Juvenile Idiopathic Arthritis Subtypes Research Articles

Do you have patients treated with adalimumab? Know the safety profile

Adalimumab, a fully human antibody to tumor necrosis factor (TNF), was first approved by the Food and Drug Administration (FDA) in 2002 for the treatment of rheumatoid arthritis. In 2008, it was approved for treatment of polyarthritis juvenile idiopathic arthritis and has since been approved for other pediatric indications that cross several subspecialties, including dermatology, gastroenterology and ophthalmology. Thus, it is important for a growing number of pediatricians, including those in primary care, to be aware of the safety profile of this widely used biologic medication. Horneff et al described the medium- to long-term safety profile of adalimumab in 577 patients (median use of 1.6 years, maximum 7.7 years) who participated in 7 Abbvie-sponsored clinical trials across several diseases, including 2 subtypes of juvenile idiopathic arthritis, Crohn's disease, and psoriasis. The major finding was that the safety profile is similar to that seen in adults. Although almost all patients developed adverse effects, especially infections, most were usual pediatric infections (including the serious infections) with very few opportunistic infections. The most common opportunistic infection was Herpes zoster with only one case of active tuberculosis. There appeared to be more serious adverse events and infections in patients with Crohn's disease, many from disease flares or infections related to disease complications, like perianal of fistula-related infections. There were also higher rates of infection among those treated concomitantly with corticosteroids. There were no malignancies and no deaths related to the medication in this cohort. Although encouraging, the median follow-up of patients in the study was relatively short and further post-marketing surveillance in “real-life” settings is necessary, in addition to data from industry sponsored clinical trials. Article page 166 ▶ Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's DiseaseThe Journal of PediatricsVol. 201PreviewTo evaluate the safety of adalimumab in pediatric patients who participated in clinical trials of juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and pediatric enthesitis-related arthritis), psoriasis, and Crohn's disease. Full-Text PDF Open Access

Classifications and imaging of juvenile spondyloarthritis.

Juvenile spondyloarthritis may be present in at least 3 subtypes of juvenile idiopathic arthritis according to the classification of the International League of Associations for Rheumatology. By contrast with spondyloarthritis in adults, juvenile spondyloarthritis starts with inflammation of peripheral joints and entheses in the majority of children, whereas sacroiliitis and spondylitis may develop many years after the disease onset. Peripheral joint involvement makes it difficult to differentiate juvenile spondyloarthritis from other juvenile idiopathic arthritis subtypes. Sacroiliitis, and especially spondylitis, although infrequent in childhood, may manifest as low back pain. In clinical practice, radiographs of the sacroiliac joints or pelvis are performed in most of the cases even though magnetic resonance imaging offers more accurate diagnosis of sacroiliitis. Neither disease classification criteria nor imaging recommendations have taken this advantage into account in patients with juvenile spondyloarthritis. The use of magnetic resonance imaging in evaluation of children and adolescents with a clinical suspicion of sacroiliitis would improve early diagnosis, identification of inflammatory changes and treatment. In this paper, we present the imaging features of juvenile spondyloarthritis in juvenile ankylosing spondylitis, juvenile psoriatic arthritis, reactive arthritis with spondyloarthritis, and juvenile arthropathies associated with inflammatory bowel disease.

Evaluation of plasma microRNA expressions in patients with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood, yet its etiology is unknown. It is known that microribonucleic acids (miRNAs) play a role in immunoregulation. We aimed to evaluate the plasma expression of some candidate miRNAs that are associated with the pathogenesis of autoimmunity. Thirty-one patients diagnosed with JIA and age-sex-matched 31 healthy children were enrolled for the study. The plasma levels of four candidate miRNAs (miRNA-16, miRNA-155, miRNA-204, and miRNA-451), which are known to be associated with autoimmunity, were examined in all the subjects. The plasma levels of miRNAs were measured with real-time PCR in the patients in active and inactive periods and in the healthy controls. The groups were compared with each other. The plasma miRNA-155 levels were found to increase in the JIA patients compared to the healthy controls, and it was statistically more significant in the inactive period. We found that the JIA patients had the higher levels of miRNA-16 and the lower levels of miRNA-204/miRNA-451 expressions compare with the control group, but there was no statistically significant difference. A statistically significant decrease in the plasma levels of miRNA-204 was found in the patients that were in inactive disease with only methotrexate therapy. The plasma miRNA expressions were compared in the JIA subtypes, and it was observed that miRNA-204 levels were higher in polyarticular JIA and miRNA-451 levels were higher in enthesitis-related arthritis without statistical significance. The significant alterations in the plasma expression of miRNA-155 and miRNA-204 suggest to us that these molecules may be related to the pathogenesis of JIA. More comprehensive and functional researches about the role of these molecules are needed in this regard.

Identification of enhanced IFN-γ signaling in polyarticular juvenile idiopathic arthritis with mass cytometry.

Polyarticular juvenile idiopathic arthritis (JIA) is among the most challenging of the JIA subtypes to treat. Even with current biologic therapies, the disease remains difficult to control in a substantial subset of patients, highlighting the need for new therapies. The aim of this study was to use the high dimensionality afforded by mass cytometry with phospho-specific antibodies to delineate signaling abnormalities in immune cells from treatment-naive polyarticular JIA patients. Peripheral blood mononuclear cells were isolated from 17 treatment-naive polyarticular JIA patients, 10 of the patients after achieving clinical remission, and 19 healthy controls. Samples were stimulated for 15 minutes with IL-6 or IFN-γ and analyzed by mass cytometry. Following IFN-γ stimulation, increased STAT1 and/or STAT3 phosphorylation was observed in subsets of CD4 T cells and classical monocytes from treatment-naive patients. The enhanced IFN-γ signaling was associated with increased expression of JAK1 and SOCS1 in CD4 T cells. Furthermore, substantial heterogeneity in surface marker expression was observed among the subsets of CD4 T cells and classical monocytes with increased IFN-γ responsiveness. The identification of enhanced IFN-γ signaling in CD4 T cells and classical monocytes from treatment-naive polyarticular JIA patients provides mechanistic support for investigations into therapies that attenuate IFN-γ signaling in this disease.

Autoantibodies and Gastrointestinal Symptoms in Colombian Children with Juvenile Idiopathic Arthritis.

Juvenile Idiopathic Arthritis (JIA) is the most common inflammatory joint disease in children. JIA and autoimmune inflammatory Gastrointestinal (GI) diseases share common etiologic mechanisms, including genetic predisposition and environmental influences. To Investigate association between gastrointestinal, rheumatologic clinical variables and the presence of autoantibodies in patients with JIA in treatment. In a cross-sectional study of patients with JIA according to diagnostic criteria and the ILAR classification. GI symptoms and autoantibody expression were evaluated with respect to their association with JIA clinical variables. Anti-Saccharomyces Cerevisiae IgG/IgA (ASCA), 6 antigen associated with anti polymorphonuclear neutrophil (ANCA), anti Transglutaminase (tTG) IgG/IgA, anti deaminated gliadin peptide (DGP) IgG/IgA autoantibodies, ANAS and IgA were measured in all patients. The association between clinical variables and auto-antibodies were evaluated using the Fisher test with significant value of p <0.05. The study was approved by the ethics committee of the all institutions. Samples were collected from ninety-seven patients, 63% of whom were female. The average age was 14 years. The JIA subtype associated with the most common GI symptoms was enthesitis- related arthritis. Of these patients, 44.3% and 14% reported abdominal pain and diarrhea, respectively. Anti-DPG and anti-tTG antibodies were found in 9.28% and 7.22%, respectively and 11.34% were positive for p-ANCA, and 2% were positive for ASCA. GI symptoms and autoantibodies associated with inflammation of the GI mucosa were detected in JIA patients but were not associated with autoantibodies or clinical variables. However, it is the monitoring of these patients diagnosis is important.

Juvenile Idiopathic Arthritis in a Tertiary Rheumatology Clinic

Background: Juvenile Idiopathic Arthritis (JIA) is one of the common chronic diseases in childhood. The inflammatory process in the joint is triggered by pro-inflammatory cytokines. The treatment is directed at alleviation of pain, inhibition of disease activity and preservation of range of motion. Objectives: To describe the spectrum of clinical presentations, laboratory parameters and drug therapy among patients with Juvenile Idiopathic Arthritis seen at a Tertiary Health Centre. Methods: All the patients who fulfilled the classification criteria of the International League of Associations for Rheumatology for JIA between July 2012 and June 2016 were included in the study. The clinical features, results of laboratory investigations and the treatment received were recorded. Results: A total of 1910 patients were seen at the Out-Patient Rheumatology Clinic over the 4-year period but only 18 case files of patients with JIA (0.95% of total) were retrieved. There were 13 females and 5 males with a female-to-male ratio of 2.6:1. The age range was 8-15 years with a mean of 10.3 ± 2.1 years. The duration of symptoms prior to presentation ranged between 2 years and 7 years with a mean of 4.2 ± 1.3 years. Polyarticular presentation was observed among 61.1% (11/18), pauciarticular in 27.8% (5/18) and systemic in 11.1% (2/18). Fever was uniformly seen among the patients with systemic onset, while fever and joint swelling were the common presentations in the other groups. Knee and ankle joints were most commonly affected. Erythrocyte Sedimentation Rate was elevated in 88.9% of the patients. Methotrexate was used in 61.1% and combination therapy was used as necessary. Conclusion: JIA is relatively uncommon in the setting of study. Polyarthritis form of JIA was the commonest type and response to steroid was uniformly good. Early recognition of the subtypes of JIA will enhance effective management of cases.

Role of musculoskeletal ultrasonography in the detection of subclinical synovitis in oligo and polyarticular juvenile idiopathic arthritis children

Aim of the workTo study the ability of ultrasound to detect subclinical synovitis in children with oligoarticular and polyarticular juvenile idiopathic arthritis (JIA) and to assess the disease activity according to the clinical, laboratory, and musculoskeletal ultrasonographic (MSUS) evaluation. Patients and methodsThe study included 40 children with oligoarticular or polyarticular JIA diagnosed according to the ILAR criteria. 800 joints (20 joints for each patient: knees, wrists, 2nd–5th metacarpophalangeal and 2nd–5th proximal interphalangeal joints) were subjected to MSUS scanning for synovial hypertrophy, joint effusion and power Doppler (PD) signals. Disease activity assessment using Juvenile Arthritis Disease Activity Score (JADAS-10), and functional assessment By Childhood Health Assessment Questionnaire (CHAQ) were done for all patients. ResultsThe mean age of patients was 10.3 ± 3.9 (3–16) years, 24 females and 16 males and the disease duration was 3.7 ± 2.8 (0.5–12) years. There was a significant difference between number of clinically (n = 192; 24%) and MSUS (440 by gray scale and 240 by PD) affected joints (p < 0.001). Comparing clinical and ultrasound activity, 70 joints were clinically inactive but showed PDUS signals. There was a significant (p < 0.05) correlation of the MSUS findings with the disease duration, number of clinically activite joints, JADAS10, CHAQ and acute phase reactants. ConclusionMSUS is superior to clinical examination in early detection of synovitis. It is a reliable method for disease activity assessment in JIA patients, so it can be used in association with standard clinical examination for better classification, diagnosis, treatment strategy and prognosis of JIA subtypes.

Juvenile Psoriatic Arthritis: A Report from the GRAPPA 2017 Annual Meeting.

Juvenile psoriatic arthritis (JPsA), a subtype of juvenile idiopathic arthritis (JIA), constitutes 5% of JIA. The literature is inconsistent regarding features of JPsA, and physicians debate whether it is a distinct entity within JIA. A biphasic age of onset distribution has been noted. Early-onset disease is characterized by female predominance, small joint involvement, dactylitis, and positive antinuclear antibodies. Late-onset JPsA resembles adult-onset psoriatic arthritis (PsA), with male predominance, psoriasis, enthesitis, and axial disease. Recent studies report improved outcomes, likely due to the widespread use of traditional and biologic disease-modifying antirheumatic drugs. Conflicting HLA associations have been reported in JPsA, but notably both HLA class I and II allele associations are suggested. Similar to PsA cohorts, subjects with JPsA have a lower frequency of a protective interleukin 23R allele than controls or other JIA subtypes. Data in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) patient registry suggest the aggressive characteristics of JPsA: 24.6% of children have joint damage 4.6 years after symptom onset. Pediatric and adult PsA classification criteria define different JPsA cohorts within the registry and support a previous suggestion that the International League of Associations for Rheumatology criteria for JPsA may be overly stringent. Increased collaboration between pediatric and adult physicians and comparative research on these clinically related conditions are warranted.

PRM94 - Quality of Life of Adults with a History of Juvenile Idiopathic Arthritis: A Systematic Review

Juvenile idiopathic arthritis (JIA) is a rheumatologic disease affecting 1 in 1,000 children resulting in life-long disability. New treatments for JIA have the potential to alter disease course. However, a challenge in economic evaluations of JIA drug treatment is to obtain quality of life (QoL) data, by JIA subtype, related to the transition of care from childhood to adulthood to inform life-time horizon cost effectiveness models. Our objective is to conduct a systematic review to identity QoL of adults with JIA. MEDLINE and EMBASE databases were searched. Studies in English that collected primary data evaluating QoL in adults with a history of JIA were included. Abstracts and full-text were screened independently by 2 reviewers. Data extracted included publication year, QoL instrument, QoL results, and sample size. We identified 1031 articles, and included 15 published between 1997-2017. Fourteen unique questionnaires were completed by 4023 individuals. QoL instruments included 3 generic multi-dimensional, 6 generic uni-dimensional (dimensions: pain, fatigue, well-being, vision, coping), 2 disease-specific multi-dimensional, and 2 generic multi-dimensional utility-based instruments. The most commonly used were the Health Assessment Questionnaire (n=10 studies), and SF-36 (n=9). Disease-specific instruments were Childhood Health Assessment Questionnaire (n=2), and Arthritis Impact Measurement Scale (n=1). Two studies reported EQ5D index scores: 0.902 (range:0.03-1; using German value set), and 0.8 (range:0.1-1; value set undefined). There was significant variability in reporting of QoL results, even within instrument. Few studies reporting utility data were identified, and utilities were not stratified by disease status or subtype. Data reported are not sufficient to inform life-time horizon models. Generic QoL instruments were used more often than disease-specific instruments. The heterogeneity in reporting QoL results highlights the need for standardization. It remains a need for rigorous QoL assessment during and after the transition of care to inform economic evaluations of early interventions.

Update on the epidemiology, risk factors and disease outcomes of Juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common inflammatory joint condition of childhood and represents seven JIA subtypes characterised by distinct clinical and laboratory variables. Genetic and environmental factors are known to influence JIA, although many unanswered questions remain. Measurement of health outcomes in JIA is imperative for both clinical practice and research. Patient-reported outcomes present particular challenges in paediatric rheumatology in view of the importance of collecting reports from both the child/young person and the parent. Another challenge is the need for continuity of outcome measurement across the paediatric-adult interface during the process of transition in terms of both measurement tools and the mechanisms in the system to facilitate tracking of the young person into adult care. Finally, the need for adults with JIA to be seen as a distinct group in adult rheumatology practice is important for both service provision and outcome research.

The correlation between the Childhood Health Assessment Questionnaire and disease activity in juvenile idiopathic arthritis.

The Childhood Health Assessment Questionnaire (CHAQ) has been adapted from the Stanford Health Assessment Questionnaire for assessing functional ability in children. The present study aimed to determine the correlation between CHAQ and disease activity in juvenile idiopathic arthritis (JIA) during active and inactive disease. JIA patients in the Pediatric Department, Ramathibodi Hospital, between January 2011 and December 2013, were included in the study. The CHAQ disability index (DI) and disease activity variables, including active and limited joint count, erythrocyte sedimentation rate, patient's global assessment (PtGA), physician's global assessment (PGA) and 27-joint Juvenile Arthritis Disease Activity Score (JADAS27), were collected from medical records for each patient over six visits. At each visit, each patient was classified as having either active or inactive disease. The correlations between CHAQ-DI and disease activity variables were analysed using Spearman's correlation. The classification of 139 JIA patients consisted of enthesitis-related arthritis (30.9%), systemic JIA (28.1%), oligoarthritis (16.5%), rheumatoid factor (RF)-negative polyarthritis (15.1%), RF-positive polyarthritis (6.5%) and undifferentiated arthritis (2.9%). Out of 812 patient visits, 606 were in active disease and 206 were in inactive disease. RF-negative polyarthritis had the highest CHAQ-DI (0.39 ± 0.66), while oligoarthritis had the lowest (0.20 ± 0.32). There was a good correlation between CHAQ-DI and JADAS27, PGA and PtGA in all JIA subtypes (p < 0.05) during active disease, but a poor correlation between CHAQ-DI and disease activity variables during inactive disease. CHAQ-DI had a good correlation with disease activity during active disease but a poor correlation during inactive disease. Therefore, CHAQ is only useful for assessing functional ability during active disease.

Treat to Target in Juvenile Idiopathic Arthritis: Challenges and Opportunities

This article reviews current knowledge around the paradigm “treat to target” (T2T) that has emerged as a successful treatment strategy for chronic diseases. While the majority of the current literature in rheumatic diseases has focused on formally designing and implementing interventions in rheumatoid arthritis (RA), we provide evidence that supports the application of a T2T strategy in the treatment of juvenile idiopathic arthritis (JIA). There is strong evidence for use of T2T in RA, and a recent trial demonstrated success of a Learning Collaborative intervention to implement T2T in clinical practice. While there are no existing clinical trials directly comparing T2T to other treatment strategies for JIA, there is indirect evidence that T2T is not inferior to other treatment strategies. Potential challenges in applying T2T to JIA include the heterogeneity between JIA subtypes, the heterogeneity in outcome measures, and the complexity of successfully incorporating shared decision making in clinical practice. However, there are also several potential benefits of implementingT2T in JIA, and a single-center pilot study has shown initial significant improvement in clinical outcomes. A movement towards adoption of a T2T strategy for JIA has commenced. Further study will be needed to determine best practices for implementation, there is indication that the framework of a Learning Health System may facilitate successful adoption.

Prior to extension, Transcriptomes of fibroblast-like Synoviocytes from extended and Polyarticular juvenile idiopathic arthritis are indistinguishable

BackgroundOur intent was to identify differences between the transcriptome of fibroblast-like synoviocytes (FLS) in oligoarticular juvenile idiopathic arthritis (JIA) before extension when compared to persistent subtype of JIA, when the two are clinically indistinguishable. Additionally, we sought to determine if differences between the transcriptomes of FLS from extended-to-be and polyarticular course JIA could be detected. Our hypothesis was that intrinsic differences in the transcriptome of the FLS from extended-to-be JIA would distinguish them from persistent oligoarticular JIA, before the course is clinically apparent.MethodsGlobal gene expression was defined in cultured FLS from 6 controls, 12 JIA with persistent course, 7 JIA prior to extension (extended-to-be), 4 JIA with extended course and 6 polyarticular onset, using Affymetrix Human GeneChips 133plus2.0.ResultsBioconductor Linear Models for Microarray Analysis revealed 22 probesets with differential expression between persistent and extended-to-be FLS at 15% FDR, however only 2 probesets distinguished extended-to-be from extended and none distinguished extended-to-be and polyarticular at 15% FDR. Differences in extended and polyarticular gene expression profiles were not detected. Confirmation of select genes was done on the RNA level by RT-qPCR and on the protein level in synovial fluid by ELISA.ConclusionsThe transcriptome of FLS from extended-to-be juvenile idiopathic arthritis is distinct from persistent course before a clinical distinction can be made. Additionally, the transcriptome of extended-to-be and polyarticular course, including those who have already extended, are indistinguishable. These gene expression data suggest that FLS already reflect a polyarticular behavior early in disease course, suggesting that extended-to-be may be “latent polyarticular” at onset. These differences can be used to develop early biomarkers of disease course, allowing for better-informed treatment decisions.

Bone mineral density in children with juvenile idiopathic arthritis after one year of treatment with etanercept

Introduction/Objective. Juvenile idiopathic arthritis (JIA) is the most frequent chronic inflammatory, rheumatic disease of childhood, associated with disturbance of bone mineral metabolism, which develops gradually and progressively, and if untreated eventually leads to osteoporosis in adulthood. The aim of our study was to evaluate bone mineral density (BMD) in patients with JIA treated with etanercept over a period of one year. Methods. The prospective cohort study included 94 JIA patients (66 female, 28 male), their median age being 14.77 years. BMD was measured by dual-energy X-ray absorptiometry on the lumbar spine. Disease activity was assessed using the American College of Rheumatology Pedi 50 criteria. Results. After one year of treatment with etanercept, we found a statistically significant increment in all osteodensitometry variables (p &lt; 0.001). Annual enhancement for the whole group was as follows: bone mineral content 15.8%, BMD 7.2%, BMDvol 4.2%. Z-score improved from -0.86 to -0.58 SD at the last visit, but decreased in rheumatoid factor-positive polyarthritis patients. Patients with systemic JIA had the lowest Z-score. Z-score correlated with functional disability level. BMD was lower in the group treated with glucocorticoids. Conclusion. Our results showed significant improvement of bone mineral density in children with JIA after one year of treatment with etanercept. Rheumatoid factor-positive and systemic JIA subtypes and treatment with glucocorticoids are the risk factors for impairing bone mineral metabolism.

Impact of Uveitis on Quality of Life in Adult Patients With Juvenile Idiopathic Arthritis.

To establish the impact of uveitis on the quality of life (QoL) in adult patients with juvenile idiopathic arthritis (JIA). Adult patients with a history of JIA, both with (n = 31) or without (n = 51) chronic anterior uveitis, were included. Their scores on 3 validated QoL questionnaires (National Eye Institute Visual Functioning Questionnaire [NEI VFQ-25], Medical Outcomes Study 36-Item Short Form health survey [SF-36], and EuroQol 5-domain questionnaire [EQ-5D]) were analyzed to find factors that could influence QoL. The median overall composite score (OCS) of the NEI VFQ-25 was significantly worse in the uveitis group compared to the non-uveitis group (respectively, 83.4 [range 15.2-94.7] and 94.9 [range 46.3-100]; P < 0.001). Nearly all subscale scores were lower in patients with uveitis than in patients without uveitis (P < 0.001 for all). After adjusting for duration of arthritis, JIA subtype, arthritis onset before or after 1990, and the use of systemic immunomodulatory medication, the QoL was still worse in patients with uveitis (NEI VFQ-25 OCS regression coefficient = -11.7; P = 0.002). No significant differences were found between the groups for the SF-36 and the EQ-5D. In the total JIA group, the use of systemic medication appeared to negatively influence some general QoL scores. Having a history of uveitis has a substantial negative effect on the vision-related QoL in JIA in adulthood, despite good visual acuity. General QoL scores did not differ between uveitis and non-uveitis patients, but the use of systemic immunomodulatory treatment, independent of uveitis, did negatively influence general QoL scores in adult JIA patients.

Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis

One of the complications of systemic juvenile idiopathic arthritis (SJIA) is macrophage activation syndrome (MAS), which may be considered as a form of secondary haemophagocytic lymphohistiocytosis. Trigger factors are drugs (aspirin, nonsteroidal anti-inflammatory drugs, gold preparations, methotrexate, and tumour necrosis factor blocking agents), drug change, drug side effects, or initiation of biological drugs and infections. The pathogenesis of MAS is still unclear and it may be explained by uncontrolled activities of macrophages. A lot of proinflammatory cytokines such as tumour necrosis factor-α, interleukin (IL)-1, IL-6, and interferon gamma play important roles in the pathogenesis of MAS. The diagnosis of MAS is often challenging. In 2016, the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) approved classification criteria for MAS complicating SJIA. Corticosteroid and cyclosporin A treatment have been used in the treatment of MAS. Intravenous immunoglobulin treatment has been used in some cases of MAS. Biologic agents have been used, such as anakinra (IL-1 alpha and beta inhibition), canakinumab (IL-1 beta inhibition), and tocilizumab (IL-6 inhibition). Early detection and early intervention are vital to avoid poor outcomes in MAS. SJIA is a subtype of juvenile idiopathic arthritis, and MAS is a serious, potentially fatal, complication of SJIA that occurs most commonly in children.

Juvenile Idiopathic Arthritis in Adults: Long-Term Observation of Ukrainian Patients

The assessment of long-term outcome of functional disability and disease activeness in adult patients with juvenile idiopathic arthritis appears to be complicated due to the absence of a unified approach to the classification and estimation of disease activeness, as well as the loss of supervision over a patient because of remission or his/her transition from pediatric to adult rheumatic service. The objective of the research was to determine how adults with the history of juvenile idiopathic arthritis fulfill the classification criteria for adult rheumatic diseases, as well as to assess activeness of these diseases, the degree of functional disorders, and social activeness of patients in Ukraine. Materials and methods. Patients with juvenile idiopathic arthritis older than 18 years and with more than 3 years of disease duration living in different parts of Ukraine were included into the study. Data regarding sociodemographic features, fulfillment of adult classification criteria, Health Assessment Questionnaire, articular and extra-articular Juvenile Arthritis Damage Index and disease activity were analyzed.Results. We observed 122 adult patients with the history of juvenile idiopathic arthritis irrespective of the presence of active inflammation at the moment of the examination. This group included patients from different regions of Ukraine diagnosed with juvenile idiopathic arthritis during 1984-2013. An adult rheumatologist examined all patients and the diagnosis was revised according to the adult classification of rheumatic diseases. Typical diagnostic criteria for rheumatoid arthritis were estimated in 32.8% of patients, ankylosing spondylitis – in 31.1% of patients, undifferentiated arthritis – in 13.9% of patients, Still’s disease – in 4.9% of patients, psoriatic arthritis – in 0.8% of patients, steady clinical laboratory remission – in 16.5% of patients. Most patients (81.8%) with rheumatoid factor positive polyarticular juvenile idiopathic arthritis fell under rheumatoid arthritis criteria in adulthood, and in 85% of patients with enthesitis-related arthritis as well as 53.8% of patients with extended oligoarthritis ankylosing spondylitis developed in adulthood. 68.8% of patients with systemic juvenile idiopathic arthritis, 68% of patients with rheumatoid factor negative polyarthritic subtype and 55% of patients with enthesitis-related arthritis had disability and incapacitation. Minimal disorders of the patients’ general condition according to the Health Assessment Questionnaire in adult age were found in most subtypes of juvenile idiopathic arthritis classified according to the International League of Associations for Rheumatology (extended and persistent oligoarthritis, rheumatoid factor positive polyarthritis, systemic subtype); moderate disorders of the general condition were found in enthesitis-related arthritis and rheumatoid factor negative polyarthritis. Side effects of juvenile idiopathic arthritis according to the articular Juvenile Arthritis Damage Index included severe articular damage being most frequently found in systemic and rheumatoid factor positive polyarthritis subtypes of juvenile idiopathic arthritis, while side effects of juvenile idiopathic arthritis according to the extra-articular Juvenile Arthritis Damage Index included extra-articular damage being found in systemic and rheumatoid factor negative polyarthritis subtypes of juvenile idiopathic arthritis, that was confirmed by the assessment of physical health according to the Short Form Health Survey-36, which was the worst in patients with systemic (40.3±12.6) and rheumatoid factor negative polyarthritis (38.9±9.4) subtypes of juvenile idiopathic arthritis.Conclusions. Further research of remote consequences of juvenile idiopathic arthritis in adult age and long-term observation of such patients require a detailed study to improve diagnostics and provide adequate treatment of rheumatic diseases with juvenile onset in adult age.

Antibodies to Cyclic Citrullinated Peptides in Patients With Juvenile Idiopathic Arthritis and Patients With Rheumatoid Arthritis: Shared Expression of the Inherently Autoreactive 9G4 Idiotype.

Antibodies to cyclic citrullinated peptides (anti-CCP) in rheumatoid arthritis (RA) can express the inherently autoreactive gene VH 4-34, detected using the rat monoclonal antibody 9G4. Patients with the polyarticular subtype of juvenile idiopathic arthritis (JIA) share some but not all of the features of adult patients with RA. This study was undertaken to compare serologic findings for rheumatoid factor (RF), anti-CCP, and 9G4-expressing anti-CCP in a large JIA cohort with a cohort of adult RA patients. Serum from 88 patients with polyarticular JIA, 29 patients with enthesitis-related arthritis, 38 patients with extended oligoarthritis, 31 adolescent controls, 35 patients with RA, and 30 adult controls were tested for RF, for IgG, IgA, and IgM anti-CCP, and for 9G4-expressing anti-CCP by enzyme-linked immunosorbent assay. Total serum 9G4-positive IgM was also measured. Of 65 patients with RF-negative polyarticular JIA, 4 (6.2%) were IgG anti-CCP positive. Sera from 20 of 23 patients with RF-positive polyarticular JIA (87.0%), 24 of 35 patients with RA (68.6%), and 1 patient with extended oligoarthritis contained IgG anti-CCP. IgA and IgM anti-CCP levels were lower in the adolescent group (P < 0.01). Levels of 9G4-expressing anti-CCP were higher in patients with RF-positive polyarticular JIA than in those with RF-negative polyarticular JIA (P < 0.0001). Median levels of 9G4-expressing anti-CCP in patients with RF-positive polyarticular JIA and those with RA did not differ. Expression of 9G4 on serum total IgM was greater in patients with RF-positive polyarticular JIA than other adolescent groups (P < 0.01), but similar to adult RF-positive RA. In healthy individuals, 9G4-positive B cells comprise 5-10% of the peripheral blood pool but serum immunoglobulins utilizing VH 4-34 are disproportionately low. The idiotope recognized by 9G4 was detected on anti-CCP antibodies in >80% of patients with RF-positive polyarticular JIA. VH 4-34 usage by anti-CCP in both JIA and RA patients suggest elicitation of these autoantibodies through shared pathogenic B cell selection processes.

UNIQUE MONOARTHRITIS PRESENTATIONS IN OLIGOARTICULAR JUVENILE IDIOPATHIC ARTHRITIS: A CASE SERIES

Abstract BACKGROUND: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of seven immune-mediated chronic inflammatory diseases that target the joints in children younger than 16 years of age. In Canada and worldwide, the estimated prevalence of JIA is approximately 1 per 1,000 children. Almost half of JIA patients are diagnosed with oligoarticular juvenile idiopathic arthritis (oligoJIA). OligoJIA, the most common chronic inflammatory arthritis of childhood, usually affects the knees and ankles. OligoJIA monoarthritis presenting with atypical, severe joint involvement is exceedingly rare and may have poor prognosis. OBJECTIVES: To identify the cases of children that presented with atypical monoarthritis and were diagnosed with oligoJIA in our Pediatric Rheumatology Clinic. Our aim is to describe their demographic, clinical, laboratory, and imaging features. In addition, we reviewed ten similar cases published in the literature. DESIGN/METHODS: This is a retrospective case series study. Fifty-three children with JIA from our inception cohort established in September 2015 were screened for the study. Other JIA subtypes and oligoJIA with ≥ 2 joints affected were excluded. RESULTS: Twenty-five out of 53 (47%) children with JIA were diagnosed with oligoJIA. Four of these 25 children (16%) presented with atypical monoarthritis of the hip, wrist or elbow. None had uveitis. All four were girls with a median age of 11.5 ± 3.5 years (range 9-16 years). Median duration of symptoms prior to diagnosis was 9.5 months. Median follow-up was 5.5 ± 3.5 months. All four patients had normal inflammatory markers. Two children were HLA-B27 positive and had hip arthritis. Three out of four (75%) children had second degree relatives with rheumatologic diseases. Three children (75%) diagnosed with hip, wrist and elbow arthritis respectively had cartilage loss and significant bone changes at presentation, including erosions.Only 10 cases of oligoJIA presenting with atypical monoarthritis have been published to date: 7 children with wrist involvement and 3 others with elbow arthritis. Five out of 7 (71%) children presenting with wrist oligoJIA had bone damage, whereas none of those with elbow arthritis had bone changes at presentation. CONCLUSION: Hip, wrist and elbow oligoJIA can have an aggressive course and present with bone damage. Prompt diagnosis is essential in avoiding irreversible bone and joint damage. Early referral to specialized care can improve their diagnosis, treatment and outcome.

Multicenter inception cohort of enthesitis-related arthritis: variation in disease characteristics and treatment approaches

BackgroundEnthesitis-related arthritis (ERA) is a specific subtype of juvenile idiopathic arthritis (JIA) defined according to the International League of Associations for Rheumatology (ILAR) criteria. We aimed to characterize the clinical features and treatment regimens in an inception cohort of children with ERA.MethodsWe performed a retrospective, cross-sectional, multicenter cohort study including subjects diagnosed with ERA between 1989 and 2012. Patients all fulfilled the ILAR criteria for ERA within 3 months of initial presentation to the rheumatology clinic. Differences in the prevalence of clinical criteria across study sites and by human leukocyte antigen (HLA)-B27 status were assessed using the Wilcoxon rank-sum or chi-square test, as appropriate.ResultsTwo hundred thirty-four children met the inclusion criteria. Their median age at diagnosis was 11.6 years, and 59% were HLA-B27-positive. Sixty-nine percent had enthesitis and arthritis at the time of diagnosis. Seventy-eight percent had a pauciarticular onset. The prevalence of all ILAR criteria at diagnosis, except arthritis and acute anterior uveitis, differed significantly across sites (all p < 0.01). Medication use varied significantly across sites for children with peripheral arthritis (p < 0.001), but not for sacroiliitis or enthesitis only. Nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs were the most commonly prescribed treatments, with anti-TNF agents primarily being initiation for sacroiliitis. HLA-B27 positivity was associated with male sex, higher active joint count, sacroiliitis, and higher disease activity at disease onset.ConclusionsThe majority of children had a pauciarticular onset, and several statistically significant clinical differences based on HLA-B27 status were identified. The observed heterogeneity in clinical presentation across sites reflects either true differences in patient populations or differences in how the ILAR criteria are being applied.