Vibke Lilleby

Association analysis of the 1858C>T polymorphism in the PTPN22 gene in juvenile idiopathic arthritis and other autoimmune diseases.

A functional single nucleotide polymorphism, 1858C>T, in the PTPN22 gene, encoding a tyrosine phosphatase, has been reported to be associated with type I diabetes and some other autoimmune diseases. To further investigate whether this polymorphism may be a general susceptibility factor for autoimmunity, we performed an association study in five different autoimmune diseases, three previously not tested. We found an association with juvenile idiopathic arthritis (OR=1.41; P=0.04), not previously reported, and a tendency for an association with coeliac disease (OR=1.35; P=0.08). In primary sclerosing cholangitis, no association was observed (OR=0.95; P=0.8). Furthermore, we confirmed the increased risk in rheumatoid arthritis (OR=1.58; P=0.001), but could not find support for an association with systemic lupus erythematosus (OR=0.94; P=0.8). Altogether, we have provided further evidence of an association between autoimmune diseases and the 1858C>T polymorphism in PTPN22.

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.

Preliminary definitions for the sonographic features of synovitis in children

Musculoskeletal ultrasonography (US) has the potential to be an important tool in the assessment of disease activity in childhood arthritides. To assess pathology, clear definitions for synovitis need to be developed first. The aim of this study was to develop and validate these definitions through an international consensus process.

Chest abnormalities in juvenile-onset mixed connective tissue disease: Assessment with high-resolution computed tomography and pulmonary function tests:

Background: Mixed connective tissue disease (MCTD) is associated with several chest manifestations. Only a few studies have focused on chest manifestations in juvenile-onset MCTD (jMCTD), and the true prevalence of pulmonary abnormalities on high-resolution computed tomography (HRCT) in these patients is unknown. Purpose: To investigate the occurrence of pulmonary abnormalities in jMCTD with particular reference to interstitial lung disease (ILD), and to evaluate a possible association between pulmonary findings and disease-related variables. Material and Methods: Twenty-four childhood-onset MCTD patients with median disease duration of 10.5 years (range 1–21 years) were investigated in a cross-sectional study by means of HRCT, pulmonary function tests (PFT), and clinical assessment. Results: Discrete ILD was identified in six patients (25%). Median extent of ILD was 2.0%, and all except one of the patients had very mild disease in which 5% or less of the parenchyma was affected. The CT features of fibrosis were mainly microcystic and fine intralobular. The most frequently abnormal PFT was carbon monoxide uptake from the lung, which was abnormal in 33% of the patients. PFT and disease duration were not significantly associated with HRCT findings of ILD. Conclusion: The prevalence of ILD in childhood-onset MCTD patients was lower than previously believed. In most of the patients with ILD, the findings were subtle and without clinical correlation. The results suggest a low extent of ILD in childhood-onset MCTD, even after long-term disease duration.

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.

Long-term outcome in juvenile-onset mixed connective tissue disease: a nationwide Norwegian study.

Objectives To describe the characteristics, outcome and predictive factors of juvenile mixed connective tissue disease (JMCTD) in a nationwide cohort of patients. Methods We examined 55 patients with JMCTD after a mean disease duration of 16.2 years (SD 10.0). Patients were registered according to Kasukawas criteria. Remission criteria were defined according to those for juvenile idiopathic arthritis, plus absence of cytopenia, myositis, progressive sclerodactyly, lung and oesophageal manifestations. Organ damage was assessed with the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index and the Juvenile Arthritis Damage Index (JADI). Medical records were reviewed for early predictors for outcome, which were assessed by multivariate logistic regression analyses. Results Three patients developed systemic lupus erythematosus (SLE). Fifty-two patients had continuous JMCTD; the most common manifestations were: Raynaud (100%), arthritis (94%), puffy hands (77%) and pulmonary manifestations (58%). SLE-like, systemic sclerosis (SSc)-like and polymyositis (PM)-like findings were found in 98%, 77% and 48%, respectively. Over time, SLE-like and PM-like manifestations decreased, and SSc-like findings increased. At follow-up, 35 patients (67%) had active disease and 17 (33%) were in remission. In 34 patients (65%), SLICC or JADI≥1 assessments indicated organ damage. Active disease was associated with higher anti-ribonucleoprotein antibody titres at follow-up and positive rheumatoid factor (RF) at diagnosis and follow-up. Conclusions Most patients with JMCTD had active disease and organ damage after a mean follow-up of 16.2 years. Active disease was associated with higher anti-ribonucleoprotein antibody levels and positive RF. The presence of RF at diagnosis predicted persistent disease activity.

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.

Clinical outcome in a Norwegian cohort of patients with chronic recurrent multifocal osteomyelitis

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease, characterized by non-infectious, recurrent osteomyelitis, which typically affects the metaphyseal regions of lo...

Pulmonary Manifestations and Progression of Lung Disease in Juvenile-onset Mixed Connective Tissue Disease

Objective. To assess the occurrence and extent of interstitial lung disease (ILD) in patients with juvenile mixed connective tissue disease (JMCTD), compare pulmonary function in patients and matched controls, study associations between ILD and disease-related variables, and examine progression of pulmonary manifestations over time. Methods. A cohort of 52 patients with JMCTD were examined in a cross-sectional study after a mean 16.2 (SD 10.3) years of disease duration with high-resolution computed tomography (HRCT) and pulmonary function tests (PFT) comprising spirometry, DLCO, and total lung capacity (TLC). Matched controls were examined with PFT. Previous HRCT and PFT were available in 37 and 38 patients (mean 8.8 and 10.3 yrs before study inclusion), respectively. Results. Compared to controls, patients with JMCTD had lower forced vital capacity (FVC), DLCO, and TLC (p < 0.01). The most frequent abnormal PFT was DLCO in 67% of patients versus 17% of controls (p < 0.001). Fourteen patients (27%) had ILD on HRCT. Most had ILD in < 10% of their lungs. ILD was associated with low values for FVC and TLC, but not with DLCO. HRCT findings did not progress significantly over time, but FVC declined (p < 0.01). Conclusion. Compared to controls, patients with JMCTD had impaired pulmonary function. ILD was present in 27% of patients after a mean 16 years of disease duration, mostly as mild disease, and did not progress. ILD seems to be less common in juvenile-onset than in adult-onset MCTD, and ILD in JMCTD seems mostly mild and stable over time.