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Rationale and Objectives: The temporomandibular joint (TMJ) is commonly involved in children with juvenile idiopathic arthritis. The diagnosis and evaluation of the disease progression is dependent on medical imaging. The precision of this imaging is under debate. SeveralR scoring systems have been proposed but transparent testing of the precision of the constituents of the scoring systems is lacking. The present study aims to test the precision of 25 imaging features based on magnetic resonance imaging (MRI). Materials and Methods: Clinical data and imaging were obtained from the Norwegian juvenile idiopathic arthritis study, The NorJIA study. Twenty-five imaging features of the TMJ in MRI datasets from 86 study participants were evaluated by two experienced radiologists for inter- and intraobserver agreement. Agreement of ordinal variables was measured with Cohen s linear or weighted Kappa as appropriate. Agreement of continuous measurements was assessed with 95% limit of agreement according to Bland-Altman. Results: In the osteochondral domain, the ordinal imaging variables “loss of condylar volume,” “condylar shape,” “condylar irregularities,” “shape of the eminence/fossa,” “disk abnormalities,” and “condylar inclination” showed inter- and intraobserver agreement above Kappa 0.5. In the inflammatory domain, the ordinal imaging variables “joint fluid,” “overall impression of inflammation,” “synovial enhancement” and “bone marrow oedema” showed inter- and intraobserver agreement above Kappa 0.5. Continuous measurements performed poorly with wide limits of agreement. Conclusion: A precise MRI-based scoring system for assessment of TMJ in JIA is proposed consisting of seven variables in the osteochondral domain and four variables in the inflammatory domain. Further testing of the clinical validity of the variables is needed.

Objective: To evaluate the predictive value of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of inflammatory cytokines in order to differentiate the child with acute lymphoblastic leukemia (ALL) from juvenile idiopathic arthritis (JIA).Study design: In this cross-sectional study, we measured S100A9, S100A12, and 14 cytokines in serum from children with ALL (n = 150, including 27 with arthropathy) and JIA (n = 236). We constructed predictive models computing areas under the curve (AUC) as well as predicted probabilities in order to differentiate ALL from JIA. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated 10-fold cross-validation and recalibration, adjusted for age.Results: In ALL, the levels of S100A9, S100A12, interleukin (IL)-1 beta, IL-4, IL-13, IL-17, matrix metalloproteinase-3, and myeloperoxidase were low compared with JIA (P < .001). IL-13 had an AUC of 100% (95% CI 100%-100%) due to no overlap between the serum levels in the 2 groups. Further, IL-4 and S100A9 had high predictive performance with AUCs of 99% (95% CI 97%-100%) and 98% (95% CI 94%-99%), respectively, exceeding both hemoglobin, platelets, C-reactive protein, and erythrocyte sedimentation rate.Conclusions: The biomarkers S100A9, IL-4, and IL-13 might be valuable markers to differentiate ALL from JIA. Objective: To evaluate the predictive value of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of inflammatory cytokines in order to differentiate the child with acute lymphoblastic leukemia (ALL) from juvenile idiopathic arthritis (JIA). Study design: In this cross-sectional study, we measured S100A9, S100A12, and 14 cytokines in serum from children with ALL (n = 150, including 27 with arthropathy) and JIA (n = 236). We constructed predictive models computing areas under the curve (AUC) as well as predicted probabilities in order to differentiate ALL from JIA. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated 10-fold cross-validation and recalibration, adjusted for age. Results: In ALL, the levels of S100A9, S100A12, interleukin (IL)-1 beta, IL-4, IL-13, IL-17, matrix metalloproteinase-3, and myeloperoxidase were low compared with JIA (P < .001). IL-13 had an AUC of 100% (95% CI 100%-100%) due to no overlap between the serum levels in the 2 groups. Further, IL-4 and S100A9 had high predictive performance with AUCs of 99% (95% CI 97%-100%) and 98% (95% CI 94%-99%), respectively, exceeding both hemoglobin, platelets, C-reactive protein, and erythrocyte sedimentation rate. Conclusions: The biomarkers S100A9, IL-4, and IL-13 might be valuable markers to differentiate ALL from JIA.

TRAF1/C5 was among the first loci shown to confer risk for inflammatory arthritis in the absence of an associated coding variant, but its genetic mechanism remains undefined. Using ImmunoChip data from 3,939 juvenile idiopathic arthritis (JIA) patients and 14,412 controls, we identified 132 plausible common non-coding variants, reduced serially by SNP-seq, electrophoretic mobility shift, and luciferase studies to the single variant rs7034653 in the third intron ofTRAF1. Genetically manipulated experimental cells and primary monocytes from genotyped donors establish that the risk G allele reduces binding of Fos-Related Antigen 2 (FRA2), resulting in reduced TRAF1 expression and enhanced TNF production. Conditioning on this variant eliminates attributable risk for rheumatoid arthritis, implicating a mechanism shared across the arthritis spectrum. These findings reveal that rs7034653, FRA2, and TRAF1 mediate a pathway through which a non-coding causal variant drives risk of inflammatory arthritis in children and adults.

Purpose To assess the long-term outcome of uveitis in juvenile idiopathic arthritis (JIA). Design Population-based, multicenter, prospective JIA cohort, with a cross-sectional assessment of JIA-associated uveitis (JIA-U) 18 years after the onset of JIA. Participants A total of 434 patients with JIA, of whom 96 had uveitis, from defined geographic areas of Denmark, Finland, Norway, and Sweden. Methods Patients with onset of JIA between January 1997 and June 2000 were prospectively followed for 18 years. Pediatric rheumatologists and ophthalmologists collected clinical and laboratory data. Main Outcome Measures Cumulative incidence of uveitis and clinical characteristics, JIA and uveitis disease activity, ocular complications, visual outcome, and risk factors associated with the development of uveitis-related complications. Results Uveitis developed in 96 (22.1%) of 434 patients with JIA. In 12 patients (2.8%), uveitis was diagnosed between 8 and 18 years of follow-up. Systemic immunosuppressive medication was more common among patients with uveitis (47/96 [49.0%]) compared with patients without uveitis (78/338 [23.1%]). Active uveitis was present in 19 of 78 patients (24.4%) at the 18-year visit. Ocular complications occurred in 31 of 80 patients (38.8%). Short duration between the onset of JIA and the diagnosis of uveitis was a risk factor for developing ocular complications (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1–1.8). Patients with a diagnosis of uveitis before the onset of JIA all developed cataract and had an OR for development of glaucoma of 31.5 (95% CI, 3.6–274). Presence of antinuclear antibodies (ANAs) was also a risk factor for developing 1 or more ocular complications (OR, 3.0; 95% CI, 1.2–7.7). Decreased visual acuity (VA) Conclusions Our results suggest that uveitis screening should start immediately when the diagnosis of JIA is suspected or confirmed and be continued for more than 8 years after the diagnosis of JIA. Timely systemic immunosuppressive treatment in patients with a high risk of developing ocular complications must be considered early in the disease course to gain rapid control of ocular inflammation.

ObjectiveDistinction on clinical grounds between acute lymphoblastic leukaemia presenting with arthropathy (ALLarthropathy) and juvenile idiopathic arthritis (JIA) is difficult, as the clinical and paraclinical signs of leukaemia may be vague. The primary aim was to examine the use of lectin complement pathway proteins as markers to differentiate ALLarthropathy from JIA. The secondary aims were to compare the protein levels at baseline and follow-up in a paired number of children with ALL and to examine the correlation with haematology counts, erythrocyte sedimentation reaction (ESR), C-reactive protein (CRP), blasts, relapse and death.Study designIn this observational study, we measured M-ficolin, CL-K1 and MASP-3 in serum from children with ALL (n=151) and JIA (n=238) by time-resolved immunofluorometric assays. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated ‘10-fold cross-validation’ with 100 repetitions computing the area under the curve (AUC) as well as positive and negative predictive values in order to evaluate the predictive performance.ResultsThe level of M-ficolin was higher in JIA than ALLtotal and the ALLarthropathy subgroup. The M-ficolin level normalised after remission of ALL. M-ficolin could differentiate ALL from JIA with an AUC of 94% and positive predictive value (PPV) of 95%, exceeding CRP and haemoglobin. In a dichotomised predictive model with optimal cut-offs for M-ficolin, platelets and haemoglobin, AUC was 99% and PPV 98% in detecting ALL from JIA.ConclusionM-ficolin is a valuable marker to differentiate the child with ALL from JIA.

Background Children and adolescents with juvenile idiopathic arthritis (JIA) may suffer pain from temporomandibular disorder (TMD). Still, routines for the assessment of temporomandibular joint (TMJ) pain in health and dental care are lacking. The aims of this study were to examine the prevalence of TMD in children and adolescents with JIA compared to their healthy peers and to investigate potential associations between JIA and TMD. Methods This comparative cross-sectional study is part of a longitudinal multicentre study performed during 2015–2020, including 228 children and adolescents aged 4–16 years with a diagnosis of JIA according to the ILAR criteria. This particular substudy draws on a subset of data from the first study visit, including assessments of TMD as part of a broader oral health examination. Children and adolescents with JIA were matched with healthy controls according to gender, age, and centre site. Five calibrated examiners performed the clinical oral examinations according to a standardised protocol, including shortened versions of the diagnostic criteria for TMD (DC/TMD) and the TMJaw Recommendations for Clinical TMJ Assessment in Patients Diagnosed with JIA. Symptoms were recorded and followed by a clinical examination assessing the masticatory muscles and TMJs. Results In our cohort of 221 participants with JIA and 221 healthy controls, 88 (39.8%) participants with JIA and 25 (11.3%) healthy controls presented with TMD based on symptoms and clinical signs. Painful TMD during the last 30 days was reported in 59 (26.7%) participants with JIA vs. 10 (5.0%) of the healthy controls (p Conclusion Symptoms and clinical signs of TMD were seen in approximately half of the JIA patients compared to about one fourth of their healthy peers. Painful palpation to masticatory muscles and decreased vertical unassisted jaw movement were more frequent in participants with JIA than among healthy controls and should be part of both medical and dental routine examinations in patients with JIA.

Objective To describe risk factors for IBD development in a cohort of children with JIA. Methods JIA patients who developed IBD were identified from the international Pharmachild register. Characteristics were compared between IBD and non-IBD patients and predictors of IBD were determined using multivariable logistic regression analysis. Incidence rates of IBD events on different DMARDs were calculated, and differences between therapies were expressed as relative risks (RR). Results Out of 8942 patients, 48 (0.54% ) developed IBD. These were more often male (47.9% vs 32.0%) and HLA-B27 positive (38.2% vs 21.0%) and older at JIA onset (median 8.94 vs 5.33 years) than patients without IBD development. They also had more often a family history of autoimmune disease (42.6% vs 24.4%) and enthesitis-related arthritis (39.6% vs 10.8%). The strongest predictors of IBD on multivariable analysis were enthesitis-related arthritis [odds ratio (OR): 3.68, 95% CI: 1.41, 9.40] and a family history of autoimmune disease (OR: 2.27, 95% CI: 1.12, 4.54). Compared with methotrexate monotherapy, the incidence of IBD on etanercept monotherapy (RR: 7.69, 95% CI: 1.99, 29.74), etanercept with methotrexate (RR: 5.70, 95% CI: 1.42, 22.77) and infliximab (RR: 7.61, 95% CI: 1.27, 45.57) therapy was significantly higher. Incidence on adalimumab was not significantly different (RR: 1.45, 95% CI: 0.15, 13.89). Conclusion IBD in JIA was associated with enthesitis-related arthritis and a family history of autoimmune disease. An increased IBD incidence was observed for etanercept therapy regardless of concomitant methotrexate use.

Background To determine the serum levels of the lectin pathway proteins early in the disease course and 17 years after disease onset and to correlate the protein levels to markers of disease activity in participants from a population-based Nordic juvenile idiopathic arthritis (JIA) cohort. Additionally, to assess the predictive value of lectin pathway proteins with respect to remission status. Methods A population-based cohort study of consecutive cases of JIA with a disease onset from 1997 to 2000 from defined geographical areas of Finland, Sweden, Norway and Denmark with 17 years of follow-up was performed. Clinical characteristics were registered and H-ficolin, M-ficolin, MASP-1, MASP-3, MBL and CL-K1 levels in serum were analyzed. Results In total, 293 patients with JIA were included (mean age 23.7 ± 4.4 years; mean follow-up 17.2 ± 1.7 years). Concentrations of the lectin protein levels in serum were higher at baseline compared to the levels 17 years after disease onset (p ≤ 0.006, n = 164). At baseline, the highest level of M-ficolin was observed in systemic JIA. Further, high M-ficolin levels at baseline and at 17-year follow-up were correlated to high levels of ESR. In contrast, high MASP-1 and MASP-3 tended to correlate to low ESR. CL-K1 showed a negative correlation to JADAS71 at baseline. None of the protein levels had prognostic abilities for remission status 17 years after disease onset. Conclusion We hypothesize that increased serum M-ficolin levels are associated with higher disease activity in JIA and further, the results indicate that MASP-1, MASP-3 and CL-K1 are markers of inflammation.

Background We aimed to examine psychosocial function, suicidality and school dropout in a clinical psychiatric population over a 3-year period from adolescence to young adulthood and explore associations with negative life events. Methods This study is part of the Health Survey in Department of Children and Youth, St. Olavs hospital, Norway. In the first study visit (T1), 717 (43.5% of eligible) participated, aged 13–18 years (2009–2011), and 3 years later (T2), 570 answered a questionnaire (school functioning and negative life events), and 549 completed Kiddie SADS as telephone interview assessing DSM-IV diagnoses, psychosocial functioning and suicidality. Results Suicidal ideation was more frequent among girls (17.9%) than among boys (5.4%) (risk difference; RD = 12.5%, CI (7.2 to 17.7), p p p p = 0.006). For those with a psychiatric disorder, 24.8% of girls had suicidal ideation and 30.0% suicidal behavior, which was larger than for boys (RD = 18.0%, CI (10.8 to 24.7), p p p p p p p = 0.011). Conclusions The high frequency of suicidality and school dropout confirms the severity of adolescent psychiatric disorders, especially among girls. Specific life events were associated risk factors and should be target points for prevention and intervention.

Background We aimed to examine symptom load in a clinical adolescent population at three-year follow-up and explore associations with standard care treatment procedures and resilience factors upon first presenting at Child and Adolescent Mental Health Services. Methods This study is part of a prospective longitudinal cohort study: The Health Survey in Department of Children and Youth, St. Olavs hospital, Norway. A clinical population of 717 (43.5% of eligible) adolescents aged 13–18 years participated in the first study visit (T1, 2009–2011). Of these, 447 adolescents with psychiatric disorders, with treatment history from medical records and self-reported resilience factors (Resilience Scale for Adolescents; READ) at T1, reported symptom load (Achenbach System of Empirically Based Assessment - Youth Self Report; YSR) three years later aged 16–21 years (T2). Result At T1, 93.0% received individual treatment. The frequency of psychotherapy and medication varied by disorder group and between genders. Overall, psychotherapy was more frequent among girls, whereas medication was more common among boys. Total READ mean value (overall 3.5, SD 0.8), ranged from patients with mood disorders (3.0, SD 0.7) to patients with Attention Deficit Hyperactivity disorder (3.7, SD 0.7), and was lower for girls than boys in all diagnostic groups. At T2, the YSR Total Problem mean T-score ranged across the diagnostic groups (48.7, SD 24.0 to 62.7, SD 30.2), with highest symptom scores for those with mood disorders at T1, of whom 48.6% had T-scores in the borderline/clinical range (≥60) three years later. Number of psychotherapy sessions was positively associated and Total READ score was negatively associated with the YSR Total Problems T-score (regression coefficient β = 0.5, CI (0.3 to 0.7), p Conclusions Self-reported symptom load was substantial after three years, despite comprehensive treatment procedures. Higher self-reported resilience characteristics were associated with lower symptom load after three years. These results highlight the burden of adolescent psychiatric disorders, the need for extensive interventions and the importance of resilience factors for a positive outcome.

Background Optimal utilization of dental caries data is crucial in epidemiological research of individuals with juvenile idiopathic arthritis (JIA). The aims were to: explore whether caries is more prevalent among children and adolescents with JIA compared to controls; examine presence of caries according to JIA group, socio-behavioral and intraoral characteristics, and the extent to which surface-specific caries varies between and within individuals; assess whether surface-specific caries varies according to JIA group and dentition; and investigate whether disease-specific clinical features of JIA are associated with presence of caries. Methods In this comparative cross-sectional study, calibrated dentists examined index teeth (primary 2. molars, 1. permanent molars) of 4–16-year-olds with JIA (n = 219) and matched controls (n = 224), using a detailed caries diagnosis system (including enamel caries). JIA-specific characteristics were assessed by pediatric rheumatologists and socio-behavioral information collected by questionnaires. Multilevel mixed-effect logistic regressions reporting odds ratios (OR) with 95% confidence interval (CI) were applied (caries at surface level as outcome variable). Potential confounders were adjusted for, and the effect of dependency of surface-specific caries data was estimated by calculating intra-class correlation coefficients (ICC). Results At individual level, no significant difference in caries prevalence was found between individuals with JIA and controls, regardless of inclusion of enamel caries. Proportion of enamel lesions exceeded dentine lesions. JIA was not associated with presence of caries, but in both groups, low maternal educational level was associated with presence of caries (OR: 2.07, 95% CI: 1.24–3.46). Occlusal and mesial surfaces, compared to buccal surfaces, had generally higher OR according to presence of caries than distal and lingual surfaces (ICC = 0.56). Surface-specific caries in the permanent dentition differed significantly according to group affiliation. Some JIA disease-specific variables were suggested to associate with presence of caries. Conclusions No overall difference in caries prevalence between individuals with JIA and controls was observed, but for both groups, low maternal educational level and tooth surface associated with presence of caries. Associations between JIA disease-specific variables and presence of caries cannot be excluded. Due to predominance of enamel lesions, the potential of preventative dental strategies is considerable.

Additional file 1: Figure S1. The distribution of fatigue scores at the 18-year follow-up of participants with juvenile idiopathic arthritis (JIA) in the Nordic JIA study and in the Norwegian control group. Fatigue is measured with Fatigue Severity Scale (FSS) global score, 1–7 (1 = lowest, 7 = highest). The dot-plot illustrating the distribution of fatigue scores for individual participants within each group as dots, and the group median indicated with the horizontal spiked line.

Background. Children and adolescents with JIA may suffer pain from temporomandibular disorder (TMD) and routines for the assessment of temporomandibular joint (TMJ) pain for the health and dental care are lacking. The aims were to examine the prevalence of TMD in children and adolescents with juvenile idiopathic arthritis (JIA) as compared to their healthy peers and to examine potential associations between JIA and TMD.Methods. This comparative cross-sectional study is part of a longitudinal multicenter study performed during 2015 - 2020, including 228 children and adolescents aged 4-16 years, with a diagnosis of JIA according to the ILAR criteria. This sub-study draws on a subset of data from the first study visit, including assessments of TMD as part of a broader oral health examination. Participants with JIA were matched with healthy controls according to gender, age, and center site. Calibrated examiners performed the clinical oral examinations according to a standardized protocol, including shortened versions of diagnostic criteria for TMD (DC/TMD) and the former EuroTMJoint Recommendations for Clinical TMJ Assessment in Patients Diagnosed with JIA. Symptoms were recorded and followed by a clinical examination assessing the masticatory muscles and TMJ`s.Results. In our cohort of 221 participants with JIA and corresponding controls, 88 participants with JIA (39.8%) and 25 (11.3%) controls revealed TMD based on symptoms and clinical signs. Painful TMD during the last 30 days was reported in 59 (26.7%) participants with JIA vs. 10 (5.0%) of the healthy controls (pConclusion. Symptoms or clinical signs of TMD were seen in approximately half of the JIA patients compared to about one fourth of their healthy peers. Painful palpation to masticatory muscles and decreased vertical unassisted jaw movement were more frequent in participants with JIA than among healthy controls and should be part of both medical and dental routine examinations in JIA.

To assess the long-term outcome of uveitis in juvenile idiopathic arthritis (JIA).Population-based, multicenter, prospective JIA cohort, with a cross-sectional assessment of JIA-associated uveitis (JIA-U) 18 years after the onset of JIA.A total of 434 patients with JIA, of whom 96 had uveitis, from defined geographic areas of Denmark, Finland, Norway, and Sweden.Patients with onset of JIA between January 1997 and June 2000 were prospectively followed for 18 years. Pediatric rheumatologists and ophthalmologists collected clinical and laboratory data.Cumulative incidence of uveitis and clinical characteristics, JIA and uveitis disease activity, ocular complications, visual outcome, and risk factors associated with the development of uveitis-related complications.Uveitis developed in 96 (22.1%) of 434 patients with JIA. In 12 patients (2.8%), uveitis was diagnosed between 8 and 18 years of follow-up. Systemic immunosuppressive medication was more common among patients with uveitis (47/96 [49.0%]) compared with patients without uveitis (78/338 [23.1%]). Active uveitis was present in 19 of 78 patients (24.4%) at the 18-year visit. Ocular complications occurred in 31 of 80 patients (38.8%). Short duration between the onset of JIA and the diagnosis of uveitis was a risk factor for developing ocular complications (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8). Patients with a diagnosis of uveitis before the onset of JIA all developed cataract and had an OR for development of glaucoma of 31.5 (95% CI, 3.6-274). Presence of antinuclear antibodies (ANAs) was also a risk factor for developing 1 or more ocular complications (OR, 3.0; 95% CI, 1.2-7.7). Decreased visual acuity (VA)6/12 was found in 12 of 135 eyes (8.9%) with uveitis, and 4 of 80 patients (5.0%) with JIA-U had binocular decreased VA6/12.Our results suggest that uveitis screening should start immediately when the diagnosis of JIA is suspected or confirmed and be continued for more than 8 years after the diagnosis of JIA. Timely systemic immunosuppressive treatment in patients with a high risk of developing ocular complications must be considered early in the disease course to gain rapid control of ocular inflammation.

BACKGROUND. Undifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify diseases with available targeted treatments. METHODS. Sixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing. RESULTS. Thirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator [NEMO]), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome-like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody-positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS. CONCLUSIONS. In patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18-mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5-autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression. Fil: de Jesus, Adriana A.. National Institute Of Allergy And Infectious Diseases; Estados Unidos Fil: Hou, Yangfeng. Shandong University; China Fil: Brooks, Stephen. National Institute Of Arthritis And Musculoskeletal And Skin Diseases; Estados Unidos Fil: Malle, Louise. cahn School of Medicine at Mount Sinai; Estados Unidos Fil: Biancotto, Angelique. No especifíca; Fil: Huang, Yan. National Institute Of Allergy And Infectious Diseases; Estados Unidos Fil: Calvo, Katherine R.. National Institutes of Health; Estados Unidos Fil: Marrero, Bernadette. No especifíca; Fil: Moir, Susan. No especifíca; Fil: Oler, Andrew J.. National Institute Of Allergy And Infectious Diseases ; Estados Unidos Fil: Deng, Zuoming. National Institute Of Arthritis And Musculoskeletal And Skin Diseases; Estados Unidos Fil: Montealegre Sanchez, Gina A.. National Institute Of Allergy And Infectious Diseases ; Estados Unidos Fil: Ahmed, Amina. No especifíca; Fil: Allenspach, Eric. Washington State University; Estados Unidos Fil: Arabshahi, Bita. Virginia Commonwealth University; Estados Unidos Fil: Behrens, Edward. University of Pennsylvania; Estados Unidos Fil: Benseler, Susanne. University of Calgary; Canadá Fil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bout Tabaku, Sharon. No especifíca; Fil: Brescia, AnneMarie C.. No especifíca; Fil: Brown, Diane. No especifíca; Fil: Burnham, Jon M.. University of Pennsylvania; Estados Unidos Fil: Caldirola, Maria Soledad. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina Fil: Carrasco, Ruy. No especifíca; Fil: Chan, Alice Y.. University of California; Estados Unidos Fil: Cimaz, Rolando. Università degli Studi di Milano; Italia Fil: Dancey, Paul. Janeway Children's Hospital And Rehabilitation Centre; Canadá Fil: Dare, Jason. University of Arkansas for Medical Sciences; Estados Unidos Fil: DeGuzman, Marietta. Baylor College Of Medicine; Estados Unidos Fil: Dimitriades, Victoria. No especifíca; Fil: Ferguson, Ian. University of Yale. School of Medicine; Estados Unidos Fil: Ferguson, Polly. University of Iowa; Estados Unidos Fil: Finn, Laura. University of Washington; Estados Unidos Fil: Gattorno, Marco. No especifíca; Fil: Grom, Alexei A.. No especifíca; Fil: Hanson, Eric P.. No especifíca; Fil: Hashkes, Philip J.. No especifíca; Fil: Hedrich, Christian M.. University of Liverpool; Reino Unido Fil: Herzog, Ronit. University of New York; Estados Unidos Fil: Horneff, Gerd. Universitat zu Köln; Alemania Fil: Jerath, Rita. Augusta University; Estados Unidos Fil: Kessler, Elizabeth. University of Missouri; Estados Unidos Fil: Kim, Hanna. No especifíca; Fil: Kingsbury, Daniel J.. No especifíca; Fil: Laxer, Ronald M.. University Of Toronto. Hospital For Sick Children; Canadá Fil: Lee, Pui Y.. Children's Hospital Boston; Estados Unidos Fil: Lee Kirsch, Min Ae. Technische Universität Dresden; Alemania Fil: Lewandowski, Laura. No especifíca; Fil: Li, Suzanne. Hackensack University Medical Center; Estados Unidos Fil: Lilleby, Vibke. Oslo University Hospital; Noruega Fil: Mammadova, Vafa. Azerbaijan Medical University; Azerbaiyán Fil: Moorthy, Lakshmi N.. Robert Wood Johnson Medical School; Estados Unidos Fil: Nasrullayeva, Gulnara. Azerbaijan Medical University; Azerbaiyán Fil: O'Neil, Kathleen M.. Riley Hospital for Children; Estados Unidos Fil: Onel, Karen. Hospital for Special Surgery; Estados Unidos Fil: Ozen, Seza. Hacettepe University; Turquía Fil: Pan, Nancy. Hospital for Special Surgery; Estados Unidos Fil: Pillet, Pascal. Children Hospital Pellegrin-Enfants; Francia Fil: Piotto, Daniela G.P.. Universidade Federal de Sao Paulo; Brasil Fil: Punaro, Marilynn G.. University of Texas; Estados Unidos Fil: Reiff, Andreas. University of Nebraska; Estados Unidos Fil: Reinhardt, Adam. University of Nebraska; Estados Unidos Fil: Rider, Lisa G.. No especifíca; Fil: Rivas Chacon, Rafael. Nicklaus Children’s Hospital; Estados Unidos Fil: Ronis, Tova. Children’s National Health System; Estados Unidos Fil: Rösen Wolff, Angela. Technische Universität Dresden; Alemania Fil: Roth, Johannes. Children’s Hospital of Eastern Ontario; Canadá Fil: Mckerran Ruth, Natasha. Medical University of South Carolina; Estados Unidos Fil: Rygg, Marite. Norwegian University of Science and Technology; Noruega Fil: Schmeling, Heinrike. University of Calgary; Canadá Fil: Schulert, Grant. Children’s Hospital Medical Center; Estados Unidos Fil: Scott, Christiaan. University of Cape Town; Sudáfrica Fil: Seminario, Gisella. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Shulman, Andrew. University of California at Irvine; Estados Unidos Fil: Sivaraman, Vidya. Nationwide Children’s Hospital; Estados Unidos Fil: Son, Mary Beth. Boston Children’s Hospital; Estados Unidos Fil: Stepanovskiy, Yuriy. Shupyk National Medical Academy for Postgraduate Education; Ucrania Fil: Stringer, Elizabeth. Dalhousie University Halifax; Canadá Fil: Taber, Sara. Hospital for Special Surgery; Estados Unidos Fil: Terreri, Maria Teresa. Universidade Federal de Sao Paulo; Brasil Fil: Tifft, Cynthia. No especifíca; Fil: Torgerson, Troy. University of Washington; Estados Unidos Fil: Tosi, Laura. Children’s National Health System; Estados Unidos Fil: van Royen Kerkhof, Annet. Wilhelmina Children’s Hospital Utrech; Países Bajos Fil: Wampler Muskardin, Theresa. New York University School of Medicine; Estados Unidos Fil: Canna, Scott W.. University of Pittsburgh; Estados Unidos Fil: Goldbach Mansky, Raphaela. National Institute Of Allergy And Infectious Diseases ; Estados Unidos

Additional file 4: Supplementary Table S4. Estimated differences in pain threshold: mild versus severe pain intensity / low versus high pain interference.

Additional file 2: Supplementary Table S2. Median thermal and pressure pain thresholds in juvenile idiopathic arthritis (JIA) and controls.

Additional file 3: Supplementary Table S3. Estimated differences in pain threshold per unit score in self-reported VAS pain.

Additional file 1: Supplementary Table S1. Thermal detection thresholds among juvenile idiopathic arthritis (JIA) and controls.

Background Observational studies examining the association between oral health and juvenile idiopathic arthritis (JIA) among children and adolescents have reported inconsistent findings. The aims of this systematic review and meta-analysis were to ascertain a potential difference in oral health and oral health-related quality of life (OHRQoL) among children and adolescents with JIA and healthy peers, and to assess the association of prevalence of oral diseases/conditions, temporomandibular disorders (TMD), including temporomandibular joint (TMJ) diseases, in relation to activity and severity of JIA. Method Medline Ovid, Embase, CINAHL, SweMed+ and Cochrane Library were searched up to 25 November 2018. All articles published in English, German and Scandinavian languages focusing on children and adolescents with JIA and without JIA in relation to oral health measures, were considered. Two authors independently evaluated observational studies for inclusion. The study quality was assessed using modified Newcastle Ottawa Scale. Meta-analysis was performed for studies focusing on dental caries as an outcome. Results Nineteen articles met the inclusion criteria, covering a range of oral diseases/conditions and OHRQoL. Eighteen studies had cross-sectional design. No mean difference of dmft/DMFT indices (decayed/missed/filled teeth) was observed between the JIA - and healthy group. None of the oral health measures including dental erosive wear, enamel defects, dental maturation and OHRQoL, indicated better oral health among children and adolescents with JIA compared to healthy group. However, periodontal conditions and TMD were more predominant among children and adolescents with JIA compared to healthy peers. Conclusions Based on the cross-sectional studies, periodontal diseases and TMD were found to be more frequent in children and adolescents with JIA compared to healthy peers. Furthermore, more high-quality studies with large sample size are needed before we infer any concrete conclusion regarding the association between the prevalence of oral and TMJ diseases or oral conditions in relation to activity and severity of JIA.

This is a pre-copyediting, author-produced PDF of an article accepted for publication in The Journal of Rheumatology following peer review. The definitive publisher-authenticated version Hetlevik, S.O., Flatø, B., Aaløkken, T.M., Lund, M.B., Reiseter, S., Mynarek, G.K. ... Lilleby, V. (2019). Pulmonary Manifestations and Progression of Lung Disease in Juvenile-onset Mixed Connective Tissue Disease. The Journal of Rheumatology, 46(1), 93-100, is available online at: https://doi.org/10.3899/jrheum.180019. 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.

Objectives. To evaluate the demographic, disease activity, disability and health-related quality of life (HRQoL) differences between children with juvenile idiopathic arthritis (JIA) and their healthy peers, and between children with JIA with and without clinical temporomandibular joint (TMJ) involvement and its determinants. Methods. This study is based on a cross-sectional cohort of 3343 children with JIA and 3409 healthy peers, enrolled in the Pediatric Rheumatology International Trials Organisation (PRINTO) health-related quality of life (HRQoL) study or in the methotrexate trial. Potential determinants of TMJ involvement included demographic, disease activity, disability and HRQoL measures selected through univariate and multivariable logistic regression. Results. Clinical TMJ involvement was observed in 387/3343 (11.6%) JIA children. Children with TMJ involvement, compared to those without, more often had polyarticular disease course (95% versus 70%), higher Juvenile Arthritis Disease Activity Score (JADAS) (odds ratio (OR) 4.6), more disability and lower HRQoL. Children with TMJ involvement experienced clearly more disability and lower HRQoL compared to their healthy peers. The multivariable analysis, showed that cervical spine involvement (OR 4.6), disease duration > 4.4 years (OR 2.8), and having more disability (Childhood Health Assessment Questionnaire Disability Index >0.625) (OR 1.6) were the most important determinants for TMJ involvement. Conclusion. Clinical TMJ involvement in JIA is associated with higher disease activity, higher disability and impaired HRQoL. Our findings indicate the need for dedicated clinical and imaging evaluation of TMJ arthritis especially in children with cervical spine involvement, polyarticular course and longer disease duration. This article is protected by copyright. All rights reserved.

Supplemental Digital Content is available in the text., Objective: To investigate self-reported pain in young adults with a low birth weight. Materials and Methods: This study was a part of a long-term follow-up study of preterm very low birth weight (VLBW; birth weight ≤1500 g), term small for gestational age (SGA; birth weight 6 months and being moderate, severe, or very severe during the past 4 weeks. Results: The prevalence of chronic pain at 26 years was 16% in the VLBW group, 21% in the term SGA group, and 7% in the control group. The VLBW and the term SGA groups had higher odds ratios for chronic pain (crude OR, 2.6; 95% CI, 0.9-7.6 for the VLBW group and crude OR, 3.6; 95% CI, 1.3-9.9 for the term SGA group vs. controls). The main results remained after adjusting for potential confounding factors. Some attenuation was observed when adjusting for anxiety and depressive problems. Moderate to very severe pain increased from 16% to 41% in the term SGA group from 19 to 26 years, whereas less changes were seen in the VLBW and the control groups. Discussion: Results of our study imply that pain should be in focus when conducting long-term follow-up programs of individuals with a low birth weight.

To test the hypothesis that non-HLA single-nucleotide polymorphisms (SNPs) associated with the risk of juvenile idiopathic arthritis (JIA) are risk factors for an unfavourable disease outcome at long-term follow-up.The Nordic JIA cohort is a prospective multicentre study cohort of patients from the Nordic countries. In all, 193 patients met the inclusion criteria of having an 8 year follow-up assessment and available DNA sample. Seventeen SNPs met the inclusion criteria of having significant associations with JIA in at least two previous independent study cohorts. Clinical endpoints were disease remission, actively inflamed joints and joints with limitation of motion (LOM), articular or extra-articular damage, and history of uveitis.Evidence of associations between genotypes and endpoints were found for STAT4, ADAD1-IL2-IL21, PTPN2, and VTCN1 (p = 0.003-0.05). STAT4_rs7574865 TT was associated with the presence of actively inflamed joints [odds ratio (OR) 20.6, 95% confidence interval (CI) 2.2- 100, p = 0.003] and extra-articular damage (OR 7.9, 95% CI 1-56.6, p = 0.057). ADAD1_rs17388568 AA was associated with a lower risk of having joints with LOM (OR 0.1, 95% CI 0-0.55, p = 0.016). PTPN2_rs1893217 CC was associated with a lower risk of having joints with LOM (OR 0.2, 95% CI 0-0.99, p = 0.026), while VTCN1_rs2358820 GA was associated with uveitis (OR 3.5, 95% CI 1-12.1, p = 0.029).This exploratory study, using a prospectively followed JIA cohort, found significant associations between long-term outcome and SNPs, all previously associated with development of JIA and involved in immune regulation and signal transduction in immune cells.