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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
31379214 Biologics for the treatment of adult-onset still's disease. 2019 Nov Introduction: Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology, and approximately 60-70% of patients develop a chronic form. Up to 20-30% of patients who are refractory to conventional therapy need biologic agents. Recently, anti-cytokine biologic agents according to pathophysiology have resulted in significant progress in the treatment of AOSD. Area Covered: Due to rarity and heterogeneous features of the disease, treatment of AOSD is not based on the controlled study but on case-based retrospective data. Here, we review the current status of the pathogenesis, limitations of therapeutic guidelines and outcome measures, utility of biologic agents, and future perspectives for treatment. Expert opinion: IL-1 inhibitors are more effective for systemic manifestations and IL-6 inhibitors for both joint disease and systemic features. Anti-TNF agents would be useful for patients with the pure rheumatoid subgroup. Systemic manifestations respond rapidly, but arthritis shows rather slow response. Clinical response must be obtained within 2 to 3 months, and biologics with different mechanisms of action are required for non-responders. For patients in prolonged remission, we need to try tapering of biologics. Randomized controlled studies, new therapeutic agents, and composite biomarkers are required to improve the outcome of patients with AOSD.
31427751 Effects of immunomodulatory drugs on depressive symptoms: A mega-analysis of randomized, p 2020 Jun Activation of the innate immune system is commonly associated with depression. Immunomodulatory drugs may have efficacy for depressive symptoms that are co-morbidly associated with inflammatory disorders. We report a large-scale re-analysis by standardized procedures (mega-analysis) of patient-level data combined from 18 randomized clinical trials conducted by Janssen or GlaxoSmithKline for one of nine disorders (N = 10,743 participants). Core depressive symptoms (low mood, anhedonia) were measured by the Short Form Survey (SF-36) or the Hospital Anxiety and Depression Scale (HADS), and participants were stratified into high (N = 1921) versus low-depressive strata based on baseline ratings. Placebo-controlled change from baseline after 4-16 weeks of treatment was estimated by the standardized mean difference (SMD) over all trials and for each subgroup of trials targeting one of 7 mechanisms (IL-6, TNF-α, IL-12/23, CD20, COX2, BLγS, p38/MAPK14). Patients in the high depressive stratum showed modest but significant effects on core depressive symptoms (SMD = 0.29, 95% CI [0.12-0.45]) and related SF-36 measures of mental health and vitality. Anti-IL-6 antibodies (SMD = 0.8, 95% CI [0.20-1.41]) and an anti-IL-12/23 antibody (SMD = 0.48, 95% CI [0.26-0.70]) had larger effects on depressive symptoms than other drug classes. Adjustments for physical health outcome marginally attenuated the average treatment effect on depressive symptoms (SMD = 0.20, 95% CI: 0.06-0.35), but more strongly attenuated effects on mental health and vitality. Effects of anti-IL-12/23 remained significant and anti-IL-6 antibodies became a trend after controlling for physical response to treatment. Novel immune-therapeutics can produce antidepressant effects in depressed patients with primary inflammatory disorders that are not entirely explained by treatment-related changes in physical health.
31061580 Rheumatoid subacromial-subdeltoid bursitis with rice bodies: A case report. 2019 May Subacromial-subdeltoid bursitis of a shoulder with rice bodies is relatively uncommon. The understanding of the pathogenesis of rice body formation is yet approximate only but some clinical conditions like rheumatoid arthritis, tuberculous arthritis, seronegative inflammatory arthritis, juvenile rheumatoid arthritis and osteoarthritis are related to it. We describe a case of a 44 years old female with subacromial-subdeltoid bursitis of her right shoulder with numerous rice bodies' formation as a presenting feature of rheumatoid arthritis. She underwent subacromial and subdeltoid bursectomy with the removal of rice bodies and had immediate improvement of symptoms.
31523427 Factors influencing physical activity in patients with early rheumatoid arthritis: A mixed 2019 OBJECTIVE: The goal of this study was to provide a greater understanding of physical activity in patients with early rheumatoid arthritis. The aim was twofold: first to explore if physical activity was associated with factors in the clinical picture of rheumatoid arthritis in this patient group, and second, to explore factors influencing physical activity in patients with early rheumatoid arthritis. METHODS: A total of 66 patients with early rheumatoid arthritis were included in the study. A sequential explanatory mixed-methods design was used, where quantitative data from a questionnaire were analysed with Mann-Whitney, post hoc Kruskal-Wallis and χ(2) test in order to detect differences between groups, and find possible associations between physical activity and independent variables, such as disease activity, health-related quality of life and physical function. Qualitative data were collected in a follow-up questionnaire with open-ended questions that focused on factors influencing physical activity. RESULTS: Associations between physical activity, disease activity and health-related quality of life were seen in patients with early rheumatoid arthritis together with strong negative correlations between physical activity and physical function. Patients on sick leave showed the strongest associations between disease-related variables and lower levels of physical activity. The findings from the qualitative analysis showed that physical limitations, awareness as a motivational factor and external environment factors influenced physical activity in patients with early rheumatoid arthritis. CONCLUSION: The results showed a complex underlying motive where physical, psychological and environmental factors influenced the physical activity in patients with early rheumatoid arthritis. In order to provide more effective health interventions, it is important to consider the complex nature of practicing physical activity, where a person-centred approach should be considered. Factors such as physical limitations, economic aspects and time for practicing physical activity should be included in the person-centred approach.
31720163 Relationship between Ulcerative Colitis and Rheumatoid Arthritis: A Review. 2019 Sep 18 Ulcerative colitis (UC) is a colonic disease characterized by chronic inflammation. Rheumatoid arthritis (RA) is a rheumatological chronic inflammatory disease characterized by joint swelling and tenderness. It is also considered an autoimmune disorder. We want to discover if a link exists between UC and RA and if so, how UC affects the progress of arthritis.  We used PRISMA guidelines. In this study, we used PubMed, PubMed Central (PMC), and Google Scholar to collect data. Studies conducted more than 50 years ago, non-English articles, and animal studies were excluded. All types of studies were included. We used keywords like "ulcerative colitis", "rheumatoid arthritis", or "colitic arthritis" in the search. We identified the following sets of results: 187,611 PubMed studies, 197,610 PMC studies, and 2,282,000 Google scholar studies. After applying inclusion and exclusion criteria, the number of appropriate studies was narrowed down to 50. Arthritis is the most common complication of ulcerative UC. The radiological changes are similar to those seen in RA. There are common genes and antigens found in both diseases, such as human leukocyte antigen (HLA-B27), interleukin 15, IgA. Certain drugs used for the treatment of both disorders, including omega-3. Many studies revealed that a large number of patients with UC developed RA within a few years. All the findings prove that there is a relation between ulcerative colitis and rheumatoid arthritis. This study is useful for doctors, scientists, and patients.
31258598 Gene expression of Interleukin-18 in rheumatoid arthritis patients on disease modifying an 2019 BACKGROUND & OBJECTIVES: The hallmark of rheumatoid arthritis is the inflammation that is mediated by the macrophages and monocytes that cause release of pro-inflammatory cytokines like interleukin-18. It is highly expressed in serum of patients suffering from rheumatoid arthritis and has a positive association with disease activity. The aim of this study was to analyze the gene expression of interleukin-18 in rheumatoid arthritis patients on disease modifying anti-rheumatic drug therapy. METHODS: The cross sectional comparative study is conducted at Department of Biochemistry and Molecular Biology and Center for Research in Experimental and Applied Medicine (CREAM-1Lab), Army Medical College, Rawalpindi, in collaboration with Rheumatology Department, Military Hospital, Rawalpindi. Study was conducted on two groups consisting of Group-I of rheumatoid arthritis patients on diseases modifying anti-rheumatic drugs and control Group-II comprising of normal healthy individuals. Non-probability purposive sampling was done from patients and controls. The duration of study was one year i-e from November 2015 to November 2016. Relative quantification of gene expression of interleukin-18 was done by Real time PCR using ∆∆CT method. RESULTS: Expression analysis for interleukin-18 showed down regulation of gene in rheumatoid arthritis patients as compared to controls. CONCLUSION: Interleukin-18 gene shows down regulation in rheumatoid arthritis patients on disease modifying anti-rheumatic drugs therapy.
31363455 The Influence of Porphyromonas Gingivalis Bacterium Causing Periodontal Disease on the Pat 2019 May 28 Periodontal pathologies are highly widespread throughout the world. Epidemiological studies have shown that as much as 1% of the population is suffering from periodontal disease. In recent years, there has been a growing number of studies linking these diseases with autoimmune diseases, especially with rheumatoid arthritis. This literature review evaluates changes in the relationship between periodontal pathologies caused by the bacterium Porphyromonas gingivalis and rheumatoid arthritis. The systematic review of the literature was performed according to the PRISMA analysis protocol. The review was performed with articles from the PubMed database. Searched articles were not older than 5 years. Only full texts and research performed with people were selected. A total of 56 results were received. A review and analysis of their full texts have been carried out and 10 articles were selected according to the established criteria. They were analyzed and results were presented. The results obtained from the literature were based on the influence of Porphyromonas gingivalis on the pathogenesis of rheumatoid arthritis. In the literature, the activity of this bacterium is explained by the analysis of its enzyme peptidylarginine deiminase and its principle of action. Studies have also been found to prove the presence of Porphyromonas gingivalis not only in the oral cavity but its DNA is also found in synovial fluid and plasma. In the researched articles, direct links between Porphyromonas gingivalis and rheumatoid arthritis have led doctors to draw attention to patients' oral hygiene and the condition of parodentium, as this may be the cause of autoimmune lesions. Treatment of periodontal disease will not only help maintain a healthy oral cavity but prevent the spread of bacteria to the surrounding tissues.
31879489 Long-term clinical results of bipolar hemiarthroplasty for osteoarthritis and rheumatoid a 2020 Jan We aimed to clarify the possibility of using bipolar hip arthroplasty (BHA) for degenerative diseases by examining long-term results postoperatively in 336 hips. Patients' average age was 61.0 years (range, 34-88 years), and the average follow-up period was 12.5 years (range, 5.0-27.3 years). The 5-year, 10-year, and 20-year Kaplan Meier survival rates (end point: revision) were 92.1%, 81.8%, and 20.1% in the osteoarthritis group and 96.4%, 90.1%, and 24.6% in the rheumatoid arthritis group, respectively. Since the survival rate for more than 10 years decreases rapidly, the use of BHA for treating degenerative diseases should be restricted.
30997344 Influence of genetic copy number variants of the human GLUT3 glucose transporter gene SLC2 2019 Jun OBJECTIVES: The gene encoding glucose transporter 3 (GLUT3, SLC2A3) is present in the human population at variable copy number. An overt disease phenotype of SLC2A3 copy number variants has not been reported; however, deletion of SLC2A3 has been previously reported to protect carriers from rheumatoid arthritis, implicating GLUT3 as a therapeutic target in rheumatoid arthritis. Here we aim to perform functional analysis of GLUT3 copy number variants in immune cells, and test the reported protective association of the GLUT3 copy number variants for rheumatoid arthritis in a genetic replication study. METHODS: Cells from genotyped healthy controls were analyzed for SLC2A3/GLUT3 expression and glycolysis capacity. We genotyped the SLC2A3 copy number variant in four independent cohorts of rheumatoid arthritis and controls and one cohort of multiple sclerosis and controls. RESULTS: Heterozygous deletion of SLC2A3 correlates directly with expression levels of GLUT3 and influences glycolysis rates in the human immune system. The frequency of the SLC2A3 copy number variant is not different between rheumatoid arthritis, multiple sclerosis and control groups. CONCLUSIONS: Despite a robust SLC2A3 gene copy number dependent phenotype, our study of large groups of rheumatoid arthritis cases and controls provides no evidence for rheumatoid arthritis disease protection in deletion carriers. These data emphasize the importance of well powered replication studies to confirm or refute genetic associations, particularly for relatively rare variants.
32007401 Established rheumatoid arthritis - Redefining the concept. 2019 Oct During the last few years, there has been a shift of focus in rheumatoid arthritis (RA) research towards earlier disease states. The terms early and established RA are inseparable, and having a clear definition of these two terms is crucial in conducting research and trying to understand the immunopathological mechanisms behind these different disease states. Established RA has been connected to chronic inflammation and a high burden of long-standing disease, with joint damage and comorbidities as a consequence of chronic inflammation. A chronological definition does not ensure us clear differentiation between early and established disease, because diagnosis can be delayed significantly. Similarly, a radiological definition does not ensure a clear differentiation either, as there is significant heterogeneity in the RA patient population, with some patients never developing structural damage, even after many years of disease. As the focus is now more on the early stages of disease, we propose to use the term established RA from the time of a definite clinical diagnosis of RA, irrespective of the symptoms' duration or the presence of irreversible damage, to distinguish established disease to a stage of undifferentiated arthritis (UA) or risk for developing RA, which might never progress to RA.
31490084 Total external ophthalmoplegia: First clinical manifestation of Sjögren's syndrome. 2019 Dec Sjögren's syndrome (SS) is an autoimmune disease causing destruction of the exocrine glands secondary to lymphocytic infiltration. Common clinical symptoms of SS are xerostomia, xerophthalmia, myalgia, arthritis, and vasculitis. Neurological symptoms may precede the diagnosis of SS by up to 2 years in about 80% of patients. A 28-year-old female presented to us with complaints of horizontal and vertical diplopia along with inability to move the right eye and sudden drooping of the right upper eyelid. She was a recently diagnosed case of type 2 diabetes mellitus and had a history of foreign body sensation in both eyes for 4 months. Schirmers I test revealed less than 5 mm of wetting in both eyes after 5 min, suggesting dry eyes. On immunological blood investigations, serum c-peptide was normal, rheumatoid factor was negative, antinuclear antibodies were positive, and proliferating cell nuclear antigens were positive. Extractable Nuclear Ag profile RO 52 was strongly positive suggestive of primary SS. Lip biopsy revealed mild-to-moderate chronic inflammation showing irregular acanthotic epidermis, and dermis had perivascular lymphocytic infiltrate. Thus, the possible diagnosis of primary SS with type 2 diabetes mellitus and right-sided total external ophthalmoplegia was made. Patient was prescribed subcutaneous insulin, multivitamins, tear substitutes and alternate patching. Later on insulin was replaced by oral hypoglycemics. The external ophthalmoplegia completely resolved within 6 weeks. So, total external ophthalmoplegia can be added to the spectrum of central nervous system involvement in SS.
31844440 Comparative Analysis of Approaches and Treatment Results of Patients with Early and Nonear 2019 Sep 15 The article presents the results of a comparative analysis of different therapy regimens impact on the effectiveness of treatment of patients with early and late rheumatoid arthritis in steady-state. Data on ongoing basis anti-inflammatory therapy of rheumatoid arthritis and the treatment of associated conditions were obtained by continuous copying from case histories of hospital department patients. The observations lasted 12 months. The activity of rheumatoid arthritis before and after the treatment was determined by the DAS 28 (Disease Activity Score) index. The treatment results were evaluated as per the laboratory research and the DAS 28 index, including the counting of painful and swollen joints, erythrocyte sedimentation rate, and health assessment of the patient on a visual analogue scale.
35415477 A New Approach for the Correction of Type I Thumb Deformity Owing to Rheumatoid Arthritis. 2020 Jan A major transition in the surgical treatment of rheumatoid arthritis has been facilitated by a recent paradigm shift in its diagnosis and treatment. Improved outcomes in the treatment of the rheumatoid thumb are desirable; however, the results of conventional surgery are less than ideal. Even if the rheumatoid arthritis is well-controlled, the progression of thumb deformity may persist owing to an ineffective deformity correction and an insufficient understanding of the mechanism by which the deformity occurs. The mechanism of rheumatoid thumb deformity should be considered, using it to base the appropriate correction. We applied a new deformity correction procedure that accounts for the mechanism of type I rheumatoid thumb deformity and obtained positive results without recurrence. Although the primary cause of type I thumb deformity is believed to be an extensor mechanism failure resulting from synovitis of the metacarpophalangeal (MCP) joint, surgical outcomes are negatively affected as a result of flexion contracture caused by the adductor pollicis (ADP). Because the ADP attaches to the ulnar sesamoid on the palmar side of MCP joint, we release the ADP tendon to improve flexion contracture of the MCP joint. We consider release of ADP to be effective in preventing the recurrence of flexion contracture of the MCP joint and re-tensioning of the extensor pollicis brevis. Rheumatoid thumb deformity can be restored by applying this procedure, improving a patient's outcome.
31646135 A Rare Case of Multicentric Reticulohistiocytosis with Concurrent Rheumatoid Arthritis. 2019 Aug 24 Multicentric reticulohistiocytosis (MRH) is a rare multisystem macrophage disorder of unknown etiology characterized by papulonodular skin and mucosal lesions, rapidly progressive erosive symmetric polyarthritis, and inflammation of internal organs. Most often, it is misdiagnosed as rheumatoid arthritis (RA). Here, we report the case of a 60-year-old woman found to have features of both MRH and RA with positive rheumatoid factor and high titer of anti-cyclic citrullinated peptide antibody in serum. It was confirmed by a histopathology of skin lesions, which showed diffuse histiocytic infiltrate with multinucleated giant cells. She was treated with methotrexate, hydroxychloroquine, corticosteroids, and nonsteroidal anti-inflammatory drugs and bisphosphonate.
31745501 Interstitial Lung Disease as the Initial Manifestation of Rheumatoid Arthritis: A Case Rep 2019 BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder that primarily affects synovial joints. Approximately 18-41% of patients with RA develop extra-articular manifestations [1]. However, extra-articular manifestations preceding or occurring without articular symptoms in RA have rarely been reported. Such atypical presentations of RA pose a diagnostic challenge to the clinician and may delay treatment. CASE PRESENTATION: A 57-year-old female with long standing diabetes, hypertension, hyperlipidemia and Raynaud's phenomenon presented shortness of breath, cough and new subcutaneous nodules. Four years before, she had been diagnosed with non specific interstitial pneumonia but had declined treatment. The physical exam did not reveal any signs suggestive of RA however, she was seropositive for rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA). Treatment for RA-associated interstitial lung disease was discussed. CONCLUSION: Extra-articular involvement of RA can be observed as initial presentation of the disease in a handful of cases. However, RA diagnosis must be achieved to correctly manage these patients which can at that time receive targeted therapeutic interventions. From our literature review, pulmonary involvement was seen in over half of the cases in seropositive RA patients who lacked articular involvement at initial presentation.
31835340 Pseudoerosions of Hands and Feet in Rheumatoid Arthritis: Anatomic Concepts and Redefiniti 2019 Dec 9 Rheumatoid arthritis is a chronic inflammatory disease characterized by the development of osseous and cartilaginous damage. The correct differentiation between a true erosion and other entities-then often called "pseudoerosions"-is essential to avoid misdiagnosing rheumatoid arthritis and to correctly interpret the progress of the disease. The aims of this systematic review were as follows: to create a definition and delineation of the term "pseudoerosion", to point out morphological pitfalls in the interpretation of images, and to report on difficulties arising from choosing different imaging modalities. A systematic review on bone erosions in rheumatoid arthritis was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following search terms were applied in PubMed and Scopus: "rheumatoid arthritis", "bone erosion", "ultrasonography", "radiography", "computed tomography" and "magnetic resonance imaging". Appropriate exclusion criteria were defined. The systematic review registration number is 138826. The search resulted ultimately in a final number of 25 papers. All indications for morphological pitfalls and difficulties utilizing imaging modalities were recorded and summarized. A pseudoerosion is more than just a negative definition of an erosion; it can be anatomic (e.g., a normal osseous concavity) or artefact-related (i.e., an artificial interruption of the calcified zones). It can be classified according to their configuration, shape, content, and can be described specifically with an anatomical term. "Calcified zone" is a term to describe the deep components of the subchondral, subligamentous and subtendinous bone, and may be applied for all non-cancellous borders of a bone, thus representing a third type of the bone matrix beside the cortical and the trabecular bone.
31534869 Intracerebral Hemorrhage in a Patient with Untreated Rheumatoid Arthritis: Case Report and 2019 Jul 19 Rheumatoid vasculitis (RV) occurs in patients with long-standing rheumatoid arthritis (RA) or high levels of immunological factors and can result in devastating cardiovascular (CV) events. Here we report a case of a 38-year-old male who presented with hypertensive emergency and intracerebral hemorrhage (ICH). In the literature, a few observational studies have indicated the association of RA with hypertension; however, little evidence exists supporting a direct relationship between RA and ICH. In this case, we attempted to evaluate the complex relationship between all of these factors and found that early detection and treatment of RA may be beneficial in reducing ICH; however, large studies in the future are warranted to validate our observation.
32305962 Contribution of neutrophils in the pathogenesis of rheumatoid arthritis. 2019 Oct 24 Neutrophils are major innate immune effector cells for host defense and have been a topic of active research for their participation in the pathogenesis of autoimmune inflammatory diseases including rheumatoid arthritis (RA) due to recently discovered neutrophil extracellular trap (NET) formation. NET formation and other mechanisms leading to the release of neutrophil nuclear and cytoplasmic contents are implicated as a source of citrullinated antigens in RA. Further investigations are required to delineate what factors diverge neutrophils from host defense to autoimmune response in RA.
31341750 The Utility and Experience with Disease Biomarkers in Juvenile Onset Arthritis vs. Adult O 2019 Jul 13 Juvenile idiopathic arthritis (JIA) is the most common but extremely heterogeneous group of rheumatic diseases of childhood. There are no reliable, well-researched and published biomarkers for diagnosis or monitoring in juvenile idiopathic arthritis as there are for rheumatoid arthritis (RA) in adults. Biomarkers are not utilized in classifying JIA as they are in adult RA, making the JIA classifications less clinically effective and informative. The situation presents a lost opportunity for early aggressive therapy in JIA patients. Various researchers have used diverse biomarkers anecdotally in JIA and more systematically in RA patients and have drawn inferences on their utility from their experiences. The experience with biomarkers from RA patients cannot necessarily be extrapolated for JIA patients because they are dissimilar diseases. This article reconnoiters the comparative utility of various arthritis biomarkers in adult as well as in JIA patients. In contrast to RA, JIA is in itself a diverse group of arthritis with clinically overlapping subgroups with diverse etiology. The difference in the etiopathogenesis of arthritis subgroups demands identifying subgroup-specific biomarkers for diagnosis/monitoring and subgroup-specific therapies for management. The diagnostic/prognostic value of the individual biomarker could be different in different types of arthritis and in different types of hosts. Understanding the utility of individual biomarkers and careful selection of the assay are important to achieve the best disease outcomes.
31019857 Severe Neutropenia Complicated with Necrotizing Fasciitis Unveils a Diagnosis of Rheumatoi 2019 Feb 15 Felty syndrome, a rare extra-articular manifestation of rheumatoid arthritis (RA), usually affects patients with long-standing disease. Patients with this syndrome typically present with neutropenia, splenomegaly, in addition to erosive RA. The development of unexplained neutropenia in healthy patients should prompt the work up for Felty syndrome, especially in patients with suggestive demographics, signs, and symptoms. Differentiation between large granular lymphocyte (LGL) leukemia and Felty syndrome is necessary as both can present with neutropenia, and are associated with RA. Immunosuppressive therapy has improved the prognosis of patients with Felty syndrome given the decreasing rates of splenectomies done in those patients over the last decades.