Rheumatoid Arthritis: Rosenberg AM

Rosenberg AM. · No affiliation provided · J Rheumatol. · Pubmed #12415576 No free full text.

This publication has no abstract.

Rosenberg AM. · Department of Pediatrics, University of Saskatchewan, Royal University Hospital, Canada. · Curr Opin Rheumatol. · Pubmed #12192252 No free full text.

Abstract: Optimal management of childhood rheumatic diseases requires an appreciation of their multisystem nature. The eye represents an important site of involvement, and inflammation of the uveal tract is a particularly frequent and potentially debilitating extra-articular feature of some childhood rheumatic diseases. Anterior uveitis associated with oligoarticular juvenile idiopathic arthritis is an especially distinctive entity. Other disorders in children, however, can be associated with posterior and intermediate uveal tract inflammation. The potentially debilitating consequences of uveitis associated with childhood rheumatic diseases, the inadequacies of existing therapies, and the immunopathogenic basis for particular forms of uveitis have prompted the use of immunomodulatory therapy, including new biologic agents, to treat childhood uveitis. This review summarizes recent contributions to the literature that help to clarify the spectrum of conditions associated with uveitis in children, consider evidence for immunopathogenic processes associated with uveitis, and address new approaches to therapy.

Rosenberg AM. · Section of Rheumatology, Department of Pediatrics, University of Saskatchewan, Royal University Hospital, 103 Hospital Drive, Saskatoon, Saskatchewan S7N 0W8, Canada. · J Rheumatol. · Pubmed #16206357 No free full text.

Abstract: OBJECTIVE: To analyze a prospectively maintained pediatric rheumatology clinic disease registry. METHODS: A total of 3269 consecutive referrals to the Pediatric Rheumatology Clinic, University of Saskatchewan, during the period 1981-2004 were analyzed. RESULTS: Among 3269 patients, a diagnosis was established in 2098 (64.2%). Within this group, 72 subjects (3.4%) were determined to be healthy. Of the remaining 2026 diagnosed patients (62.0% of the total population), 1032 (50.9%) had a rheumatic disease and 994 (49.1%) a nonrheumatic disease. A diagnosis was not established in 1171 patients (35.8%). Among the 1032 patients with a rheumatic disease, 326 (31.6%) had juvenile rheumatoid arthritis (JRA), 360 (34.9%) a spondyloarthropathy (SpA), and 225 (21.8%) a collagen vascular/connective tissue rheumatic disease. The remaining 121 patients with a rheumatic disease (11.7%) had a variety of other conditions. Of the 994 nonrheumatic disease patients, 37 (3.7%) with ocular inflammatory conditions had been referred to exclude an associated rheumatic disease. The remaining group of 957 patients comprised 345 (36.1%) with an orthopedic, mechanical or traumatic condition, 231 (24.1%) had an infection, 45 (4.7%) a hematologic or neoplastic disease, and 336 (35.1%) a variety of other conditions. Current clinic point prevalences for JRA, SpA, and collagen vascular diseases are 35.0, 16.9 and 17.7/100,000, respectively. The mean annual clinic referral incidences of JRA, SpA, and collagen vascular/connective tissue diseases were, respectively, 4.7, 5.2, and 1.7/100,000 children. CONCLUSION: Disease registries help establish the frequencies and spectrum of childhood rheumatic diseases and the role of pediatric rheumatology programs in evaluating and caring for children with a wide variety of conditions. Longitudinal disease registries aid in characterizing clinical, epidemiologic, and demographic features of childhood rheumatic diseases.

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.

Liem JJ, Rosenberg AM. · Section of Rheumatology, Department of Pediatrics, University of Saskatchewan, Saskatoon, Canada. · Clin Exp Rheumatol. · Pubmed #14611121 No free full text.

Abstract: OBJECTIVE: To define patterns of growth in juvenile rheumatoid arthritis (JRA) and to evaluate possible associated clinical and laboratory correlates. METHODS: The study population comprised 67 children with JRA who had been followed for 5 years or longer and whose follow-up period did not extend beyond 18 years of age. Height and weight z scores were calculated with reference to age-related standards for each of the annual follow-up intervals and correlated with JRA subtype, the presence of rheumatoid factor (RF), the erythrocyte sedimentation rate (ESR), alkaline phosphatase level (ALP) and medication history. RESULTS: Initial height-for-age (HAZ) scores for pauciarticular, polyarticular and systemic JRA onset groups (PaJRA, PoJRA and SJRA respectively) were +0.27, -0.07 and +0.40 respectively. A significantly lower HAZ score in the SJRA population compared to the PaJIA population first became apparent at year 2 and the difference was maintained throughout the 9-year follow-up period. A significantly lower HAZ score in the SJRA population compared to the PoJRA population first became apparent at year 6 and the difference was maintained until the ninth year. During the 9-year follow-up period, RF-positive children tended to have negative HAZ scores whereas RF-negative children tended to have positive HAZ scores. The SJRA onset group displayed significantly lower HAZ scores, as compared to the HAZ score at onset, for 7 of the 9 subsequent follow-up intervals. Only 2 patients had heights < 2SD below the mean at final determination. Delay in generalized linear growth occurred predominantly in the SJRA population and to a lesser degree in those with PoJRA associated with RF positivity. CONCLUSIONS: Delay in linear growth occurs in some children with JRA. Patients with pauciarticular and RF-negative polyarticular disease can have growth patterns similar to normal children. Children with RF-positive polyarticular and systemic JRA have more significant growth retardation that occasionally can be sustained and extreme.

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.

Rosenberg AM, Cordeiro DM. · Department of Pediatrics, University of Saskatchewan, Saskatoon, Canada. · J Rheumatol. · Pubmed #11036848 No free full text.

Abstract: OBJECTIVE: To compare the frequencies of antibodies to high mobility group proteins 1 and 2 (HMG-1, HMG-2) in boys and girls with juvenile idiopathic arthritis (JIA). METHODS: Sera of 60 children (44 girls, 16 boys) with JIA were screened for the presence of anti-nuclear antibodies (ANA) and antichromatin antibodies by indirect immunofluorescence (IIF) on eukaryotic cells and were assayed further for the presence of antibodies to purified HMG-1 and HMG-2 by enzyme immunoassays. RESULTS: A positive test for ANA was significantly associated with the presence of antibodies to both HMG-1 and HMG-2. There was a significant association between antibodies targeting the chromosomal regions of metaphase cells and antibodies to both HMG-1 and HMG-2. Females were significantly more likely than males to have ANA, and specifically more likely to have antibodies to HMG-1. There was a significant association between the presence of antibodies to HMG proteins and chromosomal reactivity detected by IIF on HEp-2 cells. CONCLUSION: The results suggest that females with JIA are more likely to be ANA positive than males and more likely than males to have antibodies to HMG-1.