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ID PMID Title PublicationDate abstract
30570239 Extra-articular rheumatoid arthritis. 2018 Dec 20 Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly affects the joints, though a consistent proportion of patients may also display extra articular manifestations (EAMs). From rheumatoid nodules to interstitial lung disease, from cardiovascular events to vasculitis, the spectrum of EAMs encompasses various conditions with different prognoses. EAMs may also occur as first RA manifestation, therefore the coordination with other health professionals, including general practitioners, is needed. The aim of this article is to provide an overview on EAMs in RA with particular focus on the recognised risk factors and the available recommendations for managing them, as well as comorbidities in RA patients.
30527425 Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis. 2018 Apr Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation, which affects approximately 1% of the population. The benefit of early recognition and treatment has led to an increased interest in the early phases of disease. With the aim of classifying patients earlier in their disease course, new RA classification criteria have been developed. Much attention has been devoted to the identification in the prearthritis phase of arthralgia. The discovery of new risk factors and autoantibodies has led to new theories about the putative mechanisms involved in disease development. Finally, the outcome measures have also evolved, with more emphasis on sustained drug-free remission and patient-reported outcomes. This article reviews the new developments in RA research and discusses the latest insights into epidemiology, risk factors, predisease states, and outcomes.
29588276 Defining refractory rheumatoid arthritis. 2018 Jul While biologic disease-modifying antirheumatic drugs (bDMARDs) have transformed outcomes of people with rheumatoid arthritis (RA), a proportion of patients are refractory to multiple bDMARDs. Definitions of refractory RA thus far have been arbitrary, and outcome data and impact of such cohorts remain limited. Extrapolation from randomised controlled trial and some real-life data suggest approximately 20% progress onto a third bDMARD with a more modest proportion failing additional bDMARDs. This viewpoint discusses an opinion of refractory RA disease and proposes key principles to accurately identify refractory cohorts. These include demonstrating presence of persistent inflammation despite multiple therapies and acknowledging development of antidrug antibody. Potential basis of refractory disease is summarised, and suggestions for an initial approach in the future evaluation of refractory disease are offered. Specific investigation of refractory RA disease is necessary to inform the clinical need and provide a basis for robust investigation of underlying mechanisms.
30366684 Rheumatoid arthritis and depression: an inflammatory perspective. 2019 Feb The coexistence of immune-mediated inflammatory diseases with depression has long been recognised. Data that illustrate the intimate associations between peripheral and brain immune responses raise the possibility of shared pathophysiological mechanisms. These associations include the negative effects of proinflammatory cytokines on monoaminergic neurotransmission, neurotrophic factors, and measures of synaptic plasticity. The evidence supporting this association is accumulating and includes findings from clinical trials of immunomodulatory therapy, indicating that these interventions can provide benefits to mental health independent of improvements in physical disease scores. In this Review, we assess this evidence in relation to rheumatoid arthritis and depression, with a focus on innate immune and molecular responses to inflammation, and discuss the challenges of assessing causation in this population, acknowledging the difficulty of assessing the confounding and contributory effects of pain and fatigue. We also discuss how future clinical and preclinical research might improve diagnosis of depression in people with rheumatoid arthritis and shed light on mechanisms that could be substrates for therapeutic interventions.
30297553 Rheumatoid arthritis in temporo-mandibular joint: A review. 2018 Oct This article summarizes the temporomandibular joint (TMJ) rheumatoid arthritis (RA). In particular, TMJ-RAs are collected in a short summary by examining every aspect of RA; the treatment of TMJ-RA is also briefly mentioned. TMJ-RA is usually characterized by bilateral pain, tenderness and swelling, and limitation of jaw movements. Due to these symptoms, patients may experience limitations in their daily activities, such as eating, speaking, and swallowing. MEDLINE and Scopus databases were searched electronically using the terms "temporomandibular joint" and "rheumatoid arthritis." The electronic search includes articles or books published in English and December 2017. A search of the reference lists of selected articles was also carried out.
30274624 Renal Manifestations of Rheumatoid Arthritis. 2018 Nov Renal manifestations in rheumatoid arthritis (RA) have evolved as RA management has improved. In the past, older disease-modifying antirheumatic drugs, uncontrolled systemic inflammation, and chronic nonsteroidal antiinflammatory drug (NSAID) use contributed to kidney disease. Over time, the use of methotrexate and biologic medications, decrease in NSAID use, and a treat-to-target strategy have contributed to a decrease in renal manifestations. Chronic kidney disease in RA now is more likely to be caused by cardiovascular risk factors than uncontrolled RA disease severity. In patients with renal dysfunction, NSAIDs, methotrexate, and tofacitinib may need to be adjusted or avoided to prevent adverse events.
30536757 Strategies toward rheumatoid arthritis therapy; the old and the new. 2019 Jul Currently, medications used to treat rheumatoid arthritis (RA) are glucocorticoids (GCs) and nonsteroidal anti-inflammatory drugs (NSAIDs), predominantly used for controlling the pain and inflammation, disease-modifying antirheumatic drugs (DMARDs), administered as first-line medication for newly diagnosed RA cases, and biological therapies, used to target and inhibit specific molecules of the immune and inflammatory responses. NSAIDs and other GCs are effective in alleviating the pain, inflammation, and stiffness due to RA. DMARDs that are used for RA therapy are hydroxychloroquine, methotrexate, leflunomide, and sulfasalazine. The biological therapies, on the contrary, are chimeric anti-CD20 monoclonal antibody, rituximab, inhibitors of tumor necrosis factor-α (TNF-α) like etanercept, infliximab, and adalimumab, a recombinant inhibitor of interleukin-1 (IL-1), anakinra, and costimulation blocker, abatacept. Moreover, newly under evaluation biological therapies include new TNF-α inhibitors, JAK inhibitors, anti-interleukin-6-receptor monoclonal antibodies (mABs), and antibodies against vital molecules involved in the survival and development of functional B cells. The new strategies to treat RA has improved the course of the disease and most of the patients are successful in remission of the clinical manifestations if the diagnosis of the disease occur early. The probability of remission increase if the diagnosis happens rapidly and treat-to-target approach are implemented. In this review article, we have attempted to go through the treatment strategies for RA therapy both the routine ones and those which have been developed over the past few years and currently under investigation.
29256100 The effects of the Mediterranean diet on rheumatoid arthritis prevention and treatment: a 2018 May Rheumatoid arthritis is a progressive autoimmune disease characterised by severely swollen and painful joints. To compliment pharmacotherapy, people living with rheumatoid arthritis often turn to dietary interventions such as the Mediterranean diet. The aim of the present systematic review is to discuss the effects of the Mediterranean diet on the management and prevention of rheumatoid arthritis in human prospective studies. Four studies met the inclusion criteria, including two intervention studies reporting improvement in the pain visual analogue scale (p < 0.05) and a decrease in the health assessment questionnaire for rheumatoid arthritis score (p < 0.05) in the Mediterranean diet groups. Only one study reported a reduction in the 28 joint count disease activity score for rheumatoid arthritis for the Mediterranean diet group (p < 0.05). This review has identified beneficial effects of the Mediterranean diet in reducing pain and increasing physical function in people living with rheumatoid arthritis. However, there is currently insufficient evidence to support widespread recommendation of the Mediterranean diet for prevention of rheumatoid arthritis.
29206659 What are the dominant cytokines in early rheumatoid arthritis? 2018 Mar PURPOSE OF REVIEW: Rheumatoid arthritis is a systemic disease of evolving immune dysregulation that culminates in joint destruction and disability. The principle by which pro-inflammatory cytokines may be therapeutically targeted to abrogate disease is well established, but has yet to translate into reliable cures for patients. Emerging insights into cytokine-mediated pathobiology during rheumatoid arthritis development are reviewed, and their implications for future treatment strategies considered. RECENT FINDINGS: Accumulating data highlight cytokine perturbations before the clinical onset of rheumatoid arthritis. Some of these have now been linked to the arthritogenic activation of autoantibodies and associated pain and bone destruction in affected joints. These observations suggest cytokines may trigger the transition from systemic immunity to arthritis. Cytokine exposure could furthermore 'prime' synovial stromal cells to perpetuate a dominant pro-inflammatory environment. By facilitating cross-talk between infiltrating immune cells and even sustaining ectopic lymphoid structure development in some cases, cytokine interplay ultimately underpins the failure of arthritis to resolve. SUMMARY: Successful therapeutic stratification will depend upon an increasingly sophisticated appreciation of how dominant players amongst cytokine networks vary across time and anatomical space during incipient rheumatoid arthritis. The prize of sustained remission for all patients justifies the considerable effort required to achieve this understanding.
31427060 Malignancy and rheumatoid arthritis: Epidemiology, risk factors and management. 2018 Dec Rheumatoid arthritis (RA) is a chronic inflammatory condition that can result in pain and functional disability. It is also associated with an increased occurrence of comorbidities, including an increased risk of certain cancers such as lung cancer and lymphoma. The aetiopathogenesis of this increased cancer risk is likely multifactorial and includes shared risk factors as well as chronic inflammation. There is also a concern that the treatment for RA itself may increase this risk further, particularly treatment with biologic disease-modifying anti-rheumatic drugs (DMARDs). This paper aims to review the evidence for the increased risk of cancer in RA as well as the latest evidence for the association between DMARDs and tumorigenesis. It also discusses the evidence for the management of patients with biologic DMARDs in the setting of existing cancer.
29974224 [Rheumatoid arthritis]. 2018 Nov Rheumatoid arthritis (RA) is a chronic and progressive systemic disease of the connective tissue, which is particularly manifested with destructive alterations to the joints. Inflammatory reactions in the synovium lead to the influx of peripheral inflammatory cells as well as the activation of local cells. Released growth factors, chemokines and especially cytokines play a key role in chronic inflammatory responses. In addition to the central lymphocytes, the T and B cells and their subpopulations, locally resident cells, such as neutrophils, macrophages and fibroblasts as well as cells of bone metabolism are activated by the inflammatory milieu and contribute to and drive inflammation and tissue damage. The destruction of cartilage and bone substance by local tissue cells, synovial fibroblasts and osteoclasts is characteristic for this disease. Untreated, the local inflammatory and destructive processes as well as systemic inflammatory factors lead to progressive and irreversible joint destruction. Cellular and immunological processes in RA are closely interwoven; therefore, besides the general inhibition of immunological processes, specific inhibition of central key molecules can reduce or completely stop the inflammatory destructive processes; however, a high heterogeneity can be observed among RA patients and disease progression. Therefore, an expansion of the therapeutic options is desirable as not all patients are able to equally benefit from the therapeutic treatment. It is important to characterize new molecular mechanisms, which could lead to the development of new therapeutic options. Some of the more recent insights are summarized in this overview.
29583150 Rheumatoid arthritis and risk of cardiovascular disease. 2018 Sep/Oct 23 In developing countries, rheumatoid arthritis (RA) remains a seriously under-prioritised disease, particularly among the underprivileged, often resulting in presentation of patients late in the course of their disease, further complicated by limited therapeutic options and inconsistent follow up. The consequences are often severe with irreversible disability, increased frequency of co-morbidities, especially cardiovascular disease (CVD), and higher mortality rates, relative to developed countries. Despite addressing traditional cardiovascular risk factors, the impact of subclinical or 'residual' inflammation from uncontrolled RA needs to be considered. This narrative review explores the prevalence and pathogenesis of CVD in RA, including the impact of tobacco use. It discusses pitfalls in the risk assessment of CVD in patients with RA, and the effect of disease-modifying anti-rheumatic therapy on cardiovascular co-morbidity.
29626222 Measuring hand grip strength in rheumatoid arthritis. 2018 May Rheumatoid arthritis (RA) is a systemic inflammatory disease with a particular predilection for causing pain, deformity and functional limitation affecting the hands. Measures of the severity of RA, such as the disease activity score with 28 joint count may not fully reflect the regional impact of RA on the hands. Hand grip strength measurements are a form of objective assessment that focuses specifically on the hands in RA. This review explores what is currently known about the assessment of hand grip strength; what it may indicate, how it is measured, some of the practical aspects and challenges associated with performing these tests, and how this information can be applied in a clinical setting. It summarises the role that grip strength has in assessing patients with RA and finishes with some recommendations for how to use grip strength measurements in clinical practice, and what direction future research might take.
29862535 Rheumatoid arthritis and lymphoma: Incidence, pathogenesis, biology, and outcome. 2018 Dec Patients with rheumatoid arthritis (RA) have a greater risk of developing both Hodgkin lymphoma (HL) and non-HL than the general population. Non-Hodgkin lymphoma is more common than HL in these patients, and diffuse large B cell lymphoma is the most frequent subtype observed. Although the clinical course of lymphoma in RA is often aggressive, the prognosis in these cases is similar to that of lymphoma in the general population. In this review, we summarize data derived from both retrospective and prospective studies, regarding incidence, pathogenesis, and outcome of lymphomas in RA patients and outline the possible mechanisms and hypotheses linking these 2 disorders. Over the years, 3 main theories have been suggested to explain this association. These hypotheses relate to genetic predisposition, persistence of long standing disease activity with continued immune stimulation, and the role of anti-RA therapy given. A common genetic predisposition linking RA and lymphoma has not been established. As for treatment of RA, this includes immunosuppressive antitumor necrosis factor drugs or conventional disease modifying antirheumatic drugs like methotrexate. Neither of these drug categories appears to be associated with a higher risk of lymphoma in RA. The impact of continuing disease activity and immune stimulation appears to be the most significant in lymphomagenesis in these patients.
30128836 Mechanisms for Joint Pain in Rheumatoid Arthritis (RA): from Cytokines to Central Sensitiz 2018 Oct PURPOSE OF REVIEW: Pain in rheumatoid arthritis (RA) may be due to different etiologies, ranging from peripheral inflammation to dysregulation of central nervous system (CNS) processing. This review evaluates relevant literature published on RA pain mechanisms in recent years. RECENT FINDINGS: Despite successes of disease-modifying antirheumatic drugs (DMARDs), pain persists for many RA patients. Studies involving patient-reported outcomes, quantitative sensory testing, and neuroimaging indicate that, in addition to joint inflammation, abnormalities in CNS pain processing may contribute to pain. Some DMARDs (e.g., janus kinus inhibitors) may work via multiple pathways to decrease pain. Adjunctive treatments (e.g., antidepressants, antiepileptics) may also be useful in managing pain in RA patients with well-controlled disease. Both peripheral and central mechanisms play key roles in the expression of pain in RA. To effectively manage pain, physicians need accurate assessment tools to identify the pathways involved in each patient so that treatments may be appropriately targeted.
30657068 Adipokines in rheumatoid arthritis. 2018 Aug 15 Rheumatoid arthritis affects millions of people worldwide and is considered a chronic multisystem disease whose causes are unknown. In general, the main objective of rheumatoid arthritis treatment is to improve the quality of life of patients by relieving pain, maintaining or improving functional capacity, preventing thus, disability. In recent years the role of adipokines in the pathogenesis of rheumatoid arthritis has been discussed but results are still conflicting. Although results from some studies have shown the implications of adipokines in the pathophysiology of autoimmune diseases, including rheumatoid arthritis, their role in the pathogenesis of disease progression is not clear. Thus, this review aimed to describe the association of key adipokines (leptin, resistin, visfatin and adiponectin) and rheumatoid arthritis, given the high prevalence of this disease and the important social impact caused by this chronic disabling disease.
28378441 Physical Activity to Reduce Fatigue in Rheumatoid Arthritis: A Randomized Controlled Trial 2018 Jan OBJECTIVE: Effective treatments for rheumatoid arthritis (RA) fatigue are limited. We tested the effect of a pedometer-based intervention on increasing physical activity and decreasing fatigue among individuals with RA. METHODS: Participants completed baseline questionnaires; had 1 week of activity monitoring; were randomized to control (education [EDUC]), pedometer and step-monitoring diary (PED), or pedometer and diary plus step targets (PED+) groups, and were followed for 21 weeks. At week 10, questionnaires were administered by phone to all participants. During the final week, all participants again had 1 week of activity monitoring. Primary outcomes were changes in average weekly steps and fatigue (Patient-Reported Outcomes Measurement Information System 7-item questionnaire) from baseline to week 21. Secondary outcomes were self-reported disease activity, physical function, pain interference, and depressive symptoms. Changes in steps were tested using a linear mixed model. Changes in fatigue were tested with repeated-measures models, including baseline, week-10, and week-21 scores. RESULTS: A total of 96 individuals participated. Eight did not complete the 21-week assessments. Both intervention groups significantly increased steps (+1,441 [P = 0.004] for PED and +1,656 [P = 0.001] for PED+), and the EDUC group decreased steps (-747 [P = 0.14]) (group-by-time interaction P = 0.0025). Between-group changes in fatigue were not significantly different (interaction P = 0.21). Mean changes in fatigue scores from baseline to week 21 were -1.6 (with-group P = 0.26), -3.2 (P = 0.02), and -4.8 (P = 0.0002) for EDUC, PED, and PED+ groups, respectively. Function and self-reported disease activity also improved in the PED and PED+ groups. CONCLUSION: Provision of pedometers, with and without providing step targets, was successful in increasing activity levels and decreasing fatigue in this sample of individuals with RA.
28833647 Rheumatoid arthritis in review: Clinical, anatomical, cellular and molecular points of vie 2018 Mar Rheumatoid arthritis (RA) is the most common chronic autoimmune disease of the joints affecting close to 0.5-1.0% of the general population. Although the etiopathogenesis of RA remains elusive, the involvement of dendritic cells and type 17 T-helper cells appears to be pivotal in maintaining a state of chronic inflammation. RA is generally characterized by small joint involvement. A chronic inflammatory process leads to joint destruction and to tendon and ligament laxity and disintegration. These processes result in an imbalance of forces acting on the joints causing joint deformities including swan neck deformity, boutonniere deformity of the hands, flexion deformity of the wrist, lesser toe deformities, and others. In some instances, bony erosions subsequent to the RA disease process can result in life-threatening events including, for example, atlanto-axial subluxation, which can cause myelopathy and paralysis; and basilar invagination, which can cause brain stem injury and imminent death. Although less commonly involved, larger joints are not spared, as evidenced by the involvement of the elbow, hip, and shoulder joints in a sizable proportion of RA patients. The progression and prognosis of this disease entity are variable, guarded and dependent on the efficacy and response to treatment modalities employed. Inadequate management results in disease progression, which ultimately leads to joint erosion, destruction, deformities and substantial decrease in the functional quality of life. Clin. Anat. 31:216-223, 2018. © 2017 Wiley Periodicals, Inc.
29595275 [Rheumatoid arthritis]. 2018 Spring Rheumatoid arthritis is an autoimmune disease manifested by a persistent inflammation of synovial joints, bone destruction, loss of cartilage and increased risk of cardiovascular and other intercurrent diseases. The treatment of rheumatoid arthritis should be based on the strategy of treat to target therapy which is achieving remission, in some cases low activity of the disease. Essential to the treat to target therapy are more frequent checkups and optimization of treatment based on disease activity. Methotrexate continues to be the essential medicine from the group of disease modifying antirheumatic drugs for rheumatoid arthritis treatment. At the start are frequently added glucocorticoids. If the effect is insufficient, biological therapy or use of targeted synthetic drugs can be considered. In this overview, the author will focus on epidemiology and risk factors, pathophysiology and in particular on the diagnostics, evaluation of activity and treatment of rheumatoid arthritis.Key words: diagnostics - disease activity - rheumatoid arthritis - treatment.
30593423 Rheumatoid arthritis revisited. 2019 Jan The generally accepted theory of the etiopathology of rheumatoid arthritis has not led to a breakthrough so far, and the root cause of RA is still unknown. Surgical experience does not support the idea that the damage in the joint is caused by synovitis. Synovial tissue does not spread on the surface of the cartilage and thus destroy it, and neither is the erosion caused by the synovial tissue. Macroscopically and microscopically synovitis in RA is no different to synovitis in arthrosis. Perhaps the etiopathogenesis should once more be reconsidered.