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ID PMID Title PublicationDate abstract
14527109 A case study on rheumatoid arthritis. 2003 Sep At a time when many managed care organizations increasingly shift costs to patients through tiered formularies and widening copay differentials, biologic agents represent a significant clinical and financial challenge unlikely to be managed optimally with tiered formularies and greater patient cost sharing. The information discussed in this article is intended for healthcare professionals involved with rheumatoid arthritis therapy, including but not limited to physicians in both the inpatient and outpatient setting, and for other managed care professionals, including medical directors, pharmacy directors, long-term care decision makers, nurses, pharmacists, and case managers.
15074026 [Magnetic resonance imaging of the hand in rheumatoid arthritis]. 2004 Jan The aim of the study was to show the magnetic resonance (MR) images of changes in hands of patients with rheumatoid arthritis (RA). The SE sequence T1-weighted (TR600, TE15) and fat-suppressed (A-250, TR1155, TE22) were obtained with 3 mm coronal scans and matrix 256 x 512, both before and after contrast medium administration. Knee coil was used. The images in both sequences of the following changes were obtained: bone erosions, synovitis, periarticular oedema, joint effusion, tendonitis and bone marrow oedema. The administration of intravenous contrast was found very useful. Changes of the joint synovium in osteoarthritis were characterised to differentiate them from changes due to RA. The authors suggest that MR imaging--because of its exceptional diagnostic value--may become a basic imaging method in evaluation of patients with RA.
15243852 Affective distress and fibromyalgia. 2004 May 1 PRINCIPLES: Elevated rates of lifetime and current psychiatric disorders, elevations of psychological self-report measures assessing depression, anxiety and hypochondriasis have been reported in fibromyalgia syndrome (FMS) patients as well as studies refuting these findings. Studies comparing FMS patients with rheumatoid arthritis (RA) patients provide discrepant data. The aim of this paper is to compare FMS patients with RA patients and healthy controls with respect to psychological measures in a case control design. METHODS: Fifty subjects with FMS, 20 with RA and 42 healthy controls were assessed with respect to anxiety, depression, pain intensity and disability. Three logistical regression models were performed to test whether higher levels of a psychological measure (disability, depression or anxiety) are associated with one disease rather than another, or with one disease rather than with healthy controls. For each regression model, the best exploratory covariates were determined using receiver operating characteristic (ROC) curves. RESULTS: In the logistic regression, anxiety scores were the most important covariate determining the likelihood of having FMS whereas depression scores increased the chances of being an RA patient. Age and disability scores did not differ between FMS and RA. CONCLUSIONS: Affective distress is not specific to FMS patients, but the manner in which affective distress is incorporated into the patient's life is worth studying. FMS.seems to be associated with anxiety rather than depression.
12417057 Evaluation of the cholesterol influence in type II collagen-induced arthritis in DBA/1J mi 2002 Jul In order to verify the cholesterol influence in RA severity in DBA/1J mice, we quantified the cholesterol present in the knee joints of normal (N) and with collagen II induced arthritis (CIA). Forty male DBA/1J mice, were divided in normal (n=20) and CIA group (n=20). Mice in CIA group were injected with 100 microg of collagen II emulsified in Freund's complete adjuvant. Sixteen DBA/1J (8 N and 8 CIA) received an injection of 2.96 x 10(6) Bq of (3)H-cholesterol and were anesthetized and sacrificed. Semi-fine sections were covered with LM-1 emulsion, exposed for six weeks and developed. Collagen induced edema, erythema and dysfunction of knee joints in CIA group. Radioactive cholesterol was located more on the synovial membrane, where we found the greatest density of silver grains, significantly (P<0.0001) higher in group CIA vs. controls (61-/+2.3 X 18-/+0.7). We conclude that the cholesterol deposits on the synovial membrane is related to CIA severity.
12975321 Synoviolin/Hrd1, an E3 ubiquitin ligase, as a novel pathogenic factor for arthropathy. 2003 Oct 1 Rheumatoid arthritis (RA) is one of the most critical articular diseases with synovial hyperplasia followed by impairment of quality of life. However, the mechanism(s) that regulates synovial cell outgrowth is not fully understood. To clarify its mechanism(s), we carried out immunoscreening by using antirheumatoid synovial cell antibody and identified and cloned "Synoviolin/Hrd1", an E3 ubiquitin ligase. Synoviolin/Hrd1 was highly expressed in the rheumatoid synovium, and mice overexpressing this enzyme developed spontaneous arthropathy. Conversely, synoviolin/hrd1(+/-) mice were resistant to collagen-induced arthritis by enhanced apoptosis of synovial cells. We conclude that Synoviolin/Hrd1 is a novel causative factor for arthropathy by triggering synovial cell outgrowth through its antiapoptotic effects. Our findings provide a new pathogenetic model of RA and suggest that Synoviolin/Hrd1 could be targeted as a therapeutic strategy for RA.
14740454 Agreement among Ayurvedic practitioners in the identification and treatment of three cases 2003 Nov OBJECTIVE: To conduct a preliminary investigation into the consistency of approach between three Ayurvedic medicine experts on treatments for inflammatory polyarthritis. METHODS: A convenience sample of three experienced Ayurvedic practitioners was recruited. These practitioners independently assessed three subjects with inflammatory polyarthritis for health status, treatment history, and lifestyle, conducted a physical examination, and then independently determined the treatment plan. The treatment plan was recorded on standardized collection forms. The subject examination order was randomized for each practitioner. Following completion of the assessments, a facilitated discussion among the practitioners permitted each to discuss all aspects of the recommended therapies. Proceedings were audio-taped and the content analyzed. RESULTS: All three practitioners agreed upon a unified concept of Ayurvedic disease origin, disease diagnosis, and treatment approach for each patient. Seven specific treatment groupings (i.e. modalities) emerged: diet, exercise, relaxation, analgesic, anti-inflammatory, immune-enhancing, and detoxification/cleansing. Based on the single visit, the practitioners agreed upon 17 of 21 treatment groups for the three patients. CONCLUSION: Despite Ayurvedic medicine's individualized approach, considerable agreement existed among the practitioners studied. The identified Ayurvedic treatment approaches require investigation in a controlled clinical setting.
12509608 Fibrin generated in the synovial fluid activates intimal cells from their apical surface: 2003 Jan OBJECTIVE: Fibrin deposits adhered to the synovial surface are typical of rheumatoid joints. Since fibrin appears to have a role in arthritis perpetuation our aim was to investigate how these deposits are formed and the consequences of their adhesion to the tissue. METHODS: The appearance of fibrin aggregates either free in the synovial fluid or attached to the membrane was studied in rabbits with antigen-induced arthritis by histological techniques at different time points from challenge. In the fixed synovial membranes areas of fibrin-bound synovium were evaluated by qualitative variables to obtain a sequential profile of morphological changes. RESULTS: Fibrin aggregates appeared from the initial stages of the disease in the synovial effusion. Later on, they were localized on the synovial surface and progressive changes were noted at the fibrin-tissue interface, ending with the invasion of the aggregates by synovial cells and their incorporation into the tissue. CONCLUSION: Fibrin aggregates generated inside the joint cavity may constitute a source of activation and acquisition of invasiveness of the synovial fibroblasts, a process to explore within the perpetuating mechanisms of rheumatoid arthritis.
15137195 [High performance liquid chromatography in cortisol kinetics and its kinetic parameters in 2004 Mar The kinetics of cortisol was investigated in 26 healthy subjects and in 9 patients with rheumatoid arthritis induced by exogenous glucocorticosteroids. The cortisol concentration was determined in blood serum by using a high-efficiency liquid chromatography method. The cortisol kinetic parameters were found by empirically constructed formulae. An inadequate synthesis of cortisol was found in patients with rheumatoid arthritis after prednisolone administration. The results can be used for evaluating the pharmacodynamic properties of glucocorticosteroids.
15190385 The soluble tumor necrosis factor receptor etanercept: a new strategy for the treatment of 2004 Apr Rheumatoid arthritis is a severe, debilitating condition for which existing therapies are of limited efficacy. In addition, the most common structure of treatment for patients with rheumatoid arthritis has recently been called into question, and many believe it should be reversed so that stronger treatments are administered earlier in the progression of the disease. Pivotal to the changes in rheumatoid arthritis treatment is the introduction of the pro-inflammatory tumor necrosis factor (TNF) antagonists. Overexpression of cytokines in inflamed joints plays an important role in joint inflammation and tissue damage, and the place of cytokines in the pathology of rheumatoid arthritis has offered hope that their antagonism will reduce symptoms and slow the advancement of the condition. With this in mind, etanercept, a fully human soluble TNF receptor fusion protein, was developed. The potency of this novel drug in blocking TNF activity has been shown in animal models and in clinical trials. The latter have demonstrated a positive safety profile and efficacy in reducing pain and the number of tender and swollen joints in rheumatoid arthritis patients. The effects of etanercept have also been observed soon after administration and have been sustained over several years. Etanercept has offered encouragement for those seeking new, more efficacious and less toxic methods of treating rheumatoid arthritis in children, adults and the elderly. In addition to the treatment of adult and juvenile rheumatoid arthritis, etanercept has also demonstrated utility in treating ankylosing spondylitis and psoriatic arthritis.
12904893 The KRN mouse model of inflammatory arthritis. 2003 Aug In 1996 a new murine model of spontaneous arthritis was described by the group of Benoist and Mathis. Mice transgenic for a T cell receptor recognizing an epitope of bovine RNase and bred onto a NOD background developed severe destructive arthritis, which resembles human rheumatoid arthritis in many respects. The development of disease requires the presence of T and B lymphocytes and is dependent on the MHC class II molecule I-A(g7). B cell activation by antigen and an additional CD40-CD40 ligand interaction was found to give rise to the production of autoantibodies. Glucose-6-phosphate isomerase was identified as the target of the autoantibodies; moreover, the transgenic T cells were demonstrated to exhibit a dual specificity for both bovine RNase and glucose-6-phosphate isomerase. Importantly, the arthritis is serum transferable to normal recipients, enabling the examination of the pathogenic mechanisms of joint inflammation and destruction. Recent studies suggest the crucial involvement of the innate immune system in the development of antibody-induced arthritis. Complement components, Fc receptors and neutrophils are indispensable for disease induction. An overview of the existing data is given and the emerging concepts of the pathogenesis of the K/BxN arthritis are discussed with respect to their relevance for human rheumatoid arthritis. Because of the reliable and robust induction of joint inflammation by serum transfer this new disease model has been and will be a valuable means to address the as-yet-unanswered key questions related to the development of arthritis.
15243535 Clonal identity between skin and synovial tissue in a case of mycosis fungoides with polya 2004 Jul Polyarthritis in the presence of a cutaneous T-cell lymphoma is a rare phenomenon. We describe a case of mycosis fungoides with development of a symmetric erosive polyarthritis of the small hand joints and feet, diagnosed as rheumatoid arthritis. An identical monoclonal T-cell population in the skin and in the synovium was detected by T-cell receptor gene rearrangement analysis, illustrating articular dissemination of lymphoma cells. Differentiating mycosis fungoides-associated arthritis from rheumatoid arthritis may have important implications for treatment. Based on this case, the relevant literature, and the newest disease concepts, pathogenic mechanisms and therapeutic options of mycosis fungoides-associated arthritis are discussed.
12926654 Bone and joint diseases around the world. France: rheumatoid polyarthritis, chronic juveni 2003 Aug Since its creation, the Association française des Polyarthrites is doing everything possible to come to the aid of people with polyarthritic diseases and to help medical research make advances against this illness. Each year, with the help of sponsors, we organize a national information campaign with first-hand accounts and presentations by sufferers on radio and television stations, so that polyarthritis should be better understood by the general public. Last year, together with other associations, we asked the Minister of Health about the barriers to receiving innovative treatment for polyarthritis because of the cost. Because of this action, the Minister has made additional funds available so that more sufferers can benefit from new treatment. Recently, several associations dealing with chronic and serious inflammatory rheumatic illnesses who came together as an action group presented a text to the Minister of Health about the urgent need to make these illnesses a public health priority. Working sessions between the Minister, patient associations, and rheumatologists to consider how to implement a public health plan are in progress.
15476205 Interaction between RANKL and HLA-DRB1 genotypes may contribute to younger age at onset of 2004 Oct OBJECTIVE: To determine whether the RANKL and HLA-DRB1 "shared epitope" (SE) genotypes contribute to the development of rheumatoid arthritis (RA). METHODS: We studied 237 patients with early RA (within 15 months of symptom onset) who were seropositive for rheumatoid factor. HLA-DRB1 genotyping was performed using the polymerase chain reaction (PCR)-based oligonucleotide probe assay. RANKL polymorphisms were analyzed using PCR pyrosequencing for SNP1 and fluorescence-based PCR for the presence or absence of the TAAA insertion. RESULTS: The presence of SE-containing DRB1*04 alleles was associated with an earlier age at RA onset (mean +/- SD 47 +/- 12.7 years versus 53 +/- 12.5 years in SE- patients; P = 0.0004). The 2 novel RANKL polymorphisms were in strong linkage disequilibrium (P < 0.0001) and were associated with earlier ages at disease onset (e.g., for the CC versus CT/TT genotypes, 44 +/- 13.5 years versus 51 +/- 12.7 years; P = 0.0080). The mean age at disease onset in SE+ patients with the RANKL-CC genotype (35 +/- 7.2 years) was a mean of 18 years younger than in SE- patients with RANKL-CT/TT (53 +/- 12.5 years; P < 0.0001) and was 17 years younger than in SE- patients with RANKL-CC (52 +/- 13.2 years; P = 0.0005). The proportion of patients with both the SE and RANKL risk alleles was highest (23%) in those who developed RA during their third decade of life (ages 20-30 years), with a declining trend among those who developed RA during their fourth (16%), fifth (5%), and sixth or later (0%) decades. Interestingly, 92% of the patients diagnosed as having RA between ages 20 and 30 years carried at least 1 of the RA-associated DRB1*04 alleles, suggesting a strong influence of the SE in the early onset of RA. The majority of patients who developed RA symptoms in their third to fifth decades (74 of 119 [62%]) carried at least 1 copy of the DRB1*04 alleles; in contrast, fewer than half of the patients who developed RA in their sixth decade or later (50 of 118 [42%]) had DRB1*04 alleles. RANKL genotypes were not associated with erosive disease at baseline or with the yearly progression rate of radiographic joint damage. CONCLUSION: This study provides the first evidence that novel RANKL polymorphisms were associated with an earlier age at RA onset in SE+, but not SE-, patients and that an interaction between SE-containing HLA-DRB1 and RANKL polymorphisms increased the disease penetrance, resulting in a mean age at RA onset that was 18-20 years younger. Our results also suggested genetic differences between patients with early-onset and those with late-onset RA.
15589432 Rheumatoid arthritis: direct and indirect costs. 2004 Nov Rheumatoid arthritis (RA) causes disability, deformities, progressive radiological joint damage often with a need for joint replacement surgery, premature death, and alterations in quality of life. The economic burden created by RA is enormous. Direct costs per patient have been estimated at 1812-11,792 Euro annually and indirect costs at 1260-37,994 Euro annually. These mean values are approximations, as variations occur across countries, healthcare system organizations, and geographic locations. Direct costs account for one-fourth to slightly over a half of the total cost. Costs associated with inpatient care contribute up to 75% of direct costs, as compared to only about 20% for medications, although wide variations occur in costs related to drug monitoring and side-effect management. Physician visits account for about 20% of direct costs. As compared to indirect health costs for individuals from the general population, those for RA patients are increasing at a rapid rate. Indirect costs account for 80% of the excess cost related to RA. Cost estimates may change over time and show huge variations across individuals, with a small minority of patients accounting for most of the costs. Disability as measured by the Health Assessment Questionnaire (HAQ) has a major impact on costs. Early effective treatment may not only postpone and slow disease progression, thereby improving quality of life, but also decrease costs by preserving productivity and reducing the need for surgery, admission to acute-care and extended-care hospitals, and social service utilization. Data are beginning to accumulate on the excess costs associated with biotherapies and other new second-line drugs. They indicate acceptable excess costs relative to the additional medical benefits and to the cost-effectiveness of other healthcare programs. Nevertheless, the threshold that defines an acceptable excess cost is arbitrary and varies with local economic conditions.
14680500 Neural immune pathways and their connection to inflammatory diseases. 2003 Inflammation and inflammatory responses are modulated by a bidirectional communication between the neuroendocrine and immune system. Many lines of research have established the numerous routes by which the immune system and the central nervous system (CNS) communicate. The CNS signals the immune system through hormonal pathways, including the hypothalamic-pituitary-adrenal axis and the hormones of the neuroendocrine stress response, and through neuronal pathways, including the autonomic nervous system. The hypothalamic-pituitary-gonadal axis and sex hormones also have an important immunoregulatory role. The immune system signals the CNS through immune mediators and cytokines that can cross the blood-brain barrier, or signal indirectly through the vagus nerve or second messengers. Neuroendocrine regulation of immune function is essential for survival during stress or infection and to modulate immune responses in inflammatory disease. This review discusses neuroimmune interactions and evidence for the role of such neural immune regulation of inflammation, rather than a discussion of the individual inflammatory mediators, in rheumatoid arthritis.
11824973 Occurrence of extraarticular disease manifestations is associated with excess mortality in 2002 Jan OBJECTIVE: To investigate the occurrence of extraarticular manifestations (ExRA) in a well defined community based cohort of patients with rheumatoid arthritis (RA), and to examine their effect on mortality. METHODS: Using the resources of the Rochester Epidemiology Project, a retrospective medical record review was conducted of a cohort of 424 cases of RA in Olmsted County, MN, USA, diagnosed during the period 1955-1985. These cases had been classified using the American College of Rheumatology 1987 criteria for RA. Patients were followed 1955-1998 (median followup 14.8 yrs; range 0.2-42.8 yrs), and incident ExRA manifestations were recorded according to predefined criteria. Data on comorbidities were extracted using the definitions of the Charlson comorbidity index. Survival was compared to the general population using Kaplan-Meier estimates. RESULTS: ExRA occurred in 169 patients, corresponding to an incidence rate of 3.67/100 person-yrs. Compared to the general population, survival among patients with RA was decreased. Survival among patients with ExRA was markedly decreased compared to the general population and to patients without ExRA (p < 0.001). A particularly poor prognosis was noted in a subgroup of 63 patients (incidence rate 1.04/100 person-yrs) who fulfilled predefined criteria for severe ExRA (i.e., vasculitis, pericarditis, pleuritis, and/or Felty's syndrome). For RA patients who did not fulfill these criteria, there was no significant increase of mortality (p = 0.09). In a multivariate model of mortality, including age, sex, and the presence of known comorbidities, the presence of one or more of these ExRA was the strongest predictor of mortality. CONCLUSION: In this first community based study of extraarticular manifestations in RA, virtually all the excess mortality occurred in a subgroup of patients with severe extraarticular disease, suggesting that extraarticular disease is the major predictor of mortality in patients with RA.
12067756 Regulation of TNF-alpha-mediated hyperplasia through TNF receptors, TRAFs, and NF-kappaB i 2002 Sep 2 Although the etiology of rheumatoid arthritis (RA) has not been clearly understood to date, the hyperplasia of the synovial membrane imposed by pro-inflammatory cytokines has been suggested to play a crucial role in the progression of this disease. TNF-alpha, a potent pro-inflammatory cytokine, was detected at highly enhanced concentrations in the blood and synovial fluids of patients with RA relative to those of patients with osteoarthritis and normal subjects. To evaluate the role of TNF-alpha in the synovial hyperplasia during the pathogenic state, we investigated cellular outcomes and molecular mechanisms of synoviocytes in response to TNF-alpha. Following TNF-alpha treatment, fibroblast-like synoviocytes (FLS) obtained from patients with RA proliferated, unlike the cells from a normal subject that were unaffected. This TNF-alpha induced proliferation of synoviocytes obtained from RA patients coincided with down-regulation of TNFR1 and up-regulation of TNFR2 and TRAF1-6, as well as NF-kappaB activation. TNF-alpha-induced proliferation of synoviocytes was inhibited by transfection with a dominant negative mutant form of I-kappaBalpha cDNA (I-kappaBalphadN). Moreover, following TNF-alpha treatment, transfectants with I-kappaBalphadN underwent apoptosis, whereas mock-transfectants did not. Taken together, these results suggest that high levels of TNF-alpha present in RA synovium play an important role in the synovial hyperplasia of RA by suppressing apoptosis and promoting proliferation of synoviocytes through NF-kappaB-dependent signaling pathways mediated by up-regulated TNFR2 and TRAF1-6 molecules.
12673891 Interleukin-6, soluble interleukin-2 receptor and soluble interleukin-6 receptor in the se 2003 Jan OBJECTIVE: The present study was conducted to investigate whether the serum levels of interleukin 6 (IL-6), soluble IL-2 receptor (sIL-2R) and sIL-6R are associated with the morphological appearance of rheumatoid arthritis (RA). METHODS: Using the ELISA technique we measured the IL-6, sIL-2R and sIL-6R concentrations in the serum of 34 patients with RA and 28 patients with osteoarthritis (OA). Histological analysis of synovial samples distinguished 2 types of rheumatoid synovitis. Twenty-one RA specimens presented diffuse infiltrates of mononuclear cells without any specific microanatomical organization. In remaining 13 samples the formation of lymphocytic follicles with germinal center-like structures was found. RESULTS: Serum levels of IL-6, sIL-2R and sIL-6R were elevated in patients with RA compared to the OA control group (p < 0.001, p < 0.001 and p < 0.05 respectively). Concentrations of IL-6 and sIL-2R were highest in the serum of RA patients with follicular synovitis in comparison to patients with diffuse synovitis (p < 0.001 and p < 0.01 respectively) and could distinguish RA patients with these two histological variants of the disease. Serum levels of IL-6 and sIL-2R correlated with markers of disease activity such as ESR and CRP levels. In addition, the clinical data suggest a more severe disease among RA patients with follicular synovitis. CONCLUSION: Distinct histological types of rheumatoid synovitis associated with unique serum concentrations of IL-6 and sIL-2R reflect levels of disease activity and confirm the concept of RA heterogeneity.
15552525 Benefits and risks of biological agents: lymphomas. 2004 Sep Lymphomas are uncommon malignancies of unknown aetiology. Rheumatoid arthritis is a known risk factor for lymphoma, and some studies show that this risk is higher in patients with more severe disease. The causes of the association between RA and lymphoma are not understood. Conventional anti-rheumatic agents may increase the risk for lymphoma, but these associations are relatively weak at most. For the currently available TNF-alpha antagonists, available data include the possibility of a somewhat higher risk for lymphoma than for patients not treated with such agents, but also point to several sources of bias that could explain a possible association. Current practice recommendations should probably not go further than an awareness of the possibility of lymphoma in any patient with RA exhibiting unexplained systemic symptoms.
15571207 Antimetabolites in the treatment of arthritis: current status of the use of antimetabolite 2004 Oct Rheumatoid arthritis (RA) is an autoimmune disease characterized by a chronic inflammation of the synovial joints and infiltration of blood-derived cells. In daily practice rheumatologists use the antimetabolites methotrexate (MTX) and leflunomide for the treatment of patients with rheumatoid arthritis. The current clinical status (efficacy/toxicity) of these 2 antimetabolites in the treatment of RA will be discussed.