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Øystein Førre

Oslo University Hospital

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Berit Flatø

Oslo University Hospital

Margaretha Haugen

Norwegian Institute of Public Health

Odd Vinje

Oslo University Hospital

Jens Kjeldsen‐Kragh

Lund University

Rafał Płoski

Medical University of Warsaw

Dag Sørskaar

Oslo University Hospital

Erik Thorsby

Oslo University Hospital

Gunhild Lien

Diakonhjemmet Hospital

Tore K Kvien

Diakonhjemmet Hospital

Erik Kåss

Norwegian Cancer Society

Cooperative Institutions

Oslo University Hospital

127

University of Oslo

116

Institute of Immunology

Center for Rheumatology

University of Pennsylvania

Children's Hospital of Philadelphia

Karolinska Institutet

University College London

University of Bergen

Karolinska University Hospital

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Outcome and predictive factors in juvenile rheumatoid arthritis and juvenile spondyloarthropathy.

PubMed (1998)

Berit Flatø Astrid Aasland Odd Vinje Øystein Førre

To describe outcome and determine predictive factors in juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthopathy (JSpA).Seventy-two children with chronic arthritis were studied on first admission to the pediatric rheumatology clinic and after a mean of 9.7 +/- 1.8 yrs of disease duration.At followup, 53 patients had JRA and 19 had JSpA. Eleven (21%) of the patients with JRA did not meet the criteria for JRA on first admission, and 12 (22%) of 54 children diagnosed as having JRA on first admission were later reclassified as having another disease. Remission occurred in 43 (60%) of the 72 patients with JRA and JSpA. Forty-four patients (60%) reported no disability by the childhood or adult Health Assessment Questionnaire and 18 patients (25%) had developed joint erosions. Disease modifying antirheumatic drugs (DMARD) were given to 49 patients (68%) after a median of 0.8 yrs (range 0.2-10.8) disease duration. The patients who developed erosions and disability tended to have started treatment later than those who did not (NS). Active disease 5 years after onset was a predictor of disability in JRA and JSpA (OR 4.5, 95% CI 1.6-12.5). Predictors of joint erosions were long duration of elevated erythrocyte sedimentation rate (ESR) (OR 3.7/yr of elevated ESR, 95% CI 1.9-7.2), long disease duration before first admission (OR 1.5/yr of duration, 95% CI 1.1-2.1), long disease duration before treatment with DMARD (OR 1.8, 95% CI 1.0-3.3), and IgM rheumatoid factor (OR 12 x 10(4), 95% CI 0-1.2 x 10[52]).The longterm outcome in JRA and JSpA was more favorable than previously reported. This may be explained by less selection in favor of severely diseased patients and by the use of early aggressive treatment regimes.

Juvenile rheumatoid arthritis

Erythrocyte sedimentation rate

Rheumatoid factor

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Citations (154)

Genetic sharing and heritability of paediatric age of onset autoimmune diseases

Nature Communications (2015)

Leslie A. Lange Sihai Dave Zhao Jin Li Jonathan P. Bradfield Maedeh Mohebnasab

Abstract Autoimmune diseases (AIDs) are polygenic diseases affecting 7–10% of the population in the Western Hemisphere with few effective therapies. Here, we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, UC, CD, PS, SPA and CVID, attributable to common genomic variations (SNP -h 2 ). SNP- h 2 estimates are most significant for T1D (0.863±s.e. 0.07) and JIA (0.727±s.e. 0.037), more modest for UC (0.386±s.e. 0.04) and CD (0.454±0.025), largely consistent with population estimates and are generally greater than that previously reported by adult GWAS. On pairwise analysis, we observed that the diseases UC-CD (0.69±s.e. 0.07) and JIA-CVID (0.343±s.e. 0.13) are the most strongly correlated. Variations across the MHC strongly contribute to SNP -h 2 in T1D and JIA, but does not significantly contribute to the pairwise rG . Together, our results partition contributions of shared versus disease-specific genomic variations to pAID heritability, identifying pAIDs with unexpected risk sharing, while recapitulating known associations between autoimmune diseases previously reported in adult cohorts.

SNP

Genome-wide Association Study

Missing heritability problem

10.1038/ncomms9442

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Citations (77)

Radiographic and clinical outcome in early juvenile rheumatoid arthritis and juvenile spondyloarthropathy: a 3-year prospective study.

PubMed (2006)

Anne M. Selvaag Berit Flatø Knut Dale Gunhild Lien Odd Vinje

To describe radiographic findings at disease onset and 3-year followup in patients with juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthropathy (JSpA), to assess radiographic progression and its predictors, and to prospectively assess clinical outcome and predictors of persistent disease at 3-year followup.A total of 197 patients with JRA/JSpA were examined every 6 months for 3 years. Radiographic examination was performed at baseline and 3-year followup of knees and ankles (all patients) and of other joints on clinical indication. Remission was defined as minimum 6 months without medication and no clinical signs of active disease.Radiographic abnormalities were found in 88% of the patients at onset and in 81% after 3 years. Frequency of swelling/osteoporosis decreased and frequency of abnormal growth increased from baseline to followup. Knees, hands, and wrists had most frequently radiographic abnormalities. Radiographic progression occurred in 38% of the patients. Joints with swelling/osteoporosis on radiographs, young age, and a large number of mobility-restricted joints at baseline were predictors of radiographic progression. At 3 years, 26% of the patients were in remission and 75% had been treated with disease-modifying antirheumatic drugs. Reduced well-being, a large number of active joints and negative antinuclear antibody at baseline were predictors of persistent disease after 3 years.After 3 years most patients had radiographic abnormalities and persistent disease. Young age, many affected joints, reduced well-being, and negative antinuclear antibody at onset increased the risk of radiographic progression and persistent disease after 3 years.

Juvenile rheumatoid arthritis

Spondyloarthropathy

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VEGETARIAN DIET FOR PATIENTS WITH RHEUMATOID ARTHRITIS: CAN THE CLINICAL EFFECTS BE EXPLAINED BY THE PSYCHOLOGICAL CHARACTERISTICS OF THE PATIENTS?

Lara D. Veeken (1994)

Jens Kjeldsen‐Kragh Margaretha Haugen Øystein Førre H. LAACHE Ulrik Fredrik Malt

In a controlled, single blind clinical trial we have demonstrated recently a beneficial effect of fasting and vegetarian diet in RA. In the present study we compared 53 patients who participated in this clinical trial with 71 other RA patients with regard to some psychological parameters. The patients who participated in the clinical trial differed significantly from other RA patients. Firstly, they had a higher internal score and a lower chance score on the Multi-dimensional Health Locus of Control Scale (MHLCS). Secondly, their belief in the effect of ordinary medical treatment, evaluated by a 10-cm visual analogue scale, was lower, and their belief in the effect of 'alternative', unconventional forms of treatment was higher. Of the patients who were randomized to a vegetarian diet, there was no significant difference between diet responders and diet non-responders with regard to the MHLCS scores. But, diet responders had a significantly lower belief in the effect of ordinary medical treatment compared with diet non-responders. The psychological distress imposed on the patients by changing from an omnivorous diet to a vegetarian diet was monitored during the clinical trial by means of the General Health Questionnaire. Throughout the clinical trial, this variable favoured the vegetarians compared with the omnivorous and the diet responders vs the diet non-responders. We conclude, firstly, that patients with certain psychological characteristics were selected to the clinical trial; secondly, that the MHLCS scores could not explain the clinical improvement, but it may have been influenced by the patients' beliefs in ordinary and 'alternative' forms of treatment; and thirdly, that dietary treatment decreased psychological distress.

Psychological Distress

10.1093/rheumatology/33.6.569

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Citations (30)

Increased Brain Uptake of Copper and Zinc in Mice Caused by Diethyldithiocarbamate

Acta Pharmacologica et Toxicologica (1979)

Jan Aaseth Nils E. Seli Øystein Førre

Mice given 64CuCl2 and 65ZnCl2 (10 mumol/kg) were treated with sodium diethyldithiocarbamate (0.5 mmol/kg). The treatment increased the brain level of radioactive copper five-fold and that of radioactive zinc three-fold. Such redistribution of metal ions may be explained from the formation of lipophilic metal chelates. The increased brain levels may involve neurotoxic effects.

Sodium diethyldithiocarbamate

10.1111/j.1600-0773.1979.tb02358.x

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Citations (49)

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

Pediatric Rheumatology (2010)

Gunhild Lien Thor Ueland Kristin Godang Anne M. Selvaag Øystein Førre

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.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.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.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.

10.1186/1546-0096-8-30

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Citations (18)

Frequency of osteopenia in children and young adults with childhood‐onset systemic lupus erythematosus

Arthritis & Rheumatism (2005)

Vibke Lilleby Gunhild Lien Kathrine Frey Frøslie Margaretha Haugen Berit Flatø

Abstract Objective To determine the frequency of osteopenia in patients with childhood‐onset systemic lupus erythematosus (SLE) compared with that in healthy matched controls, and to evaluate the relationship between disease‐related variables and bone mineral mass. Methods Bone mineral density (BMD) and bone mineral content (BMC) were measured in a cohort of 70 patients with childhood‐onset SLE (mean ± SD disease duration 10.8 ± 8.3 years, mean ± SD age 26.4 ± 9.9 years) and 70 age‐ and sex‐matched healthy controls. BMD and BMC of the femoral neck, lumbar spine, total body, and distal one‐third of the radius were measured by dual x‐ray absorptiometry. We investigated the relationship between BMC and the following disease variables: cumulative dose of corticosteroids, organ damage, current use of corticosteroids, use of cyclophosphamide, age at disease onset, and disease activity at the time of diagnosis. Biochemical markers of bone metabolism were also measured. Results BMD values for the lumbar spine and femoral neck were significantly lower in patients than in healthy controls. The reduction in BMD of the lumbar spine was significantly greater than that of the total body. In multiple linear regression analyses, a higher cumulative corticosteroid dose was significantly associated with lower BMC of the lumbar spine and femoral neck. Decreased lumbar spine BMC was also related to male sex. Conclusion The frequency of osteopenia was higher in patients with childhood‐onset SLE than in matched controls. The lumbar spine was the most seriously affected skeletal site, followed by the femoral neck. The cumulative dose of corticosteroids was shown to be an important explanatory variable for BMC values in the lumbar spine and femoral neck.

Osteopenia

Cumulative dose

Bone disease

10.1002/art.21115

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Citations (77)

Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci

Faculty of Health; Institute of Health and Biomedical Innovation (2013)

A. Cortés J. Hadler J.P. Pointon Philip C. Robinson Tugce Karaderi

Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis-associated haplotypes at 11 loci. Two ankylosing spondylitis-associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.

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Trace Elements in Serum and Urine of Patients with Rheumatoid Arthritis

Scandinavian Journal of Rheumatology (1978)

Jan Aaseth E Munthe Øystein Førre E. Steinnes

Patients with rheumatoid arthritis were found to have elevated urinary copper excretion rates. They also had increased serum levels of coeruloplasmin and presumably also of a non-coeruloplasmin copper fraction. The zinc levels in serum and urine did not differ significantly from control values. Serum selenium and serum iron were decreased as compared with those of the healthy controls. It is suggested that an increased copper-to-selenium ratio may be of pathogenetic signficance. Biochemical changes induced by copper may be antagonized (at least partly) by the treatment with gold thiomalate and D-penicillamine. If serum selenium deficiency in RA can be confirmed in larger materials, selenium supplementation as a therapeutic measure should be considered.

Penicillamine

Serum concentration

Gold salts

10.3109/03009747809095662

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Citations (91)

Vegetarian diet for patients with rheumatoid arthritis — Status: Two years after introduction of the diet

Clinical Rheumatology (1994)

Jens Kjeldsen‐Kragh Margaretha Haugen C F Borchgrevink Øystein Førre

10.1007/bf02242946

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Citations (46)