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ID PMID Title PublicationDate abstract
30238988 Genetics and rheumatoid arthritis susceptibility in Iran. 2019 May Rheumatoid arthritis (RA) is an autoimmune disorder with a number of risk factors, including both genetic and environmental. A number of RA risk associated genomic loci has been identified. In this review, we summarize the association of genetic factors with RA reported in population studies in Iran. No significant association was found between the majority of genetic factors identified in other populations and risk for RA in the Iranian subjects. This conflicting result could be due to the ethnic differences and diversity that are present in Iran. We conclude that there is a need to investigate larger groups of Iranian subjects, encompassing different regions of Iran, to either prove or refute these initial findings.
30570235 [Rheumatoid arthritis and cardiovascular risk factor : literature review]. 2018 Dec The rheumatoid arthritis remains a common condition and constitutes a diagnostic and therapeutic challenge, especially in the elderly. Rheumatoid arthritis is known to be associated with increased mortality, including coronary and cerebrovascular atherosclerosis. A literature review is conducted on the role of rheumatoid arthritis as a cardiovascular risk factor.
29946747 Preclinical Rheumatoid Arthritis and Rheumatoid Arthritis Prevention. 2018 Jun 26 PURPOSE OF REVIEW: This review is to provide an update on the current understanding of rheumatoid arthritis (RA) development related to disease development prior to the onset clinically apparent synovitis and opportunities for disease prevention. RECENT FINDINGS: A growing number of studies have demonstrated that serum elevations of autoantibodies rheumatoid factor and antibodies to citrullinated protein/peptide antigens (ACPA) are highly predictive of future development of IA/RA. This has underpinned the development of several prevention trials in RA. The full results from most of these prevention trials are pending, but ultimately, they should further inform several critical issues in RA prevention including identification and enrollment of individuals at high risk of imminent RA, the efficacy, safety and cost-effectiveness of prevention, and potentially the identification of new targets for prevention. Results from studies in RA prevention as well as other ongoing natural history studies of RA will help to change the paradigm of how RA is managed, potentially adding prevention to the possibilities for management.
29943203 Optimizing Rheumatoid Arthritis Patients for Surgery. 2018 Jun 25 PURPOSE OF REVIEW: The purpose of this review is to guide providers on how best to optimize the health of patients with rheumatoid arthritis (RA) planning surgery, to reduce risk and complications and achieve the best outcomes. RECENT FINDINGS: The American College of Rheumatology (ACR) and the American Association of Hip and Knee Surgeons (AAHKS) have issued a recent guideline on perioperative management of antirheumatic medications in patients with RA. Patients with RA will continue to need surgery. Newer literature is helping to plan the perioperative period to help reduce complications and improve outcomes.
29981377 Predictors of treatment response in rheumatoid arthritis. 2019 Mar The expanding array of drugs available for treating rheumatoid arthritis is creating challenges in drug selection for the individual patient. The identification of biomarkers that predict the treatment response prior to drug exposure is therefore a current priority. This new approach, known as theranostics, is a component of personalized medicine, which involves selecting the management strategies that are most effective for a given patient at a given point in time. Antibodies to citrullinated peptides, rheumatoid factor, and the interferon signature are the most robust and best validated biomarkers identified to date. Matrices containing clinical or laboratory parameters of diagnostic or prognostic relevance may help to select the best treatment for the individual patient. Furthermore, the development of large-scale approaches requiring no a priori knowledge, such as functional genomics and metabolomics, hold considerable promise, despite persistent difficulties in replicating findings. The complexity of the treatment response in a given patient and substantial variability across patients suggest that biomarkers may be more helpful in combination than singly. The objectives of this review article are to discuss the approaches used to identify theranostic biomarkers and to present an overview of currently available biomarkers and of their performance in everyday clinical practice. However, the range of biomarkers suitable for use in daily practice remains extremely narrow.
29558351 [Rheumatoid arthritis as a connective tissue disease]. 2018 The available data indicate that seropositive rheumatoid arthritis (RA) develops as a result of systemic, autoimmune reaction directed against a range of "self" peptides/proteins that have undergone specific forms of post-translational modification. The development and progress of autoimmunity may be triggered by non-specific, local inflammatory processes outside the joints, for example in the oral or respiratory mucous membrane. The disease occurs in genetically susceptible individuals under the influence of environmental risk factors that promote autoimmunity and consequently the inflammatory process. Smoking is particularly linked with RA pathogenesis. Synovitis of multiple, symmetrical, peripheral joints is the most typical feature of RA which results in irreversible damage to joints structure and as a consequence in disability of patients. However, the inflammatory process in the course of RA has a systemic, constitutional nature. Therefore, extra-articular symptoms with internal organ involvement may occur additionally to synovitis, what is an unfavorable prognostic factor. Extra-articular manifestations of RA are associated with the high disease activity both inflammatory and immunological. They occur in patients with severe form of the disease and contribute to a significant lifespan reduction. This is usually associated with progressive atherosclerosis and cardiovascular complications. The systemic inhibition of an abnormal immune system activity is the mainstay of the effective RA treatment. The currently used disease modifying antirheumatic drugs affect the activity and function of different constituents of the immune system, including B and T lymphocytes and the main pro-inflammatory cytokines, and contribute to autoimmune and inflammatory processes.
28400099 Quality of life and functional capacity in patients with rheumatoid arthritis - Cross-sect 2018 Nov OBJECTIVES: To analyze the Health related Quality of Life (HRQoL) and physical function in rheumatoid arthritis (RA) patients and compare it with the general population. We also intended to analyze about disease activity influence in HRQoL and functional capacity, as well as determine potential determinants for these outcomes. MATERIAL AND METHODS: A cross-sectional study was conducted in RA patients from a university hospital of Portugal. We obtained Short Form 36, EuroQoL 5D, health assessment questionnaire, visual analog scale for pain and patient's assessment of disease activity. Comparisons between SF-36 and EQ-5D values with our population reference values were conducted using the Mann-Whitney test. Data were compared in different levels of disease activity, using Kruskal Wallis test and Fisher's exact test. A multiple regression analysis was conducted to identify the potential determinants of outcomes. RESULTS: RA sample showed significantly lower values than the portuguese general population on physical summary measure of SF-36 (median=32 vs. 50, p<0.001) and EQ-5D (median=0.620 vs. 0.758 respectively; p<0.001). Lower disease activity levels had better PROs and this was true even when compared patients achieving remission with those in low disease activity. The HAQ (r(2)=67%), VAS-P (r(2)=62%) and VAS-DA (r(2)=58%) were the variables that strongly related to SF-36. Considering HAQ, the strongest relation was found with VAS-P, VAS-DA and age (r(2)=60%, 61% and 33%, respectively). Multiple regression analysis identified HAQ, VAS-P and educational status as determinants of the HRQoL; age, female gender, employment, VAS-P and VAS-DA as determinants of physical function. CONCLUSION: Impairment of HRQoL in RA patients is enormous. We found significant differences between different levels of disease activity, showing higher HRQoL and functional capacity at lower disease activity levels.
29710545 Cancer chemotherapeutics in rheumatoid arthritis: A convoluted connection. 2018 Jun Chemotherapy is one of the most popular therapeutic strategies to treat cancer. However, cancer chemotherapeutics have often been associated with impairment of the immune system, which might consequently lead to an augmented risk of autoimmune disorders, such as rheumatoid arthritis. Though the accurate mechanistic facets of rheumatoid arthritis induction have not been interpreted yet, a conglomeration of genetic and environmental factors might promote its etiology. What makes the scenario more challenging is that patients with rheumatoid arthritis are at a significantly elevated risk of developing various types of cancer. It is intriguing to note that diverse cancer chemotherapy drugs are also commonly used to treat symptoms of rheumatoid arthritis. However, a colossal multitude of such cancer therapeutics has demonstrated highly varied results in rheumatoid arthritis patients, including both beneficial and adverse effects. Herein, we attempt to present a holistic account of the variegated modalities of this complex tripartite cross-talk between cancer, rheumatoid arthritis and chemotherapy drugs in order to decode the sinuous correlation between these two appalling pathological conditions.
29110355 Long non-coding RNAs in rheumatoid arthritis. 2018 Feb Rheumatoid arthritis, a disabling autoimmune disease, is associated with altered gene expression in circulating immune cells and synovial tissues. Accumulating evidence has suggested that long non-coding RNAs (lncRNAs), which modulate gene expression through multiple mechanisms, are important molecules involved in immune and inflammatory pathways. Importantly, many studies have reported that lncRNAs can be utilized as biomarkers for disease diagnosis and prognostication. Recently, dysregulation of lncRNAs in rheumatoid arthritis and other autoimmune diseases has been revealed. Experimental studies also confirmed their crosstalk with matrix metalloproteinases, nuclear factor-κB signalling and T-cell response pertinent to autoimmunity and inflammation. Circulating lncRNAs, such as HOTAIR, differentiated patients with rheumatoid arthritis from healthy subjects. Taken together, lncRNAs are good candidates as biomarkers and therapeutic targets in rheumatoid arthritis. Further investigation on in vivo delivery of these regulatory molecules and large-cohort validation of their clinical applicability may be useful.
29389831 Rheumatoid arthritis treatment in patients with a history of cancer. 2018 May PURPOSE OF REVIEW: What is the best treatment option in patients with active rheumatoid arthritis who have a history of malignant disease? Rheumatologists are increasingly faced with this question in their daily practice. As uncontrolled high disease activity is an important risk factor for further comorbidities and shortened life expectancy, the treatment has to be effective, without bearing a higher risk for cancer recurrence. What data is available today to guide treatment decisions and how robust is its evidence? RECENT FINDINGS: As patients with prior cancer are usually not included in randomized controlled trials, all data we have to elucidate this topic stems from observational cohort studies, mainly biologics registers established in several European countries. The registries investigated the risk of recurrence of cancer mainly by comparing treatments with csDMARDs and TNF inhibitors. Few results are available so far for the treatment with rituximab. However, because of their observational design, the data can only reflect current clinical practice. Because of the lack of evidence, questions such as: are biologics soon after cancer diagnosis safe, remain. SUMMARY: There is still insufficient data for patients with a very recent history of cancer. However, in patients with cancer being in longer remission, observational data suggest no increased risk of overall cancer recurrence when they are treated either with TNF inhibitors or rituximab.
30253957 Emergent Complications of Rheumatoid Arthritis. 2018 Nov BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease resulting in polyarthritis and systemic effects that may result in morbidity and mortality. OBJECTIVE: This review provides the emergency physician with an updated analysis of acute complications seen with RA, as well as an evidence-based approach to the management of these complications. DISCUSSION: While the joint characteristics of RA are commonly recognized, the extra-articular manifestations may be overlooked. Of most concern to the emergency clinician is the involvement of the airway, cardiovascular, and pulmonary systems; however, RA can affect all organ systems. In addition, complications can arise from the specific therapies used to treat RA. Certain patient populations can have atypical presentations of the disease or may have an exaggerated response to the medications. An understanding of the involvement of these organ systems and complications can direct physicians to a broader differential that can identify disease processes that may have otherwise gone unnoticed. It is not necessarily the role of the clinician to diagnose RA in its earliest phases or initiate long-term immunosuppressive therapy from the emergency department; however, detection of some of the disease's characteristics can lead to earlier referral to specialists to begin therapy and potentially avoid life-threatening complications. If those problems are encountered in the emergency department, this review aims to provide insight into management of those conditions. CONCLUSIONS: Prompt recognition of the acute complications of RA is crucial to treat these conditions. This review investigates these issues in a succinct manner for emergency clinicians.
29745893 Cell therapies for refractory rheumatoid arthritis. 2018 Sep Rheumatoid arthritis (RA), an autoimmune disease, is characterised by a persistent synovitis in the joints and systemic inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and disease-modifying antirheumatic drugs (DMARDs) are widely used to treat RA patients. However, a portion of patients still have inadequate response to traditional medications. Recently, cell-based therapies have become the focus, attracting more attention due to their potential for remission induction. Several immune-regulatory cell types, such as haematopoietic stem cells, mesenchymal stem cells and regulatory T cells have been defined as novel targets. In this paper, we have summarised and reviewed current clinical trials using cell-based therapeutic approaches for the treatment of RA.
30075997 Emerging anti-osteoclast therapy for rheumatoid arthritis. 2018 Sep Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder characterized by progressive destruction of affected synovial joints. Recently, it was demonstrated that osteoclasts play critical roles in bone destruction in RA. Receptor activator of NF-κB ligand (RANKL), which belongs to the tumor necrosis factor superfamily, is indispensable for osteoclast differentiation and bone destruction in RA. Denosumab, a monoclonal antibody against human RANKL, not only increased bone mineral density, but also efficiently suppressed the progression of bone erosion in RA patients in a randomized controlled study. However, denosumab did not reduce the cartilage destruction or disease activity in RA, and further investigation is required to establish the appropriate positioning of denosumab in the treatment strategy of RA.
29508003 [Pharmacological treatment of rheumatoid arthritis and its comorbidities]. 2018 Apr Due to therapeutic advances, rheumatoid arthritis (RA) today has developed into a satisfactorily treatable disease in most cases, with remission being the target of treatment. Early diagnosis with immediate treatment initiation following treat-to-target strategy is the key to a favorable long-term outcome. A guideline-directed treatment algorithm determines the use of conventional synthetic disease-modifying anti-rheumatic drugs (DMARD; e.g., methotrexate), biological DMARD, and targeted oral DMARD (Janus kinase inhibitors). Comorbidities-in particular cardiovascular and interstitial lung disease-affect 80% of RA patients and represent the leading causes for mortality. The choice of drug treatment is influenced by the presence of comorbidities.
29855620 Microvascular endothelial dysfunction in rheumatoid arthritis. 2018 Jul The systemic autoimmune disease rheumatoid arthritis (RA) is characterized by increased cardiovascular mortality and morbidity and is an independent cardiovascular risk factor. Cardiovascular diseases (CVDs) result from accelerated atherogenesis, which is a consequence of endothelial dysfunction in the early stages of the disease. Endothelial dysfunction is a functional and reversible alteration of endothelial cells and leads to a shift in the properties of the endothelium towards reduced vasodilation, a pro-inflammatory state, and proliferative and prothrombotic properties. In RA, endothelial dysfunction can occur in the large vessels (such as the conduit arteries) and in the small vessels of the microvasculature, which supply oxygen and nutrients to the tissue and control inflammation, repair and fluid exchange with the surrounding tissues. Growing evidence suggests that microvascular endothelial dysfunction contributes to CVD development, as it precedes and predicts the development of conduit artery atherosclerosis and associated risk factors. As such, numerous studies have investigated microvascular endothelial dysfunction in RA, including its link with disease activity, disease duration and inflammation, the effect of treatments on endothelial function, and possible circulating biomarkers of microvascular endothelial dysfunction. Such findings could have important implications in the cardiovascular risk management of patients with RA.
30111803 Rheumatoid arthritis and the mucosal origins hypothesis: protection turns to destruction. 2018 Sep Individuals at high risk of developing seropositive rheumatoid arthritis (RA) can be identified for translational research and disease prevention studies through the presence of highly informative and predictive patterns of RA-related autoantibodies, especially anti-citrullinated protein antibodies (ACPAs), in the serum. In serologically positive individuals without arthritis, designated ACPA positive at risk, the presence of mucosal inflammatory processes associated with the presence of local ACPA production has been demonstrated. In other at-risk populations, local RA-related autoantibody production is present even in the absence of serum autoantibodies. Additionally, a proportion of at-risk individuals exhibit local mucosal ACPA production in the lung, as well as radiographic small-airway disease, sputum hypercellularity and increased neutrophil extracellular trap formation. Other mucosal sites in at-risk individuals also exhibit autoantibody production, inflammation and/or evidence of dysbiosis. As the proportion of individuals who exhibit such localized inflammation-associated ACPA production is substantially higher than the likelihood of an individual developing future RA, this finding raises the hypothesis that mucosal ACPAs have biologically relevant protective roles. Identifying the mechanisms that drive both the generation and loss of externally focused mucosal ACPA production and promote systemic autoantibody expression and ultimately arthritis development should provide insights into new therapeutic approaches to prevent RA.
29524589 Air pollution as a determinant of rheumatoid arthritis. 2019 Jan Pollution has long been incriminated in many cardiovascular and respiratory diseases. More recently, studies evaluated the potential role for particulate pollutants in autoimmune diseases, including rheumatoid arthritis (RA). The incidence of RA was found to be higher in urban areas. Living near air pollution emitters was associated with higher risks of developing RA and of producing RA-specific autoantibodies. Nevertheless, no strong epidemiological evidence exists to link one or more specific air pollution particles to RA. The presence in the bronchi of lymphoid satellite islands (inducible bronchus-associated lymphoid tissue, iBALT) is strongly associated with both inflammatory lung disease and RA-associated lung disease. Diesel exhaust particles can stimulate iBALT formation. The induction by air pollution of an inflammatory environment with high citrullination levels in the lung may induce iBALT formation, thereby causing a transition toward a more specific immune response via the production of anti-citrullinated peptide antibodies. Air pollution not only triggers innate immune responses at the molecular level, increasing the levels of proinflammatory cytokines and reactive oxygen species, but is also involved in adaptive immune responses. Thus, via the aryl hydrocarbon receptor (AHR), diesel exhaust particles can trigger a T-cell switch to the Th17 profile. Finally, in the murine collagen-induced arthritis model, animals whose lymphocytes lack the AHR develop milder arthritis.
29149929 Gastrointestinal and Hepatic Disease in Rheumatoid Arthritis. 2018 Feb Gastrointestinal (GI) manifestations of rheumatoid arthritis (RA) are rare, but can be impactful for patients. Some GI processes are directly related to RA, whereas others may be sequelae of treatment or caused by concomitant autoimmune diseases. This article discusses the role of the GI tract in RA pathogenesis; the presentation, epidemiology, and diagnosis of RA-related GI manifestations; concomitant GI autoimmune diseases that may affect those with RA; and GI side effects of RA treatment. The importance of appropriately considering conditions unrelated to RA in the differential diagnosis when evaluating new GI symptoms in patients with RA is noted.
30347191 Rheumatoid arthritis - a mathematical model. 2019 Jan 14 Rheumatoid arthritis (RA) is a common autoimmune disease that mainly affects the joints. It is characterized by synovial inflammation, which may result in cartilage and bone destruction. The present paper develops a mathematical model of chronic RA. The model is represented by a system of partial differential equations (PDEs) in the synovial fluid, the synovial membrane, and the cartilage. The model characterizes the progression of the disease in terms of the degradation of the cartilage. More precisely, we assume a simplified geometry in which the synovial membrane and the cartilage are planar layers adjacent to each other. We then quantify the state of the disease by how much the cartilage layer has decreased, or, equivalently, how much the synovial layer has increased. The model is used to evaluate treatments of RA by currently used drugs, as well as by experimental drugs.
29600949 Clinical remission in rheumatoid arthritis and psoriatic arthritis. 2018 Sep It is currently recognised that remission can be an achievable target for several rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients by a treat-to-target approach. For RA different remission criteria have been proposed, depending on the disease activity scores used, on the importance given to the inclusion of patients' perspective into the definition of remission, and on their applicability in clinical practice, that generate highly different remission rates. Conversely, for PsA, remission is still insufficiently defined and represents a partially unmet need. For both conditions, several first- and second-line treatment strategies are now available - disease-modifying anti-rheumatic drugs (DMARDs) of synthetic and biologic origin - that make the achievement of remission or at least low/minimal disease activity a realistic goal. This paper is a narrative review of the different criteria of remission, in the light of the available treatment strategies for RA and PsA, and in the attempt to provide rheumatologists an opportunity to improve the outcome to the greatest extent possible in their clinical practice.