Berit Flatø

• Frid, Paula Hanna Therese; Halbig, Josefine Mareile; Alstergren, Per; Berstad, Johanna Elisabeth Rykke; Cetrelli, Lena Elisabet & Feuerherm, Astrid Jullumstrø [Show all 15 contributors for this article] (2025). Cytokines in saliva, serum, and temporomandibular joint synovial fluid in children with juvenile idiopathic arthritis: An explorative cross-sectional study. Pediatric Rheumatology. 23. doi: 10.1186/s12969-025-01118-y. Full text in Research Archive Show summary

  Background Proinflammatory cytokines are central to disease mechanisms and important therapeutic targets in inflammatory chronic diseases. This exploratory study aimed to compare cytokine concentrations in saliva, serum, and temporomandibular joint (TMJ) synovial fluid in children with juvenile idiopathic arthritis (JIA) and controls. Methods In this cross-sectional study, we included consecutive children with JIA and TMJ arthritis, planned for a TMJ corticosteroid injection, and non-JIA controls from three different centers in Norway. Data on demographics, disease activity, presence of TMJ arthritis, and medication were obtained. Samples of unstimulated saliva, serum, and TMJ synovial fluid were collected. The amount of recovered synovial fluid in each sample, collected by the push-and-pull technique, was quantified with the hydroxocobalamin method. Cytokine levels were analyzed using Luminex xMAP technology. Results Fifteen patients with JIA and TMJ arthritis (JIA-TMJ) (median age 15.0 (interquartile range (IQR) 11.0–16.0) years) and 34 controls (median age 13.0 (IQR 9.8–15.0) years) were consecutively recruited. Samples of saliva (JIA-TMJ, n = 13, and controls, n = 28), serum (JIA-TMJ, n = 11, and controls, n = 16), and TMJ synovial fluid (JIA-TMJ, n = 8) were collected. In saliva from JIA-TMJ, we found significantly higher levels of the cytokines IL-1β, IL-4, IL-5, IL-9, IL-10, IL-12, IL-13, IL-17, Eotaxin, FGF basic, GM CSF, PDGF bb, TNF, and RANTES, while IP-10 was found in significantly lower concentration compared to controls. In serum, there were no significant differences in these cytokine concentrations between JIA-TMJ and controls. Three TMJ synovial samples fulfilled the strict sampling criteria and were included in the analysis. The level of detected cytokines in TMJ synovial samples was higher in JIA-TMJ compared to controls, as described in a previous Nordic study. Conclusions In this exploratory study, several proinflammatory cytokines were found in higher concentrations in saliva in JIA-TMJ compared to saliva from the controls. No differences were seen in serum between the groups. Some pro- and anti-inflammatory cytokines detected in JIA-TMJ synovial fluid were found in higher concentrations compared to TMJ synovial fluid from healthy adult reference data.

• Sande, Nina Krafft; Kirkhus, Eva; Lilleby, Vibke; Tomterstad, Anders; Aga, Anna-Birgitte & Flatø, Berit [Show all 7 contributors for this article] (2024). Validity of an ultrasonographic joint-specific scoring system in juvenile idiopathic arthritis: a cross-sectional study comparing ultrasound findings of synovitis with whole-body magnetic resonance imaging and clinical assessment. RMD Open. 10(1). doi: 10.1136/rmdopen-2023-003965. Full text in Research Archive Show summary

  Objective To assess the validity of an ultrasonographic scoring system in juvenile idiopathic arthritis (JIA) by comparing ultrasound detected synovitis with whole-body MRI and clinical assessment of disease activity. Methods In a cross-sectional study, 27 patients with active JIA underwent clinical 71-joints examination, non-contrast enhanced whole-body MRI and ultrasound evaluation of 28 joints (elbow, radiocarpal, midcarpal, metacarpophalangeal 2–3, proximal interphalangeal 2–3, hip, knee, tibiotalar, talonavicular, subtalar and metatarsophalangeal 2–3). One rheumatologist, blinded to clinical findings, performed ultrasound and scored synovitis (B-mode and power Doppler) findings using a semiquantitative joint-specific scoring system for synovitis in JIA. A radiologist scored effusion/synovial thickening on whole-body MRI using a scoring system for whole-body MRI in JIA. At patient level, associations between ultrasound synovitis sum scores, whole-body MRI effusion/synovial thickening sum scores, clinical arthritis sum scores, and the 71-joints Juvenile Arthritis Disease Activity Score (JADAS71) were calculated using Spearman’s correlation coefficients (rs). To explore associations at joint level, sensitivity and specificity were calculated for ultrasound using whole-body MRI or clinical joint examination as reference. Results Ultrasound synovitis sum scores strongly correlated with whole-body MRI effusion/synovial thickening sum scores (rs=0.74,p<0.01) and the JADAS71 (rs=0.71,p<0.01), and moderately with clinical arthritis sum scores (rs=0.57,p<0.01). Sensitivity/specificity of ultrasound in detecting synovitis were 0.57/0.96 and 0.55/0.96 using whole-body MRI or clinical joint examination as reference, respectively. Conclusion Our findings suggest that ultrasound is a valid instrument to detect synovitis, and that ultrasound synovitis sum scores can reflect disease activity and may be an outcome measure in JIA.

• Marstein, Henriette; NOMELAND, BIRGIT; Godang, Kristin; Olarescu, Nicoleta Cristina; Schwartz, Thomas & Flatø, Berit [Show all 10 contributors for this article] (2023). Adipokine profile in long-term juvenile dermatomyositis, and associations with adipose tissue distribution and cardiac function: a cross-sectional study. RMD Open. 9:e002815(1), p. 1–9. doi: 10.1136/rmdopen-2022-002815. Full text in Research Archive Show summary

  Objectives In long-term juvenile dermatomyositis (JDM), altered adipose tissue distribution and subclinical cardiac dysfunction have been described. Our aims were to compare adipokine levels in patients with JDM after long-term disease with controls, and explore associations between adipokines and (1) adipose tissue distribution and (2) cardiac function. Methods The study cohort included 59 patients with JDM (60% female, mean age 25.2 years, mean disease duration 16.9 years), and 59 age/sex-matched controls. Updated Pediatric Rheumatology International Trials Organization criteria for clinically inactive JDM were used to stratify patients into active (JDM-active) or inactive (JDM-inactive) disease groups. Lipodystrophy was clinically assessed in all patients. In all study participants, we measured adipose tissue distribution by dual-energy X-ray absorptiometry and cardiac function by echocardiography. Serum adipokines (adiponectin, apelin-12, lipocalin-2, leptin, visfatin and resistin) were analysed using ELISA. Results Patients with JDM had higher leptin levels compared with controls (p≤0.01). In JDM-active, apelin-12 and visfatin were higher compared with JDM-inactive (p≤0.05). In JDM-total and JDM-active, lower adiponectin correlated with lipodystrophy and total fat mass. Also, systolic dysfunction correlated with: lower adiponectin in JDM-total, JDM-inactive and JDM-active, and with lower apelin-12 in JDM-total and JDM-active and resistin in JDM-active (all p≤0.05). Lower adiponectin correlated with diastolic dysfunction in JDM-total and JDM-active. Conclusion After long-term disease, leptin levels were unfavourably regulated in patients with JDM compared with controls, and apelin-12 and visfatin in JDM-active versus JDM-inactive. We found associations between adipokines and both adipose tissue distribution and cardiac systolic function in all patients with JDM, which was most prominent in patients with active disease.

• Sande, Nina Krafft; Lilleby, Vibke; Aga, Anna-Birgitte; Kirkhus, Eva; Flatø, Berit & Bøyesen, Pernille (2023). Associations between power Doppler ultrasound findings and B-mode synovitis and clinical arthritis in juvenile idiopathic arthritis using a standardised scanning approach and scoring system. RMD Open. 9(1), p. 1–7. doi: 10.1136/rmdopen-2022-002937. Full text in Research Archive Show summary

  Objectives To describe power Doppler (PD) ultrasound findings in joint regions with B-mode (BM) synovitis using a standardised scanning protocol and scoring system in patients with juvenile idiopathic arthritis (JIA). Further, to examine associations between PD findings and BM synovitis, clinical arthritis, patient characteristics and disease activity. Methods In this cross-sectional study, one experienced ultrasonographer, blinded to clinical findings, performed ultrasound examinations in 27 JIA patients with suspected clinical arthritis. The elbow, wrist, metacarpophalangeal 2–3, proximal interphalangeal 2–3, knee, ankle and metatarsophalangeal 2–3 joints were assessed bilaterally and scored semiquantitatively (grades 0–3) for BM and PD findings using a joint-specific scoring system with reference atlas. Multilevel mixed-effects ordered regression models were used to explore associations between PD findings and BM synovitis, clinical arthritis, age, sex, JIA subgroups, disease duration and 10-joint Juvenile Arthritis Disease Activity Score (JADAS10). Results Twenty-one girls and six boys, median age (IQR) 8 years (6–12 years) were included. Overall, 971 joint regions were evaluated by ultrasound, 129 had BM synovitis and were assessed for PD. PD findings were detected in 45 joint regions (34.9%), most frequently in the parapatellar recess of the knee (24.4%). Increasing PD grades were associated with higher BM grades (OR=5.0,p&lt;0.001) and with clinical arthritis (OR=7.4,p&lt;0.001) but not with age, sex, JIA subgroups, disease duration or JADAS10. Conclusion Increasing severity of PD findings were significantly associated with BM synovitis and with clinical arthritis. This suggests that PD signals detected using a standardised ultrasound examination and scoring system can reflect active disease in JIA patients.

• Kim, Hanna; Saygin, Didem; Douglas, Christian; Wilkerson, Jesse; Erman, Brian & Pistorio, Angela [Show all 22 contributors for this article] (2023). Performance of the 2016 ACR-EULAR myositis response criteria in juvenile dermatomyositis therapeutic trials and consensus profiles. Rheumatology. ISSN 1462-0324. 62(11), p. 3680–3689. doi: 10.1093/rheumatology/kead111. Full text in Research Archive
• Zadig, Pia Karin Karlsen; Brandis, Elisabeth von; Flatø, Berit; Müller, Lil-Sofie Ording; Nordal, Ellen Berit & Horatio, Laura Tanturri De [Show all 8 contributors for this article] (2022). Whole body magnetic resonance imaging in healthy children and adolescents: Bone marrow appearances of the appendicular skeleton. European Journal of Radiology. ISSN 0720-048X. 153. doi: 10.1016/j.ejrad.2022.110365. Full text in Research Archive Show summary

  Background Whole-body magnetic resonance imaging (MRI) is increasingly being used in children, however, to date there are no studies addressing the reliability of the findings. Objective To examine intra- and interobserver reliability of a scoring system for assessment of high signal areas within the bone marrow, as visualized on T2-weighted, fat-saturated images. Materials and methods Ninety-six whole-body MRIs (1.5 T) in 78 healthy volunteers (mean age: 11.5 years) and 18 children with chronic nonbacterial osteomyelitis (mean age: 12.4 years) were included. Coronal water-only Dixon T2-weighted images were used to score the left lower extremity/pelvis for high signal intensity areas, intensity (0–2 scale), extension (0–4 scale) and shape and contour in a blinded fashion by two pairs of radiologists. Results For the pelvis, grading of bone marrow signal showed moderate to good intra- and interobserver agreement with kappa values of 0.51–0.94 and 0.41–0.87, respectively. Corresponding figures for the femur were 0.61–0.68 within and 0.32–0.61 between observers, and for the tibia 0.60–0.72 and 0.51–0.73. Agreement for assessing extension was moder- ate to good both within and between observers for the pelvis (k = 0.52–0.85 and 0.35–0.80), for the femur (0.52–0.67 and 0.51–0.60) and for the tibia (k = 0.59–0.69 and 0.47–0.63) except for the femur metaphysis/diaphysis, with interobserver kappa values of 0.29–0.30. Scoring of shape was moderate to good within observers, but in general poorer between observ- ers, with kappa values of 0.40–0.73 and 0.18–0.69, respectively. For contour, the corresponding figures were 0.35–0.62 and 0.09–0.54, respectively. Conclusion MRI grading of intensity and extension of high signal intensity areas within the bone marrow of pelvis and lower limb performs well and thus can be used interchangeably by different observers, while assessment of shape and contour is reli- able for the same observer but is less reliable between observers. This should be considered when performing clinical trials. Keywords Adolescents · Bone marrow · Children · Magnetic resonance imaging · Validation study · Whole-body imaging

• Tollisen, Anita; Selvaag, Anne Marit G; Aasland, Astrid; Ingebrigtsen, Trude Miljeteig; Sagen, Joachim & Lerdal, Anners [Show all 7 contributors for this article] (2022). Personally generated quality of life outcomes in adults with juvenile idiopathic arthritis. Journal of Rheumatology. ISSN 0315-162X. 49(10), p. 1138–1145. doi: 10.3899/jrheum.211245. Full text in Research Archive Show summary

  Objective To explore quality of life (QOL) using the individualized Patient Generated Index (PGI) in young adults who were diagnosed with juvenile idiopathic arthritis ( JIA) in childhood, and to examine associations between PGI ratings and standardized health-related outcome measures. Methods Patients (N = 79, mean age 25.1 [SD 4.2] yrs, 72% female) completed the PGI and the standardized measures: Health Assessment Questionnaire–Disability Index, 12-item Short Form Health Survey (SF-12; physical and mental health-related QOL [HRQOL]), Brief Pain Inventory (pain severity and interference), 5-item Hopkins Symptom Checklist, and visual analog scale for fatigue. Information on morning stiffness, medications, and demographics was also collected. Patients were compared to 79 matched controls. Results The most frequently nominated areas of importance for patients' personally generated QOL (assessed by PGI) were physical activity (n = 38, 48%), work/school (n = 31, 39%), fatigue (n = 29, 37%) and self-image (n = 26, 33%). Nomination of physical activity was associated with older age, morning stiffness, and more pain interference. Nomination of fatigue was associated with current use of disease-modifying antirheumatic drugs, whereas nomination of self-image was associated with polyarticular course JIA and pain interference. Nomination of work/school was not associated with other factors. Higher PGI scores (indicating better QOL) correlated positively with all SF-12 subscales except role emotional, and negatively with disability, pain severity, pain interference, and morning stiffness. Compared to controls, patients had more pain, poorer physical HRQOL, and less participation in full-time work or school. Conclusion Physical activity, work/school, fatigue, and self-image were frequently nominated areas affecting QOL in young adults with JIA. The PGI included aspects of QOL not covered in standardized measures.

• Li, Jin; Li, Yun R.; Glessner, Joseph T.; Yang, Jie; March, Michael E. & Kao, Charlly [Show all 28 contributors for this article] (2022). Identification of Novel Loci Shared by Juvenile Idiopathic Arthritis Subtypes Through Integrative Genetic Analysis. Arthritis & Rheumatology. ISSN 2326-5191. 74(8), p. 1420–1429. doi: 10.1002/art.42129. Full text in Research Archive Show summary

  Objective.Juvenile idiopathic arthritis (JIA) is the most common chronic immune-mediated joint disease amongchildren and encompasses a heterogeneous group of immune-mediated joint disorders classified into 7 subtypes according to clinical presentation. However, phenotype overlap and biologic evidence suggest a shared mechanistic basisbetween subtypes. This study was undertaken to systematicallyinvestigate shared genetic underpinnings of JIA subtypes.Methods.We performed a heterogeneity-sensitive genome-wide association study encompassing a total of 1,245JIA cases (classified into 7 subtypes) and 9,250 controls, followed byfine-mapping of candidate causal variants at eachgenome-wide significant locus, functional annotation, and pathway and network analysis. We further identified candi-date drug targets and drug repurposing opportunities by in silico analyses.Results.In addition to the major histocompatibility complex locus, we identified 15 genome-wide significant loci shared between at least 2 JIA subtypes, including 10 novel loci. Functional annotation indicated that candidate genesat these loci were expressed in diverse immune cell types. Conclusion.This study identified novel genetic loci shared by JIA subtypes. Ourfindings identified candidatemechanisms underlying JIA subtypes and candidate targets with drug repurposing opportunities for JIA treatment.

• NOMELAND, BIRGIT; Schwartz, Thomas; Barth, Zoltan; Taraldsrud, Eli; Samersaw-Lund, May Brit & Aaløkken, Trond Mogens [Show all 9 contributors for this article] (2022). Associations between cardiac and pulmonary involvement in patients with juvenile dermatomyositis—a cross-sectional study. Rheumatology International. ISSN 0172-8172. 42, p. 1213–1220. doi: 10.1007/s00296-021-05071-3. Full text in Research Archive Show summary

  Abstract This study aimed at exploring the association between detectable cardiac and pulmonary involvement in long-term juvenile dermatomyositis (JDM) and to assess if patients with cardiac and pulmonary involvement differ with regard to clinical characteristics. 57 JDM patients were examined mean 17.3 (10.5) years after disease onset; this included clinical examination, myositis specific/associated autoantibodies (immunoblot), echocardiography, pulmonary function tests and high-resolution computed tomography. Cardiac involvement was defined as diastolic and/or systolic left ventricular dysfunction and pulmonary involvement as low diffusing capacity for carbon monoxide, low total lung capacity and/or high-resolution computed tomography abnormalities. Patients were stratified into the following four groups: (i) no organ involvement, (ii) pulmonary only, (iii) cardiac only, and (iv) co-existing pulmonary and cardiac involvement. Mean age was 25.7 (12.4) years and 37% were males. One patient had coronary artery disease, seven had a history of pericarditis, seven had hypertension and three had known interstitial lung disease prior to follow-up. There was no association between cardiac (10/57;18%) and pulmonary (41/57;72%) involvement ( p  = 0.83). After stratifying by organ involvement, 21% of patients had no organ involvement; 61% had pulmonary involvement only; 7% had cardiac involvement only and 11% had co-existing pulmonary or cardiac involvement. Patients with co-existing pulmonary or cardiac involvement had higher disease burden than the remaining patients. Patients with either cardiac or pulmonary involvement only, differed in clinical and autoantibody characteristics. We found no increased risk of developing concomitant cardiac/pulmonary involvement in JDM. Our results shed light upon possible different underlying mechanisms behind pulmonary and cardiac involvement in JDM.

• Brandis, Elisabeth von; Jenssen, Håvard Bjørke; Avenarius, Derk Frederik Matthaus; Bjørnerud, Atle; Flatø, Berit & Tomterstad, Anders [Show all 11 contributors for this article] (2022). Automated segmentation of magnetic resonance bone marrow signal: a feasibility study. Pediatric Radiology. ISSN 0301-0449. 52, p. 1104–1114. doi: 10.1007/s00247-021-05270-x. Full text in Research Archive Show summary

  Background - Manual assessment of bone marrow signal is time-consuming and requires meticulous standardisation to secure adequate precision of findings.<p> <p>Objective - We examined the feasibility of using deep learning for automated segmentation of bone marrow signal in children and adolescents.<p> <p>Materials and methods - We selected knee images from 95 whole-body MRI examinations of healthy individuals and of children with chronic non-bacterial osteomyelitis, ages 6–18 years, in a longitudinal prospective multi-centre study cohort. Bone marrow signal on T2-weighted Dixon water-only images was divided into three color-coded intensity-levels: 1 = slightly increased; 2 = mildly increased; 3 = moderately to highly increased, up to fluid-like signal. We trained a convolutional neural network on 85 examinations to perform bone marrow segmentation. Four readers manually segmented a test set of 10 examinations and calculated ground truth using simultaneous truth and performance level estimation (STAPLE). We evaluated model and rater performance through Dice similarity coefficient and in consensus.<p> <p>Results - Consensus score of model performance showed acceptable results for all but one examination. Model performance and reader agreement had highest scores for level-1 signal (median Dice 0.68) and lowest scores for level-3 signal (median Dice 0.40), particularly in examinations where this signal was sparse.<p> <p>Conclusion - It is feasible to develop a deep-learning-based model for automated segmentation of bone marrow signal in children and adolescents. Our model performed poorest for the highest signal intensity in examinations where this signal was sparse. Further improvement requires training on larger and more balanced datasets and validation against ground truth, which should be established by radiologists from several institutions in consensus.

• Bardan, Imane; Fagerli, Karen Minde; Sexton, Joseph; Kvien, Tore Kristian Aaserud; Bakland, Gunnstein & Pawel, Mielnik [Show all 12 contributors for this article] (2022). Treatment Response to Tumor Necrosis Factor Inhibitors and Methotrexate Monotherapy in Adults With Juvenile Idiopathic Arthritis: Data From NOR-DMARD. Journal of Rheumatology. ISSN 0315-162X. 50(4), p. 538–547. doi: 10.3899/JRHEUM.220645. Full text in Research Archive Show summary

  Objective To compare the effectiveness of tumor necrosis factor inhibitors (TNFi) ± comedication and methotrexate (MTX) monotherapy between patients with adult juvenile idiopathic arthritis (JIA) and patients with rheumatoid arthritis (RA). Methods Adult patients with JIA and RA were identified from the Norwegian Antirheumatic Drug Register (NOR-DMARD) register. Disease activity measurements at baseline, 3, 6, and 12 months were compared between patients with JIA and RA starting (1) TNFi and (2) MTX monotherapy, using age- and gender-weighted analyses. We calculated differences between JIA and RA in mean changes in Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI), among other disease activity measures. DAS28, CDAI, SDAI, and American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) remission rates at 3, 6, and 12 months, as well as 6- and 12-month Lund Efficacy Index (LUNDEX)-corrected rates, were calculated. Results We identified 478 patients with JIA (TNFi/MTX monotherapy, n = 358/120) and 4637 patients with RA (TNFi/MTX monotherapy, n = 2292/2345). Patients with JIA had lower baseline disease activity compared to patients with RA across treatment groups. After baseline disease activity adjustment, there were no significant differences in disease activity change from baseline to 3, 6, and 12-months of follow-up between patients with JIA and RA for either treatment group. Twelve-month remission rates were similar between groups based on DAS28 (TNFi: JIA 55.2%, RA 49.5%; MTX monotherapy: JIA 45.3%, RA 41.2%) and ACR/EULAR remission criteria (TNFi: JIA 20.4%, RA 20%; MTX monotherapy: JIA 17%, RA 12.7%). Median drug survival (yrs) was similar for JIA and RA in both treatment groups (TNFi: JIA 1.2, RA 1.4; MTX monotherapy: JIA 1.3, RA 1.6). Conclusion TNFi and MTX monotherapy are effective in adult JIA, with similar effectiveness to that shown in RA.

• Brandis, Elisabeth von; Zadig, Pia Karin Karlsen; Avenarius, Derk Frederik Matthaus; Flatø, Berit; Knudsen, Per Kristian & Lilleby, Vibke [Show all 9 contributors for this article] (2022). Whole body magnetic resonance imaging in healthy children and adolescents. Bone marrow appearances of the axial skeleton. European Journal of Radiology. ISSN 0720-048X. 154, p. 1–9. doi: 10.1016/j.ejrad.2022.110425. Full text in Research Archive Show summary

  Objective - To describe the findings of focal high signal on T2 weighted (T2W) images of the bone marrow in the axial skeleton as assessed by whole-body MRI in healthy and asymptomatic children and adolescents.<p> <p>Material and methods - We assessed the bone marrow of the mandible, shoulder girdle, thorax, spine, and pelvis on water-only Dixon T2W sequences as part of a whole-body MRI protocol in 196 healthy and asymptomatic children aged 5–19 years. Intensity (0–2 scale) and extension (1–4 scale) of focal high signal areas in the bone marrow were scored and divided into minor or major findings, based on intensity and extension to identify the potentially conspicuous lesions in a clinical setting.<p> <p>Results - We registered 415 areas of increased signal in the axial skeleton whereof 75 (38.3%) were major findings. Fifty-eight (29.6%) individuals had at least one major finding, mainly located in the pelvis (54, 72%). We found no differences according to gender. The number of minor findings increased with age (p = 0.020), but there were no significant differences in the number of major findings. The most conspicuous findings were in the pelvis, spine and sternum.<p> <p>Conclusion - Non-specific bone marrow T2W hyperintensities in the axial skeleton are frequently detected on whole-body MRI in healthy, asymptomatic children. Awareness of this is important as some findings may resemble clinically silent lesions in children with suspected multifocal skeletal disease.

• Marstein, Henriette; Witczak, Birgit Nomeland; Godang, Kristin; Schwartz, Thomas; Flatø, Berit & Bollerslev, Jens [Show all 8 contributors for this article] (2022). Adipose tissue distribution is associated with cardio-metabolic alterations in adult patients with juvenile-onset dermatomyositis. Rheumatology. ISSN 1462-0324. 62(2), p. 1–9. doi: 10.1093/rheumatology/keac293. Full text in Research Archive Show summary

  Abstract Objectives Primary aims were to compare adipose tissue distribution in adult patients with juvenile-onset DM (JDM), with matched controls. Secondary aims were to explore how adipose tissue distribution is associated with cardio-metabolic status (cardiac dysfunction and metabolic syndrome) in patients. Methods Thirty-nine JDM patients (all aged ≥18 y, mean age 31.7 y and 51% female) were examined mean 22.7 y (s.d. 8.9 y) after disease onset and compared with 39 age/sex-matched controls. In patients, disease activity and lipodystrophy were assessed by validated tools and use of prednisolone noted. In all participants, dual-energy X-ray absorptiometry (DXA) and echocardiography were used to measure visceral adipose tissue (VAT)(g) and cardiac function, respectively. Risk factors for metabolic syndrome were measured and associations with adipose tissue distribution explored. For primary and secondary aims, respectively, P-values ≤0.05 and ≤0.01 were considered significant. Results Patients exhibited a 2.4-fold increase in VAT, and reduced HDL-cholesterol values compared with controls (P-values ≤ 0.05). Metabolic syndrome was found in 25.7% of the patients and none of the controls. Cardiac dysfunction (systolic and/or diastolic) was found in 23.7% of patients and 8.1% of controls (P = 0.07). In patients, VAT levels were correlated with age, disease duration and occurrence of metabolic syndrome and cardiac dysfunction. Occurrence of lipodystrophy (P = 0.02) and male sex (P = 0.04) tended to be independently associated with cardiac dysfunction. Conclusion Adults with JDM showed more central adiposity and cardio-metabolic alterations than controls. Further, VAT was found increased with disease duration, which was associated with development of cardio-metabolic syndrome.

• Hu, Yi; Rojahn, Astrid & Flatø, Berit (2021). Multiorgan inflammatorisk syndrom hos barn og ungdom etter SARS-CoV-2-infeksjon. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. p. 1–8. doi: 10.4045/tidsskr.20.1040. Full text in Research Archive
• Marstein, Henriette; Godang, Kristin; Flatø, Berit; Sjaastad, Ivar; Bollerslev, Jens & Sanner, Helga (2021). Bone mineral density and explanatory factors in children and adults with juvenile dermatomyositis at long term follow-up; a cross sectional study. Pediatric Rheumatology. 19(1), p. 1–11. doi: 10.1186/s12969-021-00543-z. Full text in Research Archive Show summary

  Background Juvenile dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy in children and adolescents. Both the disease and its treatment with glucocorticoids may negatively impact bone formation. In this study we compare BMD in patients (children/adolescence and adults) with long-standing JDM with matched controls; and in patients, explore how general/disease characteristics and bone turnover markers are associated with BMD. Methods JDM patients (n = 59) were examined median 16.8y (range 6.6–27.0y) after disease onset and compared with 59 age/sex-matched controls. Dual-energy X-ray absorptiometry (DXA) was used to measure BMD of the whole body and lumbar spine (spine) in all participants, and of ultra-distal radius, forearm and total hip in participants ≥20y only. Markers of bone turnover were analysed, and associations with outcomes explored. Results Reduced BMD Z-scores (<−1SD) were found in 19 and 29% of patients and 7 and 9% of controls in whole body and spine, respectively (p-values < 0.05). BMD and BMD Z-scores for whole body and spine were lower in all patients and for < 20y compared with their respective controls. In participants ≥20y, only BMD and BMD Z-score of forearm were lower in the patients versus controls. In patients, BMD Z-scores for whole body and/or spine were found to correlate negatively with prednisolone use at follow-up (yes/no) (age < 20y), inflammatory markers (age ≥ 20y) and levels of interferon gamma-induced protein 10 (IP-10) (both age groups). In all patients, prednisolone use at follow-up (yes/no) and age ≥ 20y were independent correlates of lower BMD Z-scores for whole body and spine, respectively. Conclusion In long-term JDM, children have more impairment of BMD than adults in spine and whole-body. Associations with BMD were found for both prednisolone and inflammatory markers, and a novel association was discovered with the biomarker of JDM activity, IP-10.

• NOMELAND, BIRGIT; Bollerslev, Jens; Godang, Kristin; Schwartz, Thomas; Flatø, Berit & Molberg, Øyvind [Show all 8 contributors for this article] (2021). Body composition in long-standing juvenile dermatomyositis: associations with disease activity, muscle strength and cardiometabolic measures. Rheumatology. ISSN 1462-0324. 61(7), p. 2959–2968. doi: 10.1093/rheumatology/keab805. Full text in Research Archive Show summary

  Abstract Objective To (i) compare body composition parameters in patients with longstanding juvenile dermatomyositis (JDM) and controls and (ii) explore associations between body composition and disease activity/inflammation, muscle strength, health-related quality of life (HRQL) and cardiometabolic measures. Methods In a cross-sectional study, we included 59 patients (median disease duration 16.7 y; median age 21.5 y) and 59 age- and sex-matched controls. Active/inactive disease were defined by the PRINTO criteria. Body composition was assessed by total body dual-energy absorptiometry (DXA), inflammation by hs-CRP and cytokines, muscle strength by manual muscle test (MMT-8), HRQL by 36-item short form survey physical component score (SF-36 PCS) and cardiometabolic function by echocardiography (systolic and diastolic function) and serum-lipids. Results DXA analyses revealed lower appendicular lean mass index (ALMI) (reflecting limb skeletal muscle mass), higher body fat percentage (BF%) and higher android: gynoid fat ratio (A: G ratio) (reflecting central fat distribution) in patients than controls, despite similar BMI. Patients with active disease had lower ALMI and higher BF% than those with inactive disease; lower ALMI and higher BF% were associated with inflammation (elevated monocyte attractant protein-1 (MCP-1) and hs-CRP). Lower ALMI was associated with reduced muscle strength; higher BF% was associated with impaired HRQL. Central fat distribution (higher A: G ratio) was associated with impaired cardiac function and unfavorable serum-lipids. Conclusion : Despite normal BMI, patients with JDM, especially those with active disease, had unfavorable body composition, which was associated with impaired HRQL/muscle strength and cardiometabolic function. The association between central fat distribution and cardiometabolic alterations is a novel finding in JDM.

• Sande, Nina Krafft; Bøyesen, Pernille Helen; Aga, Anna-Birgitte; Hammer, Hilde Berner; Flatø, Berit & Roth, Johannes [Show all 7 contributors for this article] (2021). Development and reliability of a novel ultrasonographic joint-specific scoring system for synovitis with reference atlas for patients with juvenile idiopathic arthritis. RMD Open. 7(2). doi: 10.1136/rmdopen-2021-001581. Full text in Research Archive Show summary

  Objective To develop an ultrasonographic image acquisition protocol and a joint-specific scoring system for synovitis with reference atlas in patients with juvenile idiopathic arthritis (JIA) and to assess the reliability of the system. Methods Seven rheumatologists with extensive ultrasound experience developed a scanning protocol and a semiquantitative joint-specific scoring system for B-mode (BM) synovitis for the elbow, wrist, metacarpophalangeal 2–3, proximal interphalangeal 2–3, hip, knee, ankle and metatarsophalangeal 2–3 joints. An ultrasonographic reference atlas for BM synovitis, divided in four age groups (2–4, 5–8, 9–12, 13–18 years), and power Doppler (PD) activity was then developed. Reliability was assessed for all joints on still images and in a live exercise including 10 patients with JIA, calculated by intraclass correlation coefficient (ICC) and weighted kappa. Results A scanning protocol and scoring system for multiple joints with reference atlas composed of images with four different score levels for BM and PD were developed. Still image scoring for BM synovitis on joint level showed good to excellent intra-reader reliability (ICC/kappa ranges: 0.75–0.95/0.63–0.91) and moderate to excellent inter-reader reliability (ICC/kappa ranges: 0.89–0.99/0.50–0.91). Still image scoring for PD activity showed excellent intra-reader and inter-reader reliability (ICC/kappa: 0.96/0.91 and ICC/kappa: 0.97/0.80, respectively). In the live scoring, inter-reader reliability (ICC/kappa) was moderate to excellent for BM synovitis (0.94/0.51) and PD activity (0.91/0.60). Conclusion An ultrasonographic image acquisition protocol and joint-specific scoring system with reference atlas were developed and demonstrated moderate to excellent reliability for scoring of synovitis in patients with JIA. This can be a valuable tool in clinical practice and future research.

• Malattia, Clara; Ruperto, Nicolino; Pederzoli, Silvia; Palmisani, Elena; Pistorio, Angela & Wouters, Carine [Show all 15 contributors for this article] (2020). Tocilizumab may slow radiographic progression in patients with systemic or polyarticular-course juvenile idiopathic arthritis: Post hoc radiographic analysis from two randomized controlled trials. Arthritis Research & Therapy. ISSN 1478-6354. 22(1), p. 1–11. doi: 10.1186/s13075-020-02303-y. Full text in Research Archive Show summary

  Background Few clinical trials have investigated the prevention of radiographic progression in children with juvenile idiopathic arthritis treated with antirheumatic drugs. This study aimed to investigate radiographic progression in patients with systemic juvenile idiopathic arthritis (sJIA) and patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with the anti–interleukin-6 receptor antibody tocilizumab for 2 years in the TENDER and CHERISH randomized controlled trials, respectively. Methods Standard radiographs of both wrists and both hands in the posteroanterior view were obtained within 4 weeks of baseline and were repeated at weeks 52 ± 4 and 104 ± 4 in both trials. All films were scored by two independent readers using the adapted Sharp–van der Heijde (aSH) and Poznanski scoring methods. Although the Poznanski score indicates bone growth limitation or cartilage growth decrease, which are not the same as joint space narrowing in rheumatoid arthritis, its change reflects damage to cartilage. Therefore, impairment in the Poznanski score as well as the aSH score was considered as a measure of structural joint damage. Radiographic progression was defined as worsening of radiographic scores beyond the smallest detectable difference. Results Poznanski and aSH scores were available at baseline and at one or more postbaseline time points for 33 and 47 of 112 sJIA patients and 61 and 87 of 188 pcJIA patients, respectively, providing a representative subset of the study populations. The inter-reader and intra-reader agreement intra-class correlation coefficient was > 0.8. Median baseline Poznanski and aSH scores, respectively, were − 2.4 and 24.6 for sJIA patients and − 1.5 and 8.0 for pcJIA patients. Compared with baseline, aSH scores remained stable for all sJIA patients at week 52, whereas 9.4% of sJIA patients had radiographic progression according to Poznanski scores at week 52; at 104 weeks, radiographic progression according to aSH and Poznanski scores was observed in 5.4% and 11.5%, respectively. In pcJIA patients, radiographic progression from baseline at 52 weeks and at 104 weeks was 12.5% and 2.9%, respectively, using aSH scoring and 6.5% and 4%, respectively, using Poznanski scoring. Conclusion Tocilizumab may delay radiographic progression in children with sJIA and children with pcJIA. Trial registration Trial registration numbers and dates: TENDER, NCT00642460 (March 19, 2008); CHERISH, NCT00988221 (October 1, 2009)

• Frid, Paula; Baraniya, Divyashri; Halbig, Josefine Mareile; Rypdal, Veronika Gjertsen; Songstad, Nils Thomas & Rosén, Annika [Show all 15 contributors for this article] (2020). Salivary Oral Microbiome of Children With Juvenile Idiopathic Arthritis: A Norwegian Cross-Sectional Study. Frontiers in Cellular and Infection Microbiology. 10, p. 1–13. doi: 10.3389/fcimb.2020.602239. Full text in Research Archive Show summary

  Background: The oral microbiota has been connected to the pathogenesis of rheumatoid arthritis through activation of mucosal immunity. The objective of this study was to characterize the salivary oral microbiome associated with juvenile idiopathic arthritis (JIA), and correlate it with the disease activity including gingival inflammation. Methods: Fifty-nine patients with JIA (mean age, 12.6 ± 2.7 years) and 34 healthy controls (HC; mean age 12.3 ± 3.0 years) were consecutively recruited in this Norwegian cross-sectional study. Information about demographics, disease activity, medication history, frequency of tooth brushing and a modified version of the gingival bleeding index (GBI) and the simplified oral hygiene index (OHI-S) was obtained. Microbiome profiling of saliva samples was performed by sequencing of the V1-V3 region of the 16S rRNA gene, coupled with a species-level taxonomy assignment algorithm; QIIME, LEfSe and R-package for Spearman correlation matrix were used for downstream analysis. Results: There were no significant differences between JIA and HC in alpha- and beta-diversity. However, differential abundance analysis revealed several taxa to be associated with JIA: TM7-G1, Solobacterium and Mogibacterium at the genus level; and Leptotrichia oral taxon 417, TM7-G1 oral taxon 352 and Capnocytophaga oral taxon 864 among others, at the species level. Haemophilus species, Leptotrichia oral taxon 223, and Bacillus subtilis, were associated with healthy controls. Gemella morbillorum, Leptotrichia sp. oral taxon 498 and Alloprevotella oral taxon 914 correlated positively with the composite juvenile arthritis 10-joint disease activity score (JADAS10), while Campylobacter oral taxon 44 among others, correlated with the number of active joints. Of all microbial markers identified, only Bacillus subtilis and Campylobacter oral taxon 44 maintained false discovery rate (FDR) < 0.1. Conclusions: In this exploratory study of salivary oral microbiome we found similar alpha- and beta-diversity among children with JIA and healthy. Several taxa associated with chronic inflammation were found to be associated with JIA and disease activity, which warrants further investigation.

• Frid, Paula; Augdal, Thomas Angell; Larheim, Tore Arne; Halbig, Josefine Mareile; Rypdal, Veronika Gjertsen & Songstad, Nils Thomas [Show all 14 contributors for this article] (2020). Efficacy and safety of intraarticular corticosteroid injections in adolescents with juvenile idiopathic arthritis in the temporomandibular joint: A Norwegian 2-year prospective multicenter pilot study. Pediatric Rheumatology. 18:75, p. 1–16. doi: 10.1186/s12969-020-00464-3. Full text in Research Archive Show summary

  Background Intraarticular corticosteroids (IACs) have been used to treat temporomandibular joint (TMJ) arthritis. However, prospective clinical studies with magnetic resonance imaging (MRI) scoring are lacking. The aim of this study was to examine efficacy and safety of a single IAC in the TMJ in adolescents with juvenile idiopathic arthritis (JIA) in a clinical setting. Methods In this Norwegian prospective multicenter pilot study 15 patients with JIA (mostly persistent oligoarthritis or RF negative polyarthritis categories) and a clinically and MRI-verified diagnosis of TMJ arthritis were treated with IACs and followed for 2 years. Demographics, systemic medication, general disease activity and outcome measures were recorded including a pain-index score and maximal incisal opening (MIO). Inflammation and bone damage scores were assessed, using two recently published MRI scoring systems with masked radiological evaluation. Results Among the 15 patients, 13 received a single IAC (5 bilateral), and 2 repeated IACs once unilaterally. Thus, the total number of IACs was 22. Median age was 15 years and the majority had an age not thought of as critical regarding mandibular growth retardation due to steroid injection. During the 2-year observation period systemic medication with disease modifying antirheumatic drugs (DMARDs) including biologics was initiated or adjusted in 10/15 (67%) patients. At the 2-months study visit after injection we observed a minimal improvement in MIO from median 44 (1st, 3rd quartiles; 36, 48) mm to 45 (43, 47) mm, p = 0.045 and decreased MRI mean additive inflammatory score from 4.4 ± 1.8 standard deviations (SD) to 3.4 ± 2.0, p = 0.040. From baseline to the 2-months follow-up pain improved in 6/11 patients but pain scores were not significantly improved. MRI-assessed damage increased in two patients with repeated IACs, and decreased in 3 patients but most of the patients were stable over the 2-year follow-up. Intra-rater repeatability of the MRI scoring system domains varied from poor to excellent. Conclusions In this pilot study of predominately single IACs to the TMJ in combination with systemic treatment we observed improvement in MRI-assessed inflammation, mostly stable condylar bone conditions and minimal clinical improvement in adolescents with JIA and TMJ arthritis. No severe side effects were seen.

• Tollisen, Anita; Selvaag, Anne Marit G; Aasland, Astrid; Lerdal, Anners & Flatø, Berit (2019). Longitudinal Health Status from Early Disease to Adulthood and Associated Prognostic Factors in Juvenile Idiopathic Arthritis. Journal of Rheumatology. ISSN 0315-162X. 46(10), p. 1335–1344. doi: 10.3899/jrheum.180948. Full text in Research Archive
• Barth, Zoltan; Schwartz, Thomas; Flatø, Berit; Aaløkken, Trond Mogens; Koller, Akos & Lund, May-Brith [Show all 8 contributors for this article] (2019). The association between nailfold capillary density and pulmonary and cardiac involvement in medium-to long-standing juvenile dermatomyositis. Arthritis care & research. ISSN 2151-464X. 71(4), p. 492–497. doi: 10.1002/acr.23687. Full text in Research Archive Show summary

  Objective To explore the associations between microvascular abnormalities as assessed by nailfold capillaroscopy (NFC) and pulmonary and cardiac involvement in patients with juvenile dermatomyositis (DM) who are assessed after medium‐ to long‐term follow‐up. Methods Fifty‐eight patients with juvenile DM were examined a mean ± SD of 17.0 ± 10.6 years after symptom onset. Nailfold capillary density (NCD) and a neovascular pattern (defined as an active or late scleroderma pattern) were analyzed, with blinding to clinical data. Pulmonary involvement was assessed by pulmonary function tests including spirometry, diffusing capacity for carbon monoxide (DLco ), and body plethysmography. High‐resolution computed tomography (HRCT) was also performed. Cardiac involvement was assessed by electrocardiography, Holter monitoring (heart rate variability), and echocardiography. Results Patients with low NCD (<6 capillaries/mm) (n = 21), compared to patients with normal NCD (≥6 capillaries/mm) (n = 37) had lower forced vital capacity (89.7% versus 98.5% predicted), total lung capacity (87.8% versus 94.5% predicted), and more often had low DLco values (15 [71%] of 21 patients versus 14 [38%] of 37 controls) (all P < 0.05). Use of HRCT to assess airway disease was more frequent in the group with low NCD (6 [30%] of 20 patients versus 3 [8%] of 36 patients in the normal NCD group; P = 0.034). No associations between NCD and cardiac parameters or between neovascular pattern and pulmonary or cardiac parameters were observed. Conclusion In patients with juvenile DM, low NCD was associated with lung involvement, which was mostly subclinical. No significant associations with cardiac involvement were observed. These results shed light on possible mechanisms underlying organ involvement, but further and preferably larger studies are needed to identify NCD as a potential biomarker for lung and cardiac involvement in juvenile DM.

• Berntsen, Kristin Schjander; Edvardsen, Elisabeth; Hansen, Bjørge Hermann; Flatø, Berit; Sjaastad, Ivar & Sanner, Helga (2019). Cardiorespiratory fitness in long-term juvenile dermatomyositis: A controlled, cross-sectional study of active/inactive disease. Rheumatology. ISSN 1462-0324. 58(3), p. 492–501. doi: 10.1093/rheumatology/key342. Full text in Research Archive Show summary

  Objectives. To compare cardiorespiratory fitness (CRF) expressed as maximal oxygen uptake (VO2max) between patients with long-term JDM and controls and between patients with active and inactive disease, as well as to explore exercise limiting factors and associations between CRF and disease variables. Methods. JDM patients (n=45) and age- and gender-matched controls (n=45) performed a cardiopulmonary exercise test (CPET) on a treadmill until exhaustion. Physical activity was measured by accelerometers. Disease activity, damage and muscle strength/function were assessed by validated tools. Clinically inactive disease was defined according to PRINTO criteria. Results. The mean disease duration was 20.8 (S.D. 11.9) years and 29/45 (64%) patients had inactive disease. A low VO2max was found in 27% of patients vs 4% of controls (P = 0.006). The mean VO2max and maximal ventilation (VEmax) were lower in patients with active and inactive disease compared with controls. Patients with active disease also had lower maximal voluntary ventilation (MVV) compared with controls and lower VEmax and MVV compared with those with inactive disease. Patients with inactive disease had lower physical activity levels compared with controls. VO2max correlated negatively with disease damage in patients with inactive disease and positively with muscle strength/function in patients with active disease. Conclusion. CRF was lower in JDM patients, both with active and inactive disease, compared with controls after a mean 20 years disease duration. Cardiopulmonary exercise test results suggested different limiting factors contributing to the reduced CRF according to disease activity, including deconditioning in inactive disease and reduced ventilatory capacity in active disease. Further research is needed to verify this.

• Consolaro, Alessandro; Giancane, Gabriella; Alongi, Alessandra; Dijkhuizen, Evert Hendrik Pieter van; Aggarwal, Amita & Al-Mayouf, Sulaiman M. [Show all 29 contributors for this article] (2019). Phenotypic variability and disparities in treatment and outcomes of childhood arthritis throughout the world: an observational cohort study. The Lancet Child and Adolescent Health. ISSN 2352-4642. 3(4), p. 255–263. doi: 10.1016/S2352-4642(19)30027-6. Full text in Research Archive Show summary

  Background To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status. Methods In this multinational, cross-sectional, observational cohort study, we asked international paediatric rheumatologists from specialised centres to enrol children with a diagnosis of juvenile idiopathic arthritis, according to International League of Associations for Rheumatology criteria, who were seen consecutively for a period of 6 months. Each patient underwent retrospective and cross-sectional assessments, including measures of disease activity and damage and questionnaires on the wellbeing and quality of life of the children. We qualitatively compared the collected data across eight geographical areas, and we explored an association between disease activity and damage and a country's gross domestic product (GDP) with a multiple logistic regression analysis. Findings Between April 4, 2011, and Nov 21, 2016, 9081 patients were enrolled at 130 centres in 49 countries, grouped into eight geographical areas. Systemic arthritis (125 [33·0%] of 379 patients) and enthesitis-related arthritis (113 [29·8%] of 379) were more common in southeast Asia, whereas oligoarthritis was more prevalent in southern Europe (1360 [56·7%] of 2400) and rheumatoid factor-negative polyarthritis was more frequent in North America (165 [31·5%] of 523) than in the other areas. Prevalence of uveitis was highest in northern Europe (161 [19·1%] of 845 patients) and southern Europe (450 [18·8%] of 2400) and lowest in Latin America (54 [6·4%] of 849), Africa and Middle East (71 [5·9%] of 1209), and southeast Asia (19 [5·0%] of 379). Median age at disease onset was lower in southern Europe (3·5 years, IQR 1·9–7·3) than in other regions. Biological, disease-modifying antirheumatic drugs were prescribed more frequently in northern Europe and North America than in other geographical settings. Patients living in countries with lower GDP had greater disease activity and damage than those living in wealthier countries. Damage was associated with referral delay. Interpretation Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographical areas and wealth status of countries. The greater disease burden in lower-resource settings highlights the need for public health efforts aimed at improving equity in access to effective treatments and care for juvenile idiopathic arthritis.

• NOMELAND, BIRGIT; Hetlevik, Siri Opsahl; Sanner, Helga; Barth, Zoltan; Schwartz, Thomas & Flatø, Berit [Show all 8 contributors for this article] (2019). Cardiac function is impaired in longstanding juvenile-onset mixed connective tissue disease - a controlled study. Journal of Rheumatology. ISSN 0315-162X. 46(7), p. 739–747. doi: 10.3899/jrheum.180526. Full text in Research Archive Show summary

  To assess cardiac function in patients with juvenile mixed connective tissue disease (JMCTD) compared to matched controls, and to investigate possible associations between cardiac impairment and disease variables and cardiovascular risk factors.Fifty JMCTD patients (86% female) examined median 14.9 (6.6–23.0) years after disease onset were compared with 50 age- and sex-matched controls. Electrocardiogram and echocardiography [including e′ as a marker for diastolic dysfunction and long-axis strain (LAS) and left ventricular (LV) ejection fraction (EF) as markers of systolic function] were performed. LV dysfunction (LVD) was defined as low EF, low LAS, or low e′. Right ventricular function was assessed with tricuspid annular plane systolic excursion (TAPSE). Cardiovascular risk factors and disease variables were assessed.LVD was found in 16% of patients and 4% of controls (p = 0.035). EF and LAS were lower in patients compared to controls (6% lower, p &lt; 0.001, and 4% lower, p = 0.044, respectively). TAPSE was 8% lower in patients versus controls (p = 0.008). No patients had signs of pulmonary hypertension. Patients had longer corrected QT time than controls (p = 0.012). LVD was associated with higher levels of apolipoprotein B, higher disease activity measured by physician’s global assessment, longer prednisolone treatment, and more organ damage assessed with the Myositis Damage Index.Patients with JMCTD had impaired left and right ventricular function compared to matched controls after median 15 years disease duration. High disease activity and longer treatment with prednisolone were factors associated with LVD.

• Hetlevik, Siri Opsahl; Flatø, Berit; Aaløkken, Trond Mogens; Samersaw-Lund, May Brit; Reiseter, Silje & Mynarek, Georg [Show all 9 contributors for this article] (2019). Pulmonary manifestations and progression of lung disease in juvenile-onset mixed connective tissue disease. Journal of Rheumatology. ISSN 0315-162X. 46(1), p. 93–100. doi: 10.3899/jrheum.180019. Full text in Research Archive Show summary

  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.

• Tollisen, Anita; Flatø, Berit; Selvaag, Anne Marit G; Aasland, Astrid; Ingebrigtsen, Trude & Sagen, Joakim [Show all 7 contributors for this article] (2019). Treatment Satisfaction with and Adherence to Disease-Modifying Antirheumatic Drugs in Adult Patients with Juvenile Idiopathic Arthritis. Arthritis care & research. ISSN 2151-464X. doi: 10.1002/acr.24113. Full text in Research Archive
• Marstein, Henriette; Schwartz, Thomas; Aaløkken, Trond M; Samersaw-Lund, May Brit; Flatø, Berit & Sjaastad, Ivar [Show all 7 contributors for this article] (2019). Novel associations between cytokines and pulmonary involvement in juvenile dermatomyositis - a cross-sectional study of long-term disease. Rheumatology. ISSN 1462-0324. 59(8), p. 1862–1870. doi: 10.1093/rheumatology/kez531. Full text in Research Archive Show summary

  To examine associations between cytokines and pulmonary involvement in patients with medium- to long-term JDM. In a cross-sectional study, 58 patients examined median (range) 16.8 (6.6–27.0) years after symptom onset were stratified in inactive (JDM-inactive) and active (JDM-active) disease (updated PRINTO criteria); 56 age/sex matched controls were included. Twenty-nine cytokines (in serum) were analysed (Luminex technology/ELISA). Pulmonary function test included forced vital capacity, total lung capacity (TLC) and diffusing capacity for carbon monoxide reported as % of predicted and low forced vital capacity/TLC/diffusing capacity for carbon monoxide. In patients, the presence of clinical pulmonary damage was assessed and high resolution computed tomography scans were scored for interstitial lung disease, chest wall calcinosis and airways disease. Median age of patients was 21 (7–55) years, 59% were female and 36% inactive. In JDM-active and all patients, higher MCP-1, IP-10 and eotaxin correlated with high-resolution computed tomography findings (rs 0.34–0.61; P &lt; 0.05). MCP-1 and eotaxin correlated with pulmonary damage in JDM-active and all patients (rs 0.41–0.49; P &lt; 0.01). Higher TGF-β1 and PDGF (growth factors) were associated with lower lung volumes (forced vital capacity/TLC measures) in all patients; PDGF in JDM-active and TGF-β1 in JDM-inactive patients. IP-10 correlated with TLC% in JDM-active patients. No associations between cytokines and pulmonary function test were found in controls. In JDM, we found a novel association (not previously described in myositis) between eotaxin and pulmonary involvement; we have previously shown an association between eotaxin and cardiac dysfunction. The associations between IP-10/growth factors/MCP-1 and pulmonary involvement are novel in JDM and were mostly seen in JDM-active patients.

• Berntsen, Kristin Schjander; Raastad, Truls; Marstein, Henriette; Kirkhus, Eva Astrid; Merckoll, Else & Cumming, Kristoffer Toldnes [Show all 9 contributors for this article] (2019). Functional and Structural Adaptations of Skeletal Muscle in Long-Term Juvenile Dermatomyositis; a Controlled Cross-Sectional Study. Arthritis & Rheumatology. ISSN 2326-5191. doi: 10.1002/art.41174. Full text in Research Archive Show summary

  Objective: To compare muscle strength and endurance of the knee extensors between patients with long‐term juvenile dermatomyositis (DM) and controls and between patients with active disease and those with inactive disease, and to explore associations between strength/endurance and 1) clinical parameters, 2) physical activity, and 3) humoral/structural adaptation in the skeletal muscle of patients. Methods: In a cross‐sectional study (44 patients and 44 age‐ and sex‐matched controls), we tested isometric muscle strength (peak torque, in Nm) and dynamic muscle endurance (total work, in Joules) of the knee extensors, physical activity (measured by accelerometer), and serum myokine levels (by enzyme‐linked immunosorbent assay). Patients were examined with validated tools (clinical muscle tests and measures of disease activity/damage and inactive disease) and using magnetic resonance imaging of the thigh muscles, which included evaluation of the quadriceps cross‐sectional area (CSA). Needle biopsy samples of the vastus lateralis muscle (obtained from 12 patients ages ≥18 years) were assessed by histochemistry. Results: After a mean ± SD disease duration of 21.8 ± 11.8 years, peak torque was lower in patients with juvenile DM compared to controls (mean difference 29 Nm, 95% confidence interval 13–46; P = 0.001). Similarly, total work of the knee extensors was lower in patients compared to controls (median 738J [interquartile range 565–1,155] versus 1,249J [interquartile range 815–1,665]; P < 0.001). Both peak torque and total work were lower in patients with active juvenile DM compared to those with inactive disease (both P < 0.019); in analyses controlled for quadriceps CSA, only total work remained lower in patients with active disease. Moreover, peak torque and total work correlated with findings from clinical muscle tests in patients with active disease (r = 0.57–0.84). Muscle biopsy results indicated that the fiber type composition was different, but capillary density was similar, between patients with active disease and those with inactive disease. Conclusion: In patients with long‐term juvenile DM, both muscle strength and endurance of the knee extensors were lower when compared to matched controls, and also lower in patients with active disease compared to those with inactive disease. Our results indicate a need for more sensitive muscle tests in this clinical setting. We hypothesize that impaired muscle endurance in patients with active juvenile DM may be influenced by structural/functional adaptations of muscle tissue independent of muscle size.

• Barth, Zoltan; NOMELAND, BIRGIT; Flatø, Berit; Koller, Akos; Sjaastad, Ivar & Sanner, Helga (2018). Assessment of Microvascular Abnormalities by Nailfold Capillaroscopy in Juvenile Dermatomyositis After Medium- to Long-Term Followup. Arthritis care & research. ISSN 2151-464X. 70(5), p. 768–776. doi: 10.1002/acr.23338. Full text in Research Archive
• Aulie, Hanne Aaserud; Estensen, Mette-Elise; Selvaag, Anne Marit G; Lilleby, Vibke; Flatø, Berit & Aakhus, Svend (2018). Arterial properties in adults with long-lasting active juvenile idiopathic arthritis compared to healthy controls. Pediatric Rheumatology. 16(85). doi: 10.1186/s12969-018-0302-5. Full text in Research Archive Show summary

  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.

• Flatø, Berit; Rygg, Marite; Nordal, Ellen Berit; Røisland, Mona; Ødegård, Hanne Beate & Hoftun, Gry Børmark [Show all 10 contributors for this article] (2018). The Norwegian version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR). Rheumatology International. ISSN 0172-8172. 38, p. 291–298. doi: 10.1007/s00296-018-3963-y. Full text in Research Archive Show summary

  The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Norwegian language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic and clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach’s alpha, interscale correlations, test–retest reliability, and construct validity (convergent and discriminant validity). A total of 301 JIA patients (3.3% systemic, 41.2% oligoarticular, 25.9% RF negative polyarthritis, and 29.6% other categories) and 74 healthy children were enrolled in three centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Norwegian version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

• Augestad, Linnea B.; Hammarström, Clara Louise; Flatø, Berit & Bjerre, Anna Kristina (2017). Nyreaffeksjon ved systemisk vaskulitt hos barn. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 137(19). doi: 10.4045/tidsskr.16.0592. Full text in Research Archive
• Frid, Paula Hanna Therese; Nordal, Ellen Berit; Bovis, Francesca; Giancane, Gabriella; Larheim, Tore Arne & Rygg, Marite [Show all 25 contributors for this article] (2017). Temporomandibular Joint Involvement in Association With Quality of Life, Disability, and High Disease Activity in Juvenile Idiopathic Arthritis. Arthritis care & research. ISSN 2151-464X. 69(5), p. 677–686. doi: 10.1002/acr.23003. Full text in Research Archive
• Berntsen, Kristin Schjander; Tollisen, Anita; Schwartz, Thomas; Kirkhus, Eva; Aaløkken, Trond Mogens & Samersaw-Lund, May Brit [Show all 9 contributors for this article] (2017). Submaximal exercise capacity in juvenile dermatomyositis after longterm disease: The contribution of muscle, lung, and heart involvement. Journal of Rheumatology. ISSN 0315-162X. 44(6), p. 827–834. doi: 10.3899/jrheum.160997. Full text in Research Archive
• Tollisen, Anita; Selvaag, Anne Marit G; Aulie, Hanne Aaserud; Lilleby, Vibke; Aasland, Astrid & Lerdal, Anners [Show all 7 contributors for this article] (2017). Physical functioning, pain, and health-related quality of life in adults with juvenile idiopathic arthritis: a longitudinal 30-year followup study. Arthritis care & research. ISSN 2151-464X. 70(5), p. 741–749. doi: 10.1002/acr.23327. Full text in Research Archive
• Selvaag, Anne Marit G; Kirkhus, Eva; Törnqvist, Lena; Lilleby, Vibke; Aulie, Hanne Aaserud & Flatø, Berit (2017). Radiographic damage in hands and wrists of patients with juvenile idiopathic arthritis after 29 years of disease duration. Pediatric Rheumatology. 15. doi: 10.1186/s12969-017-0151-7. Full text in Research Archive
• Ruperto, Nicolino; Pistorio, Angela; Oliveira, Sheila; Zulian, Francesco; Cuttica, Ruben & Ravelli, Angelo [Show all 38 contributors for this article] (2016). Prednisone versus prednisone plus ciclosporin versus prednisone plus methotrexate in new-onset juvenile dermatomyositis: a randomised trial. The Lancet. ISSN 0140-6736. 387(10019), p. 671–678. doi: 10.1016/S0140-6736(15)01021-1. Full text in Research Archive
• Kirkhus, Eva; Arvidsson, Linda Zamoline; Smith, Hans-Jørgen; Flatø, Berit; Hetlevik, Siri Opsahl & Larheim, Tore Arne (2016). Disk abnormality coexists with any degree of synovial and osseous abnormality in the temporomandibular joints of children with juvenile idiopathic arthritis. Pediatric Radiology. ISSN 0301-0449. 46(3), p. 331–341. doi: 10.1007/s00247-015-3493-7. Full text in Research Archive Show summary

  Background MRI manifestation of temporomandibular joint arthritis is frequently reported in children with juve- nile idiopathic arthritis. However, little attention has been paid to temporomandibular joint disk abnormalities. Objective To assess combinations of MRI findings in the symptomatic temporomandibular joint in children with ju- venile idiopathic arthritis with focus on disk abnormalities. Materials and methods This was a retrospective study of 46 patients with juvenile idiopathic arthritis, mean age 12 years (range: 5-17 years). Mean disease duration was 70 months (standard deviation: 61 months). MR images of 92 tempo- romandibular joints were scored for thickness of abnormal- ly enhancing synovium (synov itis), joint effusion, bone marrow oedema, abnormal bone shape, bone erosion and disk abnormalities. Results The 92 temporomandibular joints were categorized as A: No synovitis and normal bone shape (30/92; 33%), B: Synovitis and normal bone shape (14/92: 15%), C: Synovi- tis and abnormal bone shape (38/92; 41%) and D: No syno- vitis but abnormal bone shape (10/92; 11%). Thirty-six of the 46 patients (78%) had synovitis and 33/46 (72%) had abnormal bone shape, most frequently in combination (30/ 46; 65%). Disk abnormalities (flat disk, fragmented disk, adherent disk and displaced disk) were found in 29/46 pa- tients (63%). Disk abnormalities were found in all catego- ries of juvenile idiopathic arthritis involved temporoman- dibular joints (B: 8/14 [57%]; C: 25/38 [66%] and D: 7/10 [70%]). Disk displacement was found in half of the joints (7/14) in category B. Synovitis was most pronounced in this category. Conclusion Disk abnormalities were frequent. Disk displace- ment also occurred in joints with early temporomandibular joint arthritis, i.e., with normal bone shape. Other disk abnor- malities were found in joints with bone abnormalities. Atten- tion should be paid to disk abnormalities both in early and long-standing temporomandibular joint arthritis in children with juvenile idiopathic arthritis

• Selvaag, Anne Marit G; Aulie, Hanne Aaserud; Lilleby, Vibke & Flatø, Berit (2016). Disease progression into adulthood and predictors of long-term active disease in juvenile idiopathic arthritis. Annals of the Rheumatic Diseases. ISSN 0003-4967. 75(1), p. 190–195. doi: 10.1136/annrheumdis-2014-206034. Full text in Research Archive
• Anderson, Joseph H.; Anderson, K.R.; Aulie, Hanne Aaserud; Crowson, C.S.; Mason, T.G. & Ardoin, S.P. [Show all 8 contributors for this article] (2016). Juvenile idiopathic arthritis and future risk for cardiovascular disease: a multicenter study. Scandinavian Journal of Rheumatology. ISSN 0300-9742. 45(4), p. 299–303. doi: 10.3109/03009742.2015.1126345. Full text in Research Archive
• Evensen, Kristin; Aulie, Hanne Aaserud; Rønning, Ole M.; Flatø, Berit & Russell, David (2016). Carotid atherosclerosis in adult patients with persistently active juvenile idiopathic arthritis compared with healthy controls. Journal of Rheumatology. ISSN 0315-162X. 43(4), p. 810–815. doi: 10.3899/jrheum.150499. Full text in Research Archive Show summary

  Objective. Juvenile idiopathic arthritis (JIA) is the most common inflammatory rheumatic disease in childhood. It is regarded as a systemic inflammatory disease with possible increased risk of cardiovascular disease (CVD). The aim of this study was to assess carotid intima-media thickness (IMT) and carotid stenosis as surrogate measures for CVD in adults with longterm active JIA and healthy age- and sex-matched controls. Methods. Seventy-five patients with JIA (age 28–45 yrs) with persistently active disease at least 15 years after disease onset were reexamined after a median of 29 years and compared with 75 matched controls. Patients and controls were examined by color duplex ultrasound of the carotid arteries to compare carotid IMT and carotid stenosis in the 2 groups. Results. Patients with JIA did not have increased carotid IMT values compared with the controls (mean ± SD: 0.56 mm ± 0.09 vs 0.58 mm ± 0.07, p = 0.289). Patients with a higher disease activity indicated by the Juvenile Arthritis Disease Activity Score value above the median value had increased carotid IMT compared with the patients with a lower value, but not statistically different compared with controls. No carotid stenoses were detected in patients or controls. Conclusion. We found similar carotid IMT values in adult patients with JIA and controls.

• Kirkhus, Eva; Gunderson, Ragnhild B.; Smith, Hans-Jørgen; Flatø, Berit; Hetlevik, Siri Opsahl & Larheim, Tore Arne [Show all 7 contributors for this article] (2016). Temporomandibular joint involvement in childhood arthritis: comparison of ultrasonography-assessed capsular width and MRI-assessed synovitis. Dentomaxillofacial Radiology. ISSN 0250-832X. 45(8). doi: 10.1259/dmfr.20160195. Full text in Research Archive Show summary

  Objectives: Ultrasonography is an effective, low-cost, low-threshold and convenient diagnostic tool in childhood arthritis, but its value in temporomandibular joint (TMJ) involvement is not clear. The purpose of our study was to explore the reliability of ultrasonography to assess TMJ inflammation using contrast-enhanced MRI as reference standard, in order to deduce cut-off values for TMJ capsular width to detect enhanced synovial thickening (synovitis). Methods: 124 ultrasonography and MRI examinations in 55 patients [mean age 12.4 ± 3.5 years (±standard deviation)], the majority obtained within 1 day, were scored for subcondylar and condylar capsular width (ultrasonography images) and amount of synovitis (MR images). The correlations of these findings were calculated. A receiver operating characteristic (ROC) curve analysis, with MRI findings as reference standard, was obtained. Results: The correlation between ultrasonography-assessed capsular width and MRI-assessed amount of synovitis was moderate both at the subcondylar and condylar level [Spearman's rho (ρ): 0.483; p < 0.001 and 0.347; p < 0.001 respectively]. The ROC curve indicated the best discriminatory ability at the subcondylar level with an area under the curve of 0.77 (95% confidence interval 0.69–0.85) and a cut-off value of 1.2 mm (sensitivity 72%, specificity 70%) for the capsular width. Conclusions: A moderate correlation between ultrasonography-assessed capsular width and MRI-assessed synovitis was found in childhood arthritis with the best discriminatory ability at the subcondylar level. This indicates that ultrasonography may be a valuable diagnostic tool in the initial assessment of TMJ inflammation.

• Hetlevik, Siri Opsahl; Flatø, Berit; Rygg, Marite; Nordal, Ellen Berit; Brunborg, Cathrine & Hetland, Helene [Show all 7 contributors for this article] (2016). Long-term outcome in juvenile-onset mixed connective tissue disease: a nationwide Norwegian study. Annals of the Rheumatic Diseases. ISSN 0003-4967. 76(1), p. 159–165. doi: 10.1136/annrheumdis-2016-209522. Full text in Research Archive
• Constantin, Tamás; Foeldvari, Ivan; Vojinovic, Jelena; Horneff, Gerd; Burgos-Vargas, Ruben & Nikishina, Irina [Show all 31 contributors for this article] (2016). Two-year efficacy and safety of etanercept in pediatric patients with extended oligoarthritis, enthesitisrelated arthritis, or psoriatic arthritis. Journal of Rheumatology. ISSN 0315-162X. 43(4), p. 816–824. doi: 10.3899/jrheum.150430. Full text in Research Archive
• Stray-Pedersen, Asbjørg; Sorte, Hanne Sørmo; Samarakoon, Pubudu Saneth; Gambin, Tomasz; Chinn, Ivan K. & Akdemir, Zeynep H.C. [Show all 51 contributors for this article] (2016). Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders. Journal of Allergy and Clinical Immunology. ISSN 0091-6749. 139(1), p. 232–245. doi: 10.1016/j.jaci.2016.05.042. Full text in Research Archive Show summary

  Background Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/110) and management was directly altered in nearly a quarter (26/110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.

• Barth, Zoltan; NOMELAND, BIRGIT; Schwartz, Thomas; Gjesdal, Knut; Flatø, Berit & Koller, Akos [Show all 8 contributors for this article] (2016). In juvenile dermatomyositis, heart rate variability is reduced, and associated with both cardiac dysfunction and markers of inflammation: a cross-sectional study median 13.5 years after symptom onset. Rheumatology. ISSN 1462-0324. 55(3), p. 535–543. doi: 10.1093/rheumatology/kev376. Full text in Research Archive Show summary

  Objectives. Low heart rate variability (HRV) is a well-established predictor of cardiac death. The aim of this study was to investigate arrhythmias and HRV in patients with JDM, and associations between HRV and inflammatory markers, echocardiographic measurements and disease parameters. Methods. Fifty-five patients with JDM were examined 2–34 years (median 13.5 years) after disease onset, and compared with 55 age and sex matched controls. Holter ECG monitoring and echocardiography were analysed blinded to patient information. Arrhythmia and HRV (six parameters) were analysed by standard software, finally adjudicated by an experienced cardiologist. Markers of inflammation (ESR, high sensitivity (hs)CRP and cytokines) were analysed. Disease activity and organ damage were assessed by clinical examination at follow-up and retrospectively by chart review. Results. In two out of six HRV parameters, JDM patients had lower values than controls. No difference in arrhythmias was found between the groups. In patients, but not in controls, there were significant negative correlations between five out of six HRV parameters, and ESR and hsCRP (Spearman correlation coefficient, −0.306 to −0.470; P, 0.023 to <0.001). Also, in patients, negative correlations were found between three out of six HRV parameters and systolic and diastolic function. Active disease and low HRV were associated. Patients with hsCRP in the highest quartile (Q4) had lower HRV in all parameters compared with those in pooled Q1–3 (P < 0.001). Conclusion. JDM patients had reduced HRV, which was associated with elevated inflammatory markers, active disease and reduced myocardial function. This suggests reduced vagal control of the heart; further studies are needed to determine whether this is also associated with cardiac morbidity or mortality.

• Finkel, Terri H.; Li, Jin; Wei, Zhi; Wang, Wei; Zhang, Haitao & Behrens, Edward M. [Show all 33 contributors for this article] (2016). Variants in CXCR4 associate with juvenile idiopathic arthritis susceptibility. BMC Medical Genetics. 17(1). doi: 10.1186/s12881-016-0285-3. Full text in Research Archive
• Chiaroni-Clarke, Rachel C.; Li, Yun R.; Munro, Jane E.; Chavez, Raul A.; Scurrah, Katrina J. & Pezic, Angela [Show all 21 contributors for this article] (2015). The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females. Genes and Immunity. ISSN 1466-4879. 16(7), p. 495–498. doi: 10.1038/gene.2015.32. Full text in Research Archive
• Aulie, Hanne Aaserud; Selvaag, Anne Marit G; Günther, Anne; Lilleby, Vibke; Molberg, Øyvind & Hartmann, Anders [Show all 8 contributors for this article] (2015). Arterial haemodynamics and coronary artery calcification in adult patients with juvenile idiopathic arthritis. Annals of the Rheumatic Diseases. ISSN 0003-4967. 74(8), p. 1515–1521. doi: 10.1136/annrheumdis-2013-204804. Full text in Research Archive
• Li, Yun R.; Li, Jin; Zhao, Sihai D.; Bradfield, Jonathan P.; Mentch, Frank D. & Maggadóttir, Sólrún Melkorka [Show all 66 contributors for this article] (2015). Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases. Nature Medicine. ISSN 1078-8956. 21(9), p. 1018–1027. doi: 10.1038/nm.3933. Full text in Research Archive
• Aulie, Hanne Aaserud; Estensen, Mette-Lise; Selvaag, Anne Marit G; Lilleby, Vibke; Murbræch, Klaus & Flatø, Berit [Show all 7 contributors for this article] (2015). Cardiac function in adult patients with juvenile idiopathic arthritis. Journal of Rheumatology. ISSN 0315-162X. 42(9), p. 1716–1723. doi: 10.3899/jrheum.141351. Full text in Research Archive
• Ellis, Justine A.; Scurrah, Katrina J.; Li, Yun R.; Ponsonby, Anne-Louise; Chavez, Raul A. & Pezic, Angela [Show all 19 contributors for this article] (2015). Epistasis amongst PTPN2 and genes of the vitamin D pathway contributes to risk of juvenile idiopathic arthritis. Journal of Steroid Biochemistry and Molecular Biology. ISSN 0960-0760. 145, p. 113–120. doi: 10.1016/j.jsbmb.2014.10.012. Full text in Research Archive
• Li, Yun R.; Zhao, Sihai D.; Li, Jin; Bradfield, Jonathan P.; Mohebnasab, Maede & Steel, Laura [Show all 63 contributors for this article] (2015). Genetic sharing and heritability of paediatric age of onset autoimmune diseases. Nature Communications. 6:8442. doi: 10.1038/ncomms9442. Full text in Research Archive
• Sanner, Helga; Schwartz, Thomas; Flatø, Berit; Vistnes, Maria; Christensen, Geir Arve & Sjaastad, Ivar (2014). Increased levels of eotaxin and MCP-1 in juvenile dermatomyositis median 16.8 years after disease onset; associations with disease activity, duration and organ damage. PLOS ONE. 9(3). doi: 10.1371/journal.pone.0092171. Full text in Research Archive
• Schwartz, Thomas; Sjaastad, Ivar; Flatø, Berit; Vistnes, Maria; Christensen, Geir Arve & Sanner, Helga (2014). In active juvenile dermatomyositis, elevated eotaxin and MCP-1 and cholesterol levels in the upper normal range are associated with Cardiac dysfunction. Rheumatology (Sveits). ISSN 0080-2727. 53, p. 2214–2222. doi: 10.1093/rheumatology/keu256. Full text in Research Archive
• Sanner, Helga; Sjaastad, Ivar & Flatø, Berit (2014). Disease activity and prognostic factors in juvenile dermatomyositis: A long-term follow-up study applying the Paediatric Rheumatology International Trials Organization criteria for inactive disease and the myositis disease activity assessment tool. Rheumatology. ISSN 1462-0324. 53(9), p. 1578–1585. doi: 10.1093/rheumatology/keu146. Full text in Research Archive
• Schwartz, Thomas; Sanner, Helga; Gjesdal, Ola; Flatø, Berit & Sjaastad, Ivar (2013). In juvenile dermatomyositis cardiac systolic dysfunction is present after long-term follow-up, and is predicted by sustained early skin activity. Annals of the Rheumatic Diseases. ISSN 0003-4967. 73, p. 1805–1810. doi: 10.1136/annrheumdis-2013-203279. Full text in Research Archive
• Eike, Morten Christoph; Skinningsrud, Beate; Ronninger, Marcus; Stormyr, Alice; Kvien, Tore Kristian & Joner, Geir [Show all 13 contributors for this article] (2012). CIITA gene variants are associated with rheumatoid arthritis in Scandinavian populations. Genes and Immunity. ISSN 1466-4879. 13(5), p. 431–436. doi: 10.1038/gene.2012.11. Full text in Research Archive Show summary

  Expression of the major autoimmune risk loci DRB1 and DQB1 is regulated by the class II MHC (major histocompatibility complex) transactivator (CIITA), making the CIITA gene a strong autoimmune risk locus candidate. A CIITA promoter single-nucleotide polymorphism (SNP), rs3087456 (-168 A/G), has indeed been associated with several autoimmune diseases, including rheumatoid arthritis (RA). Recently, an intronic SNP rs8048002 has been suggested as a better susceptibility marker in Addison's disease. Therefore, we tested both SNPs in a panel of autoimmune diseases, consisting of Norwegian patients with RA (n=819), juvenile idiopathic arthritis (JIA; n=524), or type 1 diabetes (T1D; n=1211), and 2149 controls. We also included an independent Swedish RA cohort (n=2503) and controls (n=1416). Both rs3087456 and rs8048002 were significantly associated with RA (combined Norwegian and Swedish patients P(corrected)=0.012 and P(corrected)=0.0016, respectively), but not with JIA or T1D. Meta-analysis of 16 RA cohorts confirmed rs3087456 with only marginal significance (P=0.016). However, results were stronger in the Scandinavian subgroup (4 cohorts, P=3.8 × 10(-4)), indicating a population-dependent effect. A similar pattern was observed in a meta-analysis of rs8048002. Our results support involvement of CIITA in RA, but imply that this is population dependent and that the aetiological variant is yet to be discovered.

• Nordang, Gry Beate Namløs; Viken, Marte K; Amundsen, Svanstrøm Silja; Sanchez, Elena S.; Flatø, Berit & Førre, Øystein Thorleiv [Show all 9 contributors for this article] (2012). Interferon regulatory factor 5 gene polymorphism confers risk to several rheumatic diseases and correlates with expression of alternative thymic transcripts. Rheumatology. ISSN 1462-0324. 51(4), p. 619–626. doi: 10.1093/rheumatology/ker364. Full text in Research Archive
• Ruperto, Nicolino; Brunner, Hermine I; Quartier, Pierre; Constantin, Tamás; Wulffraat, Nico & Horneff, Gerd [Show all 36 contributors for this article] (2012). Two Randomized Trials of Canakinumab in Systemic Juvenile Idiopathic Arthritis. New England Journal of Medicine. ISSN 0028-4793. 367(25), p. 2396–2406. doi: 10.1056/NEJMoa1205099. Full text in Research Archive
• Tollisen, Anita; Sanner, Helga; Flatø, Berit & Wahl, Astrid (2012). Quality of Life in Adults With Juvenile-Onset Dermatomyositis: A Case-Control Study. Arthritis Care and Research. ISSN 0893-7524. 64(7), p. 1020–1027. doi: 10.1002/acr.21637. Full text in Research Archive
• Staalesen, Yndis; Nordvåg, Bjørn-Yngvar; Stanghelle, Johan K; Røisland, Mona; Winther, Anne & Pajunen, Pär-Arne [Show all 8 contributors for this article] (2011). Efficacy of rehabilitation for patients with ankylosing spondylitis: Comparison of a four-week rehabilitation programme in a Mediterranean and a Norwegian setting. Journal of Rehabilitation Medicine. ISSN 1650-1977. 43(6), p. 534–542. doi: 10.2340/16501977-0804. Full text in Research Archive
• Sanner, Helga; Aaløkken, Trond Mogens; Gran, Jan Tore; Sjaastad, Ivar; Johansen, Bjørn & Flatø, Berit (2011). Pulmonary outcome in juvenile dermatomyositis: a case-control study. Annals of the Rheumatic Diseases. ISSN 0003-4967. 70(1), p. 86–91. doi: 10.1136/ard.2010.131433. Full text in Research Archive
• Kirkhus, Eva; Flatø, Berit; Riise, Øystein Rolandsen; Reiseter, Tor & Smith, Hans-Jørgen (2011). Differences in MRI findings between subgroups of recent-onset childhood arthritis. Pediatric Radiology. ISSN 0301-0449. 41(4), p. 432–440. doi: 10.1007/s00247-010-1897-y. Full text in Research Archive Show summary

  Background MRI is sensitive for joint inflammation, but its ability to separate subgroups of arthritis in children has been questioned. Infectious arthritis (IA), postinfectious arthritis (PA), transient arthritis (TA) and juvenile idiopathic arthritis (JIA) are subgroups that may need early, different treatment. Objective To determine whether MRI findings differ in IA, PA/TA and JIA in recent-onset childhood arthritis. Materials and methods Fifty-nine children from a prospective study of incidence of arthritis (n = 216) were, based on clinical and biochemical criteria, examined by MRI. Joint fluid, synovium, bone marrow, soft tissue and cartilage were scored retrospectively and analysed by Pearson chi-square test and logistic regression analysis. Results Fifty-nine children had MRI of one station. IA was suggested by bone marrow oedema (OR 7.46, P = 0.011) and absence of T1-weighted and T2-weighted low signal intensity synovial tissue (OR 0.06, P = 0.015). Furthermore, soft-tissue oedema and reduced contrast enhancement in the epiphyses were more frequent in children with IA. JIA correlated positively with low signal intensity synovial tissue (OR 13.30, P < 0.001) and negatively with soft-tissue oedema (OR 0.20, P = 0.018). No significant positive determinants were found for PA/TA, but bone marrow oedema, soft-tissue oedema, irregular thickened synovium and low signal intensity synovial tissue was less frequent than in IA/JIA. Conclusion In children with high clinical suspicion of recent onset arthritis, there was a significant difference in the distribution of specific MRI features among the diagnostic groups. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

• Schwartz, Thomas; Sanner, Helga; Husebye, Trygve Guttorm; Flatø, Berit & Sjaastad, Ivar (2011). Cardiac dysfunction in juvenile dermatomyositis - a case control study. Annals of the Rheumatic Diseases. ISSN 0003-4967. 70(5), p. 766–771. doi: 10.1136/ard.2010.137968. Full text in Research Archive
• Arvidsson, Linda Zamoline; Smith, Hans-Jørgen; Flatø, Berit & Larheim, Tore Arne (2010). Temporomandibular Joint Findings in Adults with Long-standing Juvenile Idiopathic Arthritis: CT and MR Imaging Assessment. Radiology. ISSN 0033-8419. 256(1), p. 191–200. doi: 10.1148/radiol.10091810. Full text in Research Archive
• Lien, Gunhild; Ueland, Thor; Godang, Kristin; Selvaag, Anne Marit G; Førre, Øystein Thorleiv & Flatø, Berit (2010). Serum levels of osteoprotegerin and receptor activator of nuclear factor -kappa B ligand in children with early juvenile idiopathic arthritis: a 2-year prospective controlled study. Pediatric Rheumatology. 8. doi: 10.1186/1546-0096-8-30. Full text in Research Archive Show summary

  Background 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. Methods 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. Results 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. Conclusions 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.

• Fjeld, Morten; Arvidsson, Linda Zamoline; Smith, Hans-Jørgen; Flatø, Berit; Øgaard, Bjørn & Larheim, Tore Arne (2010). Relationship between disease course in the temporomandibular joints and mandibular growth rotation in patients with juvenile idiopathic arthritis followed from childhood to adulthood. Pediatric Rheumatology. p. 13–13. doi: 10.1186/1546-0096-8-13. Full text in Research Archive Show summary

  Objective To investigate the relationship between radiographic JIA disease course in the TMJs and mandibular growth rotation, compared with growth in healthy individuals. Methods From a larger series of JIA patients followed from childhood to adulthood, 26 were included; 11 without and 15 with bilateral radiographic TMJ involvement. Joint morphology and function were assessed at baseline, 2-, 4-, 6- and 27 years follow-up. Mandibular growth rotation (anterior, posterior or none) was assessed from cephalometric evaluations at childhood and adulthood, with observations from 16 healthy individuals as controls. TMJ disease course and mandibular growth rotation were assessed independently and their relationship analysed. Non-parametric statistical methods were applied to test differences between groups. Results In the normal TMJ group of JIA patients the joint morphology was similar at the follow-ups and all patients had good function both in childhood and in adulthood. The mandibular growth rotation was similar to that of healthy controls, i.e. predominantly in anterior direction. In the abnormal TMJ group different JIA TMJ disease courses were observed and associated with changes in the mandibular growth rotation (p = 0.007). Progressing JIA TMJ disease course was related to posterior mandibular growth rotation and improving disease course to anterior mandibular growth rotation. Conclusion A relationship was found between JIA disease course in the TMJs and mandibular growth rotation, suggesting that a favourable growth could be regained in patients with improvement in TMJ morphology and/or TMJ function. To confirm this, further research on larger patient series is needed.

• Ruperto, Nicolino; Pistorio, Angela; Ravelli, Angelo; Rider, Lisa G.; Pilkington, Clarissa & Oliveira, Sheila [Show all 35 contributors for this article] (2010). The Paediatric Rheumatology International Trials Organisation Provisional Criteria for the Evaluation of Response to Therapy in Juvenile Dermatomyositis. Arthritis Care and Research. ISSN 0893-7524. 62(11), p. 1533–1541. doi: 10.1002/acr.20280. Full text in Research Archive
• Østlie, Ingrid Landgraff; Johansson, Inger Signe; Aasland, Astrid; Flatø, Berit & Möller, Anders (2010). Self-rated physical and psychosocial health in a cohort of young adults with juvenile idiopathic arthritis. Scandinavian Journal of Rheumatology. ISSN 0300-9742. 39(4), p. 318–325. doi: 10.3109/03009740903505213. Full text in Research Archive Show summary

  Objective: To explore self-rated physical and psychosocial health in a cohort of young adults with juvenile idiopathic arthritis (JIA) 18.3 years after symptom onset, make comparisons with population-based data, and illuminate possible predictors of self-rated health. Methods: Of a baseline cohort of 84 patients with JIA, 55 (65.5%) answered the self-administered questionnaires of the Health Assessment Questionnaire (HAQ), the Visual Analogue Scale (VAS) of pain, fatigue, and illness, the Medical Outcomes Study 36-item Short Form Health Survey (SF-36), and the General Health Questionnaire (GHQ-30). Telephone interviews were conducted with 51/55 patients. Population-based norm-data of SF-36 were used for comparison. Results: Significantly impaired physical health but no difference in psychosocial health was found as compared to the general Norwegian population. The level of education was significantly higher whereas no difference was found in employment status as compared to norm-data. Pain was a significant correlate of the education level. Predictors of physical impairment were physical disability and pain, whereas psychiatric distress and female sex were predictors of mental ill-health. Conclusion: Physical disability does not seem to have a negative influence on the patients? functioning psychosocially.

• Sanner, Helga; Kirkhus, Eva; Merckoll, Else; Tollisen, Anita; Røisland, Mona & Lie, Benedicte Alexandra [Show all 9 contributors for this article] (2010). Long-Term Muscular Outcome and Predisposing and Prognostic Factors in Juvenile Dermatomyositis: A Case-Control Study. Arthritis Care and Research. ISSN 0893-7524. 62(8), p. 1103–1111. doi: 10.1002/acr.20203. Full text in Research Archive
• Sanner, Helga; Aaløkken, Trond Mogens; Gran, Jan Tore; Sjaastad, Ivar; Johansen, Bjørn & Flatø, Berit (2010). Pulmonary outcome in juvenile dermatomyositis: a case-controll study. Annals of the Rheumatic Diseases. ISSN 0003-4967. 70, p. 86–91. doi: 10.1136/ard.2010.131433. Full text in Research Archive

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• Hetlevik, Siri Opsahl; Lilleby, Vibke; Pesonen, Maiju; Nordal, Ellen Berit; Rygg, Marite & Austad, Cathrine [Show all 17 contributors for this article] (2026). Moving towards optimized treatment for children and adolescents with juvenile idiopathic arthritis in sustained remission randomized to continue stable treatment, methotrexate withdrawal or tumor necrosis factor inhibitor withdrawal: study protocol for the Norwegian multi-center MOVE-JIA trial. doi: 10.1186/s13063-026-09539-0. Full text in Research Archive
• Herder, Ingrid; Hetlevik, Siri Opsahl; Gehin, J. E.; Pesonen, Maiju; Lilleby, Vibke & Rygg, Marite [Show all 17 contributors for this article] (2025). PT006 Adalimumab serum levels and associations with disease activity in juvenile idiopathic arthritis. Pediatric Rheumatology. 23(2). Full text in Research Archive
• Bøyesen, Pernille; Aga, Anna-Birgitte; Lilleby, Vibke; Pesonen, Maiju; Rygg, Marite & Nordal, Ellen Berit [Show all 17 contributors for this article] (2025). O09 Long-term treatment efficacy of intra-articular triamcinolone hexacetonide injections in juvenile idiopathic arthritis patients starting tumor necrosis factor inhibitor therapy: 48-week results from a randomized, phase 4 trial - the myjia trial. Pediatric Rheumatology. 23(2). Full text in Research Archive
• Flatø, Berit & Dahle, Merete Lindén (2024). Hvordan bør barn og unge med barneleddgikt som har inaktiv sykdom (remisjon) best behandles? doi: https:/www.forskersonen.no/kronikk-meninger/unge-voksne-med-barneleddgikt-har-fatt-redusert-livskvalitet/2318975. Full text in Research Archive
• Brandis, Elisabeth von; Avenarius, Derk Frederik Matthaus; Bjørnerud, Atle; Flatø, Berit; Tomterstad, Anders & Lilleby, Vibke [Show all 11 contributors for this article] (2022). Correction to: Automated segmentation of magnetic resonance bone marrow signal: a feasibility study (Pediatric Radiology, (2022), 10.1007/s00247-021-05270-x). Pediatric Radiology. ISSN 0301-0449. 52. doi: 10.1007/s00247-022-05315-9. Full text in Research Archive
• Tollisen, Anita; Selvaag, Anne Marit; Aasland, Astrid; Lerdal, Anners & Flatø, Berit (2021). Fatigue, smerte, fysisk funksjon og helserelatert livskvalitet hos unge voksne med barneleddgikt. Full text in Research Archive
• Gjersvik, Petter; Rojahn, Astrid Elisabeth & Flatø, Berit (2021). Inflammatorisk multisystemsyndrom ved covid-19. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 141(17). doi: 10.4045/tidsskr.21.0683. Full text in Research Archive
• Tollisen, Anita; Selvaag, Anne Marit; Ingebrigtsen, Trude Miljeteig; Aasland, Astrid; Lerdal, Anners & Flatø, Berit (2018). Treatment satisfaction in patients with juvenile idiopathic arthritis. Full text in Research Archive
• Hetlevik, Siri Opsahl; Aaløkken, Trond Mogens; Lund, M B; Flatø, Berit; Nordal, Ellen Berit & Rygg, Marite [Show all 7 contributors for this article] (2017). Pulmonary manifestations in juvenile onset mixed connective tissue disease after longterm disease duration – a Norwegian case-control study. Full text in Research Archive
• Witzcak, Birgit; Godang, Kristin; Schwartz, Thomas; Flatø, Berit; Bollerslev, Jens & Sjaastad, Ivar [Show all 7 contributors for this article] (2015). In adults with juvenile onset dermatomyositis, visceral adipose tissue is increased compared with controls, and is associated with serum lipids. Full text in Research Archive
• Tollisen, Anita; Selvaag, Anne Marit; Aulie, Hanne Aaserud; Lerdal, Anners & Flatø, Berit (2015). Health Related Quality of Life in Adults with JIA - a 30 Year Longitudinal Study. Full text in Research Archive
• Johnsson, Anders Carl G.; Flatø, Berit; Knudsen, Per Kristian & Lilleby, Vibke (2015). Clinical outcome in a Norwegian cohort of patients with chronic recurrent multifocal osteomyelitis. Scandinavian Journal of Rheumatology. ISSN 0300-9742. 44(6), p. 513–514. doi: 10.3109/03009742.2015.1055514. Full text in Research Archive
• Barth, Zoltan; Witzcak, Birgit; Schwartz, Thomas; Gjesdal, Knut; Flatø, Berit & Koller, A'kos [Show all 8 contributors for this article] (2015). Heart rate variability is related to inflammation and cardiac function in juvenile dermatomyositis. Full text in Research Archive
• Barth, Zoltan; Witzcak, Birgit; Schwartz, Thomas; Gjesdal, Knut; Flatø, Berit & Koller, A'kos [Show all 8 contributors for this article] (2015). Heart rate variability is related to inflammation and cardiac function in juvenile dermatomyositis. Full text in Research Archive
• Hetlevik, Siri Opsahl; Flatø, Berit; Nordal, Ellen Berit; Rygg, Marite & Lilleby, Vibke (2015). Long term outcome and clinical characteristics in childhood-onset mixed connective tissue disease – a Norwegian nationwide study. Annual European Congress of Rheumatology, Fiera di Roma, Rome, Italy, 10 - 13 June 2015. Annals of the Rheumatic Diseases. ISSN 0003-4967. 74, p. 184–184. Full text in Research Archive
• Lilleby, Vibke; Haydon, Joanna; Sanner, Helga; Krossness, B.K.; Ringstad, Geir Andre & Flatø, Berit (2014). Severe macrophage activation syndrome and central nervous system involvement in juvenile dermatomyositis. Scandinavian Journal of Rheumatology. ISSN 0300-9742. 43(2), p. 171–173. doi: 10.3109/03009742.2013.863968. Full text in Research Archive
• Aulie, Hanne Aaserud; Selvaag, Anne Marit G; Lilleby, Vibke; Molberg, Øyvind; Hartmann, Anders & Holdaas, Hallvard [Show all 7 contributors for this article] (2013). Increased Pulse Wave Velocity In Juvenile Idiopathic Arthritis Patients Compared To Controls From The General Population. Arthritis and Rheumatism. ISSN 0004-3591. 65, p. S1142–S1142. Full text in Research Archive
• Selvaag, Anne Marit G; Aulie, Hanne Aaserud; Lilleby, Vibke & Flatø, Berit (2013). Disease Progression Into Adulthood In Patients With Juvenile Idiopathic Arthritis - a Longitudinal 30 Year Follow-Up Study. Arthritis and Rheumatism. ISSN 0004-3591. 65, p. S1142–S1143. Full text in Research Archive
• Stray-Pedersen, Asbjørg; Sorte, Hanne Sørmo; Rødningen, Olaug Kristin; Lyle, Robert; Gonzaga-Jauregui, C G & Hanson, C I [Show all 16 contributors for this article] (2012). THE UTILITY OF EXOME SEQUENCING IN PRIMARY IMMUNODEFICIENCY DISEASES AND IMMUNODYSREGULATIVE DISORDERS. Journal of Clinical Immunology. ISSN 0271-9142. 32(Supp. 1), p. 184–185. Full text in Research Archive
• Schwartz, Thomas; Sjaastad, Ivar; Flatø, Berit; Vistnes, Maria; Christensen, Geir Arve & Sanner, Helga (2012). Monocyte Chemoattractant Protein-1 and Eotaxin Are Associated with Parameters of Cardiac Dysfunction in Juvenile Dermatomyositis. Arthritis and Rheumatism. ISSN 0004-3591. 64(10), p. S381–S381. Full text in Research Archive
• Schwartz, Thomas; Sanner, Helga; Husebye, EE; Flatø, Berit & Sjaastad, Ivar (2011). Cardiac dysfunction in juvenile dermatomyositis - a case control study. Full text in Research Archive
• Schwartz, Thomas; Sanner, Helga; Vistnes, Maria; Christensen, Geir Arve; Flatø, Berit & Sjaastad, Ivar (2011). Increased levels of MCP-1 and eotaxin are associated with cardiac dysfunction in juvenile dermatomyositis. Full text in Research Archive
• Tollisen, Anita; Sanner, Helga; Flatø, Berit & Wahl, Astrid Klopstad (2011). Health-related Quality of Life in Adults with Juvenile Dermatomyositis. Clinical and Experimental Rheumatology. ISSN 0392-856X. 29(2), p. 389–389. Full text in Research Archive
• Arvidsson, Linda Zamoline; Fjeld, Morten; Smith, Hans-Jørgen; Flatø, Berit; Øgaard, Bjørn & Larheim, Tore Arne (2010). Relationship between disease course in the temporomandibular joints and mandibular growth rotation in patients with juvenile idiopathic arthritis followed from childhood to adulthood. Full text in Research Archive
• Flatø, Berit; Lerdal, Anners; Selvaag, Anne Marit & Tollisen, Anita (2020). Patient-reported outcomes and medication satisfaction in adults with juvenile idiopathic arthritis. Universitetet i Oslo. Full text in Research Archive Show summary

  Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease. The severity and disease course are highly variable and JIA can be a life-long disorder. The aims of this study were to assess patient-reported outcomes in adults with JIA regarding pain, physical disability and health-related quality of life (HRQOL), examine longitudinal changes and predictors of these outcomes, and explore treatment satisfaction with and adherence to medication in patients currently treated with disease-modifying antirheumatic drugs (DMARDs). Two cohorts of patients were included in the study. 96 patients (previously assessed each 6 months for 3 years at early disease course) were reassessed 19 years after disease onset and 176 patients (previously assessed after 15 and 23 years of disease duration) were reassessed after 30 years. Controls were recruited from the general population. In both cohorts, patients had lower physical HRQOL than controls and almost half of patients reported some physical disability. After 19 years patients also had more pain than controls. Patients` levels of wellbeing and physical HRQOL deteriorated during the longitudinal follow-ups after 15, 23 and 30 years, while fatigue and proportion with physical disability increased from 3 to 19-year follow-up. Patients on DMARDs (n=52) 19 years after disease onsets were more satisfied with biological drugs than with methotrexate, and 46% reported low medication adherence. Low medication satisfaction was associated with lower physical HRQOL. Pain, physical disability, fatigue, low wellbeing and active joints predicted unfavourable patient-reported outcomes. Late pain recovery at early disease course, predicted more pain, physical disability and lower HRQOL after 19 years. Our findings suggest that JIA has a detrimental effect on health-related outcomes. Information about long-term consequences of JIA and patients` medication experiences may increase health-care professionals` understanding of the burden of JIA.

• Staalesen, Yndis & Flatø, Berit (2011). The efficacy of rehabilitation in warm and cold climates for patients with rheumatic and neurological diseases : Three randomised controlled studies. Universitetet i Oslo. ISSN 9788282641661. Full text in Research Archive Show summary

  The Section for Climate Therapy offers a 4-week in-patient rehabilitation programme in a warm and sunny climate for some selected chronic diseases. The main purpose of this PhD thesis was to investigate the effect of a multidisciplinary rehabilitation programme, and to compare the effect of this intervention given in a warm versus a cold climatic setting. One randomised controlled trial included patients with rheumatoid arthritis (n=124) and ankylosing spondylitis (n=107), they were randomised to rehabilitation either in a Norwegian or in a Mediterranean rehabilitation centre, and followed up after 3 and 6 months. Patients with postpolio syndrome (n=88) and heredital neuromuscular diseases (n=60) were included in two other studies with a similar design. Immediate improvements were demonstrated in different aspects of health in both climatic settings for all included diagnoses. In general, most improvements were larger and sustained longer when rehabilitation was performed in a warm climatic setting. When the attained reductions in pain and fatigue were sustained after therapy in a warm climatic setting only, improvements in the physical capacity were sustained more independently of the climatic setting. Some more specific effects of the treatment in a warm climate, were a larger reduction in disease activity parameters in rheumatoid arthritis, a sustainable increase in spinal mobility in 91% of the ankylosing spondylitis patients, and reduced depression in the postpolio patients. In conclusion, our studies show improvements of an in-patient rehabilitation programme at different levels of health for all included diagnosis, and support an additional effect when this intervention is performed in a warm climatic setting. This PhD thesis is written within the rehabilitation and rheumatology field, and the studies have been conducted at the Section for Climate Therapy at Oslo University Hospital Rikshospitalet in cooperation with Sunnaas Rehabilitation Hospital.

• Sanner, Helga & Flatø, Berit (2010). Outcomes and prognostic factors in Juvenile Dermatomyositis. Universitetet i Oslo. Full text in Research Archive Show summary

  Background: Juvenile Dermatomyositis is a rare, presumably autoimmune disease of childhood, with an annual incidence of 1.9-3.2 per million children. Lately, validated measures for disease activity and damage in myositis have been developed, but scarce data about long-term outcome is available. Objectives: To investigate outcomes and predictors for outcomes in a Norwegian inception cohort of Juvenile Dermatomyositis patients, and to see how measures for muscular, pulmonary and health outcomes in JDM patients differ from that of matched controls from the general population. Methods: Patients with probable or definite JDM according to the Bohan-Peter criteria, diagnosis after 1970, disease onset < 18 years of age and disease duration > 2 years were identified from Norwegian hospital registries. The patients were clinically examined median 16.8 years (range 2.0-38.1) after symptom onset and were compared with age- and sex-matched controls (randomly selected from the Norwegian population register). Muscle strength was measured by the Manual Muscle Test (MMT) and Child Myositis Assessment Scale (CMAS); physical health by SF-36 PCS and pulmonary function by spirometry, body plethysmography and diffusion capacity for CO (DLCO). In patients, high resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) of thigh muscles were carried out, and disease activity and damage was measured by Disease Activity Score (DAS), Myositis Damage Index (MDI) and Health Assessment Questionnaire (HAQ/child-HAQ). Early disease characteristics were assessed by chart review. Results: Sixty seven JDM patients were identified, which correspond to an average annual incidence of at least 1.8/million children in Norway from 1970-2005. 4 patients had died (6%); the remaining 63 could all be tracked, and 60 (95%) of those participated in the study (60% female). In patients, cumulative organ damage was found in 90% (included calcinosis in 47%), and physical disability in 40% (HAQ/child-HAQ>0). Muscle strength and physical function was lower in patients than controls (P`s < 0.001 and 0.014, respectively). Muscle weakness was found in 31% (CMAS) and 42% (MMT), but the impairment was mostly mild. MRI detected muscular damage was found in 52% (included muscular atrophy, calcinosis and fatty infiltration), and correlated with CMAS and MDI (P`s < 0.01). Patients had smaller lung volumes than controls (P=0.011). In patients, restrictive ventilatory defects and reduced diffusion capacity were found in 26% and 49%, respectively. HRCT abnormalities were found in 37%, and included interstitial lung disease (14%), calcinosis in the chest wall (14%) and airways disease (15%). High disease activity and damage 6 and 12 months post-diagnosis, predicted cumulative organ damage, calcinosis, muscle weakness and MRI detected muscle damage at follow-up. Conclusions: After median 16.8 years disease duration, a substantial portion of our JDM patients had cumulative organ damage, mild physical disability and unfavorable muscular outcomes. Although mostly subclinical, pulmonary involvement was found in the majority of patients. Our findings show that JDM patients have impaired function many years after diagnosis and that sustained early disease activity and damage predict an unfavorable outcome; also our study highlights the systemic nature of the disease. Hopefully, JDM outcomes will improve with advances in treatment.

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