Early-onset Juvenile Idiopathic Arthritis Research Articles

Normal neonatal TREC and KREC levels in early onset juvenile idiopathic arthritis

Dysregulated central tolerance predisposes to autoimmune diseases. Reduced thymic output as well as compromised central B cell tolerance checkpoints have been proposed in the pathogenesis of juvenile idiopathic arthritis (JIA). The aim of this study was to investigate neonatal levels of T-cell receptor excision circles (TRECs) and kappa-deleting element excision circles (KRECs), as markers of T- and B-cell output at birth, in patients with early onset JIA. TRECs and KRECs were quantitated by multiplex qPCR from dried blood spots (DBS), collected 2-5days after birth, in 156 children with early onset JIA and in 312 matched controls. When analysed from neonatal dried blood spots, the median TREC level was 78 (IQR 55-113) in JIA cases and 88 (IQR 57-117) copies/well in controls. The median KREC level was 51 (IQR 35-69) and 53 (IQR 35-74) copies/well, in JIA cases and controls, respectively. Stratification by sex and age at disease onset did not reveal any difference in the levels of TRECs and KRECs. T- and B-cell output at birth, as measured by TREC and KREC levels in neonatal dried blood spots, does not differ in children with early onset JIA compared to controls.

Acute monoarthritis in young children: comparing the characteristics of patients with juvenile idiopathic arthritis versus septic and undifferentiated arthritis

Acute arthritis is a common cause of consultation in pediatric emergency wards. Arthritis can be caused by juvenile idiopathic arthritis (JIA), septic (SA) or remain undetermined (UA). In young children, SA is mainly caused by Kingella kingae (KK), a hard to grow bacteria leading generally to a mild clinical and biological form of SA. An early accurate diagnosis between KK-SA and early-onset JIA is essential to provide appropriate treatment and follow-up. The aim of this work was to compare clinical and biological characteristics, length of hospital stays, duration of intravenous (IV) antibiotics exposure and use of invasive surgical management of patients under 6 years of age hospitalized for acute monoarthritis with a final diagnosis of JIA, SA or UA. We retrospectively analyzed data from < 6-year-old children, hospitalized at a French tertiary center for acute mono-arthritis, who underwent a joint aspiration. Non-parametric tests were performed to compare children with JIA, SA or UA. Bonferroni correction for multiple comparisons was applied with threshold for significance at 0.025. Among the 196 included patients, 110 (56.1%) had SA, 20 (10.2%) had JIA and 66 (33.7%) had UA. Patients with JIA were older when compared to SA (2.7 years [1.8–3.6] versus 1.4 [1.1–2.1], p < 0.001). Presence of fever was not different between JIA and SA or UA. White blood cells in serum were lower in JIA (11.2 × 109/L [10–13.6]) when compared to SA (13.2 × 109/L [11–16.6]), p = 0.01. In synovial fluid leucocytes were higher in SA 105.5 × 103 cells/mm3 [46–211] compared to JIA and UA (42 × 103 cells/mm3 [6.4–59.2] and 7.29 × 103 cells/mm3 [2.1–72] respectively), p < 0.001. Intravenous antibiotics were administered to 95% of children with JIA, 100% of patients with SA, and 95.4% of UA. Arthrotomy-lavage was performed in 66.7% of patients with JIA, 79.6% of patients with SA, and 71.1% of patients with UA. In children less than 6 years of age with acute mono-arthritis, the clinical and biological parameters currently used do not reliably differentiate between JIA, AS and UA. JIA subgroups that present a diagnostic problem at the onset of monoarthritis before the age of 6 years, are oligoarticular JIA and systemic JIA with hip arthritis. The development of new biomarkers will be required to distinguish JIA and AS caused by Kingellakingae in these patients.

Switched Memory B Cells Are Increased in Oligoarticular and Polyarticular Juvenile Idiopathic Arthritis and Their Change Over Time Is Related to Response to Tumor Necrosis Factor Inhibitors

To investigate whether abnormalities in B cell subsets in patients with juvenile idiopathic arthritis (JIA) correlate with clinical features and response to treatment. A total of 109 patients diagnosed as having oligoarticular JIA or polyarticular JIA were enrolled in the study. B cell subsets in peripheral blood and synovial fluid were analyzed by flow cytometry. Switched memory B cells were significantly increased in patients compared to age-matched healthy controls (P < 0.0001). When patients were divided according to age at onset of JIA, in patients with early-onset disease (presenting before age 6 years) the expansion in switched memory B cells was more pronounced than that in patients with late-onset disease and persisted throughout the disease course. In longitudinal studies, during methotrexate (MTX) treatment, regardless of the presence or absence of active disease, the number of switched memory B cells increased significantly (median change from baseline 36% [interquartile range {IQR} 15, 66]). During treatment with MTX plus tumor necrosis factor inhibitors (TNFi), in patients maintaining disease remission, the increase in switched memory B cells was significantly lower than that in patients who experienced active disease (median change from baseline 4% [IQR -6, 32] versus 41% [IQR 11, 73]; P = 0.004). The yearly rate of increases in switched memory B cells was 1.5% in healthy controls, 1.2% in patients who maintained remission during treatment with MTX plus TNFi, 4.7% in patients who experienced active disease during treatment with MTX plus TNFi, and ~4% in patients treated with MTX alone. Switched memory B cells expand during the disease course at a faster rate in JIA patients than in healthy children. This increase is more evident in patients with early-onset JIA. TNFi treatment inhibits this increase in patients who achieve and maintain remission, but not inthose with active disease.

Phenotypic Characterization of Juvenile Idiopathic Arthritis in African American Children.

Juvenile idiopathic arthritis (JIA) affects children of all races. Prior studies suggest that phenotypic features of JIA in African American (AA) children differ from those of non-Hispanic white (NHW) children. We evaluated the phenotypic differences at presentation between AA and NHW children enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, and replicated the findings in a JIA cohort from a large center in the southeastern United States. Children with JIA enrolled in the multicenter CARRA Registry and from Emory University formed the study and replication cohorts. Phenotypic data on non-Hispanic AA children were compared with NHW children with JIA using the chi-square test, Fisher's exact test, and the Wilcoxon signed-rank test. In all, 4177 NHW and 292 AA JIA cases from the CARRA Registry and 212 NHW and 71 AA cases from Emory were analyzed. AA subjects more often had rheumatoid factor (RF)-positive polyarthritis in both the CARRA (13.4% vs 4.7%, p = 5.3 × 10(-7)) and the Emory (26.8% vs 6.1%, p = 1.1 × 10(-5)) cohorts. AA children had positive tests for RF and cyclic citrullinated peptide antibodies (CCP) more frequently, but oligoarticular or early onset antinuclear antibody (ANA)-positive JIA less frequently in both cohorts. AA children were older at onset in both cohorts and this difference persisted after excluding RF-positive polyarthritis in the CARRA Registry (median age 8.5 vs 5.0 yrs, p = 1.4 × 10(-8)). Compared with NHW children, AA children with JIA are more likely to have RF/CCP-positive polyarthritis, are older at disease onset, and less likely to have oligoarticular or ANA-positive, early-onset JIA, suggesting that the JIA phenotype is different in AA children.

A family case of early onset juvenile idiopathic arthritis with uveitis: lessons of the past and the present

Early onset of juvenile idiopathic arthritis (eoJIA) associated with pauci?polyarthicular joints involvement, antinuclear factor and uveitis is a special subtype of JIA. Generally accepted opinion of pediatric rheumatologists this JIA category isn`t belong to ankylosing spondylitis (AS)-related group of diseases.

Histone antibodies as a biomarker of uveitis in JIA

Uveitis is the most common extraarticular manifestation of juvenile idiopathic arthritis (JIA). The nature of JIA-associated uveitis is often insidious and asymptomatic, and baseline predictors can aid early diagnosis of eye disease for prompt and adequate treatment. Antihistone antibodies (AHA) are among subtypes of antinuclear antibodies (ANA) identified in children with JIA. An association between early-onset JIA, oligoarthritis and uveitis is shown in some studies, and we have previously shown that AHA is a significant predictor of chronic uveitis in a Norwegian JIA cohort. New interest for histones has emerged because epigenetic alterations of these DNA-binding molecules may be involved in the pathological processes of autoimmunity.

Female sex and oligoarthritis category are not risk factors for uveitis in Italian children with juvenile idiopathic arthritis.

To investigate the risk factors for chronic anterior uveitis in patients with juvenile idiopathic arthritis (JIA). The clinical charts of patients followed between January 1987 and December 2011 were reviewed to establish whether they had uveitis. Inclusion criteria were a diagnosis of JIA and a disease category of persistent oligoarthritis, extended oligoarthritis, rheumatoid factor-negative polyarthritis, psoriatic arthritis, or undifferentiated arthritis. Risk factors included sex, age at arthritis onset, disease category, and antinuclear antibody (ANA) status. The association of risk factors with occurrence of uveitis was evaluated by survival analysis, with first episode of uveitis as the event of interest, and Cox regression analysis. Of a total of 1189 patients, 278 (23.4%) had uveitis a median of 1.1 years after onset of arthritis. There was no difference in the cumulative probability of developing uveitis between males and females and between patients belonging to different JIA categories, whereas uveitis was strongly associated with age at arthritis onset ≤ 3.5 years and positive ANA. Patients possessing the latter 2 factors in combination had a greater probability of having uveitis than patients who had either of them alone. In our patients, the risk of uveitis was related to younger age at onset of arthritis and presence of ANA, but not to female sex and disease category. This finding suggests that the patients who require the most intensive ophthalmologic screening are those who have early-onset JIA and are ANA-positive, regardless of their sex or disease subtype.

AB0675 First episode of chronic anterior uveitis in patients with juvenile idiopathic arthritis and relationship with administered treatments

BackgroundChronic anterior uveitis is one of the most serious complications of juvenile idiopathic arthritis (JIA), showing an increased incidence in patients with early-onset disease, oligoarticualar, positive ANA. Biologic therapy used...

Bone status in adults with early-onset juvenile idiopathic arthritis following 1-year anti-TNFα therapy and discontinuation of glucocorticoids

Juvenile idiopathic arthritis (JIA) is an inflammatory disease associated with bone loss and low bone mineral density (BMD). The treatment involves disease-modifying antirheumatic drugs, glucocorticoids (GCs) and biological agents. The aim of this study was to evaluate effects of 12-month therapy with the anti-tumor necrosis factor alpha (anti-TNFα) preparations on bone mineral density (BMD) and biochemical turnover markers (BTM) in adult patients with JIA who were previously either treated or not treated with glucocorticoids (GC) and to assess effects of the discontinuation of GCs on their bone status. Nineteen adult patients (12 women, 7 men) aged 18-33years with active JIA were prospectively enrolled to receive the anti-TNFα therapy (infliximab, etanercept or adalimumab). BMD and BTMs were determined at baseline and 1-year follow-up. The anti-TNFα therapy resulted in a significant reduction in disease activity score 28 (DAS28) and C-reactive protein (CRP) and a significant increase in BMD at the lumbar spine and total body and in serum N-terminal propeptide of type I procollagen (PINP, marker of bone formation). No significant changes in serum beta C-terminal telopeptide of type I collagen (βCTX, marker of osteoclastic bone resorption) and osteocalcin (marker of bone remodeling) were found. A significant negative correlation was observed between the change in the DAS28, CRP and serum PINP. The change in serum PINP concentrations positively correlated with the change in lumbar spine BMD. A significant increase in serum PINP was observed only in patients discontinuing GCs during the anti-TNFα treatment. After the initiation of the anti-TNFα therapy in young adults with JIA, the increase in new bone formation can be explained by discontinuation of GCs administration as the patients with the largest reduction in DAS28 and CRP probably are the ones most likely to stop GC.

Imaging in early-onset juvenile idiopathic arthritis: ultrasonography (US) and MRI favours conventional radiography in detecting early inflammatory changes in joints

Results Synovitis in affected joints was detected by US and MRI but not by X-ray. Conclusion US and MRI favours conventional radiography in detecting early inflammatory changes in smaller children with EO-JIA. Although detailed information is given by MRI, the use of MRI is limited to one anatomical region and the smaller children it cannot be performed without general anaesthesia. Thus, US seem most helpful in detecting early inflammatory changes in EO-JIA. from 15th Paediatric Rheumatology European Society (PreS) Congress London, UK. 14–17 September 2008

Frequency of osteopenia in adolescents with early-onset juvenile idiopathic arthritis: a long-term outcome study of one hundred five patients.

To determine the frequency of low bone mineral content (BMC) and low bone mineral density (BMD) as long-term complications in adolescents with early-onset juvenile idiopathic arthritis (JIA), and to identify disease variables, patient characteristics, and biochemical bone markers related to low bone mass. One hundred five (87%) of 121 adolescent patients with early-onset JIA (ages 13-19 years, 80 girls and 25 boys, mean age at onset of JIA 2.8 years), from a cohort first admitted to the hospital between 1980 and 1985, were assessed after a mean disease duration of 14.2 years. BMC and BMD of the total body, the lumbar spine at L2-L4, and the femoral neck were measured by dual-energy x-ray absorptiometry. Age- and sex-specific reference values from a pooled, healthy reference population were used to calculate Z scores. Low bone mass was defined as a Z score less than -1 SD. Among the 103 adolescent JIA patients who underwent total-body imaging, 41% had low total-body BMC and 34% had low total-body BMD. Compared with adolescent JIA patients who had normal total-body BMC, those with low BMC had lower mean weight (P < 0.001), height (P < 0.001), lean mass (P < 0.001), and remission rates (P = 0.016), had longer duration of active disease (P = 0.013), had higher numbers of active and mobility-restricted joints (P < 0.001 and P = 0.001, respectively), had more disability (P = 0.011), had higher frequencies of joint erosions (P < 0.001), and had higher erythrocyte sedimentation rates (P = 0.033). In multiple linear regression analyses of total-body BMC, 88% of the variance was explained by the duration of active disease, the number of joints with restricted mobility, the bone area, urinary deoxypyridinoline values, age, weight, and height. Forty-one percent of the adolescents with early-onset JIA had low bone mass >11 years after disease onset. The development of low total-body BMC was related to the duration of active disease, disease severity, measures of bone resorption, weight, and height.