Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
9572710 Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxic 1998 Apr OBJECTIVES: To provide an update of the current knowledge of the mechanism of action of low-dose methotrexate (MTX) in the treatment of patients with rheumatoid arthritis (RA), with an emphasis on the mechanisms involved in toxicity. We also considered strategies currently used to prevent or decrease toxicity of MTX. METHODS: We reviewed the literature dealing with the subjects of MTX treatment of RA, the mechanisms of action of low-dose MTX regarding efficacy and toxicity, and strategies used to prevent or decrease MTX toxicity. RESULTS: MTX is a fast working and effective second-line antirheumatic agent (SLA). Its use is limited mainly because of side effects. The mechanisms of action regarding efficacy and toxicity are probably determined by different metabolic pathways. Recent data indicate that the antiinflammatory effect of MTX is mediated by adenosine. However, MTX side effects can only partly be explained by folate antagonism and may also depend on its action on other related metabolic pathways. The latter include the homocysteine-methionine-polyamine pathway and purine metabolism. Variants in these metabolic routes (ie, the C677T mutation in the methylene-tetrahydrofolate reductase [MTHFR] gene), may predispose to the development of side effects. Currently the most promising strategy to decrease or prevent toxicity of MTX is concomitant prescription of folic acid or folinic acid. Other strategies are currently under investigation. CONCLUSIONS: MTX benefits a majority of RA patients. Approximately 30% of patients, however, abandon treatment because of drug-related side effects. Folic acid or folinic acid likely reduces MTX toxicity. More data, however, are needed to evaluate a potential detrimental effect on the antirheumatic efficacy of MTX.
10366114 An assessment of the annual and long-term direct costs of rheumatoid arthritis: the impact 1999 Jun OBJECTIVE: To describe the distribution of direct medical care costs of rheumatoid arthritis (RA) over 1-year and 11-year periods, and to evaluate the impact of poor function and functional decline on direct costs. METHODS: The present study uses data from the University of California, San Francisco, RA Panel Study in which 1,156 persons with RA have been followed up for as long as 15 years through annual structured interviews and periodic updates on severity from rheumatologists. We present annual direct medical care cost data for the years 1995 and 1996 and estimates of cumulative costs for the period 1986-1996 for the 272 persons followed up continuously for this period. RESULTS: Medical care costs for RA averaged $5,919 a year from a societal perspective; persons with RA incur another $2,582 in medical care costs for non-RA reasons. Of the RA total costs, hospital admissions account for more than half. Costs are highly skewed, with the costs in the 90th, 95th, and 100th percentiles totaling $8,209, $31,059, and $85,469 a year, respectively. Cumulative costs for the period 1986-1996 averaged $57,201, with cumulative costs in the 90th, 95th, and 100th percentiles totaling $114,844, $142,563, and $191,540, respectively. Persons with RA in the worst quartile of function experienced total annual direct costs that were 2.55 times as high and total hospital costs that were 6.97 times as high as those in the best (e.g., the first) quartile. Poor baseline functional status and declining functional status had similar, large effects on cumulative medical care costs. CONCLUSION: Medical care costs for RA over 1 year and 1 decade are highly skewed. Persons with RA with poor and declining function experience much higher costs of care.
10914849 The comparative risk and predictors of adverse gastrointestinal events in rheumatoid arthr 2000 Jul OBJECTIVE: It has been suggested that rheumatoid arthritis (RA) itself may be a risk factor for adverse gastrointestinal (GI) events, but this hypothesis has not been studied in a large sample, nor has the effect of time on risk factors been studied. We investigated rates and risk factors for GI events in RA and osteoarthritis (OA) and assessed the additional risks conveyed by having RA. METHODS: A prospective study of patients with OA and RA from a single center was undertaken using questionnaires mailed at 6 month intervals. The relationship between drug therapy and GI events was assessed in the same 6 month time frame. Over 13 years of biannual assessments, 2,131 patients were studied for serious GI events and adverse GI symptoms during 9,621 patient-years of observation. RESULTS: The incidence rate (IR) for GI hospitalization was 1.56 and 1.28 per 100 patient-years, and for GI bleeding or perforation was 0.50 and 0.58 for RA and OA, respectively. After controlling for age, sex, nonsteroidal antiinflammatory drug (NSAID) and steroid use, the incidence rate ratio (IRR) for RA versus OA did not differ for hospitalization [IRR 1.07 (95% CI 0.66, 1.74)] or for bleeding or perforation [IRR 0.63 (95% CI 0.29, 1.35)]. In multivariate analyses for both groups combined, the IRR was 2.95 (2.05, 4.24) for prednisone use, 1.41 (1.08, 1.85) for NSAID use, and 1.46 (1.22, 1.74) for every 10 year increase in age. In additional multivariate models, Health Assessment Questionnaire disability was also a significant risk factor. During the study period, the odds of NSAID use decreased 2.94 times per 10 year period, while the odds of prednisone use increased by 1.49. Dysphagia [IRR 1.11 (1.00, 1.24)], anorexia [IRR 1.13 (1.03, 1.23)], nausea [IRR 1.13 (1.04, 1.25)], heartburn [IRR 1.12 (1.05, 1.19)], vomiting [IRR 1.20 (1.02, 1.42)], peptic ulcer symptoms [IRR 1.20 (1.11, 1.29)], and abdominal pain [IRR 1.11 (1.01, 1.22)] were associated with NSAID use, but not with steroids. CONCLUSION: Patients with RA and OA do not differ in the rates and risk factors for GI hospitalizations and symptoms after controlling for age, steroid use, NSAID use, or (for OA) body mass index. Prednisone is a more important risk factor among patients with RA than NSAID.
10577970 The rationale for the current boom in anti-TNFalpha treatment. Is there an effective means 1999 Nov Progress in understanding mechanisms of disease are necessary to usher in major changes in treatment. A new era in rheumatoid arthritis (RA) and related chronic autoimmune/inflammatory diseases is now beginning, with a variety of anti-TNFalpha treatments licensed for use in both RA and Crohn's disease. The rationale for this new treatment lies in an understanding that cytokines are critical, rate limiting molecules lying at the heart of the chronic autoimmune/inflammatory disease process. This understanding was developed from the critical evaluation of a hypothesis that was proposed linking cytokines, antigen presentation and autoimmunity in 1983. Detailed analysis focusing on the major site of the disease, the rheumatoid synovium was essential to developing indications that blockade of TNFalpha might be efficacious. This clue was validated using anti-TNFalpha treatment of an animal model of RA, murine collagen induced arthritis, and by immunohistochemical demonstration of upregulated TNF and TNF-R expression in the synovium. With this three pronged rationale, the authors were able to convince Centocor, Inc, which had developed a chimaeric anti-TNFalpha antibody for use in sepsis, to work with them to test the concept that TNFalpha blockade would be beneficial in RA. With the success of that first trial, other companies have subsequently tested their anti-TNF strategies successfully. Current interests extend to understanding the processes that regulate TNF production in the rheumatoid joint. Progress in this area is discussed, using adenoviruses to infect normal macrophages and rheumatoid synovium.
11276803 The Swedish ACCES model: predicting the health economic impact of celecoxib in patients wi 2000 Dec The Arthritis Cost Consequence Evaluation System (ACCES) pharmacoeconomic model was used to evaluate the economic and health impact of the recent introduction of celecoxib for treatment of osteoarthritis (OA) and rheumatoid arthritis (RA) in Sweden. The model demonstrates that use of celecoxib can be expected to reduce the incidence of gastrointestinal adverse events, resource utilization and treatment costs. In a cost-effectiveness analysis, celecoxib demonstrated economic dominance (i.e. improved health at reduced cost) compared with the currently available alternatives for OA, and demonstrated economic dominance against a clinically relevant base-case scenario for RA. In sensitivity analyses, the results were shown to be relatively robust; celecoxib demonstrated economic dominance or favourable cost-effectiveness ratios in all analyses. Based on these data, it can be concluded that the use of celecoxib in Sweden will provide societal benefits by improving health care at reduced cost for patients with OA and RA.
11083282 The role of CD40 ligand and tumor necrosis factor alpha signaling in the transgenic K/BxN 2000 Nov OBJECTIVE: Spontaneous arthritis in the KRN transgenic mouse (K/BxN) model is due to the autoreactivity of the transgenic T cell receptor and subsequent induction of autoantibodies directed against glucose-6-phosphate isomerase (G6PI). This study sought to analyze the potential of anti-CD40 ligand (anti-CD40L) and anti-tumor necrosis factor alpha (anti-TNFalpha) antibodies in preventing and treating arthritis in this murine model. METHODS: Groups of K/BxN mice were injected with anti-CD40L and anti-TNFalpha antibodies during various stages of arthritis. Disease was assessed by clinical scoring, measurements of paw swelling, and histology. The results were correlated with the levels of autoantibodies in the serum, as assessed by enzyme-linked immunosorbent assay. RESULTS: Anti-CD40L antibody treatment was able to diminish significantly the arthritis development in K/BxN mice when given a week before the onset of clinically apparent disease. However, no effect on disease was seen when the antibodies were administered after clinical onset. Surprisingly, neutralizing anti-TNFalpha antibodies were unable to prevent arthritis in K/BxN mice. The success of antibody treatment in preventing disease correlated with low levels of anti-G6PI antibodies in the serum. CONCLUSION: These results suggest that anti-CD40L treatment can prevent arthritis development in a model of immunoglobulin-mediated arthritis, but anti-TNFalpha treatment cannot. The unsuccessful treatment of established disease was possibly due to the continued presence of autoreactive antibodies in the arthritic mice.
10587554 Serum lysozyme: a potential marker of monocyte/macrophage activity in rheumatoid arthritis 1999 Dec OBJECTIVE: Estimate the contribution of monocytes/macrophages to the disease process in rheumatoid arthritis (RA), by measuring the serum levels of the leucocyte-derived granular proteins: lysozyme, myeloperoxidase (MPO), lactoferrin and human neutrophil lipocalin (HNL). METHODS: Serum levels of these granular proteins were measured in patients with RA (n=23) and in healthy controls (n=27), and in 10 patients with RA after treatment with low-dose prednisolone. The serum levels of the granular proteins were also measured before and after treatment with metyrapone, a substance that inhibits the synthesis of cortisol in the adrenals. RESULTS: The serum levels of lysozyme and MPO were elevated in patients with RA, while the concentrations of lactoferrin and HNL were similar in both groups. Prednisolone treatment decreased the serum concentration of lysozyme and MPO. Metyrapone did not influence the level of the granular proteins measured. CONCLUSIONS: The increased serum levels of lysozyme and MPO, but not of HNL and lactoferrin in RA could indicate a stimulated secretory activity of mononuclear phagocytes. The measurement of serum lysozyme, as an indicator of monocyte/macrophage activity, might be used to study disease activity in RA.
10540788 Prevalence of rheumatoid arthritis in Dublin, Ireland: a population based survey. 1999 Jul The prevalence of Rheumatoid Arthritis (RA) in Ireland has never been established. Studies from different countries show varying rates, being almost 100 per cent greater in the highlands of Scotland (10/1,000) than in rural Lesotho (6/1,000). A recent study also suggests a fall in the prevalence of RA among women in the London urban area. Given these variations the validity of extrapolating prevalence rates established for other countries to Ireland is questionable. This study aimed to establish a prevalence rate for RA in a defined Dublin population. A self-administered questionnaire was sent to 2,500 people chosen at random from the electoral register. The questionnaire was designed to select out both undiagnosed patients and those with definite arthritis. Respondents whose replies indicated an arthritic process, but in whom no diagnosis had been made, were asked to attend for further assessment and investigations as appropriate. Those who responded that they had been diagnosed with arthritis were asked for consent to inspect their hospital or general practitioner records. A diagnosis of RA was based on American Rheumatism Association (ARA) criteria. Valid responses were received from 1,227 people surveyed (response rate = 49 per cent). Six cases of RA were identified including 2 previously undiagnosed cases. A prevalence rate of 5/1,000 has been estimated based on these findings.
9506878 Rheumatoid factor isotypes, disease activity and the outcome of rheumatoid arthritis: comp 1998 The value of rheumatoid factor (RF) isotypes for assessing rheumatoid arthritis (RA) remains debatable. We investigated whether using different antigens to measure RF alters the relationships between RF isotypes and clinical variables. The association between IgA and IgM RF, disease activity, and cumulative anatomical joint damage in RA was studied in 140 patients. The RF isotypes were measured using both rabbit IgG and horse IgG as antigens. Cumulative anatomical damage was assessed radiologically using Larsen's score and disease activity was determined by C-reactive protein (CRP), the health assessment questionnaire (HAQ), and a combined disease activity score (DAS). Patients positive for IgA RF and IgM RF against rabbit IgG had significantly higher disease activity and more radiological damage than negative patients. With horse IgG as antigen these differences were smaller or absent. Patients positive for only IgM RF had milder disease than patients positive for IgA RF with or without IgM RF. The clinical relationships of RF isotypes are related to the antigen used. Measuring IgA RF against rabbit IgG provides most information about disease activity, functional impairment and joint damage.
11404821 Magnetic resonance imaging of rheumatoid arthritis: the evolution of clinical applications 2001 Jun Powerful techniques are being developed for evaluating rheumatoid arthritis with magnetic resonance imaging (MRI). Much of this development is being driven by the pharmaceutical and biotechnology industries searching for novel therapies for this disease. Accordingly, the imaging tools that ultimately will be used to direct patients to specific therapies and then to monitor treatment effectiveness and safety are currently being refined and validated in rigorous multicenter and multinational clinical trials aimed at gaining regulatory approval of these new therapies. As these trials approach completion, rheumatologists can anticipate an increased demand for expertise and experience in evaluating disease progression and treatment response with these techniques and the emergence of MRI systems specifically designed for this market. The following discussion reviews this novel pathway for evolving imaging techniques for clinical use through clinical drug trials, lists the most promising MRI markers available today for evaluating joint destruction in rheumatoid arthritis, and speculates on how these techniques will find their way into clinical practice.
11352257 Chronic relapsing homologous collagen-induced arthritis in DBA/1 mice as a model for testi 2001 May OBJECTIVE: To test whether the chronic relapsing arthritis induced by immunizing DBA/1 mice with homologous type II collagen is a valuable model for testing disease-modifying antiarthritic drugs. METHODS: Six-week-old male DBA/1 mice were immunized with murine type II collagen in Freund's complete adjuvant, resulting in a chronic relapsing polyarthritis in >80% of the mice 4 weeks after immunization. At the onset of clinical arthritis, mice were treated for 4 weeks with different treatments, including anti-tumor necrosis factor (anti-TNF) and antiinterleukin-12 (anti-IL-12) antibodies, salbutamol, or indomethacin. Alternatively, treatment was administered as a pulse at the beginning of clinical arthritis. Pulse treatments tested included anti-CD3 in combination with anti-TNF, anti-TNF alone, and anti-CD4, either alone or in combination with anti-TNF. After 4 weeks of arthritis, mice were killed and hind paws were assessed histologically for joint damage. RESULTS: Anti-TNF and salbutamol both suppressed clinical arthritis more effectively than indomethacin and, moreover, protected the joints from damage, whereas indomethacin did not. Anti-IL-12 treatment initiated after the onset of clinical symptoms accelerated disease. Pulse therapy with anti-CD3 plus anti-TNF was found to induce remission, clinically as well as histologically, whereas a pulse with either anti-CD4, anti-TNF, or the combination of anti-CD4 plus anti-TNF was less effective. CONCLUSION: Chronic relapsing homologous collagen-induced arthritis is a valuable model for identifying remission-inducing antiarthritic drugs and has predictive value with respect to their joint-protective potency.
9811045 T cell receptor peptide vaccination in rheumatoid arthritis: a placebo-controlled trial us 1998 Nov OBJECTIVE: Restricted T cell receptor (TCR) gene usage has been demonstrated in animal models of autoimmune disease and has resulted in the successful use of TCR peptide therapy in animal studies. This clinical trial was undertaken to determine the safety and efficacy of a combination of Vbeta3, Vbeta14, and Vbeta17 TCR peptides in Freund's incomplete adjuvant (IFA) in patients with rheumatoid arthritis (RA). METHODS: A double-blind, placebo-controlled, multicenter, phase II clinical trial was undertaken using IR501 therapeutic vaccine, which consists of a combination of 3 peptides derived from TCRs (Vbeta3, Vbeta14, and Vbeta17) in IFA. A total of 99 patients with active RA received either 90 microg (n = 31) or 300 microg (n = 35) of IR501 or IFA alone (n = 33) as a control. The study medication and placebo were administered as a single intramuscular injection (1 ml) at weeks 0, 4, 8, and 20. RESULTS: Treatment with IR501 was safe and well tolerated. None of the patients discontinued the trial because of treatment-related adverse events. Efficacy was measured according to the American College of Rheumatology 20% improvement criteria. Using these criteria, patients in both IR501 dosage groups showed improvement in disease activity. In the most conservative analysis used to evaluate efficacy, an intent-to-treat analysis including all patients who enrolled, the 90-microg dosage group showed a statistically significant improvement compared with control patients at the 20-week time point after the third injection. Trends toward improvement were shown in both the 90-microg and the 300-microg dosage groups at week 24 after the fourth injection. CONCLUSION: IR501 therapeutic vaccine therapy was safe and well tolerated, immunogenic, and demonstrated clinical improvement in RA patients. Additional clinical trials are planned to confirm and extend these observations.
10769433 Rheumatoid arthritis and osteoporosis. 2000 Some controversial issues in the current literature in relation to osteoporosis and rheumatoid arthritis are updated and discussed. Because most studies agree that osteoporosis in postmenopausal women and in men with RA is more evident at the hip and radius than at the spine, and that the most important determinants of bone loss are disability, local disease activity, and cumulative corticosteroid dose, osteoporosis is not a common systemic extra-articular manifestation of RA. In early arthritis, periarticular osteoporosis does indeed reflect disease activity because it is closely related to the acute phase reactants, but once periarticular osteoporosis is established it is no longer a marker of disease severity. The threshold dose for corticosteroid-induced osteoporotic fractures is the cumulative rather than the actual dose. Statements based on quantitative tomography concerning the acute effects (and their reversal) of corticosteroids on bone have to be interpreted with care because of important body composition changes, in particular in bone marrow fat, during corticosteroid treatment. At present there is no evidence that anti-resorbing drugs can change the progress of RA erosions, probably because erosions are the result of non-osteoclast mediated mechanisms. Stress fractures in RA are underdiagnosed and are often confused with synovitis, and therefore it is likely that they are more frequent than commonly thought, especially in the lower limbs. Methotrexate osteopathy is known in oncological practice. Whether low dose methotrexate is toxic for bone is not clear, but a number of clinical observations suggest that the occurrence of spontaneous fractures and lower extremity pain is more frequent in methotrexate treated patients than expected. Prospective studies are necessary to confirm these impressions.
9830880 The social environment and health in rheumatoid arthritis: marital quality predicts indivi 1998 Oct OBJECTIVE: To examine prospective relations between a wide array of measures of social functioning and pain, while controlling for disease duration and activity and functional grade. METHODS: As part of a larger study on health care utilization, longitudinal data were collected from 136 Dutch and 98 German outpatients on clinical status and pain. Social data included information on sexual handicap, spouse behavior, loneliness, daily emotional support, and the maintenance of pleasurable life domains. Pain severity was assessed at baseline and 12 months later with standard measures of pain and analyzed with hierarchical regressions. RESULTS: Social measures obtained at baseline were consistently associated with pain at followup. Depression was a moderate correlate of pain in the Dutch and German samples. The regressions revealed that patient reports of negative spouse behavior (such as avoidance and critical remarks) and baseline depression predicted worse pain outcome, and this association remained significant in analyses controlling for baseline pain. The level of formal education was a weak correlate of disability, emotional support, and pain. Daily emotional support and social life domains associated with positive affect had an indirect influence on outcome. The absence of strong rather than weak social ties was the component of the loneliness construct linked to pain. These associations between social prognostic factors and pain severity, however, were mediated by psychological functioning at baseline. CONCLUSION: The social environment was found to operate on the core health outcome, pain severity, via several pathways. Social functioning may be affected by rheumatoid arthritis (RA) progression, but it also appears to form a determinant of future health outcome. Not only the status of being married but also the quality of the relationship in terms of long-term stress and emotional support may be useful prognostic factors in RA.
10743802 Modeling therapeutic strategies in rheumatoid arthritis: use of decision analysis and Mark 2000 Mar OBJECTIVE: The management of patients with rheumatoid arthritis (RA) is controversial, with a number of different proposed treatment strategies based on different conceptions of the natural history of the disease and different interpretations of the efficacy and effectiveness of the drugs used for treatment. We attempted to develop a theoretical framework to assess the effectiveness of different treatment regimens for RA. METHODS: We used decision analysis to structure the problem of comparing sequential monotherapy to a combination strategy. Subsequently, we used 3 different estimates of drug effectiveness: one from expert rheumatologists; a metaanalysis; and a recent nationwide survey of American rheumatologists, in a Markov model. Last, we utilized published duration of therapy data to model drug treatment over time. RESULTS: Estimates of drug effectiveness differed substantially among rheumatologists, but regardless of the estimates and the treatment strategy used, the model predicted over 90% of patients improved by the 3rd drug trial. Over time, treatment patterns in our model resemble the "sawtooth" pattern previously observed. CONCLUSION: Treatment strategies in RA are difficult to model because of uncertainty in both the structure of the model and the data needed to perform the analysis. These models tend to overestimate the effectiveness of drug sequences because of nonindependence between therapies, probably due to sequence effects, a change in responsiveness over time, or resistant subgroups. Our preliminary analysis suggests that the most effective agent, possibly methotrexate, should be used first if the objective is to get as many patients into remission as quickly as possible.
10813279 Factors influencing length of time taking methotrexate in rheumatoid arthritis. 2000 May OBJECTIVE: Duration of therapy has been suggested to represent a measure of effectiveness. Life table analyses of therapy with methotrexate (MTX) in rheumatoid arthritis (RA) have indicated a longer duration than with other drugs. However, individual patients continue taking MTX for different periods of time. We assessed the influence of patient variables at treatment onset upon subsequent duration of MTX therapy. METHODS: Patients with RA (n = 437) from 8 North American databank centers beginning MTX therapy after January 1, 1988, were followed prospectively. Age at onset of MTX treatment, sex, years of education, age at onset of disease, years with disease, number of comorbid conditions, number of disease modifying antirheumatic drugs (DMARD) and nonsteroidal antiinflammatory drugs (NSAID) taken just prior to MTX. disability level, pain, and global assessment prior to starting MTX were used in univariate Kaplan-Meier analyses to predict number of months taking MTX alone. An index that divided the patients into risk strata for predicting duration of therapy was constructed to be clinically useful. RESULTS: The median number of months continuing MTX without addition of other DMARD was 41 months and the median for the total course taking MTX was 52 months. The retention rate was lowest for patients with the most negative initial health state. High level of initial pain, long duration of disease, and not using a DMARD just prior to MTX were associated with low retention rate and can be used to predict expected durations of MTX treatment ranging from 17 to 52 months. For practical guidance in clinical decisions an index was computed based on the predictor variables: level of initial pain, duration of disease, and number of DMARD; this index identifies subgroups with very different durations taking MTX alone. Disease duration at baseline was strongly related to time taking MTX alone and could therefore also be used as a simplified rule in clinical work. CONCLUSION: Expected duration of MTX treatment is influenced by clinical variables, and these may suggest those patients likely to have more or less satisfactory experiences with MTX. The time taking drug alone (therapeutic segment) may be a more logical and sensitive indicator of effectiveness than the total course on the medication.
11426018 Osteoprotegerin and receptor activator of nuclear factor kappaB ligand (RANKL) regulate os 2001 Jun OBJECTIVE: This study investigated the involvement of the recently identified regulators of osteoclast formation RANKL [receptor activator of nuclear factor kappaB (RANK) ligand, osteoclast differentiation factor, TRANCE, osteoprotegerin ligand] and its natural inhibitor, osteoprotegerin (OPG), in the bone erosion of rheumatoid arthritis (RA). METHODS: mRNA was extracted from cells isolated from the pannus and synovial membrane regions of joints of 11 RA patients. Semiquantitative reverse transcription-polymerase chain reaction was carried out, and the isolated cells were also cultured to determine their ability to form osteoclasts. RESULTS: mRNAs encoding RANKL, RANK, OPG and macrophage-colony stimulating factor were expressed by cells isolated from RA joints. In addition, mRNA encoding for tumour necrosis factor apoptosis-inducing ligand and the osteoclast markers tartrate-resistant acid phosphatase and calcitonin receptor were also often expressed. Osteoclasts capable of forming resorption lacunae were generated from cells in the RA joints. At 50 ng/ml, recombinant OPG completely inhibited the resorptive activity of these cells. There was a significant correlation between the ratio of RANKL mRNA to OPG mRNA and the number of resorption pits produced (P = 0.028). CONCLUSION: These data suggest that RANKL is an essential factor for osteoclast formation by cells in the rheumatic joint and that OPG may prevent the bone erosion seen in RA joints.
10378714 Determinants of WOMAC function, pain and stiffness scores: evidence for the role of low ba 1999 Apr OBJECTIVES: The Western Ontario MacMaster (WOMAC) is a validated instrument designed specifically for the assessment of lower extremity pain and function in osteoarthritis (OA) of the knee or hip. In the clinic, however, we have noted that OA patients frequently have other musculoskeletal and non-musculoskeletal problems that might contribute to the total level of pain and functional abnormality that is measured by the WOMAC. In this report, we investigated back pain and non-articular factors that might explain WOMAC scores in patients with OA, rheumatoid arthritis (RA) and fibromyalgia (FM) in order to understand the specificity of this instrument. METHODS: RA, OA and FM patients participating in long-term outcomes studies completed the WOMAC and were assessed for low back pain, fatigue, depression and rheumatic disease symptoms by mailed questionnaires. RESULTS: Regardless of diagnosis, WOMAC functional and pain scores were very much higher (abnormal) among those complaining of back pain. On average, WOMAC scores for back pain (+) patients exceeded those of back pain (-) patients by approximately 65%,, and 52% of OA patients reported back pain. In regression analyses, study symptom variables explained 42, 44 and 38% of the variance in WOMAC function, pain and stiffness scores, respectively. In the subset of OA patients, radiographic scores added little to the explained variance. The strongest predictor of WOMAC abnormality in bivariate and multivariate analyses was the fatigue score, with correlations of 0.58, 0.60 and 0.53 with WOMAC function, pain and stiffness, respectively. The WOMAC performed well in RA and FM, and correlated strongly with the Health Assessment Questionnaire (HAQ) disability scale and a visual analogue scale (VAS) pain scale. CONCLUSION: The WOMAC captures more than just knee or hip pain and dysfunction, and is clearly influenced by the presence of fatigue, symptom counts, depression and low back pain. WOMAC scores also appear to reflect psychological and constitutional status. These observations suggest the need for care in interpreting WOMAC scores as just a measure of function, pain or stiffness, and indicate the considerable importance of psychological factors in rheumatic disease and rheumatic disease assessments.
11065254 Interstitial pneumonia complicated by Sjögren's syndrome, Hashimoto's disease, rheumatoid 2000 Nov A 66-year-old woman diagnosed as having Hashimoto's disease and rheumatoid arthritis manifested interstitial pneumonia. We diagnosed Sjögren's syndrome and primary biliary cirrhosis as complications in this case. Steroid therapy was relatively effective for the interstitial pneumonia which was in an active state; however, during tapering of the steroid, there was a relapse and also severe dry throat. Cyclophosphamide was added and was effective in the prevention of recurrence. Even after discontinuation of steroid therapy, her general condition is stabilized. It is very important to carefully investigate other organ involvement as a prognostic factor in cases in which there are multiple autoimmune diseases.
9890677 Cytokines and soluble CD4 and CD8 molecules in rheumatoid arthritis: relationship to syste 1998 Vascular involvement in rheumatoid arthritis (RA) is associated with a wide range of extra-articular complications. Damage to internal organs occurs through a widespread disorder of the microvasculature. Vasculitis, as an integral part of the disease process, is associated with immune system abnormalities. To evaluate the relationship between capillaroscopic abnormalities, extra-articular involvement and immunological alterations, serum levels of soluble CD4 (sCD4), CD8 (sCD8), tumour necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) were determined by an enzyme-linked immunosorbent assay in 80 RA patients. In all patients with signs of extra-articular manifestations, severe or moderate changes in nailfold capillaroscopy were found. Serum levels of TNF-alpha, IL-6, sIL-6R and sCD4 were significantly higher in RA patients compared with 30 healthy subjects. RA patients with clinical signs of systemic vasculitis showed significantly higher levels of TNF-alpha and IL-6 compared with those without vascular involvement. Moreover, a significant correlation between sCD4 levels and the capillaroscopy findings was found. These results point to a pathogenic role of the cytokine network in rheumatoid vasculitis and further may suggest an important role of cellular immune activation in the pathogenesis of microvascular damage.