Inflammatory Biomarkers Can Differentiate Acute Lymphoblastic Leukemia with Arthropathy from Juvenile Idiopathic Arthritis Better Than Standard Blood Tests.

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.

Dental plaque and gingival bleeding in adolescents with juvenile idiopathic arthritis and controls: a multilevel analysis.

OBJECTIVE: To explore whether plaque and gingival bleeding are more frequently experienced by adolescents with juvenile idiopathic arthritis (JIA) compared to matched controls without JIA; explore whether surface- and site-specific periodontal outcomes vary between the two groups; and for participants with JIA, investigate associations between disease-specific features and periodontal outcomes. MATERIAL AND METHODS: In this comparative cross-sectional study, selected surfaces, and sites of index teeth in 10-16-year-olds with JIA and matched controls were examined by modified versions of Simplified Oral Hygiene Index (OHI-S) and Gingival Bleeding Index (GBI). Mixed-effects logistic regressions, reporting odds ratios (OR) with 95% confidence interval (CI), were applied. Intra-class correlation coefficients (ICCs) were calculated to quantify the degree of dependency of measures within the same individual. RESULTS: 144 and 159 adolescents with JIA were evaluated according to OHI-S and GBI; corresponding numbers of controls were 154 and 161. Plaque and gingival bleeding were more frequent in individuals with JIA than controls. Adjusted analyses showed association between JIA status and OHI-S > 0 (OR = 2.33, 95% CI: 1.47 - 3.67, ICC = 0.45) and GBI > 0 (OR = 1.54, 95% CI: 1.10 - 2.16, ICC = 0.41 and 0.30). Surface-specific distribution of plaque varied among the two groups. CONCLUSIONS: Our results highlight the importance of increased awareness of oral health care in patients with JIA and that surface- and site-specific differences in periodontal outcomes exist between individuals with JIA and controls. Few JIA disease-specific variables associated with plaque or gingival bleeding.

Oral health-related quality of life, impaired physical health and orofacial pain in children and adolescents with juvenile idiopathic arthritis - a prospective multicenter cohort study.

BACKGROUND: Knowledge on oral health-related quality of life (OHRQoL) in children and adolescents with juvenile idiopathic arthritis (JIA) is limited, and longitudinal studies are lacking. We aimed to describe OHRQoL in children and adolescents with JIA compared to controls, and to explore the validity and internal consistency of the Early Childhood Oral Health Impact Scale (ECOHIS) and the Child Oral Impact on Daily Performance (Child-OIDP). Furthermore, we wanted to investigate associations between OHRQoL and orofacial pain, physical health, disease activity, and temporomandibular joint (TMJ) involvement in JIA. METHODS: The Norwegian prospective, multicenter cohort study recruited participants with JIA between 4 and 16 years of age and corresponding controls from three pediatric university hospital departments and public dental health services. In the present study, we analyzed OHRQoL in all children < 12 years with the ECOHIS and adolescents ≥ 12 years with the Child-OIDP at the first visit and the two-year follow-up. Associations between OHRQoL and JIA characteristics, collected in clinical exam and questionnaires, were analyzed in logistic regressions. RESULTS: The same OHRQoL questionnaire was completed both at first visit and two-year follow-up in 101 children < 12 years (47 JIA, 54 controls) and 213 adolescents ≥ 12 years (111 JIA, 102 controls). The frequency of OHRQoL impacts in children was similar at the first visit and the two-year follow-up (ECOHIS > 0: JIA group 81% and 85%, p = 0.791; control group 65% and 69%, p = 0.815), while adolescents with JIA reported fewer impacts at the two-year follow-up (Child OIDP > 0: JIA group 27% and 15%, p = 0.004; control group 21% and 14%, p = 0.230). The internal consistency of the OHRQoL instruments was overall acceptable and the criterion validity indicated that the instruments were valid at both visits. Orofacial pain was more frequent in children and adolescents with JIA than in controls. We found associations between OHRQoL impacts and orofacial pain, impaired physical health, disease activity, and TMJ involvement. CONCLUSIONS: Children and adolescents with orofacial pain or impaired physical health were more likely to report impacts on daily life activities than those without. Pediatric rheumatologists and dentists should be aware of impaired OHRQoL in individuals with JIA with active disease or temporomandibular joint involvement. TRIAL REGISTRATION: Registered on clinicaltrials.gov (NCT03904459, 05/04/2019).

Increased incidence of inflammatory bowel disease on etanercept in juvenile idiopathic arthritis regardless of concomitant methotrexate use.

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.

Vitamin D, oral health, and disease characteristics in juvenile idiopathic arthritis: a multicenter cross-sectional study.

BACKGROUND: Vitamin D deficiency has been associated with autoimmune diseases and oral health. Knowledge about the association between vitamin D status and oral conditions in JIA is limited. We aimed to investigate vitamin D status in a cohort of Norwegian children and adolescents with JIA and possible associations between serum vitamin D levels, clinical indicators of oral health, and JIA disease characteristics. METHODS: This multi-center, cross-sectional study, included individuals with JIA aged 4-16 years from three geographically spread regions in Norway. Demographic data, age at disease onset, disease duration, JIA category, disease status, medication, and vitamin D intake were registered. One blood sample per individual was analyzed for 25(OH) vitamin D, and the level of insufficiency was defined as < 50 nmol/L. A clinical oral examination was performed applying commonly used indices in epidemiological studies of dental caries, dental erosion, enamel defects, gingival bleeding, and oral hygiene. Serum vitamin D was used as exposure variable in multivariable regression analyses to estimate the associations between insufficient vitamin D level, JIA disease status, and oral conditions, with adjustments for age, sex, geographical region, BMI, seasonal blood sampling, and parental education. RESULTS: Among the 223 participants with JIA, 97.3% were Caucasians, 59.2% were girls, and median age was 12.6 years. Median disease duration was 4.6 years, and 44.4% had oligoarticular JIA. Mean serum vitamin D level was 61.4 nmol/L and 29.6% had insufficient levels. Vitamin D levels did not differ between sexes, but between regions, iso-BMI categories, age groups, and seasons for blood sampling. Insufficient vitamin D levels were associated with dentin caries (adjusted OR 2.89, 95% CI 1.43-5.86) and gingival bleeding (adjusted OR 2.36, 95% CI 1.10-5.01). No associations were found with active JIA disease or more severe disease characteristics. CONCLUSION: In our study, nearly 30% had vitamin D insufficiency, with a particularly high prevalence among adolescents. Vitamin D insufficiency was associated with dentin caries and gingival bleeding, but not with JIA disease activity. These results point to the need for a multidisciplinary approach in the follow-up of children with JIA, including an increased focus on vitamin D status and oral health.

Oral health-related quality of life in 4-16-year-olds with and without juvenile idiopathic arthritis.

BACKGROUND: Few studies have investigated oral health-related quality of life (OHRQoL) in young individuals with juvenile idiopathic arthritis (JIA). Aims were to investigate whether OHRQoL differs between children and adolescents with JIA compared to controls without JIA, while adjusting for socio-demographic-, behavioral- and oral health-related covariates. Furthermore, to explore whether socio-behavioral and oral health-related covariates of OHRQoL vary according to group affiliation and finally, specifically for individuals with JIA, to investigate whether disease-specific features associate with OHRQoL. We hypothesized that participants with JIA have poorer OHRQoL compared to participants without JIA. METHODS: In this comparative cross-sectional study participants with JIA (n = 224) were matched to controls without JIA (n = 224). OHRQoL was assessed according to Early Childhood Oral Health Impact Scale (ECOHIS) (4-11-years-olds) and the child version of Oral Impacts on Daily Performances (Child-OIDP) (12-16-years-olds). JIA-specific characteristics were assessed by pediatric rheumatologists and socio-demographic, behavioral and self-reported oral health information collected by questionnaires. Index teeth were examined for caries by calibrated dentists. Multiple variable analyses were performed using logistic regression, reporting odds ratio (OR) and 95% confidence interval (CI). Two-way interactions were tested between group affiliation and the socio-behavioral- and oral health-related variables on the respective outcome variables. RESULTS: In total, 96 participants with JIA and 98 controls were evaluated according to ECOHIS, corresponding numbers for Child-OIDP was 125 and 124. Group affiliation was not associated with impaired ECOHIS or Child-OIDP in adjusted analyses (OR = 1.95, 95% CI 0.94-4.04 and OR = 0.99, 95% CI 0.46-2.17, respectively). Female adolescents with JIA were more likely than males to report oral impacts according to Child-OIDP. Continued activity or flare was found to adversely affect Child-OIDP, also self-reported outcome measures in JIA associated with Child-OIDP. CONCLUSIONS: This study did not provide consistent evidence to confirm the hypothesis that children and adolescents with JIA are more likely to have impaired OHRQoL compared to their peers without JIA. However, female adolescents with JIA were more likely than males to report impacts on OHRQoL. Furthermore, within the JIA group, adolescents with continued disease activity, flare or reporting pain, physical disability, had higher risk than their counterparts of impaired OHRQoL.

Uveitis in Juvenile Idiopathic Arthritis: 18-Year Outcome in the Population-based Nordic Cohort Study.

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) <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 VA <6/12. 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.

Suicidality, function and associated negative life events in an adolescent psychiatric population at 3-year follow-up.

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 < 0.001), as was suicidal behavior (25.0% vs. 9.5%, RD = 15.5%, CI (9.2 to 21.4), p < 0.001). Girls had lower psychosocial functioning than boys (Children's Global Assessment Scale; Mean score 68.2 vs. 75.2, Mean difference = - 7.0, CI (- 9.4 to - 4.7), p < 0.001), and more school dropout (22.5% vs. 13.2%, RD = 9.3%, CI (2.8 to 15.5), 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 < 0.001, and RD = 18.3%, CI (10.2 to 25.8), p < 0.001, respectively). Exposure to negative life events was frequent for both genders, but more girls had experienced sexually uncomfortable or abusive situations, the last 3 years (23.5% vs. 2.9%, RD = 20.6%, CI (15.4 to 25.7), p < 0.001), and ever (44.4% vs. 7.9%, RD = 36.5%, CI (29.9 to 42.7), p < 0.001). Suicidal behavior was associated with having been threatened, physically harassed or violently hurt (RD = 16.7%, CI (9.5 to 23.9), p < 0.001), and for girls been put into sexually uncomfortable or abusive situations (RD = 20.1%, CI (10.4 to 29.9), p < 0.001) and seen others violently hurt (RD = 14.6%, CI (3.4 to 25.8), 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.

Association of treatment procedures and resilience to symptom load three-years later in a clinical sample of adolescent psychiatric patients.

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 ß = 0.5, CI (0.3 to 0.7), p < 0.001 and ß = - 15.7, CI (- 19.2 to - 12.1), p < 0.001, respectively). The subscale Personal Competence was associated with the lowest Total Problem score for both genders. 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.

Psychiatric morbidity, somatic comorbidity and substance use in an adolescent psychiatric population at 3-year follow-up.

Knowledge is scarce on the course of psychiatric disorders in adolescence. We aimed to assess changes in the frequency of psychiatric disorders, somatic disorders, pain, and substance use in a clinical psychiatric cohort from adolescence to young adulthood. This study is part of the Health Survey in Department of Children and Youth, St. Olavs Hospital, Norway. At age 13-18 years, 717 (43.5% of eligible) participated in the first study visit (T1) in 2009-2011, 549 were reassessed 3 years later with telephone interview (T2), and 464 had diagnostic evaluation at both time points. Data included: ICD-10 diagnoses (T1), DSM-IV diagnoses (T2), self-reported pain and substance use (T1 and T2). The overall rate of psychiatric disorders decreased (T1 vs. T2: 94.8% vs. 72.2%, p < 0.001); while, an increased rate of anxiety disorders was marked among girls (37.5% vs. 55.9%, p < 0.001), with accompanying raised frequencies of psychiatric comorbidity (14.1% vs. 42.6%, p < 0.001), somatic comorbidity (9.4% vs. 19.5%, p = 0.001), chronic pain (31.6% vs. 49.4%, p < 0.001), smoking, alcohol use and trying illicit drugs. Chronic pain, smoking and trying illicit drugs were associated with persisting psychiatric disorders, with highest risk differences for girls (RD = 25.4%, p = 0.002, RD = 15.6%, p = 0.008, RD = 18.0%, p = 0.001, respectively). Three out of four adolescents still had a psychiatric disorder after 3 years. Unlike boys, girls had an increasing rate of anxiety disorders and comorbidities. Chronic pain, smoking and trying illicit drugs were associated with persisting psychiatric disorders. Despite methodological limitations, these findings emphasize the importance of early targeted intervention for adolescents with psychiatric disorders.

Dental caries in children and adolescents with juvenile idiopathic arthritis and controls: a multilevel analysis.

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.

Oral health in children and adolescents with juvenile idiopathic arthritis - a systematic review and meta-analysis.

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.

The Norwegian version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

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.

Normal magnetic resonance appearances of the temporomandibular joints in children and young adults aged 2-18 years.

BACKGROUND: Knowledge of normal appearances of the temporomandibular joint (TMJ) is paramount when assessing the joint for disease in juvenile idiopathic arthritis. Reliable features defining normal TMJs in children are limited. OBJECTIVE: To establish reliable normal standards for the TMJ at magnetic resonance imaging (MRI). MATERIALS AND METHODS: We included children and young adults aged 2-18 years undergoing a head MRI for reasons not believed to affect the TMJs. We assessed TMJ anatomy and contrast enhancement using a high-resolution 3-D T1-weighted sequence. We noted joint fluid and bone marrow oedema based on a T2-weighted sequence. Three experienced radiologists read all examinations twice in consensus and defined intraobserver consensus agreement. RESULTS: We evaluated the TMJs in 101 children and young adults (45 female), mean age 10.7 years (range 2-18 years). The intraobserver consensus agreement for the assessment of anterior condylar inclination in the sagittal/oblique plane was moderate to good (Cohen κ=0.7 for the right side). Cohen κ for intraobserver consensus agreement for condylar shape in the coronal plane on a 0-2 scale was 0.4 for the right and 0.6 for the left. Intraobserver agreement for measurement of joint space height and assessment of bone marrow oedema was poor. There was a statistically significant increase in anterior inclination by age in the sagittal plane on a 0-2 scale (P<0.0001). Eighty percent of the condyles showed a rounded shape in the coronal plane while 20% showed mild flattening. Thirty-five of 36 right TMJs showed contrast enhancement (mild enhancement in 32 joints, moderate in 3 joints). CONCLUSION: Subjective assessment of the anterior condylar inclination in the sagittal/oblique plane and condylar flattening in the coronal plane can be considered precise features for describing TMJ anatomy in healthy children. There is an increasing anterior inclination by age. Mild contrast enhancement of the TMJs should be considered a normal finding.

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

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

High-sensitive CRP as a predictive marker of long-term outcome in juvenile idiopathic arthritis.

To evaluate whether C-reactive protein (CRP), including variation within the normal range, is predictive of long-term disease outcome in Juvenile Idiopathic Arthritis (JIA). Consecutive patients with newly diagnosed JIA were included prospectively from defined geographic areas of the Nordic countries from 1997 to 2000. Inclusion criteria were availability of a baseline serum sample within 12 months after disease onset and 8-year clinical assessment data. Systemic onset JIA was not included. CRP was measured by high-sensitive ELISA (detection limit of 0.2 mg/l). One hundred and thirty participants with a median follow-up time of 97 months (range 95-100) were included. At follow-up, 38% of the patients were in remission off medication. Absence of remission was associated with elevated level of CRP at baseline (odds ratio (OR) 1.33, confidence interval (CI) 1.08-1.63, p = 0.007). By applying a cutoff at the normal upper limit (>10 mg/l), the risk of not achieving remission was increased to an OR of 8.60 (CI 2.98-24.81, p < 0.001). Variations of CRP within the normal range had no predictive impact on disease activity at follow-up. Baseline levels of ESR were available in 80 patients (61%) and elevated ESR was associated with absence of remission in a multivariable logistic regression analysis (OR 2.32, CI 1.35-4.00, p = 0.002). This results of this study indicate that baseline CRP concentrations above 10 mg/l are predictive of a poor outcome at 8-year follow-up. We could not demonstrate any predictive value of CRP variations within the normal range.

Ankle arthritis predicts polyarticular disease course and unfavourable outcome in children with juvenile idiopathic arthritis.

OBJECTIVES: To evaluate the occurrence, clinical characteristics and prognostic factors associated with ankle arthritis in children with juvenile idiopathic arthritis (JIA). METHODS: 440 children with JIA were followed for eight years in a prospective Nordic population-based cohort study. Data on remission was available for 427 of these children. Occurrence of clinically assessed ankle arthritis was analysed in relation to JIA category, clinical characteristics and remission data eight years after disease onset. RESULTS: In 440 children with JIA, 251 (57%) experienced ankle arthritis during the first eight years of disease. Ankle arthritis was least common in the persistent oligoarticular category (25%) and most common in children with extended oligoarticular (83%) and polyarticular RF-negative (85%) JIA. Children who developed ankle arthritis during the first year of disease were younger at disease onset (median age 4.9 (IQR 2.1-8.8) vs. 6.6 (IQR 2.8-10.1) years, p<0.003) and had more cumulative affected joints at 8-year follow-up (median involved joints 10 (IQR 6-16) vs. 3 (IQR 2-9), p<0.001). The odds ratio for not achieving remission eight years after disease onset, if the ankle joint was involved during the first year of disease was 2.0 (95 % CI:1.3-3.0, p<0.001). Hind-, mid- and forefoot involvements were more common compared to patients without ankle arthritis. CONCLUSIONS: In this Nordic population-based 8-year follow-up study, occurrence of ankle arthritis during the first year was associated with an unfavourable disease outcome. We suggest that ankle arthritis should be recognised in the assessment of prognosis and choice of treatment strategy in JIA.

Disease activity trajectories from childhood to adulthood in the population-based Nordic juvenile idiopathic arthritis cohort.

OBJECTIVES: To identify long-term disease activity trajectories from childhood to adulthood by using the clinical Juvenile Arthritis Disease Activity Score (cJADAS10) in juvenile idiopathic arthritis (JIA). Second, to evaluate the contribution of the cJADAS10 components and explore characteristics associated with active disease at the 18-year follow-up. METHODS: Patients with onset of JIA in 1997-2000 were followed for 18 years in the population-based Nordic JIA cohort. We used a discrete mixture model for longitudinal clustering of the cJADAS10 and its components. We assessed factors potentially associated with higher scores on the patient's global assessment of well-being (PaGA) by hierarchical clustering and correlation analysis. RESULTS: Four disease activity trajectories were identified based on the cJADAS10 components among 427 patients. In trajectory-group 2, the PaGA and the physician's global assessment of disease activity (PhGA) increased significantly during the course, but not the active joint count. The increase in the PaGA was significantly higher than the increases in the PhGA and the active joint count (p<0.0001). A similar pattern was found among all the patients with active disease in the total cohort. Patients with higher PaGA scores had unfavourable scores on several other patient-reported outcomes. CONCLUSIONS: We have identified groups of patients based on long-term disease activity trajectories. In our study the PaGA was the most important driver of disease activity into adulthood assessed by cJADAS10. We need to better understand how our patients interpret global well-being and implement strategies to achieve inactive disease perceived both by the patient and the physician.

Inflammatory biomarkers predicting long-term remission and active disease in juvenile idiopathic arthritis: a population-based study of the Nordic JIA cohort.

OBJECTIVES: To assess the ability of baseline serum biomarkers to predict disease activity and remission status in juvenile idiopathic arthritis (JIA) at 18-year follow-up (FU) in a population-based setting. METHODS: Clinical data and serum levels of inflammatory biomarkers were assessed in the longitudinal population-based Nordic JIA cohort study at baseline and at 18-year FU. A panel of 16 inflammatory biomarkers was determined by multiplexed bead array assay. We estimated both univariate and multivariate logistic regression models on binary outcomes of disease activity and remission with baseline variables as explanatory variables. RESULTS: Out of 349 patients eligible for the Nordic JIA cohort study, 236 (68%) had available serum samples at baseline. We measured significantly higher serum levels of interleukin 1ß (IL-1ß), IL-6, IL-12p70, IL-13, MMP-3, S100A9 and S100A12 at baseline in patients with active disease at 18-year FU than in patients with inactive disease. Computing receiver operating characteristics illustrating the area under the curve (AUC), we compared a conventional prediction model (gender, age, joint counts, erythrocyte sedimentation rate, C reactive protein) with an extended model that also incorporated the 16 baseline biomarkers. Biomarker addition significantly improved the ability of the model to predict activity/inactivity at the 18-year FU, as evidenced by an increase in the AUC from 0.59 to 0.80 (p=0.02). Multiple regression analysis revealed that S100A9 was the strongest predictor of inactive disease 18 years after disease onset. CONCLUSION: Biomarkers indicating inflammation at baseline have the potential to improve evaluation of disease activity and prediction of long-term outcomes.

Body mass index is associated with health-related quality of life and disease characteristics in young adults with juvenile idiopathic arthritis.

BACKGROUND: There is a growing interest concerning the relationship between obesity and several medical conditions and inflammation. Nevertheless, there is a lack of studies regarding body mass index (BMI) among patients with juvenile idiopathic arthritis (JIA). Our aim was to investigate the impact of BMI on health-related quality of life (HRQoL) measured with a 36-Item Short Form Survey (SF-36), disease activity, and disability in young adults with JIA. METHODS: This study is a part of the population-based Nordic JIA cohort study. All newly diagnosed patients with JIA were recruited consecutively between 1997-2000 in specific regions in the Nordic countries. Patients in this sub-study were enrolled from 434 patients who attended their 18-year follow-up visit. Patients were classified according to the World Health Organization (WHO) into four groups based on their BMI. HRQoL, disease characteristics, disability, fatigue, sleep quality, physical activity, pain, comorbidities, and social status were assessed. RESULTS: Three hundred fifty-five patients from the original study cohort were enrolled in this study and 72% of them were female. Mean age was 23.9 (± SD 4.4) years. A significant relationship was found between the JIA categories and BMI groups (p = 0.014). A significant relationship was also found between BMI and disease activity scores (DAS28) (p = 0.028), disability (p < 0.001), pain (p = 0.013), fatigue (p = 0.035), and sleep quality (p = 0.044). Moreover, a significant relationship between BMI and HRQoL regarding bodily pain (p = 0.010) and general health (p = 0.048) was revealed when adjusted for sex, age, and JIA subtype. CONCLUSION: We discovered that BMI was significantly related to HRQoL, disease activity, and disability. BMI deserves more attention considering the treatment options and outcome of JIA in young adults.