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ID PMID Title PublicationDate abstract
14687914 Rheumatoid arthritis: regulation of synovial inflammation. 2004 Mar Rheumatoid arthritis (RA) is a systemic, inflammatory autoimmune disorder that presents as a symmetric polyarthritis associated with swelling and pain in multiple joints, often initially occurring in the joints of the hands and feet. Articular inflammation causes activation and proliferation of the synovial lining, expression of inflammatory cytokines, chemokine-mediated recruitment of additional inflammatory cells, as well as B cell activation with autoantibody production. A vicious cycle of altered cytokine and signal transduction pathways and inhibition of programmed cell death contribute to synoviocyte and osteoclast mediated cartilage and bone destruction. A combination of targeted interventions at various stages in the pathogenesis of RA will likely be required to control symptoms in certain patients with this complex and potentially disabling disease. The regulation of rheumatoid synovial inflammation will be reviewed, followed by a brief summary of the therapeutic implications of these advances, including strategies targeting key cytokines, signal transduction molecules, co-stimulatory molecules, B cells, chemokines, and adhesion molecules.
12435163 Rheumatoid arthritis: principles of early treatment. 2002 Nov Early diagnosis and effective treatment is considered to be important in the prevention of joint damage and disability in patients with rheumatoid arthritis (RA). This hypothesis has led to the establishment of special early arthritis clinics in many centers. The lag times between onset of symptoms of RA and diagnosis, and the introduction of disease modifying antirheumatic drugs, have been greatly reduced. Treatment strategies have become increasingly refined. Moreover, newer therapies have increased the options for limiting early joint damage and subsequent disability.
12524563 Rheumatoid arthritis of the cervical spine. 2002 Jun The cervical spine is commonly affected in patients with rheumatoid arthritis. Erosive synovitis of the joints of the cervical spine can result in various types of subluxations. Subluxations and pannus formation can cause significant pain and neurological compromise. Surgery is an important treatment modality for patients with intractable neck pain and neurological deficits. This article reviews the indications for surgery and surgical procedures of decompression and arthrodesis. New surgical fixation techniques have resulted in improved arthrodesis rates. However, long-term effects on adjacent motion segments is not known. The cornerstone of good surgical outcome remains careful selection of patients and appropriate choice of surgical decompression and fusion.
12915162 Rheumatoid arthritis in the developing world. 2003 Oct The general impression is that rheumatoid arthritis (RA) has a lower prevalence and a milder course in developing countries. Epidemiological studies from different regions show that varying prevalence is possibly related to urbanization. The data suggest that where severe disability does occur, it presents a significant health challenge because of scarce medical and social resources. Disease-modifying anti-rheumatic drugs (DMARDs) remain the mainstay of therapy to alter the natural history of the disease. New therapies are unlikely to be of general benefit in the developing world because of financial constraints and increased risk of infections, particularly tuberculosis, associated with the use of tumour necrosis factor-alpha blockers. Instead, future research in poorer communities should be directed at assessing the burden of disease, the role of early aggressive therapy with DMARDs in combination with glucocorticoids for the majority of patients with RA, and finally, sourcing targeted biological therapies through clinical trials and grants for compassionate use in patients with refractory disease.
12819477 Effects of rheumatoid arthritis on bone. 2003 Jul The effects of rheumatoid arthritis on bone include structural joint damage (erosions) and osteoporosis. The latter may lead to increased risk for fractures, which are associated with increased morbidity and mortality. Osteoporosis in rheumatoid arthritis is characterized by a complexity of risk factors, including primary osteoporosis risk factors in addition to inflammation, immobilization, and use of corticosteroids. Quantitative assessment of periarticular and generalized bone loss in rheumatoid arthritis may be reliable indicators of future disease course and potential response variables in intervention studies. The osteoclast cell in rheumatoid arthritis plays a crucial role in the development of erosions and periarticular and generalized osteoporosis, suggested to be mediated through the osteoprotegerin/receptor activator of Nuclear Factor (NF)-kappabeta/receptor activator of NF-kappabeta ligand signaling system. Based on an improved understanding of this biology, new treatment opportunities exist.
12106492 Homing chemokines in rheumatoid arthritis. 2002 In about 20% of patients with rheumatoid arthritis, B and T lymphocytes recruited into the inflamed synovium are organized into complex microstructures, which resemble secondary lymphoid organs. The development of such lymphoid aggregates with germinal centers appears to contribute to the pathogenesis of the disease. Growing evidence indicates that chemokines and their receptors control the recruitment and positioning of leukocytes as well as their organization into node-like lymphoid structures. Here, we comment on recent studies highlighting the importance of chemokines in rheumatoid arthritis, in particular of B-cell-activating chemokine-1 in lymphoid neogenesis in the inflamed synovium.
14531955 Atherosclerotic cardiovascular disease in rheumatoid arthritis. 2003 Aug The past 3 years have seen a remarkable growth in the interest of cardiovascular disease in rheumatoid arthritis. There have been studies published documenting an increased incidence and prevalence of cardiovascular conditions in patients with rheumatoid arthritis compared with individuals without rheumatoid arthritis. There has also been interest in the occurrence of cardiovascular risk factors in rheumatoid arthritis and in the role of antirheumatic therapy, including cyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs, methotrexate, corticosteroids, and tumor necrosis factor inhibitors. A number of studies using noninvasive means to detect atherosclerosis have shown that patients with rheumatoid arthritis may be prone to atherosclerosis. This information should be important to physicians who provide care to patients with rheumatoid arthritis, given the difficulty of recognizing cardiovascular signs and symptoms among patients with the disease.
15680099 A review of rheumatoid arthritis affecting the foot and ankle. 2004 Dec Rheumatoid arthritis is a systemic disease that often affects the foot and ankle. Approximately 20% of patients with rheumatoid arthritis present initially with foot and ankle symptoms, and most patients will eventually develop foot and ankle symptoms. Although early intervention includes conservative measures, operative treatment often is needed to adequately treat rheumatoid patients. Treatment of foot and ankle problems in patients with rheumatoid arthritis is directed to maintaining ambulatory capacity. This article reviews the clinical presentation, evaluation, and treatment of rheumatoid arthritis affecting the foot and ankle.
14650090 Rheumatoid arthritis. Targeted interventions can minimize joint destruction. 2003 Nov Rheumatoid arthritis can cause joint erosion and deformity, pain, stiffness, and decreased function and range of motion. Early diagnosis is crucial to prevent permanent joint damage. In this article, Drs Williams and Fye discuss articular and extra-articular manifestations of rheumatoid arthritis as well as the evolving treatment approaches to this complex disease.
15274231 [Internist's therapy of rheumatoid arthritis]. 2004 Jun Rheumatoid arthritis is the most common inflammatory joint disease and is characterized by chronic, symmetric, erosive synovitis of small joints of hands and feet. Prevalence in women is threefold higher than in man. Structural damage of the joints starts between the first and second year of the disease. Early therapeutic interventions can alter the course of rheumatoid arthritis by delaying the progression of radiographic joint destruction, which correlates with the grade of disability. Approval of new biologic antirheumatic drugs in the last few years improved the outcome of rheumatoid arthritis.
12955191 [Imaging in rheumatoid arthritis of the elbow]. 2003 Aug Early specific radiologic changes of rheumatoid arthritis can usually be detected in the hands and feet. Later stages of the disease process show a typical centripetal spread of the affected joints, i.e., shoulder, elbow, and knee. For prognostic assessment of cubital rheumatoid arthritis, conventional radiography still remains the gold standard. X-rays allow objective scoring and thus classification into standardized stages. A concentric destruction of the rheumatic joint as compared to deformity in the degenerative joint is the typical radiologic symptom to look for. For soft tissue assessment, ultrasound (US) should be the diagnostic tool of choice. Due to the thin surrounding soft tissue layer, as well as the advanced high-resolution technology, bony structures can also be well demonstrated in any plane. In the early arthritic stages, particularly the small changes, e.g., minimal erosions of the cortical area, are very well detectable by US. The use of "color" allows good evaluation of the synovial inflammatory status. Modern imaging methods such as computer- assisted tomography (CAT) scan and magnetic resonance imaging (MRI) are restricted to a few set indications and should not be chosen for routine examination. More invasive methods such as arthrography are no longer indicated for assessment of cubital rheumatoid arthritis.
15201937 [Outcome predictors in rheumatoid arthritis]. 2004 Jan Predicting which patients will develop severe rheumatoid arthritis is essential for selection of the most appropriate treatment regimen in early arthritis. The key outcomes in rheumatoid arthritis are persistence of the disease, joint damage (evaluated by X-ray progression), functional disability, and mortality rate. Rheumatoid factor positivity and number of swollen joints appear to be related to all of these outcomes, while radiologic scores are mostly related to joint damage and health assessment questionnaire (HAQ) to functional disability. Other relevant prognostic parameters are erythrocyte sedimentation rate or serum C-reactive protein levels, and antibodies to citrullinated peptides.
12558557 [Pathogenesis of osteoporosis in rheumatoid arthritis]. 2003 Osteoporosis is a major clinical problem in rheumatoid arthritis. Patients with rheumatoid arthritis frequently not only present with juxta articular osteopenia and bone erosions but also with generalized axial and appendicular osteoporosis at sites distant from inflamed joints. The pathogenesis of bone loss in rheumatoid arthritis is multifactorial; disease activity certainly is a major determinant of bone mass. Further pathogenetic factors include effects of anti-inflammatory therapies (in particular glucocorticoids), reduced mobility, estrogen and/or androgen deficiency. Recently, receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG), a decoy receptor for receptor activator of nuclear factor kappa B ligand, were identified as central regulators of osteoclast recruitment and activation. Osteoprotegerin and receptor activator of nuclear factor kappa B ligand production is modulated by several cytokines, growth factors and hormones. In rheumatoid synovium both fibroblasts and activated T cells express receptor activator of nuclear factor kappa B ligand and thereby promote osteoclast recruitment and activation. Thus, osteoprotegerin and receptor activator of nuclear factor kappa B ligand appear to represent important molecular links between the immune system and bone metabolism in rheumatoid arthritis.
12387195 [Prognostic factors in rheumatoid arthritis]. 2002 Sep 1 Rheumatoid arthritis is a chronic, progressive, inflammatory joint disease, affecting primarily the small joints of the hands and feet symmetrically and characterized by joint destruction, progressive disability, and premature death. Rheumatoid arthritis shows a wide spectrum of clinical phenotypes from mild disease to severe arthritis. Aggressive disease implies a rapidly progressive course affecting most joints, with little or no response to drug therapy, and sometimes complicated by life-threatening extraarticular involvement. The eventual multiple joint destruction requires major surgery, and severe disability results in loss of occupation and dependence on others. Many prospective cohort studies have attempted to predict outcomes and develop prognostic markers, especially in early disease. Probably most useful are those factors that independent of disease activity, such as the presence of rheumatoid factor, the so-called shared epitope of HLA-DR. In addition, clinical indicators (e.g., higher affected joint counts, the presence of extra-articular features, subcutaneous nodules, considerable degree of physical disability at onset), laboratory variables (e.g., longstanding increased acute-phase response, decreased hemoglobin) are indicating a poor prognosis. Some sociodemographic markers, such as female sex and a lower level of formal education are associated with a poor prognosis. An ideal prognostic marker should be reliable, simple, accurate and independent of the stage and inflammatory activity of RA so that they can be used early of the disease. Patients with a poor outcome should be treated promptly and aggressively with disease-modifying antirheumatic drugs to limit or prevent further disease progression.
14969066 Early rheumatoid arthritis in African-Americans: the CLEAR Registry. 2003 Sep African-Americans have been under-represented in genetic studies of rheumatoid arthritis (RA) susceptibility and severity. Genetic and non-genetic factors influencing the radiographic severity of RA and its response to treatment are poorly understood, particularly in African-Americans. The Consortium for the Longitudinal Evaluation of African-Americans with early RA (CLEAR) Registry, a collaborative effort among four institutions in the southeast USA, will hopefully provide a useful resource to study these issues.
12033742 Development of anti-TNF therapy for rheumatoid arthritis. 2002 May The aetiology of systemic, autoimmune, chronic inflammatory diseases--such as rheumatoid arthritis--is not known, and their pathogenesis is complex and multifactorial. However, progress in the characterization of intercellular mediators--proteins that are now known as cytokines--has led to the realization that one cytokine, tumour-necrosis factor (TNF; previously known as TNF-alpha), has an important role in the pathogenesis of rheumatoid arthritis. This discovery heralded a new era of targeted and highly effective therapeutics for rheumatoid arthritis and, subsequently, other chronic inflammatory diseases.
14731052 Infliximab: a pharmacoeconomic review of its use in rheumatoid arthritis. 2004 Infliximab (Remicade), a biological disease-modifying antirheumatic drug (DMARD), binds to and inhibits the activity of tumour necrosis factor-alpha, which is thought to play an important role in the pathophysiology of rheumatoid arthritis. Intravenous infliximab plus methotrexate is recommended in patients with rheumatoid arthritis who have not achieved satisfactory disease control with adequate courses of other DMARDs. Pharmacoeconomic analyses have been based on efficacy data from the pivotal placebo-controlled Anti-Tumour Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) trial in patients with active, refractory rheumatoid arthritis. Infliximab every 8 weeks plus methotrexate demonstrated rapid and sustainable improvements in clinical response, delayed radiographic progression, and/or improved functional status and health-related QOL compared with placebo plus methotrexate at weeks 30, 54 and 102. In cost-utility analyses of infliximab plus methotrexate conducted from a healthcare payer and/or societal perspective in the US, Europe, Portugal, Sweden and the UK, infliximab 3 mg/kg every 8 weeks plus methotrexate was associated with acceptable (<$US50,000 per discounted QALY gained) cost-utility ratios relative to methotrexate alone in patients with active, refractory rheumatoid arthritis. When only direct costs were considered, the lifetime incremental cost per discounted QALY gained with infliximab plus methotrexate relative to methotrexate alone was $US30,500-38,700 (year of costing 1998 or not reported; treatment duration 54 or 102 weeks or lifelong) in the US and Europe analyses, and euro39 500 (year of costing not reported; lifelong treatment) in the Portuguese analysis. The cost-utility ratios were more favourable when lost productivity costs or the additional benefit of infliximab on radiographic stabilisation were considered. In the Swedish and UK analyses with a 10-year time horizon, infliximab plus methotrexate for 1 or 2 years was associated with cost-utility ratios of euro28 600-56 100 (year of costing not reported) when direct costs were considered, and euro3440-48 200 when direct costs plus loss-of-productivity costs were considered. In conclusion, cost-utility analyses, which were based on modelling of data from the pivotal clinical trial of infliximab plus methotrexate, indicate that infliximab plus methotrexate is associated with acceptable cost-effectiveness ratios (<$US50,000 per discounted QALY gained) relative to methotrexate monotherapy in patients with active rheumatoid arthritis who have not responded to previous methotrexate or other DMARD therapy. The cost effectiveness of infliximab versus other DMARDs is at present unclear, but will be clarified when appropriate data from directly comparative clinical and/or pharmacoeconomic studies become available. In patients in whom adequate courses of other DMARDs have failed to achieve satisfactory disease control, infliximab plus methotrexate may prevent or delay disability, which may produce reductions in nondrug costs that can help offset its acquisition cost.
15301984 The treatment of rheumatoid arthritis. 2004 Aug The treatment of rheumatoid arthritis has changed dramatically in the last 10 years and in parallel the definition and expectations of patients and clinicians of the effects of disease-modifying anti-rheumatic agents has changed as well. Current expectations of efficacy now include improvement of signs and symptoms of disease activity as well as slowing, if not complete inhibition, of disease progression as measured by X-ray progression along with significant improvement in patient physical function. In addition, clinicians assess the safety profile of these agents more critically in an attempt to improve the risk:benefit profile. Drugs, such as methotrexate, sulfasalazine and leflunomide have provided patients with substantial relief of symptoms and improvement in terms of X-ray progression, but they have been hampered by the occurrence of significant adverse events along with the inability to maintain benefit for prolonged periods of time. With the increased understanding of the basic biological mechanisms of the disease process, there has been the introduction of four biological disease modifying therapies and other drugs into clinical practice, which have altered aspects of the risk:benefit ratio for patients with various rheumatic diseases.
15172040 Associations between rheumatoid arthritis and malignancy. 2004 May There are many complex associations between rheumatoid arthritis(RA) and malignancy. Patients with rheumatic diseases on the whole appear to be at increased risk for the development of certain malignancies. The data from several studies are persuasive that the presence of RA conveys an increased risk for the development of lymphoproliferative disorders and may convey a decreased risk for the development of malignancies of the digestive tract. Understanding the complex interrelationships between RA and malignancy will lead to more accurate diagnosis of underlying pathology, more effective treatment of symptoms and underlying disease, and appropriate surveillance for the development of later complications.
15338252 [Radiological diagnostics of cervical rheumatoid arthritis]. 2004 Aug Rheumatoid arthritis leads to characteristic findings at the synovial joints, the intervertebral discs and the processes of the cervical spine. Isolated findings are not specific for rheumatoid arthritis. In fact, due to common underlying pathophysiologic changes they also develop in other inflammatory diseases affecting the cervical spine. Therefore, each radiological examination is to be understood and used as a piece in the diagnostic puzzle. Only in conjunction with clinical information does it add to a conclusive diagnosis. Nevertheless certain patterns of findings help in narrowing the list of differential diagnosis. Besides their role in initial diagnosis, radiological examinations are crucial tools in the peri- and post-operative work-up and in the detection of typical complications of rheumatoid arthritis with cervical manifestations, i. e. various instabilities and their consequences, as those have an impact on the therapeutic approach and prognosis.