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ID PMID Title PublicationDate abstract
34974970 Infectious mimics of rheumatoid arthritis. 2022 Mar Rheumatoid arthritis (RA) can have various infectious mimics. As immunosuppressive agents used in treatment can aggravate the underlying infections, correct diagnosis of RA and ruling out infections is important. Numerous viral infections (Parvovirus B19, Hepatitis B, Hepatitis C, Chikungunya and other alphaviruses, human immunodeficiency virus (HIV) and various other viruses), mycobacterial infections (Poncet's disease, tubercular septic arthritis, and leprosy), bacterial arthritis, brucellosis and Lyme disease are among common infections that mimic RA. Widespread travel and tourism, especially to exotic areas, high risk sexual behavior and widespread use of immunosuppressive and chemotherapeutic agents has led to numerous outbreaks of infections in areas where these infections were never reported before. Hence, rheumatologists all over the world should be familiar with musculoskeletal manifestations of infections. History of travel, comorbid fever, skin rash, genital ulcers, urethral discharge, the consumption of unpasteurized milk, lymphadenopathy, tenosynovitis, low platelet count, and positive Mantoux test can offer potential diagnostic clues. Serological testing, cultures, specific radiological signs and deoxyribonucleic Acid (DNA) amplification techniques often aid in diagnosis. Treatment mainly consists of antimicrobial agents, analgesics, and nonsteroidal anti-inflammatory drugs (NSAIDs). However, immunosuppressive agents including steroids and disease modifying anti-rheumatic drugs (DMARDs) are needed occasionally in different refractory and prolonged illnesses. Most of the times, episodes of arthritis are self-limiting and respond to treatment of underlying cause. However, few infections like Chikungunya and Lyme's disease can lead to chronic arthritis as well.
34302692 Hydrogen Sulfide: a Novel Immunoinflammatory Regulator in Rheumatoid Arthritis. 2021 Hydrogen sulfide (H(2)S), an endogenous, gaseous, signaling transmitter, has been shown to have vasodilative, anti-oxidative, anti-inflammatory, and cytoprotective activities. Increasing evidence also indicates that H(2)S can suppress the production of inflammatory mediators by immune cells, for example, T cells and macrophages. Inflammation is closely related to an immune response in several diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and cancer. Considering these biological effects of H(2)S, a potential role in the treatment of immune-related RA is being exploited. In the present review, we will provide an overview of the therapeutic potential of H(2)S in RA treatment.
32822056 Prevalence of rheumatoid arthritis in Edmonton and Northern Alberta. 2021 Apr OBJECTIVE: The purpose of this study was to compare and contrast the prevalence of rheumatoid arthritis in Northern Alberta estimated by health administrative data and data from a rheumatologist-based prescription database. METHODS: The study was performed using administrative health data from the province of Alberta through the local health authority. The cases and population identified in the database were reported from the year 2016. Rheumatology prescribing data was accessed through the Physician Learning Program and based on Alberta health billing data of actively practicing rheumatologists between the years 2012 and 2016. Ethics was provided by the Conjoint Health Research Ethics Boards at the University of Calgary (REB 13-0459). RESULTS: The total population of the area examined was determined to be 2,086,181. The administrative health database identified 42,354 cases of RA based on their case definition with a prevalence of 2.08%. Based on rheumatologist diagnosis and prescribing data, the number of cases identified was 11,273 cases of RA with a prevalence of 0.542%. The average percentage of identified RA patients being seen by a rheumatologist was determined to be 26.7% with the range of 19.8 to 39.9%. CONCLUSION: In conclusion, this study compares and contrasts the prevalence of rheumatoid arthritis reported by administrative data versus identification by specialists. Our study again illustrates that accuracy of case definitions when studying chronic conditions such as rheumatoid arthritis is paramount. The results also suggest a lack of access to rheumatologist services in Northern Alberta and reiterate the need for ongoing recruitment of new rheumatologists as has been highlighted previously. Key Points • The main contribution of this paper is to compare and contrast the prevalence of rheumatoid arthritis as reported by administrative data versus identification by specialists. • Our study also shows the distribution of rheumatoid arthritis in a large geographical area and illustrates a lack of access to subspecialty care in certain regions.
34015765 Rheumatoid arthritis and osteoporosis: a bi-directional Mendelian randomization study. 2021 May 18 Many observation studies have demonstrated a close relationship between rheumatoid arthritis (RA) and osteoporosis (OP). However, the causal genetic correlation between RA and OP remains unclear. In this study, we performed bi-directional Mendelian randomization (MR) analyses to explore causal inference between these two traits. The instrumental variables for RA were selected from a large-scale genome-wide association study (GWAS) (1,523 cases and 461,487 controls). Bone mineral density (BMD) at five different sites (heel (n=265,627), forearm (FA) (n=8,143), femoral neck (FN) (n=32,735), lumbar spine (LS) (n=28,498), and total body (n=28,498)) were used as phenotypes for OP. The inverse variance weighted (IVW) method did not detect any causal effect of BMDs on RA except heel BMD (beta = -7.57 × 10-4, p = 0.02). However, other methods (MR-Egger, weighted median, weighted mode, MR-PRESSO, and MR-RAPS) showed no causal association between heel BMD and RA. Likewise, we did not find a causal effect of RA on BMD at any sites. In conclusion, we found no evidence that RA is causally associated with OP/BMD, or vice versa. We suggested that the associations found in previous observational studies between RA and OP/BMD are possibly related to secondary effects such as antirheumatic treatment and reduced physical activity.
33962037 Integrated nanomaterials for non-invasive photothermal therapy of rheumatoid arthritis. 2021 Oct Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that causes swelling, redness, and arthralgia of multiple joints. Despite significant research and development on the treatment modalities for RA, there is still no established effective treatment option for eradicating joint damage and inflammation. In recent years, photothermal therapy (PTT) has emerged as a practical approach to treat RA. In this review, we outline various factors that affect the effective treatment of RA. Moreover, we discuss various PTT-based nanomaterials that can be used to treat RA.
34948469 Endothelial Progenitor Cells and Rheumatoid Arthritis: Response to Endothelial Dysfunction 2021 Dec 20 Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease characterized by the swelling of multiple joints, pain and stiffness, and accelerated atherosclerosis. Sustained immune response and chronic inflammation, which characterize RA, may induce endothelial activation, damage and dysfunction. An equilibrium between endothelial damage and repair, together with the preservation of endothelial integrity, is of crucial importance for the homeostasis of endothelium. Endothelial Progenitor Cells (EPCs) represent a heterogenous cell population, characterized by the ability to differentiate into mature endothelial cells (ECs), which contribute to vascular homeostasis, neovascularization and endothelial repair. A modification of the number and function of EPCs has been described in numerous chronic inflammatory and auto-immune conditions; however, reports that focus on the number and functions of EPCs in RA are characterized by conflicting results, and discrepancies exist among different studies. In the present review, the authors describe EPCs' role and response to RA-related endothelial modification, with the aim of illustrating current evidence regarding the level of EPCs and their function in this disease, to summarize EPCs' role as a biomarker in cardiovascular comorbidities related to RA, and finally, to discuss the modulation of EPCs secondary to RA therapy.
33939021 Exogenous miRNA: A Perspective Role as Therapeutic in Rheumatoid Arthritis. 2021 Apr 30 Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease that causes joint deformation. Till now several studies has been carried out promising its cure, but curing has not yet achieved to the satisfactory levels. Herbal approach to treat disease by a cross-kingdom mechanism via exogenous miRNA is an emerging trend to target associated genes with RA pathogenesis as a therapeutic potential. The concept of acquired/exogenous miRNA into pathophysiological prospect provides an opportunity to explore inter-species kingdom like regulation of plant miRNAs on human health. The change in gene expression was attributed by a short 22-24 nucleotide long sequence that binds to its complementary region to suppress/silence the gene expression. This makes exogenous miRNA a novel approach for targeted therapy to treat complex chronic inflammatory diseases. Here, aim of the review was to address significance of plant derived miRNA based targeted therapy to regulate inflammation in RA.
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.
33689031 [Glucocorticoid-free and low-dose glucocorticoid treatment of rheumatoid arthritis]. 2021 May Systemic glucocorticoids (GC) are a commonly used component in the treatment of rheumatoid arthritis. The aim of this article is to show the evidence for low-dose GC or GC-free RA treatment regimens. Furthermore, concepts for the de-escalation of GC treatment for RA are presented. There is sufficient evidence in the initial phase that GC treatment in addition to methotrexate (MTX) improves the patient's response to the disease activity as well as the subjective perception of impairments. The dosage of GC, however, needs to be weighed critically and the guideline-based gradual reduction leading eventually to discontinuation must consistently be pursued. In the later phases of the treatment algorithm the risks of GC administration outweigh the benefits and long-term GC treatment should therefore be reserved for exceptional cases. The lowest possible dosage always needs to be determined individually. This can be achieved by using a clinically tested scheme of reducing the prednisolone intake by 1 mg every 4 weeks. The scheme should be considered for patients with a low disease activity or remission due to disease-modifying antirheumatic drug (DMARD) treatment, if they receive 5 mg of prednisolone as long-term treatment. On the whole the positive subjective effects of GC treatment must always be weighed up against the risks of such treatment for RA patients. An ongoing process of readjusting treatment following shared-decision rules must both consistently adapt GC doses and constantly check the indications. Even if a GC-free treatment does not seem realistic, a low-dose GC treatment of RA still is and should be pursued to reduce the risks associated with the treatment.
34132789 Rheumatoid arthritis and osteoporosis: shared genetic effect, pleiotropy and causality. 2021 Oct 13 Rheumatoid arthritis (RA) is associated with increased localized and generalized bone loss, but the complex genetic mechanism between them is still unknown. By leveraging large-scale genome-wide association studies summary statistics and individual-level datasets (i.e. UK Biobank), a series of genetic approaches were conducted. Linkage disequilibrium score regression reveals a shared genetic correlation between RA and estimated bone mineral density (eBMD) (rg = -0.059, P = 0.005). The PLACO analysis has identified 74 lead (8 novel) pleiotropic loci that could be mapped to 99 genes, the genetic functions of which reveal the possible mechanism underlying RA and osteoporosis. In European, genetic risk score (GRS) and comprehensive Mendelian randomization (MR) were utilized to evaluate the causal association between RA and osteoporosis in European and Asian. The increase in GRS of RA could lead to a decrease of eBMD (beta = -0.008, P = 3.77E-6) and a higher risk of facture [odds ratio (OR) = 1.012, P = 0.044]. MR analysis identified that genetically determined RA was causally associated with eBMD (beta = -0.021, P = 4.14E-05) and fracture risk (OR = 1.036, P = 0.004). Similar results were also observed in Asian that osteoporosis risk could be causally increased by RA (OR = 1.130, P = 1.04E-03) as well as antibodies against citrullinated proteins-positive RA (OR = 1.083, P = 0.015). Overall, our study reveals complex genetic mechanism between RA and osteoporosis and provides strong evidence for crucial role of RA in pathogenesis of osteoporosis.
33950225 Phase III trials of JAK1 selective inhibitors in rheumatoid arthritis. 2021 May 5 Upadacitinib and filgotinib, two JAK1 selective drugs have undergone extensive phase III clinical trials in RA and have demonstrated rapid improvements in disease activity, function and patient reported outcomes. Six global phase III randomized controlled clinical trials (SELECT phase III program) evaluated the efficacy and safety of upadacitinib and four clinical phase III trials (the FINCH program) evaluated the efficacy and safety of filgotinib. This article is a critical review of all these studies with focus on the therapeutic efficacy in RA. The aim is to display the data that could allow the approval of these new drugs for the treatment of RA (upadacitinib has been already approved in most of the markets around the world).
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.
34715065 New potential therapeutic approaches targeting synovial fibroblasts in rheumatoid arthriti 2021 Dec Synovial cells play a key role in joint destruction during chronic inflammation. In particular, activated synovial fibroblasts (SFs) undergo intrinsic alterations leading to an aggressive phenotype mediating cartilage destruction and bone erosion in rheumatoid arthritis (RA). Recent research has revealed a number of targets to control arthritogenic changes in SFs. Therefore, identification of SF phenotypes, control of epigenetic changes, modulation of cellular functions, or regulation of the activity of cation channels and different signaling pathways has been investigated. Although many of these approaches have shown efficacy in vitro and in animal models of RA, further research is needed to select the most relevant targets for drug development. This review is focused on the role of SFs as a potential strategy to discover novel therapeutic targets in RA aimed at preserving joint architecture and function.
34006686 [Rheumatoid Meningitis]. 2021 May Rheumatoid meningitis, a central nervous system complication of rheumatoid arthritis, has low morbidity but poor prognosis without treatment. Contrast-enhanced meningeal lesions on one side of the brain on MRI and hyperintensity of the pia mater on FLAIR image are characteristic features and should trigger the suspicion of rheumatoid meningitis. Steroids are effective for treatment, and good outcomes can be obtained through early diagnosis and intervention.
33397492 Identification of differentially expressed genes, signaling pathways and immune infiltrati 2021 Jan 4 BACKGROUND: The disability rate associated with rheumatoid arthritis (RA) ranks high among inflammatory joint diseases. However, the cause and potential molecular events are as yet not clear. Here, we aimed to identify differentially expressed genes (DEGs), pathways and immune infiltration involved in RA utilizing integrated bioinformatics analysis and investigating potential molecular mechanisms. MATERIALS AND METHODS: The expression profiles of GSE55235, GSE55457, GSE55584 and GSE77298 were downloaded from the Gene Expression Omnibus database, which contained 76 synovial membrane samples, including 49 RA samples and 27 normal controls. The microarray datasets were consolidated and DEGs were acquired and further analyzed by bioinformatics techniques. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed using R (version 3.6.1) software, respectively. The protein-protein interaction (PPI) network of DEGs were developed utilizing the STRING database. Finally, the CIBERSORT was used to evaluate the infiltration of immune cells in RA. RESULTS: A total of 828 DEGs were recognized, with 758 up-regulated and 70 down-regulated. GO and KEGG pathway analyses demonstrated that these DEGs focused primarily on cytokine receptor activity and relevant signaling pathways. The 30 most firmly related genes among DEGs were identified from the PPI network. The principal component analysis showed that there was a significant difference between the two tissues in infiltration immune. CONCLUSION: This study shows that screening for DEGs, pathways and immune infiltration utilizing integrated bioinformatics analyses could aid in the comprehension of the molecular mechanisms involved in RA development. Besides, our study provides valuable data related to DEGs, pathways and immune infiltration of RA and may provide new insight into the understanding of molecular mechanisms.
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.
33870928 Diagnosing and managing patients with rheumatoid arthritis. 2021 May 1 Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory condition that affects about 1% of the world's population. The multifactorial nature of RA has created continuous research discoveries leading to improved identification of specific pathways for the pathogenesis of RA. Improved understanding of the pathways has allowed the development of new targeted drugs. Clinicians must understand the most common pathways for pathogenesis of RA, proper diagnostic techniques, and the appropriate management of this disease given the many possible options at their disposal.
33109042 Deciphering Role of Cytokines for Therapeutic Strategies Against Rheumatoid Arthritis. 2021 Rheumatoid Arthritis (RA) is a systemic, chronic, autoimmune, inflammatory disorder that affects both large and small synovial joints in a symmetric pattern. RA initiates as painful inflammation of the joints leading to stiffness of joint, joint destruction and further worsens the condition causing permanent irreversible damage to the joints, making them physically disabled. Across the globe, there are around 1.2 million cases of RA reported. Inspite of various available therapeutic and pharmacological agents against RA, none of the treatments assure complete cure. Understanding the in depth-role of cytokines and interleukins in the disease pathogenesis of RA could help in exploiting them for developing novel therapeutic strategies against RA. This review provides insights into the pathogenesis of RA and gives a brief overview of cytokines, which play an important role in the progression of the disease. We have also discussed the possible role of interleukins in the context of RA, which could help future researchers to explore them for identifying new therapeutic agents.
33597206 Risk for infections with glucocorticoids and DMARDs in patients with rheumatoid arthritis. 2021 Feb Immunomodulatory therapy for rheumatoid arthritis (RA) carries risk for infectious complications. Understanding the risks of different therapeutic options is essential for making treatment decisions and appropriately monitoring patients. This review examines data on the risks for serious infections and other key infections of interest for the major classes of agents in use for RA: glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologics and Janus kinase (JAK) inhibitors. Conventional synthetic DMARDs have an excellent safety profile with recent data available supporting the relative safety of methotrexate. Tumour necrosis factor (TNF) inhibitors are associated with an increase in the risk of serious infections. Risk with other biological agents and with JAK inhibitors varies somewhat but overall appears similar to that of TNF inhibitors, with JAK inhibitors also associated with a greater risk of herpes zoster. Glucocorticoids have a dose-dependent effect on serious infection risk-at higher doses risk of infection with glucocorticoids is substantially greater than with other immunomodulatory therapies, and even low-dose therapy carries a risk of infection that appears to be similar to that of biological therapies.
33813621 Heel fat pad involvement in rheumatoid arthritis: a review and case series. 2021 Nov Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease affecting not only the synovial joints but also multiple extra-articular sites, including ankle and foot soft tissue. Hindfoot abnormalities usually follow those in the forefoot, with up to 4 out of 10 patients experiencing talalgia during their disease course. Enthesophytosis, retrocalcaneal bursitis, and plantar fasciitis are among the most common etiologies, while heel fat pad abnormalities like subcalcaneal bursitis are rare. Here, we report two cases of subcalcaneal bursitis, and the first case of heel fat pad and subcalcaneal bursa herniation in patients with established RA, along with a comprehensive literature review of subcalcaneal bursitis and other heel fat pad abnormalities in RA. Subcalcaneal bursitis, also referred to as panniculitis, inflammatory-edematous lesion, or adventitial (adventitious) bursitis has been reported in up to 10% of patients with RA. It appears as a compressible, heterogeneous, and hypoechoic subcalcaneal mass on ultrasound (US), with peripheral vascularization on Doppler US. Patients may present with heel discomfort. Ultrasonographic assessment is usually sufficient to confirm the presence of heel fat pad pathologies. Rest, analgesics, and mechanical aids with or without addition of disease-modifying antirheumatic drugs are usually employed, while intervention is rarely required.