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

ID PMID Title PublicationDate abstract
23053722 Cutaneous necrobiotic conditions associated with rheumatoid arthritis: important extra-art 2013 Jul Rheumatoid arthritis (RA) presents with various skin conditions as extra-articular manifestations. Rheumatoid nodule is the representative specific skin lesion, histologically exhibiting central necrosis (necrobiosis) surrounded by palisaded macrophages, and being further perivascularly infiltrated with inflammatory cells in the outer regions. Also, there are several skin lesions which histologically show necrobiotic conditions with altered connective tissue degeneration. Necrobiosis may be closely associated with the pathogenesis of RA, i.e., collagen degeneration, recruitment of activated neutrophils, production of various cytokines, and vascular injury. On the other hand, rheumatoid nodule is suggested to develop during therapies with certain drugs such as methotrexate and biologics. These findings may be a clue to understanding the pathomechanisms of rheumatoid nodules. This paper describes several necrobiotic conditions associated with RA, and also discusses the possible pathogenesis and differential diagnosis of rheumatoid nodules. Necrobiosis is the major pathologic condition of cutaneous involvement associated with RA.
22885986 Advances in research on animal models of rheumatoid arthritis. 2013 Feb At present, rheumatoid arthritis (RA) is considered a type of autoimmune disease. Its pathology is not certain, and effective drugs with less toxicity have not been established. The establishment and application of animal models are effective methods for RA research, especially using animal models similar to humans. Arthritis is more heterogeneous, and this is an important starting point when discussing animal models for arthritis. Animal models are instrumental in understanding the etiology and pathogenetic mechanisms of RA. Appropriate animal models should be selected according to experiments because they have different traits. Various methods have been applied to induce arthritis in animal experimental models, which have provided important insights into the etiopathogenetic mechanisms of human RA. This review was written to give a broad introduction of the current stage of RA model and hope to offer beneficial help for RA-related research.
22009497 [Total ankle replacement in rheumatoid arthritis]. 2011 Nov Rheumatoid arthritis is a systemic disease directly involving multiple joints and indirectly damages bone due to specific medicinal therapy. When deciding on the optimal surgical treatment of inflammatory ankle arthritis (fusion versus arthroplasty), specific factors have to be considered. This review discusses the advantages and disadvantages of total ankle arthroplasty for patients with rheumatoid arthritis and highlights important surgical aspects related to this disease.
21932019 Beyond the joints: neurological involvement in rheumatoid arthritis. 2012 Jan Although arthritis is the most notable component, rheumatoid arthritis (RA) is a systemic inflammatory disorder where extra-articular manifestations are common; among them, central and peripheral nervous system involvement is frequent and associated with significant morbidity and, in some cases, reduced life span. It may produce a myriad of symptoms and signs ranging from subtle numbness in a hand, to quadriparesis and sudden death. Central and peripheral neurologic manifestations may arise from structural damage produced by RA in diarthroidal joints, by the systemic inflammatory process of the disease itself or by the drugs used to treat it. Neurologic syndromes may appear suddenly or developed slowly through months, and emerge early or after years of having RA. Neurologic manifestations may be easily overlooked or incorrectly assigned to peripheral arthritis unless the attending physician is aware of these complications. In this article, we review neurologic involvement in RA patients with emphasis on clinical approach for early detection.
22077951 Integrins and their ligands in rheumatoid arthritis. 2011 Integrins play an important role in cell adhesion to the extracellular matrix and other cells. Upon ligand binding, signaling is initiated and several intracellular pathways are activated. This leads to a wide variety of effects, depending on cell type. Integrin activation has been linked to proliferation, secretion of matrix-degrading enzymes, cytokine production, migration, and invasion. Dysregulated integrin expression is often found in malignant disease. Tumors use integrins to evade apoptosis or metastasize, indicating that integrin signaling has to be tightly controlled. During the course of rheumatoid arthritis, the synovial tissue is infiltrated by immune cells that secrete large amounts of cytokines. This pro-inflammatory milieu leads to an upregulation of integrin receptors and their ligands in the synovial tissue. As a consequence, integrin signaling is enhanced, leading to enhanced production of matrix-degrading enzymes and cytokines. Furthermore, in analogy to invading tumors, synovial fibroblasts start invading and degrading cartilage, thereby generating extracellular matrix debris that can further activate integrins.
21814022 [RANKL/RANK signaling in rheumatoid arthritis]. 2011 Aug Rheumatoid arthritis (RA) is a chronic inflammatory disease, which is induced by abundant inflammatory cytokines releasing from synovial fibroblasts and T lymphocytes. These cytokines differentiate monocyte-macrophage lineage cells to mature osteoclasts, which cause bone resorption and then joint destruction. RANKL is involved in the development of osteoclasts, cooperating with another key molecule, M-CSF. Indeed, RANKL is over-expressed in the synovium of RA. We summarize RANKL/RANK signaling in RA, including recent therapeutic topics.
21359507 The burden of illness of rheumatoid arthritis. 2011 Mar It is necessary to understand the full burden of illness of a disease before the value of interventions can be assessed. Rheumatoid arthritis (RA) has an impact on a variety of stakeholders, including patients, healthcare systems, and society as a whole. This overview discusses the societal and patient perspectives, distinguishing several domains of impact. Epidemiology is important from a societal perspective, as it affects the total impact on health and costs related to RA and influences healthcare organization priorities. Co-morbidities, such as cardiovascular disease, are important factors contributing to the impact of RA. The impact on health is, naturally, relevant to both patients and society as a whole, and is summarized by health-related quality-of-life measures from the point of view of the patient and by utilities from the societal perspective. Similarly, work participation is important for both patients and society. Withdrawal from the labor force and short- and long-term sick leave are extensively studied in RA and lead to substantial productivity costs at the societal level and to income loss for patients. In addition, the recent concept of presenteeism, which reflects the problems that patients experience while at work, is considered. Finally, the costs of illness of RA are summarized. Societal costs are mainly driven by the costs of drug treatment and inpatient care, including surgery. Patient and family costs are mainly driven by the need for formal and informal care. Overall, RA has a significant impact on the health of and costs to patients and society, suggesting that effective interventions to reduce the impact are of value.
21427575 Genetics of rheumatoid arthritis: time for a change! 2011 May PURPOSE OF REVIEW: To review recent progress in the genetics of rheumatoid arthritis (RA) and discuss the implications for understanding the pathogenesis of the disease as well as clinical application. RECENT FINDINGS: Protection against anticitrullinated protein antibody (ACPA) positive RA was shown to be associated wit DRB1*1301. Genome-wide association studies (GWASs) added about 10 new loci to the list of already more than 20 loci associated with RA, so the list is now over 30. Typing for the known risk loci is not helpful for prediction of the risk for RA. It is remarkable how few functional studies have been published. SUMMARY: Known genetic factors explain 50-60% of the genetic variance for susceptibility to ACPA-positive and 30-50% for ACPA-negative RA. Searching for the remaining missing or hidden heritability is in all probability not going to yield much for prediction and/or targeted intervention. Therefore, I conclude that if you want to find more genes you should have a lot of patience, time and money, stop with convential GWAS and invest in large-scale sequencing of selected patients and controls. I have a better suggestion, however: use the information that is already available to perform functional studies in order to understand the mechanism of the known associations!
22018197 Glucocorticoid treatment in early rheumatoid arthritis. 2011 Sep Glucocorticoids (GCs) have been an invaluable tool in the treatment of patients with rheumatoid arthritis (RA) for decades, with a focus mainly on symptom management. In addition, several studies in the last 15 years have shown that GCs are also disease-modifying in patients with RA - which implies that they inhibit radiographic progression. These effects seem to be especially important in the early course of disease. Nonetheless, there is still a lack of knowledge concerning optimal therapeutic strategies with GCs, particularly regarding patient selection and optimal dosage schedules.
21723592 Rheumatoid arthritis recapitulates events relevant in blastocyst implantation and embryoge 2011 Dec OBJECTIVES: Theoretical considerations support the hypothesis that functionally relevant genes were not positively selected for symptomatic chronic inflammatory diseases (CIDs) because of 3 major reasons: 1) high negative selection pressure with loss of reproducibility; 2) no selection pressure at all (many CIDs of today manifest in higher ages, and due to low life expectancy of our ancestors, they did not suffer from CIDs that we know today); 3) there was no time for natural selection (various CIDs did not exist long enough). Nevertheless, genes can be transferred before outbreak of a CID and can confer an increased risk. However, these genes were positively selected for fitness in reproduction and survival at younger ages independent of a symptomatic CID (antagonistic pleiotropy). Thus, relevant genes were conserved for non-life-threatening inflammatory episodes (NOLTIES) such as infection or wound healing, which did not impede positive selection. Importantly, blastocyst implantation and embryogenesis are NOLTIES. We hypothesized that factors relevant in blastocyst implantation and embryogenesis are also found in active tissue inflammation of a CID. METHODS: Rheumatoid arthritis (RA) was used as a paradigmatic CID. An extensive database search in PubMed and OMIM of the U.S. National Library of Medicine was conducted. RESULTS: Many important similarities between RA and blastocyst implantation/embryogenesis were found including stem cell pathways, hormonal pathways, angiogenesis, neuronal pathways, the wingless (Wnt) pathway, the Notch pathway, the TGF-beta superfamily, matrix metalloproteinases, and others. CONCLUSIONS: It turned out that many factors of RA inflammation were borrowed from the non-life-threatening episode of blastocyst implantation and embryogenesis.
23164162 Epigenetic contributions in the development of rheumatoid arthritis. 2012 Nov 9 Rheumatoid arthritis (RA) is an autoimmune disease, characterized by chronic inflammation of the joints with severe pain and swelling, joint damage and disability, which leads to joint destruction and loss of function. Despite extensive research efforts, the underlying cause for RA is still unknown and current therapies are more or less effective in controlling symptoms but still fail to cure the disease. In recent years, epigenetic modifications were found to strongly contribute to the development of RA by affecting diverse aspects of the disease and modifying gene expression levels and behavior of several cell types, first and foremost joint resident synovial fibroblasts (SF). RASF are the most common cell type at the site of invasion. Owing to their aggressive, intrinsically activated phenotype, RASF are active contributors in joint damage. RASF are characterized by their ability to secrete cytokines, chemokines and joint-damaging enzymes. Furthermore, these cells are resistant to apoptosis, leading to hyperplasia of the synovium. In addition, RASF have invasive and migratory properties that could lead to spreading of the disease to unaffected joints. Epigenetic modifications, including DNA methylation and post-translational histone modifications, such as histone (de)acetylation, histone methylation and histone sumoylation were identified as regulatory mechanisms in controlling aggressive cell activation in vitro and in disease outcome in animal models in vivo. In the last 5 years, the field of epigenetics in RA has impressively increased. In this review we consider the role of diverse epigenetic modifications in the development of RA, with a special focus on epigenetic modifications in RASF.
21176795 Advances in the medical treatment of rheumatoid arthritis. 2011 Feb Over the past 2 decades, the treatment of rheumatoid arthritis (RA) has been revolutionized by advances in the understanding of its pathologic mechanisms and the development of drugs that target them. These newer medications have shown great promise at improving disease outcomes, but they come with notable side effects that can pose long-term treatment challenges and difficulties in the perioperative arena. In this article, the major manifestations of RA and the current medical options for management are discussed. Complications from treatment are then reviewed, and special consideration is given to perioperative medication recommendations.
22166850 Biologics-based therapy for the treatment of rheumatoid arthritis. 2012 Jan Rheumatoid arthritis (RA) remains a major clinical problem, but treatments involving biologics have revolutionized its management. They target pathogenically relevant cytokines such as tumor necrosis factor and immune cells such as B cells. In RA, biologics reduce joint inflammation, limit erosive damage, decrease disability, and improve quality of life. Infections are the main risk associated with their use. Because of the high prices of biologics, their cost-effectiveness is a matter of debate. They are mainly coadministered with disease-modifying drugs such as methotrexate when the latter are found to achieve insufficient disease control on their own.
22910444 Progress toward personalized treatment of rheumatoid arthritis. 2012 Oct Treatment of rheumatoid arthritis (RA) has advanced significantly over the past decade, in part because of the identification of key elements in the immunopathogenesis of the disease, leading to the development of targeted immune-based therapies. Despite the availability of many highly specific therapies, the process of selecting a treatment regimen for an individual patient remains empirical. Personalized treatment, focused on predicting efficacy, non-response, and toxicity to better guide medication selection, moves closer to realization as genomic methods continue to be extended and refined.
21176799 Rheumatoid elbow. 2011 Feb The elbow is often involved in the progression of rheumatoid arthritis. Because of the elbow's unique role in maneuvering and positioning the hand in space, loss of normal elbow motion, loss of stability, or increased pain with the use of the elbow are all significant sources of impairment in patients with rheumatoid arthritis. The improvements in disease-modifying medications have greatly diminished the prevalence of severe elbow degeneration among patients with rheumatoid arthritis. However, it hasn't been eliminated. In this article the authors discuss strategies for managing it.
23097394 What is causing my arthritis, doctor? A glimpse beyond the usual suspects in the pathogene 2013 Mar Rheumatoid arthritis (RA) is a common, but heterogeneous, disease. Usually, when it comes to the pathogenesis of RA the physician faces a complex network of cytokines and cells of the immune system-the so-called effector level. However, is this network 'the cause' of the disease? Or is this rather the level most physicians are somewhat familiar with, as modern anti-rheumatic medications are having their targets there? In this review, we are looking beyond the usual culprits from the physician's perspective and discuss how other factors, such as genes, epigenetics, environmental factors, local joint characteristics or processes of aging might influence the clinical phenomenon RA.
22763856 Role of ultrasound in managing rheumatoid arthritis. 2012 Oct Ultrasound (US) is a valid and reliable imaging tool for evaluation of joint and tendon inflammation as well as cartilage and erosions in patients with rheumatoid arthritis (RA). Synovitis is usually scored semiquantitatively for both gray scale synovitis and power Doppler activity, and use of an atlas for US scoring has shown excellent reliability. Several scores are shown to be responsive to medical treatment, but the optimal joint/tendon score is to be explored. Doppler activity may be quantified by use of pixel counts and flow may be examined by use of resistive index. US-guided injections are better tolerated and have increased efficacy, as compared with palpation guidance, and should thus be included in rheumatologic practice. Different methods such as three-dimensional US, contrast-enhanced US and fusion imaging methods are all possible US approaches that may be used in treatment of RA patients in the future.
23253922 Advances in sonographic scoring of rheumatoid arthritis. 2013 Apr Accurate assessment of disease activity and joint damage in rheumatoid arthritis (RA) is important for monitoring treatment efficiency and for prediction of the outcome of the disease. Therefore, a reliable imaging method needs to be used. Musculoskeletal ultrasound (US) is a sensitive method for the detection of both early inflammatory soft tissue lesions (eg, synovitis, tenosynovitis, and bursitis) and early bone lesions (eg, erosions) in arthritic joint diseases and correlates well with MRI. Several musculoskeletal US scores are used for monitoring RA disease activity. Different qualitative (0/1) and semiquantitative (0-3) systems and quantitative measurements are used. The semiquantitative four-grade system developed by Skudlarek et al, which evaluates joint effusion, synovial thickening, bone erosion and power Doppler activity, is used most often. The new seven-joint ultrasound (US7) score is the first US sum score system which combines soft tissue (synovitis and tenosynovitis/paratenonitis) and destructive lesions (erosions) in a composite scoring system. The US7 score provides a fast overview of disease activity in daily rheumatological practice. This article reviews different US scores and sum scoring systems and current and proposed activity in this field.
22162279 Custom foot orthoses for rheumatoid arthritis: A systematic review. 2012 Mar OBJECTIVE: To identify and critically appraise the evidence for the effectiveness of custom orthoses for the foot and ankle in rheumatoid arthritis. METHODS: Studies were identified in appropriate electronic databases (from 1950 to March 2011). The search term "rheumatoid arthritis" with "foot" and "ankle" and related terms were used in conjunction with "orthoses" and synonyms. Included studies were quantitative longitudinal studies and included randomized controlled trials (RCTs), case-control trials, cohort studies, and case series studies. All outcome measures were investigated. Quality assessment was conducted using the Cochrane Collaboration criteria with additional criteria for sample population representativeness, quality of statistical analysis, and compliant intervention use and presence of cointerventions. Meta-analyses were conducted for outcome domains with multiple RCTs. Qualitative data synthesis was conducted for the remaining outcome domains. Levels of evidence were then assigned to each outcome measure. RESULTS: The inclusion criteria were met by 17 studies. Two studies had high quality for internal validity and 3 studies had high quality for external validity. No study had high quality for both internal and external validity. Six outcome domains were identified. There was weak evidence for custom orthoses reducing pain and forefoot plantar pressures. Evidence was inconclusive for foot function, walking speed, gait parameters, and reducing hallux abductovalgus angle progression. CONCLUSION: Custom orthoses may be beneficial in reducing pain and elevated forefoot plantar pressures in the rheumatoid foot and ankle. However, more definitive research is needed in this area.
22176928 [Alternatives in the treatment of rheumatoid arthritis: reasons for using abatacept]. 2012 May Rheumatoid arthritis (RA) is an aggressive and progressive disease in which the prognosis has improved dramatically since the arrival of biological therapies at the end of the nineties. Nowadays, the main management strategies focus on early diagnosis and treatment, which is now more feasible due to the development of new classification criteria orientated towards diagnosis and classification of early and undifferentiated disease. The implementation of early, individualized and intensive treatment, with the aim of achieving remission or a low disease activity state, has notably improved the results obtained in a great percentage of patients, especially in those with a poorer prognosis. Abatacept is one of the biotechnological agents that have become part of the first line therapeutic armamentarium for early and aggressive RA. The efficacy and safety profile of this drug are very promising for the treatment of patients with RA.