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ID PMID Title PublicationDate abstract
19072521 Rheumatoid arthritis: a female challenge. 2008 Mar Rheumatoid arthritis (RA) is two- to three-fold more frequent in women than in men and a strong association with sex hormones has been demonstrated. There is strong evidence that autoimmunity is under genetic control, and genes in sexual chromosomes can play a role in supporting the female prevalence. On the other hand, it is widely accepted that sex hormones--estrogens in particular--may regulate the immune response by favoring the survival of forbidden autoreactive clones and ultimately the prevalence of autoimmunity in women. Accordingly, estrogens have been suggested to be associated with the development of RA. Pregnancy in RA women is a common situation and most pregnant patients experience a remission. This has been closely related to a switch from Th1 to Th2 immune responses and to a decreased production of proinflammatory cytokines, at least in part supported by the changes of the hormonal profile in pregnancy. Pregnancy planning is required in RA in order to avoid unwanted complications. In particular, the need to control the disease requires safe use of antirheumatic drugs both during the pregnancy itself and in the breastfeeding period. Hormonal treatment for contraception is contraindicated in the case of positivity for antiphospholipid antibodies owing to the increased thrombophilic risk. Similarly, replacement hormonal treatment in postmenopausal women with RA to control osteoporosis is no longer recommended as a result of its ability to increase the cardiovascular risk closely associated with RA itself.
17852027 Rheumatoid arthritis and the complement system. 2007 Complement activation contributes to a pathological process in a number of autoimmune and inflammatory diseases, including rheumatoid arthritis (RA). In this review we summarize current knowledge of complement contribution to RA, based on clinical observations in patients and in vivo animal models, as well as on experiments in vitro aiming at elucidation of underlying molecular mechanisms. There is strong evidence that both the classical and the alternative pathways of complement are pathologically activated during RA as well as in animal models for RA. The classical pathway can be initiated by several triggers present in the inflamed joint such as deposited autoantibodies, dying cells, and exposed cartilage proteins such as fibromodulin. B cells producing autoantibodies, which in turn form immune complexes, contribute to RA pathogenesis partly via activation of complement. It appears that anaphylatoxin C5a is the main product of complement activation responsible for tissue damage in RA although deposition of membrane attack complex as well as opsonization with fragments of C3b are also important. Success of complement inhibition in the experimental models described so far encourages novel therapeutic approaches to the treatment of human RA.
16864922 Pregnancy and rheumatoid arthritis. 2006 Aug Pregnancy in most cases, is associated with remission of rheumatoid arthritis (RA), but a quarter of patients continue to have active disease or even worsening of the disease and most patients who improve, relapse in the postpartum period. The pathophysiology of this improvement in disease activity during pregnancy remains unknown, but hormonal, cell-mediated immunological and humoral immunological changes during pregnancy, have been proposed responsible for this. Most of the pregnant women with RA have an uneventful course, with no significant complications. In general, no significant increase in maternal or fetal morbidity seems to be attributable to RA. Patients with RA do not have decreased fertility. A majority of patients with RA may go in remission and anti-rheumatic treatment may not be required as soon as women become pregnant. But other patients who continue with the disease activity require treatment. The preferred disease-modifying agents during pregnancy are sulfasalazine and hydroxychloroquine. Azathioprine and cyclosporine can be used if the benefits outweigh the risks. Paracetamol and low dose prednisone are preferred and considered safe, both for mother and fetus. Methotrexate and lefunomide are contraindicated and must be prophylactically withdrawn before a planned pregnancy. Biologics generally should be stopped when pregnancy is discovered. An overall rational approach is highly warranted to treat RA during pregnancy.
16991011 [Rheumatoid arthritis and cardiovascular complications]. 2006 Oct Rheumatoid arthritis is associated with increased morbidity and mortality due to cardiovascular events. Elevated concentrations of acute-phase proteins and cytokines and endothelial dysfunction, demonstrated also by lack of traditional risk factors, play an important role in these complications. Antirheumatic drug treatment can modify the frequency and severity of cardiovascular events.
17985417 Early rheumatoid arthritis -- is there a window of opportunity? 2007 Nov The early diagnosis and treatment of nascent rheumatoid arthritis (RA) has become a prime objective for rheumatologists and clinicians who care for patients with arthritis. Population-based studies have consistently shown that patients with RA are at substantial risk for progressive joint damage, disability, and increased morbidity and mortality. These inevitable outcomes are closely linked to the consequences of rheumatoid inflammation, which begins early and is progressive in all. At issue is whether early diagnosis, coupled with aggressive therapy, might alter the natural history of this RA. If this "window of opportunity" exists, then outcomes should be substantially altered by delivering the right therapies at the right time. A growing body of evidence has emphasized the consistent clinical and radiographic benefits of early, aggressive treatment of RA. These studies confirm that all therapies - monotherapy, combination disease modifying antirheumatic drugs (DMARD), biologics - work better in early disease than in long-established RA. Earlier identification, referral, and an accurate diagnosis of RA can now be rewarded with highly effective DMARD or biologic therapies. Rheumatologists should rise to the challenge and educate clinicians about this window of opportunity, the potential for remission, and superior clinical responses when patients with early RA or undifferentiated arthritis are referred to and managed by experts in aggressive rheumatologic care.
18388528 Lung disease in rheumatoid arthritis. 2008 May PURPOSE OF REVIEW: To examine the role of lung disease in rheumatoid arthritis from a clinical, epidemiologic, pathophysiologic, and therapeutic perspective. RECENT FINDINGS: Lung disease in rheumatoid arthritis is pleomorphic and has a marked adverse impact on the morbidity and premature mortality of patients with this disease. Recent advances in the understanding of the pathophysiology of lung disease associated with rheumatoid arthritis reveal it to be characterized by more active cellular infiltrates of both T cells and B cells, as well as other immunologically active cells, including mast cells, than many of the other forms of interstitial lung disease. Satisfactory treatment is lacking; available biologic response modifiers have been reported to have both beneficial and adverse effects on the lung. Newer approaches targeting cellular immunologic dysfunction including T-cell-directed and B-cell-directed therapies hold the promise of reducing lung damage related to the underlying disease. SUMMARY: Lung disease in rheumatoid arthritis is a heterogeneous and oftentimes serious condition, with a profound impact on patient wellbeing and survival. Advances in the understanding of its etiology and targeted application of available, as well as development of new, more specific therapeutics will be of benefit to patients with rheumatoid arthritis who are suffering from lung disease.
16462519 Genetic epidemiology of rheumatoid arthritis. 2006 Mar PURPOSE OF REVIEW: This review aims to summarize articles published between October 2004 and November 2005 that have investigated the genetic epidemiology of rheumatoid arthritis. RECENT FINDINGS: The consistent replication of an association between the R620W single nucleotide polymorphism in PTPN22 and rheumatoid arthritis clearly establishes this polymorphism as an important risk factor for rheumatoid arthritis. SUMMARY: Genetic investigations of rheumatoid arthritis have predominantly been single nucleotide polymorphism-based candidate gene association studies searching for markers of susceptibility, severity or treatment response. Studies of the human leukocyte antigen region have refined and added to our understanding of the complex associations to polymorphisms with this locus. PTPN22 has emerged strongly as a genuine rheumatoid arthritis susceptibility gene with replications of the association to the R620W single nucleotide polymorphism. Many investigations have been conducted on the genetics of treatment response -- some 'generic' and others specific in terms of identifying genetic influences to the mode of action and metabolism of particular agents.
17870029 Established rheumatoid arthritis: clinical assessments. 2007 Oct Clinical assessment of established rheumatoid arthritis (RA) can have several purposes. It can be used to evaluate prognosis, disease course or interventions at both the individual and the group level (i.e. in a clinical trial), over the short or long term. The instruments used for the different purposes are not always the same. For example, information on prognosis is very useful when assessing the risk:benefit ratio of early aggressive pharmacotherapy; however, established prognostic factors are currently of limited use in individual patients with established RA. As, at the individual patient level, disease activity, disability and joint damage have variable courses, the course of the disease should be evaluated regularly both with process (i.e. erythrocyte sedimentation rate, joint counts) and with outcome (i.e. radiological progression, sum of past process) measures. For the evaluation of interventions, 'core sets' of valid measures to assess disease activity, outcome and specific criteria for improvement are used; these can, to some extent, be useful in clinical practice.
16582694 Cardiovascular disease in rheumatoid arthritis. 2006 May PURPOSE OF REVIEW: Individuals with rheumatoid arthritis are at increased risk for morbidity and mortality from cardiovascular disease (CVD). The purpose of this review is to discuss recent advances in our understanding of the pathogenesis, prevalence, treatment, and prevention of accelerated atherosclerotic disease in rheumatoid arthritis. RECENT FINDINGS: Recent reports have highlighted the increased risk for silent myocardial infarction and sudden death in rheumatoid arthritis, and the potential roles of traditional and nontraditional risk factors for CVD, including abnormal revascularization of damaged peripheral blood vessels and genetic polymorphisms. Several studies have also added important information on the possible role of anti-tumor necrosis factor-alpha therapy, other disease modifying antirheumatic drugs, and nonsteroidal anti-inflammatory drugs in decreasing CVD risk. SUMMARY: The pathogenic mechanisms involved in accelerated cardiovascular complications in rheumatoid arthritis appear to be complex and multifactorial. Both traditional and nontraditional risk factors potentially contribute to the increased cardiovascular risk. Good control of the inflammation, immunologic disturbances, and metabolic changes seen in rheumatoid arthritis are crucial in the prevention of this potentially lethal complication. There is a need for heightened awareness of the increased risk for silent ischemia, early myocardial infarction, and sudden death. Further exploration of the mechanisms of vascular repair and their potential role in premature atherosclerosis is needed.
18987647 Rheumatoid arthritis: a view of the current genetic landscape. 2009 Mar The field of genetics and autoimmune diseases is undergoing a rapid and unprecedented expansion with new genetic findings being reported at an astounding pace. It is now clear that multiple genes contribute to each of the major autoimmune disorders, with significant genetic overlaps among them. Rheumatoid arthritis (RA) is no exception to this, and emerging data are beginning to reveal the outlines of new diagnostic subgroups, complex overlapping relationships with other autoimmune disorders and potential new targets for therapy. This review describes the evolving genetic landscape of RA, with the full knowledge that our current view is far from complete. However, with the first round of genome-wide association scans now completed, it is reasonable to begin to take stock of the direction in which the major common genetic risk factors are leading us.
17372744 [Autoantibody profile in rheumatoid arthritis]. 2007 May Antibodies against citrullinated protein/peptides antigens (ACPA) are well recognized serological markers for rheumatoid arthritis. In addition to rheumatoid factor, they provide high diagnostic specificity and are also useful diagnostic tools in the search for early disease manifestation. As shown by several studies, both autoantibodies correlate with disease severity and the radiologic progression of rheumatoid arthritis. However, it is important to note that only the detection of rheumatoid factors is internationally standardized. Whether autoantibody profiling is also of significance for the stratification and monitoring of rheumatoid arthritis is the focus of ongoing investigations.
16729626 Rheumatoid arthritis: acute presentations and urgent complications. 2006 May Rheumatoid arthritis is a common chronic disorder. Its many complications, comorbidities and adverse effects of treatment often involve general physicians. Particular risks are septic arthritis, systemic infections, upper gastrointestinal ulcers and systemic vasculitis. Delayed diagnosis will result in poor outcomes.
17824174 Pathogenesis and therapy of rheumatoid arthritis. 2006 Rheumatoid arthritis is a chronic disabling disease affecting at least 1% of the population on a worldwide basis. Research aimed at understanding the pathogenesis of this disease led to the identification of TNFalpha as a major pro-inflammatory cytokine expressed in the inflamed joints of patients with rheumatoid arthritis. Subsequently, in vitro studies provided evidence to suggest that TNFalpha played an important role in driving the expression of additional pro-inflammatory cytokines, such as IL-1, GM-CSF, IL-6, and IL-8, in synovial cell cultures. Another important finding that confirmed the pathological significance of TNFalpha was that mice genetically engineered to overexpress TNFalpha spontaneously developed arthritis. Subsequently, the therapeutic effect TNFalpha blockade was tested in animal models prior to clinical trials in human patients, which provided unequivocal verification of the validity of TNFalpha as a therapeutic target. Anti-TNFalpha therapy is now accepted as a fully-validated treatment modality for rheumatoid arthritis.
16431343 S100A4 (Mts1): is there any relation to the pathogenesis of rheumatoid arthritis? 2006 Feb S100A4 (Mts1) belongs to the S100 family of calcium binding proteins, which are involved in diverse biological regulatory activities. An association between S100A4 and tumor progression has been demonstrated in several studies. S100A4 binds to distinct intracellular target proteins and regulates specific functions involved in tumor progression such as cell motility, proliferation and apoptosis as well as remodelling of the extracellular matrix. Once released from the tumor or tumor-activated stromal cells, it may influence certain functions of target cells towards a more aggressive phenotype. Extracellular S100A4 has been demonstrated to contribute to angiogenesis and the increased production of matrix-degrading enzymes by both endothelial and tumor cells. Moreover, S100A4 might be responsible for TCRgammadelta T-cell mediated lysis and negative regulation of matrix mineralization. Increased expression of S100A4 mRNA has recently been found in proliferating rheumatoid arthritis synovial fibroblasts and synovial tissues from rheumatoid arthritis patients. Synovial hyperplasia in rheumatoid arthritis consists of inflammatory cells and activated synovial lining cells which contribute to the progressive destruction of the joints during the disease. Since several phenomena are similar between rheumatoid arthritis and malignant tumors it can be hypothesized that S100A4 contributes to the invasive and tumor-like behavior of rheumatoid arthritis synovium.
17367692 Rheumatic disease in the elderly: rheumatoid arthritis. 2007 Feb This article summarizes the different aspects of rheumatoid arthritis and the spectrum of diseases that can present as rheumatoid arthritis in the elderly population. With the ageing of the western population, different forms of inflammatory arthritis' prevalence and incidence are increasing in elderly persons. Difficulties in establishing the diagnosis and introducing new treatment modalities in this patient group pose a great challenge for clinicians. The management of inflammatory arthritis in the elderly requires special consideration in regard to the comorbidities and increased frequency of adverse events. There is substantial need for improving aspects of diagnostic and therapeutic interventions that will reduce the impact of inflammatory arthritis in the growing elderly population.
17121483 The pathogenesis of rheumatoid arthritis. 2006 Rheumatoid arthritis (RA) is due to a combination of phagocytosis and anaphylaxis gone awry. Immune complexes create their havoc via Fc gamma III receptors that signal via the tyrosine phosphorylation immunoreceptor pathway. Anaphylatoxins, mainly C5a, signal via the MEK kinase cascade, and both engage in cross-talk via NF kappa B. Aspirin-III blocks signals sent by both: immune complexes via FCR, and anaphylatoxin via C5 receptors. Drugs that affect both pathways, for example anti-B cell monoclonal antibodies, such as rituximab, and anti-C5 monoclonal antibodies, such as pexelizumab are currently being investigated. We now appreciate that cytokines are important mediators of inflammation in RA but are downstream of the primary insults: immune complexes and anaphylatoxins. We can therefore begin to ask what the antigen or antigens might be that produce IgGs reactive to 7 S or 19 S rheumatoid factors. The primary antigens of RA could well be CPs, formed perhaps by oral bacteria. Once immunoglobulins become recognized by rheumatoid factors, immune complexes form, and these activate anaphylatoxins. Phagocytosis and anaphylaxis are the proximal events of RA.
17684873 Rheumatoid arthritis: current pharmacologic treatment and anesthetic considerations. 2007 Jun A diagnosis of rheumatoid arthritis carries with it a lifelong progressive disease; however twenty percent of patients enjoy periods of partial to total remission. After remission, the disease will frequently plague previously unaffected joints. Life expectancy is reduced by an average of three to seven years. Complications of RA include vasculitis and amyloidosis affecting any vessel, including the aorta. Additionally, complications of therapy such as chronic NSAID use leading to GI bleeding and infections associated with long term steroid use, can add to the difficulties of the disease. The recent discovery and use of anticytokines and DMARDs has lead to greatly reduced symptomology associated with RA and greater patient comfort. Side effects of drugs should be well understood including the risk of bleeding from NSAIDs. Management and surgical intervention of problems that arise from this disease vary dramatically. The anesthesiologist must be aware of airway pathologies, pain management techniques, and available pharmacology parameters.
16526162 An overview of rheumatoid arthritis. 2006 Feb 22 This article aims to inform general nurses about the management of patients with rheumatoid arthritis. It outlines the signs and symptoms, disease processes and treatment, and highlights the importance of the nurse's role in supporting these patients.
17169137 What is MRI bone oedema in rheumatoid arthritis and why does it matter? 2006 MRI bone oedema occurs in various forms of inflammatory and non-inflammatory arthritis and probably represents a cellular infiltrate within bone. It is common in early rheumatoid arthritis and is associated with erosive progression and poor functional outcome. Histopathological studies suggest that a cellular infiltrate comprising lymphocytes and osteoclasts may be detected in subchondral bone and could mediate the development of erosions from the marrow towards the joint surface. There is emerging evidence from animal models that such an infiltrate corresponds with MRI bone oedema, pointing towards the bone marrow as a site for important pathology driving joint damage in rheumatoid arthritis.
18373887 Recent developments in the immunobiology of rheumatoid arthritis. 2008 Progress into the understanding of immunopathology in rheumatoid arthritis is reviewed in the present article with regard to pro-inflammatory cytokine production, cell activation and recruitment, and osteoclastogenesis. Studies highlight the potential importance of T helper 17 cells and regulatory T cells in driving and suppressing inflammation in rheumatoid arthritis, respectively, and highlight other potential T-cell therapeutic targets. The genetic associations of the HLA shared epitope alleles with antibodies to citrullinated peptides in rheumatoid arthritis patients indicate that T cells are providing help to B cells to produce autoantibodies, and there is increasing evidence that these autoantibodies are pathogenic in rheumatoid arthritis.