Anne M Selvaag

Disease progression into adulthood and predictors of long-term active disease in juvenile idiopathic arthritis.

Objectives To describe disease activity 30 years after disease onset in a previously studied cohort of patients with juvenile idiopathic arthritis (JIA) and reveal predictors of long-term active disease. Methods Patients with JIA, first referred 1980–1985 and re-examined 15 and 23 years after onset, were invited to attend. All 176 patients were assessed by questionnaires. Patients with signs of active disease at 15 years or later also came to a clinical re-examination (n=90). Disease activity was assessed by the clinical juvenile arthritis disease activity score (JADAS3) and by the criteria for remission in JIA, and health status by Health Assessment Questionnaire (HAQ) and Medical Outcome Study 36-item Short Form Health Survey (SF-36). Results At 30-year follow-up, 59% of the patients were in clinical remission off medication, 7% were in remission on medication and 34% had active disease. 70% of the patients were in the same category of disease activity at 15 and 30 years. The JADAS3 was ≤2.0 in 54%, 2.1–4.5 in 18% and >4.5 in 28%. HLA-DRB1*01, physicians global assessment and a short total time in remission at 15 years, predicted active disease. Physicians global assessment also predicted a JADAS3 >4.5. From 15 to 30 years (n=90), physicians global assessment, number of active joints, erythrocyte sedimentation rate and C reactive protein improved significantly, but patients global assessment, HAQ and SF-36 did not. Conclusions 41% of the patients with JIA had active disease or were on medication after 30 years and 28% had a high symptom state. Remission rates and patient-reported health status at 15 years were comparable with rates at 30 years.

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

BackgroundThe chemokine receptor CCR5 has been detected at elevated levels on synovial T cells, and a 32 bp deletion in the CCR5 gene leads to a non-functional receptor. A negative association between the CCR5Δ32 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 CCR5Δ32 polymorphism is associated with RA or JIA in Norwegian cohorts.Methods853 RA patients, 524 JIA patients and 658 controls were genotyped for the CCR5Δ32 polymorphism.ResultsThe CCR5Δ32 allele frequency was 11.5% in the controls vs. 10.4% in RA patients (OR = 0.90; P = 0.36) and 9.7% in JIA patients (OR = 0.85; P = 0.20). No decreased homozygosity was observed for CCR5Δ32, as previously suggested.ConclusionOur data do not support an association between the CCR5Δ32 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 CCR5Δ32 in RA, albeit substantially weaker than the effect first reported.

Arterial haemodynamics and coronary artery calcification in adult patients with juvenile idiopathic arthritis

Objective To compare arterial haemodynamics in adults with long-term juvenile idiopathic arthritis (JIA) to that of healthy controls, and explore the influence of traditional cardiovascular risk factors and disease characteristics on arterial haemodynamics plus coronary artery calcification. Methods 87 JIA patients (median age 38.4 years) with persistently active disease at least 15 years after disease onset (registered by longitudinal follow-up), were re-examined after median 29 years and compared with 87 matched controls. Arterial haemodynamics were characterised by arterial stiffness and blood pressure. Sphygmocor was used to measure the arterial stiffness markers pulse wave velocity (PWV) and augmentation index (AIx). Coronary calcification was assessed by CT. Results Compared to controls, patients had significantly higher PWV (7.2 vs 6.9 m/s, p=0.035), and systolic and diastolic blood pressure (SBP, p=0.050 and DBP, p=0.029). AIx was numerically higher in the patients compared to the controls, but no statistically significant difference was found. Coronary calcification was present in 22 (26%) of the patients. Daily smoking was more frequent (p=0.043), and insulin resistance was higher (p=0.034) in patients than controls. In patients, DBP, but no disease variables were determinants of PWV. Disease variables as well as traditional cardiovascular risk factors were associated with higher AIx, DBP and the presence of coronary calcification. Conclusions JIA patients with long-term active disease had altered arterial haemodynamics compared with controls in our study. PWV was mainly determined by increased DBP, a parameter that again was associated with JIA disease and treatment variables.

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

BackgroundThe 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.MethodsNinety 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.ResultsSerum 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.ConclusionsThe 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.

Physical Functioning, Pain and Health‐Related Quality of Life in Adults with Juvenile Idiopathic Arthritis: A Longitudinal 30‐Year Follow‐Up Study

To describe physical functioning, pain, and health‐related quality of life (HRQoL) in adults with juvenile idiopathic arthritis (JIA), investigate changes over time, and identify predictors of poorer HRQoL after 30 years of disease.

Cardiac Function in Adult Patients with Juvenile Idiopathic Arthritis

Objective. To compare cardiac function in adults with longterm juvenile idiopathic arthritis (JIA) with that of healthy controls, and to investigate the influence of inflammation, disease severity, and use of antirheumatic medication on cardiac function. Methods. Eighty-five patients with JIA (median age 38.6 yrs) with active disease for at least 15 years were reexamined at a median of 29 years after disease onset and compared with 46 matched controls. Echocardiography, including tissue Doppler imaging and longitudinal peak-systolic global strain, was used to assess diastolic and systolic myocardial function, and 12-channel electrocardiography was performed. Results. The interventricular septum was thicker in patients than controls (mean ± SD 0.8 ± 0.2 cm vs 0.7 ± 0.1 cm, p = 0.036). Diastolic function in patients was altered compared with controls characterized by lower mitral E wave deceleration time (165 ± 36 ms vs 180 ± 40 ms, p = 0.029), higher surrogate marker of left ventricular (LV) filling pressure (median lateral E/e’ 5.3, interquartile range 4.6–6.3 vs 4.8, 3.9–5.7, p = 0.036), and larger left atrial area (16.4 ± 2.9 cm2 vs 15.1 ± 2.8 cm2, p = 0.015). Systolic and diastolic blood pressures were higher in patients (120 ± 15 mmHg vs 114 ± 9 mmHg, p = 0.021 and 76 ± 10 mmHg vs 71 ± 8 mmHg, p = 0.009, respectively). QT corrected interval was similar in patients and controls. High high-sensitivity C-reactive protein (CRP), polyarticular disease course, and extended joint affection at 29-year followup, as well as duration of active disease, cumulative erythrocyte sedimentation rate, and CRP, and prednisolone use were associated with higher lateral E/e’. Conclusion. Adult patients with JIA did not differ from controls in LV systolic function, but had mildly thicker interventricular septum and indications for higher LV filling pressure, and most in patients with a higher disease burden.

PReS-FINAL-2003: Remission and predictors of persistent disease activity at 30 years follow-up in a Norwegian cohort of juvenile idiopathic arthritis patients

Long-term studies of remission rates in juvenile idiopathic arthritis (JIA) are few and difficult to compare because of different definitions of remission.