Marite Rygg

Ongoing disease activity and changing categories in a long‐term nordic cohort study of juvenile idiopathic arthritis

OBJECTIVE To describe the disease characteristics, long-term course, and outcome of patients with juvenile idiopathic arthritis (JIA) in a population-based setting. METHODS Consecutive cases of JIA from defined geographic areas of Denmark, Finland, Sweden, and Norway in whom disease onset occurred in 1997-2000 were included in a prospective, multicenter cohort study. The study was designed to be as close to a population-based study as possible, with centers participating only if they were able to include in their catchment area all children in whom JIA was diagnosed. RESULTS Of 500 children included, 440 (88.0%) had repeated visits, with the last visit occurring at least 7 years after disease onset (median 98 months, range 84-147 months). Changes in the International League of Associations for Rheumatology category were observed in 10.8% of the children, and, in addition, extended oligoarthritis developed in 34.7% of the group with oligoarticular JIA. During the observation period, 58.0% of the children were treated with disease-modifying antirheumatic drugs, including biologic medications. Ongoing disease activity was mostly mild, but some JIA-related damage developed in 22.9% of the children. At the last followup visit, remission off medication was observed in 42.4% of the children, 8.9% were in remission on medication, and 48.7% were not in remission. The highest rates of remission were observed in patients with persistent oligoarticular JIA and in those with systemic JIA. CONCLUSION In this long-term prospective study of JIA in a population-based Nordic setting, ongoing disease was evident in a majority of the children. The present results underline the need to identify early predictors of outcome, to further improve therapy, and to continue long-term followup of patients with JIA.

Chronic idiopathic pain in adolescence--high prevalence and disability: the young HUNT Study 2008.

Summary Chronic idiopathic pain in adolescence is common, and often multisite, and may have a major negative impact on everyday life, with high disability. Abstract The aim of this study was to determine the prevalence of self‐reported chronic idiopathic pain among adolescents in relation to age and gender, and to explore how pain interferes with daily activities. The study was performed in Nord‐Trøndelag County, Norway in 2006–2008. All adolescents were invited to participate; the response rate was 78%. Participants completed a comprehensive questionnaire, including questions about pain and interference with everyday life. Chronic idiopathic pain was defined as pain at least once a week during the last 3 months, not related to any known disease or injury. The final study population, with complete pain questionnaires, consisted of 7373 adolescents aged 13–18 years. Chronic pain was reported by 44.4% of the participants, and 25.5% reported pain in at least 2 locations. Chronic idiopathic musculoskeletal pain was most prevalent (33.4%), and the neck/shoulder was most commonly affected. Musculoskeletal pain in 3 or more locations was reported by 8.5%. Pain almost daily was reported by 10.2%. More girls than boys reported pain. In girls, the prevalence of pain increased with age. A high number of pain‐associated disabilities were reported, and 58.5% described difficulties doing daily activities in leisure time. Subjective disabilities were higher in girls, and increased with the frequency of pain and the number of pain locations, as shown by high disability in adolescents with musculoskeletal pain in 3 or more locations. Chronic idiopathic pain, especially multisite pain, is common among adolescents, and those suffering from it report a major impact on several areas of daily living.

Factors Associated With Adolescent Chronic Non-Specific Pain, Chronic Multisite Pain, and Chronic Pain With High Disability: The Young–HUNT Study 2008

UNLABELLED The aim of this study was to assess the association of chronic pain with different lifestyle factors and psychological symptoms in a large, unselected adolescent population. Pain was evaluated as chronic non-specific pain, chronic multisite pain, and in additional analyses, chronic pain with high disability. The study was performed during 2006 to 2008 in Nord-Trøndelag County, Norway. Adolescents aged 13 to 18 years were invited to participate. The response rate was 78%. The final study population consisted of 7,373. Sedentary behavior and pain were associated only in girls. In both sexes, overweight and obesity were associated with increased odds of pain. Whereas both smoking and alcohol intoxication showed strong associations with pain, the associations were attenuated after adjustments for psychosocial factors. Symptoms of anxiety and depression showed the strongest associations with pain (odds ratio 4.1 in girls and 3.7 in boys). The odds of pain increased gradually by number of unfavorable lifestyle factors reported. This study revealed consistent associations between lifestyle factors, anxiety and depression, and chronic pain, including multisite pain and pain with high disability. The consistency across the different pain categories suggests common underlying explanatory mechanisms, and despite the cross-sectional design, the study indicates several modifiable targets in the management of adolescent chronic pain. PERSPECTIVE This study showed a clear and consistent relation between different lifestyle factors, anxiety and depression, and the pain categories chronic non-specific pain, multisite pain, and also pain with high disability. Independent of causality, it underlines the importance of a broad perspective when studying, preventing, and treating chronic pain in adolescents.

Association of Parental Chronic Pain With Chronic Pain in the Adolescent and Young Adult: Family Linkage Data From the HUNT Study

OBJECTIVES To examine a possible association of parental chronic pain with chronic pain in the adolescent and young adult and to explore whether a relationship could be explained by socioeconomic and psychosocial factors or may be affected by differences in family structure. DESIGN Unselected, population-based, cross-sectional study. SETTING Nord-Trøndelag County, Norway. PARTICIPANTS All inhabitants of Nord-Trøndelag County who were 13 years or older were invited to enroll in the study. In total, 8200 of 10 485 invitees (78.2%) participated in the investigation. Among 7913 participants in the target age group (age range, 13-18 years), 7373 (93.2%) completed the pain questions. The final study population consisted of 5370 adolescents or young adults for whom one or both parents participated in the adult survey. MAIN OUTCOME MEASURES The primary outcome measure was chronic nonspecific pain in adolescents and young adults, defined as pain in at least 1 location, unrelated to any known disease or injury, experienced at least once a week during the past 3 months. Chronic multisite pain was defined as chronic pain in at least 3 locations. RESULTS Maternal chronic pain was associated with chronic nonspecific pain and chronic multisite pain in adolescents and young adults (odds ratio, 1.5; 95% CI, 1.3-1.8). Paternal chronic pain was associated with increased odds of pain in adolescents and young adults. The odds of chronic nonspecific pain and chronic multisite pain in adolescents and young adults increased when both parents reported pain. Adjustments for socioeconomic and psychosocial factors did not change the results, although differences in family structure did. Among offspring living primarily with their mothers, clear associations were observed between maternal pain and pain in adolescents and young adults, but no association was found with paternal pain. CONCLUSIONS Parental chronic pain is associated with chronic nonspecific pain and especially with chronic multisite pain in adolescents and young adults. Family structure influences the relationship, indicating that family pain models and shared environmental factors are important in the origin of chronic pain.

Biomarkers of Chronic Uveitis in Juvenile Idiopathic Arthritis: Predictive Value of Antihistone Antibodies and Antinuclear Antibodies

Objective. To study the predictive value of antinuclear autoantibody (ANA) tests and antihistone antibodies (AHA) as risk factors for development of chronic asymptomatic uveitis of insidious onset in juvenile idiopathic arthritis (JIA). Methods. ANA by indirect immunofluorescence using HEp-2 cells (IF-ANA), ELISA for ANA (E-ANA), and AHA were analyzed in sera of 100 children with recent-onset JIA and in 58 control sera. Clinical features, including age at onset, JIA subgroup, and presence of uveitis, were recorded in this prospective population-based cohort study. Results. E-ANA was positive in 4 of the 100 sera, and was not associated with uveitis. Chronic uveitis developed in 16 children with JIA: in 14 of 68 positive for IF-ANA ≥ 80, and in 13 of 44 positive for AHA ≥ 8 U/ml. IgM/IgG AHA were found in higher proportions in children with uveitis (mean 12.4 U/ml) than in those with JIA and no uveitis (mean 6.9 U/ml) or in healthy controls (mean 4.3 U/ml). Conclusion. No association was found between E-ANA and uveitis, and most IF-ANA-positive sera were E-ANA-negative. E-ANA is not clinically relevant in this setting and should never be used to determine frequencies of eye examinations to detect new uveitis in JIA. AHA ≥ 8 U/ml, IF-ANA titer ≥ 320, and young age at onset of arthritis were significant predictors for development of chronic uveitis. The diagnostic value of AHA ≥ 8 U/ml as a biomarker of chronic uveitis in JIA is very similar to IF-ANA ≥ 80.

Validity and predictive ability of the juvenile arthritis disease activity score based on CRP versus ESR in a Nordic population-based setting

Objective To compare the juvenile arthritis disease activity score (JADAS) based on C reactive protein (CRP) (JADAS-CRP) with JADAS based on erythrocyte sedimentation rate (ESR) (JADAS-ESR) and to validate JADAS in a population-based setting. Methods The CRP and ESR values and the corresponding JADAS scores (JADAS10/27/71) were compared in a longitudinal cohort study of 389 children newly diagnosed with juvenile idiopathic arthritis (JIA) in the Nordic JIA study. The construct validity and the discriminative and predictive ability of JADAS were assessed during a median disease course of 8 years by comparing JADAS with other measures of disease activity and outcome. Results At the first study visit the correlation between JADAS27-CRP and JADAS27-ESR was r=0.99 whereas the correlation between CRP and ESR was r=0.57. Children with higher JADAS scores had an increased risk of concomitant pain, physical disability and use of disease-modifying antirheumatic drugs (DMARDs). A higher JADAS score at the first study visit also significantly predicted physical disability, damage and no remission off medication at the final study visit, and also use of DMARDs during the disease course. Sensitivity to change, demonstrated as change in JADAS score compared with the American College of Rheumatology paediatric measures of improvement criteria, mostly showed excellent classification ability. Conclusion The JADAS-CRP and JADAS-ESR correlate closely, show similar test characteristics and are feasible and valid tools for assessing disease activity in JIA.

A longitudinal PRINTO study on growth and puberty in juvenile systemic lupus erythematosus

Objective To obtain longitudinal data on growth/puberty in a large-scale, multi-national prospective cohort of juvenile systemic lupus erythematosus (SLE). Methods Data from 331/557 (59.4%) patients ≤18 years old with juvenile SLE in active phase, with anthropometric data available at four follow-up visits, were studied. Results There was a significant reduction in parent-adjusted height z score with time in females and males (p<0.0001), with a significant gender difference (p<0.0001) and with male height being most affected. Median body mass index z score peaked at 6 months and was still significantly above baseline after 26 months (p<0.01), with no gender difference. Standardised height reduction was inversely related to age at onset. Females with onset age <12 years had a median parent-adjusted height z score of −0.87 with no catch-up growth. At the end of the study, growth failure was seen in 14.7% of the females and 24.5% of the males. Height deflection (less than −0.25/year) was found in 20.7% of the females and 45.5% of the males. Delayed pubertal onset was seen in 15.3% and 24% of the females and males, respectively, and delayed/absent menarche was seen in 21.9%, while 36.1% of the females and 44% of the males had some degree of delayed pubertal development. Growth failure baseline determinants were previous growth failure (OR: 56.6), age at first visit ≤13.4 years (OR: 4.2) and cumulative steroid dose >426 mg/kg (OR: 3.6). Conclusions The children at risk of having a negative effect on height and pubertal development are prepubertal and peripubertal children treated with >400 mg/kg cumulative dose of corticosteroids.

HLA-B27 Predicts a More Chronic Disease Course in an 8-year Followup Cohort of Patients with Juvenile Idiopathic Arthritis

Objective. We investigated associations of HLA-B27 with clinical manifestations and longterm outcome in a near population-based setting among patients with juvenile idiopathic arthritis (JIA). Methods. We studied clinical and serological data from 410 patients with HLA-B27 results among 440 prospectively collected patients with JIA with 8-year followup data in a Nordic database. The study was structured to be as close to a population-based study as possible. Results. HLA-B27 was analyzed in 93% of patients, and was positive in 21% of the cohort, in 18.4% of the girls and in 25.9% of the boys. Boys who were HLA-B27-positive had significantly higher age at onset compared to HLA-B27-negative boys and compared to both HLA-B27-negative and positive girls. This difference in onset age in relation to HLA-B27 was not found in girls. HLA-B27 was associated with clinical signs of sacroiliitis, enthesitis, and tenosynovitis in boys, but not in girls. After 8 years of disease, 46 children (11.2%) were classified as having enthesitis-related arthritis (ERA). Boys with ERA had clinical signs of sacroiliitis more often than girls with ERA. HLA-B27-positive children, as well as children with clinical signs of sacroiliitis, enthesitis, and hip arthritis, had higher odds of not being in remission off medication after 8 years of disease. Conclusion. In this near population-based Nordic JIA cohort we found significant differences between HLA-B27-positive boys and girls in age at disease onset, clinical signs of sacroiliitis, and ERA classification. HLA-B27 was negatively associated with longterm remission status, possibly because of its association with clinical disease characteristics, such as sacroiliitis, rather than being a general marker of persistent disease.

Molecular and phenotypic characterization of invasive group B streptococcus strains from infants in Norway 2006-2007.

Multilocus sequence typing of an almost complete collection of invasive group B streptococcus (GBS) strains from infants in Norway, conducted in 2006-2007, revealed 27 sequence types (ST), of which 23 clustered into five clonal complexes. The case fatality rate of invasive GBS disease in infants was 16/98 (16.3%). Type V strains were predominant among strains resistant to erythromycin and clindamycin (11/18; 61.1%). All type V strains from fatal cases (5/16) were ST1, resistant to erythromycin and clindamycin, and belonged to three pulsed-field gel electrophoresis-clusters. Further analysis of virulence characteristics of these apparently highly virulent subtypes of type V, ST1 GBS strains is warranted.

Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases.

Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides. Methods Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed. Results We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA. Conclusions The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services.