Browse

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

ID PMID Title PublicationDate abstract
23700041 Assessing rheumatoid arthritis disease activity with ultrasound. 2013 Sep In practice, composite indices are used for rheumatoid arthritis (RA) disease activity evaluation. Despite valid and widely used, not rarely composite indices miss accuracy. Ultrasound (US) is more precise than clinical examination in synovitis appraisal. US-based disease activity estimation depends on the detection of synovitis. The most common synovitis abnormalities are proliferation, effusion, and neoangiogenesis. Gray scale ultrasound identifies synovial hypertrophy and effusion with its good soft tissue contrast. Additionally, power Doppler ultrasound depicts neoangiogenesis within synovia, remarking local inflammation. Several studies have combined local US findings to develop a patient level disease activity index. Most of them summed selected joint scores in an overall score of disease activity and evaluated its correlation with clinical composite indexes. To be incorporated into clinical practice, an overall US score must have some fundamental characteristics such as reproducibility, viability, and sensitivity to change over time. In global US score development, finding the joints that truly estimate individual disease activity is highly challenging. This article presents an up-to-date literature review on assessing RA disease activity with US and depicts the challenges in finding the perfect global US score.
25295921 Preference of surgical procedure for the forefoot deformity in the rheumatoid arthritis pa 2015 May OBJECTIVES: The deformed rheumatoid forefoot may be treated with resection of lesser metatarsal heads combined with arthrodesis or resection of the first metatarsophalangeal joint. Recurrent hallux valgus deformity has been reported by resection. We performed a prospective, randomized, internal-controlled study to compare results between arthrodesis and resection. METHODS: We resected the lesser metatarsal heads bilaterally and performed arthrodesis of the first metatarsophalangeal joint on one side and resection on the opposite side. We investigated 26 patients (52 feet) who were followed at least one year. Patients were assessed for clinical score, hallux valgus angle (HVA), angle between first and second metatarsals, and angle between first and fifth metatarsals preoperatively, postoperatively and at final follow-up. We evaluated callosities, claw toes, recurrences, and procedure preferences. RESULTS: The mean follow-up period was 4.1 years. No significant differences between arthrodesis and resection were seen, with the exception of HVA. That was significantly less on arthrodesis side (11.5°) than on resection side (17.0°, p < 0.05). Seven callosities on resection side and four on arthrodesis side were observed. On resection side, hallux valgus deformity often recurred (15.3%). Patients expressed a significant preference for arthrodesis over resection (p = 0.008). CONCLUSIONS: Arthrodesis provides better results for maintaining HVA.
24959977 Increased risk of levothyroxine-treated hypothyroidism preceding the diagnosis of rheumato 2014 Jul OBJECTIVES: To evaluate the prevalence of levothyroxine-treated hypothyroidism in rheumatoid arthritis (RA) patients at the time of RA diagnosis in comparison to age- and sex-specific general population. Other objectives were to determine whether the risk of hypothyroidism varies by age at the onset of RA, or by sex or rheumatoid factor (RF) status. METHODS: We identified 7,209 incident RA patients diagnosed between January 2004 and December 2007 from a Finnish nationwide register of special reimbursements for medication costs. The presence of hypothyroidism at RA diagnosis was identified from the same register based on special reimbursement decisions for levothyroxine substitution. The prevalence of levothyroxine-treated hypothyroidism was compared to that of an age- and sex-specific Finnish population, and a standardised rate ratio (SRR) for hypothyroidism was calculated. RESULTS: The SRR for levothyroxine-treated hypothyroidism preceding RA was 1.51 (95% CI 1.35 to 1.67). Neither RF status nor sex modified the risk, although the results did not reach statistical significance among men. The SRR was highest, almost 2.5 among younger female RA patients (20-49 years of age), the excess prevalence of hypothyroidism decreasing steadily and wearing off among patients who were older at the time of diagnosis. The absolute prevalence of hypothyroidism, however, increased with age as it does in the general population. CONCLUSIONS: The risk of hypothyroidism is increased among RA patients already at the disease onset, especially among the young women, regardless of RF status. This calls for attention to screening for hypothyroidism in RA patients, preferably when RA has already been diagnosed.
23052405 [Regression of peripheral and pulmonary rheumatoid nodules under therapy with rituximab]. 2013 Mar We report on a retrospective study of 16 rheumatoid arthritis (RA) patients with reduction in size of pulmonary and peripheral rheumatoid nodules following treatment with rituximab (RTX). The 8 female and 8 male patients had an average disease duration of 12.2 years, 88 % were anti-CCP positive and 94 % seropositive. Prior treatment included an average of 2.9 DMARD and 1.4 biological therapies. On average 6.1 rheumatoid nodules were found on hands and elbows and 5 patients had pulmonary nodules. In 6 out of 16 patients the nodules disappeared completely, in 2 patients a pulmonary nodule disappeared. In 10 out of 16 patients the size of the nodules decreased by approximately 50%, 1 out of the 16 patients with significant increase in size and number of nodules prior to RTX therapy showed a reduction in size but no new nodules occurred. The regression in size of the nodules occurred 34.2±39.1 weeks following RTX therapy, correlating with 1.3±0.59 RTX infusion cycles. Overall, increases in size or new nodules were reported in none of the patients. One nodule examined histologically following RTX therapy did not show any specific differences. RTX may lead to a marked reduction in size of rheumatoid nodules in RA patients. More studies are necessary to confirm whether this is an RTX-specific effect.
23773638 Comparison of anti-mutated citrullinated vimentin, anti-cyclic citrullinated peptides, ant 2013 Apr AIM: To evaluate the diagnostic value of anti-mutated citrullinated vimentin antibodies (anti-MCV), anti-cyclic citrullinated peptides antibodies (anti-CCP), anti-glucose-6-phosphate isomerase antibodies (anti-GPI) and anti-keratin antibodies (AKA) and rheumatoid factor (RF) in rheumatoid arthritis (RA). METHODS: The five auto-antibodies were detected in serum samples of 56 patients with RA, 21 patients with systemic lupus erythematosus (SLE), 11 with ankylosing spondylitis (AS), six with Sjögren's syndrome (SS), four with connective tissue disease (CTD) and 20 healthy controls. Anti-MCV, anti-CCP and anti-GPI were detected by enzyme-linked immunosorbent assays (ELISA), AKA was determined by indirect immunofluorescence and RF was determined by rate nephelometry. RESULTS: In RA, anti-MCV and anti-GPI had the highest sensitivity (78.6% and 75.0%, respectively), anti-CCP and AKA had the highest specificity (97.6%). Anti-GPI had the lowest specificity (64.3%), and AKA had the lowest sensitivity (48.2%). When two antibodies were detected together, the sensitivity of anti-MCV/anti-CCP/RF were highest (92.9%) with a lower specificity (73.8%). The combination of anti-MCV/anti-CCP had a slightly decreased sensitivity (89.3%) and the same specificity (73.8%). CONCLUSIONS: The combination RF/anti-MCV/anti-CCP or anti-MCV/anti-CCP are usefully serologic tests for the diagnosis of RA in Chinese patients.
24447879 Association study of human leukocyte antigen-DRB1 alleles with rheumatoid arthritis in Alg 2017 Dec INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory and multifactorial disease. Genetic predisposition seems to play an important role. The aim of this study is to explore the relationship between human leukocyte antigen (HLA)-DRB1 alleles and susceptibility, clinical and biological features of RA in an Algerian patient population. METHODS: Using polymerase chain reaction - sequence specific primers (SSP), 134 RA patients and 132 healthy controls were genotyped for HLA-DRB1 and HLA-DRB1*04 subtypes. RESULTS: HLA-DRB1*04 was found to have increased frequency in the RA group compared to controls (P < 0.001, OR = 3.14), and was associated with anti-citrullinated protein antibodies positivity (ACPA) (P = 0.01, OR = 2.35). In contrast, HLA-DRB1*07 was found to have a decreased frequency in patients compared to controls (P = 0.003, OR = 0.44) and significant decrease was observed in patients with the rheumatoid factor (RF) positivity subgroup (P = 0.009, OR = 0.29). HLA-DRB1*04:05 was associated with RA (P = 0.005, OR = 3.41), whereas, HLA-DRB1*04:02 showed a protective effect against RA (P = 0.003, OR = 0.20). CONCLUSIONS: HLA-DRB1*04 was associated with increased risk for RA and ACPA positivity, while HLA-DRB1*07 was associated with reduced risk for RA and RF synthesis in Algerian patients.
25048496 Regulatory B cells are inversely associated with disease activity in rheumatoid arthritis. 2014 Sep PURPOSE: The function of regulatory B lymphocytes is known to be abnormal in inflammatory diseases. However, a recent study indicates that IL-10+ B cells seem to be expanded in rheumatoid arthritis (RA). Therefore, the state of IL-10+ B cells in the peripheral blood from RA patients and healthy controls were investigated. MATERIALS AND METHODS: CD19+ cells in peripheral blood mononuclear cells were purified from blood samples of RA patients and age and gender-matched healthy controls, and stimulated with CD40 ligand and CpG for 48 hours. Then, intracellular IL-10 in CD19+ cells was analyzed using flow cytometry. RESULTS: There was no significant difference in the proportion of IL-10+ B cells between 10 RA patients and 10 healthy controls (RA, 0.300±0.07 vs. healthy control 0.459±0.07, p=0.114). The proportion of induced IL-10+ B cells to total B cells in RA patients was significantly higher than those in controls (RA, 4.44±3.44% vs. healthy control 2.44±1.64%, p=0.033). However, the proportion of IL-10+ B cells to total B cells correlated negatively with disease activity in RA patients (r=-0.398, p=0.040). Erythrocyte sedimentation rate or C-reactive protein or medication was not associated with the proportion of IL-10+ B cells. CONCLUSION: The proportion of induced IL-10+ B cell increased in RA patients compared to healthy control, however, negatively correlated with disease activity in RA.
24638248 In vivo therapy monitoring of experimental rheumatoid arthritis in rats using near-infrare 2014 Mar An in vivo near-infrared fluorescence (NIRF) imaging technique is described for therapy monitoring of ankle joints affected by collagen-induced arthritis, a model of human rheumatoid arthritis. Arthritis was induced in rats by intradermal injections of collagen and Freund's incomplete adjuvant. For in vivo imaging, the nonspecific NIR dye tetrasulfocyanine (TSC) was used. Prior to and after treatment with a nonsteroidal anti-inflammatory drug, meloxicam, or analgesic drug, tramadol hydrochloride (which served as no-therapy control), normalized fluorescence intensities of each ankle joint were measured. Additionally, each ankle joint was characterized by clinical arthritis scoring and histopathology. Over a 3-week treatment period, a significant difference in disease progression between animals treated with meloxicam and tramadol hydrochloride was detected. A statistically significant improvement in ankle joint pathology from high- or moderate-grade to moderate- or low-grade upon meloxicam therapy, as determined by clinical evaluation, translated into a significant decrease in fluorescence intensity. In contrast, all arthritic joints of the no-therapy control group deteriorated to high-grade arthritis with high-fluorescence intensities in NIRF imaging.
25028381 Effect of remission definition on healthcare cost savings estimates for patients with rheu 2014 Aug OBJECTIVE: Sustained remission in rheumatoid arthritis (RA) results in healthcare utilization cost savings. We evaluated the variation in estimates of savings when different definitions of remission [2011 American College of Rheumatology/European League Against Rheumatism Boolean Definition, Simplified Disease Activity Index (SDAI) ≤ 3.3, Clinical Disease Activity Index (CDAI) ≤ 2.8, and Disease Activity Score-28 (DAS28) ≤ 2.6] are applied. METHODS: The annual mean healthcare service utilization costs were estimated from provincial physician billing claims, outpatient visits, and hospitalizations, with linkage to clinical data from the Alberta Biologics Pharmacosurveillance Program (ABioPharm). Cost savings in patients who had a 1-year continuous period of remission were compared to those who did not, using 4 definitions of remission. RESULTS: In 1086 patients, sustained remission rates were 16.1% for DAS28, 8.8% for Boolean, 5.5% for CDAI, and 4.2% for SDAI. The estimated mean annual healthcare cost savings per patient achieving remission (relative to not) were SDAI $1928 (95% CI 592, 3264), DAS28 $1676 (95% CI 987, 2365), and Boolean $1259 (95% CI 417, 2100). The annual savings by CDAI remission per patient were not significant at $423 (95% CI -1757, 2602). For patients in DAS28, Boolean, and SDAI remission, savings were seen both in costs directly related to RA and its comorbidities, and in costs for non-RA-related conditions. CONCLUSION: The magnitude of the healthcare cost savings varies according to the remission definition used in classifying patient disease status. The highest point estimate for cost savings was observed in patients attaining SDAI remission and the least with the CDAI; confidence intervals for these estimates do overlap. Future pharmacoeconomic analyses should employ all response definitions in assessing the influence of treatment.
24877127 B cells in rheumatoid arthritis: from pathogenic players to disease biomarkers. 2014 The therapeutic benefit of depleting B cells in rheumatoid arthritis (RA) has refocused attention on B cells with increasing awareness on their role in autoimmunity and their function beyond autoantibody production. The rapid increase in our comprehension of B-cell pathobiology is progressively opening novel perspectives in the area of B cell-targeted therapies with the expectation to define more specific approaches able to preserve the homeostasis of the humoral response while disrupting the pathogenic components. In parallel, B-cell activity in RA is starting to be explored in its clinical value, in search of novel biomarkers embedded in the pathogenic process that could help classifying the disease and predicting its heterogeneous outcome beyond inflammation dynamics. In this review, we summarize current knowledge on the multiple roles that B cells play in several aspects of RA. We also analyze their distribution and potential function in different anatomic compartments with specific reference to the main sites in which the disease may be sustained and exert its detrimental effects: the systemic circulation, synovium, bone marrow, and draining lymph nodes. We also highlight novel data encouraging further research in the field of biomarkers related to B cells and their regulatory factors.
24878794 Hemochromatosis simulating rheumatoid arthritis: a case report. 2014 Jan This is a report of a patient who had a previous diagnosis of rheumatoid arthritis, nonerosive, rheumatoid factor negative, that despite the therapeutic approach presented progressive worsening of the articular and general condition. After extensive research, she had a diagnosis of hemochromatosis. Joint symptoms are common manifestations in hemochromatosis. The arthropathy of hemochromatosis may resemble inflammatory arthropathy mimicking RA, particularly in the most common sites as 2nd and 3rd metacarpophalangeal. Radiologically are observed decreased joint space, subchondral sclerosis, cyst formation and chondrocalcinosis. Treatment with disease modifying drugs for rheumatoid arthritis tend to worsen the clinical picture, since the liver is the major site of deposition of iron in hemochromatosis and these medications are known to be hepatotoxic. Phlebotomy treatment for hemochromatosis is apparently ineffective in reversing the articular manifestations, which requires the association with iron chelating drugs. Due to the apparent difficulty in differentiating between the two diseases, a screening profile of iron in patients with rheumatoid arthritis with atypical progression is necessary.
23740236 Evaluation of the RABBIT Risk Score for serious infections. 2014 Sep OBJECTIVE: To evaluate the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) Risk Score for serious infections in patients with rheumatoid arthritis (RA). METHODS: The RABBIT Risk Score for serious infections was developed in 2011 on a cohort of RA patients enrolled in the German biologics register RABBIT between 2001 and 2007. To evaluate this score, we used data from patients enrolled in RABBIT after 1 January 2009. Expected numbers of serious infections and expected numbers of patients with at least one serious infection per year were calculated by means of the RABBIT Risk Score and compared with observed numbers in the evaluation sample. RESULTS: The evaluation of the score in an independent cohort of 1522 RA patients treated with tumour necrosis factor α (TNFα) inhibitors and 1468 patients treated with non-biological disease-modifying antirheumatic drugs (DMARDs) showed excellent agreement between observed and expected rates of serious infections. For patients exposed to TNF inhibitors, expected as well as observed numbers of serious infections were 3.0 per 100 patient-years (PY). For patients on non-biological DMARDs the expected and observed numbers were 1.5/100 PY and 1.8/100 PY, respectively. The score was highly predictive in groups of patients with low as well as with high infection risk. CONCLUSIONS: The RABBIT Risk Score is a reliable instrument which determines the risk of serious infection in individual patients based on clinical and treatment information. It helps the rheumatologist to balance benefits and risks of treatment, to avoid high-risk treatment combinations and thus to make informed clinical decisions.
25510838 Validation of the rheumatoid arthritis diagnosis in the Swedish National Patient Register: 2014 Dec 15 BACKGROUND: The Swedish National Patient Register offers unique possibilities for identification of large cohorts, such as patients with rheumatoid arthritis (RA). Although the overall diagnostic validity in the register has been reported as good, the aims of this study were to a) specifically validate the RA diagnosis from contemporary outpatient specialist care in this register, and b) assess the proportion of patients identified via algorithms to define incident RA in the register who in clinical practice also have new-onset disease. METHODS: 211 individuals with prevalent or incident RA in the National Patient Register were included. By extracting diagnosis-related parameters from their medical records, we determined if the patient fulfilled the 2010 ACR/EULAR- and the 1987 ACR-classification criteria for RA. We also determined whether clinical diagnosis was synchronous with disease onset as defined through register-based algorithms. RESULTS: For 91% of the prevalent patients, the RA diagnosis in the National Patient Register fulfilled classification criteria or clinical diagnosis for RA. Among individuals identified with incident RA using a strict algorithm for new-onset disease, the RA diagnosis was substantiated in 91%, of whom 92% also represented new-onset disease. CONCLUSIONS: The validity of the RA diagnosis in the National Patient Register was high and, by using specific algorithms, new-onset RA can be defined. These findings strengthen the notion that the National Patient Register may be used to define RA populations with high validity to allow for high-quality epidemiological studies.
24441152 Vasculitis associated with rheumatoid arthritis: a case-control study. 2014 May OBJECTIVE: The aim of this study was to determine the clinical correlates and predictors of rheumatoid vasculitis (RV). METHODS: A retrospective cohort of patients with RV evaluated at a tertiary referral centre between 1 January 2000 and 1 January 2010 was identified. RV cases were compared in a 1:2 ratio to controls (RA without vasculitis) to identify risk factors for developing RV. RESULTS: Eighty-six RV cases (58% women, 88% white) were identified. Histopathological confirmation was available for 58% of patients. Cutaneous vasculitis was the most common presentation, followed by vasculitic neuropathy. The median age at presentation was 63 years and the median duration of RA was 10.8 years. One third were current smokers. The majority were seropositive and had elevated inflammatory markers. Treatment was with a range of immunomodulating agents. At 6 months, 38% of patients achieved complete remission, 52% had partial improvement and 10% noted no clinical improvement. Thirty-six per cent relapsed by 5 years and 26% died. After adjusting for age and disease duration, current smoking at RA diagnosis [odds ratio (OR) 1.98], coexistent peripheral vascular disease (OR 3.98), cerebrovascular disease (OR 6.48), severe RA (OR 2.02) (characterized by radiographic erosions, nodulosis on clinical examination or requirement of joint surgery) and the use of biologics (OR 2.80) were found to increase the odds for developing RV; the use of HCQ (OR 0.54, CI 0.31, 0.94) and low-dose aspirin (OR 0.42, CI 0.21, 0.85) was associated with decreased odds for developing RV. CONCLUSION: This largest single-centre series of patients with RV suggests that even in recent years, RV remains a serious complication of RA and is associated with significant mortality.
24831189 Intravenous golimumab in rheumatoid arthritis. 2014 Jul Intravenous golimumab in a dosage of 2 mg/kg, initially given every 4 weeks but then every 8 weeks, in addition to methotrexate, is effective in the treatment of patients with rheumatoid arthritis. This weight-based infusion is administered over thirty minutes with an acceptable safety profile. Since it is a relatively new formulation, more time will be required to assess its specific role in the rheumatologists' armamentarium and to appreciate more fully its long-term safety.
23371304 Mitogen-activated protein kinases as therapeutic targets for rheumatoid arthritis. 2013 Feb Rheumatoid arthritis (RA) is a chronic autoimmune disease in which imbalances in pro- and anti-inflammatory cytokines promote the induction of autoimmunity, inflammation and joint destruction. Methotrexate, the standard disease-modifying anti-rheumatic drug (DMARD), has shown a gradual loss of efficacy in a significant proportion of patients, probably due to the onset of drug resistance, and thus it was hoped that the development of biologics would revolutionise RA management. Even though biologics have improved the therapy of patients refractive to DMARDs, they require parenteral administration and may leave patients open to serious infection and cancer. Therefore, attention has also been focused on inhibitors of mitogen-activated protein kinases (MAPKs), signalling enzymes that play key roles in pathogenic cytokine production, and their downstream effector pathways, in order to create safe and effective oral drugs. This article therefore provides an overview of the structure and function of MAPKs and their role in the pathogenesis of RA as context to describing the advances in the development of specific, druggable MAPK inhibitors. Their potential as therapies in the management of RA is also discussed.
23994996 Development of adult T-cell leukemia in a patient with rheumatoid arthritis treated with t 2013 Tocilizumab (TCZ) was administered from 2004 to 2008 in a 52-year-old woman with rheumatoid arthritis (RA) refractory to methotrexate (MTX) as a clinical trial. TCZ therapy with MTX was resumed in March 2009 due to exacerbation of RA. The patient was an human T-lymphotropic virus type I (HTLV-I) carrier, and, in April 2011, a peripheral blood smear showed many atypical lymphocytes, thus leading to a diagnosis of adult T-cell leukemia (ATL). Complete remission of ATL was achieved with a standard therapeutic regimen.
23020882 Mechanisms of premature atherosclerosis in rheumatoid arthritis and lupus. 2013 Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), the two most common systemic autoimmune disorders, have both unique and overlapping manifestations. One feature they share is a significantly enhanced risk of atherosclerotic cardiovascular (CV) disease that significantly contributes to morbidity and mortality. The primary mechanisms that drive CV damage in these diseases remain to be fully characterized, but recent discoveries indicate that distinct inflammatory pathways and immune dysregulation characteristic of RA and SLE likely play prominent roles. This review focuses on analyzing the major mechanisms and pathways potentially implicated in the acceleration of atherothrombosis and CV risk in SLE and RA, as well as in the identification of putative preventive strategies that may mitigate vascular complications in systemic autoimmunity.
23992261 Cross-cultural adaptation and validation of a Bengali Health Assessment Questionnaire for 2013 Aug AIM: To translate and adapt the Health Assessment Questionnaire Disability Index (HAQ-DI) into Bengali (B-HAQ) for use in Bangladeshi populations and to test its reliability and validity in patients with rheumatoid arthritis (RA). METHOD: The HAQ-DI was translated using rigorous forward-backward protocols and the translated version was subsequently cognitively pretested in a sample of 30 outpatients with RA. The pre-final version of the questionnaire was psychometrically tested for internal consistency and construct validity in a new sample of 100 consecutive RA outpatients. RESULTS: Ten questions were changed to suit the Bengali culture. Pretests showed that the items included in the B-HAQ were well understood by Bengali patients, while some of the original items were difficult to understand for a majority of patients. The resulting B-HAQ showed good internal consistency and construct validity in the psychometric validation study. CONCLUSION: This study suggests that the B-HAQ is a reliable and valid instrument for measuring functional disability in a Bengali-speaking population with RA. Future studies should examine the test-retest reliability and responsiveness of the B-HAQ before it can be confidently recommended as an outcome measure in intervention studies.
24432692 [Regulatory roles of compound danshen in the downstream path of cyclooxygenases in rheumat 2013 Oct Rheumatoid arthritis (RA) belongs to Bi syndrome (arthralgia) in Chinese medicine. Till now there lacks effective therapeutic methods. Recently cyclooxygenases (COXs) inhibitors, having regulator roles for many pro-inflammatory cytokines, have been widely used in RA treatment. But due to existing cardiovascular risks, researches on targeting the downstream specific factors of COXs have been under discussion. Considering the key role of blood stasis syndrome (BSS) in the pathology of RA and the fact that thromboxane A2 (TXA2) plays a pivotal role in BSS, we theoretically explored possible regulatory roles of Compound Danshen, a representative therapy in blood activating stasis removing method in the downstream path of COXs in synovial cells of RA. We proposed a brand new research direction of RA researches.