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ID PMID Title PublicationDate abstract
30996848 Studying anemia of chronic disease and iron deficiency in patients with rheumatoid arthrit 2019 Feb 19 Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the two most important types of anemia in rheumatoid arthritis (RA). Functional iron deficiency in ACD can be attributed to overexpression of the main iron regulatory hormone hepcidin leading to diversion of iron from the circulation into storage sites resulting in iron-restricted erythropoiesis. The aim is to investigate the role of circulating hepcidin and to uncover the frequency of IDA in RA. The study included 51 patients with RA. Complete blood counts, serum iron, total iron binding capacity, ferritin, and hepcidin-25 were assessed. ACD was found in 37.3% of patients, IDA in 11.8%, and combined (ACD/IDA) in 17.6%. Serum hepcidin was higher in ACD than in control and the other groups (P≤0.001). It was strongly and positively correlated with ferritin (P<0.001), while hemoglobin, serum iron, and total iron binding capacity were negatively correlated with hepcidin (P=0.016, 0.022 and <0.001, respectively). High serum hepcidin was significantly associated with ACD in RA. IDA alone or combined with ACD was encountered in about a third of patients.
31497022 Synovial Tissue Inflammation Mediated by Autoimmune T Cells. 2019 In rheumatoid arthritis (RA), various hematopoietic and non-hematopoietic cells present in the synovial tissue secrete numerous inflammatory mediators including pro-inflammatory cytokines critical for the induction of chronic joint inflammation and bone destruction. Fibroblast-like synoviocytes (FLSs) in the non-hematopoietic cell compartment are key inflammatory cells activated in inflamed joints and driving the disease; yet how synovial tissue inflammation is modulated by autoimmune T cells is not fully understood. In this review, mainly based on recent findings with a mouse model of spontaneous autoimmune arthritis, we discuss the mechanism of Th17-mediated synovial tissue inflammation; that is, what environmental stimuli and arthritogenic self-antigens trigger arthritis, how arthritogenic T cells initiate joint inflammation by stimulating FLSs, and how the cellular sources of GM-CSF from lymphoid and tissue stromal cells in the synovium contribute to the development of arthritis. We also highlight possible plasticity of Th17 cells toward pathogenic GM-CSF producers, and the functional instability of regulatory T cells under inflammatory conditions in RA joints.
30539584 Use of a Citrullinated Peptide Panel for Detection of Anti-Citrullinated Protein Antibodie 2019 Anti-citrullinated protein antibodies (ACPA)s are a hallmark of rheumatoid arthritis (RA) and are essential for serological diagnosis of RA.ACPAs are not specific for a single citrullinated target; in fact, several citrullinated ACPA target proteins have been described. As a consequence, ACPAs are primarily detected by enzyme-linked immunosorbent assays, where several citrullinated peptides are used as target antigens.This chapter focuses on the detection of ACPAs using a recently developed peptide panel in enzyme-linked immunosorbent assays.
30987884 Is Palindromic Rheumatism a Pre-rheumatoid Arthritis Condition? Low Incidence of Rheumatoi 2021 Jan OBJECTIVES: Palindromic rheumatism (PR) is characterized by repetitive, afebrile episodes of acute arthritis and peri-arthritis. The aim of this study was considering the long-term outcomes of patients with PR who were treated with tight control strategy using Disease-modifying anti-rheumatic drugs (DMARDs). METHODS: We reviewed the charts of 106 patients diagnosed with PR who were referred to the Connective Tissue Diseases Research Center (CTDRC). We recruited all the patients diagnosed with PR according to the criteria of Hannonen. They visited the CTDRC clinic regularly and were treated with hydroxychloroquine and low dose prednisolone because of active episodes of PR. In cases that the attacks did not come under control in 3-6 months, methotrexate was added or replaced and the dose was increased up to 25mg/week. In resistant cases, sulfasalazine was added, followed by the addition of leflunomide and then azathioprine. Disease outcome was evaluated by getting complete or partial remission and prevention of disease evolution to rheumatoid arthritis (RA) or other inflammatory connective tissue diseases. RESULTS: This study included 92 patients with PR who were treated with DMARDs. Attacks were controlled completely or partially in 76 (82.6%) patients. Medications free remission was obtained in 16.3% of the patients. RA developed in 8.7% of the patients. By multivariate logistic regression analysis, age ≤40 at disease presentation, non-adherence to therapy and PIP joints involvement were the only factors which independently predicted the risk of treatment failure. CONCLUSIONS: Tight control strategy by using DMARDs may control PR and prevent disease progression to RA.
31225429 "Living a normal life": a qualitative study of patients' views of medication withdrawal in 2019 BACKGROUND: Withdrawal of disease-modifying anti-rheumatic drugs (DMARDs) once disease remission is achieved is endorsed by current international rheumatoid arthritis (RA) management guidelines. However, very little data exists concerning patients' views of this practice. In this qualitative study, we aimed to explore patients' perspectives on DMARD withdrawal in the setting of established RA. METHODS: In this qualitative interview study, patients with stable established RA were recruited from rheumatology outpatient clinics at a large UK teaching hospital. The perceived advantages and disadvantages of DMARDs and views on DMARD withdrawal were explored in semi-structured interviews. Interview transcripts were analysed using standard qualitative techniques to construct an analytical framework. RESULTS: Thirteen participants (8 female, median [IQR] age 65 [61-73]) expressed their views of DMARD treatment in the context of their "normal lives". For some patients, disadvantages such as medication side-effects and the inconvenience of safety monitoring were sufficient hindrances to their lifestyle to justify DMARD withdrawal. However, patients who were vulnerable to loss of physical function, or who had prior experience of severe rheumatoid arthritis, expressed a strong preference against DMARD withdrawal, viewing the potential for increased pain and future disability as unacceptable risks. CONCLUSIONS: Patients view DMARD withdrawal in the context of either restoring or threatening their "normal lives". In this model, social and personal factors play a crucial role in influencing patients' opinions of DMARD therapy beyond a simple consideration of medication side-effects alone. A formulaic approach to DMARD withdrawal determined and imposed by clinicians would not be successful. Instead, the discussion of DMARD withdrawal should take place with the identification of patients' priorities and in the context of their personal disease experiences. TRIAL REGISTRATION: clinicaltrials.gov (NCT02064400), retrospectively registered 17 February 2014.
30723716 US-Guided Biopsies: Overarching Principles. 2019 Gathering synovial tissue from any swollen joint especially in early arthritis patients is critical for good quality research and to obtain further insight into the pathophysiology of inflammatory joint diseases. Multiplying biopsy sites is a challenge in terms of the techniques needed for each different joint but also in terms of safety and tolerability. It is important to provide the best care especially in very early arthritis patients who have only had the disease for a few months. This review discusses the minimal requirements applying to antiseptic techniques for the operator's hands, patient preparation, local anesthesia, and post-procedure care.
31157181 Do Bilateral Pleural Effusions Always Have the Same Cause? 2019 A 67-year-old man with a history of seropositive rheumatoid arthritis (RA) was admitted to the Internal Medicine ward for bilateral pleural effusion. Two years before this episode, coinciding with an exacerbation of the RA, he was incidentally diagnosed with asymptomatic left pleural effusion compatible with rheumatoid exudate, which was resolved with a tube thoracostomy. Three weeks before admission, the patient developed asthenia, orthopnoea and progressive dyspnoea. A chest x-ray revealed bilateral pleural effusion occupying the lower third of the left hemithorax and a smaller portion of the right hemithorax along with marked elevation of N-terminal fragment of pro-brain natriuretic peptide levels. The patient was admitted with a diagnosis of left-sided heart failure. Transthoracic echocardiography and cardiac catheterization confirmed the existence of ischaemic cardiomyopathy. After 2 days of diuretic treatment, the right pleural effusion resolved, but the left effusion persisted. A needle thoracentesis was performed, draining 800 ml of milky fluid compatible with rheumatoid pseudochylothorax. LEARNING POINTS: Bilateral pleural effusions nearly always have the same cause, and usually thoracentesis on only one side is needed.Rarely, however, there can be two separate causes: this is known as Contarini's syndrome.
30938236 Peptide-targeted liposomal delivery of dexamethasone for arthritis therapy. 2019 Jun Aim: Rheumatoid arthritis is an autoimmune disease affecting the joints. Antiarthritic drugs are given systemically, thereby exposing various healthy organs to these drugs, resulting in adverse reactions. Accordingly, there is an urgent need for targeted drug delivery methods for inflamed joints. Materials & methods: We developed a liposomal drug delivery system using a novel peptide ligand (CKPFDRALC) named ART-2, which homes to the inflamed joints when injected intravenously to rats with adjuvant-induced arthritis. Results: The ART-2-coated liposomes encapsulating an antiarthritic drug, dexamethasone (DEX), were more effective in inhibiting arthritis progression than control-DEX liposomes or free DEX, despite a comparable safety profile. Conclusion: Peptide-targeted therapy has advantages over conventional drug delivery and can be adapted for rheumatoid arthritis therapy.
30727927 Potent Inhibitory Effects of Quercetin on Inflammatory Responses of Collagen-Induced Arthr 2019 BACKGROUND: Production of tumor necrosis factor (TNF)-α by inflammatory cells in lesions is the hallmark of the pathogenesis of rheumatoid arthritis (RA). Regulation of inflammatory responses in knee joints of patients with RA is critical for improving severe symptoms. Flavonoids have inhibitory effects on the acute and chronic inflammatory responses caused by TNF-α. The flavonoid quercetin (QUER) is one of the most prominent dietary antioxidants. OBJECTIVE: The present study investigated the preventive and therapeutic effects of QUER on inflammatory responses in collagen-induced arthritis (CIA) in mice. METHODS: Mice with CIA, a mouse model for RA, were treated with QUER orally three times a week either from the second immunization with collagen (day 21) or day 28 when symptoms of CIA had developed midway. RESULTS: In both cases, inflammation-related clinical scores of knee joints were significantly reduced by treatment with QUER. Histological analyses showed that the representative characteristics of RA, such as damage to interchondral joints, infiltration of inflammatory cells, and pannus formation, were significantly reduced by QUER treatment. Oral administration of QUER significantly decreases lipopolysaccharide (LPS)-induced TNF-α production in a dose-dependent manner. Expression of TNF- α mRNA in knee joints was decreased in QUER-treated mice, compared with those of CIA controls. CONCLUSION: These results suggest that oral administration of QUER might effectively improve symptoms of RA.
31552259 Nutrition Interventions in Rheumatoid Arthritis: The Potential Use of Plant-Based Diets. A 2019 Rheumatoid arthritis (RA), a chronic inflammatory autoimmune disease, affects roughly 1% of the world's population. RA pathogenesis remains unclear, but genetic factors account for 50-60% of the risk while the remainder might be linked to modifiable factors, such as infectious diseases, tobacco smoking, gut bacteria, and nutrition. Dietary triggers may play an inciting role in the autoimmune process, and a compromised intestinal barrier may allow food components or microorganisms to enter the blood stream, triggering inflammation. In addition, excessive body weight may affect pharmacotherapy response and the likelihood of disease remission, as well as the risk of disease mortality. Evidence suggests that changes in diet might play an important role in RA management and remission. Several studies have shown improvements in RA symptoms with diets excluding animal products. Studies have also shown that dietary fiber found in these plant-based foods can improve gut bacteria composition and increase bacterial diversity in RA patients, thus reducing their inflammation and joint pain. Although some of the trigger foods in RA patients are individualized, a vegan diet helps improve symptoms by eliminating many of these foods. This review examines the potential role of a plant-based diet in mediating RA symptoms. Further research is needed to test the effectiveness of plant-based diets on joint pain, inflammation, and quality of life in patients with RA.
32158482 Clinical trials: their contribution to the efficiency of the clinical management of rheuma 2019 BACKGROUND: This article presents a descriptive analysis of our Clinical Research Unit (CRU) at the Rheumatology Department in the University and Polytechnic Hospital La Fe (RD-UPH La Fe), Valencia (Spain), as well as an estimation of the economic impact of conducting clinical trials for the Spanish Health System in terms of avoided costs. METHODS: During the period 2011-2015, a retrospective observational study was conducted based on the trials performed in our CRU, along with a cost analysis from the health authority perspective. RESULTS: Most of the trials conducted during this period were phase III studies in patients with rheumatic disorders, particularly rheumatoid arthritis. An economic evaluation study showed that the implementation of these studies in our CRU resulted in an annual saving of €13,935.30 per patient. CONCLUSION: Our CRU is an efficacy and efficiency tool for cost saving in the healthcare system.
31413489 Functional and Radiographic Outcomes of the Sauvé-Kapandji and Darrach Procedures in Rheu 2019 Aug Background Deterioration of the distal radioulnar joint (DRUJ) in rheumatoid arthritis (RA) manifests as pain, weakness, and reduced range of motion. The Darrach and Sauvé-Kapandji (S-K) procedures are used when medical management fails to control these symptoms. However, there is a paucity of literature comparing the outcomes of these procedures. The purpose of this study is to compare the clinical and radiographic outcomes of the Darrach and S-K procedures in RA patients. Materials and Methods This is a retrospective, single institution cohort study of RA patients who underwent the Darrach or S-K procedure between 2008 and 2016. Ulnar translation, range of motion, and functional improvement were compared. Results Nine patients (13 wrists) underwent the Darrach procedure, and nine patients (11 wrists) underwent the S-K procedure. The average length of follow-up was 1.3 years. Pain, function, and range of motion improved in both groups. The degree of ulnar translation did not significantly change after either procedure. Conclusion Given their similar outcomes, we found no evidence that the S-K procedure is superior to the Darrach procedure or vice versa. However, when surgery is indicated for younger RA patients with DRUJ disease and ulnar translation, the S-K may be better suited to prevent radiocarpal joint dislocation.
30941350 Synovial Tissue Heterogeneity in Rheumatoid Arthritis and Changes With Biologic and Target 2019 The treatment of rheumatoid arthritis (RA) has been transformed with the introduction of biologic disease modifying anti-rheumatic drugs (bDMARD) and more recently, targeted synthetic DMARD (tsDMARD) therapies in the form of janus-kinase inhibitors. Nevertheless, response to these agents varies such that a trial and error approach is adopted; leading to poor patient quality of life, and long-term outcomes. There is thus an urgent need to identify effective biomarkers to guide treatment selection. A wealth of research has been invested in this field but with minimal progress. Increasingly recognized is the importance of evaluating synovial tissue, the primary site of RA, as opposed to peripheral blood-based investigation. In this mini-review, we summarize the literature supporting synovial tissue heterogeneity, the conceptual basis for stratified therapy. This includes recognition of distinct synovial pathobiological subtypes and associated molecular pathways. We also review synovial tissue studies that have been conducted to evaluate the effect of individual bDMARD and tsDMARD on the cellular and molecular characteristics, with a view to identifying tissue predictors of response. Initial observations are being brought into the clinical trial landscape with stratified biopsy trials to validate toward implementation. Furthermore, development of tissue based omics technology holds still more promise in advancing our understanding of disease processes and guiding future drug selection.
30897745 Golimumab for Rheumatoid Arthritis. 2019 Mar 20 Since the advent of infliximab for the treatment of rheumatoid arthritis (RA), new genetically-engineered molecules have appeared. This review aims to present the current data and body of evidence for golimumab (GLM). Safety, efficacy, tolerability and immunogenicity are all being investigated, not only through phase III trials (GO-BEFORE, GO-FORWARD, GO-AFTER, GO-MORE, GO-FURTHER, GO-NICE), but also through studies of real-world data. It seems that GLM in the subcutaneous form is an efficacious molecule with a good safety profile at the standard dosage scheme, but a 100 mg subcutaneous dose is associated with a higher risk of opportunistic infections, lymphoma and demyelination. Furthermore, when compared to other tumor necrosis factor-α molecules, it is non-inferior, and, at some points, such as when it comes to immunogenicity and persistence of the drug, it has a better profile. In summary, GLM is an effective, well-tolerated option for the treatment of RA, for both the clinician and patients who are seeking a convenient dosage scheme.
31573475 Clinical features and current treatments of adult-onset Still's disease: a multicentre sur 2019 Nov OBJECTIVES: As a rare systemic autoinflammatory disease, adult-onset Still's disease (AOSD) has heterogeneous clinical manifestations, response to treatment and outcome. This study tried to assess the clinical characteristics, laboratory tests, and treatments of Chinese AOSD patients, and make a retrospective analysis. METHODS: We collected from 7 hospitals in China a total of 517 Chinese patients with AOSD who satisfied the Yamaguchi criteria. We retrospectively evaluated their clinical features, laboratory tests, treatments and compared them with published data from different studies. All the data in this study were from medical records and further statistic analyses. RESULTS: We evaluated a total of 517 AOSD patients, 72% female, average age of onset was 37.7; spiking fever, rash and arthralgia occurred in 472 (91.3%), 413 (79.9%), 378 (73.1%) cases, respectively. There were 439/513 (85.6%) cases with leukocytosis and 456/476 (95.8%) cases with raised serum ferritin. The highest frequently used medications and regimens for remission were glucocorticoids (498/517, 96.3%), methotrexate (273/517, 52.8%) and hydroxychloroquine (174/517, 33.7%). 84.4%. 357/423 of AOSD cases were able to achieve initial remission with different regimens, mostly including glucocorticoids, methotrexate or hydroxychloroquine. 47.2% of them (244/517) received 30
31464675 One year in review 2019: Sjögren's syndrome. 2019 May Primary Sjögren's syndrome (pSS) is a complex and heterogeneous disorder characterised by a wide spectrum of glandular and extra-glandular features. Novel insights into disease pathogenesis and the discovery of novel biomarkers are allowing us to characterise the disease not only phenotypically on the basis of clinical presentation, but also on the basis of the endotype. Ultimately, a better stratification of patients may pave new avenues for novel targeted therapies, opening new possibilities for the application of personalised medicine in pSS.
31383831 Adult-onset Still's Disease as a Differential Diagnosis in Prolonged Fever: Diagnosis and 2019 Apr Adult onset Still's disease is a rare systemic disease that may involve many organs and may mimick many disease such as infection, autoimmune disease, and also malignancy. The diagnostic approach and treatment strategies have not been well established due to its rarity; however, there are some diagnostic criteria that may help. We present a case of 36-year old man who experienced high prolonged fever which firstly thought as infection. He also had unilateral wrist and knee joint pain and maculopapular rash. Laboratory examination showed high leukocytes count with elevated polymorphonuclear neutrophil count, high platelet count, high ferritin level, and negative results of many infection markers (typhoid antibody, procalcitonin, malaria test, blood culture, urine culture, IgM pneumonia, ASTO, syphilis test, antiHIV, HBsAg, antiHCV, etc). Chest X-ray, joint X-ray, ultrasonography, and echocardiography showed normal result. The patient was then diagnosed with Adult-onset Still's disease and received intravenous methylprednisolone and the fever was disappeared in 3 days. Six months later the arthralgia appeared again, methotrexate was administered and the pain was then relieved.
31686925 Current Perspectives On Emerging Biomarkers For Rheumatoid Arthritis-Associated Interstiti 2019 Rheumatoid arthritis (RA) is a common systemic autoimmune disease whose fibro-inflammatory manifestations may affect a number of tissues and organs, including the lungs. In fact, interstitial lung disease (ILD) is a leading cause of mortality among patients with RA. RA-related interstitial lung disease (RA-ILD) most often presents in an injury pattern called usual interstitial pneumonia (UIP), which portends a relatively worse prognosis than other less commonly occurring patterns of RA-ILD, like non-specific interstitial pneumonia (NSIP). Biomarkers from serum or bronchoalveolar lavage fluid could aid in the identification of patients at risk for RA-ILD, the detection of patients most likely to develop the UIP pattern of RA-ILD, and the prediction of disease behaviour over time. Notably, the use of highly sensitive serologic biomarkers, including rheumatoid factor (RF) and antibodies targeting cyclic citrullinated peptides, while somewhat specific for RA joint disease, have only limited utility as biomarkers for RA-ILD. Candidate biomarkers for RA-ILD include these and other autoantibodies as well as certain genes and molecules that hold promise as biomarkers in other forms of ILD. In this manuscript, we summarize the state of knowledge on biomarkers for the development and progression of RA-ILD.
31057722 Single Nucleotide Polymorphism of TYK2 Gene and Susceptibility to Rheumatoid Arthritis in 2019 Apr BACKGROUND: Rheumatoid Arthritis (RA) is a debilitating disorder in which the immune system mainly targets the synovial tissue. Janus kinase family including tyrosine kinase 2 (TYK2) is one of the crucial mediators of the downstream signaling pathway of inflammatory cytokines that further contributes to RA pathogenesis. In this study, the association of TYK2 gene rs34536443 polymorphism, which may affect the function of TYK protein and, hence, the inflammatory settings, with RA susceptibility was investigated. Moreover, its correlation with demographic and serological features of the patients was assessed. METHODS: In the present study, 700 RA patients and 700 sex, age and ethnicity-matched healthy individuals as the control group were included. MGB TaqMan real-time allelic discrimination method was used to determine the rs34536443 polymorphism. Rheumatoid factor, anti-cyclic citrullinated peptide antibody, erythrocyte sedimentation rate and C-reactive protein were also measured. RESULTS: The frequency of rs34536443 minor allele (C allele) was not different between patients and control group [1.7 vs. 2.61 percent, OR (95% CI)=1.35 (0.78-2.33);p=0.27]. There was not a statistically significant association between rs34536443 genotypes and RA susceptibility. Genotypes of rs34536443 polymorphism were associated nor with demographic neither with serological features of RA patients. CONCLUSION: In the present study, there was not any association between TYK2 gene rs34536443 polymorphism with either disease susceptibility, demographic and serological features of Iranian RA patients. These findings are not compatible with previous works from other ethnicities, further supporting the role of genetics in disease susceptibility.
31334277 Value of serum glucose-6-phosphate isomerase in patients with rheumatoid arthritis and cor 2019 BACKGROUND: Rheumatoid arthritis (RA) is a common multisystemic autoimmune disease with peripheral joint involvement. Many autoantibodies have been introduced in the course of RA; some of them have diagnostic and prognostic value. In this study, our aim is to determine the value of serum glucose-6-phosphate isomerase (G6PI) antigen (Ag) as a diagnostic and prognostic marker in RA. MATERIALS AND METHODS: Eighty-seven known cases of RA who referred to an outpatient clinic of Shiraz University of Medical Sciences and 76 healthy controls were selected. Serum G6PI Ag was measured using sandwich enzyme-linked immunosorbent assay method, and the enzyme level was compared in the patient and control group, we also compared the enzyme level of patient group with disease activity, disease duration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) antibody (Ab). The data were analyzed using SPSS V 16 software. RESULTS: Positivity for G6PI was detected in 34.5% (30/87) of RA patients and 9.2% (7/76) of control group (P < 0.001). There was no significant correlation between enzyme level and disease activity, disease duration, ESR, CRP, RF, and anti-CCP Ab. CONCLUSIONS: Overall, in our study, although there was a significant difference in serum G6PI Ag between patient and control group, no significant correlation was detected between serum G6PI level and disease activity score, ESR, CRP, and anti-CCP Ab, but relative correlation with ESR and disease duration could be challenging. G6PI Ag could be introduced as a diagnostic marker in RA, but its role as a prognostic marker is controversial.