Disability and health-related quality of life are associated with restricted social participation in young adults with juvenile idiopathic arthritis.

OBJECTIVES: To describe a cohort of Finnish juvenile idiopathic arthritis (JIA) patients, to recognize those young adults who are at risk of becoming socially restricted by their long-term rheumatic disease, and to assess which areas of self-rated health-related quality of life (HRQoL) are associated with the emergence of restricted social participation. METHODS: A total of 195 young adults with JIA completed questionnaires addressing demographics, health behaviour, physical activity, functional ability, HRQoL, depressive symptoms, and self-esteem. Patients were classified as having non-restricted social participation if they were engaged in studying, working, maternity leave, or military service, and restricted social participation if they were unemployed or on disability pension. RESULTS: Of the patients, 162 (83%) were considered as having non-restricted social participation and 33 (16%) restricted social participation. Among patients with restricted social participation, five (15%) were on disability pension and 28 (85%) were unemployed. Patients with restricted social participation participated less in leisure-time non-physical activities (p = 0.033), felt more disturbed during their leisure time (p = 0.010), had lower self-esteem (p = 0.005), and had higher disability scores (p = 0.024). HRQoL scores revealed statistically significant differences between the groups: physical functioning (p = 0.043), social functioning (p = 0.016), and emotional well-being (p = 0.049) were all lower in patients with restricted social participation. CONCLUSIONS: Socially restricted patients showed a higher degree of disability, and lower levels of physical functioning, self-esteem, emotional well-being, and social functioning. These patients should be recognized earlier and interventions provided to enhance their social participation.

Pain interference and associated factors in young adults with juvenile idiopathic arthritis.

Objective: Pain is a common and distressing feature of juvenile idiopathic arthritis (JIA). Pain interference (PI) is underexplored in long-term conditions such as JIA. The aim of this study was to explore the factors associated with PI in young adults with JIA. Methods: All consecutive JIA patients aged 18-30 years in three tertiary rheumatology and rehabilitation centres in Finland between September 2015 and April 2016 were included. The patients completed questionnaires addressing demographics, disability, depressive symptoms, pain anxiety, pain intensity, and PI. PI was measured with a single item from the RAND-36 questionnaire. Five response categories were coded into three groups: patients reporting 'extremely', 'quite a bit' or 'moderate' were classified as having significant PI; 'a little bit' as having minor PI; and 'not at all' as having no PI. A leisure-time physical activity metabolic equivalent of task (LTPA MET) was calculated. Statistical comparisons between PI and categorical variables were made using chi-squared or Fisher-Freeman-Halton tests. Results: Of the total 195 patients, 97 (50%) patients reported PI. PI was associated with a wide spectrum of sociodemographic and disease-related variables. Pain intensity scores were higher in patients expressing greater PI (p < 0.001). Greater PI was associated with higher disability (p < 0.001), higher pain anxiety scores (p < 0.001), lower LTPA MET (p = 0.027), and poorer leisure-time activity (p < 0.001). Conclusions: PI is common in young adults with JIA. We suggest that PI should be taken into account in future outcome studies exploring the impact of pain in children and young adults with JIA.

Occurrence of chronic inflammatory rheumatic diseases among parents of multiple offspring affected by juvenile idiopathic arthritis.

OBJECTIVE: The rarity of reports on extended multiplex families points out that the genetic component in juvenile idiopathic arthritis (JIA) might not be particularly strong. Our objective was to determine the frequency of chronic inflammatory rheumatic diseases among the parents who had two or more offspring affected by JIA. METHODS: During the last 17 years patients with JIA treated at the Rheumatism Foundation Hospital in Heinola and their parents have been systematically asked about the familial occurrence of rheumatic diseases. A total of 45 families with more than one sibling affected by JIA were found among about 2,300 JIA cases. In these "multicase families", 9 parents from 8 families also had a diagnosis of chronic inflammatory rheumatic disease. Their case histories were studied. RESULTS: Four of the parents had had JIA (one subsequently developed ankylosing spondylitis), and 4 had rheumatoid factor-negative chronic arthritis (one had also had chronic iritis since the age of 10, resembling that seen in JIA). Three of them had features of JIA and only one met the classification criteria for rheumatoid arthritis. One had ankylosing spondylitis. CONCLUSIONS: Since the expected number of JIA cases among the 90 parents was about 0.2, there was drastic increase in JIA frequency among the parents in families with multiple offspring also affected by JIA. These results suggest that JIA susceptibility genes may likely be clustered in these families.

Juvenile idiopathic arthritis in multicase families.

OBJECTIVE: To characterize juvenile idiopathic arthritis (JIA) patients from multicase families. METHODS: The study series comprised 80 affected siblings belonging to 37 families. Comparisons were made with a population-based series of JIA patients from Finland and with a sibling series from the United States. RESULTS: The distribution of cases according to onset type was similar in the sibling and population-based series. The age at diagnosis was significantly lower in the sibling series (4.8 years vs 7.4 years; p < 0.001). There was more intra-pair similarity in onset and course types in the United States series compared to the Finnish series and the proportion of girls was higher in the former. CONCLUSION: The only significant difference between familial and sporadic cases with JIA is an earlier onset of disease in familial cases. There is no essential difference in clinical features of the disease between patients in the multicase and sporadic groups. Differences between the Finnish and US series may be due to selection bias in the latter.

Finnish case-control and family studies support PTPN22 R620W polymorphism as a risk factor in rheumatoid arthritis, but suggest only minimal or no effect in juvenile idiopathic arthritis.

Several studies have identified the PTPN22 allelic variant 1858 C/T that encodes the R620W amino-acid change as a putative susceptibility factor in autoimmune diseases. The current study was undertaken to examine a large cohort of Finnish rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) subjects using both population control and, importantly, family-based association methods. The latter is particularly important when, as is the case for the 1858 C/T polymorphism, the frequency of the variant allele (T) differs in both major ancestral populations and in subpopulations. The analysis of rheumatoid factor-positive 1030 RA probands from Finland provides strong support for association of this variant in both population studies (allele specific odds ratio (OR)=1.47, 95% confidence interval (CI)=1.27-1.70, P=3 x 10(-7)) and in family studies (P<10(-6)). In contrast, no allelic association was seen with JIA (230 probands) and only weak evidence for a genotypic effect of 1858T homozygotes was observed in this population.

Uveitis in sibling pairs with juvenile idiopathic arthritis.

OBJECTIVE: To ascertain the occurrence and characteristics of uveitis in sibling pairs affected with juvenile idiopathic arthritis (JIA). METHODS: The sibling series comprised 80 JIA patients from 37 families with two or three JIA children, seen at the paediatric department of the Rheumatism Foundation Hospital in Heinola, Finland. An ophthalmologist examined the children for uveitis two to four times a year and the course of the condition was recorded during the follow-up. RESULTS: Uveitis was diagnosed in 21 of the 80 patients (26%). Three pairs (3.4 pairs expected) were concordant for the presence of asymptomatic uveitis. Two patients with enthesitis-related arthritis had acute unilateral uveitis. Among the remaining cases, uveitis was chronic and continuously active at the end of follow-up in 13 instances, but in spite of this only one patient had impaired vision. HLA allele B27 occurred more frequently in patients with uveitis than in those without uveitis (52 vs 30%, P=0.073) and all six subjects in the pairs concordant for chronic uveitis carried this allele. CONCLUSIONS: The observed concordance rate for uveitis did not differ from that expected. Although the uveitis was chronic in most instances, its course was usually mild.

HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: more complexity within the MHC.

This study further defines genetic susceptibility to JIA in the region centromeric to HLA-DRB1. DNA from 234 Finnish JIA nuclear families and 639 elderly Finnish control individuals was genotyped for five functional SNPs within the TAP2 and TAP1 loci ( approximately 200 kb centromeric of HLA-DRB1). Subsets of the controls (186) and patients (145) that had been previously typed for HLA-DRB1 were also genotyped by sequence for the HLA-DPB1 locus. Case/control and transmission disequilibrium test (TDT) methods revealed an association with the DPB1(*)030101 allele for JIA (OR 2.3, 95% CI 1.5-3.5). Notably, a detailed haplotypic analysis of the TAP2/TAP1 loci and their interaction with the HLA-DPB1(*)030101 and DRB1(*)08 and (*)11 alleles showed a variety of over-represented and under-represented TAP2/TAP1 haplotypes not evident in the single marker analysis. The strongest effect was observed in the polyarticular RF negative JIA subgroup for the 2-2-1-2-1 TAP2/TAP1 haplotype (TAP2B and TAP1A alleles) which showed an independent effect from both DRB1(*)08 and (*)11 (P<0.000003) and DPB1(*)030101 (P=0.02). We have provided evidence that the extended haplotypes (including HLA-DRB1, TAP2/TAP1, and HLA-DPB1) of pauciarticular and polyarticular RF negative disease are distinct. This observation may have implications for functional etiological differences between the pauciarticular and polyarticular JIA patients.

Analysis of MHC region genetics in Finnish patients with juvenile idiopathic arthritis: evidence for different locus-specific effects in polyarticular vs pauciarticular subsets and a shared DRB1 epitope.

This study used Finnish juvenile idiopathic arthritis (JIA) probands with pauciarticular and rheumatoid factor (RF) negative polyarticular subtypes of JIA to further define the genetic susceptibility to JIA. We examined 16 markers spanning an 18 cM region of chromosome 6 encompassing the MHC and surrounding genomic region in a set of 235 Finnish JIA nuclear families and 639 Finnish control individuals. Analysis by case/control association and transmission disequilibrium test (TDT) methods each demonstrated strong evidence for a susceptibility locus near the D6S2447 microsatellite (P<10(-6) for both methods) that is flanked by DQB1 and DRB1. Analysis of the DRB1 locus suggested that DRB1*0801 and DRB1*1101 rather than DQA1 or other HLA alleles may be responsible for conferring susceptibility to disease. These findings are consistent with the most compelling results of previous reports on HLA associations and suggest a JIA DRB1 shared epitope encompassing critical amino-acid residues in the third hypervariable region of this molecule. Most importantly, in pauciarticular patients, the strong association does not extend to proximal markers as it does in polyarticular patients (P<0.00001). Analysis strongly suggests that the difference is because of additional JIA susceptibility loci within the MHC being present in polyarticular RF negative patients.