ObjectivesJuvenile 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.MethodsDense 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.ResultsWe 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.ConclusionsThe 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.
A disability assessment tool, the Juvenile Arthritis Functional Assessment Scale, was developed for, and validated in, patients with juvenile rheumatoid arthritis (JRA). Standards for this 10-item tool were developed using the scores of 63 normal school children as controls and comparing these results with those of 71 agematched JRA patients (age 7-16 years). The JRA patients scored statistically significantly higher on the scale, which also demonstrated excellent internal and convergent validity and internal reliability. The test is easily administered in 10 minutes by a physical or occupational therapist in a clinical or office setting. This tool represents the first normalized disability assessment tool developed for JRA patients.Juvenile rheumatoid arthritis (JRA) is a complex disease of varying severity and prognosis. It is the most frequently encountered pediatric rheumatic disease, one of the more common chronic diseases of
Objective. To determine the extent of significant osteopenia in prepubertal patients with juvenile rheumatoid arthritis (JRA) not treated with corticosteroids and to identify variables that are highly related to bone mineralization in this population.Methods. In a cross-sectional study, 48 JRA patients and 25 healthy control subjects ages 4.6-11.0 years were evaluated. Total body bone mineral density (TB BMD) was determined by Hologic dual energy x-ray absorptiometry. All patients were prepubertal (Tanner stage 1 or 11) and had never taken corticosteroids. For comparison, JRA patients were divided into c'lo~7' TB BMD (Z score 5-1) or "normal" TB BMD (Z score >-1).Results. The overall mean k SD TB BMD scores did not differ between the JRA subjects (0.75 2 0.06 gm/cm2) and controls (0.73 k 0.07 gm/cm2; P > 0.30).However, 29.2% of the JRA patients had low TB BMD, whereas only 16% would be expected to have low TB BMD based on the standard normal distribution (goodness of fit 2 = 4.84, P = 0.01). The mean Z score for the JRA patients with low TB BMD was -1.43, and for those with normal TB BMD, it was 0.32. The JRA subjects with low TB BMD were significantly younger, had more active articular disease, greater physical function limitation, higher erythrocyte sedimentation rate, higher joint count severity score, lower body mass index, lower lean body mass, less participation in organized sports, and more protein and vitamin D in their diet compared with JRA patients with normal TB BMD (all P < 0.05). Using logistic regression, a model including age at JRA onset, Juvenile Arthritis Functional Assessment Report (JAFAR) score, triceps skinfold percentiles, percentage US recommended daily allowance for dietary magnesium intake, and serum 1,25-dihydroxyvitamin D levels was able to accurately segregate 79.6% of the JRA subjects into either the low or normal TB BMD groups (2 = 20.5, P = 0.001).Conclusion. This study demonstrated that in a mildly to moderately ill prepubertal JRA population that had never been exposed to corticosteroids, almost 30% had significantly low TB BMD. The patients with low TB BMD had more active and severe articular disease and greater physical function limitation. Disease-related parameters in JRA appear to exert a negative effect on bone mineralization even in prepubertal children, which can be demonstrated despite the exclusion of corticosteroid-treated patients.
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