Browse

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

ID PMID Title PublicationDate abstract
19962613 Complexities in assessment of rheumatoid arthritis: absence of a single gold standard meas 2009 Nov The clinical approach to patients with inflammatory rheumatic diseases differs substantially from the approach to patients with many typical chronic diseases, such as hypertension or diabetes. Further elucidation of these differences may be informative in efforts to advance quantitative scientific patient assessment and management in rheumatic diseases, with improved patient outcomes.
19561159 Multipotent mesenchymal stromal cells and rheumatoid arthritis: risk or benefit? 2009 Oct Multipotent mesenchymal stromal cells (MSCs) have raised interest mainly because of cartilage/bone differentiation potential which is now partly eclipsed by their capacity to counteract inflammation and suppress host immune responses as well as to prevent fibrosis. MSCs have been identified within joint tissues including synovium, cartilage, subchondral bone, periosteum or adipose tissue. They are characterized by their phenotype and their ability to differentiate into three lineages, chondrocytes, osteoblasts and adipocytes. MSCs have also paracrine effects through the secretion of a number of cytokines and growth factors. This may explain the trophic effects that may be of therapeutic value for rheumatic diseases including OA and RA. On the other hand, MSCs have been associated with tumour growth. MSCs migrate to the tumour stroma, express chemokines involved in the attraction of carcinoma cells in metastasis. Indeed, the aim of this review is not only to focus on new potential therapeutic applications in osteo-articular diseases, but also to assess the potential risk of MSC-based cell therapy.
20969553 TNF inhibitors - new and old agents for rheumatoid arthritis. 2010 The development of tumor necrosis factor (TNF) inhibitor therapy has revolutionized the treatment of rheumatoid arthritis (RA). Unfortunately, no one single agent is fully effective in every patient; different patients respond to different therapies in different ways, even to those agents with the same mechanism of action. In this regard, newer TNF inhibitor agents, such as golimumab and certolizumab pegol, are a welcome addition to the treatment armamentarium of RA. This article addresses some of the recent advances in TNF inhibitor therapy for RA, including therapy involving these two newer agents and recent recommendations about well established TNF inhibitors (infiximab, etanercept, adalimumab) that may affect various aspects of RA treatment strategies.
20964640 The influence of early life factors on the risk of developing rheumatoid arthritis. 2011 Jan Rheumatoid arthritis (RA) is a chronic inflammatory disease that develops as a result of the interaction between genetic and environmental risk factors. Although increasing evidence shows the importance of genes in determining the risk of RA, it is clear that environmental factors also have a vital role. Studies to date have tended to concentrate on environmental influences around the time of disease onset. However, a number of pieces of evidence, including the fact that autoantibodies, such as rheumatoid factor (RF), can develop several years before the onset of clinical disease, suggest that environmental factors may influence disease susceptibility during early life. Several recent studies lend weight to this possibility, with an increased risk of RA in the offspring of mothers who smoked during pregnancy and in those with higher birth weight. There has also been a suggestion that the risk of RA is reduced in breast-fed infants. We describe the evidence surrounding the effect of early life factors on the risk of developing RA and possible mechanisms by which they may act.
20807655 Chondroitin sulfate and abnormal contact system in rheumatoid arthritis. 2010 Rheumatoid arthritis (RA) is a heterogeneous autoimmune disease that affects 1% of the population worldwide. In the K/BxN mouse model of RA, autoantibodies specific for glucose-6-phosphate isomerase (GPI) from these mice can transfer joint-specific inflammation to normal mice. The binding of GPI/autoantibody to the cartilage surface is a prerequisite for autoantibody-induced joint-specific inflammation in the mouse model. Chondroitin sulfate (CS) on cartilage surface is the long sought high-affinity receptor for GPI. The binding affinity and structural differences between mouse paw/ankle CS and knee/elbow CS correlate with the distal to proximal disease severity in these joints. The data presented in this chapter indicate that autoantigen/autoantibodies in blood circulation activate contact system to produce vasodilators to allow immune complex, protein aggregates, and other plasma proteins to get into the joints. Cartilage surface CS binds and retains autoantigen/autoantibodies. The CS/autoantigen/autoantibody complexes could induce C3a and C5a production through contact system activation. C3a and C5a trigger degranulation of mast cells, which further recruit plasma contact system and complement proteins, immune cells, and immune activation factors to facilitate joint-specific tissue destruction. Therefore, either reducing autoantibody production or inhibiting autoantibody-induced contact system activation might be effective in RA prevention.
20493416 Rheumatoid pneumoconiosis (Caplan's syndrome). 2010 Jun In 1953, Caplan described a characteristic radiographic pattern in coal miners with rheumatoid arthritis (RA) that was distinct from the typical progressive massive fibrosis pattern of coalworkers' pneumoconiosis. It consists of multiple well-defined rounded nodules on chest X-ray, from about 0.5 to about several centimetres in diameter, distributed throughout the lungs but predominantly at the lung periphery. Lesions appear often in crops, may coalesce and form a larger confluent nodule. Nodules often cavitate or calcify. They typically occur in the setting of pre-existing mild pneumoconiosis, but pneumoconiosis is not a prerequisite. The onset of the nodules is typically sudden, and their course varies thereafter, ranging from regression to progression. Histologically, the nodules have a characteristic appearance and are distinguishable from silicotic nodules or progressive massive fibrosis. Individual susceptibility is considered to play a role in the development of the disease. However, the pathogenetic link between exposure to silica, pneumoconiosis and RA has not been clarified conclusively. This review summarizes history, definition and current knowledge on epidemiology, pathology, pathophysiology, clinical presentation and treatment of Caplan's syndrome.
20067592 Effective rheumatoid arthritis treatment requires comprehensive management strategies. 2009 Work by Lee and colleagues has shown that decreased sleep quality and increased psychiatric distress increase pain sensitivity at both articular and nonarticular sites in rheumatoid arthritis (RA) patients. This work is consistent with prior studies showing that factors independent of RA disease activity can influence RA outcome measures. Owing to increasing pressure on rheumatologists to use outcome measures to inform treatment decisions, the work by Lee and colleagues highlights the need for comprehensive RA management strategies to understand and address the human factors that influence outcomes measures. Such strategies will ensure appropriate use of increasingly expensive therapies while maximizing patient satisfaction and reimbursement.
19657708 Rheumatoid arthritis associated with osteopetrosis. 2009 Osteopetrosis is an inherited disorder characterized by reduced bone resorption. We here report a rare case of osteopetrosis associated with rheumatoid arthritis. The patient was diagnosed as autosomal dominant osteopetrosis type II in his youth and developed rheumatoid arthritis at 42 years of age. In spite of the severe inflammation and rapid progression of cartilage destruction, the progression of bone erosion was slow in this patient.
19962630 Criterion contamination of depression scales in patients with rheumatoid arthritis: the ne 2009 Nov The validity of information on a patient questionnaire may not necessarily be generalizable to all individuals and situations, and may depend on the context in which a person provides the information. Examples may be seen in responses of people with rheumatoid arthritis on the Minnesota Multiphasic Personality Inventory (MMPI), on the original Beck Depression Inventory (BDI), and on the Centers for Epidemiologic Studies Depression Scale (CES-D). Several reports have indicated tendencies toward hypochondriasis, depression, and/or hysteria on the MMPI, and tendencies toward depression on the original BDI and CES-D. However, these interpretations were based in large part on responses to such statements as "I am in just as good physical health as most of my friends," "I can work about as well as before," and "I could not get going." These responses would suggest psychological concerns in people who have no somatic disease, the type of subjects in whom these scales were validated, but would also appear appropriate for people with rheumatoid arthritis, including those with no psychological problems. Rheumatologists confirmed independently the likelihood that people with rheumatoid arthritis would respond differently from the general population in responding to these and other statements. This phenomenon, known as criterion contamination, would explain much, but not all, of elevations in scores on these scales in patients with rheumatoid arthritis. The BDI was revised in 1996, as the Beck Depression Inventory-II (BDI-II), to eliminate the items reflecting somatic disease.
19962616 Radiographic measures to assess patients with rheumatoid arthritis: advantages and limitat 2009 Nov Radiographs present several attractive features for the assessment and monitoring of patients with rheumatoid arthritis (RA). Radiographic erosions are the closest to a pathognomonic sign in RA. Radiographs provide a permanent record of permanent damage. Excellent quantitative scoring systems have been developed by Larsen, Sharp, van der Heijde, Genant, Rau, and others. However, quantitative radiographic scoring is used only in research studies and is not included in usual treatment. Furthermore, magnetic resonance imaging and ultrasonography may be more sensitive than radiography in detecting abnormalities. Moreover, treatment of patients with RA should be initiated before evidence of damage. Reports that biologic therapy is superior to methotrexate in preventing radiographic progression are accurate for groups of patients, although methotrexate and other disease-modifying antirheumatic drugs control inflammation in 70% to 80% of patients and most patients present no radiographic progression with methotrexate. Radiographic findings are also much less significant and functional measures are far more significant in the prediction of severe outcomes of RA, including costs and mortality. Whereas prevention of radiographic progression is certainly desirable, it appears that prevention of functional disability is far more important for successful patient outcomes.
19798034 Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis. 2009 Oct Cytokines such as tumor necrosis factor (TNF) are expressed at high levels in rheumatoid joint tissue, where they contribute significantly to inflammation and articular destruction. TNF was the first cytokine to be fully validated as a therapeutic target for rheumatoid arthritis (RA). In nearly a decade since anti-TNF agents-such as infliximab, etanercept and adalimumab-were launched as the first biologic therapies to be licensed for RA, much has been learnt about how and when in the disease course this class of drug can be used to achieve optimal therapeutic benefit. Other cytokine targets, such as interleukin (IL)-6 or IL-1, have also been validated and several are in the process of being tested. However, TNF is likely to remain the preferred target of first-line biologic therapy for the foreseeable future as, in populations with active RA despite ongoing, nonbiologic, DMARD therapy, biologic inhibition of either IL-6 or IL-1 demonstrates no obviously superior outcomes to TNF blockade. Furthermore, new approaches to blockade of signaling mediated by bioactive TNF might have the potential to generate higher-magnitude clinical responses than are currently elicited.
19602456 Methods used to assess remission and low disease activity in rheumatoid arthritis. 2010 Jan The aim of the treatment in rheumatoid arthritis (RA) is to prevent articular damage and functional loss by decreasing the activity of the disease. The overall goal is the full suppression of the activity of the disease, also called clinical remission. The most reliable indices to assess RA activity were defined by the American College of Rheumatology (ACR), the European League Against Rheumatism (EULAR) and the International League Against Rheumatism (ILAR) and are habitually used for the evaluation of remission. The Food and Drug Administration (FDA) established three increasingly restrictive categories of disease remission: complete clinical response, major clinical response, and remission. Then, OMERACT (Outcome Measures in Rheumatoid Arthritis Clinical Trials) advanced the concept of low disease activity state (LDAS) or minimal disease activity (MDA). Thus, those reported by FDA are the only criteria for remission which consider radiographic arrest of the disease. This review aims to describe the criteria for RA remission and to discuss their advantages and limitations.
20193005 Secondary and ectopic lymphoid tissue responses in rheumatoid arthritis: from inflammation 2010 Jan Rheumatoid arthritis is a chronic systemic inflammatory disease primarily affecting the synovium of diarthrodial joints. Despite the currently unknown etiology, overwhelming evidence indicates that both innate and adaptive immunity play a central role in disease pathogenesis. In this review, we consider recent evidence examining the mechanisms of lymphoid tissue reactivity in rheumatoid arthritis with a focus on the dynamics controlling secondary and ectopic lymphoid tissue response. We then examine the cellular and molecular mechanisms regulating the biopathology of these processes with specific emphasis on cell trafficking, contribution to autoimmunity, and joint damage-repair. We finally provide a brief overview of the most recent studies addressing the clinical relevance of synovial lymphoid tissue analysis as a diagnostic and prognostic tool as well as its response to current biological therapies.
19822055 Health-related quality of life in patients with rheumatoid arthritis and in patients with 2009 Jul In this review the influence of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) on a wide range of health-related quality of life (HRQoL) domains will be described. The domains most frequently studied are pain, functional disability, fatigue and mental problems. In addition, age and socio-economic aspects such as employment and economic status as well as education affect patient-reported HRQoL.Although many studies have assessed the impact on HRQoL of a single disease state, either RA or AS, few studies have focused on a direct comparison between those both diagnostic groups. In general, patients with RA and AS report significant decrements in HRQoL in comparison with the general population. It has been shown that the magnitude of the impairment is similar among both patients group.
20877761 Living with rheumatoid arthritis. 2010 Sep I was first diagnosed with rheumatoid arthritis in 1999 when I was 27 years of age. I was lucky in some ways - my diagnosis took place in the emergency department of my local hospital. I had presented there with intense pain, swelling and tenderness in my left hand; less so in my right hand. I saw a rheumatologist immediately, without the usual waiting period for an appointment with a specialist. The rheumatologist who diagnosed me that day has subsequently been my doctor for almost 12 years.
18973928 Thymic Hassall's corpuscles, regulatory T-cells, and rheumatoid arthritis. 2010 Apr OBJECTIVE: To review evidence for the involvement of thymic Hassall's corpuscles (HC) in the pathogenesis of rheumatoid arthritis (RA). METHODS: We used PubMed to search for articles dedicated to the involvement of HC and regulatory T-cells (Tregs) in the pathogenesis of RA, and articles on thymic B-cells. RESULTS: Tregs are central players mediating tolerance to self. The functional defects in Tregs observed in patients with active RA may contribute to RA pathogenesis, promoting the premature immunosenescence of T-cells. This may partly explain the persisting expansion of CD4+ effector T-cell clones in peripheral blood, as well as the parallel improvement of RA activity and numbers of Tregs observed in the third trimester of pregnancy. HC play a major role in the selection of natural Tregs in the thymus, potentially altering the peripheral Tregs repertoire. The promiscuous expression of tissue-specific antigens by thymic medullary epithelial cells shapes the repertoire of natural Tregs. Thus, the presence of 2 major RA autoantigens (immunoglobulins and filaggrin) in the cytoplasm of normal human HC is puzzling, particularly given that thymic B-cells are also concentrated around HC, where CD55 (DAF) and CD59 are strongly expressed. Defects in HC could alter the repertoire of thymic B-cells and Tregs in RA patients, promoting the onset of this disorder. CONCLUSION: The identification of other joint-specific antigens, like gp-39, in HC and medullary epithelial cells, would provide new insights into the mechanisms of RA pathogenesis and may lead to more specific and physiologic methods of immunomodulation.
20730549 An overview of commonly used radiographic scoring methods in rheumatoid arthritis clinical 2011 Jan Despite the advent of magnetic resonance imaging and musculoskeletal ultrasound, the plain radiographs of the hands and feet remain an important tool for a practising rheumatologist both in clinical and research settings. This review focuses on providing a historical overview of commonly used methods of scoring radiographs in rheumatoid arthritis and discusses technical issues related to radiographic scoring, limitations and advantages of radiographs, and current recommendations regarding reporting radiographic data in clinical trials.
19250239 Quantifying disease activity and damage by imaging in rheumatoid arthritis and osteoarthri 2009 Feb Traditional imaging, represented by radiographs, provides a very concise description of anatomical pathology of bony structures. Both degenerative and inflammatory joint diseases are characterized by progressive joint destruction, and valid, reproducible measures of disease impact are available. Much effort has been expended to develop scoring systems for joint destruction in both osteoarthritis and rheumatoid arthritis, and the most common internationally accepted semiobjective scores are presented. The anatomical pathology mirrors the past activity of the disease, and advanced imaging gives an impression of the actual disease processes, which subsequently lead to the damage. Such information is required to facilitate the development of efficient therapy against arthritis. Newer technology, exemplified by MRI and ultrasound Doppler, supplements images of structural change with functional data of ongoing disease activity. This chapter focuses on the possibilities for quantification of images in MRI and ultrasound, in which postcontrast enhancement and Doppler information, respectively, are of special interest for the evaluation of the inflammatory changes of arthritis. To save time and eliminate human bias, automation is mandatory. In ultrasound, semiautomatic evaluations are coming that allow for a real-time, reproducible estimate of disease activity. With MRI fully automated algorithms have been developed for processing of data of bony structures, cartilage, and soft tissue, and are currently being implemented into everyday clinical practice.
19962618 Patient questionnaires in rheumatoid arthritis: advantages and limitations as a quantitati 2009 Nov In many chronic diseases, objective gold standard measures such as blood pressure, cholesterol, and bone densitometry often provide most of the information used to establish a diagnosis and guide therapy. By contrast, in inflammatory rheumatic diseases, information from a patient history usually is considerably more prominent in clinical management. Patient history data can be recorded as standardized, quantitative scientific data through use of validated self-reported questionnaires. Patient questionnaires address the primary concerns of patients and their families. Questionnaire scores distinguish active from control treatments in clinical trials at similar levels to swollen and tender joint counts or laboratory tests. Patient questionnaire data are correlated significantly with joint counts, radiographic scores, and laboratory tests, but usually are far more significant than these measures in the prognosis of severe outcomes of rheumatoid arthritis (RA), including work disability, costs, and premature death. Limitations of patient questionnaires are based on cultural features involving variation in responses among ethnic groups, and a need for translation, although translated questionnaires can be as valuable as a translator. Patient questionnaires do not replace further medical history, physical examination, laboratory tests, and imaging data, and they require interpretation in a context of these standard sources of information at any clinical encounter. Patient questionnaires are useful to monitor patient status in usual clinical care, with almost no effort on the part of the physician and staff if distributed by the receptionist in the infrastructure of office practice.
20190639 Update on the use of conventional disease-modifying antirheumatic drugs in the management 2010 May PURPOSE OF REVIEW: The present review will focus on the role of conventional disease-modifying antirheumatic drugs (DMARDs) in the current management of rheumatoid arthritis (RA). RECENT FINDINGS: Over the past several decades, the treatment of RA has been revolutionized, not only by the development of highly effective biologic agents but also through a better understanding of the critical importance of early DMARD treatment with a goal of remission or low disease activity and of how to effectively and safely use conventional DMARDs, either as monotherapy or in combinations. SUMMARY: Conventional DMARDs have proven efficacy in the management of RA and remain a valid treatment option, either in monotherapy or as a component of combination regimens. Although conventional DMARDs have associated toxicities, these are distinct from those of the biologic DMARDs. In addition, conventional DMARDs are much less expensive than biologic DMARDs, and in many cases can be successful in achieving similar control of disease activity. The goal for all patients should be achieving remission, or at least low disease activity, with the most cost-effective therapy possible.