Rheumatoid Arthritis: Oen K

Oen K. · Department of Pediatrics and Child Health, University of Manitoba, RR149-Rehabilitation Centre, 800 Sherbrook Street, Winnipeg, Canada, R3A 1M4. · Best Pract Res Clin Rheumatol. · Pubmed #12387804 No free full text.

Abstract: Prediction of the long-term outcome for patients with juvenile idiopathic arthritis requires assessment of disability, psychosocial and socioeconomic function. Measures for the first have evolved from Steinbrocker functional classifications to validated self-administered questionnaires. The proportion of patients with severe disability has decreased during the past three decades but significant numbers of patients enter adulthood with some disability detected with the newer measures. Despite careful study, few early predictors of a poor outcome have been identified. The most consistent are early age at onset, persistent fever and thrombocytosis in patients with systemic juvenile idiopathic arthritis. Reports of psychosocial and socioeconomic outcomes are controversial and further analyses of these spheres are required. An increased risk of osteoporosis and osteopenia has been reported in adults with juvenile idiopathic arthritis. The most significant problem faced by patients during adulthood is persistent disease activity as disability, radiographic damage and the risk of osteoporosis all increase with increasing duration of disease.

Oen K. · Department of Pediatrics and Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, Canada. · Curr Opin Rheumatol. · Pubmed #10990177 No free full text.

Abstract: Publications from different countries collectively confirm distinctions in the occurrence of pediatric rheumatic diseases among different populations. In part, this heterogeneity is due to differences in the distribution of human leukocyte antigen alleles. The epidemiology of the various forms of pediatric chronic arthritis has been studied most extensively. However, it is clear that these are complex conditions involving multiple genes as well as environmental and probably developmental factors. Other publications during the past year have updated the epidemiology of Kawasaki disease, Behcet disease, and acute rheumatic fever.

Brown GT, Wright FV, Lang BA, Birdi N, Oen K, Stephens D, McComas J, Feldman BM. · Monash University, Frankston, Victoria, Australia. · Arthritis Rheum. · Pubmed #16342103 links to  free full text

Abstract: OBJECTIVE: The Childhood Health Assessment Questionnaire (CHAQ), Juvenile Arthritis Functional Assessment Report (JAFAR), and Juvenile Arthritis Functional Status Index (JASI) are widely used functional measures for juvenile idiopathic arthritis (JIA) that differ in content, format, and completion time. We compared the responsiveness and child-parent agreement of the JAFAR, CHAQ, and JASI in a prospective, multicenter study. METHODS: Children and adolescents from 5 rheumatology centers were enrolled. Subjects were about to undergo therapy (intraarticular corticosteroid injections [IAS] and methotrexate or hip surgery (MTX/hip]) expected to produce a functional improvement. All subjects were studied before the intervention and at 6 weeks and 6 months posttreatment. At each study visit, the 3 measures were administered in randomized, balanced order to both parents and children. RESULTS: A total of 92 subjects (mean age 12.8 years) were enrolled in the study, 74 of which were in the IAS group. The responsiveness of all 3 measures was moderate to strong. The standardized response mean at 6 weeks for the IAS group on the JAFAR, CHAQ, and JASI was 0.41 (95% confidence interval [95% CI] 0.18, 0.64), 0.70 (95% CI 0.47, 0.93), and 0.36 (95% CI 0.13, 0.59), respectively. The CHAQ was somewhat more responsive to change at 6 weeks (IAS group: relative efficiency 0.34 [JAFAR], 0.27 [JASI]), but less responsive at 6 months (MTX/hip group: relative efficiency 5.1 [JAFAR], 3.9 [JASI]). All 3 questionnaires showed acceptable parent-child agreement, and overall, there were few differences between the 3 questionnaires. CONCLUSION: The functional outcome measures currently used for JIA are all adequately responsive for use in trials or in the clinic setting. The choice of which measure to use should therefore be based on the time available for completion, the intended clinical/research use, and the depth of content required.

El-Gabalawy HS, Robinson DB, Hart D, Elias B, Markland J, Peschken CA, Smolik I, Montes-Aldana G, Schroeder M, Fritzler MJ, Cheang M, Oen K. · Department of Medicine, University of Manitoba Arthritis Centre, RR149 - 800 Sherbrook Street, Winnipeg, Manitoba R3A 1M4, Canada. · J Rheumatol. · Pubmed #19411392 No free full text.

Abstract: OBJECTIVE: To determine the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in unaffected relatives of North American Native probands with rheumatoid arthritis (RA); and the associations of the shared epitope (SE) and HLA-DRB1*0901 with RA and anti-CCP antibodies. METHODS: The subjects were RA probands, affected relatives, unaffected first-degree (FDR) and more distant relatives, and unaffected controls from the same population. HLA-DRB1 typing was determined by DNA sequencing and anti-CCP antibodies were determined by ELISA. RESULTS: DRB1*0901, SE, and SE/DRB1*0901 genotypes were all associated with RA. SE/DRB1*0901, but not other SE genotypes, was associated with disease onset at age<16 years. The frequency of anti-CCP antibodies was 82% in RA probands, 17% in FDR, 11% in more distant relatives, and 3% in controls. Among unaffected relatives, a significant increased risk of anti-CCP was associated with SE/DRB1*0901 genotype, but not with SE. CONCLUSION: An independent association of the non-SE allele DRB1*0901 with RA was confirmed in this population, and this allele in combination with a SE allele was associated with younger age at disease onset. FDR of RA probands have a higher prevalence of anti-CCP antibodies than more distant relatives and unrelated controls, suggesting a gradient of risk for disease development. Immunogenetic risks may act early in disease pathogenesis at the level of initiation of RA autoantibody formation; however, it is not clear what additional genetic and environmental risks are involved in progression to clinical disease.

Oen K, Robinson DB, Nickerson P, Katz SJ, Cheang M, Peschken CA, Canvin JM, Hitchon CA, Schroeder ML, El-Gabalawy HS. · Department of Paediatrics and Child health; and the School of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. · J Rheumatol. · Pubmed #15940756 No free full text.

Abstract: OBJECTIVE: A number of North American native (NAN) populations have high prevalence rates of both rheumatoid arthritis (RA) and the shared epitope (SE). We examined the phenotype and familial incidence of RA in a NAN population, and investigated how the SE and cytokine genes may affect disease risk within affected families. METHODS: NAN patients with seropositive RA or polyarthritis rheumatoid factor (RF) positive juvenile idiopathic arthritis (JIA) were identified from clinical databases. Patients were recruited consecutively as they presented for clinic visits. Family pedigrees were constructed and consenting relatives were interviewed and examined. The risk of RA within families was calculated by multiple logistic regression. Input variables were the SE and cytokine genotypes. Probands and affected relatives were entered as the affected group, and unaffected relatives within families as the unaffected group. Results were confirmed among unrelated subjects, i.e., unrelated patients and unaffected relatives of other probands. RESULTS: The familial prevalence of RA was 0.50 (95% confidence intervals 0.30, 0.70) among 28 families studied. The interleukin 10 (IL-10) promoter -1082 G/A genotype decreased the odds of RA relative to the A/A genotype in affected families (OR 0.247, 95% CI 0.081, 0.751; p = 0.014) and among unrelated subjects (OR 0.203, 95% CI 0.064, 0.640; p = 0.006). The G/G genotype yielded an OR of 0.093 (95% 0.013, 0.676; p = 0.019) among unrelated subjects. The SE had no effect in these calculations. CONCLUSION: There was a high familial prevalence of RA in this NAN cohort. In susceptible NAN families, the risk of RA was reduced by IL-10 genotypes, whereas the SE did not affect risk. Study of healthy NAN controls is required to determine if these conclusions apply to this NAN population as a whole.

Oen K, Malleson PN, Cabral DA, Rosenberg AM, Petty RE, Nickerson P, Reed M. · Department of Paediatrics, University of Manitoba, Winnipeg, Canada. · Rheumatology (Oxford). · Pubmed #15901906 links to  free full text

Abstract: OBJECTIVES: Single nucleotide polymorphisms (SNPs) in cytokine genes have been associated with risk of a number of autoimmune diseases. Moreover, some SNPs are associated with variations in rates of in vitro gene expression, and it is therefore possible that these functional polymorphisms may differentially affect inflammatory processes and disease outcome. This project's objective was to determine whether cytokine genotypes correlate with disease outcomes in patients with juvenile rheumatoid arthritis (JRA). METHODS: Genotypes of SNPs of pro-inflammatory cytokines, tumour necrosis factor-alpha -308G -->A, interleukin-6 (IL-6) -174G -->C and interferon-gamma +874G -->A, and anti-inflammatory, immunosuppressive cytokines, interleukin-10 -1082G -->A, -819C -->T and -592A -->C and transforming growth factor-beta1 (TGF-beta1) codon 10T -->C and codon 25G -->C, were determined for patients with JRA who previously participated in a long-term outcome study. Cytokine genotypes and clinical variables showing significant correlations with clinical outcomes at the alpha = 0.100 level in univariate analyses were entered in multivariate tests. RESULTS: In multivariate tests, the IL-6 genotype -174G/G was positively correlated with pain [regression coefficient B = 0.899, 95% confidence intervals (CI) 0.185, 1.612, P = 0.014]. The homozygous TGF-beta1 codon 25G/G genotype showed a protective effect against joint space narrowing on radiographs taken within 2 yr of disease onset, but confidence intervals were wide [odds ratio (OR) 0.176, 95% CI 0.037, 0.837 P = 0.029]. CONCLUSIONS: The correlation of IL-6 genotype with pain and the possible association of the TGF-beta1 codon 25 genotype with short-term radiographic damage (G/C with greater risk and G/G with decreased risk) suggests that both these polymorphisms may be useful early prognostic indicators. Further studies of the relation between cytokine genotypes and outcomes in patients with all forms of juvenile idiopathic arthritis (JIA) are warranted.

Malleson PN, Oen K, Cabral DA, Petty RE, Rosenberg AM, Cheang M. · University of British Columbia, Vancouver, British Columbia, Canada. · Arthritis Rheum. · Pubmed #15077263 links to  free full text

Abstract: OBJECTIVE: To examine demographic and disease-related variables that affect pain in a large cohort of patients with juvenile rheumatoid arthritis (JRA). METHODS: Selection criteria were an onset of JRA >/=5 years prior to study and age >/=8 years at the time of the study. Pain was measured by a self-administered 10-cm visual analog scale. Possible explanatory variables studied included age at study, sex, race, onset subtype, active disease duration, active joint count, and physician's global assessment (PGA). RESULTS: In a multiple regression model, active disease duration, PGA, and age at study were independent predictors explaining 22% of the variation in pain scores. Stratified analyses showed an effect of age in the 8-15-year group, but not in older patients. CONCLUSION: Disease-related factors explain only a small proportion of the variation in pain scores. Age has an effect on pain scores only in younger patients. The role of other factors, including psychosocial factors, needs further study.

Oen K, Reed M, Malleson PN, Cabral DA, Petty RE, Rosenberg AM, Cheang M. · Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada. · J Rheumatol. · Pubmed #12672208 No free full text.

Abstract: OBJECTIVE: To determine the radiologic outcome in juvenile rheumatoid arthritis (JRA) and the relationship of radiologically detected joint damage to functional disability using multivariate analyses. METHODS: Selection criteria included a diagnosis of JRA made by 1977 American College of Rheumatology criteria, onset of arthritis > or = 5 years prior to study, current age > or = 8 years, a minimum grade 3 reading ability, and the availability of radiographs. Disability was measured by the Childhood Health Assessment Questionnaire (CHAQ) and Steinbrocker classifications. Radiographs taken within 2 years after onset (early) and the most recent radiographs (late) were examined by a single pediatric radiologist blinded to patients' identities, diagnoses, and outcomes. Multiple regression analyses were performed. RESULTS: On late radiographs the frequencies of joint space narrowing were 38, 14, 43, and 79%, respectively, among patients with systemic, pauciarticular, rheumatoid factor (RF) negative polyarticular, and RF positive polyarticular onset; erosions occurred in 63, 25, 39, and 75%, respectively. Early erosions were most frequent in patients with RF+ polyarticular onset, while both joint space narrowing and erosions occurred early in systemic onset. Radiologic signs of joint damage were most frequent at hips and wrists, while knees and ankles were relatively spared. Based on patients who had radiographs performed within one year of clinical study, 17.7% of the variation in CHAQ score was explained by joint space narrowing, 32.4% by pain, and 5% by a severe rating on physician's global estimate of disease activity. The odds of a Steinbrocker class > I were increased by joint space narrowing, pain, systemic onset, and active joint count. CONCLUSION: Differences in the frequencies and patterns of joint damage occur both among JRA onset subtypes and among individual joints. Radiographic damage, especially joint space narrowing, correlates with functional disability. However, pain is the major contributor to variation in CHAQ scores.

Oen K, Malleson PN, Cabral DA, Rosenberg AM, Petty RE, Reed M, Schroeder ML, Cheang M. · Departments of Paediatrics, Radiology, and Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. · J Rheumatol. · Pubmed #12610821 No free full text.

Abstract: OBJECTIVE: To determine early predictors of longterm outcome in juvenile rheumatoid arthritis (JRA) in a multicenter cohort. METHODS: Patients were selected if they were > or = 8 years of age; the onset of arthritis occurred > or = 5 years before study; and a diagnosis of JRA was made at a participating center. Outcome variables were scores on self-administered Childhood Health Assessment Questionnaires (CHAQ) and active disease duration. Possible explanatory variables assessed included characteristics present at onset, HLA alleles, in particular the rheumatoid arthritis associated shared epitope (RASE), and radiographic indicators of joint damage within 2 years of onset. Data for 393 patients were available. Multivariate analyses were performed for the total group and for each onset subtype. RESULTS: Male sex correlated with worse disability in systemic onset JRA but less disability in RF negative, and a shorter active disease duration in RF positive polyarticular onset JRA. Positive antinuclear antibody correlated with a longer active disease duration in patients with pauciarticular onset JRA. Younger age at onset predicted longer active disease duration in pauciarticular and RF negative polyarticular, and a shorter active disease duration in systemic onset JRA. Residence on a reserve, rather than native North American race, correlated with worse disability. The RASE correlated with less disability in systemic JRA; but no correlation with outcome was evident for patients with rheumatoid factor positive polyarticular JRA. CONCLUSION: Variables predictive of longterm outcome in JRA are specific for each onset subtype. The most important early predictors were age at onset and sex of the patient. Place of residence may have a greater effect on disability than race. RASE may associate with a more favorable outcome in systemic onset disease.

Oen K, Malleson PN, Cabral DA, Rosenberg AM, Petty RE, Cheang M. · Department of Paediatrics, University of Manitoba, Winnipeg, Canada. · J Rheumatol. · Pubmed #12233897 No free full text.

Abstract: OBJECTIVE: To determine the disease course and outcome in a multicenter cohort of patients with juvenile rheumatoid arthritis (JRA). METHODS: All patients with JRA seen at 3 pediatric rheumatology centers were identified from databases and/or clinic records. Inclusion criteria were a diagnosis of JRA (1977 American College of Rheumatology criteria), a followup period of at least 5 years since onset, and a minimum age of 8 years. Patients were examined and completed a Childhood Health Assessment Questionnaire (CHAQ). Kaplan-Meier curves were constructed to estimate rates of remission, relapse, and arthroplasty. Remission was defined as absence of active arthritis while off treatment for at least 2 years. Outcome measures were active disease duration, CHAQ scores, pain determined by visual analog scales, physician's global assessments, and Steinbrocker functional classifications. Years of education and employment status were ascertained. RESULTS: We studied 392 patients of 652 (60%) who met the selection criteria. The probabilities of remission at 10 years after onset were 37, 47, 23, and 6% for patients with systemic, pauciarticular, RF- polyarticular, and RF+ polyarticular JRA, respectively. The probability of relapse varied from 30 to 100% at 15 years. The probability of arthroplasty varied from 13 to 57% after 15 years of active disease. We found 2.5% of patients assessed were in Steinbrocker Classes III or IV and 6% were in the highest CHAQ score (> 1.5) group. Compared with national statistics, fewer female patients received post-secondary education and unemployment rates for patients 20 to 24 years of age were higher. CONCLUSION: Our results indicate that JRA is a disease that often extends into adulthood. Compared to previous decades, functional outcome has improved; however, the estimated rate of arthroplasty remains very high. Patients with JRA may have difficulty entering the workforce.