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ID PMID Title PublicationDate abstract
17601357 Inflammatory cells and bone loss in rheumatoid arthritis. 2007 Pathogenic bone erosion is often associated with inflammation. The destructive bone erosion that is often seen in rheumatoid arthritis is probably due to the close proximity of inflamed tissues to bone. Over the past decade, major advances have been made in our understanding of the factors that are crucial in regulating osteoclast bone resorption. It is not surprising that these factors are expressed by inflammatory cells that are present in the rheumatoid joint. It now appears that we can add neutrophils to the list of inflammatory cells found in the inflamed rheumatoid joint that express factors that regulate bone erosion.
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.
19007421 T cells in rheumatoid arthritis. 2008 Over the past decade and a half, advances in our understanding of the pathogenesis of immune-mediated diseases such as rheumatoid arthritis (RA) have translated directly into benefit for patients. Much of this benefit has arisen through the introduction of targeted biological therapies. At the same time, technological advances have made it possible to define, at the cellular and molecular levels, the key pathways that influence the initiation and persistence of chronic inflammatory autoimmune reactions. As our understanding grows, it is likely that this knowledge will be translated into a second generation of biological therapies that are tailor-made for the patient. This review summarizes current perspectives on RA disease pathogenesis, with particular emphasis on what RA T cells look like, what they are likely to see, and how they contribute to persistence of the chronic inflammatory response.
18335856 Rheumatoid factor and anti-CCP autoantibodies in rheumatoid arthritis: a review. 2008 Winter For many years, laboratory diagnosis of rheumatoid arthritis has relied on the detection of rheumatoid factor. A new assay that detects antibodies to citrullinated peptides, called the anti-CCP assay, has demonstrated a comparable sensitivity but a much higher specificity than the RF test. This paper reviews RF and anti-CCP in rheumatoid arthritis and examines the usefulness of each autoantibody in RA testing.
17969665 Management of patients with rheumatoid arthritis. 2007 Oct 3 Rheumatoid arthritis is a chronic inflammatory disease, which mainly affects the peripheral joints. Nurses are integral to the care of patients with this disease. This article discusses the role of the rheumatology nurse in the management of patients with this disabling condition.
16701130 Rheumatoid arthritis: silicone metacarpophalangeal joint arthroplasty indications, techniq 2006 May Silicone implant arthroplasty has been used for more than 40 years for severe rheumatoid disease at the metacarpophalangeal (MCP) joint. Multiple investigations have shown that silicone arthroplasty places the MCP joint in a more extended posture, with some improvement in the total arc of motion. Ulnar drift is also improved, but strength and other objective measures have not demonstrated marked changes postoperatively. The lack of prospective data and more complete outcome assessment has been, at least in part, responsible for the marked difference in opinions between rheumatologists and hand surgeons on the effectiveness of MCP arthroplasty. Recent reports using patient-centered outcome measures have shown that early outcome is favorable, with improvements in appearance, pain, and function.
18777027 [Effectiveness of arthroscopic synovectomy in rheumatoid arthritis]. 2008 Oct Arthroscopic synovectomy in rheumatoid arthritis has proven beneficial in terms of pain relief and joint function, both for upper limb joints (shoulder, elbow, wrist) and the knee. The clinical long-term improvement, such as pain reduction and improved joint mobility, seems more distinct in joints with no or mild joint destruction (early synovectomy) compared to advanced joint damage (late synovectomy). Late-stage elbow arthritis, synovitis of the metacarpophalangeal and proximal interphalangeal joints and the rheumatoid ankle can better be addressed by an open approach. Although a real joint-preserving effect has not been demonstrated, pain reduction and improvement in joint function recommend arthroscopic synovectomy as a substantial treatment option in patients with rheumatoid arthritis.
16283676 Rheumatoid arthritis, a complex multifactorial disease: on the way toward individualized m 2006 Jan With the availability of the human genome sequence and those of related species like chimpanzee, mouse, and rat, data driven research for tackling the molecular grounds of rheumatoid arthritis (RA), a multifactorial polygenic disease, can be considered a realistic challenge to the scientific community. A comprehensive research strategy is presented enabling the integration of multiple research efforts on studying autoimmunity by so called systems biology approaches. An integrative scientific concept is discussed of how to unravel molecular mechanisms of complex diseases by making use of state-of-the-art methodologies in functional and comparative genomics. A continuous interchange of data-driven and hypothesis-driven research is adjoined to determine the nature of rheumatic diseases with autoimmune background. Instead of studying single genes and proteins, RNA and protein microarray profiles are currently obtained in numerous research projects producing read-outs termed gene signatures rather than DNA and/or protein markers. A comprehensive study of the RNA, protein, and metabolite regimes is undertaken that eventually will lead to a "holistic" view of how all respective molecules, pathways and cells themselves interact with each other. Some of the above mentioned research aspects have already been studied by the authors, hopefully leading to new diagnostics and therapeutics in the future.
18155418 Epigenetic clues to rheumatoid arthritis. 2008 Feb The innate immune response needs to be tightly regulated to balance elimination of microorganisms with the magnitude of inflammation. The rupture of this balance is crucial for the outcome of diseases such as rheumatoid arthritis (RA) in which an overflowed proinflammatory response is associated with self-damage. Epigenetics alludes to systems controlling gene expression and silencing independent of the germline, but stable enough to be inherited by daughter cells upon mitosis. We will show in this review how pathological processes in RA can be shaped by epigenetics, which may in turn explain differences in phenotypes between subgroups of patients and also between subsets of fibroblasts within the joint. On the whole, the concourse of epigenetic mechanisms can precipitate the aggressive behaviour of cells and the rupture of peripheral tolerance. Targeting these emerging regulatory pathways is a promising approach for RA therapeutics.
19007425 Abatacept in the treatment of rheumatoid arthritis. 2008 T-cell biology has regained importance in the pathogenesis of rheumatoid arthritis. Despite the significant improvements associated with the introduction of tumor necrosis factor-alpha blockade, reasonable proportions of failures and suboptimal responses have been reported, necessitating a search for alternative targeted therapies. This has included drug therapy designed to interrupt T-cell activation via the co-stimulation pathway. Abatacept is a recombinant fusion protein that blocks the co-stimulatory signal mediated by the CD28-CD80/86 pathway, which is required for T-cell activation. Several clinical trials have confirmed the safety and efficacy of this drug in the treatment of rheumatoid arthritis. This review summarizes the clinical data supporting this line of treatment and considers the safety and efficacy data from phase II and III trials.
18388523 Activity assessments in rheumatoid arthritis. 2008 May PURPOSE OF REVIEW: To describe the importance of assessing disease activity in general, aiming for significant improvement particularly low disease activity and remission, and the value of employing simplified instruments toward this end in rheumatoid arthritis RECENT FINDINGS: Various instruments have either been newly developed, validated or assessed in the recent two years. Additional insights relate to the frequency of attainment of low disease activity and remission in clinical trials and clinical practice, as well as to therapeutic strategies, which involve comprehensive and tight evaluation of disease activity in the adaptation of therapy, including biologicals. All studies assessing these instruments reveal that simplified scores perform at least similar compared with more complex indices, and often better, in the evaluation of disease activity and response to treatment. SUMMARY: Simplified indices can be routinely used in clinical practice and trials and adaptation of therapy on the basis of tight control of disease activity will lead to improved outcomes of rheumatoid arthritis.
16583201 [Systemic manifestations of rheumatoid arthritis]. 2006 May Extra-articular manifestations of rheumatoid arthritis are gaining in importance both in rheumatology and other specialities. This report provides information on various organ manifestations and interactions between mere disease-related symptoms and therapeutic effects. Diagnostic radiology plays a crucial role in finding the diagnosis, planning and monitoring of treatment, early detection of complications and drug-related adverse events.
18261675 Treatment of the wrist in rheumatoid arthritis. 2008 Jan Wrist involvement is common in rheumatoid arthritis and affects up to 50% of patients within the first 2 years after the onset of the disease, including bilateral involvement. It is a progressive disease that destroys the articular cartilage and surrounding soft tissues, thus leading to severe deformities. Radiological changes are characteristic and include narrowing of the joint line, cysts, and periarticular osteoporosis. Clinical changes are characterized by different scoring systems, indicating different therapeutic options. Surgical orthopedic treatment options include joint-preserving techniques to prevent further damage (radiosynoviorthesis, synovectomy, or axial correction with tendon transfers in earlier stages) and joint replacing techniques to restore function (arthrodesis, resection arthroplasty or total joint arthroplasty in later stages). This article reviews pathologic changes in the rheumatoid hand and their surgical treatment alternatives.
17870037 The course of established rheumatoid arthritis. 2007 Oct Rheumatoid arthritis (RA) varies over time in individual patients and there are marked differences between patients in its impact and progression. The course of RA is therefore unique to each individual patient and is affected by the overall pattern of disease; many patients have classical polyarticular disease but there is also a range of subtypes, such as fibromyalgic and polymyalgic disease. Some patients with RA enter a period of sustained remission; this varies between 10% and 36% of cases; its frequency is mainly influenced by the different approaches to studying RA patients over time, and does not represent a true difference in disease outcome. Most patients have persisting synovial inflammation and disease activity scores average between 3 and 4; there is some evidence that inflammation is less marked in late RA. Persisting synovitis results in increasing disability - this worsens by an average of 0.6% each year - and in joint damage, which increases by an average of 2% each year. Comorbidities and extra-articular features are commonplace: about one-third of patients, respectively, have associated cardiovascular disease, lung disease or extra-articular features, although severe extra-articular problems like vasculitis affect only about 10% of patients. Some aspects of the course of RA are influenced by genetic risks; currently these are only weak predictors but it is anticipated their value will increase with time.
16548834 Reducing the cardiovascular disease burden in rheumatoid arthritis. 2006 Mar 20 Rheumatoid arthritis is associated with an increase in cardiovascular mortality and morbidity; this increase is independent of traditional cardiovascular risk factors. Effective treatment of rheumatoid arthritis with disease-modifying antirheumatic drugs appears to reduce cardiovascular mortality. The optimal approach to prevention of cardiovascular disease in rheumatoid arthritis is evolving, but will include a combination of: cardiovascular risk factor screening and management; effective and sustained control of joint and systemic inflammation; and a high index of suspicion for silent cardiac disease.
16932686 T-cell-targeted therapies in rheumatoid arthritis. 2006 Apr T cells regulate the disease process in rheumatoid arthritis (RA) on multiple levels and represent a logical choice for anti-inflammatory therapy. In the inflamed joint they promote neoangiogenesis and lymphoid organogenesis, and stimulate synoviocyte proliferation and development of bone-eroding osteoclasts. The design of T-cell-targeted therapies for RA needs to take into account the uniqueness of T-cell generation, turnover and differentiation in affected patients. Patients accumulate 'old' T cells that respond to alternate regulatory signals because of an accelerated immune aging process; any therapeutic interventions that increase the replicative stress of T cells should, therefore, be avoided. Instead, therapeutic approaches that raise the threshold for T-cell activation are more promising. As a rule, antigen-derived signals synergize with co-stimulatory signals to stimulate T cells; such co-stimulatory signals are now targeted in novel immunosuppressive therapies. An example is abatacept (soluble cytotoxic-T-lymphocyte-associated protein 4-immunoglobulin), which binds with high affinity to CD80/CD86 and effectively suppresses inflammatory activity in RA. The therapeutic benefits gained by disrupting T-cell co-stimulation indicate that the pathogenesis of RA is driven by a more generalized abnormality in T-cell activation thresholds rather than a highly selective action of arthritogenic antigens.
16226478 Gene therapy for patients with rheumatoid arthritis. 2006 Mar Gene therapy seeks either to supply a missing or dysfunctional gene or to ensure continuous long-lasting production of a therapeutic protein. Rheumatoid arthritis is a candidate for gene therapy, as the mechanisms leading to joint inflammation and destruction have been partly elucidated. Nevertheless, several crucial questions need to be addressed. Knowledge of the underlying pathophysiological mechanisms is needed to guide selection of the candidate gene. In the light of current data, TNF and IL-1 antagonists are generating interest. A choice must be made between a viral vector (adenovirus, retrovirus, adeno-associated virus) and a nonviral vector (naked DNA, administered by electrotransfer or in liposomes). Finally, the relative merits of intraarticular and systemic administration need to be considered. Safety is a primary concern. The transgene and/or vector may induce adverse effects. For instance, a transgene inserted within the host genome (when a retroviral vector is used) may induce a mutation. A number of vectors and transgenes induce immune responses. Numerous studies are ongoing to investigate the safety and efficacy of gene therapy strategies in experimental models of rheumatoid arthritis. These studies will have to be completed before further clinical trials of gene therapy in rheumatoid arthritis are considered.
18655507 Managing patients with resistant rheumatoid arthritis. 2008 Jul 2 This article describes the management of patients with difficult to treat rheumatoid arthritis. Pharmacological treatment of patients using disease-modifying and biologic drugs is discussed. Clinical measures of disease activity are also described.
16903767 Early rheumatoid arthritis: pitfalls in diagnosis and review of recent clinical trials. 2006 The treatment of rheumatoid arthritis (RA) has changed dramatically in the past decade as advancements in the understanding of the pathobiology of the disease have led to novel therapeutic agents. The recognition that early diagnosis and treatment leads to improvements in morbidity and mortality has altered the therapeutic strategy such that early therapy is now considered the standard of care. This review focuses on the challenges in making the diagnosis of early RA, including a broad differential diagnosis for inflammatory polyarthritis, poor performance of the standard classification criteria, difficulty in clinical assessment of synovitis, absence of absolute laboratory tests, inability of conventional radiography to detect bony changes early, and barriers to rheumatology care. Additionally, the pathogenesis of RA is highlighted, with particular emphasis on cytokine biology as it relates to therapeutic regimens. Relevant clinical trials in early RA are reviewed and discussed, including trials of combination disease-modifying antirheumatic drugs and biological therapy. The role of induction therapy as a novel therapeutic approach is highlighted. The search for predictors of response is reviewed and the external validity of the trials is analysed. Finally, the trials in early RA therapy suggest that swift intervention with combinations of medications is required for patients with severe RA. However, further research is needed to determine which regimen is appropriate for the individual patient with RA.
16367927 Early environmental factors and rheumatoid arthritis. 2006 Jan The precise cause of autoimmune diseases such as rheumatoid arthritis (RA) remains uncertain. In recent years there has been extensive investment in pursuing genes important in RA. However, estimates suggest that the risk of developing RA is at most 50% determined by genes. There has been limited success defining the environmental factors important in developing RA. We hypothesize that this lack of success may be due to a concentration on the time around disease onset. There is evidence of production of the autoantibodies rheumatoid factor (RF) and anti-cyclic citrullinated peptides (anti-CCP) and increased levels of C-reactive protein (CRP) years before RA becomes clinically apparent. In addition, early life events including intrauterine growth retardation (IUGR) may have long lasting effects on immune function. We review the evidence that the early environment through effects on growth and infectious exposure may influence the likelihood of developing autoimmune diseases such as RA.