Browse

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

ID PMID Title PublicationDate abstract
21176804 Reconstruction of digital deformities in rheumatoid arthritis. 2011 Feb Digital deformities result from rheumatoid synovitis. These deformities are easier to treat in the early stage, when the deformity is passively correctable. Treatment options become limited as the disease progresses and the deformity becomes fixed. Surgical treatment of digital deformities is last in the priority of surgical procedures for the rheumatoid hand and wrist. It is therefore important to understand the patient's needs and expectations for improvement and attempt to match them with the surgical options that can predictably improve the patient's function. A close collaboration with the patient's rheumatologist is helpful in the overall management of patients.
21837725 Nanotherapeutic approaches for the treatment of rheumatoid arthritis. 2011 Nov Rheumatoid arthritis (RA) is a common inflammatory disease characterized by progressive bone and cartilage destruction, resulting in severe functional limitations, shortened lifespan, and increased mortality rates. Recent advances and new treatment approaches have significantly delayed disease progression and improved the quality of life for many patients. Yet few patients attain or can be maintained in disease remission without continuous immunosuppressive therapy. In addition, a sizable portion of patients also fails to respond or eventually develops tolerance to current therapies. Thus there is a continued need for the development of new therapeutic strategies for the treatment of RA. Unlike conventional drugs, nanosystems are designed to deliver therapeutic agents specifically to the site of inflammation, therefore avoiding potential systemic and off-target unwanted effects. They allow investigators to consider or reconsider therapeutic agents that were previously deemed too toxic to deliver through a systemic route. This article reviews recent nanotechnology-based strategies that are being developed for the treatment of inflammatory arthritis.
22100329 miRNAs and related polymorphisms in rheumatoid arthritis susceptibility. 2012 Jul The epigenetic mechanisms in regulation of genes' expression seem to be another field of research that gains land in genetic association studies of rheumatoid arthritis (RA) susceptibility factors. Recently, a new class of molecules has been discovered, the microRNAs (miRNAs). miRNAs are related to post-transcriptional regulation of genes' expression. Different expression patterns of mir-146a, miRNA-155, miRNA-124a, mir-203, mir-223, mir-346, mir-132, mir-363, mir-498, mir-15a, and mir-16 were documented in several tissue sample types of RA patients. The polymorphisms of these miRNAs and their gene targets, which previously have been associated with RA or other autoimmune diseases, are also reviewed. Finally, using web-based tools we propose polymorphisms of the discussed miRNAs and their gene-targets that worth to be studied for their role in RA predisposition.
21719977 [Early diagnosis and staging of rheumatoid arthritis by MR imaging and ultrasonography]. 2011 Jul Advanced imaging modalities, such as MR imaging or ultrasonography (US), are useful in evaluating disease activity and therapeutic outcome of rheumatoid arthritis (RA). MR imaging can demonstrate bone erosion and edema, which are important in predicting structural articular damage. MR findings are nonspecific but can be helpful in diagnosing RA in its early stage. US can access relatively easily to multiple joints, and power Doppler US allows to visualize the vascularity of synovium. Standardization of imaging and analysis procedures are needed for clinical application of these imaging modalities.
22400361 [Interstitial lung disease in rheumatoid arthritis]. 2011 Nov 23 Interstitial lung disease (ILD) is found in up to 30% of patients with rheumatoid arthritis (RA) and is clinically manifest in 5 to 10%, resulting in significant morbidity and mortality. The most frequent histopathological forms are usual interstitial pneumonia and nonspecific interstitial pneumonia. Another recently described presentation is combined pulmonary fibrosis and emphysema. Similarly to idiopathic pulmonary fibrosis, acute exacerbation of ILD may occur in RA and is associated with severe prognosis. Smoking is a known risk factor of RA and may also play a role in the pathogenesis of RA-associated ILD, in combination with genetic and immunologic mechanisms. Several treatments of RA may also lead to drug-induced ILD.
23137580 Perioperative drug safety in patients with rheumatoid arthritis. 2012 Nov The expansion of therapeutic options for rheumatoid arthritis (RA) has improved the functional, quality of life, and radiographic outcomes for patients, although immunomodulatory and immunosuppressive effects may increase the potential for complications related to infection risk or wound healing after orthopedic surgery. Additionally, medications without significant effects on the immune system, such as nonsteroidal anti-inflammatory drugs, may have consequences in terms of bleeding or cardiovascular disease. Increased vigilance is required when using these medications, particularly in the perioperative period. This article considers the recent literature and data on the perioperative use of medications commonly used in RA.
21880506 Therapeutic potential of Tregs to treat rheumatoid arthritis. 2011 Jun There is accumulating evidence for regulatory T cell defects in rheumatoid arthritis and that some biologic interventions, in particular anti-TNF, can target this population. Despite the challenges in defining regulatory T cells in patients, there are a number of approaches currently being developed to utilise their potent immunosuppressive properties. Through genetic manipulation Tregs can be generated ex vivo or in vivo that target antigens present in the inflamed joint. Here we discuss these approaches, their refinement to restore tolerance in patients with rheumatoid arthritis, and strategies to prevent their conversion towards a Th17 phenotype.
22037509 Mutated citrullinated vimentin antibodies in rheumatoid arthritis. 2012 Jan 18 Rheumatoid arthritis (RA) is the most common inflammatory systemic autoimmune disease, primarily affecting the peripheral joints. The past decade has been marked with revolutionary changes both in the therapeutic and diagnostic perspectives of RA. The discovery of an RA-specific citrullination-driven immune reaction gave a substantial contribution in the diagnostic approach to RA. Efforts directed towards the identification of the antigenic target specifically recognized by these autoantibodies resulted in the identification of vimentin in citrullinated form as the potential native antigen, among other proteins. Furthermore, it was found that the mutation of vimentin represents an independent trigger of antigenic properties, in addition to citrullination. As a result of this discovery, a commercial ELISA using mutated citrullinated vimentin (MCV) was developed. Increasingly, data now support the use of anti-MCV in RA diagnosis and prognosis for errosion. This review summarizes the research to date on the use of anti-MCV in RA diagnosis and prognosis and its potential use as a therapeutic marker. The pathologic role of these antibodies in RA disease is also discussed.
22068002 Treating to target in rheumatoid arthritis: biologic therapies. 2011 Nov 10 Treating to target is an established concept in the management of a number of long-term conditions to improve outcomes and prevent disease progression. Treatment targets in rheumatoid arthritis (RA) are to control the signs and symptoms of significant inflammatory disease activity, with the ultimate goal of remission from disease. The previous article in this series (Firth, 2011) outlined treating RA to target with conventional disease modifying drugs (DMARDs), including the role of the nurse in assessing disease activity, promoting shared clinical-decision making and monitoring treatment. In recent years, biologic agents have increased the treatment options for RA, but their use is reserved for patients with severe disease activity who fail to respond to treatment with two or more DMARDs. This article outlines the role of biologic therapies in treating RA to target, including eligibility criteria and the role of the nurse in optimizing outcomes.
20390282 Platelet function in rheumatoid arthritis: arthritic and cardiovascular implications. 2011 Feb Patients with rheumatoid arthritis (RA) are at high risk of cardiovascular events. Platelet biomarkers are involved in inflammation, atherosclerosis and thrombosis. Cardiovascular and RA-associated factors can alter the structure and function of platelets, starting from megakaryocytopoiesis. Reactive megakaryocytopoiesis increases circulating platelets count and triggers hyperactivity. Hyperactive platelets target synovial membranes with subsequent local rheumatoid inflammation. Hyperactive platelets interact with other cells, and target the vascular wall. Accumulating evidence suggests that disease modifying anti-rheumatic drugs (DMARD) decrease platelet activity.
22137921 Established rheumatoid arthritis: rationale for best practice: physicians' perspective of 2011 Aug Developments in the understanding of the pathogenesis of rheumatoid arthritis (RA) and the introduction of targeted biologic therapies have greatly advanced the management of RA in clinical practice. The management of RA is now aimed at achieving remission, to prevent joint damage and disability. In particular, a critical period early in disease is recognised, in which early aggressive treatment with disease-modifying therapy is advocated. Although a state of remission is the ideal, this chapter discusses the difficulties which may arise in achieving this goal in patients with established disease. The evidence for best management, aimed at achieving clinical remission in established disease, is reviewed. The consequences of incomplete control of chronic inflammation in established disease, including pain, disability and co-morbidities (such as cardiovascular disease and osteoporosis), also pose a significant clinical challenge. The rationale for a multidisciplinary team approach in reducing the associated morbidity and mortality of the disease are examined.
22819088 Evolution of classification criteria for rheumatoid arthritis: how do the 2010 criteria pe 2012 May Classification criteria are created in an attempt to produce a homogenous group of subjects with rheumatoid arthritis (RA) who can be used for clinical and basic research. The 1987 revised criteria lead to improved performance and more confidence in correct classification compared with the 1958 criteria. As therapies were introduced and early, aggressive approaches to RA management became common, there was a growing need for clinical trials focusing on early RA. The 2010 criteria were created to facilitate study of subjects at earlier stages in the disease. This article reviews the diagnostic performance of the 2010 criteria.
21285713 Strategies to prevent rheumatoid arthritis in high-risk patients. 2011 Mar PURPOSE OF REVIEW: To examine potential interventions, including modification of environmental risk factors and use of pharmacologic agents, in at-risk populations to prevent progression to (or development of) rheumatoid arthritis (RA). This review is timely given the increasing interest in early intervention strategies and new opportunities to identify patients early in the pathogenesis of RA. RECENT FINDINGS: Despite the growing literature demonstrating a link between anticitrullinated protein antibodies, synovitis, genetic and environmental risk factors such as smoking and RA, there are no studies that have evaluated the effect of modifying environmental risk factors in late preclinical RA. This article describes several studies that have evaluated the ability of pharmacologic interventions to modify outcomes in patients at risk for RA. SUMMARY: The prevention of RA in at-risk populations is feasible; however, this will necessitate novel efforts to identify patients very early in disease development to examine the effectiveness and cost of preventive interventions.
23257071 The role of glycoprotein 96 in the persistent inflammation of rheumatoid arthritis. 2013 Feb 1 The 96-kDa glycoprotein (gp96) is an endoplasmic reticulum (ER) resident molecular chaperone. Under physiologic conditions, gp96 facilitates the transport of toll-like receptors (TLRs) to cell or endosomal membranes. Under pathologic circumstances such as rheumatoid arthritis, gp96 translocates to the cell surface and extracellular space, serving as an endogenous danger signal promoting TLR signaling. Macrophages play a central role in regulating innate and adaptive immunity, and are the major source of proinflammatory cytokines and chemokines in rheumatoid arthritis (RA). Macrophage numbers in the sublining of RA synovial tissue correlate with clinical response. This review focuses on the recent findings that implicate gp96 induced macrophage activation mediated through TLR signaling in the pathogenesis of RA and provides insights concerning the targeting gp96 and the TLR signaling pathway as therapeutic approaches for patients with RA and possibly other chronic inflammatory conditions.
20216205 Perioperative management of biologic agents used in treatment of rheumatoid arthritis. 2011 Sep Patients with rheumatoid arthritis, an inflammatory arthritis that can destroy joint structures, are often on multiple disease-modifying antirheumatic medications to control disease activity. These medications have significant toxicities, most notably immunosuppression leading to increased risk of infection. Furthermore, certain disease-modifying antirheumatic medications have been reported to affect the healing process. Over the course of their lifetime, patients with rheumatoid arthritis may undergo many surgical procedures, often orthopedic interventions, including total joint arthroplasty, reconstructive surgeries, or cervical stabilization. How to manage antirheumatic medications and their toxicities in the perioperative period is a challenging question, especially with regard to the biologic therapies such as antitumor necrosis factor alpha agents. We conducted a review of the available literature pertaining to the perioperative use of biologic agents used to treat rheumatoid arthritis. Although existing data directly addressing complications during specific orthopedic procedures are sparse, information on general surgical complications in rheumatic and other patient populations may be used as a basis for conservative recommendations.
22648081 Molecular characterization of rheumatoid arthritis with magnetic resonance imaging. 2011 Apr Several recent advances in the field of magnetic resonance imaging (MRI) may transform the detection and monitoring of rheumatoid arthritis (RA). These advances depict both anatomic and molecular alterations from RA. Previous techniques could detect specific end products of metabolism in vitro or were limited to providing anatomic information. This review focuses on the novel molecular imaging techniques of hyperpolarized carbon-13 MRI, MRI with iron-labeled probes, and fusion of MRI with positron emission tomography. These new imaging approaches go beyond the anatomic description of RA and lend new information into the status of this disease by giving molecular information.
22137920 Assessment of control of rheumatoid arthritis disease activity. 2011 Aug As very effective targeted biological therapies have become available to treat rheumatoid arthritis (RA), remission is now the goal of treatment. Since 1981, efforts have been undertaken to develop criteria for clinical remission in RA. Although several different measures of disease activity have been proposed, many issues remain unresolved. Active joint inflammation, even if involving only a few joints, negatively impacts a patient's quality of life and may ultimately result in structural damage. Thus, a low disease activity state (LDAS), which has been adopted as the target in clinical trials of 'treat to target', may not be the optimal treatment target in clinical practice. Similarly, the definitions of remission used in clinical trials may not be appropriate for use in daily clinical practice because some allow for the presence of several tender and swollen joints. Measures of disease activity do not necessarily correlate with structural remission, which implies halting progression of radiographic evidence of damage over time. Because no single measure of RA disease activity fully quantifies the global burden of disease, rheumatologists must follow multiple parameters to assess disease activity thoroughly and to adjust treatment optimally.
22249350 Risk factors for cardiovascular disease in rheumatoid arthritis. 2012 Mar PURPOSE OF REVIEW: To highlight recent evidence regarding the contribution of traditional and nontraditional [e.g. inflammatory markers, rheumatoid arthritis (RA) features] risk factors toward the excess cardiovascular risk in RA. RECENT FINDINGS: The impact of traditional risk factors on the development of cardiovascular disease in persons with RA is an area of active research. Some are more prevalent among people with RA (e.g. smoking); others appear to have paradoxical relationships (e.g. body mass index), and findings remain inconsistent with others (e.g. dyslipidemia). Collectively the data suggest that cardiovascular risk factors behave differently in RA. Thus, risk scores developed for the general population based on traditional cardiovascular risk factors alone are unlikely to accurately estimate cardiovascular risk in RA, highlighting the need for RA-specific risk prediction tools.Nontraditional risk factors, in particular RA disease activity/severity measures, including inflammatory markers, disease activity scores, seropositivity, physical disability, destructive changes on joint radiographs, extra-articular manifestations, and corticosteroid use, have repeatedly shown significant associations with increased cardiovascular risk. Medications used to treat RA may also affect cardiovascular risk. A recent meta-analysis suggests that all nonsteroidal anti-inflammatory drugs confer some cardiovascular risk. The cardiovascular risks/benefits associated with use of disease-modifying antirheumatic drugs and/or biologics remain controversial, as does the role of statins in RA. SUMMARY: Cardiovascular disease remains a major problem for people with RA. Future work should focus on further delineating the underlying biological mechanisms involved, developing and evaluating risk assessment tools and biomarkers, as well as prevention/treatment strategies specific to the RA population.
23192911 The risk of infections associated with rheumatoid arthritis, with its comorbidity and trea 2013 Jan RA is known to be associated with an increased risk of serious infection. Even more than 50 years ago, observational studies showed a greater than 2-fold increased risk of serious infection in RA. This was reinforced by various subsequent cohort studies. The elevated susceptibility of patients with RA can be explained by the pathobiology of the disease itself, the impact of chronic comorbid conditions, as well as sequelae of immunosuppressive treatment. It has been suggested that premature ageing of the immune system in RA contributes to weakened protection against infectious organisms. In addition, chronic comorbid conditions such as diabetes or chronic lung or kidney disease, disease-related functional disability, as well as lifestyle factors such as smoking, increase the risk in individual patients. For a long time glucocorticoids (GCs) have been used as potent immunosuppressive drugs in RA. There is evidence that they increase the risk of serious infections up to 4-fold in a dose-dependent manner. TNF-α inhibitors increase the serious infection risk up to 2-fold. They have, however, the potential to outweigh their risk when higher GC doses can be tapered down. If patients need higher dosages of GCs in addition to treatment with biologic agents, their risk of infection is substantial. This combination should be used carefully and, if possible, avoided in patients with additional risk factors such as older age or comorbid conditions.
21570636 The new criteria for classification of rheumatoid arthritis: what we need to know for clin 2011 Jun The new criteria for classification of Rheumatoid Arthritis have been recently released. They incorporate the anti-Citrullinated Protein antibody testing and the other classic criteria in a score system (the diagnosis of definite rheumatoid arthritis is made by a total score ≥6). These criteria try to meet the pressing needs to gain sensitivity in early disease. Symptoms, elevated acute-phase response, serologic abnormality, joint involvement were all considered for scoring after confirming the presence of synovitis in at least 1 joint in the absence of an alternative diagnosis that better explains the synovitis. However, no sensitivity and specificity has been showed. Moreover, Area Under Curve of the Receiver Operating Characteristic curves (a measure of performance of the test) was not optimal in almost two of the three studied cohorts. On the contrary, the old criteria of the American College of Rheumatology had been tested to calculate sensitivity and specificity. Moreover, sensitivity and specificity of anti-citrullinated peptide auto-antibodies are available for clinical reasoning based on pre-test and post-test probabilities of the disease. The use of likelihood ratios applied to both the old criteria and anti-citrullinated autoantibodies could help clinicians to effectively manage early arthritis patients implementing Bayesian reasoning. Here, we tried to explain the methodology applied to the body of knowledge currently available about rheumatoid arthritis for diagnostic decision-making based on the Bayesian approach.