012) were compared to Canadian Health Measures Survey (CHMS) data (n=4027, data collection 2007-2011). We compared 25-hydroxy vitamin D (25(OH)D) concentrations with measures of inflammation, vitamin D supplement use, milk intake, and season of birth. Mean 25(OH)D level was significantly higher in patients with JIA (79 ± 3.1 nmol/L) than in healthy controls (68 ± 1.8 nmol/L P.05). Patients with JIA more often used vitamin D containing supplements (50% vs. 7%; P.05). The prevalence of 25(OH)D deficiency (30 nmol/L) was 6% for both groups. Children with JIA with 25(OH)D deficiency or insufficiency (50 nmol/L) had higher C-reactive protein levels. Children with JIA were more often born in the fall and winter compared to healthy children. In contrast to earlier studies, we found vitamin D levels in Canadian children with JIA were higher compared to healthy children and associated with more frequent use of vitamin D supplements. Among children with JIA, low vitamin D levels were associated with indicators of greater inflammation.

ObjectiveTo develop Canadian recommendations for the screening, monitoring, and treatment of uveitis associated with juvenile idiopathic arthritis (JIA).MethodsRecommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach. A working group of 14 pediatric rheumatologists, 6 ophthalmologists, 2 methodologists, and 3 caregiver/patient representatives reviewed recent American College of Rheumatology (ACR)/Arthritis Foundation (AF) recommendations and worked in pairs to develop evidence-to-decision (EtD) tables. A survey to assess agreement and recommendations requiring group discussion was completed. EtD tables were presented, discussed, and voted upon at a virtual meeting, to produce the final recommendations. A health equity framework was applied to all aspects of the adolopment process including the EtD tables, survey responses, and virtual meeting discussion.ResultsThe survey identified that 7 of the 19 recommendations required rigorous discussion. Seventy-five percent of working group members attended the virtual meeting to discuss controversial topics as they pertained to the Canadian environment, including timing to first eye exam, frequency of screening, escalation criteria for systemic and biologic therapy, and the role of nonbiologic therapies. Equity issues related to access to care and advanced therapeutics across Canadian provinces and territories were highlighted. Following the virtual meeting, 5 recommendations were adapted, 2 recommendations were removed, and 1 was developed de novo.ConclusionRecommendations for JIA-associated uveitis were adapted to the Canadian context by a working group of pediatric rheumatologists, ophthalmologists with expertise in the management of uveitis, and parent/patient input, taking into consideration cost, equity, and access.

This report presents 2 pediatric cases of multisystem inflammatory syndrome in children and adults (MIS-C/A) post severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination (MIS-V). Both children presented with MIS-V within 6 weeks of receiving their first and only dose of Pfizer-BioNTech’s SARS-CoV-2 vaccine. The first patient had symptoms of MIS-C/A with peri-myocarditis and shock, and the second 1 had classic Kawasaki disease features. Both responded well to intravenous immunoglobulins and/or systemic corticosteroids. Both children were positive only for SARS-2-CoV antispike (S) (and not for antinucleocapsid [NC]) antibodies consistent with a postvaccine, and not a postinfection, event. Surveillance for rare adverse events following immunization should continue, especially now that SARS-CoV-2 vaccination is approved in the 5 to 11 year age group that has had the highest risk of developing MIS-C post SARS-CoV-2 infection. Our patients did not receive any further SARS-CoV-2 vaccines. Our report highlights the importance of measuring differentiating antibodies (anti-S and anti-NC) that can be used within a specific timeframe to help determine if a patient has MIS-V post vaccine (only anti-S present), or MIS-C/A post SARS-CoV-2 infection (both anti-S and anti-NC present).

Objective To identify differences between baseline Canadian JIA practices and the 2019 ACR guidelines for JIA. Methods Canadian paediatric rheumatologists were surveyed for their opinions on reasonable a priori target adherence rates for JIA guideline recommendations. Prospectively collected data for 266 newly diagnosed children from 2017 to 2019 were analysed to calculate observed adherence rates. Kaplan–Meier survival curves were used to estimate the cumulative incidence of starting synthetic or biologic DMARDs (sDMARD or bDMARD, respectively) for different patient groups. Results A total of 25/61 (41%) eligible physicians answered the survey. Most survey respondents (64%) felt that adherence targets should vary depending on the strength of the recommendation and quality of evidence, from a mean of 84% for strong recommendations with high-quality evidence to 29% for conditional recommendations with very low-quality evidence. Data showed 13/19 (68%) recommendations would have met proposed targets and 10/19 (53%) had ≥80% observed adherence. Exceptions were the use of subcutaneous vs oral MTX (53%) and infrequent treatment escalation from NSAIDs to bDMARDs in patients with sacroiliitis (31%) or enthesitis (0%). By 12 weeks, 95% of patients with polyarthritis received sDMARDs, 38% of patients with systemic JIA received bDMARDs and 22% of patients with sacroiliitis received bDMARDs. Conclusion Canadian paediatric rheumatology practices were in line with many 2019 JIA guideline recommendations before their publication, except for frequent use of oral MTX and infrequent direct escalation from NSAIDs to bDMARDs in sacroiliitis and enthesitis.

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. For each child, all observed treatment changes over time were assessed by independent physicians using prospectively collected data and published response criteria. Success was defined as attainment of inactive disease or maintenance of this state when stepping down treatment; minimally active disease was deemed acceptable for children with polyarticular JIA. Success rates were calculated for treatments tried ≥25 times, and logistic regression analysis identified features associated with success. RESULTS A total of 4,429 treatment episodes were observed in 1,352 children. Nonsteroidal antiinflammatory drug (NSAID) monotherapy was attempted 697 times, mostly as initial treatment when

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. Probabilistic principal component analysis identified sets of composite variables, or principal components, from 191 original variables. To discern new clinical-biomarker clusters (clusters), Gaussian mixture models were fit to the data. Newly-defined clusters and JIA categories were compared. Agreement between the two was assessed using Kruskal–Wallis analyses and contingency plots. Results Three principal components recovered 35% (three clusters) and 40% (five clusters) of the variance in patient profiles in visits 1 and 2, respectively. None of the clusters aligned precisely with any of the seven JIA categories but rather spanned multiple categories. Results demonstrated that the newly defined clinical-biomarker lustres are more homogeneous than JIA categories. Conclusion Applying unsupervised data mining to clinical and inflammatory biomarker data discerns discrete clusters that intersect multiple JIA categories. Results suggest that certain groups of patients within different JIA categories are more aligned pathobiologically than their separate clinical categorizations suggest. Applying data mining analyses to complex datasets can generate insights into JIA pathogenesis and could contribute to biologically based refinements in JIA classification.

Objective Childhood-onset SLE (cSLE) manifests differently than adult-onset SLE (aSLE). This study determined whether ethnic differences contribute to the differences in clinical presentation between the two groups. Methods This cross-sectional study used data from a multi-centred registry from eight adult and four paediatric Canadian centres gathered at study entry. We compared the frequency of clinical manifestations and autoantibodies between aSLE and cSLE. For those with a significant difference, a multivariable logistic regression was performed, adjusting for ethnicity, SLE onset (cSLE vs aSLE), disease duration and centre. Disease activity and damage between aSLE and cSLE were compared after stratifying by disease duration. Results Of 552 aSLE subjects, 502 (90.9%) were female and 381 (69.0%) were Caucasian. Mean age at diagnosis was 37.0 ± 13.6 years and disease duration 10.9 ± 9.6 years. Of 276 cSLE subjects, 231 (83.7%) were female and 101 (36.6%) were Caucasian. Mean age at diagnosis was 12.7 ± 3.3 years and disease duration 5.6 ± 8.2 years. In multivariable regression analysis, aSLE was associated with decreased odds of having a neurologic disorder (odds ratio = 0.49) and increased odds of having aCL antibodies (odds ratio = 1.85). Disease activity and damage accrual scores were higher in aSLE than cSLE within the same disease duration strata, although the differences were not clinically significant. Ethnicity was not associated with any differences in clinical manifestations or autoantibody frequency between aSLE and cSLE. Conclusion Although a crude comparison of aSLE and cSLE yielded several differences in clinical symptoms and autoantibodies, this difference was not attributable to ethnic differences between aSLE and cSLE.

To describe the frequency and severity of parent-reported medication side effects (SEs) in children with juvenile idiopathic arthritis (JIA) relative to physician-reported actionable adverse events (AEs), and to assess their impact on health-related quality of life (HRQoL).Newly diagnosed JIA patients recruited between 2017 and 2019 to the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry were included. Parents reported presence and severity (0 = no problem, 10 = very severe) of medication SEs at every clinic visit. Physicians were asked to report any actionable AE. HRQoL was assessed using the Quality of My Life (QoML) questionnaire (0 = the worst, 10 = the best) and parent's global assessment (0 = very well, 10 = very poor). Analyses included proportion of visits with SEs or actionable AEs, cumulative incidence by Kaplan-Meier methods, and HRQoL impact measured with longitudinal mixed-effects models.SEs were reported at 371 of 884 (42%) visits (95% confidence interval [95% CI] 39, 45%) in 249 patients, with a median of 2 SEs per visit (interquartile range [IQR] 1-3), and median severity of 3 (IQR 1.5-5). Most SEs were gastrointestinal (32.5% of visits) or behavioral/psychiatric (22.4%). SE frequency was lowest with nonsteroidal antiinflammatory drugs alone (34.7%) and highest with prednisone and methotrexate combinations (66%). SE cumulative incidence was 67% (95% CI 59, 75) within 1 year of diagnosis, and 36% (95% CI 28, 44) for actionable AEs. Parent global and QoML scores were worse with SEs present; the impact persisted after adjusting for pain and number of active joints.Parents report that two-thirds of children with JIA experience SEs impacting their HRQoL within 1 year of diagnosis. SE mitigation strategies are needed in managing JIA.

ObjectivesThis 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.MethodsPlasma 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.ResultsAt enrollment, sLRP1 levels correlated negatively with age and active joint counts. Children showed significantly higher levels of sLRP1 than adolescents (mean ranks: 55.4 and 41.9, respectively; P = 0.02). Participants with 4 or fewer active joints, compared to those with 5 or more active joints, had significantly higher sLRP1 levels (mean ranks: 56.2 and 40.7, respectively; P = 0.006). At enrollment, considering the entire cohort, sLRP1 correlated negatively with the number of active joints (r = –0.235, P = 0.017). In the entire cohort, sLRP1 levels at enrollment and 6 months later correlated with 13 and 6 pro- and antiinflammatory biomarkers, respectively. In JIA categories, sLRP1 correlations with inflammatory markers were significant in rheumatoid factor–negative polyarticular JIA, oligoarticular JIA, enthesitis-related arthritis, and psoriatic arthritis at enrollment. Higher sLRP1 levels at enrollment increased the likelihood of absence of active joints 6 months later.ConclusionPlasma sLRP1 levels correlate with clinical and biomarker indicators of short-term improvement in JIA disease activity, supporting sLRP1 as an upstream biomarker of potential utility for assessing JIA disease activity and outcome prediction.

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. Results From the original 112 features, 13 effectively predicted 18-month outcomes. They included age, number of active/effused joints, wrist, ankle and/or knee involvement, ESR, ANA positivity and plasma levels of five inflammatory biomarkers (IL-10, IL-17, IL-12p70, soluble low-density lipoprotein receptor-related protein 1 and vitamin D), at enrolment. The clinical plus biomarker panel predicted active joint count = 0, physician global assessment ≤ 1, and inactive disease after 18 months with 0.79, 0.80 and 0.83 accuracy and 0.84, 0.83, 0.88 area under the curve, respectively. Using clinical features alone resulted in 0.75, 0.72 and 0.80 accuracy, and area under the curve values of 0.81, 0.78 and 0.83, respectively. Conclusion A panel of five plasma biomarkers combined with clinical features at the time of diagnosis more accurately predicted short-term disease activity in JIA than clinical characteristics alone. If validated in external cohorts, such a panel may guide more rationally conceived, biologically based, personalized treatment strategies in early JIA.

Objective.Persistent systemic lupus erythematosus (SLE) disease activity is associated with increased morbidity and mortality. In a multicenter cohort of patients with prevalent SLE, we described persistence, patterns, and predictors of change in disease activity over time.Methods.Based on SLE Disease Activity Index (SLEDAI)-2K scores at cohort entry, patients were classified into 4 groups: low (score < 4; LOW), moderate (4 to < 6; MOD), moderately high (6 to ≤ 10; MHIGH), and very high (> 10; VHIGH). Multivariable linear and longitudinal mixed linear regression models were used to identify predictors of change over time in SLEDAI-2K.Results.There were 2019 participants, with declining followup data over 5 years (1326, 580, 274, 186, and 148 patients, respectively). At cohort entry, mean (± SD) age was 42 (± 17) years, disease duration 11 (± 10) years, and 90% were female. The 4 groups included 44% LOW (n = 891), 20% MOD (n = 400), 22% MHIGH (n = 442), and 14% VHIGH (n = 286); therefore, 36% had clinically important SLE activity. The proportion of patients in the LOW group at entry who moved to a higher activity level varied from 30% (167/557) at 1 year, to 49% (41/83) at 3 years, and 54% (30/56) at 5 years. Among 181 patients with MOD to VHIGH entry activity and 3 years of followup, 116 (64.1%) remained active. In all analyses, only higher SLEDAI-2K at cohort entry remained a significant predictor of higher SLEDAI-2K in subsequent years.Conclusion.Higher SLEDAI-2K at study entry was the single major independent predictor of higher SLEDAI-2K over time, reflecting frequent persistence of active disease, even in patients with longstanding disease. This highlights gaps in the optimal treatment of SLE.

We studied children enrolled within 90 days of juvenile idiopathic arthritis diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) prospective inception cohort to identify longitudinal trajectories of pain severity and features that may predict pain trajectory at diagnosis. A total of 1062 participants were followed a median of 24.3 months (interquartile range = 16.0-37.1 months). Latent trajectory analysis of pain severity, measured in a 100-mm visual analogue scale, identified 5 distinct trajectories: (1) mild-decreasing pain (56.2% of the cohort); (2) moderate-decreasing pain (28.6%); (3) chronically moderate pain (7.4%); (4) minimal pain (4.0%); and (5) mild-increasing pain (3.7%). Mean disability and quality of life scores roughly paralleled the pain severity trajectories. At baseline, children with chronically moderate pain, compared to those with moderate-decreasing pain, were older (mean 10.0 vs 8.5 years, P = 0.01) and had higher active joint counts (mean 10.0 vs 7.2 joints, P = 0.06). Children with mild-increasing pain had lower joint counts than children with mild-decreasing pain (2.3 vs 5.2 joints, P < 0.001). Although most children with juvenile idiopathic arthritis in this cohort had mild or moderate initial levels of pain that decreased quickly, about 1 in 10 children had concerning pain trajectories (chronically moderate pain and mild-increasing pain). Systematic periodic assessment of pain severity in the months after diagnosis may help identify these concerning pain trajectories early and lay out appropriate pain management plans. Focused research into the factors leading to these concerning trajectories may help prevent them.

Background: The assessment of disease activity plays a pivotal role in the management of children with juvenile idiopathic arthritis (JIA). Most recent recommendations require that parents’ and children’s perception is incorporated in the evaluation of the disease course and of effectiveness of therapeutic interventions. A new disease activity tool, named parent Juvenile Arthritis Disease Activity Score (parJADAS) and based only on parent-centered outcome measures, is currently under development (1). Objectives: To demonstrate, in a large multinational dataset of JIA patients, the discriminant ability of the parJADAS. Methods: The parJADAS includes 4 measures: 1) parent assessment of disease activity; 2) assessment of pain intensity; 3) proxy assessment of joint disease; 4) assessment of morning stiffness (MS). Disease activity and pain are assessed on a 21-numbered circle VAS (0 = best and 10 = worst). The active joint count is based on the count of any swollen or painful joint, irrespective of its type, up to a maximum of 10 joints. MS duration is assessed on a Likert scale, ranging from no MS (0 points) to > 2 hours of MS (10 points). Validation was conducted on a dataset of 8,656 children with JIA from 49 countries, enrolled in the study of Epidemiology, treatment and Outcome of Childhood Arthritis (2), who had all the variables included in the parJADAS available. Discriminant ability was evaluated by comparing parJADAS levels (median, [IQR]) among patients with inactive disease (ID), low disease activity (LDA), moderate disease activity (MDA), and high disease activity (HDA) according to the cJADAS10; patients in remission, continued activity, or flare according to the attending physician; patients whose parents were satisfied or not with current disease state. To assess the possible influence of the articular and extra-articular damage on the parJADAS, the levels of the score in patients with or without damage (Juvenile Arthritis Damage Index > 0) were compared. For this analysis, only subjects in inactive disease and with at least 2 years of disease course were considered (n = 2,423). Results: The levels of parJADAS in patients in ID, LDA, MDA, and HDA were 0.0 [0.0, 1.0], 3.0 [1.0, 6.0], 6.0 [2.0, 11.5], an 14.5 [8.5, 21.0], respectively (Kruskal-Wallis test, p Conclusion: The parJADAS showed excellent discriminate ability in a large multinational cohort. The score did not show to be relevantly influenced by disease damage in JIA patients in remission. References [1] Consolaro A, et al. “Development and Initial Validation of the Parent and Child Versions of the Juvenile Arthritis Disease Activity Score”. Arthritis Rheumatol. 2016; 68 (suppl 10). [2] Consolaro A, et al. “Phenotypic variability and disparities in treatment and outcomes of childhood arthritis throughout the world: results from an observational cohort study”. The Lancet Child and Adolescent Health, In press. Disclosure of Interests: Francesca Ridella: None declared, Giedre Januskeviciute: None declared, Chiara Trincianti: None declared, Gabriella Giancane: None declared, Alessandra Alongi: None declared, Soamarat Vilaiyuk: None declared, Gaelle Chedeville: None declared, Chris Pruunsild: None declared, Pekka Lahdenne: None declared, Nicolino Ruperto Grant/research support from: The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Consultant for: Received honoraria for consultancies or speaker bureaus (

Background Treatments for juvenile idiopathic arthritis (JIA) are changing rapidly. Healthcare providers and families require up-to-date knowledge of current treatment practices and expected outcomes to inform their decisions. Objectives To assess changes in treatment practices and outcomes for children in a new Canadian inception cohort diagnosed with JIA in 2017-2018, compared to children in the Research in Arthritis in Canadian Children emphasizing Outcomes cohort (ReACCh-Out) diagnosed in 2005-2010 1. Methods A new investigator-driven Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) JIA Registry was started in February 2017 to prospectively collect information on children enrolled within 3 months of JIA diagnosis. Information about disease activity, treatments, outcomes and adverse events is collected at all clinic visits. Registry data were extracted in October 2018 and clinical characteristics at presentation, use of anti-rheumatic medications, attainment of inactive disease, cJADAS10 scores and adverse events were described. Selected findings were compared to those observed in the ReACCh-Out cohort. The proportion of patients (cumulative incidence) receiving various treatments and their outcomes were estimated with Kaplan Meier survival methods. Results A total of 166 patients enrolled a median of 6 weeks after diagnosis at 10 centres were included. Median age at diagnosis was 9 years (IQR 3, 13), 61% were female and 51% had oligoarthritis. At enrolment, subjects had a median of 2 active joints (IQR 1, 3), a Physician Global Assessment of 3 (1.5, 4) and a Parent Global Assessment of 1 (0, 3). The median cJADAS10 score was 6.5 (4, 10). Table 1 compares baseline characteristics and the cumulative incidence of medication use and inactive disease at one year after diagnosis with those observed in the ReACCh-Out cohort, diagnosed on average 10 years earlier. Figure 1 shows the Kaplan Meier curves for attainment of inactive disease. Conclusion In Canada, treatments for newly diagnosed patients with JIA have intensified in the last 10 years, and 35% will now start their first biologic within 1 year of diagnosis. Short-term outcomes have improved, 81% of current patients now attaining inactive disease within one year of diagnosis. Funding: The Arthritis Society, Canada. References [1] Guzman J, Oen K, Tucker LB, et al. The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort. Ann Rheum Dis.2015;74:1854-60 Acknowledgement Funding: The Arthritis Society, Canada. Disclosure of Interests Jaime Guzman: None declared, Michelle Batthish Speakers bureau: Novartis, Abbvie, Roberta Berard: None declared, Roxana Bolaria: None declared, David Cabral: None declared, Gaelle Chedeville: None declared, Ciaran Duffy: None declared, Kerstin Gerhold: None declared, Tommy Gerschman: None declared, Adam Huber: None declared, Jean-Philippe Proulx-Gauthier: None declared, Alan Rosenberg: None declared, Dax Rumsey: None declared, Heinrike Schmeling Grant/research support from: F. Hoffmann-La Roche Ltd, Natalie Shiff: None declared, Gordon Soon: None declared, Lori Tucker: None declared

Made available in DSpace on 2019-10-05T16:54:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-04-01 IRCCS Istituto Giannina Gaslini Background To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status. Methods In this multinational, cross-sectional, observational cohort study, we asked international paediatric rheumatologists from specialised centres to enrol children with a diagnosis of juvenile idiopathic arthritis, according to International League of Associations for Rheumatology criteria, who were seen consecutively for a period of 6 months. Each patient underwent retrospective and cross-sectional assessments, including measures of disease activity and damage and questionnaires on the wellbeing and quality of life of the children. We qualitatively compared the collected data across eight geographical areas, and we explored an association between disease activity and damage and a country's gross domestic product (GDP) with a multiple logistic regression analysis. Findings Between April 4, 2011, and Nov 21, 2016, 9081 patients were enrolled at 130 centres in 49 countries, grouped into eight geographical areas. Systemic arthritis (125 [33.0%] of 379 patients) and enthesitis-related arthritis (113 [29.8%] of 379) were more common in southeast Asia, whereas oligoarthritis was more prevalent in southern Europe (1360 [56.7%] of 2400) and rheumatoid factor-negative polyarthritis was more frequent in North America (165 [31.5%] of 523) than in the other areas. Prevalence of uveitis was highest in northern Europe (161 [19.1%] of 845 patients) and southern Europe (450 [18.8%] of 2400) and lowest in Latin America (54 [6.4%] of 849), Africa and Middle East (71 [5.9%] of 1209), and southeast Asia (19 [5.0%] of 379). Median age at disease onset was lower in southern Europe (3.5 years, IQR 1.9-7.3) than in other regions. Biological, disease-modifying antirheumatic drugs were prescribed more frequently in northern Europe and North America than in other geographical settings. Patients living in countries with lower GDP had greater disease activity and damage than those living in wealthier countries. Damage was associated with referral delay. Interpretation Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographical areas and wealth status of countries. The greater disease burden in lowerresource settings highlights the need for public health efforts aimed at improving equity in access to effective treatments and care for juvenile idiopathic arthritis. Copyright (C) 2019 Elsevier Ltd. All rights reserved. Univ Genoa, Ist Giannina Gaslini, IRCCS, Clin Paediat & Rheumatol, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Epidemiol & Biostat Serv, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Sci Directory, Genoa, Italy Univ Genoa, PRINTO, IRCCS, Ist Giannina Gaslini, Genoa, Italy Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet & Maternal, Genoa, Italy Wilhelmina Childrens Hosp, Dept Pediat Immunol & Rheumatol, Utrecht, Netherlands Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India Univ Hosp 12 Octubre, Dept Pediat Rheumatol, Madrid, Spain Alfaisal Univ, Dept Pediat Rheumatol, King Faisal Specialist Hosp, Riyadh, Saudi Arabia Alfaisal Univ, Res Ctr, Riyadh, Saudi Arabia Western Univ Childrens Hosp, Hlth Sci Ctr, London, ON, Canada Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway Oslo Univ Hosp, Med Fac, Oslo, Norway Univ Oslo, Oslo, Norway Oslo Univ Hosp, Norwegian Natl Advisory Unit Rheumat Dis Children, Oslo, Norway Univ Hosp Munster, Dept Pediat Rheumatol & Immunol, Munster, Germany Hosp Sor Maria Ludovica, Rheumatol Serv, La Plata, Buenos Aires, Argentina Bucharest Emergency Hosp, Cluj Napoca, Romania Childrens Emergency Hosp, Cluj Napoca, Romania Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA Alberta Childrens Prov Gen Hosp, Div Pediat Rheumatol, Dept Pediat, Calgary, AB, Canada Sofiamed, Pediat Dept, Sofia, Bulgaria Rigshosp, Juliane Marie Ctr, Paediat Rheumatol Unit, Copenhagen, Denmark Natl Inst Rheumatism & Physiotherapy, Clin Immunol Adult & Paediat Rheumatol Dept, Budapest, Hungary Univ Latvia, Pediat Dept, Riga, Latvia Univ Latvia, Univ Childrens Hosp, Riga, Latvia Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil Shariati Hosp, Rheumatol Res Ctr, Dept Pediat & Rheumatol, Tehran, Iran Inst Rheumatol Belgrade, Div Pediat Rheumatol, Belgrade, Serbia Thessaloniki Univ, Dept Pediat 1, Hippokrat Gen Hosp, Sch Med, Thessaloniki, Greece Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Canadian varieties of English and French. The reading comprehension of the questionnaires were tested in a probe sample of ten parents and ten JIA patients for Canadian English and other ten parents and ten JIA patients for Canadian French. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach’s alpha, interscale correlations, test–retest reliability and construct validity (convergent and discriminant validity). A total of 208 JIA patients (2.9% systemic, 41.8% oligoarticular, 27.9% RF negative polyarthritis, 27.4% other categories) and 152 healthy children, were enrolled at two paediatric rheumatology centres. The JAMAR components discriminated well healthy subjects from JIA patients. Notably, there was no significant difference between the healthy subjects and their affected peers in the psychosocial quality of life variable. All JAMAR components revealed good psychometric performances. In conclusion, the Canadian English and French versions of the JAMAR are valid tools for the assessment of children with JIA and are suitable for use both in routine clinical practice and clinical research.

OBJECTIVE: To identify biomarkers of articular and ocular disease activity in patients with Blau syndrome (BS). METHODS: Multiplex plasma protein arrays were performed in five BS patients and eight normal healthy volunteers (NHVs). Plasma S100A12 and S100A8/9 were subsequently measured by ELISA at baseline and 1-year follow-up in all patients from a prospective multicentre cohort study. CRP was measured using Meso Scale Discovery immunoassay. Active joint counts, standardization uveitis nomenclature for anterior uveitis cells and vitreous haze by Nussenblatt scale were the clinical parameters. RESULTS: Multiplex Luminex arrays identified S100A12 as the most significantly elevated protein in five selected BS vs eight NHVs and this was confirmed by ELISA on additional samples from the same five BS patients. In the patient cohort, S100A12 (n = 39) and S100A8/9 (n = 33) were significantly higher compared with NHVs (n = 44 for S100A12, n = 40 for S100A8/9) (P = 0.0000004 and P = 0.0003, respectively). Positive correlations between active joint counts and S100 levels were significant for S100A12 (P = 0.0008) and S100A8/9 (P = 0.015). CRP levels did not correlate with active joint count. Subgroup analysis showed significant association of S100 proteins with active arthritis (S100A12 P = 0.01, S100A8/9 P = 0.008). Active uveitis was not associated with increased S100 levels. CONCLUSION: S100 proteins are biomarkers of articular disease activity in BS and potential outcome measures in future clinical trials. As secreted neutrophil and macrophage products, S100 proteins may reflect the burden of granulomatous tissue in BS.

Background With modern treatments, the effect of juvenile idiopathic arthritis (JIA) on growth may be less than previously reported. Our objective was to describe height, weight and body mass index (BMI) development in a contemporary JIA inception cohort. Methods Canadian children newly-diagnosed with JIA 2005–2010 had weight and height measurements every 6 months for 2 years, then yearly up to 5 years. These measurements were used to calculate mean age- and sex-standardized Z-scores, and estimate prevalence and cumulative incidence of growth impairments, and the impact of disease activity and corticosteroids on growth. Results One thousand one hundred forty seven children were followed for median 35.5 months. Mean Z-scores, and the point prevalence of short stature (height 95th percentile, 15.8% to 16.4%) remained unchanged in the whole cohort. Thirty-three children (2.9%) developed new-onset short stature, while 27 (2.4%) developed tall stature (>97.5th percentile). Children with systemic arthritis (n = 77) had an estimated 3-year cumulative incidence of 9.3% (95%CI: 4.3–19.7) for new-onset short stature and 34.4% (23–49.4) for obesity. Most children (81.7%) received no systemic corticosteroids, but 1 mg/Kg/day prednisone-equivalent maintained for 6 months corresponded to a drop of 0.64 height Z-scores (0.56–0.82) and an increase of 0.74 BMI Z-scores (0.56–0.92). An increase of 1 in the 10-cm physician global assessment of disease activity maintained for 6 months corresponded to a drop of 0.01 height Z-scores (0–0.02). Conclusions Most children in this modern JIA cohort grew and gained weight as children in the general population. About 1 in 10 children who had systemic arthritis, uncontrolled disease and/or prolonged corticosteroid use, had increased risk of growth impairment. Electronic supplementary material The online version of this article (doi:10.1186/s12969-017-0196-7) contains supplementary material, which is available to authorized users.

Objective To examine the association between smoking and cutaneous involvement in systemic lupus erythematosus (SLE). Methods We analyzed data from a multicenter Canadian SLE cohort. Mucocutaneous involvement was recorded at the most recent visit using the Systemic Lupus Erythematosus Disease Activity Index 2000 Update (rash, alopecia, and oral ulcers), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (alopecia, extensive scarring, and skin ulceration), and the ACR revised criteria for SLE (malar rash, discoid rash, photosensitivity, and mucosal involvement). Multivariate logistic regression models were used to estimate the independent association between mucocutaneous involvement and cigarette smoking, age, sex, ethnicity, lupus duration, medications, and laboratory data. Results In our cohort of 1,346 patients (91.0% women), the mean ± SD age was 47.1 ± 14.3 years and the mean ± SD disease duration was 13.2 ± 10.0 years. In total, 41.2% of patients were ever smokers, 14.0% current smokers, and 27.1% past smokers. Active mucocutaneous manifestations occurred in 28.4% of patients; cutaneous damage occurred in 15.4%. Regarding the ACR criteria, malar rash was noted in 59.5%, discoid rash in 16.9%, and photosensitivity in 55.7% of patients. In the multivariate analysis, current smoking was associated with active SLE rash (odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.07, 2.48]). Having ever smoked was associated with ACR discoid rash (OR 2.36 [95% CI 1.69, 3.29]) and photosensitivity (OR 1.47 [95% CI 1.11, 1.95]), and with the ACR total cutaneous score (OR 1.50 [95% CI 1.22, 1.85]). We did not detect any associations between previous smoking and active cutaneous manifestations. No association was found between smoking and cutaneous damage or mucosal ulcers. No interaction was seen between smoking and antimalarials. Conclusion Current smoking is associated with active SLE rash, and ever smoking with the ACR total cutaneous score. This provides additional motivation for smoking cessation in SLE.

Objective To determine the influence of ethnicity and sociodemographic factors on disease characteristics of the Canadian pediatric lupus population. Methods Childhood-onset systemic lupus erythematosus (SLE) patients at 4 pediatric centers in Halifax, Montreal, Toronto, and Vancouver were consecutively recruited. Sociodemographics and disease data were collected. Patients were categorized by their primary self-selected ethnicity, and exploratory cluster analyses were examined for disease expression by ethnicity. Results We enrolled 213 childhood-onset SLE patients, and ethnicity data were available for 206 patients: white (31%), Asian (30%), South Asian (15%), black (10%), Latino/Hispanic (4%), Aboriginal (4%), and Arab/Middle Eastern (3%). The frequency of clinical classification criteria (malar rash, arthritis, serositis, and renal disease) and autoantibodies significantly differed among ethnicities. Medications were prescribed equally across ethnicities: 76% were taking prednisone, 86% antimalarials, and 56% required additional immunosuppressants. Cluster analysis partitioned into 3 main groups: mild (n = 50), moderate (n = 82), and severe (n = 68) disease clusters. Only 20% of white patients were in the severe cluster compared to 51% of Asian and 41% of black patients (P = 0.03). However, disease activity indices and damage scores were similar across ethnicities. Conclusion Canadian childhood-onset SLE patients reflect our multiethnic population, with differences in disease manifestations, autoantibody profiles, and severity of disease expression by ethnicity.

ObjectiveTo 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.MethodsWe 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. Probability of first flare was calculated with Kaplan–Meier methods, and associated features were identified using Cox regression.Results1146 children were followed up a median of 24 months after attaining inactive disease. We observed 627 first flares (54.7% of patients) with median active joint count of 1, physician global assessment (PGA) of 12 mm and duration of 27 weeks. Within a year after attaining inactive disease, the probability of flare was 42.5% (95% CI 39% to 46%) for any flare and 26.6% (24% to 30%) for a significant flare. Within a year after stopping treatment, it was 31.7% (28% to 36%) and 25.0% (21% to 29%), respectively. A maximum PGA >30 mm, maximum active joint count >4, rheumatoid factor (RF)-positive polyarthritis, antinuclear antibodies (ANA) and receiving disease-modifying antirheumatic drugs (DMARDs) or biological agents before attaining inactive disease were associated with increased risk of flare. Systemic JIA was associated with the lowest risk of flare.ConclusionsIn this real-practice JIA cohort, flares were frequent, usually involved a few swollen joints for an average of 6 months and 60% led to treatment intensification. Children with a severe disease course had an increased risk of flare.

To evaluate the vaccination coverage rate of patients with JIA followed at a paediatric tertiary care centre and to determine the coverage rate for individual vaccines required as per the Quebec Immunization Protocol.Consecutive JIA patients coming for their scheduled visit were included if they were between 2 and 18 years of age and if they had an available written immunization record. Descriptive statistics were used to evaluate the proportion of children with complete vaccination status according to the Quebec Immunization Protocol at 2.5, 10.5 years and at their last clinic visit.A total of 200 patients were included. Complete vaccination according to schedule was identified in only 52% of patients at 2.5 years, 68% at 10.5 years and 61% at their last clinic visit. The vaccination coverage rate for individual vaccines was good overall with the exception of low measles, mumps and rubella vaccine coverage at 2.5 years (58%).Despite overall good vaccination coverage rate for individual vaccines, only 61% of our cohort had a complete vaccination status at their last clinic visit. Measures to optimize vaccination coverage, such as catch-up vaccination, should be implemented when possible.

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. There were large discrepancies in the access criteria and coverage of biologic agents across provinces, notably with age restrictions for younger children.Conclusion.Canadian children with JIA may not receive optimal internationally recognized “standard” care because pediatric coverage for biologic drugs through provincial formularies is limited and inconsistent across the country. There is urgent need for public policy to improve access to biologic therapies for these children to ensure optimal short-term and longterm health outcomes.

To formulate consensus treatment plans (CTPs) for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus erythematosus (SLE).A structured consensus formation process was employed by the members of the Childhood Arthritis and Rheumatology Research Alliance after considering the existing medical evidence and current treatment approaches.After an initial Delphi survey (response rate = 70%), a 2-day consensus conference, and 2 followup Delphi surveys (response rates = 63-79%), consensus was achieved for a limited set of CTPs addressing the induction therapy of proliferative LN. These CTPs were developed for prototypical patients defined by eligibility characteristics, and included immunosuppressive therapy with either mycophenolic acid orally twice per day, or intravenous cyclophosphamide once per month at standardized dosages for 6 months. Additionally, the CTPs describe 3 options for standardized use of glucocorticoids, including a primarily oral, a mixed oral/intravenous, and a primarily intravenous regimen. There was consensus on measures of effectiveness and safety of the CTPs. The CTPs were well accepted by the pediatric rheumatology providers treating children with LN, and up to 300 children per year in North America are expected to be candidates for the treatment with the CTPs.CTPs for induction therapy of proliferative LN in juvenile SLE based on the available scientific evidence and pediatric rheumatology group experience have been developed. Consistent use of the CTPs may improve the prognosis of proliferative LN, and support the conduct of comparative effectiveness studies aimed at optimizing therapeutic strategies for proliferative LN in juvenile SLE.

Objective To compare the criteria for Wegener's granulomatosis (WG) of the American College of Rheumatology (ACR) with those of the European League Against Rheumatism/Pediatric Rheumatology European Society (EULAR/PRES) in a cohort of children with WG and other antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides (AAVs), and to describe the interval to diagnosis, presenting features, and initial treatment for WG. Methods Eligible patients had been diagnosed by site rheumatologists (termed the “MD diagnosis”) since 2004. This diagnosis was used as a reference standard for sensitivity and specificity testing of the 2 WG classification criteria. Descriptive analyses were confined to ACR-classified WG patients. Results MD diagnoses of 117 patients (82 of whom were female) were WG (n = 76), microscopic polyangiitis (n = 17), ANCA-positive pauci-immune glomerulonephritis (n = 5), Churg-Strauss syndrome (n = 2), and unclassified vasculitis (n = 17). The sensitivities of the ACR and EULAR/PRES classification criteria for WG among the spectrum of AAVs were 68.4% and 73.6%, respectively, and the specificities were 68.3% and 73.2%, respectively. Two more children were identified as having WG by the EULAR/PRES criteria than by the ACR criteria. For the 65 ACR-classified WG patients, the median age at diagnosis was 14.2 years (range 4–17 years), and the median interval from symptom onset to diagnosis was 2.7 months (range 0–49 months). The most frequent presenting features by organ system were constitutional (89.2%), pulmonary (80.0%), ear, nose, and throat (80.0%), and renal (75.4%). Fifty-four patients (83.1%) commenced treatment with the combination of corticosteroids and cyclophosphamide, with widely varying regimens; the remainder received methotrexate alone (n = 1), corticosteroids alone (n = 4), or a combination (n = 6). Conclusion The EULAR/PRES criteria minimally improved diagnostic sensitivity and specificity for WG among a narrow spectrum of children with AAVs. Diagnostic delays may result from poor characterization of childhood WG. Initial therapy varied considerably among participating centers.

Objective To determine early predictors of 6-month outcomes in a prospective cohort of patients with juvenile idiopathic arthritis (JIA). Methods Patients selected were those enrolled in an inception cohort study of JIA, the Research in Arthritis in Canadian Children Emphasizing Outcomes Study, within 6 months after diagnosis. The juvenile rheumatoid arthritis core criteria set and quality of life measures were collected at enrollment and 6 months later. Outcomes evaluated included inactive disease, Juvenile Arthritis Quality of Life Questionnaire (JAQQ) scores, and Childhood Health Assessment Questionnaire (C-HAQ) scores at 6 months. Results Thirty-three percent of patients had inactive disease at 6 months. Onset subtype and most baseline core criteria set measures correlated with all 3 outcomes. Relative to oligoarticular JIA, the risks of inactive disease were lower for enthesitis-related arthritis, polyarthritis rheumatoid factor (RF)–negative JIA, and polyarthritis RF-positive JIA, and were similar for psoriatic arthritis. In multiple regression analyses, the baseline JAQQ score was an independent predictor of all 3 outcomes. Other independent baseline predictors included polyarthritis RF-negative and systemic JIA for inactive disease; C-HAQ score and polyarthritis RF-positive JIA for the 6-month C-HAQ score; and active joint count, pain, and time to diagnosis for the 6-month JAQQ score. Conclusion Clinical measures soon after diagnosis predict short-term outcomes for patients with JIA. The JAQQ is a predictor of multiple outcomes. Time to diagnosis affects quality of life in the short term.

To determine the prevalence of and the risk factors for vertebral fractures in a cohort of children with chronic rheumatic diseases considered at risk for osteopenia.We conducted a cross-sectional study of patients with chronic rheumatic diseases at the Montreal Children's Hospital.Of the 90 study participants (22 boys, 68 girls), 10 boys and 7 girls (19%) were found to have vertebral fractures. These 17 children had a total of 50 fractures, an average of 2.9 per affected child. Fractures in the upper thoracic region (T5-8) accounted for 55%. Only 56% of all fractures were symptomatic. With multivariate regression, we identified male sex (P.01), body mass index z-score (P.02), and cumulative glucocorticoid dose (P.01) as significant predictors of the number of vertebral fractures.Our study examined the prevalence of vertebral fractures in a high-risk pediatric population. Nineteen percent of our cohort had vertebral fractures. Significant risk factors for the development of vertebral fractures include male sex and cumulative glucocorticoid dose. Better understanding of the extent of the problem in this population will allow us to further refine screening guidelines and treatment in these patients.

Objective. – To assess changes in growth parameters associated with the response to methotrexate (MTX) therapy in pre-pubertal children with juvenile idiopathic arthritis (JIA) and who had not been treated with steroids. Methods. – We enrolled 27 pre-pubertal children with JIA who had been treated with MTX but not with steroids. The children were considered to have responded to treatment if the number of joints with active disease decreased by at least 50% 1 year after treatment initiation. We compared growth parameters (height, growth rate, weight and body mass index (BMI)) in responders and non-responders. Results. – Twenty-one children (77.8%) responded to MTX therapy. The growth parameters were similar in the responders and non-responders before the onset of treatment. After 1 year, height ( P = 0.025), growth rate ( P = 0.03), weight ( P = 0.007) and BMI ( P = 0.05) increased significantly in the responder group, but not in the non-responder group. This increase was maintained for growth rate and weight after 2 and 3 years of treatment. After 1 year, height ( P = 0.023) and growth rate ( P = 0.0009) were significantly higher in the responders than in the non-responders, and these differences were still significant after 3 years ( P = 0.01 and P = 0.033, respectively). Conclusion. – In pre-pubertal children with JIA, a clinical response to MTX therapy is associated with a significant increase in growth parameters.

Resume Objectif. – Evaluation des modifications des parametres de la croissance saturoponderale en fonction de la reponse au traitement par le methotrexate (MTX) chez les enfants prepuberes atteints d'arthrite juvenile idiopathique (AJI) n'ayant pas recu de corticotherapie. Methodes. – Nous avons inclus dans cette etude 27 enfants impuberes atteints d'AJI ayant ete traites par MTX mais pas par une corticotherapie generale. Nous avons considere qu'il y avait une reponse au MTX si le nombre d'articulations inflammatoires avait diminue au moins de moitie apres un an de traitement. Nous avons compare les parametres de la croissance que sont la taille, la vitesse de croissance, le poids et l'indice de masse corporelle (IMC), chez les patients repondeurs et chez les non-repondeurs au MTX. Resultats. – Vingt et un enfants (77,8 %) ont repondu au MTX. Avant traitement, les parametres de la croissance etaient similaires dans le groupe des repondeurs et dans celui des non-repondeurs. Apres une annee de traitement, ces parametres avaient augmente significativement dans le groupe des repondeurs, mais pas dans celui des non-repondeurs : taille (p = 0,025), vitesse de croissance (p = 0,03), poids (p = 0,007) et IMC (p = 0,05). Cette augmentation s'est maintenue apres deux et trois ans de traitement pour la vitesse de croissance et le poids. Apres une annee de traitement, la taille (p = 0,023) et la vitesse de croissance (p = 0,0009) etaient significativement plus elevees chez les repondeurs en comparaison des non-repondeurs. Cette difference etait toujours significative apres trois ans de traitement (respectivement p = 0,01 et p = 0,033). Conclusion. – Chez les enfants prepuberes atteints d'AJI, une reponse clinique au MTX s'accompagne d'une augmentation significative des parametres de la croissance staturoponderale.

Summary Background Allogeneic haemopoietic stem-cell transplantation (HSCT) is the treatment of choice for many haemological malignancies and inherited disorders. When stem cells for transplantation come from a human leucocyte antigen matched unrelated donor, or from a partly mismatched related donor, exvivo T-cell depletion of the graft can prevent development of graft-versus-host disease, but lead in turn to a delay in immune reconstitution and a concordant increase in incidence of opportunistic infections and leukaemic relapses. We aimed to infuse T cells selectively depleted in allogeneic T cells that cause graft-versus-host disease using an ex-vivo procedure designed to eliminate alloactivated donor T cells, with an immunotoxin that reacts with a cell surface activation antigen, CD25. Methods We did a phase 1/2 study, in which 1–8 × 10 5 allodepleted T cells/kg were infused between days 15 and 47 into 15 paediatric patients who had acquired or congenital haemopoietic disorders and who received HSCT on day 0. Occurrence of graft-versus-host disease and time to immune reconstitution were assessed. No treatment for graft-versus-host disease was given. Findings Less than 1% residual anti-host alloreactivity was recorded in 12 of 16 procedures. Other immune responses were preserved by the allodepletion procedure in 12 cases. No cases of severe (greater than grade II) graft-versus-host disease arose. Evidence for early T-cell expansion was shown in three patients with continuing viral infections. Specific antiviral responses, such as strong cytolytic activity, were noted. Interpretation Our results show that ex-vivo selective depletion of T cells that cause graft-versus-host disease is efficient and feasible, even in haploidentical settings.

Objective To describe clinical outcomes of juvenile idiopathic arthritis (JIA) in a prospective inception cohort of children managed with contemporary treatments. Methods Children newly diagnosed with JIA at 16 Canadian paediatric rheumatology centres from 2005 to 2010 were included. Kaplan–Meier survival curves for each JIA category were used to estimate probability of ever attaining an active joint count of 0, inactive disease (no active joints, no extraarticular manifestations and a physician global assessment of disease activity 12 months after discontinuing treatment) and of receiving specific treatments. Results In a cohort of 1104 children, the probabilities of attaining an active joint count of 0 exceeded 78% within 2 years in all JIA categories. The probability of attaining inactive disease exceeded 70% within 2 years in all categories, except for RF-positive polyarthritis (48%). The probability of discontinuing treatment at least once was 67% within 5 years. The probability of attaining remission within 5 years was 46–57% across JIA categories except for polyarthritis (0% RF-positive, 14% RF-negative). Initial treatment included joint injections and non-steroidal anti-inflammatory drugs for oligoarthritis, disease-modifying antirheumatic drugs (DMARDs) for polyarthritis and systemic corticosteroids for systemic JIA. Conclusions Most children with JIA managed with contemporary treatments attain inactive disease within 2 years of diagnosis and many are able to discontinue treatment. The probability of attaining remission within 5 years of diagnosis is about 50%, except for children with polyarthritis.

Prognostic factors in juvenile arthritis are related to many variables that must be evaluated according to the different subtypes. The International League of Associations of Rheumatologists (ILAR) recently proposed six different categories referred to as the Durban criteria, under the eponym of juvenile idiopathic arthritis (JIA). The aim of this classification was to define homogeneous groups according to their clinical and biologic features. The prognostic factors were classified into the different categories of JIA. A poor outcome in the systemic form correlated with markers of disease activity, such as fever and polyarticular involvement, within the first 6 months. The risk of joint destruction in oligoarthritis correlated with the severity of arthritis within the first 2 years. Polyarthritis with positive rheumatoid factor is associated with marked disability in adulthood. In a group of psoriatic patients, the risk of developing sacroiliitis is higher in male and HLA-B27-positive patients. Patients with enthesitis-related arthritis with lower limb, knee, and tarsal involvement also are at greater risk of developing sacroiliitis. Chronic uveitis is a complication of JIA observed mainly in patients with oligoarthritis associated with positive antinuclear antibodies in serum. Secondary amyloidosis is observed mainly in children with systemic JIA. The long-term outcome must be discussed according to the various therapies. Corticosteroids contribute to growth retardation and osteoporosis, for which the use of human recombinant growth hormone and biphosphonates may be an option. Newer encouraging therapies such as anticytokines have been proposed for children with active disease. Autologous stem cell transplantation is being evaluated in some centers with promising results; however, it has a high rate of mortality. Further discussion regarding which patients should undergo autologous stem cell transplantation is needed, as is further discussion regarding the technical adaptations necessary.

A l'heure actuelle, l'absence de compatibilite HLA lors d'une greffe de cellules hematopoietiques souches (CHS) est responsable d'un taux d'echec important, en raison, entre autres, de l'immunodeficience prolongee qui favorise les rechutes et les infections. Pour pallier ce deficit prolonge, il serait theoriquement possible d'injecter apres la greffe des lymphocytes T du donneur mais le risque de provoquer une reaction du greffon contre l'hote lethale (GVHD) rend cette option irrealisable. La strategie que nous avons developpee consiste, avant d'injecter les lymphocytes T, a eliminer ceux d'entre eux qui sont alloreactifs a l'aide d'une immunotoxine specifique pour la chaine p55 du recepteur de l'IL-2, exprimee par les lymphocytes T actives dans une culture mixte lymphocytaire (CML). Treize patients ont ete inclus dans un protocole de phase I/II depuis septembre 1998. L'un d'entre eux a recu deux greffes. Ces patients dont la moyenne d'âge a l'inclusion est de 17 mois, sont atteints soit d'hemopathies malignes (LAL ou LAM), soit de deficits immunitaires, et ne disposent pas d'un donneur familial geno-identique. Les lymphocytes T allodepletes ont ete injectes entre 14 et 30 jours post-greffe, des la sortie d'aplasie, aux doses de 100 000 (n = 3), 400 000 (n = 7) et 600 000 lymphocytes T/kg (n = 4). La depletion des lymphocytes T alloreactifs a ete complete dans 12 manipulations sur 14 avec moins de 1 % de proliferation residuelle. Dans 2 cas, cette proliferation residuelle etait de 4 et 5 % (un patient dans le groupe 400 000 et l'autre dans le groupe 600 000 cellules). Au total, 4 patients ont developpe une GVH aigue (a) de grade I a II exclusivement, dont les deux patients pour lesquels la depletion etait incomplete. Aucune de ces GVHa n'a evolue en GVH chronique. Six patients sont decedes de maladies veino-occlusives (MVO) (n = 3), d'une meningoencephalite due a une infection par le virus varicella-zooster (VZV) deja presente avant la greffe (n = 1), d'une rechute de LAL (n =1) et d'une infection a Staphylocoque (n = 1). A l'heure actuelle, la survie est de 54 % pour un suivi moyen de 8 mois (3,5 a 22 mois). Du point de vue immunologique, sur il greffes evaluables, une moyenne de 63 jours a ete necessaire pour presenter 300 CD3/μl, 97 jours pour 200 CD4/μl et 90 jours pour detecter une reponse positive aux mitogenes. Trois patients ont presente une reponse proliferative positive en presence de la toxine tetanique avant d'etre vaccines. Cette analyse intermediaire suggere que 1) la depletion alloreactive ex vivo permet d'empecher efficacement le developpement de la GVH dans un contexte d'incompatibilite HLA majeur, 2) que les lymphocytes T reinjectes sont capables de survivre et de s'expandre.

Results Case 1 An 8 yo boy was referred to our clinic in March 2008 for 2 episodes of orbital myositis. The first episode occurred in November 2007 and involved the left eye. Investigations with a CT scan and an MRI revealed changes in the left lateral rectus muscle, felt to be consistent with a myositis. This spontaneously resolved over a few days. In January 2008, the child’s right eyelid became swollen and he had an associated diplopia. The MRI revealed a normal left rectus muscle but inflammation was observed in the right rectus muscle. Again, without treatment, the symptoms resolved. It was at that time that the patient was referred to Rheumatology. On review of systems, he was noted to have longstanding epigastric pain associated with meals. His physical examination was unremarkable. Blood tests revealed iron deficiency, microcytic anemia and an elevated ESR. He was referred to Gastroenterology. He underwent an endoscopy which confirmed the diagnosis of Crohn’s disease. There has been no recurrence of the orbital myositis since the Crohn’s disease has been in remission.

Methods Childhood-onset SLE (

Purpose To examine the remission rates and functional outcomes in an inception cohort of patients with juvenile idiopathic arthritis (JIA). Methods The Research in Arthritis in Canadian Children, emphasizing Outcomes (ReACCh-Out) cohort is a 16-centre inception cohort of patients with JIA enrolled within 1 year of diagnosis. All patients who completed 5 sixmonthly study visits from baseline to 24 months were included in this analysis. Disease activity and functional measures were collected at each visit. Criteria for disease remission status in this study were defined by Wallace et al (2006) modified by omission of ESR or CRP due to incomplete data. Inactive disease (ID) was defined as no active joints, physician global assessment 0, and no active extra-articular disease; clinical remission on medications (CRM) is ID for ≥ 6 months on medications; and clinical remission (CR) is ID for ≥ 12 months off medications. Health status was measured using the Juvenile Arthritis Quality of Life Questionnaire (JAQQ), and functional status using the Child Health Assessment Questionnaire (CHAQ). Results

To the Editor: Juvenile dermatomyositis (JDM) is an autoimmune vasculopathy involving primarily the proximal muscles and skin but can involve other organ systems, particularly the gastrointestinal (GI) tract1. In the presence of cutaneous vasculitic ulcerations, one needs to monitor for signs and symptoms suggestive of GI vasculopathy2, which can lead to bowel ischemia, necrosis, ulceration, and perforation1,2,3,4,5. The presence of gas in the bowel wall, also referred to as pneumatosis intestinalis (PI), is an ominous finding when it is due to a GI vasculopathy3. PI is a radiographic finding that is associated with both benign and life-threatening causes. The benign variant of PI has been described in relation to immunosuppressive therapy6 and to JDM itself7. We describe a child with JDM complicated by cutaneous ulcerations and benign PI. An 8-year-old girl, following a 1-month history of rash and fatigue, was diagnosed with JDM based on the presence of Gottron sign, heliotrope rash, symmetric proximal muscle weakness, elevated serum muscle enzymes [creatine kinase (CK) 533 U/l (normal 44–189); lactate dehydrogenase 442 U/l (normal 142–261); aldolase 9.3 U/l (normal 0–7.6)] and findings consistent with myositis on magnetic resonance imaging of the proximal hip and shoulder girdle muscles. Antinuclear and anti-Jo1 antibodies were … Address correspondence to Dr. Scuccimarri; E-mail: rosie.scuccimarri{at}muhc.mcgill.ca

Objective To determine early outcomes and early improvements in a prospective inception cohort of children with juvenile idiopathic arthritis (JIA) treated with current standard therapies. Methods Patients selected were enrolled in an inception cohort of JIA, the Research in Arthritis in Canadian Children Emphasizing Outcomes Study. The juvenile rheumatoid arthritis core criteria set measures were completed at enrollment and 6 months later. Frequencies of normal values for each of the core set measures and the American College of Rheumatology (ACR) Pediatric 30, 50, and 70 (Pedi 70) criteria response rates achieved at 6 months after enrollment were calculated for each JIA-onset subtype group. Results Among 354 patients in the study, the median interval between diagnosis and enrollment was 0.7 months. At 6 months after enrollment, median values of active joint counts were highest in patients with rheumatoid factor (RF)–positive polyarthritis (4) and RF-negative polyarthritis (2), but were 0 or 1 for other subtypes. Fifty percent or more of patients with oligoarthritis, systemic arthritis, enthesitis-related arthritis, and undifferentiated arthritis had no active joints, and the ACR Pedi 70 criteria response rate was 48% or more in those with oligoarthritis, RF-negative polyarthritis, and systemic arthritis. Conclusion With current management strategies in clinical practice, improvement in disease activity was noted in considerable proportions of patients in all of the JIA subtype groups, but low levels of disease activity persisted in many. We expect that these early outcomes will prove to be significant predictors of long-term outcomes.

We report three pediatric cases of primary hypothyroidism presenting with musculoskeletal complaints, elevated muscle enzymes and increased creatinine. Thyroid hormone replacement led to improvement in both the clinical features and laboratory abnormalities.

To determine methotrexate (MTX) use and the degree to which Canadian pediatric rheumatologists adhere to the American College of Rheumatology (ACR) guidelines on monitoring for MTX toxicity.A 20-item questionnaire was e-mailed to 37 pediatric rheumatologists in 17 centers in Canada. A total of 28 (75.7%) responded.The oral route (PO) of administration was preferred initially by 78.6% in most cases, but for more severe cases, this fell to 42.8%. Those who chose not to start PO used the subcutaneous route (SQ). When PO was initial treatment, a switch to SQ was undertaken because of dose escalation, lack of efficacy, or GI toxicity. An initial mean dose of 0.35-0.5 mg/kg/wk was prescribed by 51.8%. For 75%, the maximum dose was 1 mg/kg/wk (up to 25 mg). Complete blood count, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were determined by 100% at baseline and in followup; albumin and creatinine by 85.7% at baseline, but by only 71.4% and 67.8%, respectively, in followup. After a change in dose, 96.3% requested blood tests at least monthly; this was extended to every 6 to 8 weeks by 78.6% when the dose was stable. Side effects of recurrent nausea and/or vomiting were reported to occur frequently. No severe toxicity, and in particular no case of cirrhosis, was reported. Prophylactic folate supplementation was prescribed by almost all physicians.Most Canadian pediatric rheumatologists follow ACR guidelines to monitor for MTX toxicity in children with rheumatic diseases who were prescribed MTX. The variation in monitoring and response to toxicity raises the question whether specific pediatric guidelines should be developed.

Kaposi’s sarcoma (KS) is rare in childhood. It may be favored by acquired immune deficiencies, but the predisposing factors to KS in other children are unclear. KS has been reported in only two children and one adult with primary immunodeficiency. We report here a Tunisian child with a Wiskott-Aldrich syndrome who developed KS at the age of 14 months. This observation expands the spectrum of primary immunodeficiencies associated with KS in childhood.

Background/Purpose: Plain radiographs (x-rays) are useful in the evaluation of children with JIA. Bone erosions are one of the finding that can be seen on x-rays. However, they are most often reported in the polyarticular RF+ subtype of JIA and are rare in most other subtypes. Methods: Herein 3 patients with JIA are presented whose diagnoses were questioned after plain x-rays were obtained. MRI later revealed significant erosive disease in these patients. Results: Case 1: A 14 yo male presented with a monoarthritis of the left wrist. Initial x-rays were normal. His work-up was unremarkable. His inflammatory markers were normal. He was thus diagnosed with JIA–oligoarthritis. After 6 months in remission, after the use of an NSAID, he flared in the same joint. Repeat x-rays showed a radiolucent area with associated sclerosis in the scaphoid of unclear etiology. An MRI was thus requested. It revealed synovitis associated with erosive disease. Post gadolinium injection, a geode in the scaphoid bone with marked synovial enhancement visible within this erosion was detected. He underwent a joint injection which put him into remission. Repeat x-rays one year later, revealed unchanged findings likely corresponding to the non-healed erosion. Case 2: An 11 yo HLA B27 + male diagnosed with ERA with polyarthritis of the lower limbs and sacroiliac joints was treated with methotrexate and an NSAID. Investigations ruled out IBD and the arthritis was felt to be well controlled despite persistently elevated inflammatory markers of unclear etiology. He presented with a severe flare in his knees and ankles. X-rays revealed well-defined lytic lesions in the anterior aspect of the proximal tibial metaphysis just below the growth plate bilaterally. Given the concern of an infiltrative process, an MRI was obtained. Post gadolinium injection, a large erosion of the tibial plateau with marked synovial enhancement within this erosion was seen, as well as a knee synovitis. Etanercept was started. Case 3: An 8 yo male presented with a monoarthritis of the right wrist evolving for five months after an initial minor trauma. X-rays revealed advanced bone maturation of the right wrist as well as a sclerotic lesion of the hamate. Given the initial trauma, an MRI was obtained which demonstrated very extensive bone marrow edema, synovitis, tenosynovitis and a large erosion within the hamate. A diagnosis of JIA–oligoarthritis was made. He underwent a joint injection with good disease control. Conclusion: Large erosions are not typical for some JIA subtypes such as oligoarthritis and ERA. Findings on x-rays led the treating physicians to question the underlying diagnosis however, MRI revealed very aggressive synovitis of the wrist and knee in these patients. MRI was useful to demonstrate the presence of synovial enhancement within the eroded bone and helped rule out another diagnosis. Awareness of this type of aggressive arthritis is needed so that patients are not over-investigated and prompt treatment can be offered.

Results A 15 yo boy was referred to Rheumatology for left wrist swelling. His past medical history was unremarkable until 8 months prior when he began to have significant pain and progressive swelling of the left wrist. He was initially diagnosed with a fracture of the scaphoid bone for which he was casted for 2 months. After the cast was removed, the patient noticed that his symptoms persisted. The pain worsened and started to wake him from sleep. After a few visits to the emergency room and another cast, he was referred to Rheumatology. The physical examination was consistent with a significant arthritis of the left wrist. The wrist was diffusely swollen, warm, very painful to touch and to movement, and the range of motion was significantly limited. No other joints were involved. An X-ray of the left wrist revealed marked joint space narrowing of the carpal bones with significant osteopenia but no other abnormalities. A diagnosis of Juvenile Idiopathic Arthritis (JIA) was made. NSAIDs were started and a joint injection was performed. No change in symptoms or physical examination was observed. The patient was taking codeine regularly for pain relief. Therefore 3 months after, a 2 joint injection was performed, with no effect. Repeat X-rays and an MRI were requested to better delineate the inflammatory process before starting methotrexate. X-rays revealed that a round sclerotic lesion had become evident in the left scaphoid bone, which was confirmed by the MRI. This was consistent with an osteoid osteoma. The MRI also revealed marked diffuse synovitis in the left wrist associated with erosive disease and joint space narrowing. The patient was referred for radiofrequency ablation. After a few months, the inflammatory process of the left wrist improved significantly with only minimal residual swelling. The patient is now off pain medication and is only taking an NSAID intermittently. Repeat X-rays demonstrate no further evidence of the osteoid osteoma but the arthritic changes of the carpal bones persist.