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OBJECTIVE: This study was undertaken to compare trabecular bone mineral density (BMD) in premenopausal rheumatoid arthritis (RA) patients and normal age-matched controls. METHOD: A protocol was designed to record age, duration of disease, use of corticosteroids (CS) and/or slow-acting antirheumatic drug (SAARD) therapy together with duration of such therapy. BMD was measured using the Hologic QDR 1,000 dual energy X-ray absorptiometer. The first four lumbar vertebrae and the left femur were measured in 56 RA patients and 165 controls. Height and weight were measured. Comparisons were made between RA patients and controls, as well as between subgroups of RA patients based on CS therapy. RESULTS: Patients with RA had significantly lower BMD (P < 0.05) at all the sites than the normal controls. The mean duration of RA at the time of study was 60 months (standard deviation 58 months). Thirteen RA patients had used CS in doses less than 10 mg daily for 6 months or longer (mean 19 months), while 25 patients had been on SAARD for an excess of 6 months (mean 23 months). The CS-treated patients had significantly lower BMD than untreated subjects at the femoral neck and inter-trochanteric region (P < 0.05), but not at the lumbar spine. However, when compared with normal controls, the CS-treated subgroups had significantly lower BMD at the lumbar spine and all femoral areas. Trochanteric BMD was the best determinant of the RA group, with a sensitivity of 65% and specificity of 77%. The positive predictive value was 16%, while the negative predictive value was 10%. Using Bayes' theorem, the prevalence of osteopenia in RA was found to be 6%. CONCLUSION: We conclude that generalised bone loss is a systemic feature of RA and that loss at the spine and femur may be aggravated by CS therapy.

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OBJECTIVE: To determine the prevalence and spectrum of pulmonary abnormalities in patients with rheumatoid arthritis (RA) in a developing country. DESIGN: This was a prospective hospital-based survey of a randomly selected group of patients with RA who were seen in a rheumatic diseases unit. SETTING: Groote Schuur Hospital and Princess Alice Orthopaedic Hospital, Cape Town. PATIENTS: A group of 104 patients with RA were randomly selected from a total of 330 patients with RA who were seen in the rheumatic diseases unit. All the patients were interviewed and a clinical assessment, chest radiographs and pulmonary function tests were performed. RESULTS: Fifty-six patients (53.8%) had evidence of one or more current or previous pulmonary diseases: rheumatoid nodule in 1 (1%), bronchiectasis in 2 (1.9%), fibrosing alveolitis in 5 (4.8%), pneumonia in 5 (4.8%), asthma in 9 (8.7%), pleural disease in 17 (16.3%) and tuberculosis in 25 (24%). Excluding patients who were smokers or ex-smokers or who had coexistent pulmonary disease, there were 20 patients (19.2%) who had pulmonary abnormalities that could be attributed to RA: rheumatoid nodule in 1 (1%), fibrosing alveolitis in 5 (4.8%) (1 of whom also had pleural disease), pleural disease alone in 8 (7.7%), diffusion defect in 5 (4.8%) and airways obstruction in 1 (1%). CONCLUSION: This study provides clinical and lung function criteria that allow a clinically useful stratification of abnormalities in relation to a spectrum of common causes of pulmonary dysfunction that need to be distinguished from pulmonary abnormalities caused by RA. Pulmonary abnormalities are common and about 20% of RA patients may have an abnormality related to RA.

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The aim of this study was to assess the prevalence of and diagnostic role of metacarpal osteopenia in rheumatoid arthritis (RA) and to evaluate its detectability using receiver operating characteristic (ROC) analysis. Metacarpal bone mineral density was measured in 98 patients with classical RA using a computer-assisted measure of 6 metacarpal diameters (radiogrammetry) in patients aged less than 50 years. Sensitivity and specificity of the technique in discriminating the RA patients from 85 normal controls and osteopenic RA subjects from their normopenic counterparts, was determined by standard statistical techniques. Clinical, laboratory and radiological variables were compared in their ability to explain the variance of metacarpal bone density. The prevalence of metacarpal osteopenia in RA was 55%. Prolonged disease and reduced function significantly differentiated osteopenic from non-osteopenic RA patients. Discriminant analysis of RA and control groups showed that measurement of 6 metacarpals was more accurate than the 2nd metacarpal measurement alone in predicting the RA patients. The sum of 6 metacarpal combined cortical width (CCW) had a sensitivity of 61% and specificity of 68% in discriminating the RA patients from the controls. Receiver operating characteristics curves showed, not surprisingly, that objective measurement of bone diameters was superior to clinical or laboratory measures of disease activity in correctly classifying a randomly chosen RA patient as osteopenic or not. Metacarpal osteopenia is common in RA and it may be a useful measure of the disease in young patients.

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The recent demonstration of cytolytic mediators within synovial CD4+ T-cells of patients with rheumatoid arthritis (RA) has suggested an additional role for these cells in the pathogenesis of the disease. In this study we have investigated the function and regulation of antigen-specific class II-restricted cytotoxic T-cells from the synovial fluid (SFMNC) and peripheral blood (PBMNC) of 20 seropositive RA patients, and correlated in vitro findings with clinical data. Regulatory factors including prostaglandin E2 (PGE2), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were measured in cell supernatants. A diversity in SFMNC antigen-specific cytotoxicity that correlated with therapy and PGE2 production was found, and shown to be mediated by synovial prostanoid (products of cyclooxygenase metabolism) inhibition of effector function. Our findings indicate that SFMNC cytotoxicity may be important in the pathogenesis and treatment of RA. Cyclooxygenase inhibition as the sole treatment early in RA may reduce the potentially beneficial inhibitory effect of synovial prostanoids on antigen-specific SFMNC cytotoxicity.

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This study compares functional changes to change in measures of disease activity following the introduction of slow-acting anti-rheumatic drugs (SAARD) in patients with active rheumatoid arthritis (RA). Clinical and laboratory variables were simultaneously monitored at 6-monthly intervals, over approximately 18 months. Function was measured by a performance testing, the Keitel function index (KFI), which was divided into sections representing small and large joints [hand (HFI); wrist (WFI) and limb function index (LFI)]. One-hundred-and-fifteen patients were studied, of whom 21 were male. The mean age of the subjects was 49 yr (S.D. +/- 12) and mean duration of disease 7 yr (S.D. +/- 7). The mean KFI at entry was 38 (S.D. +/- 18) while at the end of the study it was 31 (S.D. +/- 17) (P < 0.0001). The change in KFI following therapy correlated with the change in Ritchie articular index (RAI) (r = 0.4; P < 0.0001), early morning stiffness (EMS) (r = 0.3; P = 0.004), swollen joint count (JC) (r = 0.4; P = 0.0005), C-reactive protein (CRP) (r = 0.2; P < 0.05) and Lansbury systemic index (LSI) (r = 0.35; P = 0.002), but not with change in Westergren erythrocyte sedimentation rate (ESR) or change in time to onset of fatigue. Multiple regression analysis showed that 32% of the variation in KFI at the end of the study could be predicted by a combination of ESR, sulphasalazine therapy, RAI, disease duration and chloroquine treatment at onset (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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This study was designed to evaluate the effects of low-dose corticosteroid (CS) therapy for rheumatoid arthritis (RA) and of high-dose CS therapy for systemic lupus erythematosus (SLE) on metacarpal bone mass in young (premenopausal) subjects. Ninety-eight patients with RA, 63 patients with SLE and 85 healthy controls of comparable age, race, sex and nutritional status were studied. Metacarpal bone mass was measured by radiogrammetry using a digitiser. In the RA patients, mean bone mass of CS-treated subjects (27%) was 52.31 g/cm2, while that of untreated subjects was 56.69 g/cm2 (P < 0.02). In the SLE group, mean bone mass of CS-treated subjects (76%) was 61.47 g/cm2 and that of untreated subjects 62.36 g/cm2 (P > 0.1). Although patients with SLE required larger cumulative doses of CS for longer periods, their bone mass was higher than that of the RA subjects (P < 0.01). None of the patients had femoral neck or vertebral crush fractures. In RA, bone loss was probably a feature of severe disease rather than of CS therapy.

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There is no ideal slow-acting antirheumatic drug. Therapy of rheumatoid arthritis (RA) is currently being modified, with strong recommendations to abandon the traditional pyramidal approach. The call is for a more aggressive, earlier approach to suppress inflammation. Combination therapy rather than the use of a single agent is advocated by some. Improved methods for assessing disease activity as well as measurement of outcome have been developed. Markers of poor prognosis have helped to define patients for earlier treatment. Comparison of toxicity among such a diverse group of drugs is probably best achieved with a toxicity index measuring the number of episodes expressed in terms of patient-years of exposure. Toxicity remains the commonest reason for discontinuing an agent, while remission beyond 36 months on therapy is uncommon, except with methotrexate. The profile of toxicity is clearly defined for individual agents, but combination therapy may reveal an entirely different set of toxic manifestations. There is an urgent need to develop a set of risk factors to predict toxicity in an individual patient. Juvenile chronic arthritis behaves differently from adult RA. Drug toxicity profiles are similar, but less common. Outcome is more difficult to measure, with the major impact of disease and therapy being on growth retardation.

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We report the prevalence of metacarpal cortical thinning in systemic lupus erythematosus (SLE). Fifty-eight ambulant female patients attending a lupus clinic (mean age 32.4 years), were found to have significant thinning of metacarpal cortices (p < 0.05) when compared with 63 normal females (mean age 34.1 years). However, metacarpal bone mass was within the normal range. Measurements were made at 6 metacarpals of the 2 hands using a computer-aided technique (digitized radiogrammetry). Femoral cortical width and Singh index at the left femur, as well as the vertebral index at L3 were also recorded. The trabecular indices were in the range of normality, but the SLE group had more patients in the immediately pre-osteopenic range. Metacarpal bone loss was not related to disease duration or corticosteroid therapy. The prevalence of osteopenia in SLE is probably underestimated and the pathogenesis is likely to be multifactorial.

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Sixty-five patients with rheumatoid arthritis (RA) (mean age 37.2 years) were compared with 71 controls (mean age 33.8 years). Anthropometric measurements included body diameters and skin-fold thickness at multiple sites, while biochemical markers of nutritional status included serum albumin, thyroxine-binding pre-albumin and retinol-binding globulin levels. None of the RA subjects was outside the range that extended 2 standard deviations above and below the normal control values for lean body mass. Discriminant analysis showed that corticosteroid therapy did not significantly influence skinfold thickness in RA. A combination of bi-acromial and bi-ankle diameters had a sensitivity of 70% and a specificity of 72% in differentiating the RA group, in whom disease activity had a greater effect on body diameters than corticosteroid therapy did. Differences related to functional impairment were a manifestation of disease activity rather than a direct effect on skinfold thickness or body diameters. According to anthropometric measurements in ambulant patients, RA does not result in malnutrition in young individuals.

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Osteoporosis in RA is mediated by numerous inflammatory substances. This study was undertaken to see if SAARD could modify the rate of metacarpal bone loss in RA. Combined cortical thickness (CCT) measured at the midshaft of the right second metacarpal was used to calculate bone mass (CA%) using a digitizer. Eighty-one subjects were studied, all of whom had at least three sets of hand X-rays, the last of which was approximately 18 months following initiation of SAARD therapy. There were 12 males and 69 females. The mean age at time of starting therapy was 51 (SD 12) years while the mean duration of disease at the time was 7.6 (SD 8) years. The mean time to referral for SAARD from the general clinic was 2.5 (SD 3) years. The percentage fall in bone mass prior to therapy was 2.51%/day compared to a gain of 0.6%/day after therapy (P less than 0.05). Forty-nine patients were aged over 50 years while 32 were 50 years or younger at the time of study. Comparison showed that in the pretreatment period, the rate of change in CCT and CA% was not significantly dependent age (P less than 0.1). During that therapy, the rate of change in CCT and CA% significantly different in the two age groups. Patients aged over 50 years continued to lose bone, but at a slower rate (P less than 0.05). Patients aged 50 years or less either stopped losing or gained metacarpal bone mass during the study period (P less than 0.005). The time to referral for SAARD and disease duration (comparable in the two age groups) did not have a significant effect on changes in CA% during therapy. Change in bone mass could be predicted by change in disease activity. We conclude that SAARD have a significant sparing effect on metacarpal osteoporosis in RA. This positive effect is masked by the overwhelming influence of age (and menopause) and could be missed. Metacarpal osteoporosis seems a pathophysiologically more useful measure of radiological change in RA than erosions or joint space narrowing.

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Two variants of the HLA-DR4-linked DQw3 allele, namely DQw7 and DQw8, were analysed in patients of mixed ancestry (Cape Coloureds) with rheumatoid arthritis and in healthy individuals from the same population group using a DQ beta-specific cDNA probe. The DQw7 allele, identified by 3,4 kb Hind III or 3,7 kb and 6,9 kb Bam HI DQ beta-specific restriction fragments, was expressed in 93% of DR4-positive patients (N = 15), compared with 12.5% DR4-positive normal individuals (N = 8). This DQ variant showed a highly significant association (relative risk = 98; P less than 0.0001) with rheumatoid arthritis in this population group and may play a role in their susceptibility to this disease.

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The prevalence of biochemical and immunological abnormalities was studied in a group of 256 patients with rheumatoid arthritis (104 coloureds, 100 whites and 52 blacks). The most common biochemical abnormalities detected were a reduction in the serum creatinine value (43.4%), raised globulins (39.7%), raised serum alkaline phosphatase level (42.3%), reduction in serum albumin value (8.1%), a mild rise in serum creatinine value (6.6%), and a raised serum gamma-glutamyltranspeptidase (GGT) level (6.5%). The prevalence of a rise in the GGT was less frequent than reported in other published studies. The immunological abnormalities noted were a positive rheumatoid factor (78.9%), positive anti-nuclear factor (36%), raised serum IgG (43.3%) and IgA (10.5%) values, positive smooth-muscle antibody (12.5%) and elevated double-stranded anti-DNA antibody levels (2.3%). Inter-group comparisons showed that the serum IgG and IgA and total globulins were significantly higher in blacks and coloureds than whites; these findings may be related to a higher prevalence of malnutrition and infection in childhood in these communities. There were no significant inter-group differences that could be attributed to rheumatoid arthritis.

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Therapeutic requirements were determined for a group of 256 patients with rheumatoid arthritis (RA) attending the Rheumatic Diseases Unit in Cape Town. Two-thirds of the patients had received or were receiving physiotherapy and half occupational therapy. Antidepressants had been taken by 24.2%, and 31.3% had received tranquillisers. All the patients had received non-steroidal anti-inflammatory drugs and 84 (32.8%) oral corticosteroids. One hundred and eighty-two patients (71.1%) had received one or more intra-articular or intralesional corticosteroid injections. A remittive agent or immunomodulatory drug had been prescribed to 163 patients (63.7%). Half the patients had undergone one or more surgical procedures for their RA. The outcome of management was favourable in the majority of patients, 78.1% having little or no functional disability. The management of patients with RA requires a team effort involving many different health professionals, and patients often require multiple drugs for the control of their disease.

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Radiogrammetry remains a convenient method of bone mass measurement. It is the only objective means of quantifying metacarpal osteoporosis (OP) in rheumatoid arthritis (RA). An automated technique using a digitizer (interfaced with an IBM PC) for measurement of combined cortical width (CCW) at the mid-shaft of six metacarpals was evaluated in three groups of individuals under 50 years of age (98 normal controls, 96 RA, 63 SLE). Intra-observer, inter-observer, and inter-institution reproducibility was assessed with a 'phantom' embedded in a rectangular mould of wax. Intra-patient variation was also assessed in RA patients seen on two occasions less than a month apart. Two hundred and fifty-seven subjects were studied. The method was found to be reproducible for a single observer, among five different observers and in two separate institutions. The RA subjects seen on two occasions showed no significant differences in CCW. The technique showed significant differences of CCW in the three groups of premenopausal subjects (controls; RA; SLE) studied (p less than 0.001). The six metacarpal bone mass was calculated in less than 5 min. The technique of digitized radiogrammetry is an improvement on the Vernier caliper technique. The method is useful for epidemiological cross-sectional studies and for evaluation of long-term radiological changes in RA.

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The nutritional status was assessed in a group of 220 patients with rheumatoid arthritis from three communities (coloured 89 patients, white 88 and black 43). The triceps skinfold (TSF) thickness, upper arm muscle circumference (UAMC), body mass index (BMI) and percentage of ideal body weight (% IBW) were measured and the serum albumin value determined. The mean age of the coloured patients was 49.8 years, white 57.7 years and black 44.8 years. Forty-five patients (20.5%) had a reduction of one or more anthropometric measurements (TSF, UAMC and/or %IBW) and a further 6 patients (2.7%) had a reduction of the serum albumin value alone. These 51 patients were considered to be malnourished and had a higher mean erythrocyte sedimentation rate and more severe functional disability than the remainder of the patients. The prevalence of malnutrition was lower if diagnosed only on abnormality of the TSF, UAMC and %IBW, since 25 patients (11.4%) had a reduction of only one measurement, 12 (5.5%) had a reduction of 2 and 8 (3.6%) had a reduction of all three measurements. Obesity (BMI greater than 30) was noted in 10.5% and there were no differences in the functional disability, disease activity and use of steroid therapy in the obese patients compared with the rest of the patients.

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