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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.

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.

Context Osteoporotic fractures are an important cause of morbidity in children with glucocorticoid-treated rheumatic disorders. Objective This work aims to evaluate the incidence and predictors of osteoporotic fractures and potential for recovery over six years following glucocorticoid (GC) initiation in children with rheumatic disorders. Methods Children with GC-treated rheumatic disorders were evaluated through a prospective inception cohort study led by the Canadian STeroid-induced Osteoporosis in the Pediatric Population (STOPP) Consortium. Clinical outcomes included lumbar spine bone mineral density (LS BMD), vertebral fractures (VF), non-VF, and vertebral body reshaping. Results A total of 136 children with GC-treated rheumatic disorders were enrolled (mean age 9.9 years, SD 4.4). The 6-year cumulative fracture incidence was 16.3% for VF, and 10.1% for non-VF. GC exposure was highest in the first 6 months, and 24 of 38 VF (63%) occurred in the first 2 years. Following VF, 16 of 19 children (84%) had complete vertebral body reshaping. Increases in disease activity and body mass index z scores in the first year and declines in LS BMD z scores in the first 6 months predicted incident VF over the 6 years, while higher average daily GC doses predicted both incident VF and non-VF. LS BMD z scores were lowest at 6 months (mean –0.9, SD 1.2) and remained low by 6 years even when adjusted for height z scores (–0.6, SD 0.9). Conclusion VF occurred early and were more common than non-VF in children with GC-treated rheumatic disorders. Eighty-four percent of children with VF underwent complete vertebral body reshaping, whereas vertebral deformity persisted in the remainder of children. On average, LS BMD z scores remained low at 6 years, consistent with incomplete recovery.

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.

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.

Objective Adrenal suppression (AS), a glucocorticoid (GC) side effect with potentially significant morbidity, is poorly understood. The purpose of our study was to determine frequency, duration, and predictors of AS following a gradual taper of GC in children with rheumatic conditions. Methods A prospective, observational cohort study was conducted. All patients ages ≤16 years ready to discontinue GC after >4 weeks of therapy were included. Morning cortisol was tested 4 weeks after GC taper to physiologic doses and then repeatedly until normalization. GCs were subsequently discontinued and a low-dose adrenocorticotropic hormone stimulation test was performed. Results The study was completed by 31 of 39 patients. The median age was 12.9 years and median duration of GC therapy was 39.6 weeks. Seventeen patients (54.8%) had AS. Of the patients with AS, 50% showed recovery by 7 months. Two patients had persistent AS at 12 months and 1 patient at 2 years. A higher maximum GC dose was a significant predictor for the development of AS. Conclusion More than 50% of our patients had AS after GC discontinuation, despite a gradual taper of GC. Stress steroids should be considered in children treated with long-term GC, even after steroid discontinuation, to prevent possible adrenal crisis.

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.We studied an inception cohort of children with juvenile idiopathic arthritis (JIA) to (1) identify distinct disease courses based on changes over 5 years in 5 variables prioritized by patients, parents, and clinicians; and (2) estimate the probability of a severe disease course for each child at diagnosis.Methods.Assessments of quality of life, pain, medication requirements, patient-reported side effects, and active joint counts were scheduled at 0, 6, 12, 18, 24, 36, 48, and 60 months. Patients who attended at least 6 assessments were included. Multivariable cluster analysis, r2, and silhouette statistics were used to identify distinct disease courses. One hundred candidate prediction models were developed in random samples of 75% of the cohort; their reliability and accuracy were tested in the 25% not used in their development.Results.Four distinct courses were identified in 609 subjects. They differed in prioritized variables, disability scores, and probabilities of attaining inactive disease and remission. We named them Mild (43.8% of children), Moderate (35.6%), Severe Controlled (9%), and Severe Persisting (11.5%). A logistic regression model using JIA category, active joint count, and pattern of joint involvement at enrollment best predicted a severe disease course (Controlled + Persisting, c-index = 0.87); 91% of children in the highest decile of risk actually experienced a severe disease course, compared to 5% of those in the lowest decile.Conclusion.Children in this JIA cohort followed 1 of 4 disease courses and the probability of a severe disease course could be estimated with information available at diagnosis.

Physical activity is promoted for optimal health but may carry risks for children who require medically necessary activity restrictions. The sensitivity, specificity, and reliability of the Get Active Questionnaire (GAQ) for identifying children needing special considerations during physical activity was evaluated among parents of 207 children aged 3 to 14 years (97 (47%) female, mean age of 8.4 ± 3.7 years). GAQ responses were compared with reports obtained directly from the treating physician (n = 192/207) and information in the medical chart (clinic notes/physician letter, n = 111/207). Parent GAQ responses (either “No to all questions” or “Yes to 1 or more questions”) agreed with physician (κ = 0.16, p = 0.003) and medical record (κ = 0.15, p = 0.003) reports regarding the need for special consideration during physical activity (Yes/No). Sensitivity was 71% (20/28) and specificity was 59% (96/164), with few false-negative responses. The GAQ was most effective for rheumatology and cardiology patients. False positives were 29% to 46%, except among chronic pain (80%) and rehabilitation (75%) patients. Test–retest reliability was moderate (Cronbach’s α = 0.70) among 57 parents who repeated the GAQ 1 week later. The GAQ effectively identified children not requiring physical activity restrictions and those with medical conditions similar to those of concern among adults. Additional questions from a qualified exercise professional, as recommended for a “Yes” response on the GAQ, should reduce the false-positive burden. Indicating the timeframe of reference for each question and including an option to describe other special considerations (e.g., medication, supervision) are recommended.

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 describe a case of pediatric central nervous system (CNS) venulitis. Background Primary angiitis of the CNS is a rare but increasingly well-recognized cause of morbidity in children. It primarily involves the arteries and arterioles of the CNS, with only 1 published case of a pediatric patient found to have isolated CNS venulitis on brain biopsy. Case Report A 17-year-old female with a 4-year history of migraines presented with increasingly frequent migraines and right-sided hemiplegia. Infectious, hematologic, and rheumatologic work-ups were negative. Brain magnetic resonance imaging showed multiple rim-enhancing lesions consistent with calcifications affecting the deep left white matter. On brain biopsy, there was evidence of an inflammatory process involving small veins and venules. The patient displayed clinical improvement with a course of high-dose steroids and 6 monthly cyclophosphamide infusions followed by maintenance therapy with mycophenolate mofetil. Discussion We describe a case of pediatric CNS venulitis presenting with migraine.

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.

Background: Despite the wealth of clinical research carried out in children with juvenile idiopathic arthritis (JIA), little is known about the emotional experiences of their parents. This article describes the predominant emotional experiences reported by parents of children with JIA in two Canadian cities. Methods: Research participants included 15 experienced parents and 8 novice parents (

Objective To assess whether children with juvenile idiopathic arthritis (JIA) in clinical remission show pathologic findings on either gray-scale or power Doppler ultrasound of their joints. Methods Children with JIA were eligible if they were in clinical remission for at least 3 months, as defined by the absence of clinically active joints and serologic markers of inflammation. Gray-scale as well as power Doppler ultrasonography of the wrist, knee, and ankle were carried out on previously affected joints and unaffected contralateral joints. Images were read by 2 independent readers. Findings were categorized as 1) structural abnormalities in the case of synovial thickening or increased joint fluid on gray-scale ultrasound or 2) power Doppler positive in the case of an abnormal power Doppler signal. Results The study cohort consisted of 28 patients. Eight of 14 patients with previous wrist involvement had pathologic gray-scale findings, and 3 of these 14 patients also had pathologic Doppler findings in the wrist. None of the 20 patients with past knee involvement had pathologic gray-scale or Doppler findings in the knee. Six of 15 patients with previous ankle involvement had pathologic gray-scale findings and 1 of the 15 patients had pathologic Doppler findings in the tibiotalar joint. Conclusion This study demonstrates that some patients who meet clinical criteria for remission continue to show ongoing pathology on joint ultrasound, which may be suggestive of persistent inflammation.

Purpose: To report a case of atypical Kikuchi-Fujimoto disease (KFD) that illustrates several overlapping features with systemic lupus erythematosus (SLE). Methods: A case is reported followed by a review of the current literature. Case report: A 16-year-old boy with an unusual manifestation of Kikuchi-Fujimoto disease (KFD) is described. The patient presented with fever, weight loss and severe abdominal pain, due to extensive necrotizing retroperitoneal and mesenteric lymphadenopathy. During the course of his illness, he developed several symptoms suggestive of systemic lupus erythematosus (SLE): a pericardial effusion, cotton wool spots on the retina and antibodies against nuclear antigens (ANA), Smith (Sm) and ribonucleoprotein (RNP) antigens. However, no additional features of SLE were found. The patient subsequently fully recovered within two months, without initiation of immunosuppressive therapy. His autoantibodies became negative five months after initial presentation and he remains well at his 23 month follow up visit. Discussion: We hypothesize that the autoantibodies developed by our patient were secondary to self-antigen induced autoimmunity related to his extensive tissue necrosis. Despite initially having clinical features suggestive of SLE, our patient’s full and spontaneous recovery strongly supports the diagnosis of KFD. This illustrates the need for careful diagnosis, in order to avoid unnecessary and potentially toxic treatment with immunosuppressive agents.

Vertebral fractures are an important yet underrecognized manifestation of osteoporosis in children with chronic, glucocorticoid-treated illnesses. Our goal was to determine the incidence and clinical predictors of vertebral fractures in the 3 years following glucocorticoid initiation among pediatric patients with rheumatic disorders. Incident vertebral fractures were evaluated according to the Genant semiquantitative method on lateral radiographs at baseline and then annually in the 3 years following glucocorticoid initiation. Extended Cox models were used to assess the association between vertebral fractures and clinical risk predictors. A total of 134 children with rheumatic disorders were enrolled in the study (mean ± standard deviation (SD) age 9.9 ± 4.4 years; 65% girls). The unadjusted vertebral fracture incidence rate was 4.4 per 100 person-years, with a 3-year incidence proportion of 12.4%. The highest annual incidence occurred in the first year (6.0%; 95% confidence interval (CI) 2.9% to 11.7%). Almost one-half of the patients with fractures were asymptomatic. Every 0.5 mg/kg increase in average daily glucocorticoid (prednisone equivalents) dose was associated with a twofold increased fracture risk (hazard ratio (HR) 2.0; 95% CI 1.1 to 3.5). Other predictors of increased vertebral fracture risk included: (1) increases in disease severity scores between baseline and 12 months; (2) increases in body mass index Z-scores in the first 6 months of each 12-month period preceding the annual fracture assessment; and (3) decreases in lumbar spine bone mineral density Z-scores in the first 6 months of glucocorticoid therapy. As such, we observed that a clinically significant number of children with rheumatic disorders developed incident vertebral fractures in the 3 years following glucocorticoid initiation. Almost one-half of the children were asymptomatic and thereby would have been undiagnosed in the absence of radiographic monitoring. In addition, discrete clinical predictors of incident vertebral fractures were evident early in the course of glucocorticoid therapy.

BACKGROUND: Pediatric Musculoskeletal (pMSK) complaints are common and lead to important diagnostic considerations. However, international studies suggest that pediatric health providers (residents and consultants) are not confident in their pMSK assessments. At present, little is known about the confidence of Canadian pediatric residents in performing MSK examinations. OBJECTIVES: Our study evaluates the confidence of Canadian pediatric residents in performing pMSK examinations. In a subgroup of residents, we assessed changes in confidence after targeted training. DESIGN/METHODS: All pediatric residents enrolled in an accredited Canadian pediatric residency during the 2015-2016 academic year were invited to participate in an anonymous nationwide questionnaire. Survey respondents rated their confidence in performing pMSK examinations alone and in comparison to other body systems using a 10-point Likert scale. Pediatric residents enrolled in two centers participated in a one-day standardized pMSK examination workshop to learn the pediatric Gait, Arms, Legs, and Spine exam, a validated screening tool to facilitate pediatric joint examination; focused regional joint examinations were also reviewed. A follow-up confidence questionnaire was distributed immediately and six months’ after the intervention. RESULTS: 143 pediatric residents from 14 Canadian residency programs responded to the nationwide survey. Of the respondents, 56% (n=80) were previously taught the pMSK examination yet only 14% (n=20) reported routinely examining a child’s musculoskeletal system as part of a complete physical examination. The vast majority of respondents were “somewhat confident” with their pMSK examination, with an average confidence level of 4.6 (95%CI 4.3-4.9; 1=No confidence, 10=Very confident). Confidence was lower in comparison to cardiovascular, respiratory, and abdominal exams, but higher in comparison to peripheral nervous system and ophthalmologic examinations. In our subgroup analyses (n=50), we found an average increase in confidence by 2.1 points immediately after the intervention, from an initial confidence level of 4.9 (95% CI 4.5-5.4) to 7.1 (95% CI 6.6-7.5). This increase was sustained with a mean confidence rating of 6.9 (95% CI 6.1-7.7) six months post-workshop. The most frequently reported barriers to musculoskeletal examination confidence were limited practice (n=34,68%) and limited training opportunities (n=19,38%). CONCLUSION: Few Canadian pediatric trainees perform a pMSK examination as part of a complete examination, and self-rated confidence in pMSK examination was evaluated as “average” by the majority. We demonstrate that a standardized educational intervention can lead to increased confidence in performing pMSK examinations, but a decline in confidence is observed with time and without consistent practice.

Objective.To assess which clinical features are most important for patients, parents, and clinicians in the course of juvenile idiopathic arthritis (JIA).Methods.Forty-nine people participated in 6 audience-specific focus group discussions and 112 reciprocal interviews in 3 Canadian cities. Participants included youth with JIA, experienced English- and French-speaking parents, novice parents (< 6 mos since diagnosis), pediatric rheumatologists, and allied health professionals. Participants discussed the importance of 34 JIA clinical features extracted from medical literature. Transcripts and interview reports underwent qualitative analysis to establish relative priorities for each group.Results.Most study participants considered medication requirements, medication side effects, pain, participant-defined quality of life, and active joints as high priority clinical features of JIA. Active joint count was the only American College of Rheumatology core variable accorded high or medium priority by all groups. Rheumatologists and allied health professionals considered physician global assessment as high priority, but it had very low priority for patients and parents. The parent global assessment was considered high priority by clinicians, medium to high by parents, and low by patients. Child Health Assessment Questionnaire scores were considered low priority by patients and parents, and moderate or high by clinicians. The number of joints with limited motion was given low to very low priority by all groups. Parents gave high priority to arthritis flares.Conclusion.If our findings are confirmed, medication requirements, medication side effects, pain, participant-defined quality of life, and active joint counts should figure prominently in describing the course of JIA.

Objective To examine the temporal and dose-related effects of glucocorticoids (GCs) on body mass index (BMI) in children with rheumatic diseases. Methods Children initiating GCs for a rheumatic disease (n = 130) were assessed every 3 months for 18 months. BMI, weight, and height Z score trajectories were described according to GC starting dosage in prednisone equivalents: high (≥1.0 mg/kg/day), low (

Corticosteroid related changes in body mass index in children and adolescents with rheumatic diseases Natalie Shiff, Rollin Brant, David A Cabral, Jaime Guzman, Peter B Dent, Janet E Ellsworth, Kristin M Houghton, Adam Huber, Roman Jurencak, Bianca A Lang, Maggie Larche, Claire MA LeBlanc, Paivi M Miettunen, Kiem G Oen, Johannes Roth, Claire Saint-Cyr, Rosie Scuccimarri, Leanne M Ward, Canadian STOPP Consortium

Objective. To determine the frequency of incident vertebral fractures (IVF) 12 months after glucocorticoid (GC) initiation in children with rheumatic diseases and to identify children at higher risk. Methods. Children with rheumatic diseases initiating GC were enrolled in a prospective observational study. Annual spine radiographs were evaluated using the Genant semiquantitative method. Spine areal bone mineral density (aBMD) was measured every 6 months. Clinical features, including cumulative GC dose, back pain, disease and physical activity, calcium and vitamin D intake, and spine aBMD Z scores, were analyzed for association with IVF. Results. Seven (6%) of 118 children (95% confidence interval 2.9-11.7%) had IVF. Their diagnoses were: juvenile dermatomyositis (n = 2), systemic lupus erythematosus (n = 3), systemic vasculitis (n = 1), and mixed connective tissue disease (n = 1). One child was omitted from the analyses after 4 months because of osteoporosis treatment for symptomatic IVF. Children with IVF received on average 50% more GC than those without (P = 0.030), had a greater increase in body mass index (BMI) at 6 months (P = 0.010), and had greater decrements in spine aBMD Z scores in the first 6 months (P = 0.048). Four (67%) of 6 children with IVF and data to 12 months had spine aBMD Z scores less than-2.0 at 12 months compared to 16% of children without IVF (P = 0.011). Conclusion. The incidence of VF 12 months following GC initiation was 6%; most children were asymptomatic. Children with IVF received more GC, had greater increases in BMI, and had greater declines in spine aBMD Z scores in the first 6 months. © 2012, American College of Rheumatology.

Background/Purpose: To determine the incidence of vertebral fracture (VF) in the three years following glucocorticoid (GC) initiation, and the effect of GC on the risk of incident VF in children with rheumatic disorders (RD). Methods: Children with RD were enrolled within 30 days of GC initiation and followed for 3 years, with VF assessed at baseline and then annually using the Genant method on lateral spine radiographs. An incident VF was defined as a new fracture in a previously normal vertebral body or worsening of an existing VF. The annual and the 3 year cumulative incidences were calculated as the number of new cases divided by the number of subjects who completed VF assessment at the specified time periods. Six different time-dependent GC exposure measures were constructed: cumulative dose, average daily dose, duration on GC therapy, dose intensity (cumulative dose divided by duration on GC therapy) over 3 years, recent average daily dose and duration on GC therapy over the preceding 12 months. Extended Cox's models were used with alternative time-dependent variables, adjusting for factors at baseline including age, gender, body mass index, vitamin D and calcium supplementation, disease activity, bone mineral density, physical activity, and presence of prevalent VF. Results: 136 enrolled children (mean ± SD age 9.9 ± 4.4 years, 65% girls) held the following diagnoses: 22% juvenile dermatomyositis (JDM), 21% non-systemic juvenile idiopathic arthritis (JIA), 19% systemic lupus erythematosus (SLE), 18% systemic JIA, 12% systemic vasculitis, and 9% other RD. 9 children had VF at baseline (3 JDM, 2 systemic JIA, 2 SLE, 1 systemic vasculitis, 1 localized scleroderma), with an estimated prevalence of 6.6% (95% confidence interval (CI) 2.4–10.8%). 18 incident VF were identified in 15 children during the 3 years following GC initiation (6 JDM, 4 SLE, 2 systemic vasculitis, 2 systemic JIA, and 1 non-systemic JIA). The 3-year cumulative VF incidence was 13.0%, at a rate of 4.9 per 100 person-years. Of the 18 incident VF events, 7 occurred during the first year at an annual incidence of 6.0% (95% CI 1.7–10.3%); 6 VF occurred during the second year (annual incidence 5.6%; 95% CI 1.2–9.9%); 5 VF occurred during the third year (annual incidence 4.3%; 95% CI 1.0–8.1%). 64% of patients had mild incident VF as the worst grade, 36% had moderate fractures, and none had severe fractures. Of those with incident fractures, 21% had no complaints of back pain in the preceding 12 months. Multivariable models showed that every 100 mg/kg increase in cumulative GC dose was associated with a 30% increased incident VF risk (hazard ratio (HR) = 1.3, 95% CI 1.1, 1.6). Every 0.5mg/kg increase in average daily dose over the 3 year period was associated with a 4.2 fold increased VF risk (HR = 4.2, 95% CI 2.3, 7.7), and every 0.5 mg/kg increase in daily dose during the preceding 12 months was associated with a 2.7 fold increased incident VF risk (HR =2.7, 95% CI 1.3, 5.2). Conclusion: We have shown that 13.0% of children with RD sustained VF within three years followingGC initiation, of which 36% had moderate fractures. Cumulative dose, average daily GC dose, and recent average daily GC dose were associated with a significantly increased VF risk. Funded by CIHR FRN 64285

Objective.(1) To evaluate the spectrum of serum autoantibodies in pediatric-onset systemic lupus erythematosus (pSLE) with a focus on ethnic differences; (2) using cluster analysis, to identify patients with similar autoantibody patterns and to determine their clinical associations.Methods.A single-center cohort study of all patients with newly diagnosed pSLE seen over an 8-year period was performed. Ethnicity, clinical, and serological data were prospectively collected from 156/169 patients (92%). The frequencies of 10 selected autoantibodies among ethnic groups were compared. Cluster analysis identified groups of patients with similar autoantibody profiles. Associations of these groups with clinical and laboratory features of pSLE were examined.Results.Among our 5 ethnic groups, there were differences only in the prevalence of anti-U1RNP and anti-Sm antibodies, which occurred more frequently in non-Caucasian patients (p < 0.0001, p < 0.01, respectively). Cluster analysis revealed 3 autoantibody clusters. Cluster 1 consisted of anti-dsDNA antibodies. Cluster 2 consisted of anti-dsDNA, antichromatin, antiribosomal P, anti-U1RNP, anti-Sm, anti-Ro and anti-La autoantibody. Cluster 3 consisted of anti-dsDNA, anti-RNP, and anti-Sm autoantibody. The highest proportion of Caucasians was in cluster 1 (p < 0.05), which was characterized by a mild disease with infrequent major organ involvement compared to cluster 2, which had the highest frequency of nephritis, renal failure, serositis, and hemolytic anemia, or cluster 3, which was characterized by frequent neuropsychiatric disease and nephritis.Conclusion.We observed ethnic differences in autoantibody profiles in pSLE. Autoantibodies tended to cluster together and these clusters were associated with different clinical courses.

Objectives To define distinct disease course groups among children with JIA based on observed changes in quality of life, pain, medication requirements, medication side-effects and active joint counts during the first 5 years of the disease. These variables were prioritized by patients, parents and clinicians in a previous study. Methods We used data from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. We included 618 children newly diagnosed with JIA between 2005 and 2010 with information for at least 6 study visits within the first 5 years after diagnosis. Health-related quality of life and pain were measured with validated 10 cm visual analogue scales. Each current medication was given a weight and weights were added to obtain a medication requirements score. Medication side effects were reported using the Juvenile Arthritis Quality of Life Questionnaire and were weighted according to how frequently they were experienced by the child to obtain a side-effects score. Active joint counts (AJC) were reported by the attending pediatric rheumatologist. We grouped patients by course using multivariable cluster analysis and K-means clustering. Silhouette coefficients, R-Square statistics and clinical judgment were used to select the ideal number of clusters. The frequency of each disease course was described by JIA category. Results Four clusters provided the best discrimination: 1) Mild (33.7% of children)-almost normal quality of life throughout the disease course with initial mild pain and low AJC requiring minimal treatment, followed by normalization; 2) Moderate (43.0%)-moderate initial impact on quality of life and mild to moderate pain and AJC, followed by normalization; 3) Severe Controlled (11.6%)-moderate initial impact on quality of life and moderate pain levels with high AJC requiring aggressive treatment, followed by normalization; 4) Severe Persisting (11.6%)-persisting mayor impact on quality of life and moderate pain with moderate decreasing AJC, but ongoing treatment needs and side-effects. Children with oligoarthritis most often followed a Moderate course. Almost half the children with RF negative polyarthritis, systemic and psoriatic JIA followed a Mild course. Children with RF positive polyarthritis most often followed a Severe Controlled course. The Severe Persisting course was observed in all JIA categories but it was infrequent in systemic JIA and oligoarthritis. Conclusions Using patient-relevant variables the course of JIA can be described by four disease course groups with two of them reflecting a severe disease course, one that responded to treatment despite severe initial presentation and one with persisting impact on quality of life and pain despite moderate decreasing AJC. Disclosure of Interest None declared

Background/Purpose: During a recent study we conducted to identify patients, parents, and clinicians' priorities in describing the course of juvenile idiopathic arthritis (JIA), parents expressed intense emotions related to the disease and its management even a decade after their children's diagnosis. Here we describe the predominant emotional experiences reported by parents and how they relate to different phases of the disease manifestation, treatments, and interactions with peers and healthcare providers. Methods: We analyzed focus group transcripts and reciprocal interview answers involving 9 experienced English-speaking parents, 5 experienced French-speaking parents and 8 novice parents (between 2 and 6 months since diagnosis). Their children were 2 to 16 years of age and had a variety of JIA subtypes and disease severity. Qualitative analysis included review of audio recordings to enrich transcripts (based on pauses, noises, and other non-verbal cues), coding of emotional experiences by two investigators using a list of 69 emotion labels, coding verification by two other investigators, and analytical discussion and synthesis by our interdisciplinary team (to agree on what emotions were predominant at different stages of the disease, who or what were those emotions directed at, and how disease characteristics or parent background shaped them). Results: The time between onset and diagnosis was described by parents as a period of mounting anxiety, confusion and frustration with healthcare providers before a firm diagnosis was reached. The time shortly after diagnosis was described as a time of shock, disbelief, and fear during which parents often used denial as a coping mechanism; combined with feeling overwhelmed by a sea of information about the disease. Later in the disease course, at times of disease quiescence the predominant emotions were annoyance and worry about treatment side effects, and the fear of unpredictable flares. At times of increasing or ongoing symptoms the predominant emotions were admiration for the way their children coped with the disease, and frustration with peers and teachers that could not appreciate justification for the changes in the child's willingness to engage in physical activity and school work. This was also a time of frustration with increasing treatment and side effects. Throughout the disease parents felt a sense of powerlessness and that the disease was a “time-consuming roller coaster.” The subtype of arthritis did not affect the range of emotions experienced, but influenced the proportion of time in quiescence or ongoing symptoms, and the intensity of treatments and side-effects. Conclusion: The emotional experiences of parents of children with JIA can be conceptualized, as a parent put it, as roller coaster ride made of intensely emotional ups and downs. This is similar to the emotional turmoil faced by parents of children with other chronic illnesses, but JIA usually does not confront them with the chronic grief produced by progressive degenerative illnesses or the threat of imminent death.

Background/Purpose: Procedural pain may have long-term negative effects on children. The aim of this study was to evaluate the amount of pain associated with weekly subcutaneous injections of methotrexate. Methods: A prospective observational cohort study was conducted from June 2013 through August 2013. All patients with appointments in rheumatology clinic during this period were screened for eligibility. Patients between the ages of 4\N17 years who were currently receiving weekly subcutaneous methotrexate injections for at least 4 weeks were invited to participate in the study. Patients and families underwent a focused interview, conducted by one interviewer, exploring their experience with methotrexate injections. Thereafter, they were trained to use the Faces Pain Scale\NRevised (FPS-R) tool to be able rate pain associated with future methotrexate injections. Associations between pain scores and age, duration of therapy, and presence of side effects were tested using simple and multiple linear regression. Results: 41 out of 42 eligible patients consented to the study. Four patients were switched from subcutaneous to oral route of methotrexate at the time of study enrolment. Of the remaining 37 patients, 29 (78%) returned the completed pain scales. The mean age was 11.2 years (SD = 3.9 years) and 68% were female. Most of these patients were diagnosed with JIA (73%). Mean duration of therapy with subcutaneous injections of methotrexate was 2.5 years (SD = 2.1 yrs) and the dosing range was 0.3–1 mg/kg/week (maximum 25 mg/week). The upper arm was the preferred injection site in 71% of patients. Median amount of pain in the subset of 29 patients was 2/10; 18 (62%) patients reported mild pain (FPS-R score 0–2), 9 (31%) reported moderate pain (FPS-R score 4–6) and 2 participants reported severe pain (FPS-R 8–10). In univariate testing, higher intensity of pain was associated with presence of side effects (p = 0.004), but not duration of therapy (p = 0.20) or age (p = 0.24). Results were largely unchanged in multiple linear regression. Injection pain was successfully alleviated by ice in 10/14 patients (71%), comfort positions in 14/21 patients (67%), rewards in 13/20 patients (65%), reassurance in 11/22 patients (50%), distraction in 10/21 patients (48%), and analgesics in 4/9 patients (44%). Conclusion: While the average amount of pain associated with subcutaneous injections of methotrexate is mild, patients who suffer from methotrexate associated side-effects report significantly higher levels of pain. Patients and families reported using various effective strategies to alleviate injection associated pain.

Incident vertebral fractures 12 months following glucocorticoid initiation in children with rheumatic disorders Bianca A Lang, Celia Rodd, Timothy Ramsay, David A Cabral, Peter B Dent, Janet E Ellsworth, Kristin M Houghton, Adam Huber, Roman Jurencak, Maggie Larche, Claire MA LeBlanc, Brian Lentle, MaryAnn Matzinger, Paivi M Miettunen, Kiem Oen, Johannes Roth, Claire Saint-Cyr, Rosie Scuccimarri, Nazih Shenouda, Leanne M Ward, Canadian STOPP Consortium

The aim of our work is to assess musculoskeletal examination skills of pediatric residents. A self-assessment questionnaire with five-point Likert scale (1=strongly disagree, 5=strongly agree) was used. After completion of questionnaires, the residents were taught proper joint examination techniques. Thereafter, the residents were asked to judge whether they had rated their skills accurately. The session was attended by 25/41 residents (61%). Overall, their reported examination skills were poor with a mean score of 3.0 for PGY1, 2.1 for PGY2, 2.2 for PGY3 and 3.0 for PGY4. After being taught the proper joint examinations techniques, 22% of residents reported they initially overestimated their skills and 5% underestimated their skills. The residents felt most comfortable with the knee exam, least comfortable with the finger and wrist joint exam. Most pediatric residents did not feel they can perform a focused musculoskeletal exam.