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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 assess long-term outcomes of children with JIA diagnosed in the biologic era. Methods Chart review of patients prospectively enrolled in the Research in Arthritis in Canadian Children Emphasizing Outcomes inception cohort at two Canadian centres. Inactive disease and remission were defined according to Wallace criteria. Results We included 247 of 254 (97%) eligible patients diagnosed 2005–10. At the last follow-up visit at a median age of 16.9 years, 47% were in remission off medications, 25% in remission on medications and 27% had active disease; 51% were on at least one anti-rheumatic medication (22% on biologics). Patients with systemic JIA had the highest frequency of remission off medications (70%) and patients with RF-positive polyarthritis had the lowest (18%) (P Conclusion Relative to historical cohorts, this study suggests a reduction in JIA permanent damage, a more favourable prognosis for systemic JIA and a lower progression to oligoarthritis extended category. However, in an era of biologic therapy, one in four patients with JIA still enter adulthood with active disease and one in two still on treatment.

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.

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 Kawasaki disease (KD) is an acute childhood vasculitis that may result in coronary aneurysms. Treatment of KD with a single infusion of 2 gm/kg intravenous immunoglobulin (IVIG) is well established, but acetylsalicylic acid (ASA) dose remains controversial. Our primary objective was to determine the difference in the incidence of IVIG resistance between 2 ASA doses. Our secondary objective was to compare the duration of hospital stay and the incidence of coronary artery aneurysm. Methods We reviewed charts of patients with KD from 2 Canadian centers to assess the impact of ASA dose on IVIG resistance (operationally defined as administration of a second dose of IVIG). Both centers used standard IVIG dosing, but center 1 used low-dose ASA from diagnosis (3-5 mg/kg/day) while center 2 used initial high-dose ASA (80-100 mg/kg/day). Results There were no significant differences in baseline characteristics between the 2 centers. Retreatment with a second dose of IVIG was required in 28 of 122 patients (23%) treated with low-dose ASA, and in 11 of 127 patients (8.7%) treated with high-dose ASA in center 1 and center 2, respectively (P = 0.003). After adjusting for confounders, low-dose ASA was associated with higher odds of IVIG resistance (OR 3.2 [95% confidence interval 1.1, 9.1]). The mean duration of hospital stay was 4.1 and 4.7 days, respectively (P = 0.37). Coronary artery aneurysms were seen in 2 of 117 and 6 of 125 patients from centers 1 and 2, respectively (P = 0.28). Conclusion Low-dose ASA was associated with 3-times higher odds of IVIG retreatment compared to high-dose ASA, with no significant difference in duration of hospital stay or incidence of coronary artery aneurysms.

The most important complication of neonatal lupus erythematosus (NLE) is congenital heart block (CHB) Infants with NLE are born to mothers who have antibodies against Ro (SSA) and/or La (SSB) antigens, although the mother may be completely asymptomatic Most children with CHB will eventually require a permanent pacemaker during childhood The risk of having a second baby with congenital heart block is within the range of 15–20%

Any child under the age of 16 years who has persistent arthritis for at least 6 weeks, satisfies criteria for juvenile idiopathic arthritis (JIA) Involvement of 4 or more than 4 joints in the first 6 months after the appearance of symptoms indicates polyarthritic JIA, otherwise it would be oligoarticular JIA Children with oligoarticular JIA, and positive ANA detected by a fluorescence assay are particularly susceptible to chronic asymptomatic anterior uveitis Positive rheumatoid factor in children with polyartheritic JIA is associated with severe erosive arthritis and with progression to adult rheumatoid arthritis

Vasculitis of the coronary arteries is a life-threatening complication of Kawasaki disease (KD) and is detected in echocardiography of up to one-quarter of the patients Younger patients are less likely to meet the classic criteria of KD and are also at greatest risk of developing coronary artery abnormalities In a child with high fever and 2 or 3 criteria for the diagnosis of Kawasaki disease, or an infant with 7 days or more of unexplained fever, a serum CRP

The EULAR criteria suggests a diagnosis of Henoch Schonlein purpura (HSP) to be made based on palpable purpura with lower limb predominance and at least one of the symptoms of abdominal pain, arthritis or arthralgia or signs of renal involvement or evidence of vasculitis in histopathology The prognosis is excellent for most children with HSP Approximately 20% of children with HSP develop renal involvement which could bear significant mortality and morbidity

Antibodies against native or double stranded DNA (anti-dsDNA) or extractable nuclear antigens (anti-ENAs) are specific for systemic lupus erythematosus Negative antinuclear antibody (ANA) in children suspected for systemic lupus erythematosus rules out the diagnosis C3, C4 complement level or total hemolytic complement with CH50 give a measure of disease activity in SLE

Objectives: Clinicians need to be aware of the growing list of defined monogenic etiologies of autoimmune diseases. This is particularly relevant when evaluating children, as these rare monogenic forms of autoimmunity tend to present very early in life. Methods and results: By harnessing the transformative power of next generation sequencing, we made the unifying diagnosis of RAS-associated autoimmune leukoproliferative disease (RALD), caused by the somatic gain -of function p.G13C KRAS mutation, in a boy with the seemingly unrelated immune dysregulatory conditions of Rosai-Dorfman and systemic lupus erythematosus (SLE). Conclusions: This case expands our understanding of the clinical phenotypes associated with the extremely rare condition of RALD, and emphasizes the importance of always considering the possibility of a monogenic cause for autoimmunity, particularly when the disease manifestations begin early in life and do not follow a typical clinical course. Crown Copyright (C) 2016 Published by Elsevier Inc All rights reserved

The medical management of juvenile idiopathic arthritis (JIA) and its complications has undergone significant changes in the last decade, a result largely of the introduction of biologics and increased availability of expertise in the diagnosis and management of rheumatic diseases in children and adolescents. The result is that clinical outcome has improved and complete disease control can often be achieved1. In 2010, the British Society for Paediatric and Adolescent Rheumatology (BSPAR) proposed guidelines for the optimal management of children and adolescents with JIA2. This advocacy statement emphasizes the importance of empowering children and their caregivers, facilitating early detection of JIA, prompt referral to a team of health professionals who are expert in the diagnosis and management of childhood rheumatic diseases, prompt access to all appropriate pharmacologic and biologic therapies, and regular followup and monitoring. The Canadian Wait Time Alliance sets acceptable wait times as 4 weeks in children with JIA, other than systemic onset JIA, and within 7 days of disease onset for children with systemic onset JIA. Screening for asymptomatic uveitis should take place within 4 weeks of the diagnosis of JIA3. Ideally, children and adolescents with JIA should be managed by a team of health professionals with training and experience in pediatric rheumatology given … Address correspondence to Dr. R.E. Petty, Division of Rheumatology, Department of Pediatrics, University of British Columbia, British Columbia’s Children’s Hospital, 4480 Oak St., Room K4-114, Vancouver, British Columbia V6H 3V4, Canada; E-mail: rpetty{at}cw.bc.ca

Objective.To revise the current juvenile idiopathic arthritis (JIA) International League of Associations for Rheumatology (ILAR) classification criteria with an evidence-based approach, using clinical and routine laboratory measures available worldwide, to identify homogeneous clinical groups and to distinguish those forms of chronic arthritis typically seen only in children from the childhood counterpart of adult diseases.Methods.The overall project consists of 4 steps. This work represents Step 1, a Delphi Web-based consensus and Step 2, an international nominal group technique (NGT) consensus conference for the new provisional Pediatric Rheumatology International Trials Organization JIA classification criteria. A future large data collection of at least 1000 new-onset JIA patients (Step 3) followed by analysis and NGT consensus (Step 4) will provide data for the evidence-based validation of the JIA classification criteria.Results.In Step 1, three Delphi rounds of interactions were implemented to revise the 7 ILAR JIA categories. In Step 2, forty-seven questions with electronic voting were implemented to derive the new proposed criteria. Four disorders were proposed: (a) systemic JIA; (b) rheumatoid factor–positive JIA; (c) enthesitis/spondylitis-related JIA; and (d) early-onset antinuclear antibody–positive JIA. The other forms were gathered under the term “others.” These will be analyzed during the prospective data collection using a list of descriptors to see whether the clustering of some of them could identify homogeneous entities.Conclusion.An international consensus was reached to identify different proposed homogeneous chronic disorders that fall under the historical termJIA. These preliminary criteria will be formally validated with a dedicated project.

Made available in DSpace on 2019-10-04T11:56:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-02-01 International Leagues of Associations for Rheumatology (ILAR) Grant Juvenile idiopathic arthritis (JIA) is the most prevalent chronic rheumatic disease in children and young people (CYP) and a major cause of pain and disability. The vast majority of the world's children and their families live in less resourced countries (LRCs) and face significant socioeconomic and healthcare challenges. Current recommendations for standards of care and treatment for children with JIA do not consider children living in less resourced countries. In order to develop appropriate recommendations for the care of CYP with JIA in less resourced countries a meeting of experienced pediatric rheumatologists from less resourced countries was convened with additional input from a steering group of international pediatric rheumatologists with experience in developing recommendations and standards of care for JIA. Following a needs assessment survey of healthcare workers caring for CYP with JIA in LRC, a literature review was carried out and management recommendations formulated using Delphi technique and a final consensus conference. Responses from the needs assessment were received from 121/483 (25%) practitioners from 25/49 (51%) less resourced countries. From these responses, the initial 84 recommendations were refined and expanded through a series of 3 online Delphi rounds. A final list of 90 recommendations was proposed for evaluation. Evidence for each statement was reviewed, graded, and presented to the consensus group. The degree of consensus, level of agreement, and level of evidence for these recommendations are reported. Recommendations arrived at by consensus for CYP with JIA in less resourced countries cover 5 themes: (1) diagnosis, (2) referral and monitoring, (3) education and training, (4) advocacy and networks, and (5) research. Thirty-five statements were drafted. All but one statement achieved 100% consensus. The body of published evidence was small and the quality of evidence available for critical appraisal was low. Our recommendations offer novel insights and present consensus-based strategies for the management of JIA in less resourced countries. The emphasis on communicable and endemic diseases influencing the diagnosis and treatment of JIA serves as a valuable addition to existing JIA guidelines. With increasing globalization, these recommendations as a whole provide educational and clinical utility for clinicians worldwide. The low evidence base for our recommendations reflects a shortage of research specific to less resourced countries and serves as an impetus for further inquiry towards optimizing care for children with JIA around the world. Univ Cape Town, Dept Pediat & Child Hlth, Red Cross War Mem Childrens Hosp, Room 515,ICH Bldg, ZA-7700 Rondebosch, South Africa Univ British Columbia, BC Childrens Hosp, Dept Pediat, Vancouver, BC, Canada Univ Nairobi, Nairobi, Kenya Univ British Columbia, Dept Pediat, Vancouver, BC, Canada Univ Toronto, Hosp Sick Children, Toronto, ON, Canada Hosp Pediat Garrahan, Buenos Aires, DF, Argentina Muhimbili Univ Hlth & Allied Sci, Sch Med, Dar Es Salaam, Tanzania Univ Zambia, Dept Paediat & Child Hlth, Sch Med, Lusaka, Zambia Univ Witwatersrand, Wits Donald Gordon Med Ctr, Johannesburg, South Africa Univ Sao Paulo, Clin Res Ctr, Ribeirao Preto Med Sch, Sao Paulo, Brazil Sao Paulo State Univ, Div Pediat Rheumatol, Sao Paulo, Brazil Univ Hosp Leuven, Dept Microbiol & Immunol & Pediat Rheumatol, Leuven, Belgium Newcastle Univ, Great North Childrens Hosp, Newcastle, England Jaslok Hosp, Dept Pediat, Mumbai, India Ist Giannina Gaslini, PRINTO, Clin Pediat & Reumatol, Genoa, Italy Sao Paulo State Univ, Div Pediat Rheumatol, Sao Paulo, Brazil

Periodic fever aphthous stomatitis pharyngitis adenitis (PFAPA), also known as Marshall syndrome, is the most commonly identified periodic fever syndrome

Background Despite recent advances in the diagnosis and understanding of many autoinflammatory diseases, there are still a great number of patients with phenotypes that do not fit any clinically- and/or genetically-defined disorders. Case presentation We describe a fourteen-year-old boy who presented at two and a half years of age with recurrent febrile episodes. Over the course of the disease, the episodes increased in frequency and severity, with new signs and symptoms continuing to appear. Most importantly, these included skin changes, splenomegaly and transaminitis. Only partial control of the disease was achieved with anti-IL-1 therapy. Extensive investigation showed generalized inflammation without immune deficiency, with increased levels of serum amyloid A and several pro-inflammatory cytokines including interferon-γ, as well as an increased type I interferon score. Exome sequence analysis identified P369S and R408Q variants in the MEFV innate immunity regulator, pyrin (MEFV) gene and T260 M and T320 M variants in the NLR family pyrin domain containing 12 (NLRP12) gene. Conclusion Patients with unclassified and/or unexplained autoinflammatory syndromes present diagnostic and therapeutic challenges and collectively form a substantial part of every cohort of patients with autoinflammatory diseases. Therefore, it is important to acquire their full genomic profile through whole exome and/or genome sequencing and present their cases to a broader audience, to facilitate characterization of similar patients. A critical mass of well-characterized cases will lead to improved diagnosis and informed treatment.

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.

Life is in a constant state of transition, from infancy through childhood to adolescence and adulthood. Continuity of medical care through the early years is usually provided by the primary care physician and pediatrician, and in the case of the child with a rheumatic disease, ideally by the pediatric rheumatologist. The care is family centered and relies to a great extent on the participation of the parents as well as the child. During adolescence, however, medical care is increasingly the responsibility of the patient and eventually changes from the pediatric setting to the adult setting. Management of this period of transition is vitally important to the adolescent child with a chronic disease requiring ongoing specialist care. Adolescence is a period in which biological, psychological, and social changes occur at a rapid pace; chronic diseases, such as the rheumatic diseases, have significant impact on the normal adolescent growth and development and, in turn, are influenced by the normal evolution of psychological and social changes in the individual during this time.

Objective.To develop international consensus-based recommendations for the orofacial examination of patients with juvenile idiopathic arthritis (JIA), for use in clinical practice and research.Methods.Using a sequential phased approach, a multidisciplinary task force developed and evaluated a set of recommendations for the orofacial examination of patients with JIA. Phase 1: A Delphi survey was conducted among 40 expert physicians and dentists with the aim of identifying and ranking the importance of items for inclusion. Phase 2: The task force developed consensus about the domains and items to be included in the recommendations. Phase 3: A systematic literature review was performed to assess the evidence supporting the consensus-based recommendations. Phase 4: An independent group of orofacial and JIA experts were invited to assess the content validity of the task force’s recommendations.Results.Five recommendations were developed to assess the following 5 domains: medical history, orofacial symptoms, muscle and temporomandibular joint function, orofacial function, and dentofacial growth. After application of data search criteria, 56 articles were included in the systematic review. The level of evidence for the 5 recommendations was derived primarily from descriptive studies, such as cross-sectional and case-control studies.Conclusion.Five recommendations are proposed for the orofacial examination of patients with JIA to improve the clinical practice and aid standardized data collection for future studies. The task force has formulated a future research program based on the proposed recommendations.

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.

Inflammatory eye diseases comprise some of the most devastating complications of childhood rheumatic diseases, especially juvenile idiopathic arthritis (JIA). Chronic (initially asymptomatic) uveitis is the most common ocular complication of oligoarticular JIA. It is predominantly an insidious onset, anterior, nongranulomatous inflammation affecting the iris and ciliary body—an iridocyclitis (Fig. 20–1). Acute (symptomatic) anterior uveitis is characteristic of human leukocyte antigen-B27 (HLA-B27)– associated diseases such as enthesitis-related arthritis. The posterior uveal tract, the choroid, is rarely affected clinically.

Children with juvenile idiopathic arthritis (JIA) may infrequently present with localized anterior knee pain or swelling, in addition to generalize knee pain induced by JIA. We report five cases of deep infrapatellar bursitis in children with JIA. The clinical features, radiological findings, management, and outcome of five children with JIA and deep infrapatellar bursitis are reviewed. Three boys and two girls with a mean age of 9.8 years (range 6-14 years) were reviewed. Four children had persistent oligoarticular JIA, and one child had extended oligoarticular JIA. The presentation of deep infrapatellar bursitis was variable. In only one patient was the bursal swelling painful. Knee magnetic resonance imaging (MRI) was performed in four patients and demonstrated coexistent knee joint synovitis in three. Treatment included targeted corticosteroid injections into the deep infrapatellar bursa in two cases with complete resolution. One case was treated with corticosteroid injection by an outside health care provider with poor clinical response. Two cases are being treated with non-steroidal anti-inflammatory drugs and methotrexate. Deep infrapatellar bursitis can occur as an isolated finding or concurrently with knee joint synovitis in patients with JIA. Awareness of this entity is important because direct injection of the bursa may be needed for treatment, as the bursa does not communicate with the knee joint. Furthermore, when bursitis is suspected in JIA, MRI can be helpful to confirm the diagnosis, detect concurrent knee joint synovitis, and exclude other pathologies.

Objective.Pleuritis is a common manifestation and independent predictor of mortality in systemic lupus erythematosus (SLE). We examined the prevalence of pleuritis and factors associated with pleuritis in a multicenter Canadian SLE cohort.Methods.We studied consecutive adults satisfying the American College of Rheumatology (ACR) classification criteria for SLE who had a completed Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) score, at least 1 evaluable extractable nuclear antigen assay, and either a SLE Disease Activity Index (SLEDAI) or a SLE Activity Measure score. Pleuritis was defined as having pleuritis by satisfying the ACR criteria or the SLEDAI. Factors related to pleuritis were examined using univariate and multivariate logistic regression.Results.In our cohort of 876 patients, 91% were women, 65% Caucasian, mean age (± SD) was 46.8 ± 13.5 years, and disease duration at study entry was 12.1 ± 9.9 years; the prevalence of pleuritis was 34% (n = 296). Notably, greater disease duration (p = 0.002), higher SDI score (p ≤ 0.0001), age at SLE diagnosis (p = 0.009), and anti-Sm (p = 0.002) and anti-RNP (p = 0.002) seropositivity were significantly associated with pleuritis. In multivariate analysis with adjustment for disease duration, age at diagnosis, and SDI score, concomitant seropositivity for RNP and Sm were related to a nearly 2-fold greater prevalence of pleuritis (OR 1.98, 95% CI 1.31–2.82).Conclusion.Pleuritis occurred in one-third of this Canadian cohort. Concomitant Sm and RNP seropositivity, greater cumulative damage, longer disease duration, and younger age at SLE disease onset were related to a higher rate of SLE pleural disease.

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.

Objective.Early recognition and treatment of pediatric rheumatic diseases is associated with improved outcome. We documented access to pediatric rheumatology subspecialty care for children in British Columbia (BC), Canada, referred to the pediatric rheumatology clinic at BC Children’s Hospital, Vancouver.Methods.An audit of new patients attending the outpatient clinic from May 2006 to February 2007 was conducted. Parents completed a questionnaire through a guided interview at the initial clinic assessment. Referral dates were obtained from the referral letters. Patients were classified as having rheumatic disease, nonrheumatic disease, or a pain syndrome based on final diagnosis by a pediatric rheumatologist.Results.Data were collected from 124 of 203 eligible new patients. Before pediatric rheumatology assessment, a median of 3 healthcare providers were seen (range 1–11) for a median of 5 visits (range 1–39). Overall, the median time interval from symptom onset to pediatric rheumatology assessment was 268 days (range 13–4989), and the median time interval from symptom onset to referral to pediatric rheumatology was 179 days (range 3–4970). Among patients ultimately diagnosed with rheumatic diseases (n = 53), there was a median of 119 days (range 3–4970) from symptom onset to referral, and 169 days (range 31–4989) from onset to pediatric rheumatology assessment.Conclusion.Children and adolescents with rheumatic complaints see multiple care providers for multiple visits before referral to pediatric rheumatology, and there is often a long interval between symptom onset and this referral.

Corticosteroids, in one form or another, are major components of the armamentarium the pediatric rheumatologist uses to treat many of the rheumatic diseases of childhood. Their introduction in 1949 revolutionized the pharmacologic care of adults with rheumatoid arthritis (RA), and soon thereafter, their use in observational studies of children with chronic arthritis and other rheumatic diseases was reported. That they continue to have a prominent place in treating children with rheumatic diseases is a reflection of their role as potent suppressors of inflammation (notwithstanding their significant side effects) and the fact that, until quite recently, there was little other effective treatment to offer children aside from symptomatic relief with nonsteroidal anti-inflammatory drugs. The early application of corticosteroids to the treatment of childhood rheumatic diseases is reviewed in this chapter.

Objective To examine demographic and disease-related variables that affect pain in a large cohort of patients with juvenile rheumatoid arthritis (JRA). Methods Selection criteria were an onset of JRA ≥5 years prior to study and age ≥8 years at the time of the study. Pain was measured by a self-administered 10-cm visual analog scale. Possible explanatory variables studied included age at study, sex, race, onset subtype, active disease duration, active joint count, and physician's global assessment (PGA). Results In a multiple regression model, active disease duration, PGA, and age at study were independent predictors explaining 22% of the variation in pain scores. Stratified analyses showed an effect of age in the 8–15-year group, but not in older patients. Conclusion Disease-related factors explain only a small proportion of the variation in pain scores. Age has an effect on pain scores only in younger patients. The role of other factors, including psychosocial factors, needs further study.

This study was performed to: (1) assess the feasibility of measuring pulse wave velocity (PWV) from aortic (AO) Doppler flow and deriving AO input and characteristic impedances and the arterial pressure strain elastic modulus; and (2) compare these indices in pediatric patients with arterial disease to control (C) patients.There were 14 healthy children in the C group, 9 with inflammatory connective tissue diseases (ICTD), and 6 with Marfan syndrome (M). Using standard echocardiographic equipment, the AO annulus, AO root diameter in systole (AO(S)) and diastole (AO(D)), and AO length (L) were measured. The time taken for the Doppler signal to travel from the ascending to descending aorta was measured. AO peak flow was calculated from AO annulus cross-sectional area x peak aortic velocity (AoV); PWV = L/time taken for the Doppler signal to travel from the ascending to descending aorta; input impedance = (systolic - diastolic blood pressure)/(AO cross-sectional area x AoV); characteristic impedance = (PWV x rho)/Ao cross-sectional area (where rho = 1.06); and pressure strain elastic modulus = (systolic - diastolic blood pressure)/[(AO(S) - AO(D))/AO(D)]; beta index = ln (systolic/diastolic blood pressure)/[(AO(S) - AO(D))/AO(D)].Results for PWV were ICTD = MC (533, 496, 362 cm/s; P.02); for input impedance were ICTDM = C (245, 120, 116; P.03); for characteristic impedance were ICTDM = C (249, 107, 142; P.05); for pressure strain elastic modulus were MICTD = C (262, 447, 187; P.003); and for beta index were MICTDC (2.91, 2.51, 2.13; P.0006).This novel, relatively simple method of assessing the biophysical properties of the aorta shows abnormal function in patients with M and ICTD. This technique may be helpful in the long-term follow up of patients with arterial disease.

Purpose We describe important characteristics of the chronic arthritides of childhood associated with anterior uveitis. Design Literature review and commentary based on the investigators’ experiences. Methods A review of pertinent publications provides a background of current understanding of those forms of childhood arthritis that are of interest to ophthalmologists caring for children. Recommendations regarding screening for asymptomatic anterior uveitis in this patient group are reviewed, and current advances in therapy are noted. A new classification of childhood arthritis is compared with existing classifications. Results Uveitis complicates several forms of juvenile idiopathic arthritis (oligoarthritis, rheumatoid factor-negative polyarthritis, psoriatic arthritis, and enthesitis-related arthritis). Uveitis is a complication in up to 30% of children with chronic arthritis, particularly in those with oligoarticular disease. Conclusions Visual prognosis is guarded for children with chronic arthritis and uveitis. Surveillance and early therapy are important factors for ensuring a good outcome.

Objective To evaluate features during the first 6 months of disease that may be associated with a poor outcome as measured principally by extension to a polyarticular disease course in patients with oligoarticular-onset juvenile rheumatoid arthritis (oligo-JRA). Methods This study was a retrospective review of patients who fulfilled the American College of Rheumatology criteria for oligo-JRA, were followed up for at least 5 years, and did not have juvenile psoriatic arthritis, spondylarthropathy-like disease, or rheumatoid factor positivity. Data from the first 6 months of disease were collected. Continuous variables were dichotomized and then screened by univariate analysis for association with poor outcome at the last followup visit, as measured by extension of involvement (>4 accumulated involved joints) and by “clinically meaningful” extension (≥10 accumulated joints). Variables significantly associated with this latter outcome, with the addition of disease duration as a confounding independent variable, were included in a multiple logistic regression analysis. The same variables were then examined in separate multiple logistic regression models to look at other measures of outcome, including use of disease-modifying antirheumatic drugs (DMARDs) at any time, erosive disease on radiographs, any remission of disease ever occurring, physician's global assessment of disease activity at the last visit, and disability as measured by the Childhood Health Assessment Questionnaire (C-HAQ)/HAQ. Results Of the 205 patients (160 of whom were female) studied for a median of 10.8 years (range 5–26.6 years), 39.5% developed extension to >4 joints and 17.6% developed arthritis in ≥10 joints. Using the logistic regression model, symmetric disease was predictive of all measures of poor outcome: extension to ≥10 joints (odds ratio [OR] 19.2), the need to use DMARDs (OR 11.5), radiographic demonstration of erosive disease (OR 4.73), inflammatory activity at last followup visit (OR 3.23), no remission of disease (OR 4.73), and disability as measured by a C-HAQ score >0.12 (OR 2.95). Ankle and/or wrist disease was predictive of extension (OR 6.61) and erosions (OR 3.59). Wrist disease alone was predictive of the need to use DMARDs (OR 5.87) and of inflammatory disease activity at the last followup visit (OR 4.01). An elevated erythrocyte sedimentation rate (ESR) was predictive of extension (OR 3.76), the need to use DMARDs (OR 6.47), and no remission of disease (OR 2.30). Disease duration was a confounding variable for extension (OR 1.18) and erosive disease (OR 1.19). Conclusion The early presence of ankle and/or wrist disease, symmetric joint involvement, and an elevated ESR in a child with oligo-JRA indicates the likelihood of disease progression.