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Objective: The goal was to assess the degree of overlap between existing International League of Associations for Rheumatology (ILAR) and preliminary Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria for juvenile idiopathic arthritis (JIA)., Methods: Participants from the Childhood Arthritis Prospective Study, a multicenter UK JIA inception cohort, were classified using the PRINTO and ILAR classification criteria into distinct categories. Systemic JIA was excluded because several classification items were not collected in this cohort. Adaptations to PRINTO criteria were required to apply to a UK health care setting, including limiting the number of blood biomarker tests required. The overlap between categories under the two systems was determined, and any differences in characteristics between groups were described., Results: A total of 1,223 children and young people with a physician's diagnosis of JIA were included. Using PRINTO criteria, the majority of the patients had "other JIA" (69.5%). There was a high degree of overlap (91%) between the PRINTO enthesitis/spondylitis- and ILAR enthesitis-related JIA categories. The PRINTO rheumatoid factor (RF)-positive category was composed of 48% ILAR RF-positive polyarthritis and 52% undifferentiated JIA. The early-onset antinuclear antibodies-positive PRINTO category was largely composed of ILAR oligoarthritis (50%), RF-negative polyarthritis (24%), and undifferentiated JIA (23%). A few patients were unclassified under PRINTO (n = 3) and would previously have been classified as enthesitis-related JIA (n = 1) and undifferentiated JIA (n = 2) under ILAR., Conclusion: Under the preliminary PRINTO classification criteria for childhood arthritis, most children are not yet classified into a named category. These data can help support further delineation of the PRINTO criteria to ensure homogenous groups of children can be identified., (© 2024 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Introduction: Polyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial role of monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity., Methods: A total of 17 healthy subjects and 18 premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated, and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level., Results: We identified 440 DEGs in pJIA patients of which 360 were upregulated and 80 downregulated. GSEA highlighted TNF-α and IFN-γ response. Importantly, this analysis not only detected genes targeted by pJIA therapy but also identified new modulators of immuno-inflammation. PLAUR , IL1B , IL6 , CDKN1A , PIM1 , and ICAM1 were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels., Conclusion: These findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hounkpe, Sales, Ribeiro, Perez, Caparbo, Domiciano, Figueiredo, Pereira and Borba.)

In the past two decades, there has been a great deal of work aimed to devise diagnostic guidelines, classification criteria, and diagnostic scores for cytokine storm syndromes (CSSs). The most notable effort has been the large-scale multinational study that led to the development of the 2016 classification criteria for macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA). Future studies should scrutinize the validity of the proposed criteria, particularly in systemic JIA patients treated with biologics, in children with subtle or incomplete forms of MAS, and in patients with MAS complicating other rheumatologic disorders. More generic CSS criteria are also available but often lack sensitivity and specificity in a wide variety of patient populations and CSSs of different etiologies. The coronavirus disease 2019 (COVID-19)-related lung disease led to an evolution of the concept of a "cytokine storm." Emerging and unsolved challenges in the diagnosis of the different forms of CSSs highlight the need for diagnostic tools and well-established classification criteria to enable timely recognition and correct classification of patients., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood. Enthesitis-related arthritis (ERA) has been one of the most controversial subtypes of JIA with a higher risk of axial involvement.  Our aim was to assess the frequency and spectrum of MRI findings of spine involvement in patients with JIA and determine if the axial involvement is always clinically symptomatic in patients with positive MRI findings. In this retrospective cross-sectional observational study we included known or suspected JIA patients who underwent spinal MRI examination between 2015 and 2017 and followed up in the Pediatric Rheumatology outpatient clinic. The demographic and clinical data were reviewed from the medical charts and electronic records. All patients were grouped as clinically symptomatic and asymptomatic for spinal involvement and MRI findings were re-evaluated for presence of inflammatory and erosive lesions. Of the 72 JIA patients, 57 (79.2%) were diagnosed with ERA, and 15 (20.8%) with non-ERA subtypes of JIA. Overall, 49 (68%) patients with JIA had positive spinal MRI findings (inflammatory and/or erosive lesions). Twenty-seven (47%) ERA patients were clinically symptomatic for spine involvement and among them, 19 (70.3%) had positive spinal MRI findings. Although 30 ERA (53%) patients were clinically asymptomatic, 23 of them (77%) had positive spinal MRI findings, as well. Eleven (73%) patients diagnosed with non-ERA JIA subtypes were clinically symptomatic for spine involvement at the time of MRI. Among them, four (36.3%) had inflammatory and/or erosive lesions on spine MRI. Four (26%) non-ERA patients were clinically asymptomatic for spine involvement, but three (75%) of them showed positive findings on spinal MRI. Inflammatory and/or erosive lesions of the thoracolumbar spine could exist in patients with JIA, regardless of the presence of symptoms. Not only because the significant proportion of ERA patients show asymptomatic axial involvement but also the presence of axial involvement in patients who were classified as non-ERA depending on current ILAR classification underlines the necessity of using MRI for accurate classification of patients with JIA., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Because of their rarity, limited awareness among non-specialists, and significant overlaps in their clinical presentation, childhood autoimmune/inflammatory conditions represent a diagnostic and therapeutic challenge. Juvenile idiopathic arthritis (JIA), with its 7 sub-forms, is the most common paediatric "rheumatic" disease. Juvenile-onset systemic lupus erythematosus (jSLE) is a severe autoimmune/inflammatory disease that can affect any organ system and shares clinical features with JIA. To overcome issues around diagnostic approaches in the context of clinical overlap, we aimed at the definition of disease sub-form specific cytokine and chemokine profiles. Serum samples from patients with JIA (n = 77) and jSLE (n = 48), as well as healthy controls (n = 30), were collected. Samples were analysed using the Meso Scale Discovery (MSD) U-PLEX Biomarker Group 1 (hu) panel. Distinct serum protein signatures associate with JIA vs jSLE disease groups. Proteins with high discriminatory ability include IL-23, MIP-1β, MCP-1, M-CSF and MDC. Furthermore, serum IL-18, MIF, MIP-5 and YKL-40 discriminate between systemic JIA and other JIA subtypes. Thus, simultaneous quantification of serum proteins in a panel format may provide an avenue for the diagnosis and monitoring of childhood autoimmune/inflammatory conditions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Chronic inflammatory arthritis in childhood is heterogeneous in presentation and course. Most forms exhibit clinical and genetic similarity to arthritis of adult onset, although at least one phenotype might be restricted to children. Nevertheless, paediatric and adult rheumatologists have historically addressed disease classification separately, yielding a juvenile idiopathic arthritis (JIA) nomenclature that exhibits no terminological overlap with adult-onset arthritis. Accumulating clinical, genetic and mechanistic data reveal the critical limitations of this strategy, necessitating a new approach to defining biological categories within JIA. In this Review, we provide an overview of the current evidence for biological subgroups of arthritis in children, delineate forms that seem contiguous with adult-onset arthritis, and consider integrative genetic and bioinformatic strategies to identify discrete entities within inflammatory arthritis across all ages.

Background: Musculoskeletal ultrasound (MSUS) has been used worldwide in adult patients with rheumatoid arthritis (RA) but is beginning to play an increasing role in patients with juvenile idiopathic arthritis (JIA). The aim of this study was to investigate the application of MSUS findings of a single indicator joint in JIA to assess the disease activity and classify disease subtype., Methods: Thirty-five non-systemic JIA patients with a total of 62 visits were retrospectively recruited in this study. Among the involved joints, the joint with highest value of grey-scale (GS) plus power Doppler (PD) (=GSPD) was selected as the indicator joint at each visit. The correlations between each MSUS parameter (GS, PD, GSPD) of indicator joints and the Physician Global Assessment (PGA) score, the Childhood Health Assessment Questionnaire-disability index (CHAQ-DI), and laboratory data were analyzed. The ultrasound features in different subtypes of JIA were also compared., Results: PD was weakly correlated with the PGA score (rho = 0.323, p = 0.010), while both GS and GSPD were moderately correlated with the PGA score (rho = 0.405, p = 0.001; rho = 0.434, p = 0.000). On the other hand, GS, PD, and GSPD were weakly correlated with CHAQ-DI. Although erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) had a weak correlation with PGA, they were not statistically correlated with GS, PD, or GSPD. The proportions of effusion, synovial hypertrophy, and enthesopathy in three different subtypes, showed significant differences (Fisher's exact test, p = 0.037; p = 0.004; p = 0.019). Enthesopathy was only seen in joints of enthesitis-related arthritis (ERA), but not in joints of polyarthritis and oligoarthritis., Conclusions: MSUS is an acceptable non-invasive tool for the patients with JIA, particularly for those with non-systemic JIA, that might assist disease classification, and whose parameters of the indicator joints may potentially contribute to the evaluation of disease activity.

Introduction: At least 50% of pediatric patients with Juvenile Idiopathic Arthritis (JIA) will require continued fo llow-up in adult rheumatology. The present International League of Associations for Rheumatology (ILAR) classification, currently under revision, differs from its classification of inflammatory arthritis in adults. Category changes have been reported in 10.8% of patients during follow-up., Objective: To analyze JIA patients in follow-up for at least 7 years to detect diagnosis changes during transition to adult care, identifying factors of poor functional prognosis., Patients and Method: Retrospective study based on medical records of JIA patients seen at the pediatric polyclinic of the Puerto Montt Hospital between 2005 and 2017, who were monitored for at least 7 years. Descriptive analysis was performed according to clinical variables: diagnostic category, evolution before diagnosis, clinical and serological activity, and evolution before starting drug therapy., Results: We evaluated 18 pa tients, corresponding to 3 patients with persistent oligoarticular arthritis (OA), 1 with extended OA, 4 with polyarticular arthritis (PA) rheumatoid factor (RF) negative, 4 with PA RF positive, 5 with syste mic JIA, and 1 with psoriatic arthritis, all have had follow-up more than 7 years. 11 out of 18 patients transitioned to adult care. Three out of 11 patients changed diagnosis to Rheumatoid Arthritis (RA) plus another autoimmune disease such as Sjögren's Syndrome + Systemic Lupus Erythematosus, Immune thrombocytopenia, or unclassified autoimmune disease, and 5 out of 11 children changed ILAR category from OA to Juvenile Rheumatoid Arthritis, extended OA to PA RF negative, and 3 from Systemic arthritis to PA RF negative. Age of onset, polyarticular forms, delay in diagnosis, and the start of therapy were associated with sequelae and persistent inflammation., Conclusions: Eight of the eleven JIA patients who transitioned to adult care changed their diagnosis or presented other autoimmune diseases. Some factors of poor prognosis must improve.

This article provides an overview of juvenile spondyloarthritis and important differences in the classification criteria, clinical presentation, outcomes, and pathology in juvenile versus adult-onset disease. Key differences in classification criteria between children and adults with spondyloarthritis are important to understand, as they can make transition from pediatric to adult care challenging. MRI and ultrasonography are increasingly relied on for the assessment of adult-onset disease activity and change over time in the pediatric population. The unique features of the maturing axial and peripheral skeleton are described for each modality, as they are key to understand for accurate interpretation of pathology in the pediatric population., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Approximately 5% of children with juvenile idiopathic arthritis (JIA) are diagnosed with the psoriatic form of the disease. In recent years, there has been substantial scholarship demonstrating both heterogeneity within the disease as well as similarities with other forms of JIA, culminating in a recent proposal for the categorization of JIA that excluded the psoriatic form altogether. The purpose of the review is to summarize the clinical, epidemiologic, and genetic features of psoriatic JIA (PsJIA), comparing it with other categories of JIA including spondyloarthritis. We conclude that there are sufficient unique clinical and genetic features within PsJIA as well as similarities with its adult counterpart that warrant including it within the JIA paradigm., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose of Review: Childhood arthritis is in need of a new system of classification, owing to deficiencies in the International League of Associations for Rheumatology (ILAR) criteria. We briefly review the history of classification of childhood arthritis, discuss the major criticisms of the current system, and highlight current initiatives to address those concerns., Recent Findings: Recent studies in both pediatric and adult rheumatology into the biologic basis of disease as well as the clinical patterns of presentation have informed the efforts toward developing a new classification system. Several efforts are currently underway to improve the classification of childhood arthritis, most notably the project of the Pediatric Rheumatology International Trials Organization (PRINTO). This international alliance of pediatric rheumatologists has begun a 4-step process to create new classification criteria for childhood arthritis. They are currently on step 3 of the process.

The periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an auto-inflammatory condition characterized by recurrent episodes of fever accompanied by aphthosis, cervical adenitis, and pharyngitis. Diagnosis of PFAPA could be challenging due to clinic overlap with familial Mediterranean fever (FMF). An international consensus has been established recently, to define a new set of classification criteria for PFAPA syndrome. We aimed to evaluate the performance of recently proposed PFAPA criteria, to assess their utility in FMF regions. Patients diagnosed with PFAPA syndrome, FMF, and juvenile idiopathic arthritis (JIA) were included. Two investigators blindly evaluated all of patients for the newly proposed PFAPA criteria. A total of 542 patients (322 with PFAPA syndrome, 118 FMF and 102 JIA) were evaluated. Mean age of patients was 6.6 ± 2.81, 12.75 ± 3.9, and 12.42 ± 4.8 years for PFAPA, FMF, and JIA, respectively. We found quite high sensitivity (89.7%) but insufficient specificity of newly proposed PFAPA criteria (69.5%). When applied to control patients separately, specificity was found to be 61% and 79.4% for FMF and JIA patients, respectively. Positive predictive value was 81%, while negative predictive value was 82%. Recently proposed PFAPA criteria have satisfactory sensitivity, but its specificity is still under expectation. There is a need for a distinctive criterion between PFAPA syndrome and FMF, in FMF endemic regions, e.g., cryptic tonsillitis rapidly responsive to single dose of glucocorticoids. Further studies with higher patients' number in different regions are needed.

Juvenile idiopathic arthritis (JIA) is not a disease but an umbrella term that gather all forms of chronic arthritis of unknown origin and with onset in childhood. Some of these disorders appear to be the childhood equivalent of adult diseases and share therefore the same therapeutic targets. A form characterized by early onset and antinuclear antibody positivity seems to be specific for children but further evidence is needed. Systemic JIA (sJIA), although equivalent to adult onset Still disease is much more frequent in childhood. Novel potential targets for sJIA as well as for macrophage activation syndrome, its more severe complication, have therefore been investigated mainly in children., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The International League of Associations for Rheumatology classification criteria define systemic juvenile idiopathic arthritis (SJIA) by the presence of fever, rash and chronic arthritis. Recent initiatives to revise current criteria recognise that a lack of arthritis complicates making the diagnosis early, while later a subgroup of patients develops aggressive joint disease. The proposed biphasic model of SJIA also implies a 'window of opportunity' to abrogate the development of chronic arthritis. We aimed to identify novel SJIA biomarkers during different disease phases., Methods: Children with active SJIA were subgrouped clinically as systemic autoinflammatory disease with fever (SJIA syst ) or polyarticular disease (SJIA poly ). A discovery cohort of n=10 patients per SJIA group, plus n=10 with infection, was subjected to unbiased label-free liquid chromatography mass spectrometry (LC-MS/MS) and immunoassay screens. In a separate verification cohort (SJIA syst , n=45; SJIA poly , n=29; infection, n=32), candidate biomarkers were measured by multiple reaction monitoring MS (MRM-MS) and targeted immunoassays., Results: Signatures differentiating the two phenotypes of SJIA could be identified. LC-MS/MS in the discovery cohort differentiated SJIA syst from SJIA poly well, but less effectively from infection. Targeted MRM verified the discovery data and, combined with targeted immunoassays, correctly identified 91% (SJIA syst vs SJIA poly ) and 77% (SJIA syst vs infection) of all cases., Conclusions: Molecular signatures differentiating two phenotypes of SJIA were identified suggesting shifts in underlying immunological processes in this biphasic disease. Biomarker signatures separating SJIA in its initial autoinflammatory phase from the main differential diagnosis (ie, infection) could aid early-stage diagnostic decisions, while markers of a phenotype switch could inform treat-to-target strategies., Competing Interests: Competing interests: OF declares the receipt of research grants and personal fees from Pfizer, Abbott and personal fees from Roche, Amgen, UCB, Celgene and Lilly. DF declares the receipt of research grant support and honoraria from Pfizer, Novartis, Sobi and Chugai-Roche. SRP declares honoraria from Celgene and is founder of Atturos, a UCD spin-out company developing advanced diagnostic tests. The other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status., Methods: In this multinational, cross-sectional, observational cohort study, we asked international paediatric rheumatologists from specialised centres to enrol children with a diagnosis of juvenile idiopathic arthritis, according to International League of Associations for Rheumatology criteria, who were seen consecutively for a period of 6 months. Each patient underwent retrospective and cross-sectional assessments, including measures of disease activity and damage and questionnaires on the wellbeing and quality of life of the children. We qualitatively compared the collected data across eight geographical areas, and we explored an association between disease activity and damage and a country's gross domestic product (GDP) with a multiple logistic regression analysis., Findings: Between April 4, 2011, and Nov 21, 2016, 9081 patients were enrolled at 130 centres in 49 countries, grouped into eight geographical areas. Systemic arthritis (125 [33·0%] of 379 patients) and enthesitis-related arthritis (113 [29·8%] of 379) were more common in southeast Asia, whereas oligoarthritis was more prevalent in southern Europe (1360 [56·7%] of 2400) and rheumatoid factor-negative polyarthritis was more frequent in North America (165 [31·5%] of 523) than in the other areas. Prevalence of uveitis was highest in northern Europe (161 [19·1%] of 845 patients) and southern Europe (450 [18·8%] of 2400) and lowest in Latin America (54 [6·4%] of 849), Africa and Middle East (71 [5·9%] of 1209), and southeast Asia (19 [5·0%] of 379). Median age at disease onset was lower in southern Europe (3·5 years, IQR 1·9-7·3) than in other regions. Biological, disease-modifying antirheumatic drugs were prescribed more frequently in northern Europe and North America than in other geographical settings. Patients living in countries with lower GDP had greater disease activity and damage than those living in wealthier countries. Damage was associated with referral delay., Interpretation: Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographical areas and wealth status of countries. The greater disease burden in lower-resource settings highlights the need for public health efforts aimed at improving equity in access to effective treatments and care for juvenile idiopathic arthritis., Funding: IRCCS Istituto Giannina Gaslini., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Beyond NSAIDs and disease-modifying antirheumatic drugs are now biologic agents and anti-interleukin drugs that can augment therapy.

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 term JIA . These preliminary criteria will be formally validated with a dedicated project.

Background: Juvenile idiopathic arthritis (JIA) can cause structural damage. However, data on conventional radiography (CR) in JIA are scant., Objective: To provide pragmatic guidelines on CR in each non-systemic JIA subtype., Methods: A multidisciplinary task force of 16 French experts (rheumatologists, paediatricians, radiologists and one patient representative) formulated research questions on CR assessments in each non-systemic JIA subtype. A systematic literature review was conducted to identify studies providing detailed information on structural joint damage. Recommendations, based on the evidence found, were evaluated using two Delphi rounds and a review by an independent committee., Results: 74 original articles were included. The task force developed four principles and 31 recommendations with grades ranging from B to D. The experts felt strongly that patients should be selected for CR based on the risk of structural damage, with routine CR of the hands and feet in rheumatoid factor-positive polyarticular JIA but not in oligoarticular non-extensive JIA., Conclusion: These first pragmatic recommendations on CR in JIA rely chiefly on expert opinion, given the dearth of scientific evidence. CR deserves to be viewed as a valuable tool in many situations in patients with JIA., Key Points: • CR is a valuable imaging technique in selected indications. • CR is routinely recommended for peripheral joints, when damage risk is high. • CR is recommended according to the damage risk, depending on JIA subtype. • CR is not the first-line technique for imaging of the axial skeleton.

Juvenile osteochondritis dissecans (JOCD) and juvenile idiopathic arthritis (JIA) are both common diseases which may affect joints and bony structures in pediatric patients. In some cases, JOCD and JIA occur at the same time. In this study, the course of JOCD in patients with JIA was therefore evaluated to provide possible recommendations for further treatment opportunities and control examinations. From 06/2012 to 03/2018 55 children with JOCD with or without JIA were examined. Inclusion criteria were: (1) age ≤ 16 years, (2) diagnosis of a JOCD with or without JIA and (3) two routine MRI controls. The JOCD evaluation based on the classification according to Bruns and the measurement of the largest extent via MRI. 18 of these 55 children met our criteria: 11 JOCD findings of 7 patients with JIA (group A) were matched according to age and localization of JOCD to 11 patients without JIA (group B). Mean age of disease onset of JIA was 8.2 years (oligo JIA) and of JOCD 11.6 years. The mean time follow-up was 17.7 months. At all observation time points more JOCD findings (with stage III° and IV°, respectively) along with a significant deterioration was seen in group A compared to group B. The comparison of the last MRI control between group A and group B shows a significant smaller defect size (decrease of 54.5%, p = 0.028) in group B (97.9 ± 48.9 mm 2 ) as in group A (185.1 ± 102.9 mm 2 ). In comparison of first (169.7 ± 84.2 mm 2 ) and last MRI (97.9 ± 48.9 mm 2 ) a significant decrease in lesion size of JOCD in group B was seen (decrease of 58.4%, p = 0.048). Patients with JIA show a more progressive and severe course of JOCD. Therefore, we recommend (1) the early use of MRI in patients with JIA and persistent joint pain to detect potential JOCD and (2) in presence of JIA and JOCD regular MRI follow-up controls to identify deteriorating JOCD findings and prevent early joint destruction in pediatric patients.

Juvenile idiopathic arthritis (JIA) comprises a group of heterogeneous diseases further divided into various categories based on shared clinical presentation, laboratory markers, and disease prognosis. Extra-articular complications include uveitis and growth abnormalities. Disease course and prognosis vary with respect to each JIA category and subsequently guide respective treatment. Over the past few decades, considerable treatment advances have significantly reduced the morbidity associated with childhood arthritis. Nevertheless, the treatments are not curative; many children continue to have active disease into adulthood. Emphasis is placed on the initiation of early aggressive therapy in hopes of delaying disease progression and inducing remission., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To determine the frequency and types of joint deformities in children with juvenile idiopathic arthritis and their association with clinical parameters and rheumatoid factor., Study Design: Cross-sectional study., Place and Duration of Study: Rheumatology Outpatient Clinic, the Children's Hospital and the Institute of Child Health, Lahore, from September 2014 to February 2015., Methodology: All patients of both genders of less than 16 years of age, who fulfilled the International League of Association for Rheumatology (ILAR) criteria for Juvenile Idiopathic Arthritis (JIA), were enrolled in this study. Their demographic data, duration of disease at the time of presentation, types of JIA, various joint deformities and rheumatoid factor (RF) were documented. Statistical analysis of data was done on SPSS version 16. Chi-square test was applied to determine the association of clinical deformity with age of patients, disease duration at presentation, types of JIA and RF., Results: Out of 70 patients enrolled during the study period, 51.4% were boys with mean age at presentation being 9.44 ±3.89 years (2-7 years) and median duration of disease being 24 months (interquartile range 42 months). Forty patients (57.1%) had joint deformities. Most common joints involved were hand (50%), wrist (50%), and knee (35.7%). The common types of joint deformities were boutonniere deformity (28.6%), ulnar deviation of wrist (28.6%), fixed flexion deformity of wrist (22.9%), and knee (31.4%). The most common type of JIA was polyarthritis RF negative with or without deformity. There was a strong association of deformities with older age of patients at presentation (p=0.036), longer duration of disease at presentation (p=0.028), polyarthritis (RF seronegative / seropositive) (p=0.013), and seropositivity (p=0.04)., Conclusion: More than 50% patients with JIA have joint deformities. Joint deformities are more likely to be seen in children with long-standing disease, those with polyarthritis JIA and seropositive patients.

The treatment of juvenile idiopathic arthritis has improved tremendously in the past 20 years as a result of appropriate legislative initiatives, large international collaborative networks, and the availability of new potent medications. Despite these considerable advances, a sizable proportion of patients are still resistant to treatment. Further improvement will stem from a better definition of the disease entities under the broad term juvenile idiopathic arthritis (which includes all forms of arthritis with disease onset before the age of 16 years); the discovery of laboratory and imaging biomarkers that could help the tuning of therapy; smoother implementation of clinical trials; more standardised links between academia, regulatory authorities, and patient organisations for the planning of future trials; and the availability of new drugs that selectively target molecules or pathways involved in inflammation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: The ideal goal of treatment for juvenile idiopathic arthritis (JIA) is disease remission. However, many sets of remission criteria have been developed and no systematic review of remission in JIA exists. The current systematic review investigated (1) how remission has been defined across JIA clinical cohorts and (2) the frequency of remission overall and within disease categories., Methods: Studies using prospective inception cohorts published after 1972 were selected if they estimated remission in cohorts of ≥50 patients. Articles focusing on specific medical interventions, not defining remission clearly or not reporting disease duration at remission assessment were excluded. Studies were selected from Medline, Embase, PubMed and bibliographies of selected articles. Risks of selection, missing outcome data and outcome reporting biases were assessed., Results: Within 17 studies reviewed, 88% had majority female participants and patient disease duration ranged from 0.5 to 17 years. Thirteen sets of criteria for clinically inactive disease and remission were identified. Uptake of Wallace's preliminary criteria was good in studies recruiting or following patients after their publication (78%). Remission frequencies increased with longer disease duration from 7% within 1.5 years to 47% by 10 years following diagnosis. Patients with persistent oligoarticular and rheumatoid-factor positive polyarticular JIA were most and least likely to achieve remission, respectively., Conclusions: Achievement of remission increased with longer disease duration, but many patients remain in active disease, even in contemporary cohorts. Multiple sets of outcome criteria limited comparability between studies., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

We validated case ascertainment algorithms for juvenile idiopathic arthritis (JIA) in the provincial health administrative databases of Manitoba, Canada. A population-based pediatric rheumatology clinical database from April 1st 1980 to March 31st 2012 was used to test case definitions in individuals diagnosed at ≤15 years of age. The case definitions varied the number of diagnosis codes (1, 2, or 3), time frame (1, 2 or 3 years), time between diagnoses (ever, >1 day, or ≥8 weeks), and physician specialty. Positive predictive value (PPV), sensitivity, and specificity with 95% confidence intervals (CIs) are reported. A case definition of 1 hospitalization or ≥2 diagnoses in 2 years by any provider ≥8 weeks apart using diagnosis codes for rheumatoid arthritis and ankylosing spondylitis produced a sensitivity of 89.2% (95% CI 86.8, 91.6), specificity of 86.3% (95% CI 83.0, 89.6), and PPV of 90.6% (95% CI 88.3, 92.9) when seronegative enthesopathy and arthropathy (SEA) was excluded as JIA; and sensitivity of 88.2% (95% CI 85.7, 90.7), specificity of 90.4% (95% CI 87.5, 93.3), and PPV of 93.9% (95% CI 92.0, 95.8) when SEA was included as JIA. This study validates case ascertainment algorithms for JIA in Canadian administrative health data using diagnosis codes for both rheumatoid arthritis (RA) and ankylosing spondylitis, to better reflect current JIA classification than codes for RA alone. Researchers will be able to use these results to define cohorts for population-based studies.

In the past years, pediatric rheumatology has seen a revolution in the treatments for rheumatic diseases, particularly juvenile idiopathic arthritis. Even if nonsteroidal anti-inflammatory drugs (NSAID), intra-articular corticosteroids (IAC) injections, and methotrexate remain the mainstay of the treatment for JIA patients, in aggressive disease, these treatments may be not sufficient to reach disease remission and to prevent long-term disability. Comprehension of immunological mechanisms involved in the pathogenesis of the diseases allowed to conceive new drugs targeting specific steps of the immune response. Several cytokines, like TNF alpha and IL-1, represent a very interesting target for biologic therapies. Due to the efficacy of these therapies, nowadays, "disease remission" in pediatric rheumatology is more and more frequent, especially in juvenile idiopathic arthritis patients, and the long-term outcomes have been significantly improved. Crucial to these advancements have been multicenter controlled clinical trials and long-term safety monitoring., Conclusions: Research in pediatric rheumatology has resulted in dramatic advances in diseases management. Biologic treatments have improved physical and functional outcomes and quality of life of patients with rheumatic disease. What is Known: • NSAID, intra-articular injection of corticoids, and methotrexate are the mainstay in treatment of JIA. • In aggressive JIA, these treatments may be not sufficient to reach disease remission and to prevent long term disability. What is New: • In recent years, management of JIA has significantly improved with the development of biologic therapies that allowed children with arthritis to reach a normal growth and to achieve a good long-term functional outcome.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic entity of childhood. The hallmark feature of all subtypes is joint inflammation. Imaging is used to evaluate the extent and severity of inflammation, degree of joint damage and response to treatment, which in turn impacts patient management. Ultrasound has become a useful adjunct to clinical examination because it shows promise in evaluating clinical and subclinical inflammation (synovitis, enthesitis) as well as cartilage and bone erosive changes. However more collaborative research is needed to help define the normal appearance of the growing skeleton, clarify the significance of subclinical findings and develop useful definitions, imaging protocols and scoring systems of disease.

Objectives: Many criteria for clinically inactive disease (CID) and minimal disease activity (MDA) have been proposed for juvenile idiopathic arthritis (JIA). It is not known to what degree each of these criteria overlap within a single patient cohort. This study aimed to compare the frequency of MDA and CID across different criteria in a cohort of children with JIA at 1 year following presentation., Methods: The Childhood Arthritis Prospective Study recruits children at initial presentation to paediatric or adolescent rheumatology in seven UK centres. Children recruited between October 2001 and December 2013 were included. The proportions of children with CID and MDA at 1 year were calculated using four investigator-defined and eight published composite criteria. Missing data were accounted for using multiple imputation under different assumptions., Results: In a cohort of 1415 children and adolescents, 67% patients had no active joints at 1 year. Between 48% and 61% achieved MDA and between 25% and 38% achieved CID using published criteria. Overlap between criteria varied. Of 922 patients in MDA by either the original composite criteria, Juvenile Arthritis Disease Activity Score (JADAS) or clinical JADAS cut-offs, 68% were classified as in MDA by all 3 criteria. Similarly, 44% of 633 children with CID defined by either Wallace's preliminary criteria or the JADAS cut-off were in CID according to both criteria., Conclusions: In a large JIA prospective inception cohort, a majority of patients have evidence of persistent disease activity after 1 year. Published criteria to capture MDA and CID do not always identify the same groups of patients. This has significant implications when defining and applying treat-to-target strategies., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides., Methods: Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed., Results: We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA., Conclusions: The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: The possible relationship between periodontitis and juvenile idiopathic arthritis (JIA) is now mostly unknown but there are common characteristics in these two diseases. The purpose of this study is to evaluate etanercept (Enbrel®) effects on periodontal conditions of children affected by JIA., Methods: For this study three group of patients were selected. The first one is represented by JIA subjects in pharmacologic therapy with etanercept (Enbrel®). The second one was composed by subjects in pharmacologic therapy with other drugs and the third one by healthy subjects. Twenty subjects for each group were selected. For each subject two periodontal scores were taken: Plaque Index and bleeding on probing. In order to check the reliability of the method a second registration has been performed in all the 3 groups after one month. A statistic Kruskal-Wallis test was performed., Results: The average Plaque Index was 48% in the first group, 37% in the second group and 20% in the control group. The average Bleeding Index was 5% in the first group, 5% in the second group and 9% in the control group., Conclusions: Etanercept seems to reduce periodontal inflammation in children affected by JIA as the other therapy.

Background: To study the impact of psoriasis and features associated with psoriasis on classification and outcome in a population-based follow-up cohort of children with juvenile idiopathic arthritis (JIA)., Methods: In all, 440 children with JIA were followed for a median of 8 years in a prospective Nordic population-based cohort study. Data for remission was available for 427 of these children. The presence of psoriasis, psoriasis-like rash, dactylitis, nail pitting, enthesitis, tenosynovitis and heredity was assessed in relation to ILAR classification and remission., Results: Clinical findings associated with psoriasis developed consecutively during the 8-year period. Six of 14 children with psoriasis were not classified as juvenile psoriatic arthritis according to the ILAR criteria at 8 year follow-up. Dactylitis was more common in children with early onset of JIA. After 8 years we found a cumulative median number of eleven arthritic joints in children with psoriasis or psoriasis-like rash compared with six in the rest of the cohort (p = 0.02). Also, the chance for not being in remission after 8 years increased significantly in patients with psoriasis, psoriasis-like rash or at least two of: 1) first-degree heredity for psoriasis or psoriatic arthritis, 2) dactylitis or 3) nail pitting, compared with the rest of the group (OR 3.32, p = 0.010)., Conclusions: Our results indicate a more severe disease over time in psoriasis-associated JIA, as features of psoriasis develop during the disease course. This group is a major challenge to encompass in a future JIA classification in order to facilitate early tailored treatment.

JIA is a chronic disease characterized by joint inflammation of unknown cause which occurs before 16 years of age. It includes 7 forms of clinical subtypes, and it affects about 1 individuals in every 10,000 Japanese children. The treatment strategy and an assessment tool for disease activity (JADAS) to evaluate the treatment efficacy have been established. In addition, induction of biologic agents for JIA patient refractory to conventional therapy resulted in remarkable improvement in the disease course and their joint prognosis. These drastic changes enforce recognition on rheumatologists that the major cause of poor prognosis of JIA at present is not due to disease severity but due to the delay or inappropriate treatment

Juvenile idiopathic arthritis is the most common inflammatory rheumatic disease of childhood and represents a series of chronic inflammatory arthritides of unknown cause. Involvement of the temporomandibular joint has been reported in up to 87% of children with juvenile idiopathic arthritis when based on magnetic tomography imaging; it can be asymptomatic and may lead to severe long term complications. In this review a summary of the contemporary literature of imaging of the temporomandibular joint in children with juvenile idiopathic arthritis will be provided, including ultrasound which is a valuable method for guided joint injections, but does not necessarily allow detection of acute inflammation, cone beam computed tomography, which has emerged as a feasible and accurate low-dose alternative as compared to conventional computed tomography to detect destructive change, and magnetic resonance imaging which is considered the method of choice for assessing acute, inflammatory change, although the lack of normative standards remains a challenge in children., (Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the consequences of disregarding first-degree relatives with psoriasis (FRP) as a classification criterion in juvenile idiopathic arthritis (JIA)., Methods: Criteria were examined in children from a prospective cohort with unclassified and psoriatic JIA., Results: FRP was the most common reason children were unclassified (57/85, 67%); all 57 children could be classified if FRP were disregarded as an exclusion criterion. FRP was a necessary inclusion criterion to classify 11/77 (14.3%) children with psoriatic JIA., Conclusion: Eliminating FRP as an exclusion criterion, but keeping it as an inclusion criterion in psoriatic JIA simplifies classification, though it is unclear whether the resulting classification would be better.

Juvenile idiopathic arthritis (JIA) is a group of diseases defined by the presence of arthritis of more than 6 weeks duration in patients aged less than 16 years and with unknown etiology. The international classification based on clinical and biological criteria define each type of JIA: systemic, oligoarticular, polyarticular with and without rheumatoid factor, enthesitis-related arthritis, and psoriatic arthritis. However, some discussions persist concerning systemic-onset juvenile idiopathic arthritis, whose clinical symptoms and pathogenic mechanisms are quite similar to those observed in autoinflammatory diseases, arthritis with antinuclear factors (poly- and oligoarticular) that could be considered as a homogenous group, and a family history of psoriasis that frequently led to unclassified arthritis. Better knowledge of the pathogenic mechanisms should improve the initial clinical classification with more homogeneous groups of patients and reduce the number of unclassified cases of arthritis., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Juvenile idiopathic arthritis (JIA) is an autoimmune disease usually occurring in children before the age of 16. As one of the most prevalent rheumatic diseases in the pediatric population, with an estimated prevalence of 2 to 20 and an incidence of 16 to 150 per 100,000 children, it is defined as an inflammation of one or more joints, with a duration of 6 weeks minimum. JIA is primarily diagnosed clinically, confirmed by laboratory and radiological findings, with the goal of early detection and assessment of the spread and progress of the disease as well as the response to medication. The current International League of Associations for Rheumatology (ILAR) classification defines eight types of arthritis.

Juvenile idiopathic arthritis, JIA, is a novel rheumatic disease in childhood introduced by the International League of Associations for Rheumatology. It is defined as a chronic, inflammatory disorder of unknown etiology, which is classified into seven categories; systemic-onset type, persistent and extended oligoarthritis, polyarthritis with rheumatoid factor negative, polyarthritis with rheumatoid factor positive, psoriatic arthritis, enthesitis-related arthritis and undifferentiated arthritis. As each category of JIA has different features in clinical phenotypes, precise subtyping is required for research and management. However, some modifications to the criteria might be helpful for getting better answers in diagnosis because of ethnical difference in prevalence and subtype distribution. Actually in Japanese population, a unique subset "B27-negative polyenthesitis" termed by Shichikawa should be included in enthesitis-related arthritis of JIA as a different type of enthesitis from B27-positive counterpart of spondyloarthritis in adulthood. Deep insights into the classification criteria will be needed for the better understanding of JIA.

Juvenile psoriatic arthritis (JPsA) has provided paediatric rheumatologists with a controversial topic for many years. The principal area of contention centres on the discordance between its treatment as a single diagnostic category in current classification schemes and the demonstration of its heterogeneous nature. A further point of debate is the distinctiveness of JPsA as an entity. Owing to these uncertainties, the concept of JPsA has evolved over the years and there have been several changes in its definition and diagnostic criteria. Recently, strong evidence has been provided that the spectrum of JPsA include at least two distinct subgroups, one that has the same characteristics as early-onset ANA-positive JIA, and another that is part of the spectrum of spondyloarthropathies and resembles the forms of psoriatic arthritis in adults that belong to the same disease family. These findings call for a revision of the classification of childhood arthritis, that refutes the assumptions that children with JPsA constitute a single homogeneous population and that JPsA should be considered an individual disease entity.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. Enthesitis-related arthritis (ERA) is one of the seven JIA subtypes classified by the International League of Associations for Rheumatology (ILAR). Due to inclusion and exclusion criteria, a pitfall of the ERA category is that it does not include all subsets of juvenile spondyloarthropathy, with many children ending up in the undifferentiated category. The ERA nomenclature also does not have a method for distinguishing between axial and peripheral disease, two phenotypes which vary in presentation and treatment requirements. This distinction is very important given the overall poor prognosis seen in ERA patients, specifically in those with axial involvement. Since axial involvement is more common and presents earlier than previously thought in ERA, the pediatric rheumatology community should develop more accurate and sensitive classification criteria based on disease course to assist in improving timely diagnosis and appropriate management.

Objective: Childhood arthritis encompasses a heterogeneous family of diseases. Significant variation in clinical presentation remains despite consensus-driven diagnostic classifications. Developments in data analysis provide powerful tools for interrogating large heterogeneous data sets. We report a novel approach to integrating biologic and clinical data toward a new classification for childhood arthritis, using computational biology for data-driven pattern recognition., Methods: Probabilistic principal components analysis was used to transform a large set of data into 4 interpretable indicators or composite variables on which patients were grouped by cluster analysis. Sensitivity analysis was conducted to determine key variables in determining indicators and cluster assignment. Results were validated against an independent validation cohort., Results: Meaningful biologic and clinical characteristics, including levels of proinflammatory cytokines and measures of disease activity, defined axes/indicators that identified homogeneous patient subgroups by cluster analysis. The new patient classifications resolved major differences between patient subpopulations better than International League of Associations for Rheumatology subtypes. Fourteen variables were identified by sensitivity analysis to crucially determine indicators and clusters. This new schema was conserved in an independent validation cohort., Conclusion: Data-driven unsupervised machine learning is a powerful approach for interrogating clinical and biologic data toward disease classification, providing insight into the biology underlying clinical heterogeneity in childhood arthritis. Our analytical framework enabled the recovery of unique patterns from small cohorts and addresses a major challenge, patient numbers, in studying rare diseases., (© 2014 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.)

JIA is the most common chronic inflammatory arthritis in children and young people and an estimated one-third of individuals will have persistent active disease into adulthood. There are a number of key differences in the clinical manifestations, assessment and management of JIA compared with adult-onset arthritis. Transition and transfer to adult services present significant challenges for many patients, their families and health care professionals. We describe key clinical issues relevant to adult rheumatology health care teams responsible for ongoing care of these young people., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The ubiquitin proteasome system plays an exceptional biological role in the antigen processing and immune response and it could potentially be involved in pathogenesis of many immunity-related diseases, including juvenile idiopathic arthritis (JIA)., Methods: The PSMB5 (rs11543947), PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827), and PSMA3 (rs2348071) proteasomal genes were genotyped on JIA subtype- and sex-specific association; plasma proteasome levels was measured in patients having risk and protective four-locus genotypes and eventual functional significance of allele substitutions was evaluated in silico., Results: Loci rs11543947 and rs1048990 were identified as disease neutral and other loci as disease susceptible (p < 0.05). The rs2277460, rs2295826, and rs2295827 loci had the strongest association with oligoarthritis [odds ratio (OR) = 2.024, 95% confidence interval (CI) 1.101-3.722; OR = 2.371, 95% CI 1.390-4.044; OR = 2.183, 95% CI 1.272-2.737, respectively), but the rs2348071 locus was associated with polyarthritis in females (OR = 3.438, 95% CI 1.626-7.265). A strong (p < 0.001) association was detected between the rs2277460/rs2295826/rs2295827/rs2348071 four-locus genotypes and the healthy phenotype when all loci were homozygous on common alleles (OR 0.439, 95% CI 0.283-0.681) and with the disease phenotype when the rs2348071 and the rs2295826 and/or rs2295827 loci were represented by risk genotypes simultaneously (OR 4.674, 95% CI 2.096-10.425). Rarely observed in controls, the double rs2277460/rs2348071 heterozygotes were rather frequent in affected males and more strongly associated with polyarthritis (p < 0.05). Haplotypes carrying the rare rs2295826/rs2295827 and rs2277460 alleles showed a strong (p < 0.001) association with oligo- and polyarthritis, respectively. The plasma proteasome level was found to be significantly higher in females having four-locus risk genotypes compared with protective genotypes (p < 0.001). Sequence affinity to transcription factors and similarity to splicing signals, microRNAs and/or hairpin precursors potentially depend on allele substitutions in disease susceptible loci., Conclusion: We demonstrate for the first time evidence of a sex-specific association of PSMA6/PSMC6/PSMA3 genetic variants with subtypes of JIA and plasma proteasome concentrations. Theoretical models of the functional significance of allele substitutions are discussed., (Copyright © 2014. Published by Elsevier B.V.)

Objective: Rheumatoid factor-positive polyarthritis (RF+ poly) is the juvenile idiopathic arthritis (JIA) category that resembles adult seropositive rheumatoid arthritis (RA). We studied children with RF+ and/or anticyclic citrullinated peptide antibody (anti-CCP)+ JIA to determine what proportion of those children meet International League of Associations for Rheumatology (ILAR) criteria for RF+ poly JIA and to assess for significant differences between children who meet RF+ poly criteria and those who are classified in other categories., Methods: Charts of children with JIA who were RF+ and/or anti-CCP+ were reviewed. Children with RF+ poly JIA were compared to children in other categories. Statistical analysis was performed using chi-square, Fisher's exact test, and the Student's t-test., Results: Of 56 children with RF+ and/or anti-CCP+ JIA, 34 (61%) met ILAR criteria for RF+ poly JIA. Twelve children had RF-/anti-CCP+ JIA with low anti-CCP titers. When these 12 children were excluded, there were few significant differences between children who met criteria for RF+ poly and those who were classified in other categories. The American College of Rheumatology/European League Against Rheumatism criteria for RA identified more RF+ children than did the ILAR RF+ poly classification (100% vs 77%)., Conclusion: A number of children with RF+ arthritis were excluded from the RF+ poly JIA classification, though many demographic features and disease measures were similar to those of children who met criteria for RF+ poly JIA. We propose prioritization of RF/anti-CCP positivity over specific exclusions, along with inclusion of anti-CCP, in future revisions of the JIA classification criteria, to improve the sensitivity of diagnosing childhood-onset RA.

In recent years, it has become increasingly clear that the term Juvenile Idiopathic Arthritis (JIA) comprises not one disease but several. Moreover, recent studies strongly suggest that some of these clinico-pathophysiologic entities appear to cross current diagnostic categories. The ultimate goal of the JIA classification is to facilitate development of better, more specific therapy for different forms of disease though improved understanding of pathophysiology. The past two decades have witnessed significant advances in treatment and improved outcomes for many children with chronic arthritis. However, understanding of the basic biologic processes underlying these diseases remains far from complete. As a result, even the best biologic agents of today represent "halfway technologies". Because they do not treat fundamental biologic processes, they are inherently expensive, need to be given for a long time in order to ameliorate the adverse effects of chronic inflammation, and do not cure the disease. Pediatric rheumatology is now entering an era in which diagnostic categories may need to change to keep up with discovery. A more precise, biologically based classification is likely to contribute to development of more specific and improved treatments for the various forms of childhood arthritis. In this review, we discuss how genetic, gene expression, and immunologic findings have begun to influence how these diseases are understood and classified., (Copyright © 2014. Published by Elsevier Ltd.)