Association of polymorphisms of the tumour necrosis factor receptors I and II and rheumatoid arthritis.
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OBJECTIVE: To assess the role of polymorphisms of the tumour necrosis factor (TNF) receptors, TNF-RI (p55) and TNF-RII (p75) in the susceptibility to and severity of rheumatoid arthritis (RA) in Dutch patients. METHODS: A total of 319 consecutive RA patients, and a cohort of 90 female RA patients with detailed 12-yr follow-up were genotyped for the TNF-RI exon 1 (+36 A to G) and TNF-RII 3' UTR (+1690 T to C) polymorphisms. RESULTS: The frequencies of the TNF-RI and TNF-RII polymorphisms were determined in both patient groups and healthy controls, but no significant differences were found. To determine the relationship of these polymorphisms to disease severity, the extent of joint damage in the cohort of 90 female RA patients was analysed. No differences in severity were observed. CONCLUSION: These TNF-RI and TNF-RII polymorphisms were not found to be associated with susceptibility to or severity of RA in the Dutch population. (+info)
Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity.
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OBJECTIVE: To determine whether functional cytokine gene polymorphisms influence disease susceptibility and phenotype in patients with psoriatic arthritis (PsA). METHODS: DNA was obtained from 147 PsA patients and 389 controls. Seven functional proinflammatory (interleukin-1beta [IL-1beta] +3953, IL-6 -174, tumor necrosis factor alpha [TNFalpha] -308, TNFbeta +252) and antiinflammatory (IL-10 -1082, IL-10 -592, IL-1 receptor antagonist [intron 2, 86 bp, variable-number tandem repeat]) gene polymorphisms were detected by polymerase chain reaction and restriction fragment length polymorphism assays. RESULTS: No significant difference in genotype frequencies was observed between the control and the PsA patient populations, and no association with Steinbrocker functional class, disease classification (polyarticular or oligoarticular), presence of spinal involvement, or age at PsA onset was observed. The presence of joint erosions was significantly associated with the TNFalpha -308 and TNFbeta +252 polymorphisms (P < 0.0001 and P = 0.0017, respectively). Frequencies of the TNFalpha -308 and TNFbeta +252 genotypes were also significantly different (P = 0.0078 and P = 0.0486, respectively) in a group of progressors (patients with early PsA in whom the number of joint erosions in the hands and feet increased over a median interval of 24 months) compared with a group of nonprogressors. Age at psoriasis onset was significantly associated with the TNFbeta +252 and TNFalpha -308 polymorphisms (P = 0.0003 and P = 0.0081, respectively). The TNFB2B2 and TNFalpha -308 AA genotypes were associated with the earliest mean ages at psoriasis onset. CONCLUSION: The TNFalpha -308 and TNFbeta +252 polymorphisms were significantly associated with age at psoriasis onset, presence of joint erosions in PsA, and progression of joint erosions in early PsA. TNF gene polymorphisms may be useful prognostic markers in PsA, and these results support the rationale for using anti-TNF treatment in patients with severe, progressive PsA. (+info)
Predicting mortality in patients with rheumatoid arthritis.
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OBJECTIVE: A number of different variables have been proposed as risk factors for mortality in patients with rheumatoid arthritis (RA), but limited prospective information on the magnitude of their effects is available. This study was undertaken to evaluate the relative predictive strength and usefulness of a wide range of variables on the risk of mortality in a large, long-term, prospectively studied cohort of patients with RA. METHODS: Over a 20-year period of followup beginning in 1981, 1387 consecutive RA patients were seen in a single clinic. A wide range of clinical and demographic assessments were recorded and entered into a computer database at the time of each clinical assessment. Assessment of predictive strength included determination of standardized and fourth-versus-first-quartile odds ratios (ORs), goodness-of-fit measures, and contributing fraction. RESULTS: The Health Assessment Questionnaire (HAQ) disability index was the strongest clinical predictor of mortality. A 1-SD change in the HAQ resulted in a much larger increase in the odds ratio for mortality compared with a 1-SD change in global disease severity, the next most powerful predictor of mortality (OR 2.31 versus 1.83). Considering the contributing fraction, mortality would be reduced by 50% for the HAQ and by 33% for global disease severity if patients in the fourth quartile for these variables could be switched to the first quartile. Global disease severity, pain, depression, anxiety, and laboratory and radiographic features were significantly weaker predictors. Disease duration, nodules, and tender joint count were clinical variables that provided very little predictive information. In multivariable analyses, HAQ and other patient self-report measures were significantly better predictors than were radiographic and laboratory variables. A single baseline observation provided the least information, with substantially increasing predictive ability associated with 1-year, 2-year, and all-time point followup observations (time-varying covariates). CONCLUSION: In this large 20-year study from routine clinical practice, the HAQ was the most powerful predictor of mortality, followed by other patient self-report variables. Laboratory, radiographic, and physical examination data were substantially weaker in predicting mortality. We recommend that clinicians collect patient self-report data, since they produce more useful clinical outcome information than other available clinical measures. (+info)
Interpreting radiographic data in rheumatoid arthritis.
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Plain film radiography is the preferred method for evaluating disease progression in rheumatoid arthritis and for establishing the efficacy of new disease modifying antirheumatic agents. However, the relative efficacy of these agents cannot be determined by comparing radiographic data from different studies, and a standardised system is needed. (+info)
Radiographic joint destruction in postmenopausal rheumatoid arthritis is strongly associated with generalised osteoporosis.
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OBJECTIVES: To investigate determinants of joint destruction and reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) not treated with bisphosphonates or hormone replacement therapy and to evaluate if there are common markers of erosive disease and bone loss. METHODS: BMD was measured using dual x ray absorptiometry and joint damage was examined by x ray examination according to the Larsen method in 88 patients with RA. Associations between BMD and Larsen score, and between demographic and disease related variables, including proinflammatory cytokines, HLA-DR4 epitopes, and markers of bone and cartilage turnover, were examined bivariately by simple and multiple linear regression analyses. RESULTS: 49/88 (56%) patients had osteoporosis in at least one site. Reduced BMD and increased joint destruction were associated with: at the forearm and femoral neck, high Larsen score, low weight, and old age (R(2)=0.381, p<0.001; R(2)=0.372, p<0.001, respectively); at the total hip, low weight, high Larsen score, and dose of injected glucocorticosteroids (R(2)=0.435, p<0.001); at the lumbar spine, low weight, reduced cartilage oligomeric matrix protein, and increased carboxyterminal propeptide of type I procollagen (R(2)=0.248, p<0.001). Larsen score was associated with long disease duration and increased C reactive protein (CRP) (R(2)=0.545, p<0.001). CONCLUSIONS: Osteoporosis is common in postmenopausal patients with RA. Low weight and high Larsen score were strongly associated with BMD reduction. Increased CRP and long disease duration were determinants of erosive disease in postmenopausal women with RA. These findings indicate common mechanisms of local and generalised bone loss in RA. (+info)
Bone edema scored on magnetic resonance imaging scans of the dominant carpus at presentation predicts radiographic joint damage of the hands and feet six years later in patients with rheumatoid arthritis.
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OBJECTIVE: Magnetic resonance imaging (MRI) is capable of revealing synovitis and tendinitis in early rheumatoid arthritis (RA), as well as bone edema and erosion. These features are visible before radiographic joint damage occurs. We sought to examine whether MRI of one body region (the wrist) can be used to predict whole-body radiography scores reflecting joint damage at 6 years. METHODS: We conducted a 6-year prospective study of a cohort of patients who fulfilled the criteria for RA at presentation, using clinical parameters, radiographs, and MRI scans of the dominant wrist. Of the 42 patients enrolled at baseline, full MRI, radiographic, and clinical data were available for 31 at 6-year followup. MRI scans were scored by 2 radiologists, using a validated scoring system. Radiographs of the hands and feet were graded using the modified Sharp scoring method. MRI and radiography scores obtained at baseline and 6 years were compared, and baseline MRI scores were examined for their ability to predict radiographic outcome at 6 years. RESULTS: At 6 years, the total Sharp score correlated significantly with the total MRI score and the MRI erosion score (r = 0.81, P < 0.0001 and r = 0.79, P < 0.0001, respectively). The 6-year Sharp score also correlated with the baseline total MRI and MRI erosion scores (r = 0.56, P < 0.0001 and r = 0.33, P = 0.03, respectively). MRI synovitis and bone edema scores remained constant for the group as a whole over 6 years, but bone erosion scores progressed (P = 0.0001), consistent with radiographic deterioration. Erosions on 6-year MRI scans were frequently preceded by MRI bone edema at baseline (odds ratio 6.5, 95% confidence interval 2.78-18.1). Regression models indicated that the baseline MRI bone edema score was predictive of the 6-year total Sharp score (P = 0.01), as was the C-reactive protein (CRP) level (P = 0.0002). Neither shared epitope status nor swollen or tender joint counts predicted radiographic outcome in this cohort. A model incorporating baseline MRI scores for erosion, bone edema, synovitis, and tendinitis plus the CRP level and the erythrocyte sedimentation rate explained 59% of the variance in the 6-year total Sharp score (R(2) = 0.59, adjusted R(2) = 0.44). CONCLUSION: MRI scans performed at the first presentation of RA can be used to help predict future radiographic damage, allowing disease-modifying therapy to be targeted to patients with aggressive disease. (+info)
Sex differences in hip osteoarthritis: results of a longitudinal study in 508 patients.
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OBJECTIVE: To evaluate sex differences in the clinical and structural presentation, and natural history of hip OA. METHODS: A multicentre, prospective, longitudinal, five year follow up study of 508 patients (302 women, 206 men, mean age 63 (7) years) with painful hip OA. Data collected were baseline demographics, symptomatic, therapeutic, and structural variables; symptomatic variables and changes in joint space width (JSW) during the first year's follow up; requirement for total hip arthroplasty (THA) between the end of the first and fifth years. STATISTICAL ANALYSIS: evaluation of sex differences (a) at baseline, in the main characteristics of hip OA using multivariate logistic regression; (b) during the first year of follow up, in the radiological progression of the disease; (c) during the five years of follow up, in the requirement for THA using Kaplan-Meier curves and the log rank test, and of the parameters related to THA, using a multivariate Cox analysis. RESULTS: At entry, women presented more frequently than men with polyarticular OA (mean (SD) articular score 306 (162) v 235 (127)), and superomedial migration of the femoral head (40% v 19%), and had more severe symptomatic disease (patient's overall assessment 46 (23) v 40 (26)). The change in JSW did not differ between women and men after one year, but a greater proportion of women had rapid structural progression (OR=2.34, 95% CI 1.1 to 5.2). THA was performed more often in women. Multivariate analysis suggested that the decision to perform surgery was related more closely to the symptomatic and structural severity of the disease than to the sex of the patient. CONCLUSION: Hip OA in women is more frequently part of a polyarticular OA, and displays greater symptomatic and structural severity. (+info)
Precision and accuracy of joint space width measurements of the medial compartment of the knee using standardized MTP semi-flexed radiographs.
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OBJECTIVE: To quantify the precision and accuracy of measurements of joint space width (JSW) and joint space narrowing (JSN) from the medial tibiofemoral compartment of knee radiographs using a simple and easily adaptable protocol. METHODS: Radiographs of a caliper (a surrogate for JSW) were obtained to determine the precision limits of the system under ideal conditions. Bilateral knee radiographs from 10 healthy volunteers were obtained at three different times using the metatarsophalangeal (MTP) semi-flexed view posterior-anterior position without fluoroscopy. A backlit digitizing tablet and three manual methods were used to measure JSW and analyses of precision were performed. The accuracy of measuring change in JSW (a measure of JSN) was estimated from radiographs of cadaver knees that were placed in a servo-hydraulic device that moved the femur relative to the tibia through known intervals. RESULTS: Radiographic measurements of the caliper inter-blade distance were comparable to the resolution limits of the backlit digitizing tablet (0.025 mm). Repeated radiography of healthy subject knees produced JSW standard deviation (SD) measurements of 0.08 mm by the median SD method, and 0.11 mm by repeated measures analysis. The accuracy of JSN measurements in the cadaver knees as a mean difference from the known reference value was 0.09 mm. CONCLUSION: The results indicate a high level of precision in measurements of JSW from MTP semi-flexed view knee radiographs of normal volunteers. Reproducibility was attained through careful subject positioning without fluoroscopy and the use of a backlit digitizing tablet. From the cadaver study we can predict that greater than 0.13 mm of measured JSN represents actual or true change in JSN. This radiographic technique can be used as a primary measure for early knee osteoarthritis (OA) when cartilage thickness is decreasing and limited bony remodeling has occurred. (+info)