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Proinflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha), have been implicated in the dysregulation of bone and cartilage remodelling characteristic of rheumatoid arthritis (RA). With respect to bone remodelling, both of these cytokines have been shown to up-regulate the production of the receptor activator of nuclear factor-kappaB ligand, which acts to enhance osteoclastic bone resorption. TNFalpha stimulates differentiation of osteoclast progenitors into mature osteoclasts and IL-1 acts directly on osteoclasts to increase the bone-resorbing capacity of these cells. IL-1 and TNFalpha also adversely affect cartilage remodelling, although IL-1 is more potent on a molar basis. This cytokine not only increases production of factors that stimulate cartilage matrix degradation, but also inhibits the synthesis of type II collagen and proteoglycans. Enhanced understanding of the mechanisms underlying the processes of joint destruction will allow more selective and specific application of therapeutic agents that target these proinflammatory cytokines and, thus, more effective management of patients with RA and other inflammatory disorders.
To explore the associations between individual subdimensions of the health assessment questionnaire (HAQ) and clinical variables in patients with rheumatoid arthritis.
304 patients with rheumatoid arthritis (73% female, mean (SD) age, 58 (13) years; disease duration 6 (9) years, 69% rheumatoid factor positive) completed the HAQ for functional capacity (0-3) and a 100 mm visual analogue scale for pain. Grip strength, range of motion of the large joints, Larsen score for radiographic damage of hand and foot joints, and the number of tender and swollen joints were recorded. A logit regression model was used to study associations between subdimensions of the HAQ and other variables.
Mean (range) total HAQ score was 0.92 (0 to 2.88) and varied from 0.73 to 1.04 in the subdimensions. Disability was lowest in the "walking" and highest in the "reach" subdimension. Pain was an explanatory variable in all individual subdimensions. Decreased grip strength, limitation of shoulder and wrist motion, and a larger number of swollen and tender joints in the upper extremities were related to several subdimensions. A higher pain score and swollen joint count in the upper extremities, decreased grip strength, and limited motion of wrist, shoulder, and knee joints explained increased disability (higher total HAQ scores).
In patients with rheumatoid arthritis, pain and range of movements of joints have the greatest impact on individual subdimensions of the HAQ. Extent of radiographic damage in peripheral joints and the number of swollen and tender joints are of lesser importance for function.
Rheumatoid arthritis is a chronic inflammatory joint disease which affects the joints and soft-tissues of the foot and ankle. The aim of this study was to evaluate biomechanical foot function and determine factors associated with localised disease burden in patients with this disease.
Seventy-four rheumatoid arthritis patients (mean (standard deviation) age, 56 years (12); median (interquartile range) disease duration, 13 (5,19)) and 54 able-bodied adults (mean (standard deviation) age, 55 years (12)) completed the Leeds foot impact scale. Biomechanical foot function was measured using three-dimensional instrumented gait analysis. Disease activity score, the number of swollen and tender foot joints, and rearfoot and forefoot deformity were recorded. Sequential multiple linear regression was undertaken to identify independent predictors of foot disease burden.
The median (interquartile range) Leeds foot impact scale scores in the impairment and activity/participation subscales were 13 (10,14) and 17 (12,22) for the rheumatoid arthritis and 1 (0,3) and 0 (0,1) for the able-bodied adults, P<0.0001 both subscales. The patients had significantly higher numbers of swollen (P<0.0001) and tender foot joints (P<0.0001) and greater rearfoot (P<0.0001) and forefoot (P<0.0001) deformity. Rheumatoid arthritis patients walked slower (P<0.0001) and had altered biomechanical foot function. Sequential regression analysis revealed that when the effects of global disease activity and disease duration were statistically controlled for, foot pain, the number of swollen foot joints and walking speed, and foot pain and walking speed were able to predict disease burden on the Leeds foot impact scale impairment (P<0.0005) and Leeds foot impact scale activity/participation (P<0.0005) subscales, respectively.
In this cohort of rheumatoid arthritis patients, foot pain, swollen foot joint count and walking speed were identified as independent predictors of impairment and activity limitation and participation restriction. The foot disease burden model comprises important elements of pain, inflammatory and functional (biomechanical) factors.
To investigate the relationship between radiographic disease progression in the presence or absence of rheumatoid arthritis (RA) linked HLA-DRB1 alleles after early introduction of disease modifying antirheumatic drug therapy in patients with RA over a study period of 6 years.
One hundred nine patients of a trial comparing intramuscular (im) gold sodium thiomalate (GSTM) and im methotrexate (MTX) in early erosive RA were followed for 6 years with regular assessments of clinical and laboratory data and yearly radiographs of hands and feet, and they were typed for HLA-DRB1 genes. Radiographic progression was analyzed for an influence of rheumatoid factor (RF) status and HLA-DRB1 genes.
Twenty-seven patients (25%) were positive for two, 46 (42%) for one, and 36 (33%) for none of the disease linked alleles. A decrease of the rate of radiographic disease progression with treatment in this group of patients was reflected by the decline in the slope of the radiographic score. Seropositive patients (n = 71, 68%) had a significantly more destructive disease course than RF negative patients. In seropositive disease, patients with a "double dose" of RA linked alleles showed a tendency to greater progression during the first 12-24 mo of treatment, but no significant difference in the longterm radiographic outcome could be detected between subgroups defined by the presence or absence of HLA-DRB1 genes. There was no significant difference throughout the study period with respect to the clinical disease course as assessed by joint swelling, C-reactive protein, and erythrocyte sedimentation rate. The majority of the seronegative population (n = 38, 32%) had a benign disease course with the exception of patients (n = 6) with the double allele; they had radiographic disease progression comparable with the seropositive patients.
Our data do not provide evidence for a more aggressive disease course in patients bearing double RA linked HLA-DRB1 alleles.