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ID PMID Title PublicationDate abstract
24179334 Early intervention in the treatment of rheumatoid arthritis: focus on tocilizumab. 2013 Tocilizumab is a fully humanized monoclonal antibody against interleukin-6 receptors that was approved for the treatment of patients with rheumatoid arthritis (RA). Several lines of evidence, obtained both from conventional disease-modifying anti-rheumatic drugs (DMARDs) and tumor necrosis factor (TNF) inhibitors, have supported the concept of "window of opportunity" as showing that these therapies consistently work better in early disease as compared to established RA. This review addresses the question of whether a window of opportunity gained with conventional DMARDs and TNF inhibitors can also be achieved with tocilizumab. To this end, data regarding the use of tocilizumab in early RA patients are summarized. Currently available data suggest that the earlier the treatment with tocilizumab, the better the clinical outcome can be, which may have implications for various aspects of RA treatment strategies.
30235560 Rheumatoid Arthritis Disease Progression Modeling. 2013 Nov Time progression models provide a significant advantage in developing clinical trials and can also be used to elicit comparisons among therapeutic agents. The authors performed a meta-analysis to construct a time progression model for rheumatoid arthritis (RA), an area of significant interest for pharmaceutical development, using the ACR20 end point. Compounds studied were chiefly monoclonal antibodies that were used in conjunction with methotrexate. The study shows that an exponential time response model adequately fits the data. From the modeling, a distribution of effects for biological RA therapies can be provided.
24829873 Impact of rheumatoid arthritis on sexual function. 2014 Apr 18 Sexuality is a complex aspect of the human being's life and is more than just the sexual act. Normal sexual functioning consists of sexual activity with transition through the phases from arousal to relaxation with no problems, and with a feeling of pleasure, fulfillment and satisfaction. Rheumatic diseases may affect all aspects of life including sexual functioning. The reasons for disturbing sexual functioning are multifactorial and comprise disease-related factors as well as therapy. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by progressive joint destruction resulting from chronic synovial inflammation. It leads to various degrees of disability, and ultimately has a profound impact on the social, economic, psychological, and sexual aspects of the patient's life. This is a systemic review about the impact of RA on sexual functioning.
23935355 Hepatitis B reactivation in a patient with rheumatoid arthritis with antibodies to hepatit 2013 Jan Hepatitis B virus (HBV) can still be found within the hepatocytes after its clearance and the control of viral replication depends on the immune response. However during immunosuppression, seroconversion of HBsAg has been described followed by disease reactivation. Hepatitis B virus reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents and in particular, by the use of rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and long-lasting immunosuppression. We describe a case of a 64-year old female patient with rheumatoid arthritis and resolved HBV infection, who experienced a severe hepatitis B reactivation after the administration of rituximab.
24229458 Periodontal disease, Porphyromonas gingivalis, and rheumatoid arthritis: what triggers aut 2013 Rheumatoid arthritis, currently regarded as a complex multifactorial disease, was initially characterized as such at the turn of the 19th century. Ever since, multiple lines of investigation have attempted to elucidate the etiological factor(s) involved in disease incidence. Genes--including those risk alleles within HLA-DR4--have been implicated but are insufficient to explain the vast majority of cases. Several environmental factors, therefore, are being studied. Among them, the role of periodontal disease and Porphyromonas gingivalis in the pathogenesis of rheumatoid arthritis has attracted both clinical and bench interest given supportive epidemiologic and mechanistic data.
24326035 Proceedings of the 5th annual perspectives in rheumatic diseases. 2013 Dec OBJECTIVES: Update on rheumatic diseases and their intersection with dermatology. RESULTS: This continuing medical education conference included more than 25 presentations and interactive sessions from leading experts in managing rheumatic diseases, comorbid conditions and related dermatologic diseases. Multiple areas were discussed, including: treating newly diagnosed rheumatoid arthritis; comparing Biologics in rheumatoid arthritis; examining changed approaches to treating SLE, psoriasis, psoriatic arthritis, ankylosing spondylitis, gout and vasculitis. Also visited were new understandings regarding chronic pain and osteoporosis. CONCLUSIONS: Multiple presentations and interactive sessions from leading experts in the management of rheumatic diseases emphasized the interconnection between rheumatology and dermatology. Practical management approaches to both specialties and their sequelae were discussed. Additional content from the conference is available at www.globalacademycme.com and through Rheumatology News at www.rheumatologynews.com.
24353404 Non-tumor necrosis factor-based biologic therapies for rheumatoid arthritis: present, futu 2014 The way rheumatoid arthritis is treated has changed dramatically with the introduction of anti-tumor necrosis factor (anti-TNF) biologics. Nevertheless, many patients still have less than adequate control of their disease activity even with these therapeutic regimens, and current knowledge fails to explain all the data already gathered. There is now a wide range of drugs from different classes of biologic disease-modifying anti-rheumatic drugs available (and soon this number will increase significantly), that provides the opportunity to address each patient as a particular case and thereby optimize medical intervention. Currently available biologics for the treatment of rheumatoid arthritis apart from anti-TNF-based therapies are reviewed, along with an analysis of the new insights they provide into the pathogenesis of the disease and a discussion of future prospects in the area.
25281507 The analysis of clonal diversity and therapy responses using STAT3 mutations as a molecula 2015 Jan T-cell large granular lymphocytic leukemia and chronic lymphoproliferative disorder of natural killer cells are intriguing entities between benign and malignant lymphoproliferation. The molecular pathogenesis has partly been uncovered by the recent discovery of somatic activating STAT3 and STAT5b mutations. Here we show that 43% (75/174) of patients with T-cell large granular lymphocytic leukemia and 18% (7/39) with chronic lymphoproliferative disorder of natural killer cells harbor STAT3 mutations when analyzed by quantitative deep amplicon sequencing. Surprisingly, 17% of the STAT3-mutated patients carried multiple STAT3 mutations, which were located in different lymphocyte clones. The size of the mutated clone correlated well with the degree of clonal expansion of the T-cell repertoire analyzed by T-cell receptor beta chain deep sequencing. The analysis of sequential samples suggested that current immunosuppressive therapy is not able to reduce the level of the mutated clone in most cases, thus warranting the search for novel targeted therapies. Our findings imply that the clonal landscape of large granular lymphocytic leukemia is more complex than considered before, and a substantial number of patients have multiple lymphocyte subclones harboring different STAT3 mutations, thus mimicking the situation in acute leukemia.
24657513 Adult-onset Still's disease. 2014 Jul First described in 1971, adult-onset Still's disease (AOSD) is a rare multisystemic disorder considered as a complex (multigenic) autoinflammatory syndrome. A genetic background would confer susceptibility to the development of autoinflammatory reactions to environmental triggers. Macrophage and neutrophil activation is a hallmark of AOSD which can lead to a reactive hemophagocytic lymphohistiocytosis. As in the latter disease, the cytotoxic function of natural killer cells is decreased in patients with active AOSD. IL-18 and IL-1β, two proinflammatory cytokines processed through the inflammasome machinery, are key factors in the pathogenesis of AOSD; they cause IL-6 and Th1 cytokine secretion as well as NK cell dysregulation leading to macrophage activation. The clinico-biological picture of AOSD usually includes high spiking fever with joint symptoms, evanescent skin rash, sore throat, striking neutrophilic leukocytosis, hyperferritinemia with collapsed glycosylated ferritin (<20%), and abnormal liver function tests. According to the clinical presentation of the disease at diagnosis, two AOSD phenotypes may be distinguished: i) a highly symptomatic, systemic and feverish one, which would evolve into a systemic (mono- or polycyclic) pattern; ii) a more indolent one with arthritis in the foreground and poor systemic symptomatology, which would evolve into a chronic articular pattern. Steroid- and methotrexate-refractory AOSD cases benefit now from recent insights into autoinflammatory disorders: anakinra seems to be an efficient, well tolerated, steroid-sparing treatment in systemic patterns; tocilizumab seems efficient in AOSD with active arthritis and systemic symptoms while TNFα-blockers could be interesting in chronic polyarticular refractory AOSD.
23966806 Serum prolidase activity in ankylosing spondylitis and rheumatoid arthritis. 2013 The aim of the present study was to emphasize the collagen turnover in 2 of the most common chronic inflammatory rheumatic diseases by evaluating serum prolidase activity (SPA) in ankylosing spondylitis (AS) and rheumatoid arthritis (RA). 30 patients who met the modified New York Criteria for the classification of AS, 29 patients who met the 2010 Rheumatoid Arthritis Classification Criteria for the classification of RA, and 31 healthy controls were enrolled in the study. Serum samples of the patients and the controls were collected and SPA was measured by a spectrophotometric method. The comparison of the SPA in these 3 groups was statistically examined. In both patient groups, the SPA was lower than in the control group. SPA in patients with AS was statistically significantly lower than in the control and RA groups (P < 0.001/P = 0.002). No statistically significant difference was found between the RA and the control groups (P = 0.891). In conclusion, lower SPA is presumably associated with decreased collagen turnover and fibrosis, leading to decreased physical functions in both chronic inflammatory musculoskeletal diseases.
24555814 Genetic background of juvenile idiopathic arthritis. 2014 Sep Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatologic disease in children. JIA is a group of disorders that share the clinical manifestation of chronic joint inflammation. The human leukocyte antigen region (HLA) seems to be a major susceptibility locus for JIA that is estimated to account for 17% of familial segregation of the disease. To date, around 20 non-HLA loci conferring susceptibility to JIA were found. At least a half of those are shared between JIA and rheumatoid arthritis (RA), an adult rheumatic disease, thereby suggesting for similarity of pathogenic mechanisms of both diseases. New findings also suggest for a likely role of epigenetic alterations in the pathogenesis of JIA that should be investigated in the future.
26029614 Pulmonary vasculitis as the first manifestation of rheumatoid arthritis. 2013 In this report, we describe a 61-year-old man that presented with isolated pulmonary vasculitis and a positive anti-cyclic citrullinated peptide (CCP) antibody. Within a few months, the patient developed the symmetric polyarthritis consistent with rheumatoid arthritis (RA). Because the anti-CCP antibody is highly specific for RA and vasculitis is a known association of RA, we suspect the pulmonary vasculitis in this patient was the first manifestation of underlying RA. This case extends on previous reports that have shown that lung disease may predate the development of articular RA and that anti-CCP positivity and lung disease may represent a pre-RA phenotype. To our knowledge, this is the first case report of pulmonary vasculitis as the first manifestation of RA.
23998050 A study on interleukin -1β and lipid profile as markers of cardiovascular risk in rheumat 2013 Jul INTRODUCTION: The dyslipidaemia in Rheumatoid Arthritis (RA) is associated with accelerated atherosclerosis. A prospective clinical evaluation study was undertaken to find out the proportion of the rheumatoid arthritis patients who were suffering from dyslipidaemia, the change in the lipid levels and the disease activity after an intervention with antirheumatic therapy. AIMS AND OBJECTIVES: To study the disease activity in Rheumatoid arthritis patients by measuring the serum levels of interleukin-1β (IL-1 β), to find out the proportion of rheumatoid arthritis patients who were suffering from dyslipidaemia, to correlate the disease activity with the lipid profile and to look for the change in the lipid levels and the disease activity after an intervention with antirheumatic therapy. MATERIAL AND METHODS: This study was done on 30 RA patients (fulfilling the American College of Rheumatology criteria). The lipid profile estimation was done by an enzymatic, colourimetric method and IL-1β was estimated by a chemiluminescence method. Dyslipidaemia was defined by taking the cut-off values of the NCEP-ATPIII guidelines. The patients with other comorbid illnesses and those who were on statins were excluded. The patients were followed up after 12 weeks of starting with the anti-rheumatic therapy. RESULTS: 36.7% of the patients had high total cholesterols, 53.3% of the patients had high triacylglycerol levels, 73.3% of the patients had decreased HDL-cholesterol and 33.3% of the patients had high LDL-cholesterols. 86.7% of the patients had IL-1β levels which were above the reference range. After the treatment, the number of patients with dyslipidaemia came down, with 23.3% patients having high total cholesterol levels, 43.3% of the patients having elevated triacylglycerol levels, 46.7% patients having low HDL-cholesterol levels and 20% patients having elevated LDL-cholesterol levels. 66.7% of the patients had IL-1β which was above the reference range. CONCLUSION: The proportion of dyslipidaemic patients had decreased in the follow up visit, along with a decrease in the disease activity, as were indicated by the decreased levels of IL-1β. The management of dyslipidaemia in RA should be a part of the general cardiovascular risk management. Therefore, a good control of the disease activity should be given priority, so that both the quality of life and the long-term outcomes can be improved.
23359008 Involvement of valgus hindfoot deformity in hallux valgus deformity in rheumatoid arthriti 2013 Jan 29 The involvement of valgus hindfoot deformity in hallux valgus deformity was confirmed in a rheumatoid arthritis case with a destructive valgus hindfoot deformity. Correction of severe valgus, calcaneal lateral offset, and pronated foot deformity instantly normalized hallux valgus deformities postoperatively. Thus, careful hindfoot status evaluation is important when assessing forefoot deformity, including hallux valgus, in rheumatoid arthritis cases.
23819062 Investigating the value of abatacept in the treatment of rheumatoid arthritis: a systemati 2013 Background. Rheumatoid arthritis is a progressive inflammatory disease that affects greatly patients' quality of life and demands for aggressive management early on during the course of the disease. The discovery of biologics has equipped rheumatologists with evolutionary treatment tools but has also impacted greatly management costs. Objectives. To conduct a systematic review in order to evaluate the cost effectiveness of abatacept in the treatment of moderate to severe rheumatoid arthritis. Methods. Pubmed, the International Society for Pharmacoeconomics and Outcomes Research Outcomes Research Digest, the National Health System Economic Evaluation Database, and the Database of Abstracts of Reviews of Effects were searched. Results. In total 301 studies were identified and 42 met the inclusion criteria. Half of the selected studies evaluated abatacept in the treatment of rheumatoid arthritis, after failure of or intolerance to tumor necrosis factor alpha inhibitors. Of those, 82% were in favor of abatacept as a cost-effective or dominant strategy versus varying alternatives, whereas 18% favored other treatments. Conclusion. The majority of evidence from the published literature supports that abatacept can be a cost-effective alternative in the treatment of moderate to severe rheumatoid arthritis, especially in patients that have demonstrated inadequate response or intolerance to anti-TNF agents or conventional disease modifying antirheumatic drugs.
24009964 Comparison of sensitivity and specificity of anti-CCP and anti-MCV antibodies in an Irania 2013 Summer Background : Anti-CCP is a test commonly used for the diagnosis of rheumatoid arthritis. The aim of this study was to determine the diagnostic values of ACCP compared to anti-MCV in rheumatoid arthritis patients in north of Iran. METHODS: The serum samples of 150 RA patients and 75 controls, with the mean age of 49.6+11.8 and 48.8+12 years respectively, were tested using the commercially available ELISA kits for ACCP and anti-MCV. Sensitivity, Specificity were determined and Roc curve were used for comparison between these two groups. RESULTS: The sensitivity of ACCP versus anti-MCV was 85% and 81%, respectively. Specificity was 96% and 95%, respectively. In the RA patients, ACCP was positive in 127 (84.7%) and anti MCV in 121 (80.7%) cases. In the control group, these parameters were positive in 3 (4%) and 4 (5.3%) (p<0.0001 and p<0.0001, respectively). The correlation coefficient for ACCP and anti-MCV was calculated at 0.63 (p<0.001). The area under the curve for ACCP was 0.941±0.015 (p<0.001), anti-MCV was 0.902±0.02 (p<0.001). The measure of agreement (Kappa) for these variables was 0.81. In these patients, there was no correlation between DAS28 and the positivity of these tests. CONCLUSION: It was concluded, compared to ACCP, anti-MCV has approximately the same accuracy for the diagnosis of rheumatoid arthritis and it does not have additional value.
26673521 Usefulness of sonography in the diagnosis of rheumatoid hand. 2013 Sep Ultrasound examination is becoming more and more common in patients with rheumatoid diseases. Above all, it enables the assessment of articular soft tissues and constitutes a non-invasive examination. In a rheumatologist's everyday practice, it is conducted at the stage of initial diagnosis as well as to monitor the treatment and to confirm the remission if the clinical picture is ambiguous. The first sign of arthritis (including rheumatoid arthritis) that is visible on ultrasound examination is the thickening of the synovial membrane of the joint cavities, tendon sheaths or bursae. It is frequently accompanied by the exudate in the joint, sheath or bursa. In a subsequent stage, in Doppler examination, enhanced vascularization of the synovial membrane is observed. Sometimes, the inflammatory process of the tendon sheaths also affects the tendons, which might lead to their damage. Moreover, ultrasound examination also reveals erosions and inflammatory cysts (geodes) which attest to the advancement of the disease. A dynamic ultrasound examination enables to diagnose the capsule-ligamentous contracture of the interphalangeal joints, which occurs due to the lack of rehabilitation that should begin at the moment of the commencement of the inflammation. The ultrasound image does not allow for the differentiation between various rheumatoid entities, including those encompassing the joints in the hand, wrist. The observed changes, i.e. thickening of the synovial membrane, hyperemia, effusions, erosions or tendon damage, may accompany various rheumatoid entities. The purpose of the ultrasound examination is to recognize these irregularities, determine their localization and advancement and, finally, to monitor the course of treatment. Furthermore, ultrasound scan enables to assess the joints and tendons in a dynamic examination in relation to local ailments of the patient as well as to monitor the biopsy, aspiration and medicine administration. Sonography is used for a US-guided administration of radioisotope substances for synoviorthesis.
24640574 Anti-arthritic actions of relaxin, in combination with estrogens, in joint and bone tissue 2013 The incidence and severity of rheumatoid arthritis decline during pregnancy. However, the role of hormones of pregnancy, including estrogens and relaxin, in attenuating the symptoms of rheumatoid arthritis, including joint inflammation and bone destruction is unknown. In rat adjuvant-induced arthritis, a model for rheumatoid arthritis, relaxin in combination with estrogens, reduced joint inflammation and circulating levels of pro-inflammatory, tumor necrosis factor alpha. In addition, relaxin together with estrogens, altered systemic levels of bone remodeling markers receptor activator of nuclear factor-kappa B, its ligand and osteoprotegerin to improve bone health when compared with arthritic controls. In vitro studies using primary rat osteoblasts and an osteoblast cell line showed a similar bon-saving response to treatment with estrogens in combination with relaxin.
23930040 Evaluation of anti-inflammatory potential of the multidrug herbomineral formulation in mal 2013 Apr BACKGROUND: Immunological and inflammatory mechanisms, which may play a role in a number of disorders like rheumatoid arthritis (RA). Ancient ayurvedic physicians had developed certain dietary and therapeutic measures to arrest or prevent these disorders. OBJECTIVE: Rheuma off gold (RG) is a herbomineral formulation recommended by ayurvedic medical practitioners for treatment of RA. This study was carried out to lend scientific evidence to the efficacy claim for RG in the management of RA in folklore medicine. MATERIALS AND METHODS: Arthritis was induced by complete Freund's adjuvant. Treatment with formulation 100 mg/kg and dexamethasone 2 mg/kg was given to rats intragastrically once a day from day 1 to day 21 and after which estimation of physical, biochemical, and hematological parameters were carried out. RESULTS: Treatment of formulation to adjuvant induced arthritic animal showed statistically significant (P < 0.05) improvement in physical parameters like arthritic index, paw edema, paw thickness as well as reduction of inflammatory markers like C-reactive protein, serum rheumatoid factor, erythrocyte sedimentation rate. The treatment also produced statistically significant (P < 0.05) increase in hemoglobin percent and improvement in splenomegaly and thymus index. In the histopathological examination, ameliorative effect of formulation was observed in hyperplasia of synovium, pannus formation, and destruction of the joint space. CONCLUSION: The results obtained in experiments indicated that the formulation significantly inhibited the adjuvant-induced arthritis which was comparable to dexamethasone and had preferable anti-inflammatory effect without significant side effect. Thus, the formulation may be a potential preventive or therapeutic candidate for the treatment of chronic inflammation and arthritis.
24612946 Sjögren's syndrome: where do we stand, and where shall we go? 2014 Jun Primary Sjögren's syndrome (pSS) is one of the most frequent autoimmune systemic diseases, mainly characterized by ocular and oral dryness due to the progressive destruction of lachrymal and salivary glands by an inflammatory process. A noteworthy proportion of patients also features extraglandular manifestations, sometimes severe and life-threatening. Until now, its management relies mostly on symptomatic interventions, long-term monitoring, and, in patients with severe systemic complications, immunosuppressive drugs can be provided. However, recent years have seen great progresses in the understanding of the pathological processes of the disease. The central role of regulatory lymphocytes, the implication of the type 1 interferon pathway in some patients or the importance of epigenetics have been highlighted. New classification criteria have been recently published and have shed in light an international attempt for a better recognition of the patients, probably thanks to the development of new diagnostic procedures such as salivary gland ultrasonography. To facilitate the detection of treatment efficacy in clinical trials and to help in determining which subgroups of patients would have benefits from intensive therapies, a better definition of activity scores and the availability of new prognostic markers are urgent. Thereby, the development of future therapies should be based on specific molecular signatures that will enable a personalized management of each patient. This review focuses on the most striking advances in the fields of pathophysiology, diagnosis and treatment of pSS, which generate a great hope for pSS patients.