Features Of Juvenile Idiopathic Arthritis Research Articles

Clinical and laboratory features of juvenile idiopathic arthritis with wrist involvement: Results of a retrospective cohort study.

Previous studies in the pre-biological era showed an association of wrist inflammation in juvenile idiopathic arthritis (JIA) with progressive disease course, polyarticular involvement and failure of methotrexate treatment. To describe features of JIA, associated with wrist arthritis. Data from about 753 JIA patients were included in this retrospective cohort study. The clinical and laboratory features of patients with and without wrist involvement were analyzed. Wrist involvement was found in oligoarthritis (5.8%), RF(-)/RF(+) polyarthritis (44.9%/15.0%), enthesitis-related arthritis (17.7%), and systemic (58.6%) JIA categories. Unilateral wrist involvement was typical for oligoarthritis patients, bilateral involvement was either equal to that of unilateral involvement or was more frequent in other categories. Wrist arthritis was found to be associated with female sex, a low incidence of uveitis, and more indications of systemic inflammation, including elevated levels of C-reactive protein, erythrocyte sedimentation rate, and platelets, as well as involvement of the cervical spine, temporomandibular, shoulder, elbow, metacarpophalangeal, proximal interphalangeal, distal interphalangeal, hip, ankle, and tarsus arthritis. The number of patients with hip osteoarthritis and hip replacement was also higher. Wrist arthritis was associated with a lower probability of achieving remission [hazard ratio (HR) = 1.3 (95%CI: 1.0-1.7), P = 0.055], and a higher probability of being treated with biologics [HR = 1.7 (95%CI: 1.3-2.10, P = 0.00009)]. Wrist arthritis in JIA patients is a marker of a severe disease course, characterized by more intensive inflammation, unfavorable outcomes, and. requiring more intensive treatment with early administration of biologics. Close monitoring of wrist inflammation with ultrasound and MR assessment with early biological treatment might improve the outcomes.

Temporomandibular Joint Involvement in Juvenile Idiopathic Arthritis: The Results from a Retrospective Cohort Tertial Center Study.

Our study aimed to evaluate the clinical and laboratory features of juvenile idiopathic arthritis (JIA) children with temporomandibular joint (TMJ) arthritis. In the retrospective cohort study, we analyzed data of 753 patients with JIA aged 2-17 years, depending on TMJ arthritis or not. TMJ arthritis can to be diagnosed in the presence of at least two of the following clinical signs of inflammation: pain in TMJ, jaw opening limitation, jaw opening deviation, and micrognathia. We compared clinical, laboratory, and treatment features in JIA patients depending on the involvement of TMJ. TMJ arthritis was detected in 43 (5.7%) of our patients and associated with a longer course of the disease, polyarticular JIA category, treatment with systemic corticosteroids, and longer achievement of the remission and involvement of cervical spine, hip, and shoulder. Active joints >8 (OR = 14.9, p = 0.0000001), delayed remission >7 years (OR = 3.1; p = 0.0004), delayed hip involvement (OR = 4.6; p = 0.041), hip osteoarthritis (OR = 4.0; p = 0.014), cervical spine arthritis (OR = 10.3, p = 0.000001), and corticosteroid treatment (OR = 2.3, p = 0.0007) were associated with TMJ involvement. Patients with TMJ arthritis require more biologics (OR = 3.2, p = 0.0006, HR = 2.4, p = 0.005) and have decreased probability of remission achievement (p = 0.014). Consequently, TMJ arthritis was associated with a severe disease course. Early biologic treatment and corticosteroid avoidance might decrease TMJ involvement.

P08 Beliefs about pain in juvenile idiopathic arthritis are significantly associated with higher reported pain and more negative affect in children and young people

Abstract Background Persistent, unpredictable pain is one of the most burdensome features of juvenile idiopathic arthritis (JIA) which is a relapsing-remitting inflammatory musculoskeletal condition presenting in children and young people under 16 years. Recent research into perceptions of illness in young people has found that conceptualisations of long-term disease are mainly about the most salient features and symptoms, not of the illness as a whole. Particularly in young people with JIA, perceptions of pain are central to the individuals’ beliefs about the chronic condition. In paediatric pain research in general, the study of pain beliefs has mainly focused on pain catastrophising. Associations between other potentially important pain beliefs and pain outcomes (e.g. reporting pain or well-being) have not been explored to date. The aim of this study was to explore a wide range of pain perceptions in young people with JIA and to investigate whether these pain beliefs were associated with pain severity or well-being. Methods Cross-sectional data from the largest UK cohort study of children with JIA were analysed (the Childhood Arthritis Prospective Study- CAPS). Participants aged over 11 years completed ‘The Pain Perceptions Questionnaire for Young People (PPQ–YP)’ which assesses pain beliefs corresponding to the Common Sense-Self Regulatory framework first proposed by Leventhal and colleagues in the 1980s. Self-reported pain severity scores were captured using a Visual Analogue Scale (VAS). Emotional well-being was assessed using the Positive and Negative Affect Scale (PANAS). Associations were explored using Spearman’s Rank Correlation. Results 223 participants (64% female) completed the PPQ-YP. 38.2% of participants had a diagnosis of oligoarthritis, 29.6% had polyarthritis and equal proportions of participants had systemic, psoriatic or enthesitis related JIA (7.3%). Higher reported pain severity was significantly correlated with stronger beliefs about the greater impact of pain on life (rho=0.494, p < 0.001), pain unpredictability (rho=0.369, p < 0.001) and pain persistence (rho=0.278,p<0.001). Higher pain controllability beliefs (that pain was controllable) were significantly associated with lower self-reported pain severity (rho=-0.526, p < 0.001). Stronger beliefs about the impact of pain on life (rho=0.425,p=0.001) and pain coherence (poorer understanding about own pain: rho=-0.295,p=0.021) were significantly associated with more negative mood. Conclusion Pain beliefs (particularly about consequences, unpredictability, persistence and understanding) are linked to levels of pain severity and well-being in children with JIA. Adding to the evidence base on the link between pain catastrophising and illness outcomes, this research enhances our understanding of long-term illness and pain perceptions in young people through the implication of a wider range of pain beliefs and cognitions on illness outcomes. The PPQ-YP identified salient pain beliefs which should be considered in the design of potential interventions to improve pain outcomes in this group. Future research should aim to explore whether these perceptions can predict other important illness outcomes. Conflicts of Interest The authors declare no conflicts of interest.

Pain interference and associated factors in young adults with juvenile idiopathic arthritis

Objective: Pain is a common and distressing feature of juvenile idiopathic arthritis (JIA). Pain interference (PI) is underexplored in long-term conditions such as JIA. The aim of this study was to explore the factors associated with PI in young adults with JIA.Methods: All consecutive JIA patients aged 18–30 years in three tertiary rheumatology and rehabilitation centres in Finland between September 2015 and April 2016 were included. The patients completed questionnaires addressing demographics, disability, depressive symptoms, pain anxiety, pain intensity, and PI. PI was measured with a single item from the RAND-36 questionnaire. Five response categories were coded into three groups: patients reporting ‘extremely’, ‘quite a bit’ or ‘moderate’ were classified as having significant PI; ‘a little bit’ as having minor PI; and ‘not at all’ as having no PI. A leisure-time physical activity metabolic equivalent of task (LTPA MET) was calculated. Statistical comparisons between PI and categorical variables were made using chi-squared or Fisher–Freeman–Halton tests.Results: Of the total 195 patients, 97 (50%) patients reported PI. PI was associated with a wide spectrum of sociodemographic and disease-related variables. Pain intensity scores were higher in patients expressing greater PI (p < 0.001). Greater PI was associated with higher disability (p < 0.001), higher pain anxiety scores (p < 0.001), lower LTPA MET (p = 0.027), and poorer leisure-time activity (p < 0.001).Conclusions: PI is common in young adults with JIA. We suggest that PI should be taken into account in future outcome studies exploring the impact of pain in children and young adults with JIA.

Imaging findings of mixed connective tissue disease in children and adolescents: a case series.

Mixed connective tissue disease (MCTD) is a rare disease in children and adolescents which overlaps features of juvenile idiopathic arthritis, polymyositis/dermatomyositis, systemic lupus erythematosus, and systemic sclerosis. We have provided an image-based approach for evaluation of MCTD in children and adolescents, outlying the most frequent imaging findings. This approach would aid imagers and clinicians to consider the diagnosis of this rare entity and be able to make an accurate list of differential diagnosis for complex rheumatologic diseases such as MCTD, thus facilitating the ultimate goal of early diagnosis and optimal management of affected children.

Retracted: Chronic Recurrent Multifocal Osteomyelitis with Concomitant Features of Juvenile Idiopathic Arthritis

[This retracts the article DOI: 10.1155/2011/210795.].

Clinical features of juvenile idiopathic arthritis: Results of a nationwide retrospective survey and review of the literature

Background: Our aim is to evaluate the clinical and laboratory features of juvenile idiopathic arthritis (JIA) in Turkish children and to compare the patterns described by studies in the other countries. Methods: Children were diagnosed using International League of Associations for Rheumatology classification criteria. Demographic characteristics including age, gender, ages at disease onset and at diagnosis and laboratory tests including complete blood count, serum reactive protein concentration, and erythrocyte sedimentation rate were reviewed. Antinuclear antibody (ANA), rheumatoid factor, human leukocyte antigen B-27, and uveitis were also evaluated. Results: A total of 81 JIA patients were included in this study. The median age of the patients was 11 (7.0-14.0) years, and the median age at onset was 9.0 (5.0-12.0) years. There were 42 girls (51.9%) and 39 boys (48.1%) in JIA patients. Oligoarticular onset JIA was the most frequent onset type (42.0%). There were 11 patients with enthesitis-related arthritis (ERA) (13.6%). ANA was positive in 16 patients (19.7%) and uveitis had seen in 6 patients (7.4%). Conclusion: We found that some features of JIA were different in Turkish children who included higher rate of ERA and lower rate of ANA positivity and uveitis than JIA patients with western countries.

Premature Cell Senescence and T Cell Receptor–Independent Activation of CD8+ T Cells in Juvenile Idiopathic Arthritis

CD8+ T cells lacking CD28 were originally reported to be a characteristic feature of juvenile idiopathic arthritis (JIA), but the relevance of these unusual cells to this disease remains to be elucidated. Because of recent evidence that loss of CD28 cells is typical of terminally differentiated lymphocytes, the aim of this study was to examine functional subsets of CD8+ T cells in patients with JIA. Blood and/or waste synovial fluid samples were collected from children with a definite diagnosis of JIA (n = 98). Deidentified peripheral blood (n = 33) and cord blood (n = 13) samples from healthy donors were also collected. CD8+ and CD4+ T cells were screened for novel receptors, and where indicated, bioassays were performed to determine the functional relevance of the identified receptor. JIA patients had a naive T cell compartment with shortened telomeres, and their entire T cell pool had reduced proliferative capacity. They had an overabundance of CD31+CD28(null) CD8+ T cells, which was a significant feature of oligoarticular JIA (n = 62) as compared to polyarticular JIA (n = 36). CD31+ CD28(null) CD8+ T cells had limited mitotic capacity and expressed high levels of the senescence antigens histone γH2AX and/or p16. Ligation of CD31, which was independent of the T cell receptor (TCR), sufficiently induced tyrosine phosphorylation, vesicle exocytosis, and production of interferon-γ and interleukin-10. These data provide the first evidence of cell senescence, as represented by CD31+CD28(null) CD8+ T cells, in the pathophysiology of JIA. Activation of these unusual cells in a TCR-independent manner suggests that they are maladaptive and could be potential targets for immunotherapy.

Surface expression and genotypes of Toll-like receptors 2 and 4 in patients with juvenile idiopathic arthritis and systemic lupus erythematosus

BackgroundChronic arthritis is a common feature of juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE). It was subsequently discovered that Toll-like receptors (TLRs) are able to upregulate cytokine production in response to endogenous ligands released after tissue damage, suggesting that TLRs can maintain an inflammatory response even in absence of pathogen. Thus, TLRs may contribute to increased inflammation in JIA and SLE patients. The aim of this study was to investigate the role of TLRs in JIA and SLE. We examined the in vivo expression and polymorphisms of TLR2 and TLR4 in peripheral monocytes of patients with JIA and SLE during active and inactive disease phases.MethodsThis single center cohort study consisted of JIA and SLE affected children and control subjects. TLR2 and TLR4 protein expression on CD14+ monocytes was examined by flow cytometry. TLR2 and TLR4 genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism method (RFLP-PCR).ResultsA significant reduction in the level of TLR4 expression (p ≤ 0.001) was observed on monocytes of patients with JIA and SLE compared with that of healthy control subjects. There was no correlation between the TLR2 or TLR4 genotypes and the observed differential TLR protein expression on monocytes.ConclusionsTo conclude, our observations suggest involvement of investigated TLRs in the pathogenesis of JIA and SLE. It still remains to be elucidated whether reduced TLR4 expression is cause of chronic arthritis or a result of some feedback loop.

A descriptive analysis of 14 cases of progressive-psuedorheumatoid-arthropathy of childhood from south India: Review of literature in comparison with Juvenile Idiopathic Arthritis

Progressive-psuedorheumatoid-arthropathy of childhood (PPAC) is an autosomal recessive single gene skeletal dysplasia involving joints. The gene attributed to its cause is WNT1-inducible-signaling pathway protein3 (WISP3). To study the clinical and radiographic presentation of PPAC in Indian patients and to compare with described features of PPAC and Juvenile Idiopathic Arthritis (JIA) from published literature. All cases (n = 14) of PPAC seen in the Rheumatology and Clinical Genetics outpatient clinic between 2008 and 2011 with classical, clinical, and radiological features were studied. The demographic and clinical data were obtained from medical records of the outpatient visits. Slight female preponderance (57%) and history of consanguinity in parents (43%) was observed in this group. The median age at onset was 4.5 years (range from birth to 9 years of age). Early presentation below the age of 3 years was seen in 3/14 patients (21%) in this group. The growth of all the patients fell below the 3rd percentile for the age. Historically, hip joint involvement was the most common presenting feature; however, elbow, wrist, knees, feet, spine, shoulder joints and small joints, namely proximal interphalangeal (PIP), distal interphalangeal (DIP), metacarpophalangeal (MCP), metatarsophalangeal joints (MTP), and interphalangeal joints (IP) of the feet, were also involved, either clinically or radiologically in varying proportions. Platyspondyly was noted in all. Molecular analysis of the WISP3 gene identified mutations in all the 5 individuals in whom it was done. This descriptive case series of PPAC from India reports distinctly differentiating clinical, radiological, and molecular markers in contrast with classically described features of JIA, its mimic. Early presentation (age of onset below 3 years) with involvement of interphalangeal joints seen in three patients (21%) was a unique finding, with missense WISP3 gene mutations in all of them. Timely diagnosis of this entity can spare the patient from unnecessary investigations and toxic medications.

Genome-scale case-control analysis of CD4+ T-cell DNA methylation in juvenile idiopathic arthritis reveals potential targets involved in disease

BackgroundJuvenile Idiopathic Arthritis (JIA) is a complex autoimmune rheumatic disease of largely unknown cause. Evidence is growing that epigenetic variation, particularly DNA methylation, is associated with autoimmune disease. However, nothing is currently known about the potential role of aberrant DNA methylation in JIA. As a first step to addressing this knowledge gap, we have profiled DNA methylation in purified CD4+ T cells from JIA subjects and controls. Genomic DNA was isolated from peripheral blood CD4+ T cells from 14 oligoarticular and polyarticular JIA cases with active disease, and healthy age- and sex-matched controls. Genome-scale methylation analysis was carried out using the Illumina Infinium HumanMethylation27 BeadChip. Methylation data at >25,000 CpGs was compared in a case-control study design.ResultsMethylation levels were significantly different (FDR adjusted p<0.1) at 145 loci. Removal of four samples exposed to methotrexate had a striking impact on the outcome of the analysis, reducing the number of differentially methylated loci to 11. The methotrexate-naive analysis identified reduced methylation at the gene encoding the pro-inflammatory cytokine IL32, which was subsequently replicated using a second analysis platform and a second set of case-control pairs.ConclusionsOur data suggests that differential T cell DNA methylation may be a feature of JIA, and that reduced methylation at IL32 is associated with this disease. Further work in larger prospective and longitudinal sample collections is required to confirm these findings, assess whether the identified differences are causal or consequential of disease, and further investigate the epigenetic modifying properties of therapeutic regimens.

The Difficult Diagnosis of Temporomandibular Joint Arthritis

Arthritis of the temporomandibular joint (TMJ) is a long-recognized feature of juvenile idiopathic arthritis (JIA). The consequences of longstanding TMJ inflammation — severe micrognathia and retrognathism — were mentioned in the original description of Sir Frederic Still1. Growth problems are common in JIA, but the extent of growth failure seen in the mandible of children with TMJ arthritis by far exceeds arthritis-related growth complications of other locations. They are caused by unique properties of the mandible: in contrast to what one would assume, the mandible does not grow at the chin. The teeth-bearing body of the mandible undergoes only minimal growth during childhood, while the majority of new bone formation takes place on the mandibular ramus and condyle2. In fact, the majority of mandibular growth originates from chondrocytes immediately adjacent to the TMJ joint space. Because of this close proximity, the inflammatory cytokines in the synovial fluid may have a direct effect on condylar growth very early on in the event of arthritis3. Further, the total growth of the mandible during childhood is considerable, and thus also the potential effect size of disturbed growth of this bone. Another unique factor of TMJ arthritis in JIA is the absence of clinical signs and symptoms in most patients. In the study of Twilt, et al 4, only 12% of patients had TMJ pain; Billiau, et al found 22% with muscle or joint tenderness5, and Argyropoulou, et al found 5%−8% with pain or chewing discomfort6. Also, clinical examination is not able to reveal early signs of active TMJ arthritis, even when performed by skilled examiners; whether they are pediatric rheumatologists or orthodontists, they will reliably find only the signs of … Address correspondence to Dr. Saurenmann; E-mail: traudel.saurenmann{at}kispi.uzh.ch

Ultrasonography for detecting enthesitis in juvenile idiopathic arthritis

Enthesitis is a major feature of juvenile idiopathic arthritis (JIA) but is difficult to diagnose clinically. Our objective was to compare the accuracy of ultrasonography with power Doppler (US-PD) versus clinical examination for diagnosing enthesitis in patients with JIA and healthy controls. Twenty-six consecutive patients with JIA and 41 healthy volunteers underwent standardized clinical and US-PD examinations of 5 entheseal sites (proximal and distal quadricepital tendon insertions, Achilles tendon, and plantar fascia). US-PD reproducibility was evaluated. US-PD enthesitis was defined as a PD signal at the enthesis insertion. Bursitis, erosions, and cartilage vascularization were recorded. In the JIA group, 27 (12.5%) of the entheseal sites exhibited clinical enthesitis (distal patellar ligament in 45% of cases) and 20 (9.4%) exhibited US-PD enthesitis (distal patellar tendon in 30%), including 10 clinically normal sites (50%). US-PD enthesitis was found in several patients with oligoarthritis or polyarthritis. Clinical enthesitis (P < 0.0001) and HLA-B27-positive (P = 0.05) status were significantly associated with US-PD enthesitis. Erosion and bursitis, but not tendon thickening, were associated with US-PD enthesitis. US-PD enthesitis was not found at any of the 410 entheseal sites in controls; grade 1 cartilage vascularization was noted at 6% of the control sites. Enthesitis is a rare phenomenon in JIA. Clinically silent enthesitis is detected by US-PD and can be found in JIA categories other than enthesitis-related arthritis. Tendon thickening and cartilage vascularization can be detected in healthy controls. These findings may have implications for patient classification of the use of US-PD.

Chronic Recurrent Multifocal Osteomyelitis with Concomitant Features of Juvenile Idiopathic Arthritis

We report a case of a 13-year-old girl with chronic recurrent multifocal osteomyelitis (CRMO) who developed severe arthritis in four different joints within the first year from the onset of the disease. Her multiple vertebrae lesions showed significant amelioration after a 2-month treatment with prednisolone. In parallel, the initial severe symmetrical arthritis of both knees showing overt synovitis and joint effusion, in the absence of lesions in the metaphyses of the femur or the tibia, responded remarkably well in intra-articular triamcinolone hexacetonide injections. However, upon discontinuation of prednisolone, the patient developed severe arthritis of her right ankle and the proximal interphalangeal joint of her right middle finger. Thus, prednisolone was reinitiated combined with methotrexate, and the patient went into remission, which persists one year after prednisolone tapering. The appearance of arthritis in both knees in the absence of bone lesions and the emergence of severe arthritis of the ankle after remission of spinal bone lesions suggest that CRMO and juvenile idiopathic arthritis may coexist and be causally related.

Maladaptive effector CD8+ T cells distinguish clinical subtypes of Juvenile Idiopathic Arthritis (135.36)

Abstract Pervasive T cell clonality is a feature of Juvenile Idiopathic Arthritis (JIA), but the role of oligoclonal T cells in this chronic disease of childhood is poorly understood. We propose that T cell clonality in JIA is indicative of replicative pressure leading to accumulation of terminally differentiated cells. Hence, we examined the T cell repertoire of children with confirmed diagnosis of JIA and their age-matched healthy counterparts. Results showed that naive T cells of children with JIA had significantly lower telomere-FISH fluorescence indicating a long replicative history. Multicolor cytometry analyses also showed that patients had over abundance of CD8+CD31+CD28null T cells in blood and synovial fluid irrespective of disease duration and medication. Frequency of these unusual T cells was significantly higher among patients with the more severe, polyarticular form of JIA disease than those with oligoarticular disease. Furthermore, these T cells expressed high levels of γH2AX and pRB suggesting senescence. In proliferation assays using CFSE, these T cells remained CFSEhi but were CD69hiCD25lo/neg, results consistent with senescence and not quiescence. In receptor crosslinking assays, ligation of CD31 alone sufficiently induced tyrosine phosphorylation, cytolysis, and production of IFNγ, TNFα, and IL-10. These data indicate premature immune senescence in JIA, with CD8+CD31+CD28nullH2AX+ T cells as maladaptive effectors, and are potential targets for therapy.

Radiologic features of juvenile idiopathic arthritis: Difference between systemic and polyarthritis

Radiologic features of juvenile idiopathic arthritis: Difference between systemic and polyarthritis

Tumour necrosis factor alpha G-->A -238 and G-->A -308 polymorphisms in juvenile idiopathic arthritis.

To study G-->A -238 and G-->A -308 polymorphisms in the promoter region of the tumour necrosis factor (TNF) alpha gene in patients with juvenile idiopathic arthritis (JIA). We analysed whether there were any associations between these polymorphisms and the type of JIA and/or the clinical course of the disease in two populations. The first group consisted of 51 Turkish JIA patients and the second consisted of 159 JIA patients from the Czech Republic. Healthy individuals (93 and 100) from each country served as controls. Subgroups of JIA were defined according to the Durban criteria. The course of the disease was defined on the basis of the physician's global evaluation of disease activity, the swollen and tender joint count and the erythrocyte sedimentation rate. In both JIA cohorts, the distribution of genotypes was not significantly different among the types of JIA. The G-->A -238 polymorphism did not have an effect on the patients' outcome in either group. The G-->A -308 polymorphism was significantly associated with a poor outcome in the Turkish group (P=0.005) but there was no association in the Czech patients. Some features of JIA in Turkish patients differed from those in Czech patients. Genetic differences may accompany the phenotypic differences found in the Turkish group. Although larger numbers of patients are clearly needed to verify this, we suggest that the G-->A -308 polymorphism may be operative in defining disease outcome in selected groups.