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ID PMID Title PublicationDate abstract
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.
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.
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.
16328755 [Early diagnosis of rheumatoid arthritis]. 2005 Nov The therapeutic concept of rheumatoid arthritis changed dramatically during the last years. There is significant evidence for the need of an early treatment with disease modifying drugs, the new therapeutic aim is remission. And then the question is: what is a rheumatoid arthritis and when does it start? There is move into the direction of an early undifferentiated arthritis, which may or may not become a persistent arthritis with or without development of erosions. Diagnostic criteria for rheumatoid arthritis are not exsisting, and this article comes after reviewing the existing instruments to the conclusion there is no need for such criteria. In fact, there is a need for instruments that evaluate the risk of an individual patient for persistence, erosive arthritis, and even better, the severity of the disease, which means a judgement of progression. And then the rheumatologists can set the crossbar for starting a DMARD-therapy.
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.
15588971 Early diagnosis of rheumatoid arthritis. 2005 Feb Early diagnosis of rheumatoid arthritis (RA) is an important challenge for clinical rheumatologists. This is because there is substantial evidence that early treatment with disease-modifying antirheumatic drugs leads to a better disease outcome. The 1987 American College of Rheumatology classification criteria for RA do not perform well as a diagnostic tool in early arthritis. Therefore, diagnostic studies are needed to develop diagnostic criteria or prediction models that enable clinicians to distinguish RA from other arthritides in an early phase of the disease. Diagnostic studies are hampered by the lack of an independent gold standard for RA. Since the most important clinical features of RA are the persistence of the arthritis and the development of erosions, arthritis outcome is a clinically relevant gold standard. Diagnosis is a phased, multivariable process in which the probability of the presence of disease is updated continuously when new diagnostic information is added to the patient profile. Therefore, besides univariate studies, multivariable diagnostic studies are needed to evaluate the value of current diagnostic practice or to evaluate the added value of a new diagnostic procedure. This chapter describes univariate and multivariate studies that have been performed in early arthritis populations to assess the diagnostic value of medical history, physical examination, laboratory tests and imaging in RA diagnosis.
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.
15911204 Rheumatic disease in the elderly: rheumatoid arthritis. 2005 Aug This review summarizes the different aspects of rheumatoid arthritis and the spectrum of diseases that can present as rheumatoid arthritis-like arthritis in the elderly population. With the aging of Western population, different forms of inflammatory arthritis' prevalence and incidence are increasing in the elderly persons. Difficulties in establishing the diagnosis and introducing new treatment modalities in this patient group poses a great challenge for the 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 definitely a substantial need for improving different 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.
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.
15951465 Rheumatoid arthritis: an overview of new and emerging therapies. 2005 Jul Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disorder characterized by symmetric inflammation of synovial joints leading to progressive erosion of cartilage and bone. The aim of treatment is to mitigate joint destruction, preserve function, and prevent disability. The American College of Rheumatology guidelines for the treatment of RA recommend that newly diagnosed patients with RA begin treatment with disease-modifying antirheumatic drugs (DMARDs) within 3 months of diagnosis. Methotrexate remains the most commonly prescribed DMARD and is the standard by which recent new and emerging therapies are measured. Increasing knowledge regarding the immunologic basis of RA and advances in biotechnology have resulted in new, targeted biological therapies against proinflammatory cytokines that have dramatically changed the treatment paradigm and outcomes of patients with RA. This article reviews the pharmacological rationale underlying RA therapy, with a focus on currently available biological therapies and new therapies in development.
15838237 How should we manage early rheumatoid arthritis? From imaging to intervention. 2005 May PURPOSE OF REVIEW: Rheumatoid arthritis is a chronic systemic and progressive inflammatory disorder of the synovium characterised by destruction of bone and cartilage. It is associated with significant morbidity and economic costs. Recent advances have shown that early diagnosis and timely, intensive therapy of rheumatoid arthritis can modify disease outcomes. RECENT FINDINGS: Current investigations into the role of ultrasonography and magnetic resonance imaging in early rheumatoid arthritis suggest these modalities will provide information to assist in the early diagnosis of rheumatoid arthritis, identify poor prognostic factors, and aid in the monitoring of response to therapy. New developments in pharmacologic therapy, particularly the development of biologic agents, allow better disease control than was previously achievable, and the early application of these drugs in combination with conventional disease-modifying antirheumatic drugs seems to produce the best outcomes. SUMMARY: The application of novel imaging techniques will aid the target application of biologic therapy within the window of opportunity and aid in the monitoring of response to therapy. This is likely to significantly decrease the rate of structural damage and offers hope of a future when the normal outcome for rheumatoid arthritis will be remission.
15639060 Rheumatoid arthritis: neuroendocrine immune integrated physiopathogenetic perspectives and 2005 Feb Current concepts of neuroendocrine immune (NEI) aspects of rheumatoid arthritis (RA) are reviewed and recent clinical trials of glucocorticoids and sex steroids are summarized. A novel physiopathogenetic perspective is presented. Data are provided of amplified NEI interactions and dysregulation, many years before symptomatic onset of RA. Chronic imbalances between the NEI, vascular endothelial, neural, and other vital counterregulatory intertwined networks are proposed to cause RA and influence its disease activity. Future research may reveal means of diminishing the onset risk as well as disease activity of RA by controlling these imbalances of NEI and other vital networks.
16544924 [Understanding rheumatoid arthritis]. 2005 Dec 15 Rheumatoid arthritis is a common and severe inflammatory rheumatic disease, for which the immune mechanisms are being decoded little by little. The pathogenic ncludes significant cellular actors of innate immunity (fibroblastic synoviocytes, macrophages, mastocytes...) and adaptive immunity (T and B lymphocytes). These actors interact through the production of and response to specific (cytokines, chemokines and auto-antibodies) and non-specific (prostaglandins, nitrous oxide [NO], complement, proteases) mediators. The chronology of this rheumatoid synovitis is becoming progressively clearer. Its initiation could be the consequence of a precocious activation of the innate immunity, induced by bacterial agents or debris (PAMP). The activation of the synoviocytes and the macrophages via specific receptors (PPR) unleashes an intense inflammatory reaction that triggers a cascade of events. The ongoing nature of this synovitis leads to the intra-articular recruitment of different cells of immunity. This cellular afflux amplifies the macrophagic and synoviocytic activation and proliferation. All of these interactive phenomena end in the production of large quantities of pro-inflammatory cytokines (TNFa, IL1, IL6, IL15, IL17, IL18) but also other pathogenic mediators (auto-antibodies, complement, prostaglandins, nitrous oxide...). This synovitis persists, as it is no longer regulated by a sufficient production of physiological regulators (soluble receptors and inhibitors of cytokines). The consequence of this intense inflammation and synovial proliferation leads to osteo-articular destruction by the production of proteases and the activation of osteoclasts by the RANK/RANK-ligand pathway under the effect of cytokines (TNFa, IL5, IL1, IL6, IL17) and other mediators (prostaglandins) liberated by synoviocytes, macrophages and lymphocytes. The decryption of this puzzle has already created new therapeutic orientations. The identification of new targets is one of the major consequences of this progress in immuno-rheumatology.
16084219 Rheumatoid arthritis: a disease associated with accelerated atherogenesis. 2005 Aug OBJECTIVES: Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with an increased prevalence of coronary heart disease and a high cardiovascular (CV) mortality. In this article, a review of mechanisms implicated in the development of accelerated atherogenesis in RA was performed. The potential role of treatment to reduce the incidence of CV events in RA was also discussed. METHODS: Retrospective review of the literature. The potential mechanisms implicated in the development of accelerated atherogenesis in RA, information on carotid ultrasonography, and the potential implication of treatment to prevent accelerated atherogenesis in individuals with RA were examined. RESULTS: Endothelial dysfunction, which is an early step in the development of atherosclerosis, has been observed in patients with RA. Deleterious effects resulting from persistent chronic inflammation may lead to endothelial dysfunction, insulin resistance, and a dyslipidemic pattern in these patients. Other mechanisms different from those related to classic atherogenesis risk factors, such as hyperhomocysteinemia and increased oxidative stress, are considered to be implicated in the pathogenesis of atherosclerosis in RA. Increased carotid intima-media thickness and carotid plaques have been found in RA patients compared with matched controls. Active MTX treatment of the disease has been associated with decreased CV mortality. Additional drugs such as statins may be considered in the management of these patients. CONCLUSIONS: The increased prevalence of CV mortality rate in RA cannot only be explained by the presence of traditional atherosclerotic risk factors. A chronic inflammatory response may promote the development of accelerated atherogenesis in these patients. Active treatment of the disease is required to reduce the risk of developing CV complications in individuals with RA.
15838236 Emerging biologic therapies in rheumatoid arthritis: cell targets and cytokines. 2005 May PURPOSE OF REVIEW: Biologic therapy for rheumatoid arthritis targets specific molecules, both cell-bound and soluble, that mediate and sustain the clinical manifestations of this complex disease. The aim of all the therapeutic strategies is to achieve complete and sustained suppression of inflammation, in the absence of unacceptable short-term and long-term toxicity. Despite the success of the currently available biologic inhibitors of tumor necrosis factor-alpha and interleukin-1, a substantial number of rheumatoid arthritis patients are refractory to these treatments. The purpose of this review is to highlight recent clinical trials of emerging biologic treatments for rheumatoid arthritis. RECENT FINDINGS: T cell co-stimulation has been targeted by the use of cytotoxic T lymphocyte-associated antigen 4-Ig, a genetically engineered fusion protein. In a large controlled clinical trial, this nondepleting approach was shown to achieve impressive clinical responses, without evidence of short-term toxicity. Likewise, rituximab, a B cell-deleting monoclonal antibody, was shown in a controlled clinical trial to have sustained benefit in patients with refractory rheumatoid arthritis. Despite profound B cell depletion with rituximab, there was an acceptable safety profile with this treatment. MRA, a monoclonal antibody that inhibits interleukin-6 by binding to its receptor interleukin-6R, demonstrated clinically significant improvement in rheumatoid arthritis and a particularly impressive reduction in the acute phase response. SUMMARY: The response of rheumatoid arthritis to a wide spectrum of therapeutic strategies attests to the complexity and heterogeneity of the disease and provides further impetus for studies that use these therapies to enhance our understanding of disease pathogenesis.
16603443 Rheumatoid arthritis is an autoimmune disease triggered by Proteus urinary tract infection 2006 Mar Rheumatoid arthritis (RA) is a chronic and disabling polyarthritic disease, which affects mainly women in middle and old age. Extensive evidence based on the results of various microbial, immunological and molecular studies from different parts of the world, shows that a strong link exists between Proteus mirabilis microbes and RA. We propose that sub-clinical Proteus urinary tract infections are the main triggering factors and that the presence of molecular mimicry and cross-reactivity between these bacteria and RA-targeted tissue antigens assists in the perpetuation of the disease process through production of cytopathic auto-antibodies. Patients with RA especially during the early stages of the disease could benefit from Proteus anti-bacterial measures involving the use of antibiotics, vegetarian diets and high intake of water and fruit juices such as cranberry juice in addition to the currently employed treatments.
16174791 Immunological therapies for rheumatoid arthritis. 2005 Rheumatoid arthritis (RA) is a chronic inflammatory arthritis of the synovial joints that causes loss of function and a shortened life expectancy. In the last 10 years there have been major advances in the treatment of RA, including more aggressive use of disease-modifying anti-rheumatic drugs and the development of immune therapies targeted to molecules and cells important in the immunopathogenesis of RA. Molecular messengers that travel between cells (cytokines) have been found to be of major importance. Blocking the cytokine tumour necrosis factor alpha (TNF-alpha) produces significant improvement in RA, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn's disease. The use of cytokine blockers has shown the extent to which immune and inflammatory pathways are shared in a number of inflammatory diseases. There has also been an important proof of principle that blocking single cytokines can produce profound effects in inflammatory diseases.
15692959 Rheumatoid arthritis in American Indians and Alaska Natives: a review of the literature. 2005 Feb BACKGROUND AND OBJECTIVES: An increased prevalence of rheumatoid arthritis (RA) has been reported in several American Indian and Alaska Native (AI/AN) populations. This article reviews the prevalence of RA in these populations, including clinical and serologic features. METHODS: References were taken from Medline through November 2003, in addition to the Arctic Health Literature Database and the American Indian and Alaska Native Health Bibliography. RESULTS: Published articles reveal an increased prevalence of RA in the Tlingit, Yakima, Pima, and Chippewa Indians. Clinically the disease in these groups is often severe, with early age of onset, high frequency of radiographic erosions, rheumatoid nodules, and positive rheumatoid factor. Studies of HLA alleles in cases and controls have found a high frequency of HLA DRB1*1402. CONCLUSIONS: The increased prevalence of RA and more severe disease in specific AI/AN populations suggest an important genetic influence on the development of RA in AI/AN populations. A high frequency of specific high-risk HLA alleles in these populations may account for some of the increased risk, but other genetic factors are likely to contribute. Environmental factors have not been studied in detail, but may also play an important role. RELEVANCE: Understanding the patterns and burden of disease in AI/AN populations may contribute to understanding the etiology of RA and to the development of preventive strategies.