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ID PMID Title PublicationDate abstract
31258091 Cardiovascular Risk in Rheumatoid Arthritis and Mechanistic Links: From Pathophysiology to 2020 Rheumatoid arthritis (RA) is an autoimmune inflammatory arthritis. Inflammation, however, can spread beyond the joints to involve other organs. During the past few years, it has been well recognized that RA associates with increased risk for cardiovascular (CV) disease (CVD) compared with the general population. This seems to be due not only to the increased occurrence in RA of classical CVD risk factors and comorbidities like smoking, obesity, hypertension, diabetes, metabolic syndrome, and others but also to the inflammatory burden that RA itself carries. This is not unexpected given the strong links between inflammation and atherosclerosis and CVD. It has been shown that inflammatory cytokines which are present in abundance in RA play a significant role in every step of plaque formation and rupture. Most of the therapeutic regimes used in RA treatment seem to offer significant benefits to that end. However, more studies are needed to clarify the effect of these drugs on various parameters, including the lipid profile. Of note, although pharmacological intervention significantly helps reduce the inflammatory burden and therefore the CVD risk, control of the so-called classical risk factors is equally important. Herein, we review the current evidence for the underlying pathogenic mechanisms linking inflammation with CVD in the context of RA and reflect on the possible impact of treatments used in RA.
32041125 Dual Role of Chondrocytes in Rheumatoid Arthritis: The Chicken and the Egg. 2020 Feb 6 Rheumatoid arthritis (RA) is one of the inflammatory joint diseases that display features of articular cartilage destruction. The underlying disturbance results from immune dysregulation that directly and indirectly influence chondrocyte physiology. In the last years, significant evidence inferred from studies in vitro and in the animal model offered a more holistic vision of chondrocytes in RA. Chondrocytes, despite being one of injured cells in RA, also undergo molecular alterations to actively participate in inflammation and matrix destruction in the human rheumatoid joint. This review covers current knowledge about the specific cellular and biochemical mechanisms that account for the chondrocyte signatures of RA and its potential applications for diagnosis and prognosis in RA.
32829543 Metabolic Syndrome In Young Rheumatoid Arthritis Patients. 2020 Jul BACKGROUND: Metabolic Syndrome is strongly associated with Rheumatoid Arthritis, which significantly increases cardiovascular complications and hence morbidity and mortality. Treating Metabolic Syndrome decreases cardiovascular related disease flares and deaths. This study evaluates prevalence of metabolic syndrome in young Rheumatoid Arthritis patients. METHODS: This Cross-sectional study was conducted in rheumatology department of a tertiary care hospital in Karachi. All diagnosed cases of rheumatoid arthritis from April to August 2018 were consecutively included. Disease activity of rheumatoid arthritis assessed by Clinical Disease Activity Index (CDAI). Associate determinants of rheumatoid arthritis were measured along with outcome variables. RESULTS: Out of 104 rheumatoid arthritis patients, 34 (32.7%) found to have metabolic syndrome in whom 20 (58.8%) of patients were seropositive. A significant association of metabolic syndrome was found with age (p-value 0.023), BMI (p-value 0.006), waist circumference (p-value 0.002), FBS (p-value <0.001), SBP (p-value <0.001), DBP (p-value <0.001), TG (p-value <0.001), HDL (p-value 0.022), and Methotrexate drug history (p-value 0.030). CONCLUSIONS: We conclude that metabolic syndrome is highly prevalent in young rheumatoid patients with rheumatoid arthritis. Treating Metabolic Syndrome decreases cardiovascular related disease flares and deaths. This young population base study will help out to estimate the exact burden of Metabolic Syndrome to decrease overall morbidity and mortality.
32613390 Rheumatoid arthritis and pyoderma gangrenosum: a population-based case-control study. 2021 Feb BACKGROUND: The association between pyoderma gangrenosum (PG) and rheumatoid arthritis (RA) was not investigated in the setting of controlled studies. The risk of PG among patients with RA is not established. OBJECTIVE: The study aims to evaluate the magnitude of the association between RA and the subsequent development of PG. Additionally, we aimed to characterize patients with RA-associated PG relative to other patients with PG. METHODS: A population-based case-control study was conducted comparing PG patients (n = 302) with age-, sex-, and ethnicity-matched control subjects (n = 1497) with respect to the presence of RA. Logistic regression models were utilized for univariate and multivariate analyses. RESULTS: The prevalence of RA was greater in patients with PG than in control subjects (4.7% vs. 1.5%, respectively; P < 0.001). More than threefold increase in the odds of PG with RA (OR, 3.29; 95% CI, 1.66-6.50) was noted. This association retained its statistical significance following a sensitivity analysis excluding RA cases diagnosed up to 2 years prior to PG (OR, 2.72; 95% CI, 1.25-5.91) and after adjusting for confounding factors (adjusted OR, 2.80; 95% CI, 1.23-5.86). RA preceded the diagnosis of PG in the majority of patients by a mean (SD) latency of 9.2 (7.4) years. Patients with RA-associated PG were older relative to the remaining patients with PG (62.2 [15.0] vs. 53.4 [20.9] years, respectively; P = 0.006). CONCLUSIONS: RA increases the odds of developing PG by more than threefold. Physicians managing patients with RA should be aware of this increased burden. Patients with RA may be advised to avoid additional precipitating factors of PG. Key Points • The odds of developing PG are increased by more than threefold in patients with RA. • PG followed the diagnosis of RA in the majority of patients with these coexistent conditions by an average latency of 9.2 years. • Patients with RA-associated were older relative to other patients with PG at the onset of PG.
33025188 Microbial Influences of Mucosal Immunity in Rheumatoid Arthritis. 2020 Oct 6 PURPOSE OF REVIEW: This review will summarize recent data defining the relationship between rheumatoid arthritis (RA) and the microbiome at mucosal sites throughout the body. It will highlight what is known, what is speculated, and current knowledge gaps regarding the microbiome in RA. RECENT FINDINGS: An extensive relationship between the microbiome and immune cell function can influence RA-related inflammation and T cell and B cell biology. Studies are beginning to characterize microbial changes in individuals who are at risk for RA, which is a critical element needed to understand the influence of the microbiome on RA pathogenesis. Expanding our understanding of the microbiome in RA beyond the bacteria at the gut and oral mucosae into the lung and urogenital surfaces, including viral and fungal components, and establishing the relationship across mucosal sites will be critical in future work. Importantly, approaches to manipulate the microbiome could lead to novel therapeutic and preventive strategies.
33254019 A mechanistic insight of phytoestrogens used for Rheumatoid arthritis: An evidence-based r 2021 Jan Assessment of the potential therapeutic benefits offered by naturally occurring phytoestrogens necessitate inspection of their potency and sites of action in impeding the chronic, systemic, autoimmune, joint destructing disorder Rheumatoid arthritis (RA). Possessing structural and functional similarity with human estrogen, phytoestrogen promisingly replaces the use of hormone therapy in eradicating RA symptoms with their anti-inflammatory, anti-oxidative, anti-proliferative, anti-angiogenesis, immunomodulatory, joint protection properties abolishing the harmful side effects of synthetic drugs. Scientific evidences revealed that use of phytoestrogens from different chemical categories including flavonoids, alkaloids, stilbenoids derived from different plant species manifest beneficial effects on RA through various cellular mechanisms including suppression of pro-inflammatory cytokines in particular tumor necrosis factor (TNF-α), interleukin(IL-6) and nuclear factor kappa B (NF-κB) and destructive metalloproteinases, inhibition of oxidative stress, suppressing inflammatory signalling pathways, attenuating osteoclastogenesis ameliorating cartilage degradation and bone erosion. This review summarizes the evidences of different phytoestrogen treatment and their pharmacological mechanisms in both in vitro and in vivo studies along with discussing clinical evaluations in RA patients showing phytoestrogen as a promising agent for RA therapy. Further investigations and more clinical trials are mandatory to clarify the utility of these plant derived compounds in RA prevention and in managing oestrogen deficient diseases in patients.
32519051 Rheumatoid meningitis and infection in absence of rheumatoid arthritis history: review of 2020 Dec A 62-year-old healthy male presents with leg weakness and fever. Imaging revealed leptomeningeal enhancement (LE). After cerebrospinal fluid (CSF) cultures were negative, he was discharged with a diagnosis of aseptic meningitis, but was readmitted due to worsening symptoms. Brain biopsy suggested rheumatoid leptomeningitis associated with elevated serum rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). Following discharge, the New York State Department of Health (NYSDOH) reported a polymerase chain reaction (PCR) on CSF and brain DNA consistent with Naegleria fowleri (NF). After dramatic improvement on steroids, the patient declined antimicrobial treatment. Upon prednisone taper, symptoms recurred which responded to rituximab (RTX). This case highlights a possible association between rheumatoid leptomeningitis (RM) onset and infection, in a patient without a history of rheumatoid arthritis (RA). Our goal is to assess whether this association is present in 69 RM cases reported since 2000. We also describe diagnosis and treatment of 31 new cases (January 2017 to March 2020). We did not identify evidence of active/latent infection in patients with RM and previous RA; however, patients without RA history appeared to have a significantly higher rate. This finding could demonstrate the necessity of evaluating for infection in de novo RM cases without antecedent RA history. We also describe characteristic clinical patterns for each group. More studies are needed to corroborate these results and expand into a possible distinct natural history of RM in each group, which might have an impact upon the clinical outcome.
31773418 Interstitial Lung Disease in Elderly Rheumatoid Arthritis Patients. 2020 Jan The increase in life expectancy together with better care of rheumatoid arthritis (RA) has led to higher proportions of elderly individuals with RA. This has challenged the treatment of the disease in older aged patients, usually characterized by comorbid conditions and polypharmacy. Overall, the lung involvement in RA is present in up to 80% of patients, depending on the assessment tools used, and interstitial abnormalities are among the most common; when present, interstitial lung disease (ILD) worsens the prognosis of RA, and is the second most common cause of mortality. The aged lung undergoes functional and structural changes termed immunosenescence and inflammaging, which facilitate the occurrence of fibrosis of the lung. Therefore, ILD tends to occur more frequently in older patients with RA. The age at onset of RA distinguishes patients as having young-onset RA (YORA, < 60 years) or late-onset RA (LORA, > 60 years); the latter are characterized by more severe features of the disease and higher rates of lung involvement. The most frequent RA-related ILD radiological pattern is usual interstitial pneumonia (UIP); this includes peripheral and basal predominant reticulation and honeycombing with or without associated traction bronchiectasis. Patients with the UIP pattern are usually older and have more rapid decline in lung function and a worse prognosis. Treatment with corticosteroids in elderly patients carries the risk of adverse effects, such as osteoporosis, infections, diabetes, peptic ulcers, and cataract. The use of disease-modifying antirheumatic drugs (DMARDs) is generally well-tolerated by the elderly. The current narrative review aims at elucidating the association between ILD and RA in older individuals.
32740794 Nociceptive related microRNAs and their role in rheumatoid arthritis. 2020 Sep Rheumatoid Arthritis (RA) is an autoimmune disease with unknown etiology and a global incidence around 1%, a positive family history increases the risk of RA roughly three to five times. Pain is one of the first symptoms to appear in this disease. MicroRNAs (miRNAs) belong to the class of small non-coding RNAs; they regulate multiple cellular processes including embryonic development, cellular proliferation, differentiation and apoptosis among others. A great deal of evidence points to the employment of miRNAs as therapeutic targets and biomarkers for several pathologies. The main objective of this Review is to assess how miRNAs participate in the pathogenesis of RA. Two advanced searches were conducted in databases, one using "micro-RNA" and "rheumatoid arthritis" as key words, and another one with "micro-RNA", "pain" and "nociception". In this Review, we describe how six miRNAs: miR-16-5p, miR-23b-3b, miR-124-3p, miR-146a-5p, miR-155-5p and miR-223-3p, involved in the modulation and transmission of the nociceptive input are unregulated in RA patients. Key molecular pathways involved in nociception, inflammation and autoimmune responses, are regulated by these miRNAs; the NF-κB, TNF-α, interleukins and TLR4. By means of gene repression, the miRNAs here described modulate the nociceptive process as well as the autoimmune response that characterize this disease.
32446676 The Role of Musculoskeletal Ultrasound Imaging in Rheumatoid Arthritis. 2020 Aug Musculoskeletal ultrasound (MSUS) is gaining popularity among rheumatologists, especially in the context of rheumatoid arthritis (RA) joint assessment, as it is a non-invasive, radiation-free imaging modality that is relatively easy to set up in a clinic setting. Although ultrasonography (US) is often regarded as being operator dependent with associated reproducibility issues, the use of consensus-based scoring system along with standardized definition of joint inflammation in RA has been shown to improve its performance/reliability as an outcome measurement tool. Through this review article, we have (i) gone through the principle US findings in RA joint assessment, (ii) discussed various scoring systems for evaluation of US joint pathologies, (iii) described the literature in the use of US in areas of RA diagnosis and disease prognostication and (iv) examined the findings of recent major randomized controlled trials incorporating US as monitoring tools to help target treatment in RA. By doing so, we hope to provide clinicians with an insight into the role of musculoskeletal US imaging in areas of RA diagnosis, prognosis and disease monitoring.
32936111 Rheumatoid arthritis with necrotic lung nodules. 2020 Sep Rheumatoid arthritis is a multisystemic inËœflammatory disease. Lungs are the commonest site of extra-articular involvement. Rheumatoid lung nodules occur infrequently and can undergo necrosis giving rise to necrobiotic lung nodules. Infections, malignancy and granulomatosis with polyangiitis are more common causes of cavitating lung nodules. Presence of rheumatoid factor, history of smoking and use of methotrexate increase the chances of developing rheumatoid lung nodulosis. Histopathological examination of the nodule is essential to make a correct diagnosis. We present a 74-year-old male with long-standing rheumatoid arthritis who had multiple cavitating lung nodules. Biopsy from the lung nodule could not be performed as the patient refused to consent. However, infection, malignancy and granulomatosis with polyangiitis were ruled out on the basis of blood investigations and bronchoscopy. He was empirically treated with a moderate dose of glucocorticoid along with conventional synthetic disease-modifying antirheumatic drugs. After three months of treatment, the lung nodules disappeared completely and his articular symptoms showed marked improvement.
33159418 Role of exosome in autoimmunity, with a particular emphasis on rheumatoid arthritis. 2021 Feb Cell-derived exosomes are identified as carriers of lipids, proteins, and genetic materials that participate in cell-cell signal communication, biological process, and cell signaling. Also, their involvement has been reported in a vast array of disorders and inflammatory conditions such as autoimmune diseases. Rheumatoid arthritis (RA), a common cause of joint disorder, is an inflammation-based disease in which the precise understanding of its pathogenesis needs to be further investigated. Also, there is only a palliative care approach for the alleviation of RA symptoms. This paper discusses the recent advances in the biology of exosomes in autoimmune disorders especially in RA, and also provides a new line of research for arthritis therapy using exosomes.
32105594 LTB4-induced anti-apoptosis and infiltration of neutrophils in rheumatoid arthritis. 2020 May Rheumatoid arthritis (RA) is the most common autoimmune disease, resulting in synovitis, joint pain and stiffness, even deformity and disability. The interactions between leukotriene B4 (LTB4) and neutrophils in RA progression have not been elucidated in detail. Our review focuses on the correlation of LTB4 and neutrophils in the development of RA especially in terms of infiltration and delayed life span of neutrophils. In this article, the roles of LTB4 in the anti-apoptosis of neutrophils will be detailed, which is achieved by suppressed pro-apoptotic Bax and up-regulated anti-apoptotic Mcl-1, and several key molecules, as well as signalling pathways and factors relevant to the enhancement of LTB4 production and functions. The mechanisms of LTB4-induced anti-apoptosis and infiltration of neutrophils provide more potential targets in the treatment of RA and recent therapeutic strategies are also discussed.
32552254 Multiple biomarker approach for the diagnosis and therapy of rheumatoid arthritis. 2021 Jan The lack of specific clinical symptoms for patients in the early stage of rheumatoid arthritis (RA) has created strong interest in the laboratory diagnosis of RA. The main laboratory markers of RA, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs), can be found in patients with other pathologies and in healthy donors. Even today, there is no single laboratory test that can diagnosis RA with high sensitivity and specificity. To improve the diagnosis and treatment of RA, alternative biomarkers, including 14-3-3η protein, connective tissue growth factor (CTGF), antibodies against PAD4, antibodies against BRAF, and anti-acetylated and anti-carbamylated protein antibodies have been studied extensively. The use of a multiple biomarker approach, the simultaneous measurement of a set of biomarkers, is an alternative strategy for the diagnosis of RA and for predicting the therapeutic effect of biological disease-modifying antirheumatic drugs (DMARDs). However, despite the large number of studies, only a few biomarker combinations have been validated and can be applied in clinical practice. In this article, results of studies focused on the multiple biomarker approach (both multiplex and combined single-analyte assays) to diagnose RA and to predict response to biological drug therapy are reviewed. Additionally, general factors limiting the use of multiplex analysis in RA diagnostics and therapy are discussed.
32458007 Fertility and infertility implications in rheumatoid arthritis; state of the art. 2020 Aug BACKGROUND: A bulk of investigations imply that women with rheumatoid arthritis (RA) deliver fewer children in comparison to healthy women. PURPOSE: This review article attempts to clarify the involvement of infertility-related issues in both RA men and women. Moreover, the effect of RA disease on the fertility quality and quantity will be discussed. RESULTS: Declined fertility rate in RA women seems to stem from modified inflammatory settings, advanced maternal age, limited sexual activity, and adverse effects of drugs on ovarian function. Women with RA may have smaller families and seem to be slower to conceive relative to their peer women. The chance of gestation in RA women may drop due to suppressed sexual function through pain and fatigue. In addition, treatment of RA women with non-steroidal anti-inflammatory drugs (NSAIDs) may prevent ovulation and therefore hinder the conception. CONCLUSIONS: A complex interaction between RA disease and fertility related issues is present. Despite an increase rate of infertility in RA females or males, the mechanisms involved in this outcome is still unknown. Plausible causes of the decreased fertility rate in RA patients might be due to inflammatory cytokines, suppressed sexual activity, drug treatments, mother age, personal choice, or a combination of these elements.
32524301 The lipid paradox in rheumatoid arthritis: the dark horse of the augmented cardiovascular 2020 Aug Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation that, if left untreated, can cause joint destruction and physical impairments. The inflammatory process is systematic, and it is associated with increased morbidity and mortality. Over the last years, mortality presents a decreasing trend; still, there is a high burden of cardiovascular disease (CVD) in RA that seems to be related to coronary atherosclerosis. Chronic inflammation, physical inactivity, and drugs used to treat RA are some of the reasons. Thus, the management of CVD risk is essential and involves the patient's stratification using distinct parameters that include assessment of the blood lipid profile. However, 'dyslipidemia' in RA patients follows a different pattern under the impact of inflammatory processes, while therapies that target the underlying disease change the levels of specific lipid components. In this review, we explore the relationship between blood lipids and inflammation in the so-called ΄lipid paradox΄ in RA, and we present the existing knowledge over the influence of antirheumatic drugs on the lipid profile of RA patients.
31397840 Lipid management in rheumatoid arthritis: a position paper of the Working Group on Cardiov 2020 Apr 1 Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity, partly due to alterations in lipoprotein quantity, quality and cell cholesterol trafficking. Although cardiovascular disease significantly contributes to mortality excess in RA, cardiovascular prevention has been largely insufficient. Because of limited evidence, optimal strategies for lipid management (LM) in RA have not been determined yet, and recommendations are largely based on expert opinions. In this position paper, we describe abnormalities in lipid metabolism and introduce a new algorithm for estimation of cardiovascular risk (CVR) and LM in RA. The algorithm stratifies patients according to RA-related factors impacting CVR (such as RA activity and severity and medication). We propose strategies for monitoring of lipid parameters and treatment of dyslipidaemia in RA (including lifestyle, statins and other lipid-modifying therapies, and disease modifying antirheumatic drugs). These opinion-based recommendations are meant to facilitate LM in RA until more evidence is available.
32168068 Treatment of immune checkpoint inhibitor-induced inflammatory arthritis. 2020 May PURPOSE OF REVIEW: This review summarizes the current evidence on treatment strategies for inflammatory arthritis because of cancer treatment with immune checkpoint inhibitors (ICI), prognosis of ICI-induced arthritis, and management of patients with preexisting inflammatory arthritis receiving ICI therapy. RECENT FINDINGS: Inflammatory arthritis is the most common rheumatic immune-related adverse event observed in patients receiving ICI therapy. Most patients can successfully be treated with low doses of corticosteroids or conventional synthetic disease modifying anti-rheumatic drugs (DMARDs). A small minority will develop severe symptoms requiring biologic therapy including TNF inhibitors and IL-6 receptor inhibitors. Many cases of inflammatory arthritis will resolve with cessation of ICI therapy. Some patients will develop persistent arthritis despite discontinuation. Patients with preexisting inflammatory arthritis (e.g. rheumatoid arthritis) commonly flare on ICI therapy, but can usually be managed with corticosteroids. SUMMARY: Inflammatory arthritis following ICI therapy for cancer is relatively common and the practicing rheumatologist should be able to recognize and manage it in conjunction with Oncology. The majority of patients respond to corticosteroids, but some will need treatment with conventional synthetic or biologic DMARDs. Additional studies should investigate the effects of immunosuppression on tumor response and the use of ICI therapy in patients with preexisting autoimmune disease.
32942096 Drug-resistance in rheumatoid arthritis: the role of p53 gene mutations, ABC family transp 2020 Oct Rheumatoid arthritis (RA) is an autoimmune disease that is associated with chronic inflammation in joints, which contribute to synovial membrane hyperplasia and cartilage damage. Conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX) and leflunomide (LEF), are the common RA therapy to reduce inflammation and disease progression. Recently, drug-resistance in RA with conventional treatment has become an issue. Mutations in p53 tumor suppressor gene and overexpression of ABCB1/MDR-1/P-gp transporters may contribute to antirheumatic drug-resistance in RA. Biologic DMARDs (bDMARDs) are often prescribed, when conventional DMARDs fail to treat RA, by targeting proinflammatory mediators such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-6. The efficacy of bDMARDs is affected by personal factors, for example, age, smoking, body mass index (BMI), immunogenicity, and genetic polymorphisms. This review highlights the role of p53 gene mutations, ABC family transporters and personal factors in antirheumatic drug-resistance, which may lead to new personalized therapies against RA with an increased drug-sensitivity.
31609811 Rheumatoid Arthritis Patient's Journey: Delay in Diagnosis and Treatment. 2020 Oct OBJECTIVES: The aims of this study were to establish delay times from articular symptoms onset to first rheumatologist consultation, rheumatoid arthritis (RA) diagnosis, and treatment initiation with disease-modifying antirheumatic drug (DMARD) therapy and to assess the impact of delayed diagnosis on structural damage. METHODS: This was an observational cohort study. Rheumatoid arthritis adult patients treated in a private health system between January 1, 1996, and December 31, 2016, were included. Electronic medical records were reviewed to obtain clinical and demographic data, dates of first disease symptom, diagnosis, and date of first treatment with DMARDs. Physical function (Health Assessment Questionnaire) and structural damage (Sharp score modified by van der Heijde) were also assessed. RESULTS: Two hundred forty-six patients (81% female), with a mean age of 67.25 (standard deviation [SD], 14.53) years, were included. At the end of follow-up period, median Health Assessment Questionnaire (n = 145) and radiological scores (n = 171) were 0.125 (interquartile range, 0-0.87) and 15 (interquartile range, 6-33), respectively. A mean of 9.2 (SD, 20) months (median, 3 months) elapsed from the first disease symptom to rheumatologist consultation, 14.2 (SD, 24) months (median, 4.8 months) to RA diagnosis, and 16.9 (SD, 25.4) months (median, 7 months) to treatment initiation with DMARDs. Significantly greater structural damage was found in patients with a diagnosis delay of more than 12 months (n = 70) (p = 0.0325). CONCLUSIONS: Despite good access to medical consultation in a private health system, there is still a delay to RA diagnosis and to start pharmacological therapy. A delay of more than 12 months was significantly associated with greater radiological damage after 5 years of follow-up.