Disease activity and outcome in juvenile idiopathic arthritis - a longitudinal cohort study in the Nordic countries

The papers of this thesis are not available in Munin: <br/>1. Ellen Nordal, Marek Zak, Kristiina Aalto, Lillemor Berntson, Anders Fasth, Troels
Herlin, Pekka Lahdenne, Susan Nielsen, Bjørn Straume and Marite Rygg: 'Ongoing Disease Activity and Changing Categories in a Long-Term Nordic Cohort Study of Juvenile Idiopathic Arthritis', Arthritis & Rheumatism (2011), vol. 63(9):2809-18. Available at <a href=http://dx.doi.org/10.1002/art.30426>http://dx.doi.org/10.1002/art.30426</a> 
<br/>2. Ellen Nordal, Marek Zak, Kristiina Aalto, Lillemor Berntson, Anders Fasth, Troels Herlin, Pekka Lahdenne, Susan Nielsen, Suvi Pältoniemi, Bjørn Straume and Marite Rygg: 'Validity and predictive ability of the Juvenile Arthritis Disease Activity Score (JADAS) based on C-reactive protein in a population-based Nordic cohort of
juvenile idiopathic arthritis' (accepted manucript version). Published version in Annals of the Rheumatic Diseases, Online First-article, 2012, available at <a href=http://dx.doi.org/10.1136/annrheumdis-2011-200237>http://dx.doi.org/10.1136/annrheumdis-2011-200237</a>
<br/>3. Ellen Nordal, Nils T. Songstad, Lillemor Berntson, Torolv Moen, Bjørn Straume and Marite Rygg: 'Biomarkers of chronic uveitis in juvenile idiopathic arthritis: predictive value of
antihistone antibodies and antinuclear antibodies', The Journal of Rheumatology (2009), vol. 36(8):1737-43. Available at <a href=http://dx.doi.org/10.3899/jrheum.081318>http://dx.doi.org/10.3899/jrheum.081318</a>SUMMARY
This thesis is based on the Nordic juvenile idiopathic arthritis (JIA) cohort study. In a multi-centre population-based setting a prospective followup of juvenile idiopathic arthritis (JIA) was performed. Pediatric rheumatology centers in Denmark, Finland, Norway and Sweden included children with newly diagnosed JIA during a 3.5 year period starting January 1st 1997. The study was focused on outcome in terms of disease characteristics, course, activity and damage the first eight years after onset. Validation of the Juvenile arthritis disease activity score (JADAS) was performed. Incidence, clinical risk factors and biomarkers of JIA-associated uveitis were also studied.

The first paper described outcome in the Nordic JIA cohort eight years after disease onset. Of the 500 children included at baseline, 440 children (88%) were followed more than 7 years. A change in JIA category during disease course was observed in 10.8% of the children, in addition to extended oligo-arthritis developing in one-third of the oligoarticular group. Disease activity was mostly mild, with low impact on daily life in patient-reported health-related quality of life (HRQoL). However, the chronicity of the disease was demonstrated as 57.6% of the children were not in medication-free remission at the final visit. 
 
In the second paper the JADAS was validated with C-reactive protein (CRP) replacing erythrocyte sedimentation rate (ESR) as an inflammatory marker. JADAS based on CRP correlated closely with the version based on ESR. JADAS was shown to be a feasible and valid tool in assessing disease activity in children with JIA in a population-based setting. 

In the third paper the predictive value of biomarkers and clinical characteristics at disease onset in regard to development of uveitis was studied in a pilot study of the Norwegian cohort of 100 children with JIA. During a mean observation time of 7 years, 16 children developed chronic uveitis. Antihistone antibodies (AHA) ≥8 U/ml, anti-nuclear antibodies detected by immunofluoresence (IF) ≥320 titer and young age at disease onset were significant predictors of uveitis development in JIA.  Presence of ANA detected by enzyme-linked immunosorbent assays (ELISA) showed no association to development of uveitis, and should never be used to determine frequencies of eye examinations in children with JIA. 

The main findings of this study support the understanding of JIA as a long-term chronic disease.  Further, we found that ILAR categories changed over time, JADAS based on C-reactive protein was a valid tool for evaluation of JIA disease activity in a population-base setting, and also that predicting uveitis in JIA remains a challenge