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ID PMID Title PublicationDate abstract
28974987 Sustained remission in rheumatoid arthritis: latest evidence and clinical considerations. 2017 Oct Sustained remission is an ultimate treatment goal in the management of patients with rheumatoid arthritis (RA). Historically the frequency of sustained remission was low but the frequency of achieved sustained remission is increasing over time. The last years' clinical studies of tight control targeted treatment and intervention trials of early use of intensive strategy suggest that these treatment strategies are associated with higher rates of sustained remission. Achievement of sustained remission, in particular but not limited to early sustained remission, can provide tapering and stopping disease-modifying antirheumatic drugs (DMARDs). With new treatment strategies drug-free sustained remission is becoming an achievable goal. Sustained remission is associated with improved outcomes in regard to function, patient-reported outcomes and survival. Drug-free sustained remission is characterized by normalized function ability and survival. Sustained remission and, in particular, drug-free sustained remission offer hope that early identification of patients with arthritis, early improved novel treatments and treatment with target to achieve remission may potentially transform the progressive course of RA disease and disrupt RA chronicity. In this review we summarize the recent evidence on sustained remission in patients with RA, treatment strategies to achieve sustained remission, management of patients in sustained remission and significance of sustained remission from the patient perspective.
28210457 Non-healing tongue ulcer in a rheumatoid arthritis patient medicated with leflunomide. An 2017 Feb Leflunomide is a member of the disease modifying anti-rheumatic drugs group used as a treatment modality in active rheumatoid and psoriatic arthritis. "Oral ulcers" are reported in 3-5% of leflunomide medicated rheumatoid arthritis patients with adverse events, but they are not described in detail in the literature. We present a case of an ulcer in the tongue of a rheumatoid arthritis patient managed with leflunomide and contemplate on its pathogenesis. Key words:Leflunomide, oral ulcer, DHODH.
28808511 Large endocardial rheumatoid nodules: a case report and review of the literature. 2017 Jul Rheumatoid nodules occur frequently in patients with rheumatoid arthritis and are the most common cutaneous manifestation of the disease. Although uncommon, rheumatoid nodules may also occur on cardiac valves, where they may be large and clinically significant. They may embolize and cause stroke. They may cause regurgitant murmurs, or they may result in valvular destruction. Echocardiographically, they may mimic an atrial myxoma or appear as a vegetation. We present a patient with seronegative rheumatoid arthritis who developed an acute embolic stroke; he had peripheral stigmata of infective endocarditis on physical examination and echocardiography revealed a mitral valve vegetation. We illustrate that these findings were due to a large, highly destructive mitral valve rheumatoid nodule. We review the literature on macroscopic endocardial nodules and emphasize their diverse clinical behavior.
28794554 Mucocutaneous Manifestations in Patients with Rheumatoid Arthritis: A Cross-sectional Stud 2017 Jul BACKGROUND: Cutaneous manifestations are fairly common in rheumatoid arthritis (RA) and they can help in early diagnosis, prompt treatment, and hence reduced morbidity from the disease. AIMS: The objective of the present study was to find out the different patterns of dermatoses in a group of patients with RA from Eastern India. METHODOLOGY: Consecutive patients fulfilling the American Rheumatism Association 1987 revised criteria for the classification of RA and who had different dermatoses were included in this cross-sectional study done over a period of 8 years in a tertiary care hospital in Eastern India. Thorough clinical examination and appropriate laboratory investigations were performed as needed. Data were recorded in a predesigned schedule, and appropriate statistical analysis was done. RESULTS: We studied 111 evaluable patients with an age range of 19-71 years and a female to male ratio of 7:1. The mean disease duration of RA was 6.5 years. Cutaneous infections as a group was the most common mucocutaneous manifestation (34.2%) followed by xerosis including ichthyotic skin changes (27%), pigmented purpuric dermatoses (14.4%), leg ulcer (9.9%), periungual telangiectasia (9.9%), rheumatoid nodules (RNs) (8.1%), purpura and ecchymoses (7.2%), small vessel vasculitis in (7.2%), corn and callosities (6.3%), palmar erythema (4.5%), and neutrophilic dermatosis (4.5%). Raynaud's phenomenon was found in 3.6% patients and panniculitis in (3.6%) patients. Rheumatoid factor (RF) and anti-cyclic citrullinated peptides antibody were positive in 74.8% and 88.3% patients, respectively. No statistically significant difference of incidence of leg ulcer, small vessel vasculitis, RN, or Raynaud's phenomenon could be noted between RF positive and negative groups. LIMITATIONS: Being an institution-based study, the study findings may not reflect the true situation in the community which remained a limitation of this study. CONCLUSION: While some of the features of this study were analogous to Western data, other features showed discordance which may be due to ethnic variations among the patients with RA.
29204673 The Role of Autoantibodies in Bone Metabolism and Bone Loss. 2018 May Many autoimmune diseases are associated with deranged bone metabolism. The resulting localized or systemic bone loss can compromise the quality of life of patients by causing local bone deformities or fragility fractures. There is emerging evidence that antibodies have a direct impact on key players of bone homeostasis, in particular osteoclasts. Clinical and pre-clinical studies provide insight into the function of autoantibodies related to Rheumatoid Arthritis (rheumatoid factor, anti-citrullinated protein antibodies, and anti-carbamylated protein antibodies) and their inflammation-independent interaction with bone cells. Furthermore, we summarize the current knowledge about neutralizing antibodies to the antiresorptive protein osteoprotegerin, which have been described in patients with Coeliac Disease, Rheumatoid Arthritis, and Spondyloarthritis.
29177078 Which patients presenting with arthralgia eventually develop rheumatoid arthritis? The cur 2017 Early initiation of treatment in patients with inflammatory arthritis at risk of persistence and/or erosive progression is important because it is associated with a reduced rate of progression of joint damage and functional disability. It has been proposed that a window of opportunity exists, during which disease processes are less matured and disease modification can be more effective. The phase of arthralgia preceding clinical arthritis is likely to be an important part of this window of opportunity, during which treatment might prevent progression to clinical arthritis. Several proof-of-concept trials in individuals with arthralgia are now evaluating this hypothesis. Central to such trials is the ability to identify groups at high risk of rheumatoid arthritis (RA) in whom preventive treatment can be tested. This review describes the relevance of adequate prediction making, as well as the accuracy of different types of predictors (including imaging and serological markers) with their value in predicting the progression of arthralgia to arthritis. Despite promising results, studies have been performed in heterogeneous patient populations and most findings have not been validated in independent studies. Future observational or preventive studies should be conducted with homogeneous patient groups (eg, patients fulfilling the European League Against Rheumatism criteria for arthralgia at risk of RA) in order to increase interstudy comparability and to allow result validation.
28860993 Tamarixinin A Alleviates Joint Destruction of Rheumatoid Arthritis by Blockade of MAPK and 2017 Background: Tamarixinin A, a natural tannin isolated from Myricaria bracteata, has been confirmed to have moderate anti-inflammatory effects in vitro and in vivo. However, how it effects rheumatoid arthritis (RA) is still unknown. Therefore, the aim of this study is to investigate the therapeutic effects of tamarixinin A on experimental RA, and explore the underlying mechanism. Methods: The anti-arthritic effects of tamarixinin A were evaluated on collagen-induced arthritis (CIA) mice and adjuvant-induced arthritis (AIA) rats. The hind paw thickness, inflammatory cytokine levels in serum, and histopathological assessments were determined. The arthritis score was evaluated. Activation of p38 and p65 in AIA rats was also determined. The anti-inflammatory effect in vitro was also tested in LPS induced macrophages, and its related anti-inflammatory signaling pathways were explored. Results: Treatment with tamarixinin A significantly suppressed the progression and development of RA in CIA mice and AIA rats. Both in CIA mice and AIA rats, arthritis scores decreased, paw swelling and thickness were reduced, and joint destruction was alleviated. In AIA rats, tamarixinin A significantly inhibited the expression of p38, p-p38 and p65. In addition, tamarixinin A inhibited the production of pro-inflammatory mediators, the phosphorylation of p38, ERK, JNK and p65, as well as the nuclear translocation of p38 in LPS- induced macrophages. Conclusion: Tamarixinin A is a potential effective candidate compound for human RA treatment, which executes anti-arthritic effects potentially through down-regulating MAPK and NF-κB signal pathway activation.
31644159 Tumor Necrosis Factor Antagonists. 2012 Tumor necrosis factor (TNF) alpha is a bioactive cytokine that is an important component of the inflammatory and pain pathways. Inhibition of TNF can decrease the inflammatory response, and this approach has been used in therapy of autoimmune conditions, most effectively in inflammatory bowel disease (IBD), rheumatoid arthritis, juvenile idiopathic arthritis (also known as juvenile rheumatoid arthritis), psoriasis, psoriatic arthritis and ankylosing spondylitis. Five anti-TNF antagonists have been developed and introduced into clinical medicine: a mouse-human chimeric monoclonal antibody to TNF (infliximab), two human monoclonal antibodies to TNF (adalimumab and golimumab), a humanized Fab fragment of anti-TNF linked to polyethylene glycol (certolizumab), and a soluble recombinant form of the TNF cellular receptor (etanercept) which, on binding, blocks the activity of TNF. These TNF antagonists have potent activity in several autoimmune diseases marked by excessive production of this proinflammatory cytokine. All five of these agents are approved for use in rheumatoid arthritis and are considered “disease modifying anti-rheumatic drugs” (DMARDs), having been shown to decrease pain, improve function, and ameliorate progressive joint damage in rheumatoid arthritis. The monoclonal antibodies to TNF have also been shown to be effective in psoriatic arthritis, ankylosing spondylitis and inflammatory bowel disease. The five agents rarely cause serum aminotransferase elevations, but have been linked to rare instances of clinically apparent, acute liver injury which often resembles autoimmune hepatitis and can be severe or require corticosteroid therapy. TNF antagonists are also immunosuppressive and can lead to reactivation of latent infections such as tuberculosis and hepatitis B. Severe and even fatal instances of reactivation of hepatitis B have been linked to several anti-TNF agents, and routine screening for HBsAg before starting therapy with these agents is recommended. Patients with HBsAg should receive prophylaxis with an oral antiviral agent during therapy with one of the TNF antagonists. Among the TNF antagonists, infliximab has been most frequently and etanercept least frequently linked to liver injury, including asymptomatic serum aminotransferase elevations, induction of clinically apparent autoimmune hepatitis, and reactivation of hepatitis B. However, infliximab has been most extensively used and studied than the other anti-TNF monoclonal antibodies, and liver injury due to these agents is probably class specific. For these reasons, all five of these agents should be considered potentially hepatotoxic, etanercept perhaps less so that the others. Drug Class: Antirheumatic Agents; Gastrointestinal Agents; Psoriasis Agents
29042950 Expression of CCR3, SOX5 and LC3 in patients with elderly onset rheumatoid arthritis and t 2017 Oct This study investigated the expression of C-C chemokine receptor type 3 (CCR3), transcription factor SOX5 (SOX5) and microtubule-associated protein 1 light chain 3 (LC3) in patients with elderly onset rheumatoid arthritis (EORA) and the clinical significance. Ninety patients with elderly onset rheumatoid arthritis were selected in our hospital from January to December in 2016 to serve as patient group. At the same time, 50 healthy people were selected as control group. Levels of CCR3, SOX5 and LC3 in serum of two groups were detected by enzyme-linked immunosorbent assay (ELISA). Expression levels of CCR3, SOX5 and LC3 mRNA in peripheral blood mononuclear cells (PBMCs) were detected by reverse transcription-PCR (RT-PCR). Expression level of CCR3 mRNA in patient group was 0.752±0.054, which was significantly higher than that in control group (0.287±0.032, t=8.932, P<0.05). Levels of CCR3, SOX5 and LC3 in serum of patients in patient group were significantly higher than those in control group (P<0.05). Positive correlations were found between serum levels of CCR3 and SOX5 (r=0.613, P<0.05), serum levels of CCR3 and LC3 (r=0.637, P<0.05), and serum levels of SOX5 and LC3 (r=0.645, P<0.05). CCR3, SOX5 and LC3 are highly expressed in PBMC and serum, which may be closely related to the occurrence and development of EORA. These indexes may be used as indicators of clinical diagnosis and prognosis of patients with EORA.
28658830 Blue Finger Syndrome: An Unusual Presentation of Rheumatoid Arthritis. 2017 May Blue Finger Syndrome (BFS) is a benign and rare condition with an idiopathic aetiology. It is characterised by an acute bluish discoloration of fingers which may be accompanied by pain. This is a case of a middle aged female who presented with painless bluish discoloration of right hand and was diagnosed to have BFS. Though BFS is idiopathic, our patient on evaluation was found to have an underlying Rheumatoid Arthritis (RA). Patients with RA are subject to Raynaud's phenomenon; but BFS presenting in a patient with RA is a rare scenario.
29029510 Adenovirus-mediated delivery of Sema3A alleviates rheumatoid arthritis in a serum-transfer 2017 Sep 12 Rheumatoid arthritis is a chronic autoimmune disease characterized by infiltration of inflammatory cells into the synovium and destruction of cartilage and bone. Macrophages, fibroblast-like synoviocytes (FLS), and osteoclasts are critical cells driving the pathogenesis of RA. Semaphorin 3A (Sema3A) is recently identified as an essential player in the bone homeostasis, however its role in RA progression especially in the macrophage polarization are poorly understood. In the present study, we found that Sems3A levels were significantly decreased in RA serum and synovial fluid compared to OA controls. There was a negative correlation between Sema3A levels and RA severity. Using in vitro cell cultures, we showed for the first time that Sema3A promoted IL-4 induced M2 macrophage polarization, whereas prohibited LPS/IFN-γ induced M1 polarization. Sema3A inhibited VEGF-induced endothelial cells proliferation and migration, suppressed VEGF-mediated invasion and IL-6 production of FLS while stimulating their apoptosis. In addition, Sema3A retarded osteoclastogenesis. In vivo data demonstrated that Sema3A administration attenuated joint tissue damage and the severity of experimental arthritis. Our findings uncovered Sema3A as a promising diagnostic biomarker and novel prevention and treatment strategies in arthritis treatment.
29088724 Inhibition of angiogenesis by arsenic trioxide via TSP-1-TGF-β1-CTGF-VEGF functional modu 2017 Sep 26 Angiogenesis is a critical factor for rheumatoid arthritis (RA). Although anti-TNF biologics work effectively on some RA patients, concerns have been raised about the possible increased development of malignancies alongside such treatments. Arsenic trioxide (As(2)O(3)) has attracted worldwide attention and has been reported to treat some cancers. However, the effects of As(2)O(3) on angiogenesis in the RA synovium remain unclear. Here, we report a systematic increased expression of TSP-1, TGF-β1, CTGF and VEGF in supernatants of a RA fibroblast-like synoviocytes (RA-FLS) and human dermal microvascular endothelial cells (HDMECs) co-culture compared with those from a normal human fibroblast-like synoviocytes (NH-FLS) and HDMECs co-culture. This increased expression may up-regulate endothelial tube formation and transwell migration, as well as microvessel sprouting in ex vivo aortic ring assay. These networked angiogenic factors mainly form a functional module regulating angiogenesis in the RA synovium. We show that As(2)O(3) inhibits angiogenesis in the collagen-induced arthritis (CIA) synovium and consequently arthritis severity via significant suppression of TSP-1, TGF-β1, CTGF and VEGF expression in the CIA synovium, plus in the RA-FLS and HDMECs co-culture as well as NH-FLS and HDMECs co-culture system along with the presence or absence of TNF-α treatment. Thus As(2)O(3) has a significant anti-angiogenesis effect on the RA-FLS and CIA synovium via its inhibition of the RA angiogenic functional module of TSP-1, TGF-β1, CTGF and VEGF and may have a potential for treating RA beyond cancer therapy.
28721679 Phytochemicals as potential antidotes for targeting NF-κB in rheumatoid arthritis. 2017 Aug Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune destructive arthropathy prevalent among people in the age group of 40-70 years. RA induces severe pain, swelling and stiffness of joints resulting in bone damage. RA leads to reduced life expectancy when left untreated. RA is characterized by synovial hyperplasia, infiltration of inflammatory cells resulting in formation of pannus. Synovial hyperplasia is mediated by proinflammatory cytokines, notably IL-1 and TNF-α. NF-κB is a predominant transcription factor in amplifying the inflammatory response. The translocation of activated NF-κB into the nucleus triggers the transcription of several genes that induce proinflammatory cytokine production. The inhibition of NF-κB translocation aids blocking the activation of proinflammatory cascades. The quest for more effective and side-effect free treatment for RA unveiled phytochemicals as efficacious and promising. Phytochemicals have been a source of therapeutic substances for many ailments from ancient times. Their therapeutic ability helps in developing potent and safe drugs targeting immune inflammatory diseases driven by NF-κB including RA. This review highlights the importance of NF-κB inflammatory cascade in RA so as to elucidate the crucial role of phytochemicals that inhibit the activity of NF-κB.
27448322 Pain in autoimmune disorders. 2017 Jun Most autoimmune diseases are associated with pathological pain development. Autoimmune diseases with pathological pain include complex regional pain syndrome, rheumatoid arthritis, and Guillian-Barré syndrome to name a few. The present Review explores research linking the immune system to the development of pathological pain in autoimmune diseases. Pathological pain has been linked to T-cell activation and the release of cytokines from activated microglia in the dorsal horn of the spinal cord. New research on the role of autoantibodies in autoimmunity has generated insights into potential mechanisms of pain associated with autoimmune disease. Autoantibodies may act through various mechanisms in autoimmune disorders. These include the alteration of neuronal excitability via specific antigens such as the voltage-gated potassium channel complexes or by mediating bone destruction in rheumatoid arthritis. Although more research must be done to understand better the role of autoantibodies in autoimmune disease related pain, this may be a promising area of research for new analgesic therapeutic targets. © 2016 Wiley Periodicals, Inc.
29262569 Evaluation of the association of UBASH3A and SYNGR1 with rheumatoid arthritis and disease 2017 Nov 28 Rheumatoid arthritis (RA) is a common complex autoimmune disorder. UBASH3A and SYNGR1 were identified recently as susceptibility genes for RA risk in Korean and European populations, but the genetic aetiology and pathogenesis of RA have not been fully elucidated. We designed a two-stage case-control study including 916 RA patients and 2,266 unrelated healthy controls to identify common genetic variants in UBASH3A and SYNGR1 that predispose Han Chinese individuals to RA. We also evaluated the role of associated variants in clinical manifestations of RA, which may provide clues to the mechanisms involved in the aetiology of RA. We successfully identified two SNPs, rs1893592 in UBASH3A and rs909685 in SYNGR1, as significantly associated with the disease status of RA using our two-stage strategy. The rs1893592 SNP in UBASH3A was related with DAS28, CRP level and bone erosion. In summary, our results indicate that genetic variants in UBASH3A and SYNGR1 may modify individual susceptibility to RA in the Han Chinese population and support the role of the UBASH3A gene in RA disease activity and severity.
29375934 Rheumatoid Arthritis in Sickle-Cell Population: Pathophysiologic Insights, Clinical Evalua 2017 The advent of hydroxyurea and advanced medical care, including immunizations has led to improved survival among patients with Sickle Cell Disease (SCD). This prolonged survival however, introduces a chronic inflammatory disorder, Rheumatoid Arthritis (RA), which presents at a relatively older age and is rarely reported among SCD patients. In this review, we highlight the epidemiological association of SCD-RA and discuss the underlying common pathogenetic mechanisms, such as endothelial dysfunction, the role of inflammatory cytokines and oxidative stress. We also point to the difficulties in ascertaining the clinical diagnosis of RA in SCD patients. Finally, we provide rationale for therapeutic options available for RA and the challenges in the management of these patients with agents that are known to increase the risk of infection and immunosuppression such as steroids, disease modifying anti-rheumatic drugs and biologics.
28867861 Effect of Integrative Naturopathy and Yoga in a Patient with Rheumatoid Arthritis Associat 2017 Jan A 54-year old married woman was diagnosed with rheumatoid arthritis in 2002, essential hypertension in 2008, type-2 diabetes in 2011 and gangrene over 2(nd) toe of right foot. She underwent conventional management in private hospitals. Her symptoms, began with moderate to severe pain associated with swelling, stiffness (more in the morning) in multiple joints especially over small joints. In July-2014 she visited our college hospital with the complaints of pain, mild swelling and stiffness over multiple joints associated with poor quality of sleep (QOS) and quality of life (QOL). Subject received integrative Naturopathy and Yoga therapies (INYT) with conventional medicine daily for 10-days. After 10-days, improvements in pain, blood sugar, depression, anxiety, stress, QOS, QOL, blood analysis with normal blood pressure (BP) was observed. This suggests that INYT could be considered as an adjuvant to conventional medicine in RA associated with type-2 diabetes and essential hypertension.
28808568 Thymosin β4 in rheumatoid arthritis: Friend or foe. 2017 Sep Rheumatoid arthritis (RA) has characteristic pannus tissues, which show tumor-like growth of the synovium through chronic joint inflammation. The synovium is highly penetrated by various immune cells, and the synovial lining becomes hyperplastic due to increased numbers of macrophage-like and fibroblast-like synoviocytes. Thus, a resultant hypoxic condition stimulates the expression of inflammation-related genes in various cells, in particular, vascular endothelial growth factor. Thymosin β4 (Tβ4), a 5-kDa protein, is known to play a significant role in various biological activities, such as actin sequestering, cell motility, migration, inflammation, and damage repair. Recent studies have provided evidence that Tβ4 may have a role in RA pathogenesis. The Tβ4 level has been shown to increase significantly in the joint fluid and serum of RA patients. However, whether Tβ4 stimulates or inhibits activation of RA immune responses remains to be determined. In the present study, we discuss the logical and clinical justifications for Tβ4 as a potential target for RA therapeutics.
32185261 Regulatory B cells in autoimmune rheumatic diseases. 2017 Jun BACKGROUND: Regulatory B cells (regulatory B cells, Breg cells) in recent years have been shown to be important immunoregulatory factors. AIM: To review the role of Breg cells in autoimmune rheumatic diseases. METHODS: This descriptional review was carried out after research on PubMed using the keywords "Bregs and rheumatoid arthritis", "systemic lupus erythematosus", "Sjögren's syndrome", "systemic sclerosis", "vasculitis", and "dermatomyositis". RESULTS: Breg cells have an inhibitory effect on pro-inflammatory Th1 and Th17 cells and prevent the development of autoimmune diseases. Breg cells mediate their effects through interleukin-10 (IL-10, IL-10+Breg cells), but recently other Breg cells have been recognized that mediate their effects through IL-35 (IL-35+Breg cells), or through transforming growth factor-β (TGFβ, TGFβ+Breg cells). In experimental models of autoimmune diseases, Breg cells are decreased, and when expanded ex vivo and re-infused back into animals, they ameliorate disease. In humans, IL-10+Breg cells are decreased in active autoimmune diseases, such as rheumatoid arthritis, ANCA-associated vasculitis, and systemic sclerosis, and may increase to normal levels in disease remission. CONCLUSIONS: The deficiency of IL-10+Breg cells during active autoimmune rheumatic disease suggests that Breg cells may be used as biomarkers and be a possible therapeutic target in these diseases.
28740485 Tuftsin-Phosphorylcholine Maintains Normal Gut Microbiota in Collagen Induced Arthritic Mi 2017 Rheumatoid arthritis (RA) is characterized by chronic autoinflammation of the joints, with a prevalence of about 1% in Western populations. Evidence in recent years has linked RA to changes in the gut microbiota (dysbiosis). Interestingly, helminths have been shown to have therapeutic activity in RA. Specifically, a glycoprotein containing phosphorylcholine (PC) extracted from helminths was found to have immunomodulatory activity. We have previously developed a novel chimeric compound composed of tuftsin-PC (TPC) that attenuates the joint destruction in mice with collagen-induced arthritis (CIA). Here, we address the interrelationship between TPC immunomodulatory activity and the gut microbiota in CIA mice. Preventive therapy with TPC in mice with arthritis maintained a physiological arthritis score as well as a steady gut microbial environment, similar to that of healthy controls, in contrast to CIA mice with severe disease. The microbial composition differed significantly between healthy and phosphate-buffered saline-treated CIA mice, enabling classifying test samples by machine learning based on levels of a small number of bacterial species. Using these bacterial biomarkers, all TPC-treated CIA mice were classified as healthy. Thus, we describe a clear correlation between TPC treatment, healthy gut microbial communities, and prevention of arthritis. This is the first study to demonstrate the immunomodulatory effect of helminth derivatives in autoimmune diseases and the link to gut microbiota.