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.

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.

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.

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<0.001) and with clinical arthritis (OR=7.4,p<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.

Performance of the 2016 ACR-EULAR myositis response criteria in juvenile dermatomyositis therapeutic trials and consensus profiles.

OBJECTIVES: The 2016 ACR-EULAR Response Criteria for JDM was developed as a composite measure with differential weights of six core set measures (CSMs) to calculate a Total Improvement Score (TIS). We assessed the contribution of each CSM, representation of muscle-related and patient-reported CSMs towards improvement, and frequency of CSM worsening across myositis response criteria (MRC) categories in validation of MRC. METHODS: Data from JDM patients in the Rituximab in Myositis trial (n = 48), PRINTO JDM trial (n = 139), and consensus patient profiles (n = 273) were included. Observed vs expected CSM contributions were compared using Sign test. Characteristics of MRC categories were compared by Wilcoxon tests with Bonferroni adjustment. Spearman correlation of changes in TIS and individual CSMs were examined. Agreement between physician-assessed change and MRC categories was evaluated by weighted Cohen's kappa. RESULTS: Of 457 JDM patients with IMACS CSMs and 380 with PRINTO CSMs, 9-13% had minimal, 19-23% had moderate and 41-50% had major improvement. The number of improved and absolute percentage change of CSMs increased by MRC improvement level. Patients with minimal improvement by MRC had a median of 0-1 CSM worsened, and those with moderate/major improvement had a median of zero worsening CSMs. Of patients improved by MRC, 94-95% had improvement in muscle strength and 93-95% had improvement in ≥1 patient-reported CSM. IMACS and PRINTO CSMs performed similarly. Physician-rated change and MRC improvement categories had moderate-to-substantial agreement (Kappa 0.5-0.7). CONCLUSION: The ACR-EULAR MRC perform consistently across multiple studies, supporting its further use as an efficacy end point in JDM trials.

Adipokine profile in long-term juvenile dermatomyositis, and associations with adipose tissue distribution and cardiac function: a cross-sectional study.

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.

Treatment Response to Tumor Necrosis Factor Inhibitors and Methotrexate Monotherapy in Adults With Juvenile Idiopathic Arthritis: Data From NOR-DMARD.

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.

Adipose tissue distribution is associated with cardio-metabolic alterations in adult patients with juvenile-onset dermatomyositis.

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.

Whole body magnetic resonance imaging in healthy children and adolescents. Bone marrow appearances of the axial skeleton.

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. 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. 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. 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.

Whole body magnetic resonance imaging in healthy children and adolescents: Bone marrow appearances of the appendicular skeleton.

OBJECTIVE: To describe the appearances of bone marrow in the appendicular skeleton on fat-suppressed T2-weighted sequences as assessed by whole-body MRI in healthy and asymptomatic children and adolescents. MATERIAL AND METHODS: Following ethical approval, we assessed the bone marrow of the extremities on water-only Dixon T2-weighted images as part of a whole-body MRI in 196 healthy and asymptomatic children aged 5-19 years. Based on a newly devised and validated scoring system, we graded intensity (0-2 scale) and extension (1-4 scale) of focal high signal bone marrow areas, and divided them into minor or major findings, based on intensity and extension, reflecting their potential conspicuousness in a clinical setting. RESULTS: In the upper extremity, we registered 366 areas with increased signal whereof 79 were major findings. In the lower extremities there were 675 areas of increased signal of which 340 were major findings. Hundred-and-fifteen (58.79%) individuals had at least one major finding, mainly located in the hand and proximal humerus, and the feet and knees. We found no differences according to gender, reported hours of sports activity, handedness, or age group, except for more minor findings in the upper extremities amongst 15-18-year-olds as compared to those aged 5-8 years. CONCLUSION: Focal areas of high signal intensity on whole-body MRI, T2-weighted fat suppressed images that, in a clinical setting could cause concern, were seen in more than half of healthy, asymptomatic children and adolescents. Awareness of this is important when interpreting whole-body MRI in this age group, particularly in the assessment of clinically silent lesions.

Personally Generated Quality of Life Outcomes in Adults With Juvenile Idiopathic Arthritis.

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.

Identification of Novel Loci Shared by Juvenile Idiopathic Arthritis Subtypes Through Integrative Genetic Analysis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common chronic immune-mediated joint disease among children 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 basis between subtypes. This study was undertaken to systematically investigate shared genetic underpinnings of JIA subtypes. METHODS: We performed a heterogeneity-sensitive genome-wide association study encompassing a total of 1,245 JIA cases (classified into 7 subtypes) and 9,250 controls, followed by fine-mapping of candidate causal variants at each genome-wide significant locus, functional annotation, and pathway and network analysis. We further identified candidate 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 genes at these loci were expressed in diverse immune cell types. CONCLUSION: This study identified novel genetic loci shared by JIA subtypes. Our findings identified candidate mechanisms underlying JIA subtypes and candidate targets with drug repurposing opportunities for JIA treatment.

Automated segmentation of magnetic resonance bone marrow signal: a feasibility study.

BACKGROUND: Manual assessment of bone marrow signal is time-consuming and requires meticulous standardisation to secure adequate precision of findings. OBJECTIVE: We examined the feasibility of using deep learning for automated segmentation of bone marrow signal in children and adolescents. 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. 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. 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.

Associations between cardiac and pulmonary involvement in patients with juvenile dermatomyositis-a cross-sectional study.

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.

Body composition in long-standing juvenile dermatomyositis: associations with disease activity, muscle strength and cardiometabolic measures.

OBJECTIVE: To compare body composition parameters in patients with long-standing JDM and controls and to explore associations between body composition and disease activity/inflammation, muscle strength, health-related quality of life (HRQoL) and cardiometabolic measures. METHODS: We included 59 patients (median disease duration 16.7 y; median age 21.5 y) and 59 age- and sex-matched controls in a cross-sectional study. Active and inactive disease were defined by the PRINTO criteria. Body composition was assessed by total body DXA, inflammation by high-sensitivity CRP (hs-CRP) and cytokines, muscle strength by the eight-muscle manual muscle test, HRQoL by the 36-item Short Form Health Survey physical component score 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 a higher android fat:gynoid fat (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 and hs-CRP). Lower ALMI was associated with reduced muscle strength, while higher BF% was associated with impaired HRQoL. Central fat distribution (higher A:G ratio) was associated with impaired cardiac function and unfavourable serum lipids. CONCLUSION: Despite normal BMI, patients with JDM, especially those with active disease, had unfavourable body composition, which was associated with impaired HRQoL, muscle strength and cardiometabolic function. The association between central fat distribution and cardiometabolic alterations is a novel finding in JDM.

Multisystem inflammatory syndrome in children and adolescents after infection with SARS-CoV-2. / Multiorgan inflammatorisk syndrom hos barn og ungdom etter SARS-CoV-2-infeksjon.

Multisystem inflammatory syndrome is a rare immune-mediated complication of infection with SARS-CoV-2 in children and adolescents. The patients can rapidly become seriously ill with high fever, gastrointestinal symptoms and cardiogenic shock. The goal of treatment is to ensure adequate circulation and prevent late complications by providing anti-inflammatory therapy.

Development and reliability of a novel ultrasonographic joint-specific scoring system for synovitis with reference atlas for patients with juvenile idiopathic arthritis.

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.

Bone mineral density and explanatory factors in children and adults with juvenile dermatomyositis at long term follow-up; a cross sectional study.

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.

Treatment Satisfaction With and Adherence to Disease-Modifying Antirheumatic Drugs in Adult Patients With Juvenile Idiopathic Arthritis.

OBJECTIVE: To examine medication satisfaction and adherence and their relationships to disease variables and health-related quality of life (HRQoL) in adults with juvenile idiopathic arthritis (JIA). METHODS: Patients (n = 96, mean age 25 years, 67% female) completed questionnaires about their health status 19 years after disease onset. Patients receiving biologic disease-modifying antirheumatic drugs (bDMARDs) or methotrexate (MTX) were assessed with the 8-item Morisky Medication Adherence Scale (MMAS-8) and the Treatment Satisfaction Questionnaire for Medication (TSQM), including dimensions of effectiveness, side effects, convenience, and global satisfaction. RESULTS: DMARDs were received by 52 patients (54%) (mean age 25 years, 75% female), of which 28 received MTX and 37 received bDMARDs. Patients receiving combination therapy of MTX and bDMARDs (n = 15) reported higher satisfaction with bDMARDs than MTX in the dimensions of side effects and global satisfaction (mean ± SD 92.9 ± 15.5 versus 56.2 ± 30.9, and mean ± SD 67.6 ± 19.8 versus 47.1 ± 21.7; P < 0.001 and P = 0.016, respectively). Patients receiving either bDMARDs (n = 22) or MTX (n = 13) reported higher satisfaction with bDMARDs than MTX for the dimensions of effectiveness and global satisfaction (mean ± SD 78.7 ± 15.4 versus 60.2 ± 19.9, and mean ± SD 73.6 ± 17.7 versus 52.3 ± 23.9; P = 0.004 and P = 0.005, respectively). Nearly one-half of patients (46%) reported low adherence (MMAS-8 score <6) and 25% high adherence (MMAS-8 score = 8). Higher levels of pain, psychological distress, more active joints, and current MTX use were the strongest correlates of lower medication satisfaction. Perceived medication effectiveness and global satisfaction correlated positively with physical and mental HRQoL. CONCLUSION: Patients with JIA were more satisfied with bDMARDs than MTX, and 46% reported low adherence. Higher medication satisfaction was associated with better HRQoL.

Salivary Oral Microbiome of Children With Juvenile Idiopathic Arthritis: A Norwegian Cross-Sectional Study.

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.

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.

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.