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

ID PMID Title PublicationDate abstract
19924709 Genetic Analysis Workshop 16: introduction to workshop summaries. 2009 Genetic Analysis Workshop 16 (GAW16) was held on September 17-20, 2008 in St. Louis, Missouri. The focus of GAW16 was on methods and challenges in analysis of single-nucleotide polymorphism data from genome-wide scans. GAW16 attracted 221 participants from 12 countries. The 168 contributions were organized into 17 discussion groups of 6-17 papers each. Three data sets were available for analysis. Two of these were data from ongoing studies, generously provided by the investigators. The North American Rheumatoid Arthritis Consortium provided case-control data on rheumatoid arthritis, and the Framingham Heart Study (FHS) made available information on cardiovascular risk factors for participants in three generations of pedigree data. The third data set included simulated phenotypes for participants in the FHS, using actual pedigree structures and genotypes. This volume includes a paper for each of the 17 discussion groups, summarizing their main findings.
19915945 Preferential reduction of bone mineral density at the femur reflects impairment of physica 2010 Feb Bone mineral density (BMD) and factors influencing BMD in rheumatoid arthritis (RA) under good or moderate control were examined to assess management of osteoporosis in RA. BMD of the lumbar spine, femur, and distal radius was measured in 105 female patients with well-controlled RA. Laboratory and clinical variables associated with disease activity were measured in the same subjects, and correlations between these variables and BMD were evaluated. The RA patients showed a greater decrease in BMD of the femoral neck than of the lumbar spine. Age, Health Assessment Questionnaire (HAQ) score, and Larsen damage score had negative correlations with BMD of the femoral neck. In multiple regression analysis of the parameters associated with BMD of the femoral neck in simple regression analysis, an increase in HAQ score showed a negative correlation with BMD of the femoral neck. After initiation of treatment with alendronate (ALN), BMD of the femoral neck increased and correlated with improvement in HAQ score. A decrease in BMD of the femoral neck is a characteristic of RA. This suggests that muscle tonus has more effect than weight-bearing activity on BMD in patients with RA. BMD of the femoral neck is a useful index for general evaluation of RA patients.
19581382 Presentation and severity of rheumatoid arthritis at diagnosis in Senegal. 2009 Sep OBJECTIVE: Early effective treatment slows structural damage in RA but requires an early diagnosis. Our objective was to determine symptoms duration and presentation patterns of RA at diagnosis in Senegal. METHODS: We conducted a cross-sectional study over a 2-year period (from March 2006 to February 2008) at the rheumatology clinic of the Le Dantec teaching hospital in Dakar, Senegal. Consecutive new patients who met ACR criteria for RA were included. RESULTS: We included 100 patients, 88 females and 12 males, with a mean age of 40.3 +/- 15.5 years and a mean symptoms duration of 54 months. One-fourth of the patients had a positive family history. Pain was the main reason for the rheumatology clinic visit. Mean pain score was 64.3 mm on a 100-mm visual analogue scale. Nocturnal arousals were reported by 69% of the patients and morning stiffness for >1 h by 74%. The tender and swollen joint counts were 10 or higher in 87% and 36% of the patients, respectively, and the mean disease activity score on 28 joints (DAS28) was 6.49 +/- 1.34. Sicca syndrome (n = 13) and rheumatoid nodules (n = 3) were the main extra-articular manifestations. Laboratory evidence of inflammation was found in 87% and RF in 78% of the patients. Antibodies to cyclic citrullinated peptides (anti-CCPs) were detected in 26 of the 29 patients. Radiographical lesions were visible in 56% of the patients; mean modified Sharp score was 21.76 +/- 47.74. CONCLUSION: The diagnosis of RA is delayed in Senegal, and the disease is highly active at diagnosis, although 44 patients have no erosions, and extra-articular manifestations are rare.
20374322 Pericardial effusions with tamponade and visceral constriction in patients with rheumatoid 2009 Apr Tumour necrosis factor-inhibitor (TNF-inhibitor) therapy is increasingly used for the treatment of rheumatoid arthritis. While it is effective for the articular manifestations of rheumatoid arthritis we have reason to believe that it is less effective for extra-articular disease. We present two cases of life-threatening cardiac tamponade in two patients with well-controlled rheumatoid arthritis on adalimumab. An extensive literature search was carried out and three other patients were found. We believe that these cases highlight the need for rheumatologists to be vigilant for extra-articular manifestations of rheumatoid arthritis even in the presence of quiescent joint disease while on TNF-inhibitors.
19896008 Outcomes of silicone arthroplasty for rheumatoid metacarpophalangeal joints stratified by 2009 Nov PURPOSE: Previous studies have demonstrated that outcomes for the ulnar digits appear to be worse than those of the radial digits after silicone metacarpophalangeal joint arthroplasty (SMPA) for the rheumatoid hand. This study examines various components of hand deformities in an effort to understand SMPA outcomes in terms of metacarpophalangeal (MCP) joint range of motion and alignment. We hypothesize that the ulnar fingers will have less improvement, marked by greater ulnar drift, extension lag, and less MCP joint arc of motion than the radial fingers. METHODS: Sixty-eight surgical patients were recruited from 3 sites in this multicenter, international prospective cohort study. All patients had a diagnosis of rheumatoid arthritis, were between the ages of 18 and 80, and were eligible to have SMPA based on measured hand deformities (extensor lag and ulnar drift). Ulnar drift, extension lag, and arc of motion for the MCP joint of each finger were measured at baseline (before surgery) and 1 year after SMPA. RESULTS: All fingers showed an improvement in ulnar drift from baseline to 1 year after surgery. The smallest improvement was in the index finger, and the largest improvement was in the little finger. Similarly, the largest improvement in extension lag was seen in the little finger, and the smallest improvement was seen in the index finger. In terms of MCP joint arc of motion, all fingers moved to a more extended posture and gained an improved arc of motion, but the biggest improvement was observed in the 2 ulnar fingers and less in the 2 radial fingers. CONCLUSIONS: Our hypothesis that the ulnar fingers would have worse outcomes than the radial fingers was not proven by this study. Although experiences have indicated that it is more difficult to maintain posture for the ring and little fingers after SMPA owing to the deforming forces, sufficient correction of the deformities in the ulnar fingers is possible, if adequate bone resection and realigning of the extensor mechanism are carefully performed during the procedure. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic I.
19403382 [Effect of sinomenine on the expression of chemokines and chemokine receptors in dendritic 2009 Apr To investigate the effect of sinomenine on the expression of chemokines and chemokine receptors of dendritic cells in patients with rheumatoid arthritis in vitro. METHODS: The peripheral blood mononuclear cells isolated from 8 patients with rheumatoid arthritis were induced to differentiate into dendritic cells with GM-CSF and IL-4. The dendritic cells were exposed to sinomenine at high (5 mmol/L), moderate (2 mmol/L), and low (1 mmol/L) concentrations or treated with the control medium. The expression of CCR5 and CCR7 on the surface of the dendritic cells were measured by flow cytometry, and the CCR5 and CCR7 mRNA expressions were detected by semi-quantitative PCR. Enzyme-linked immunosorbent assay (ELISA) was used to measure the expressions of CXCL9 (MIG), CXCL10 (IP-10) and CXCL11 (ITAC). RESULTS: Compared with the control cells, the dendritic cells treated with sinomenine, especially at high and moderate concentrations, showed significantly lowered mRNA and protein expressions of CCR5 and CCR7. Similar results were observed in the expressions of CXCL9 (MIG) and CXCL10 (IP-10), but not in CXCL11 (ITAC). CONCLUSION: Sinomenine produces therapeutic effect on rheumatoid arthritis possibly by inhibiting the expression of chemokines and chemokine receptors in the dendritic cells to suppress the chemotactic migration of the dendritic cells.
21437211 Circulating cytokine profiles and their relationships with autoantibodies, acute phase rea 2010 Our objective was to analyse the relationship between circulating cytokines, autoantibodies, acute phase reactants, and disease activity in DMARDs-naïve rheumatoid arthritis (RA) patients (n = 140). All cytokines were significantly higher in the RA cohort than in healthy controls. Moderate-to-strong positive intercorrelations were observed between Th1/Th2/macrophage/fibroblast-derived cytokines. RF correlated significantly with IL-1β, IL-2, IL-4, IL-10, IL-12, G-CSF, GM-CSF, IFN-γ, and TNF (P < .0001), and aCCP and aMCV with IL-1β, IL-2, IL-4, and IL-10 (P < .0002), while IL-6 correlated best with the acute phase reactants, CRP, and SAA (P < .0001). In patients with a DAS28 score of ≥5.1, IFN-γ, IL-1β, IL-1Ra, TNF, GM-CSF, and VEGF were significantly correlated (P < .04-.001) with high disease activity (HDA). Circulating cytokines in RA reflect a multifaceted increase in immune reactivity encompassing Th1 and Th2 cells, monocytes/macrophages, and synovial fibroblasts, underscored by strong correlations between these cytokines, as well as their relationships with RF, aCCP, and aMCV, with some cytokines showing promise as biomarkers of HDA.
18758892 Disease activity and the course of wrist joint deterioration over 10 years in the patients 2009 The objectives of this study were to evaluate the course of radiographic deterioration of the wrist joint with rheumatoid arthritis (RA), and to determine the influence of disease activity on its deterioration. A retrospective study was performed on 122 wrists in 66 patients, who started treatment using disease-modifying antirheumatic drugs within the first year of the disease and followed for more than 10 years without surgical intervention. The mean disease activity score (DAS28-CRP[3]) was high during the first 2 years, followed by a decrease and a flattening of the curve of disease activity. Generally, carpal collapse progressed more in the early stage and decreased linearly over 10 years. Individually, continuous high disease activity and progression in radiographic damage were observed in carpal collapsed groups from early stage of the disease. The cut-off values of the mean DAS28-CRP(3) during year 0-2, which indicated progression to Larsen grade III or more and Schulthess type I (ankylosis) or III (disintegration) at year 10 were 3.34 (sensitivity: 70.9% and specificity: 72.1%) and 3.63 (sensitivity: 74.3% and specificity: 77.0%), respectively. In patients with RA, deterioration of the wrist joint was influenced by disease activity. Identifying this activity and the course of wrist progression may be useful in predicting wrist deterioration.
20858714 Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis 2010 Nov 29 Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced interpatient heterogeneity. To characterize RA at the molecular level and to uncover pathomechanisms, we performed genome-wide gene expression analysis. We identified a set of 1,054 genes significantly deregulated in pair-wise comparisons between RA and osteoarthritis (OA) patients, RA and normal donors (ND), or OA and ND. Correlation analysis revealed gene sets regulated identically in all three groups. As a prominent example secreted phosphoprotein 1 (SPP1) was identified to be significantly upregulated in RA compared with both OA and ND. SPP1 expression was found to correlate with genes expressed during an inflammatory response, T-cell activation and apoptosis, suggesting common underlying regulatory networks. A subclassification of RA patients was achieved on the basis of proteoglycan 4 (PRG4) expression, distinguishing PRG4 high and low expressors and reflecting the heterogeneity of the disease. In addition, we found that low PRG4 expression was associated with a more aggressive disease stage, which is in accordance with PRG4 loss-of-function mutations causing camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Altogether we provide evidence for molecular signatures of RA and RA subclasses, sets of new candidate genes as well as for candidate gene networks, which extend our understanding of disease mechanisms and may lead to an improved diagnosis.
20859224 Oral tuberculosis in a patient with rheumatoid arthritis after long treatment with methotr 2010 Oct The treatment of rheumatoid arthritis (RA) with tumor necrosis factor α (TNF-α) inhibitors has been associated with an increased risk of tuberculosis (TB). Most patients have extrapulmonary disease. We describe a case of tonsil TB in an RA patient treated with methotrexate for 23 years and adalimumab (TNF-α inhibitor) for the last 3 years after an initial negative PPD (purified protein derivative of tuberculin) skin test. Our patient presented with a tonsil ulcer. PPD skin test was now positive; biopsy result of the lesion revealed Mycobacterium tuberculosis on culture, and a granuloma typical of TB on histologic assessment. The patient received antituberculous treatment with complete resolution of the lesion. This case illustrates that oral TB can occur after long treatment with TNF-α inhibitor and that tuberculous granulomas can be formed in such patients.
20483047 Expression of Tn and sialyl Tn antigens in synovial tissues in rheumatoid arthritis. 2010 Mar OBJECTIVES: The carbohydrate chains represented by mucins (MUCs) are expressed by a variety of normal and malignant secretory epithelial cells and induce a variety of immunoreactions. Tn and sialyl Tn antigens are tumour-associated carbohydrate antigens which are borne on the core proteins of mucins. The purpose of this study is to investigate the existence of tumour-associated carbohydrate antigens in rheumatoid arthritis (RA). METHODS: . We examined the expression of Tn and sialyl Tn antigens in synovial tissues from RA and osteoarthritis (OA) patients by immunohistochemistry. In addition, mucins from synovial fluid (SF) from RA patients are purified by gel filtration and density gradient ultracentrifugation and the existence of these antigens examined by dot and Western blotting. RESULTS: We found that Tn and sialyl Tn antigens were strongly expressed in synovial cells and infiltrating mononuclear cells on the sublining layer and lymphoid follicles in synovial tissues in RA compared with those in osteoarthritis. Tn and sialyl Tn antigens were detected in purified mucins of SF from RA patients. CONCLUSIONS: Tumour-like synovial hyperplasia cells expressed Tn and sialyl Tn antigens. This finding suggests that the mucins exhibiting with abnormal glycosylation may be in part responsible for synovial hyperplasia, leading to the joint destruction in the pathogenesis of RA.
19772790 Rheumatoid arthritis, Klippel-Feil syndrome and Pott's disease in Cardinal Carlo de' Medic 2009 Jul OBJECTIVE: A paleopathological study was carried out on the she skeletal remains of Cardinal Carlo de' Medici (1595-1666), son of the Grand Duke Ferdinando I (1549-1609) and Cristina from Lorraine (1565-1636), to investigate the articular pathology described in the archival sources. METHODS: The skeletal remains of Carlo, buried in the Basilica of San Lorenzo in Florence, have been exhumed and submitted to macroscopic and radiological examination. RESULTS: The skeleton of Carlo revealed a concentration of different severe pathologies. Ankylosis of the cervical column, associated with other facial and spine anomalies suggests a diagnosis of congenital disease: the Klippel-Feil syndrome. In addition, the cervical segment presents the results of the tuberculosis (Pott's disease) from which the Cardinal suffered in his infancy. The post-cranial skeleton shows an ankylosing disease, mainly symmetrical and extremely severe, involving the large as well as small articulations, and characterized by massive joint fusion, that totally disabled the Cardinal in his last years of life. CONCLUSIONS: The final diagnosis suggests an advanced, ankylosing stage of rheumatoid arthritis.
20470952 Conservative treatments for rheumatoid arthritis in the foot and ankle. 2010 Apr Rheumatoid arthritis (RA) is a systemic inflammatory disease that attacks peripheral joints, causing their destruction. Several pharmacologic therapies and physical modalities are available for its treatment. Because of the progressive nature of RA, complementary and alternative medicine therapy in conjunction with conventional medicine is administered to patients with RA. This article discusses the presence of undiagnosed RA in the foot and ankle and reviews the concurrent nonoperative measures in treatment, including pharmacologic and physical modalities.
20661068 Neglected spontaneous rupture of the Achilles tendon in elderly patients with rheumatoid a 2010 Aug Spontaneous Achilles tendon rupture associated with rheumatoid arthritis (RA) is a very rare complication. In this report, we have experienced neglected spontaneous rupture of the Achilles tendon in 5 elderly RA patients, and report its clinical features and management. These patients had taken corticosteroids for a long time for RA control. Moreover, they did not show any signs, such as click or impact on the rear foot at the moment of the rupture, and had few complaints or obvious symptoms around their ankles or the rear of the foot after the rupture. This suggests that the lack of severe symptoms prevented the early diagnosis of the Achilles tendon rupture, and that this injury had been neglected during treatment for RA. Therefore, careful diagnosis of the Achilles tendon rupture is needed in elderly patients with RA, even if they have little or no history of trauma.
21115552 Utility of ultrasound joint counts in the prediction of rheumatoid arthritis in patients w 2011 Mar OBJECTIVES: Early therapy improves outcomes in rheumatoid arthritis (RA). It is therefore important to improve predictive algorithms for RA in early disease. This study evaluated musculoskeletal ultrasound, a sensitive tool for the detection of synovitis and erosions, as a predictor of outcome in very early synovitis. METHODS: 58 patients with clinically apparent synovitis of at least one joint and symptom duration of ≤3 months underwent clinical, laboratory, radiographic and 38 joint ultrasound assessments and were followed prospectively for 18 months, determining outcome by 1987 American College of Rheumatology (ACR) and 2010 ACR/European League Against Rheumatism criteria. Sensitivity and specificity for 1987 RA criteria were determined for ultrasound variables and logistic regression models were then fitted to evaluate predictive ability over and above the Leiden rule. RESULTS: 16 patients resolved, 13 developed non-RA persistent disease and 29 developed RA by 1987 criteria. Ultrasound demonstrated subclinical wrist, elbow, knee, ankle and metatarsophalangeal joint involvement in patients developing RA. Large joint and proximal interphalangeal joint ultrasound variables had poor predictive ability, whereas ultrasound erosions lacked specificity. Regression analysis demonstrated that greyscale wrist and metacarpophalangeal joint involvement, and power Doppler involvement of metatarsophalangeal joints provided independently predictive data. Global ultrasound counts were inferior to minimal power Doppler counts, which significantly improved area under the curve values from 0.905 to 0.962 combined with the Leiden rule. CONCLUSION: In a longitudinal study, extended ultrasound joint evaluation significantly increased detection of joint involvement in all regions and outcome groups. Greyscale and power Doppler scanning of metacarpophalangeal joints, wrists and metatarsophalangeal joints provides the optimum minimal ultrasound data to improve on clinical predictive models for RA.
20590962 Managing inflammatory arthritides: Role of the nurse practitioner and physician assistant. 2010 Jul PURPOSE: To review the current management of the inflammatory arthritides, including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. This review examines the role of the nurse practitioner (NP) and physician assistant (PA) in the management of these chronic diseases. DATA SOURCES: A review of the scientific literature and current guidelines regarding the management of inflammatory arthritides. CONCLUSIONS: NPs and PAs play important roles in the interdisciplinary team involved in the treatment of patients with chronic inflammatory arthritic conditions. The management of inflammatory arthritides has evolved with the development of new treatment strategies and is focused on early intervention and minimizing progressive joint damage. NPs and PAs are ideally positioned to educate patients regarding treatment options and other important aspects of the disease process and to monitor disease activity using a number of validated instruments. IMPLICATIONS FOR PRACTICE: Through active disease management, NPs and PAs can influence their patients to make better, more informed choices regarding treatment, which may optimize patient outcomes.
20495432 Magnetic resonance angiography for vertebral artery evaluation in rheumatoid arthritis pat 2010 Jun OBJECTIVE: To examine the radiological features of vertebral artery (VA) displacement/occlusion associated with rheumatoid arthritis (RA) spine using magnetic resonance angiography. METHODS: Forty-seven RA patients with upper cervical lesions were evaluated for patency or abnormality of the VA by extracranial magnetic resonance angiography, with comparison of findings with those of 46 healthy volunteers. RESULTS: VA occlusion occurred in 4 patients (8.5%) and VA stenosis in 9 patients (19.1%). Anomaly of the VA was also observed in 3 patients (6.4%). No occlusion or anomaly was found in healthy volunteers, but 1 case of stenosis was found. Severity of vertical subluxation was correlated with the presence of VA abnormality in RA patients. CONCLUSION: The incidence of VA abnormality was 34% in RA patients and 2% in healthy volunteers. Magnetic resonance angiography is useful for screening for abnormality of the entire VA.
19015958 Antisense makes sense in engineered regenerative medicine. 2009 Feb The use of antisense strategies such as ribozymes, oligodeoxynucleotides (ODNs) and small interfering RNA (siRNA) in gene therapy, in conjunction with the use of stem cells and tissue engineering, has opened up possibilities in curing degenerative diseases and injuries to non-regenerating organs and tissues. With their unique ability to down-regulate or silence gene expression, antisense oligonucleotides are uniquely suited in turning down the production of pathogenic or undesirable proteins and cytokines. Here, we review the antisense strategies and their applications in regenerative medicine with a focus on their efficacies in promoting cell viability, regulating cell functionalities as well as shaping an optimal microenvironment for therapeutic purposes.
20799370 Self-management strategies used during flares of rheumatoid arthritis in an ethnically div 2010 Dec OBJECTIVES:  Effective management of flares of rheumatoid arthritis (RA) can improve symptoms and may delay disease progression. The practice of rheumatologists in managing a flare has been studied, but patients' experiences of, and responses to, disease flares remain poorly defined. This study aimed to address this issue. METHODS:  Semi-structured interviews were conducted with 21 patients from an ethnically diverse population who had suffered a recent RA flare. Open questions were asked regarding patients' definitions of a flare, causal attribution, self-management strategies, their triggers to consult health professionals, and the information they had received about RA flares from health professionals. Transcripts were studied using the grounded theory approach to identify themes. RESULTS:  Flares were usually described as worsening joint pain and swelling. Over-use of joints was identified as the most common cause of a flare, and commonly used self-management strategies included rest, gentle exercise and warming the joints. There was some variation in causal attribution and self-management with ethnicity. CONCLUSIONS:  This study identified a link between causal attribution of flares and the resultant self-management strategies. A perceived trigger of the flare in some patients formed a focus for their self-management strategies, whereas those who could not identify a cause aimed mainly to alleviate symptoms. A better understanding of patients' perspective in the context of disease flares will allow the development of educational programmes to facilitate more effective self-management of this important manifestation of disease.
18800356 The FOOTSTEP self-management foot care programme: are rheumatoid arthritis patients physic 2009 Mar BACKGROUND: The FOOTSTEP self-management foot care programme is a clinical and cost-effective programme for basic foot care in the elderly. The aim of this study was to determine if patients with rheumatoid arthritis (RA) would be physically able to participate. METHODS: A consecutive cohort of RA patients undergoing podiatry care underwent tests for sight, reach and grip strength to determine their physical ability to undertake self-managed foot care. RESULTS: Thirty RA patients (10 male, 20 female), with a median age of 61 years (range 42 to 84) and disease duration of 10 years (range one to 40), were recruited. All patients passed the sight test, whereas the reach and grip tests were passed by 77% and 67% of patients, respectively. Only 57% of patients passed all the physical tests. Patients who failed the physical tests were older, and had longer disease duration and higher physical disability, pain and general health scores but these were not statistically different. CONCLUSIONS: Just over half the patients in this present cohort may be physically able to undertake some aspects of self-managed foot care, including nail clipping and filing, callus filing and daily hygiene and inspection.