Showing papers in "The Journal of Rheumatology in 1989"

Estimates of the prevalence of selected arthritic and musculoskeletal diseases in the United States.

Abstract: The National Arthritis Data Workgroup focused its studies primarily on joint disease with the addition of osteoporosis which is a frequently occurring musculoskeletal condition and public health problem. We used national data sets as well as published studies to estimate prevalence in the United States. We report on prevalence rather than incidence because of the difficulty in defining the point of onset and because primary national data sources currently available are concerned with disease prevalence.

Comparison between 3 diagnostic criteria for mixed connective tissue disease. Study of 593 patients.

Abstract: We tested patients with a well defined connective tissue disease (CTD) against 3 different sets of criteria for mixed connective tissue disease (MCTD). Included were 200 patients with systemic lupus erythematosus (SLE), 80 with MCTD, 100 with rheumatoid arthritis (RA), 80 with scleroderma, 53 with dermato/polymyositis (DM/PM) and 80 with primary Sjogren's syndrome (SS). The 3 sets of criteria fared similarly in capturing nearly all MCTD patients. They also were similar in ruling out most of the other CTD except for 11 patients with SLE, 36 with scleroderma, 13 with DM/PM and 3 with SS who fulfilled the category of possible MCTD included in the set of criteria proposed by Sharp. Because the set of criteria we proposed includes only 5 clinical manifestations (edema of the hands, synovitis, myositis, Raynaud's phenomenon, and acrosclerosis) whereas the other 2 sets include 15 and 13, respectively, it would seem that the 5 included in our criteria are core manifestations of MCTD. Of the 80 patients with MCTD 32 had all 5, 38 had 4, and 10 had 3 of these manifestations. The sensitivity of 3 or more of these clinical criteria for MCTD was 100%, whereas the specificity which, with the clinical criteria was 91.8%, rose to 99.6% with the presence of anti-RNP antibody. However, because testing of our criteria was made internally, they should be further tested, along with the other 2 sets of criteria by unrelated groups of clinical investigators, perhaps in a multicenter study.

Primary antiphospholipid syndrome.

Abstract: An antiphospholipid antibody (APLA) syndrome has been proposed for those patients with systemic lupus erythematosus (SLE) or with other connective tissue diseases who have APLA and manifestations that seem related to their effect (venous thrombosis, arterial occlusions, thrombocytopenia, hemolytic anemia, recurrent fetal loss, leg ulcers, and livedo reticularis). Occurrence of a primary antiphospholipid syndrome has also been mentioned but not defined. We present 9 young patients who had at least 2 of the clinical manifestations that have been related to high titers of APLA, but had neither SLE nor other recognizable connective tissue disease. We propose criteria for diagnosis of such a primary antiphospholipid syndrome and discuss the possible mechanisms whereby a single autoantibody can cause systemic disease.

Evidence of significant radiographic damage in rheumatoid arthritis within the first 2 years of disease.

Abstract: Quantitative radiographic scores for joint space narrowing erosion, and malalignment in the hands and wrists of 200 patients with rheumatoid arthritis (RA) were significantly correlated with duration of disease. Nonetheless, most of the 42 patients who reported disease for less than 2 years had evidence of radiographic damage, including 35 with joint space narrowing, 28 with erosions but only one with malalignment. Significant radiographic damage in the absence of malalignment may be seen in many patients within the first 2 years after presentation of RA.

Remodeling the pyramid--a concept whose time has come.

Abstract: It is clear that the traditional treatment program, as illustrated by the pyramid, does not suppress inflammation in most patients with RA to an extent sufficient to prevent joint damage. There is no basis for the concept that slow acting drugs are uniquely disease modifying. Disease modification correlates best with control of inflammation. Contrary to popular wisdom, this has been best demonstrated with prednisone. The arbitrary concept of a drug being either antiinflammatory or disease modifying serves no useful purpose and should be dropped. Many medications provide incomplete or temporary suppression of inflammation, presumably by differing mechanisms of action. Based on this rationale, a therapeutic program is proposed, employing a combination of drugs to control inflammation in the critical early stages of RA. With this step-down bridge concept, medications are sequentially withdrawn in contrast to the traditional pyramid, in which they have been sequentially added. Our early experience with patients indicates that toxicity is no greater problem with combined drugs than with the same drugs used individually. Time and comparative observations will be needed to show the optimum combination of drugs and whether the step-down bridge concept will achieve the sought-for and presently unobtained goal of early and sustained control of inflammation, improved quality of life, and prevention of bone and joint damage.

Urinary hydroxy-pyridinium crosslinks provide indices of cartilage and bone involvement in arthritic diseases.

Abstract: The urinary concentrations relative to creatinine of the collagen crosslinks, pyridinoline (PYD) and an analogue derived specifically from bone collagen, deoxy-pyridinoline (DPD), were measured using a high performance liquid chromatography (HPLC) technique in 41 patients with rheumatoid arthritis (RA) and 45 patients with osteoarthritis (OA), and were compared with values of 118 healthy control individuals. The levels of DPD were increased significantly in both RA and OA suggesting accelerated bone degradation in both disease groups. PYD concentrations were also significantly increased in both diseases, but larger increases were detected in patients with RA, for which this index correlated with clinical measures of joint involvement and biochemical variables of inflammatory activity. Cross-sectional studies showed that treatment with disease modifying drugs (gold and D-penicillamine) led to decreased crosslink levels but longterm corticosteroids resulted in increased urinary crosslinks, probably due to the induction of bone resorption. Measurement of both pyridinium crosslinks in urine may therefore provide information on the stage, activity, level of bone involvement and efficacy of drug therapy in arthritic diseases.

Treatment of refractory rheumatoid arthritis--the thalidomide experience.

Abstract: In an open study, 17 patients (16 women, 1 man) with refractory or severe rheumatoid arthritis were treated with thalidomide. Two withdrew from the study in the first weeks. Thirteen patients received 531 +/- 63 mg/day of thalidomide for 18.8 +/- 8.8 weeks; in 2 the dose was 300 mg/day during 62 and 65 weeks. Seven patients attained complete remission, 5 partial remission, and the last 3 no improvement at all. Remissions lasted 6 years in 1 patient, 2 years in 3, 1 year in one, and varied between 8 months and 8 weeks in 7. After relapse, 5 patients received a 2nd course of treatment and attained remission again. This lasted 24, 10, and 9 months in 3; two are taking 100 mg/day of thalidomide as a maintenance dose and remain asymptomatic after 36 and 30 months. The side effects were drowsiness, constipation, hard swelling of the lower limbs, erythema of the face and limbs with local pruritus or burning sensation, hair loss, cough, nasal obstruction, fever, and skin and mucosal dryness. In 8 patients there was mild eosinophilia (less than 10%) and in 2 leukopenia. A 33-year-old woman showed amenorrhea up to 2 months after stopping treatment. After a 2nd course of treatment, 2 patients developed peripheral sensory neuropathy, which resolved spontaneously in 6 months. We believe these findings justify controlled trials with this agent.

Oligolamellar lubrication of joints by surface active phospholipid.

Abstract: Six studies have been undertaken to test the hypothesis that oligolamellar phospholipid adsorbed to the articular surface contributes to joint lubrication. Synovial fluid (SF) proved highly surface active, rapidly depositing phosphatidylcholine (DPPC) on glass surfaces, rendering them hydrophobic--a property of well rinsed articular surface removable by the same fat solvents known to increase joint friction by 150%. Electron microscope studies demonstrated lamellar bodies (surface active DPPC) on the articular surface and in SF and lamellated phospholipid in light scrapings of joint surfaces. These were consistent with the quantity of phospholipid recovered by solvent rinsing. Friction measurements in vitro demonstrated excellent boundary lubrication imparted by multimolecular layers of DPPC under high load with coefficients of kinetic friction reaching physiological ranges (0.002-0.005).

The prevalence of chondrocalcinosis in the elderly and its association with knee osteoarthritis: the Framingham Study.

Abstract: Chondrocalcinosis and osteoarthritis (OA) both increase in prevalence with age, yet previous studies assessing their association have often been too small to adjust for age and have had biased selection of subjects. We assessed the prevalence of chondrocalcinosis and its link with OA in the Framingham Knee Osteoarthritis Study, a large population based study of the elderly. After controlling for age, we found a modestly increased rate of radiographic OA in those with chondrocalcinosis (relative risk = 1.52 (95% CI 1.22, 1.90). There was a similar link between chondrocalcinosis and severe radiographic OA (relative risk = 1.52). Chondrocalcinosis was positively associated with both symptomatic and asymptomatic radiographic OA. The proportion of radiographic OA potentially attributable to chondrocalcinosis was only 4.4%. Our results confirm that chondrocalcinosis is significantly associated with OA after controlling for age, but they also suggest that chondrocalcinosis and OA increase independently with age.

Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis.

Abstract: Forty-six patients with recalcitrant rheumatoid arthritis entered a trial encompassing a 2-week inpatient period plus a 16-week, randomized double blind, parallel study comparing placebo, 5 mg/m2 and 10 mg/m2 oral weekly methotrexate (MTX). An additional 6 patients, given 20 mg/m2 MTX, contributed to the toxicity, but not the efficacy analysis. All patients had "failed" either gold or D-penicillamine. A linear dose response relationship (placebo vs 5 mg/m2 vs 10 mg/m2) was found for 5 of 11 outcome variables: patient pain and patient global scale, physician global scale, joint tenderness count and activity of daily living scale (p less than 0.05 for each). Gastrointestinal toxicity (p = 0.002), dyspepsia (p less than 0.03) and stomatitis (p less than 0.09) occurred more commonly with MTX, and a general trend, although not significant, was found toward a dose toxicity relationship.

Pulmonary hypertension in systemic lupus erythematosus.

Abstract: A prospective study was performed in our center on 60% (n = 36) of patients with systemic lupus erythematosus (SLE) to determine the prevalence and severity of pulmonary hypertension. Twenty-six healthy subjects of similar age and sex served as controls. Pulmonary artery systolic pressure was calculated from the sum of the peak tricuspid insufficiency Doppler pressure gradient and an estimate of right atrial pressure based on inferior vena cava size and its degree of inspiratory collapse. Five patients with SLE (14%) had pulmonary hypertension, defined as pulmonary artery systolic pressure greater than 30 mm Hg. Cardiac indices determined by planimetry of biplane apical 2-dimensional echocardiographic images were low or normal in the patients with pulmonary hypertension implying increased pulmonary vascular resistance as the etiology for elevated pulmonary artery pressure. The mean pulmonary artery systolic pressure in patients with SLE was 25 +/- 10 mm Hg vs 20 +/- 2 in controls (p = 0.002). No control had a pulmonary artery systolic pressure greater than 23 mm Hg. Patients with pulmonary hypertension had a shorter duration of SLE and steroid therapy and a higher prevalence of cytotoxic treatment and Raynaud's phenomenon in comparison to those with normal pulmonary artery pressures. The prevalence of systemic hypertension, interstitial lung disease, pleurisy, pericarditis, cutaneous manifestations, arthritis, renal disease, central nervous system involvement, and hematologic abnormalities was similar in patients with SLE with normal and elevated pulmonary artery pressure. Our study suggests that pulmonary hypertension in SLE is common but usually mild.

The economic impact of the rheumatic diseases in the United States.

Abstract: We review the literature and analyze data from the National Health Interview Survey to provide estimates of the economic cost and social impacts of the rheumatic diseases in the United States. Rheumatic diseases had an economic impact in 1980 of 21 billion dollars due to expenditures for health care and lost wages, an amount equal to 1% of gross national product. These conditions are responsible for 5% of all hospital discharges, 10% of all hospital procedures, and 9% of all physician visits. They are also responsible for over 2 million persons being unable to do major activities, for 5 million being limited in other ways, and for at least 1 million being severely limited in the ability to perform activities of daily living. As great these impacts would appear to be, they are likely to grow since the aging of the population increases both the prevalence and severity of impact of the rheumatic diseases.

Effects of galactose depletion from oligosaccharide chains on immunological activities of human IgG.

Abstract: We previously reported a decrease in the content of galactose residues in oligosaccharide chains of serum IgG from patients with rheumatoid arthritis, which was presumed to affect the 3 dimensional structure of CH2 domain. In the present study, we prepared the galactose depleted IgG (agalacto IgG) and characterized its immunological activities. Significant reduction in Clq binding and Fc receptor binding was observed in agalacto IgG. However, IgM rheumatoid factor binding and protein A binding were the same as with intact IgG. Our results implied the biological function of the carbohydrate moiety of human IgG.

Antiphospholipid arterial vasculopathy.

Abstract: We describe 3 relatively young patients who developed arterial occlusions in a limb requiring amputation. All 3 had antiphospholipid antibodies (APLA). In one, these appeared as part of the clinical and serologic spectrum of systemic lupus erythematosus and in the other 2 as a component of a primary antiphospholipid syndrome. Their arterial angiograms showed gradual narrowing of the arterial lumen and the histopathologic study showed striking intimal and medial proliferation as well as some increase in thickness of the adventitia. There was little evidence of thrombosis but in the 2 patients who were amputated early there was mononuclear cell infiltrate of the large arteries and in all 3 there was also leukocytoclastic vasculitis in the skin and/or muscle. We believe this represents a new form of vasculopathy, probably related to the presence of APLA, possibly triggered by the occurrence of vasculitis.

Increased carbonyl content of proteins in synovial fluid from patients with rheumatoid arthritis.

Abstract: The carbonyl content of proteins in the synovial fluid (SF) of patients with rheumatoid arthritis was significantly (p less than or equal to 0.10) elevated over levels in the SF of patients with osteoarthritis (OA). Other indicators of oxidative damage including catalse, ceruloplasmin, ferritin and superoxide dismutase also showed statistically significant differences (p less than or equal to 0.05) compared to patients with OA.

Altered sympathetic nervous system response in patients with fibromyalgia (fibrositis syndrome).

Abstract: Twenty-seven female patients with fibromyalgia and 29 female healthy controls underwent an auditive stimulation test and a left hand cold pressor test at 10 and 4 degrees C. The microcirculatory changes observed, indicate that, as a response to 80 dB, 1000 Hz, 2 seconds sounds and cooling with associated pain, the vasoconstrictory responses are less in patients with fibromyalgia than in normal controls. This could indicate altered sympathetic nervous activity in patients with fibromyalgia and that the cutaneous manifestations previously interpreted as Raynaud's phenomenon should be reconsidered.

The prevalence of anticardiolipin antibodies in a healthy elderly population and its association with antinuclear antibodies.

Abstract: The presence of anticardiolipin antibodies (aCL) has been associated with arterial and venous thrombotic events in connective tissue diseases. Previous investigations have suggested an increased incidence of aCL in the elderly population. We have studied the prevalence of aCL in large groups of 300 healthy elderly (mean age 70) and 543 younger subjects. aCL were determined by ELISA for the presence of IgG and IgM antibodies and was detected in 37 individuals (12%). This compared with an overall prevalence in a younger population of 2%. In addition, aCL was detected in 23% of elderly individuals who were also positive test for antinuclear antibodies (ANA). There was, however, no correlation with the presence of rheumatoid factor or lymphocytotoxic antibodies in this elderly group. Therefore, aCL have increased prevalence in an elderly population, and were associated with a positive test for ANA.

Skin hypersensitivity to streptococcal antigens and the induction of systemic symptoms by the antigens in Behçet's disease ― A multicenter study

Abstract: Twenty-four different antigens from 6 strains of streptococcus were prepared for skin testing and delayed hypersensitivity testing. The induction of Behçet's disease symptoms by these antigens was studied. Delayed skin reactions to whole cells and cell walls of streptococci were frequently observed in Behçet's disease, but only a few skin reactions were observed in other diseases and healthy controls. The skin reactions to the other bacteria were also strong in Behçet's disease, but the differences between Behçet's disease and the other diseases were not significant. Interestingly, the induction of systemic Behçet's disease symptoms was observed after the streptococcus skin test in 15 of 85 cases tested, but no case of induction by the other bacteria was observed. Our study supports the possible pathogenetic role of certain streptococcal antigens in Behçet's disease.

Electron microscopic studies of muscle biopsy in primary fibromyalgia syndrome: a controlled and blinded study.

Abstract: Trapezius muscle biopsy was carried out in 21 patients with primary fibromyalgia syndrome (PFS) and 11 healthy controls, and assessed blindly by electron microscopy. Common findings in both the PFS and control groups were mild myofibrillar separation, papillary projections and subsarcolemmal accumulation of glycogen. However, the differences between the 2 groups were not statistically significant in any of the findings.

Short term effects of ibuprofen in primary fibromyalgia syndrome: a double blind, placebo controlled trial.

Abstract: Therapeutic effects of ibuprofen were evaluated in 46 patients with primary fibromyalgia syndrome in a double blind, placebo controlled study for 3 weeks and in an open trial for another 3 weeks. Several features of primary fibromyalgia syndrome, including number of pain sites, fatigue, swelling feeling, and tender points significantly improved over time in both groups. However, no significant differences were found between the ibuprofen and placebo groups. Improvements in fibromyalgia features might have occurred as a result of physician or study interactions (i.e., an intervention effect). An important observation in our blinded study was that tender point sites among patients with fibromyalgia were significantly (p less than 0.001) consistent at 3 as well as 6 weeks when compared with the baseline.

Characterization of uveitis associated with spondyloarthritis.

Abstract: At a university based referral clinic, 236 consecutive patients with uveitis were evaluated by a rheumatologist; 13% of these patients had spondyloarthritis including 17 patients with Reiter's syndrome and 13 patients with ankylosing spondylitis (AS). The uveitis associated with AS or Reiter's syndrome had distinctive characteristics; it was acute in onset, unilateral, frequently recurrent, and spared the choroid and retina. Two thirds of the patients with spondyloarthritis were not suspected or known to have Reiter's syndrome or AS before referral. Since many diseases of the joints also affect the uveal tract, the recognition of the specific pattern of uveal involvement can greatly facilitate the differential diagnosis.

The origins of depressed mood in rheumatoid arthritis.

Abstract: Most studies that have considered depressed mood in patients with rheumatoid arthritis have failed to analyze the relative contribution of psychological, social and disease state variables. Using multivariate statistical analyses we identified the role played by demographic, disease related, disability and social variables. Together these variables accounted for 44% of the variation in depressed mood. Demographic factors, disability measures, disease duration, social isolation and economic deprivation all made significant contributions to the explanation of depressed mood. The results of our study underline the importance of examining a wide range of factors in order to consider their relative influence on psychological state.

Fall in antiphospholipid antibody at time of thromboocclusive episodes in systemic lupus erythematosus.

Abstract: A relationship between antiphospholipid antibodies (APLA) and thromboses has been proposed in patients with systemic lupus erythematosus (SLE). In most instances, however, the thromboocclusive episodes were historic and did not coincide with the study of APLA. We studied 6 patients with SLE who, having had sequential determinations with high levels of APLA, were found to have falls in them coincident with thromboocclusive episode(s) and not attributable to treatment. Because our patients had recurrent thrombotic episodes, higher previous and subsequent titers of APLA, and other manifestations that have been similarly proposed to associate with APLA, our observations may indicate consumption of the APLA in the course of the thromboocclusive episode.

Adjunctive use of hydroxychloroquine in childhood dermatomyositis.

Abstract: We examined retrospectively the use of hydroxychloroquine in 9 patients with childhood dermatomyositis (DM). These patients had an incomplete response to corticosteroid therapy or had disease exacerbation when attempting to taper corticosteroids. They received hydroxychloroquine in a mean dosage of 3.6 mg/kg (range 2-5 mg/kg) while maintaining corticosteroid therapy. Significant improvement was noted at 3 months of therapy in rash (p less than 0.0001), proximal (p = 0.0004) and abdominal muscle strength (p = 0.0001) and at 6 months of therapy in reduced prednisone dosage (p less than 0.02). These data suggest hydroxychloroquine may be helpful in some patients with childhood DM, particularly those with prominent cutaneous disease or significant corticosteroid toxicity.

Axial involvement in the seronegative enthesopathy and arthropathy syndrome and its progression to ankylosing spondylitis.

Abstract: We studied prospectively the clinical and radiographic features of sacroiliac and spinal involvement in 20 patients with seronegative enthesopathy and arthropathy. This group was compared with 25 patients with a polyarticular onset form of juvenile rheumatoid arthritis (JRA) and 28 with definite ankylosing spondylitis (AS) of juvenile onset. A significant increasing proportion of patients with seronegative enthesopathy and arthropathy developed back complaints and radiographic sacroiliitis fulfilling the diagnostic criteria for AS from the 3rd-5th year of disease (47.1-75.0%) and thereafter (92.3%). Back complaints were rarely seen in JRA and, furthermore, sacroiliitis of the AS type nerve occurring in this group. There were no significant differences between the group with seronegative enthesopathy and arthropathy and juvenile AS, either at onset or through the years. Clinical and radiographic assessment of axial involvement in children at risk should include a careful analysis of symptoms, periodical measurements of the spinal flexion and, starting from the 3rd year, radiographs of the pelvis.

Liver biopsy findings in patients with rheumatoid arthritis undergoing longterm treatment with methotrexate.

Abstract: Ten histological criteria were evaluated semiquantitatively in the liver biopsies of 60 patients with rheumatoid arthritis (RA) before initiation of methotrexate (MTX) and were compared with 40 biopsies taken during MTX treatment (mean cumulative dose 1.322 mg). Mesenchymal changes (Kupffer cell proliferation, portal tract infiltration) and parenchymal alterations (nuclear variability, ballooning, fatty infiltration) were very common without statistically significant difference between the 2 groups. Slight periportal and/or portal fibrosis was present in 25% of patients without statistical difference between groups. Central fibrosis occurred in 13.5-12.5%. We conclude that liver abnormalities in RA are not related to MTX treatment.

Late onset peripheral spondyloarthropathy.

Abstract: After studying 10 cases, we describe a form of late onset, B27 related disease. The patients were men over 50 with minimal involvement of the axial skeleton, mild oligoarthritis of the lower limbs, paucicellular joint fluids and fibrosis on synovial biopsy. In contrast, they appeared severely ill with erythrocyte sedimentation rates elevated and a large amount of pitting edema. Their response to nonsteroidal antiinflammatory drugs was poor. The disease did not abate for from one to several years. Five patients later presented bilateral sacroiliitis and 4 of these developed ankylosing spondylitis (AS). This clinical presentation of AS may owe its distinctive features to its late onsets.

Suppression of acute and chronic inflammation by dietary gamma linolenic acid.

Abstract: We examined the effect of diets enriched in gamma linolenic acid (GLA) on acute inflammation induced by monosodium urate crystals, and on subacute and chronic inflammation induced by complete Freund's adjuvant in the rat subcutaneous air pouch and in rats with adjuvant induced arthritis. Diets were enriched (15% fat) with borage seed oil (23% GLA) or safflower oil (less than 1% GLA). Diets enriched with GLA suppressed inflammation markedly in all models, whereas the safflower oil diet did not influence the inflammatory response. The degree of inflammation was quantified by measuring pouch exudate cell concentration, lysosomal enzyme activity, volume, protein concentration and prostaglandin E2 and leukotriene B4 concentrations. In the chronic air pouch model, the pouch lining was thickened, invaded by mononuclear cells and exhibited proliferation of lining cells 14 days after adjuvant injection. The lesion was far less severe and usual pouch lining architecture was maintained in animals given dietary GLA. Livers of rats fed borage seed oil were enriched in GLA and dihomo gamma linolenic acid (DGLA), and the DGLA/arachidonate ratio was increased 5-fold compared with animals fed safflower oil. Enrichment of diet with plant seed oils rich in GLA may provide a way to alter generation of prostaglandins and leukotrienes and to influence acute and chronic inflammatory responses.

The mechanism of chondrocyte hydrogen peroxide damage. Depletion of intracellular ATP due to suppression of glycolysis caused by oxidation of glyceraldehyde-3-phosphate dehydrogenase.

Abstract: Exposure of articular cartilage to H2O2 in vitro inhibits proteoglycan synthesis in a fashion which parallels the inhibition which occurs in cartilage in animal models of acute inflammation. Our study shows that exposure to H2O2 also inhibits other chondrocyte functions, including total protein and DNA synthesis. Since these intracellular biosynthetic processes require adenosine triphosphate (ATP), the effect of exposure of H2O2 on chondrocyte ATP was measured. Exposure to H2O2 caused an immediate (less than 2 min) dose dependent decrease in cartilage ATP levels--found to be due to the oxidative inactivation of glyceraldehyde-3-phosphate dehydrogenase (G-3-PDH). We suggest that intrachondrocyte oxidant damage occurs through oxidation of the sensitive thiol (-SH) residue at the active center of G-3-PDH, with subsequent reduction in the rate of glycolytic ATP synthesis and the intracellular concentration of ATP which is required for DNA, protein, proteoglycan and hyaluronic acid synthesis.