Early Disease Course and Predictors of Disability in Juvenile Rheumatoid Arthritis and Juvenile Spondyloarthropathy: A 3 Year Prospective Study

ABSTRACT. Objective. To describe the 3 year disease course in early juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthropathy (JSpA), to compare the health status after 3 years of followup with that of normal controls, and to investigate the relationship between physical function at followup and disease characteristics recorded during the first 6 months. Methods: One hundred and ninety-seven children (median age 6.6 yrs) with JRA and JSpA and disease duration < 1.5 years were examined by a pediatric rheumatologist every 6 months for a median of 3.1 years. Controls were randomly selected from the National Population Register. Physical and psychosocial health was assessed by means of the Child Health Questionnaire and the Childhood Health Assessment Questionnaire (CHAQ). Disease course was analyzed by analysis of variance for repeated measurements. Results. Health status and disease activity improved over time. Treatment with disease modifying antirheumatic drugs was started in 58% of the patients at baseline. Patients with persistent oligoarthritis had the most favorable disease course. The patients with juvenile ankylosing spondylitis (JAS), syndrome of seronegative enthesopathy and arthropathy (SEA), and rheumatoid factor (RF) positive polyarthritis had the poorest health status. A significant improvement for the whole group was observed after 3 years in all measures of disease activity and health status, except pain. Patients had poorer physical function and general health and more pain than controls. Predictors of reduced physical function at followup were a high CHAQ disability index and a poor well-being assessed during the first 6 months. Conclusion. Health status and disease activity improved over time in patients under medical treatment. The patients with JAS/SEA and RF positive polyarthritis had poorer health than the patients in other subtypes. A high disability index and a poor well-being at baseline predicted reduced physical function after 3 years. (J Rheumatol 2005;32:1122-30

Serum levels of osteoprotegerin and receptor activator of nuclear factor -κB ligand in children with early juvenile idiopathic arthritis: a 2-year prospective controlled study

<p>Abstract</p> <p>Background</p> <p>The clinical relevance of observations of serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor -κB ligand (RANKL) in juvenile idiopathic arthritis (JIA) is not clear. To elucidate the potential role of OPG and RANKL in JIA we determined serum levels of OPG and RANKL in patients with early JIA compared to healthy children, and prospectively explored changes in relation to radiographic score, bone and lean mass, severity of the disease, and treatment.</p> <p>Methods</p> <p>Ninety children with early oligoarticular or polyarticular JIA (ages 6-18 years; mean disease duration 19.4 months) and 90 healthy children individually matched for age, sex, race, and county of residence, were examined at baseline and 2-year follow-up. OPG and RANKL were quantified by enzyme-immunoassay. Data were analyzed with the use of t-tests, ANOVA, and multiple regression analyses.</p> <p>Results</p> <p>Serum OPG was significantly lower in patients than controls at baseline, and there was a trend towards higher RANKL and a lower OPG/RANKL ratio. Patients with polyarthritis had significantly higher increments in RANKL from baseline to follow-up, compared to patients with oligoarthritis. RANKL was a significant negative predictor for increments in total body lean mass. Patients who were receiving corticosteroids (CS) or disease-modifying antirheumatic drugs (DMARDs) at follow-up had higher OPG/RANKL ratio compared with patients who did not receive this medication.</p> <p>Conclusions</p> <p>The data supports that levels of OPG are lower in patients with JIA compared to healthy children, and higher levels of RANKL is associated with more serious disease. RANKL was a significant negative predictor of lean mass in patients with JIA. The OPG/RANKL ratio was higher in patients on DMARDs or CS treatment.</p

Lack of association between the chemokine receptor 5 polymorphism CCR5delta32 in rheumatoid arthritis and juvenile idiopathic arthritis

<p>Abstract</p> <p>Background</p> <p>The chemokine receptor CCR5 has been detected at elevated levels on synovial T cells, and a 32 bp deletion in the <it>CCR5 </it>gene leads to a non-functional receptor. A negative association between the <it>CCR5Δ32 </it>and rheumatoid arthritis (RA) has been reported, although with conflicting results. In juvenile idiopathic arthritis (JIA), an association with CCR5 was recently reported. The purpose of this study was to investigate if the <it>CCR5Δ32 </it>polymorphism is associated with RA or JIA in Norwegian cohorts.</p> <p>Methods</p> <p>853 RA patients, 524 JIA patients and 658 controls were genotyped for the <it>CCR5Δ32 </it>polymorphism.</p> <p>Results</p> <p>The <it>CCR5Δ32 </it>allele frequency was 11.5% in the controls vs. 10.4% in RA patients (OR = 0.90; <it>P </it>= 0.36) and 9.7% in JIA patients (OR = 0.85; <it>P </it>= 0.20). No decreased homozygosity was observed for <it>CCR5Δ32</it>, as previously suggested.</p> <p>Conclusion</p> <p>Our data do not support an association between the <it>CCR5Δ32 </it>allele and Norwegian RA or JIA patients. Combining our results with those from a recently published meta-analysis still provide evidence for a role for <it>CCR5Δ32 </it>in RA, albeit substantially weaker than the effect first reported.</p

Measurement properties and performance of an eight-minute submaximal treadmill test in patients with juvenile idiopathic arthritis: a controlled study

Background Poor cardiorespiratory fitness is previously reported in patients with juvenile idiopathic arthritis (JIA) measured both by maximal and submaximal exercise tests, but a submaximal exercise test with acceptable measurement properties is currently lacking for both clinical and research purposes in this patient population. The objectives of this study were to evaluate the measurement properties and performance of a submaximal treadmill test in patients with JIA, and to compare the results with those obtained in controls. Methods Fifty-nine patients (50 girls), aged 10–16 years, with oligo- (n = 30) and polyarticular (n = 29) JIA, and 59 age- and sex-matched controls performed an eight-minute submaximal treadmill test for estimating peak oxygen uptake (VO2peak) followed by a maximal treadmill test measuring VO2peak directly. During the submaximal treadmill test, the study participants walked with no inclination at a speed between 3.2–7.2 km/h for four minutes, and then continued to walk at the same speed for four minutes with five % inclination. VO2peak was directly measured during a continuous graded exercise test on treadmill until exhaustion. Thirty-seven patients participated in the evaluation of the reliability. Criterion validity and reliability were evaluated with interclass correlation coefficient (ICC); measurement errors by Bland-Altman plot, standard error of measurement and smallest detectable change. Results In patients with JIA, the ICC (95% CI) for criterion validity was acceptable at group level 0.71 (0.51, 0.82), but not at individual level. The test-retest reliability and inter-rater reliability were acceptable at individual (0.84 (0.71, 0.91) and 0.92 (0.83, 0.96), respectively) and group levels (0.91 (0.83, 0.96) and 0.96 (0.91, 0.98), respectively). The measurement errors (for test-retest reliability/inter-rater reliability) were large. Bland-Altman plots showed no systematic differences, but a large variability for both the validity and reliability. The performance of and estimated VO2peak from the submaximal test were not associated with disease variables and were comparable between patients and controls. Conclusion The submaximal treadmill test is valid for use in patients with JIA on group level, but not on individual level. The reliability is acceptable. Due to large measurement errors, the submaximal treadmill test is not optimal for use in daily clinical practice to estimate VO2peak in individual patients

Radiographic damage in hands and wrists of patients with juvenile idiopathic arthritis after 29 years of disease duration

Abstract Background There are few studies on radiographic outcome after long-term disease duration in juvenile idiopathic arthritis (JIA). We wanted to evaluate 29-year radiographic outcome in hands/wrists and predictors of damage in patients with long-term active JIA. Methods Patients diagnosed from 1980 to 1985, who had active disease at 15-, 23- or 29-year follow-up and arthritis in the wrists during the disease course, were reexamined with radiographs of hands/wrists. We used the adapted version of the Sharp van der Heijde (aSvdH) score and Carpal Height Ratio (CHR) to evaluate radiographic outcome. Results Sixty patients, mean age 38 years, were reexamined at median 29-year follow-up. 33 patients (55%) had an aSvdH score >0, median score was 4.0 (range 0–313), and 25% of the scores were high (≥53). Most patients with radiographic damage (88%) had both erosions and JSN. 52% of the patients had damage in the wrists, 43% in the MCP joints and 40% in the PIP joints. The CHR correlated strongly with the aSvdH. Both scores had high correlations with the Juvenile Arthritis Damage Index and the number of joints with limited range of motion (LROM) (rs = -0.688 to 0.743, p ≤ 0.001). The aSvdH correlated weakly with measures of disease activity. The number of joints with LROM, ESR and the HAQ disability score at 15 years and HLAB27 positivity predicted the aSvdH score and the CHR at 29-year follow-up. Conclusions The majority of patients with long-term active JIA had modest radiographic damage, but more frequently in wrists than in fingers. The radiographic scores correlated well with measures of disease damage. Restricted mobility in joints at 15 years was the most important predictor of radiographic damage at 29 years

Physical activity in patients with oligo- and polyarticular juvenile idiopathic arthritis diagnosed in the era of biologics: a controlled cross-sectional study

Background Knowledge about objectively measured levels of physical activity (PA) and PA participation (included facilitators and barriers for PA) in patients with juvenile idiopathic arthritis (JIA) diagnosed in the era of biologics is limited. We aimed to compare objectively measured PA in patients with oligo- and polyarticular JIA diagnosed in the biologic era with controls and to examine associations between PA and disease variables; furthermore, to explore participation in PA, physical education (PE) and facilitators and barriers for PA participation in patients and controls. Methods The study cohort included 60 patients (30 persistent oligo JIA/30 poly-articular disease) and 60 age- and sex-matched controls. Age range was 10–16 years and 83% were female. PA was measured with accelerometry for seven consecutive days. Disease activity, current treatment, disease duration, functional ability, pain and fatigue were assessed. Structured interviews were applied to explore participation in PA and PE, and PA facilitators and barriers. Results Patients spent less time in daily vigorous PA than controls, (mean(SE) 21(2) min vs. 26(2) min, p = 0.02), while counts per minute (cpm), steps daily, sedentary time and light and moderate PA did not differ. No differences were found between JIA subgroups. The use of biologic medication was associated with higher cpm and lower sedentary time. Most patients and controls participated in organized or unorganized PA and PE, and enjoyment was the most reported facilitator for PA participation. More patients than controls reported pain as a PA barrier. Conclusion The PA levels and participation in patients with oligo- and polyarticular JIA are mostly comparable to controls, but patients still need to be encouraged to increase vigorous PA. Enjoyment is the most important facilitator for PA participation in patients with JIA

Arterial properties in adults with long-lasting active juvenile idiopathic arthritis compared to healthy controls

Background The data on cardiovascular risk and systemic arterial properties in patients with long-lasting juvenile idiopathic arthritis (JIA) is limited. The objective of this study was to describe systemic arterial properties including characteristic impedance (Z0), total arterial compliance (C), and peripheral vascular resistance (R) in patients with long-lasting active JIA compared with matched controls, and to assess the relation to JIA disease variables and traditional cardiovascular risk factors. Findings Methods: Eighty-one JIA patients (median age 38.6) with at least 15 years of active disease were reexamined after median 29 years of disease duration and compared to 41 healthy controls. With use of echocardiography and calibrated right common carotid artery tonometric pulse traces, noninvasive estimates of pressure and blood flow from the aortic root were obtained and used to estimate the systemic arterial parameters Z0, C and R. Results: The patients had higher Z0 as assessed by Windkessel model (mean ± SD 65.0 ± 30.1 versus 53.4 ± 18.8 10− 3 mmHg/ml/s, p = 0.027), lower C as assessed by either Windkessel model or ratio of stroke volume and pulse pressure (1.57 ± 0.46 versus 1.80 ± 0.65 ml/mmHg, p = 0.030, 1.29 ± 0.37 versus 1.43 ± 0.34 ml/mmHg, p = 0.038), and similar R compared to the controls. Years on daily prednisolone and insulin resistance were the most important correlates of Z0. Metotrexat use, polyarticular disease course and erythrocyte sedimentation rate were also associated with a higher Z0. Conclusion Our results indicate that JIA patients had altered arterial properties as compared to controls. Years on daily prednisolone and insulin resistance were the most important correlates of altered arterial properties