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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
21044454 Use of methotrexate in adult-onset Still's disease. 2010 Sep Adult-onset Still's disease, a febrile, multisystem rheumatic disease, has variable outcomes. Some patients experience remission after a single or multiple inflammatory episodes, while others progress to a chronic course with substantial joint destruction. Although no controlled clinical trials with immunosuppressive agents in this disease have been reported, a number of small uncontrolled studies and case reports describe the use of methotrexate therapy. Methotrexate has shown efficacy for the control of systemic and articular symptoms and its favourable safety profile appears similar to that seen in other rheumatic diseases, when for this indication. The combination of methotrexate and corticosteroids has, over the years, become the first step in the standard of care in adult-onset Still's disease. If the response to this treatment is incomplete, additional therapies, such as biologic agents may be appropriate.
20486510 A returning traveler with fever. 2010 May Active duty military personnel and civilian government employees are at risk for exposure to a variety of pathogens as they meet their mission requirements throughout the world. When they present with a systemic disease, the clinician must entertain a broad differential diagnosis due to the multitude of infectious, neoplastic, and noninfectious inflammatory disorders that can have similar clinical presentations. Since treatment varies significantly, and lack of appropriate therapy may be deadly, the search for the definitive diagnosis should be aggressive and thorough. We present a case of adult-onset Still's disease (AOSD) masquerading as an infectious disease process in a man with recent travel to Sudan. A discussion of the differential diagnosis is included along with a review of the diagnostic criteria, prognosis, and current therapeutic options for AOSD.
20164751 A modified Schirmer test in dry eye and normal subjects: open versus closed eye and 1-minu 2010 Apr OBJECTIVE: To assess the results of 1-minute and 5-minute Schirmer test (ST) when eyes are open (STo) and closed (STc) in normal subjects and patients with dry eye disease. METHODS: In a comparative, observational case series study, 34 normal volunteers (group 1) and 34 patients with dry eye disease (DED) associated with Sjogren syndrome (group 2) were included in the study. STo and STc for 1 minute and 5 minutes were performed separately for all subjects with an interval of at least 24 hours using Whatman No. 41 (5 × 60 mm) with bended end of the paper inserted into the lateral side of the lower conjunctival fornix. RESULTS: In group 1, there were 19 females and 15 males with a mean age of 20.8 years (range 18 to 23 years). In group 2, there were 29 females and 5 males with a mean age of 53.7 years (range 35 to 75 years). Mean value of STc was significantly less than STo in both 1 minute and 5 minutes in both groups. One-minute STo and STc showed significantly less wetting than the 5-minute test in both healthy and patients with DED. Normal distribution was observed for all the values. A significant correlation between 1-minute and 5-minute tests in both STo and STc were found in the two groups. Therefore, two equations were proposed to calculate the 5-minute from 1-minute ST in each group. Statistical analysis did not provide a reliable equation for calculating the standard ST (5-minute STo) from the most comfortable state (1-minute STc). CONCLUSION: Faster and more comfortable ST (1-minute) is a reliable test to calculate the 5-minute ST in both open and closed eyes, using the provided equations. The 1-minute STc is not a reliable test to calculate the 5-minute STo.
19834709 A rare trigger for macrophage activation syndrome. 2011 Mar Macrophage activation syndrome (MAS) is a disorder characterized by increased activation of mononuclear cells leading to phagocytosis of blood cell precursors in the bone marrow. We describe a case of MAS triggered by disseminated histoplasmosis occurring in a patient with Still's disease on long-term treatment with adalimumab.
19564717 [Clinical and histological experience of labial lip biopsy in juvenile Sjögren syndrome]. 2009 Jun The therapeutic efficacy of corticosteroids and immunosuppressants on secretary glands of children with Sjögren syndrome was investigated examining the lip-biopsy specimen on both lymphocyte infiltration and fibrosis. Six children with primary Sjögren syndrome and two children with lupus-associated secondary Sjögren syndrome were evaluated according to the intensity of therapy. The shorter the term of medications of corticosteroids and immunosuppressants were, the lesser the extents of lymphocyte infiltration and fibrosis were, and the lower the doses of medications were, the lesser the efficacy was. Thus, in childhood Sjögren syndrome, appropriate corticosteroids and immunosuppressants may provide the suppressive effects on the progressive inflammatory destruction of secretary glands. Further evaluation with more patients is needed to determine the inclusion criteria of these treatments for sicca syndrome, especially in cases with no other organ involvement.
21144336 [Adult-onset Still disease as the cause of fever of unknown origin]. 2010 Sep Fever of unknown origin remains a diagnostic challenge with up to 50% of unexplained cases. Adult-onset Still disease typically present high fever, arthralgia, rash, pharyngitis and serositis, lymphadenopathy and hepatosplenomegaly, inflammatory markers and hepatic enzymes elevation and negative immunological study. The authors present a 46-year old man with previous admissions for fever of unknown origin with a 3-week history of fever and systemic symptoms. The study disclosed anaemia, inflammatory markers and hepatic enzymes elevation, splenomegaly and negative serological and immunological studies. The patient posteriorly presented polyarthralgias and cutaneous rash. The introduction of corticotherapy resolved symptoms and laboratories alterations. Adult-onset Still disease is a heterogeneous and rare disease and the lack of serologic markers as a true gold standard makes diagnosis difficult.
20361002 Vascular function and inflammation in rheumatoid arthritis: the role of physical activity. 2010 Feb 23 Inflammation disturbs biochemical pathways involved in homeostasis of the endothelium. Research has established clear links between inflammatory mediators, particularly C-reactive protein and tumour necrosis factor alpha, endothelial dysfunction, and atherosclerosis. Endothelial dysfunction and atherosclerosis may be subclinical at early stages, and thus the ability to detect them with non-invasive techniques is crucially important, particularly in populations at increased risk for cardiovascular disease, such as those with rheumatoid arthritis. This may allow the identification of interventions that may reverse these processes early on. One of the best non-pharmacological interventions that may achieve this is physical activity. This review explores the associations between inflammation, endothelial dysfunction, and atherosclerosis and discusses the role of exercise in blocking specific pathways in the inflammation, endothelial dysfunction - atherosclerosis network.
20130803 Baseline comorbidities in a population-based cohort of rheumatoid arthritis patients recei 2009 Aims. To describe the baseline characteristics of an Australian population-based cohort of rheumatoid arthritis (RA) patients commencing biological therapy. Methods. Descriptive analysis from the Australian Rheumatology Association Database (ARAD). Results. Up to October 2006, there were 681 RA patients taking biologics enrolled in ARAD. Baseline data were available for 624 (72% female, mean (SD) age 57.0 (12.5) years). Of these, 59.5% reported at least one comorbid condition, most commonly hypertension (35.7%) and osteoporosis (30.4%); 61 (9.8%) had a history of malignancy (35 nonmelanoma skin, 5 breast, 4 bowel, 5 cervix, 3 melanoma, 3 prostate and 1 each of lip, lung, myeloma, testis, uterus, vagina). Self-reported infections within the previous 6 months were common (71.5%). Conclusions. History of comorbidities, including recent infections, is common among Australian RA patients commencing biologics, and 10% have a history of malignancy. This may impact future evaluations of health outcomes among this population, including attribution of adverse events of biologic therapy.
20018055 Analysis of North American Rheumatoid Arthritis Consortium data using a penalized logistic 2009 Dec 15 We applied a penalized regression approach to single-nucleotide polymorphisms in regions on chromosomes 1, 6, and 9 of the North American Rheumatoid Arthritis Consortium data. Results were compared with a standard single-locus association test. Overall, the penalized regression approach did not appear to offer any advantage with respect to either detection or localization of disease-associated polymorphisms, compared with the single-locus approach.
20018016 Application of seventeen two-locus models in genome-wide association studies by two-stage 2009 Dec 15 The goal of this paper is to search for two-locus combinations that are jointly associated with rheumatoid arthritis using the data set of Genetic Analysis Workshop 16 Problem 1. We use a two-stage strategy to reduce the computational burden associated with performing an exhaustive two-locus search across the genome. In the first stage, the full set of 531,689 single-nucleotide polymorphisms was screened using univariate testing. In the second stage, all pairs made from the 500 single-nucleotide polymorphisms with the lowest p-values from the first stage were evaluated under each of 17 two-locus models. Our analyses identified a two-locus combination - rs6939589 and rs11634386 - that proved to be significantly associated with rheumatoid arthritis under a Rec x Rec model (p-value = 0.045 after adjusting for multiple tests and multiple models).
22334850 Correlation of lung function with disease activity rheumatoid arthritis. 2009 Apr OBJECTIVES: To find a correlation between Lung function with the disease activity in Rheumatoid arthritis (RA). METHODS: The study was carried out on 40 (35 female and 5 male) patients with active RA who fulfilled the ARA 1987 reversed criteria for the classification of RA. Patients with signs and symptoms of respiratory disease or chest injury were excluded from this study. The patients were all examined clinically by weighted and selective index for active synovitis and assessed for functional status of the follwing; ESR, Hb % level, pulmonary function tests including FEV1, VC, FEV,/ FVC and DL(CO). Another group of 30 (27 female and 3 male) patients with active RA served as a control group. RESULTS: The results showed that Hb level ranged between (7-13.3 gm/dl), ESR ranged between 11-131 mm/hr and restrictive ventilatory defect was observed in 15 (37.5%) patients. Obstructive ventilator defect was presented in 10 (25%) patients. A decreased in DLCO was detected in 23 (51.5%) patients. There was a positive correlation between PETS with Hb%, ESR, Disease duration and activity of synovitis (P<0.005). CONCLUSION: Lung function can be used to stratify abnormalities in a clinically useful manner and can be used as an indicator of disease activity in RA.
20948712 Clinically relevant advances in rheumatoid arthritis therapy. 2009 Sep 14 Owing to the success of biologics in the treatment of rheumatoid arthritis (RA), several novel drugs have been introduced in the therapeutic armamentarium, although not all of them have been approved in all countries worldwide. Among the drugs are tumour necrosis factor (TNF) inhibitors such as certolizumab pegol and golimumab (the latter of which was the first TNF blocker shown to be effective in patients who had been unsuccessfully treated with other TNF blockers and which can be applied only once a month), and the interleukin-6 receptor antagonist tocilizumab, which not only opens up a completely new field of anti-inflammatory modulation of RA pathophysiology, but also highlights the challenge of novel potential side effects. Moreover, aside from clinical studies showing efficacy in the inhibition of osteoclast activation by the anti-RANKL (receptor activator of nuclear factor-kappa B ligand) antibody denosumab, an improved form of steroid application known as slow-release 'tempus tablet' for treatment of RA and several developments in the small-molecule area have been addressed by clinical trials.
22870431 Understanding Personalized Medicine in Rheumatoid Arthritis: A Clinician's Guide to the Fu 2009 Apr Personalized medicine refers to the utilization of technologies at the molecular level to understand disease processes and improve health outcomes. In rheumatoid arthritis (RA) some factors associated with disease outcome have been identified. These factors have not yet been integrated into a clinically useful tool to predict disease outcome in individual patients. Developments in pharmacogenomics are moving the field forward quite rapidly. Genetic variants, which may have a role in drug metabolism mediating either drug response or toxicity, have been identified for both traditional disease modifying antirheumatic drugs and biologic agents. Choosing a medication based on a patient's characteristics (sociodemographic, clinical, genetic) will result in better utilization of resources and better clinical outcomes. The ethical, political, and legal implications of personalized medicine need to be considered as well.
27713309 Effects of NSAIDs on Differentiation and Function of Human and Murine Osteoclasts - Crucia 2010 May 11 Osteoclasts play a critical role in both normal bone metabolism and bone resorption in the joints of patients with rheumatoid arthritis. It has been reported that non-steroidal anti-inflammatory drugs (NSAIDs) inhibit murine osteoclastogenesis in vitro and murine arthritis models in vivo, but not the destruction of joints of patients with rheumatoid arthritis. In the current review article, we review the recent findings in the effect of NSAIDs on the formation and function of human and murine osteoclasts both in vitro and in vivo, underlining the importance of studies using human osteoclasts. Since 2009, we have suggested a novel term 'human osteoclastology'.
19125138 Silicone synovitis: longer term outcome data and review of the literature. 2009 Feb BACKGROUND: Silicone had been popular for small and medium joint prostheses from the 1960s until the 1980s when concerns about subsequent arthritis arose. There are still patients with long-standing silicone prostheses. We describe 7 cases of synovitis attributed to these. METHODS: This is a case series of patients having synovitis in the vicinity of a silicone arthroplasty. The diagnosis was determined by examination and, radiographic and operative characteristics of the joint. Underlying diseases of the patients, treatment strategies, and responses to treatment were reviewed. RESULTS: Seven charts were reviewed. The ages ranged from 53 to 90 years (mean = 71.5). Two patients had osteoarthritis, 1 had rheumatoid arthritis, 3 had trauma, and 1 had avascular necrosis. Joints included 2 metatarsal phalangeal, 3 carpal bones, 1 radial head, and 2 first carpal metacarpals. The time from arthroplasty to synovitis was 9 to 30 years (mean = 16). Five patients had surgical management and 2 had medical management. Four of the surgically managed patients had resolution of their symptoms, 1 had a recurrent synovitis requiring further surgery. One person had 2 arthroplasties, but developed synovitis at only 1 site. The 2 patients medically managed continued to have synovitis. CONCLUSIONS: Synovitis continues to be a consequence of silicone arthroplasty. It can be a late complication with our shortest time to synovitis being 9 years. Underlying pathology does not seem to predict the synovitis as patients with osteoarthritis, rheumatoid arthritis, avascular necrosis, and trauma are all represented. Surgically managed patients did well, whereas patients managed medically did not have resolution of their symptoms.
20018091 Integration of gene ontology pathways with North American Rheumatoid Arthritis Consortium 2009 Dec 15 We describe an empirical Bayesian linear model for integration of functional gene annotation data with genome-wide association data. Using case-control study data from the North American Rheumatoid Arthritis Consortium and gene annotation data from the Gene Ontology, we illustrate how the method can be used to prioritize candidate genes for further investigation.
19408347 The role of ADAMs in disease pathophysiology. 2009 May The ADAMs are a family of multidomain transmembrane and secreted proteins involved in both proteolysis and cell adhesion. Altered expression of specific ADAMs is implicated in the pathophysiology of several diseases including rheumatoid arthritis, Alzheimer's disease, cardiac hypertrophy, asthma and cancer. Of these different diseases, it is in cancer where most research has been carried out. Multiple ADAMs, including ADAM-9, ADAM-10, ADAM-12, ADAM-15 and ADAM-17, have been shown to play a role in either cancer formation or progression. Consistent with these findings, increased expression of specific ADAMs in several cancer types was found to correlate with features of aggressive disease and poor prognosis. Currently, selective ADAM inhibitors against ADAM-10 and ADAM-17 are undergoing clinical trials for the treatment of cancer. Further work is required in order to establish a causative role for ADAMs in rheumatoid arthritis, Alzheimer's disease, cardiac hypertrophy and asthma.
19370351 Measuring patients' experiences with rheumatic care: the consumer quality index rheumatoid 2009 Dec Rheumatologists and other caregivers can learn from patients’ experiences with the quality of care that can be measured with the CQ-index Rheumatoid Arthritis (CQ-index RA) survey. Patients with RA (n = 590) received this survey were they rated their actual experiences and what they find important in rheumatic healthcare. Descriptive analyses and psychometric methods were used to test the reliability. The response rate was 69%. The items in the pilot instrument could be grouped into 10 scales (α ranged from 0.77 to 0.94). The most important quality aspects according to patients concerned the alertness when prescribing medication. Providing patients with information on a special website of the hospital about RA was the highest quality improvement aspect. The results of this study show that the CQ-index RA is a reliable instrument for quality assessment from the patients’ perspective. The instrument provides rheumatologists and other caregivers with feedback for service improvement initiatives.
20018086 Application of Bayesian classification with singular value decomposition method in genome- 2009 Dec 15 To analyze multiple single-nucleotide polymorphisms simultaneously when the number of markers is much larger than the number of studied individuals, as is the situation we have in genome-wide association studies (GWAS), we developed the iterative Bayesian variable selection method and successfully applied it to the simulated rheumatoid arthritis data provided by the Genetic Analysis Workshop 15 (GAW15). One drawback for applying our iterative Bayesian variable selection method is the relatively long running time required for evaluation of GWAS data. To improve computing speed, we recently developed a Bayesian classification with singular value decomposition (BCSVD) method. We have applied the BCSVD method here to the rheumatoid arthritis data distributed by GAW16 Problem 1 and demonstrated that the BCSVD method works well for analyzing GWAS data.
20018073 Identification of gene-gene interaction using principal components. 2009 Dec 15 After more than 200 genome-wide association studies, there have been some successful identifications of a single novel locus. Thus, the identification of single-nucleotide polymorphisms (SNP) with interaction effects is of interest. Using the Genetic Analysis Workshop 16 data from the North American Rheumatoid Arthritis Consortium, we propose an approach to screen for SNP-SNP interaction using a two-stage method and an approach for detecting gene-gene interactions using principal components. We selected a set of 17 rheumatoid arthritis candidate genes to assess both approaches. Our approach using principal components holds promise in detecting gene-gene interactions. However, further study is needed to evaluate the power and the feasibility for a whole genome-wide association analysis using the principal components approach.