Biomarkers for rheumatoid and psoriatic arthritis.

PubMed

Verheul, M K; Fearon, U; Trouw, L A; Veale, D J

2015-11-01

Rheumatic diseases, such as rheumatoid and psoriatic arthritis are systemic inflammatory conditions characterized by a chronic form of arthritis, often leading to irreversible joint damage. Early treatment for patients with rheumatic diseases is required to reduce or prevent joint injury. However, early diagnosis can be difficult and currently it is not possible to predict which individual patient will develop progressive erosive disease or who may benefit from a specific treatment according to their clinical features at presentation. Biomarkers are therefore required to enable earlier diagnosis and predict prognosis in both rheumatoid arthritis and psoriatic arthritis. In this review we will examine the evidence and current status of established and experimental biomarkers in rheumatoid and psoriatic arthritis for three important purposes; disease diagnosis, prognosis and prediction of response to therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Walking ability as a measure of treatment effect in early rheumatoid arthritis.

PubMed

Hamilton, J; Brydson, G; Fraser, S; Grant, M

2001-04-01

To assess the clinical usefulness of a prototype walkmat system in patients with early rheumatoid arthritis (RA). Twenty-four subjects with early RA and symptomatic forefoot disease requiring therapy with second-line drugs were recruited. Each subject underwent clinical assessment together with gait analysis on the contact sensitive walkmat system and Kistler forceplate before and after six months of treatment with second-line drugs. Two subjects were lost to follow-up. There was the expected improvement in disease activity in response to therapy. Significant differences were also demonstrated in defined gait parameters that indicated improved weight-bearing and enhanced forefoot propulsion. Medical therapy improved walking ability in patients with RA and the walkmat system provided a useful adjunct to existing outcome measures in the assessment of lower limb function.

Impact of early diagnosis on functional disability in rheumatoid arthritis

PubMed Central

Kim, Dam; Choi, Chan-Bum; Lee, Jiyoung; Cho, Soo-Kyung; Won, Soyoung; Bang, So-Young; Cha, Hoon-Suk; Choe, Jung-Yoon; Chung, Won Tae; Hong, Seung-Jae; Jun, Jae-Bum; Jung, Young Ok; Kim, Jinseok; Kim, Seong-Kyu; Kim, Tae-Hwan; Kim, Tae-Jong; Koh, Eunmi; Lee, Hye-Soon; Lee, Jaejoon; Lee, Jisoo; Lee, Sang-Heon; Lee, Shin-Seok; Lee, Sung Won; Shim, Seung-Cheol; Yoo, Dae-Hyun; Yoon, Bo Young; Sung, Yoon-Kyoung; Bae, Sang-Cheol

2017-01-01

Background/Aims To determine whether early diagnosis is beneficial for functional status of various disease durations in rheumatoid arthritis (RA) patients. Methods A total of 4,540 RA patients were enrolled as part of the Korean Observational Study Network for Arthritis (KORONA). We defined early diagnosis as a lag time between symptom onset and RA diagnosis of ≤ 12 months, whereas patients with a longer lag time comprised the delayed diagnosis group. Demographic characteristics and outcomes were compared between early and delayed diagnosis groups. Logistic regression analyses were performed to identify the impact of early diagnosis on the development of functional disability in RA patients. Results A total of 2,597 patients (57.2%) were included in the early diagnosis group. The average Health Assessment Questionnaire-Disability Index (HAQ-DI) score was higher in the delayed diagnosis group (0.64 ± 0.63 vs. 0.70 ± 0.66, p < 0.01), and the proportion of patients with no functional disability (HAQ = 0) was higher in the early diagnosis group (22.9% vs. 20.0%, p = 0.02). In multivariable analyses, early diagnosis was independently associated with no functional disability (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40). In a subgroup analysis according to disease duration, early diagnosis was associated with no functional disability in patients with disease duration < 5 years (OR, 1.37; 95% CI, 1.09 to 1.72) but not in patients with longer disease duration (for 5 to 10 years: OR, 1.07; 95% CI, 0.75 to 1.52; for ≥ 10 years: OR, 0.92; 95% CI, 0.65 to 1.28). Conclusions Early diagnosis is associated with no functional disability, especially in patients with shorter disease duration. PMID:27618867

Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis

PubMed Central

Montiel-Jarquín, Alvaro José; Pizano-Zárate, María Luisa

2017-01-01

Characterization and understanding of gut microbiota has recently increased representing a wide research field, especially in autoimmune diseases. Gut microbiota is the major source of microbes which might exert beneficial as well as pathogenic effects on human health. Intestinal microbiome's role as mediator of inflammation has only recently emerged. Microbiota has been observed to differ in subjects with early rheumatoid arthritis compared to controls, and this finding has commanded this study as a possible autoimmune process. Studies with intestinal microbiota have shown that rheumatoid arthritis is characterized by an expansion and/or decrease of bacterial groups as compared to controls. In this review, we present evidence linking intestinal dysbiosis with the autoimmune mechanisms involved in the development of rheumatoid arthritis. PMID:28948174

Everyday ethics and help-seeking in early rheumatoid arthritis

PubMed Central

Townsend, A.; Adam, P.; Cox, S.M.; Li, L.C.

2018-01-01

Background Sociological understandings of chronic illness have revealed tensions and complexities around help-seeking. Although ethics underpins healthcare, its application in the area of chronic illness is limited. Here we apply an ethical framework to interview accounts and identify ethical challenges in the early rheumatoid arthritis (RA) experience. Methods In-depth interviews were conducted with eight participants who had been diagnosed with RA in the 12 months prior to recruitment. Applying the concepts of autonomous decision-making and procedural justice highlighted ethical concerns which arose throughout the help-seeking process. Analysis was based on the constant-comparison approach. Results Individuals described decision-making, illness actions and the medical encounter. The process was complicated by inadequate knowledge about symptoms, common-sense understandings about the GP appointment, difficulties concerning access to specialists, and patient–practitioner interactions. Autonomous decision-making and procedural justice were compromised. The accounts revealed contradictions between the policy ideals of active self-management, patient-centred care and shared decision-making, and the everyday experiences of individuals. Conclusions For ethical healthcare there is a need for: public knowledge about early RA symptoms; more effective patient–practitioner communication; and increased support during the wait between primary and secondary care. Healthcare facilities and the government may consider different models to deliver services to people requiring rheumatology consults. PMID:20610465

Matrix-mini-tablets of lornoxicam for targeting early morning peak symptoms of rheumatoid arthritis

PubMed Central

Mohd, Abdul Hadi; Raghavendra Rao, Nidagurthi Guggilla; Avanapu, Srinivasa Rao

2014-01-01

Objective(s): The aim of present research was to develop matrix-mini-tablets of lornoxicam filled in capsule for targeting early morning peak symptoms of rheumatoid arthritis. Materials and Methods: Matrix-mini-tablets of lornoxicam were prepared by direct compression method using microsomal enzyme dependent and pH-sensitive polymers which were further filled into an empty HPMC capsule. To assess the compatibility, FT-IR and DSC studies for pure drug, polymers and their physical mixture were performed. The formulated batches were subjected to physicochemical studies, estimation of drug content, in vitro drug release, drug release kinetics, and stability studies. Results: When FTIR and DSC studies were performed it was found that there was no interaction between lornoxicam and polymers which used. All the physicochemical properties of prepared matrix-mini-tablets were found to be in normal limits. The percentage of drug content was found to be 99.60±0.07%. Our optimized matrix mini-tablets-filled-capsule formulation F30 released lornoxicam after a lag time of 5.02±0.92 hr, 95.48±0.65 % at the end of 8 hr and 99.90±0.83 % at the end of 12 hr. Stability was also found for this formulation as per the guidelines of International Conference on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. Conclusion: A novel colon targeted delivery system of lornoxicam was successfully developed by filling matrix-mini-tablets into an empty HPMC capsule shell for targeting early morning peak symptoms of rheumatoid arthritis. PMID:24967065

A protocol for a randomised controlled trial of prefabricated versus customised foot orthoses for people with rheumatoid arthritis: the FOCOS RA trial [Foot Orthoses - Customised v Off-the-Shelf in Rheumatoid Arthritis].

PubMed

Gallagher, Kellie S; Godwin, Jon; Hendry, Gordon J; Steultjens, Martijn; Woodburn, Jim

2018-01-01

Foot pain is common in rheumatoid arthritis and appears to persist despite modern day medical management. Several clinical practice guidelines currently recommend the use of foot orthoses for the treatment of foot pain in people with rheumatoid arthritis. However, an evidence gap currently exists concerning the comparative clinical- and cost-effectiveness of prefabricated and customised foot orthoses in people with early rheumatoid arthritis. Early intervention with orthotics may offer the best opportunity for positive therapeutic outcomes. The primary aim of this study is to evaluate the comparative clinical- and cost-effectiveness of prefabricated versus customised orthoses for reducing foot pain over 12 months. This is a multi-centre two-arm parallel randomised controlled trial comparing prefabricated versus customised orthoses in participants with early rheumatoid arthritis (< 2 years disease duration). A total of 160 (a minimum of 80 randomised to each arm) eligible participants will be recruited from United Kingdom National Health Service Rheumatology Outpatient Clinics. The primary outcome will be foot pain measured via the Foot Function Index pain subscale at 12 months. Secondary outcomes will include foot related impairments and disability via the Foot Impact Scale for rheumatoid arthritis, global functional status via the Stanford Health Assessment Questionnaire, foot disease activity via the Rheumatoid Arthritis Foot Disease Activity Index, and health-related quality of life at baseline, 6 and 12 months. Process outcomes will include recruitment/retention rates, data completion rates, intervention adherence rates, and participant intervention and trial participation satisfaction. Cost-utility and cost-effectiveness analyses will be undertaken. Outcome measures collected at baseline, 6 and 12 months will be used to evaluate the comparative clinical- and cost- effectiveness of customised versus prefabricated orthoses for this treatment of early

Rheumatoid Arthritis

MedlinePlus

... Rheumatoid Arthritis English Español 繁體中文 한국어 tiếng Việt Rheumatoid Arthritis Basics In-Depth Download Download EPUB Download PDF What is it? Points To Remember About Rheumatoid Arthritis Rheumatoid arthritis is a disease that causes pain, ...

Identification of a transitional fibroblast function in very early rheumatoid arthritis

PubMed Central

Filer, Andrew; Ward, Lewis S C; Kemble, Samuel; Davies, Christopher S; Munir, Hafsa; Rogers, Rebekah; Raza, Karim; Buckley, Christopher Dominic; Nash, Gerard B; McGettrick, Helen M

2017-01-01

Objectives Synovial fibroblasts actively regulate the inflammatory infiltrate by communicating with neighbouring endothelial cells (EC). Surprisingly, little is known about how the development of rheumatoid arthritis (RA) alters these immunomodulatory properties. We examined the effects of phase of RA and disease outcome (resolving vs persistence) on fibroblast crosstalk with EC and regulation of lymphocyte recruitment. Methods Fibroblasts were isolated from patients without synovitis, with resolving arthritis, very early RA (VeRA; symptom ≤12 weeks) and established RA undergoing joint replacement (JRep) surgery. Endothelial-fibroblast cocultures were formed on opposite sides of porous filters. Lymphocyte adhesion from flow, secretion of soluble mediators and interleukin 6 (IL-6) signalling were assessed. Results Fibroblasts from non-inflamed and resolving arthritis were immunosuppressive, inhibiting lymphocyte recruitment to cytokine-treated endothelium. This effect was lost very early in the development of RA, such that fibroblasts no longer suppressed recruitment. Changes in IL-6 and transforming growth factor beta 1 (TGF-β1) signalling appeared critical for the loss of the immunosuppressive phenotype. In the absence of exogenous cytokines, JRep, but not VeRA, fibroblasts activated endothelium to support lymphocyte. Conclusions In RA, fibroblasts undergo two distinct changes in function: first a loss of immunosuppressive responses early in disease development, followed by the later acquisition of a stimulatory phenotype. Fibroblasts exhibit a transitional functional phenotype during the first 3 months of symptoms that contributes to the accumulation of persistent infiltrates. Finally, the role of IL-6 and TGF-β1 changes from immunosuppressive in resolving arthritis to stimulatory very early in the development of RA. Early interventions targeting ‘pathogenic’ fibroblasts may be required in order to restore protective regulatory processes. PMID:28847766

Rheumatoid Nodules.

PubMed

Tilstra, Jeremy S; Lienesch, Douglas W

2015-07-01

Rheumatoid nodules are a common manifestation of rheumatoid arthritis. These lesions are often easily identified based on typical diagnostic features and characteristic locations. When biopsied, nodules have a characteristic histologic appearance. Uncommonly, rheumatoid nodules can occur in systemic locations. There is no evidence that systemic therapy treats underlying rheumatoid nodules. Paradoxically, methotrexate and possibly tumor necrosis factor inhibitors can increase nodule development. Treatment of rheumatoid nodules is often not necessary, unless patients are experiencing pain or there is interference of mechanical function. This review outlines the available data on and associations of rheumatoid nodules. Copyright © 2015 Elsevier Inc. All rights reserved.

Rheumatoid lung disease

MedlinePlus

Lung disease - rheumatoid arthritis; Rheumatoid nodules; Rheumatoid lung ... Lung problems are common in rheumatoid arthritis. They often cause no symptoms. The cause of lung disease associated with rheumatoid arthritis is unknown. Sometimes, the medicines used to ...

Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels

PubMed Central

2014-01-01

Introduction We hypothesized that serum levels of C-X-C motif chemokine 13 (CXCL13), a B-cell chemokine, would delineate a subset of rheumatoid arthritis (RA) patients characterized by increased humoral immunity. Methods Serum from patients with established RA (the Dartmouth RA Cohort) was analyzed for CXCL13, rheumatoid factor (RF) levels, anticitrullinated peptide/protein antibody (ACPA) and total immunoglobulin G (IgG); other parameters were obtained by chart review. A confirmatory analysis was performed using samples from the Sherbrooke Early Undifferentiated PolyArthritis (EUPA) Cohort. The Wilcoxon rank-sum test, a t-test and Spearman’s correlation analysis were utilized to determine relationships between variables. Results In both the Dartmouth and Sherbrooke cohorts, CXCL13 levels were selectively increased in seropositive relative to seronegative RA patients (P = 0.0002 and P < 0.0001 for the respective cohorts), with a strong correlation to both immunoglobulin M (IgM) and IgA RF levels (P < 0.0001). There was a weaker relationship to ACPA titers (P = 0.03 and P = 0.006, respectively) and total IgG (P = 0.02 and P = 0.14, respectively). No relationship was seen with regard to age, sex, shared epitope status or inclusion high-sensitivity C-reactive protein (hsCRP) in either cohort or regarding the presence of baseline erosions in the Sherbrooke Cohort, whereas a modest relationship with Disease Activity Score in 28 joints CRP (DAS28-CRP) was seen in the Dartmouth cohort but not the Sherbrooke cohort. Conclusion Using both established and early RA cohorts, marked elevations of serum CXCL13 levels resided nearly completely within the seropositive population. CXCL13 levels exhibited a strong relationship with RF, whereas the association with clinical parameters (age, sex, DAS28-CRP and erosions) or other serologic markers (ACPA and IgG) was either much weaker or absent. Elevated serum CXCL13 levels may identify a subset of seropositive RA patients whose

Rheumatoid Arthritis

MedlinePlus

... Education Visitor Information RePORT NIH Fact Sheets Home > Rheumatoid Arthritis Small Text Medium Text Large Text Rheumatoid Arthritis Rheumatoid arthritis is an inflammatory disease affecting about ...

Anti-MCV antibodies predict radiographic progression in Greek patients with very early (<3 months duration) rheumatoid arthritis.

PubMed

Barouta, Georgia; Katsiari, Christina G; Alexiou, Ioannis; Liaskos, Christos; Varna, Areti; Bogdanos, Dimitrios P; Germenis, Anastasios E; Sakkas, Lazaros I

2017-04-01

This study aimed to assess the diagnostic and prognostic value of anti-mutated citrullinated vimentin (MCV) antibodies in very early rheumatoid arthritis (VERA) and in established rheumatoid arthritis (RA). Seventy-one patients with undifferentiated arthritis (UA) of <3 months duration, 141 with established RA, 53 with other rheumatic diseases, and 40 healthy individuals were included in the study. Anti-MCV, anti-cyclic citrullinated peptide (CCP) antibodies, and rheumatoid factor (RF) were determined and hand radiographs were recorded. Patients were assessed prospectively for 2 years, and hand radiographs were repeated. Diagnostic performance of anti-MCV was studied with receiver operating characteristic (ROC) curves and evaluation of sensitivity, specificity, and likelihood ratios. Forty-six percent of UA patients progressed to RA at 2 years. In VERA patients, sensitivity of anti-MCV was 52 %, compared to 44 % of anti-CCP and 37 % of RF, while specificity was 91 %, compared to 91 % of RF and 84 % of anti-CCP. Anti-MCV were detected in 25 % of VERA patients negative for both anti-CCP and RF. In established RA, anti-MCV did not sustain its diagnostic performance. By multivariable analysis, anti-MCV, but not anti-CCP or RF, showed significant correlation with radiographic progression in VERA patients. In established RA, anti-MCV, anti-CCP, and RF were associated with active disease (p ≤ 0.03) and joint damage (p ≤ 0.004). By multivariate analysis, the strongest factors for radiographic damage were disease duration (p = 0.000), HAQ score (p = 0.000), and RF (p = 0.002). In conclusion, in patients with very early UA, anti-MCV predict both progression to RA and radiological damage, and therefore, anti-MCV antibody testing may be useful in every day practice.

[The development of a finger joint phantom for the optical simulation of early inflammatory rheumatic changes].

PubMed

Prapavat, V; Runge, W; Mans, J; Krause, A; Beuthan, J; Müller, G

1997-11-01

In the field of rheumatology, conventional diagnostic methods permit the detection only of advanced stages of the disease, which is at odds with the current clinical demand for the early diagnosis of inflammatory rheumatic diseases. Prompted by current needs, we developed a finger joint phantom that enables the optical and geometrical simulation of an early stage of rheumatoid arthritis (RA). The results presented here form the experimental basis for an evaluation of new RA diagnostic systems based on near infrared light. The early stage of RA is characterised mainly by a vigorous proliferation of the synovial membrane and clouding of the synovial fluid. Using a double-integrating-sphere technique, the absorption and scattering coefficients (mua, mus') are experimentally determined for healthy and pathologically altered synovial fluid and capsule tissue. Using a variable mixture of Intralipid Indian ink and water as a scattering/absorption medium, the optical properties of skin, synovial fluid or capsule can be selected individually. Since the optical and geometrical properties of bone tissue remain constant in early-stage RA, a solid material is used for its simulation. Using the finger joint phantom described herein, the optical properties of joint regions can be adjusted specifically, enabling an evaluation of their effects on an optical signal--for example, during fluorography--and the investigation of these effects for diagnostically useful information. The experimental foundation for the development of a new optical system for the early diagnosis of RA has now been laid.

Rheumatoid arthritis in a military aviator.

PubMed

Moszyk, Danielle J; Sulit, Daryl J

2007-01-01

Rheumatoid arthritis is a chronic inflammatory condition whose pathogenesis is determined partially by genetic and environmental factors. Without treatment, 20 to 30% of individuals with this condition will become permanently disabled in a few years. Rheumatoid arthritis and its potential complications can cause significant disability and could seriously affect the performance of an aviator. Traditionally, disease-modifying anti-rheumatic drugs (DMARD) and biologics have not been used until disease progression occurs, but they recently have been added earlier in the course of disease for a more aggressive approach to treatment. It has been shown to significantly reduce the number of affected joints, pain, and disability. This newer treatment regimen has helped a military pilot continue his aviation career. We present the case of an experienced designated military pilot who was diagnosed with rheumatoid arthritis. He was initially treated early with a DMARD and biologic medication. He has remained in remission and currently only uses etanercept (biologic medication) and a non-steriodal anti-inflammatory drug to control his disease. He has responded favorably to therapy and has few limitations. Due to his positive response to treatment, the aviator was granted military aeromedical waivers for rheumatoid arthritis and chronic medication use.

Rheumatoid Vasculitis

MedlinePlus

... RV) is an unusual complication of longstanding, severe rheumatoid arthritis. The active vasculitis associated with rheumatoid disease occurs ... a manifestation of “extra-articular” (beyond the joint)rheumatoid arthritis and involves the small and medium-sized arteries ...

Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia

PubMed Central

Lequerré, Thierry; Bansard, Carine; Vittecoq, Olivier; Derambure, Céline; Hiron, Martine; Daveau, Maryvonne; Tron, François; Ayral, Xavier; Biga, Norman; Auquit-Auckbur, Isabelle; Chiocchia, Gilles; Le Loët, Xavier; Salier, Jean-Philippe

2009-01-01

Introduction Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia. Methods Synovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of early, LS RA and healthy synovia were linked to the biological processes involved in each situation. Results Three combinations of 719, 116 and 52 transcripts discriminated, respectively, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA. Conclusions Early and LS RA have distinct molecular signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment. PMID:19563633

The first national clinical audit for rheumatoid arthritis.

PubMed

Firth, J; Snowden, N; Ledingham, J; Rivett, A; Galloway, J; Dennison, E M; MacPhie, E; Ide, Z; Rowe, I; Kandala, N; Jameson, K

The first national audit for rheumatoid and early inflammatory arthritis has benchmarked care for the first 3 months of follow-up activity from first presentation to a rheumatology service. Access to care, management of early rheumatoid arthritis and support for self care were measured against National Institute for Health and Care Excellence quality standards; impact of early arthritis and experience of care were measured using patient-reported outcome and experience measures. The results demonstrate delays in referral and accessing specialist care and the need for service improvement in treating to target, suppression of high levels of disease activity and support for self-care. Improvements in patient-reported outcomes within 3 months and high levels of overall satisfaction were reported but these results were affected by low response rates. This article presents a summary of the national data from the audit and discusses the implications for nursing practice.

[Current treatment of rheumatoid arthritis].

PubMed

Carli, P; Landais, C; Aletti, M; Cournac, J-M; Poisnel, E; Paris, J-F

2009-12-01

Over the past 10 years, the management of rheumatoid arthritis has been revolutionized. Early diagnosis is essential and should allow an early initiation of disease modifying anti-rheumatic drugs (DMARD), if possible within the first 3 three months after disease onset, aiming at disease remission and the best long-term prognosis. Recommendations for the prescription of synthetic and biologic DMARD (mainly anti-TNFalpha agents) are available since September 2007 [6] by HAS in France. The great efficacy of these drugs has been established from many clinical trials including tens of thousands of patients. However, severe adverse side effects may occur (allergy, tuberculosis, opportunistic infections, demyelination) and rheumatologists should remain vigilant. Global care of the patient includes prescription of pharmacologic and non-pharmacologic treatments (education, physical treatment, ergotherapy, psychotherapy, surgery). A good coordination between all specialists is required. Screening and treatment of extra-articular manifestations, prevention of infections, osteoporosis and cardiovascular complications are essential to allow a better long-term prognosis, and reduce disability and mortality of rheumatoid arthritis.

[Imaging in rheumatoid arthritis of the elbow].

PubMed

Lerch, K; Herold, T; Borisch, N; Grifka, J

2003-08-01

Early specific radiologic changes of rheumatoid arthritis can usually be detected in the hands and feet. Later stages of the disease process show a typical centripetal spread of the affected joints, i.e., shoulder, elbow, and knee. For prognostic assessment of cubital rheumatoid arthritis, conventional radiography still remains the gold standard. X-rays allow objective scoring and thus classification into standardized stages. A concentric destruction of the rheumatic joint as compared to deformity in the degenerative joint is the typical radiologic symptom to look for. For soft tissue assessment, ultrasound (US) should be the diagnostic tool of choice. Due to the thin surrounding soft tissue layer, as well as the advanced high-resolution technology, bony structures can also be well demonstrated in any plane. In the early arthritic stages, particularly the small changes, e.g., minimal erosions of the cortical area, are very well detectable by US. The use of "color" allows good evaluation of the synovial inflammatory status. Modern imaging methods such as computer- assisted tomography (CAT) scan and magnetic resonance imaging (MRI) are restricted to a few set indications and should not be chosen for routine examination. More invasive methods such as arthrography are no longer indicated for assessment of cubital rheumatoid arthritis.

The interleukin-20 receptor axis in early rheumatoid arthritis: novel links between disease-associated autoantibodies and radiographic progression.

PubMed

Kragstrup, Tue Wenzel; Greisen, Stinne Ravn; Nielsen, Morten Aagaard; Rhodes, Christopher; Stengaard-Pedersen, Kristian; Hetland, Merete Lund; Hørslev-Petersen, Kim; Junker, Peter; Østergaard, Mikkel; Hvid, Malene; Vorup-Jensen, Thomas; Robinson, William H; Sokolove, Jeremy; Deleuran, Bent

2016-03-11

Rheumatoid arthritis (RA) is often characterized by the presence of rheumatoid factor, anti-citrullinated protein antibodies, and bone erosions. Current therapies can compromise immunity, leading to risk of infection. The interleukin-20 receptor (IL-20R) axis comprising IL-19, IL-20, and IL-24 and their shared receptors activates tissue homeostasis processes but not the immune system. Consequently, modulation of the IL-20R axis may not lead to immunosuppression, making it an interesting drug target. We evaluated the role of the IL-20R axis in RA and associations between plasma cytokine levels and clinical disease. Plasma IL-19, IL-20, and IL-24 levels were measured in early RA patients during a treat-to-target strategy by enzyme-linked immunosorbent assays. The IL-20R1 and IL-22R1 levels in paired peripheral blood mononuclear cells and synovial fluid mononuclear cells from a different cohort of RA patients were evaluated by flow cytometry and confocal microscopy. Monocytes/macrophages were stimulated with heat-aggregated human immunoglobulin immune complexes and immune complexes containing citrullinated fibrinogen, and osteoclasts were incubated with IL-19, IL-20, and IL-24. The plasma concentrations of IL-20 and IL-24 (but not IL-19) were increased in early RA patients compared with healthy controls (both P < 0.002) and decreased after 6 months of treatment (both P < 0.0001). The expression of IL-22R1 (but not IL-20R1) was increased on monocytes from RA synovial fluid compared with monocytes from both RA and healthy control peripheral blood. The plasma concentrations of IL-20 and IL-24 were increased in rheumatoid factor and anti-citrullinated protein antibody positive compared with negative early RA patients (all P < 0.0001). Immune complexes stimulated the production of the IL-20R cytokines by monocytes/macrophages. Increased baseline plasma concentrations of IL-20 and IL-24 were associated with Sharp-van der Heijde score progression after 24�

Dilemmas of participation in everyday life in early rheumatoid arthritis: a qualitative interview study (The Swedish TIRA Project).

PubMed

Sverker, Annette; Östlund, Gunnel; Thyberg, Mikael; Thyberg, Ingrid; Valtersson, Eva; Björk, Mathilda

2015-01-01

To explore the experiences of today's patients with early rheumatoid arthritis (RA) with respect to dilemmas of everyday life, especially regarding patterns of participation restrictions in valued life activities. A total of 48 patients, aged 20-63, three years post-RA diagnosis were interviewed using the Critical Incident Technique. Transcribed interviews were condensed into meaningful units describing actions/situations. These descriptions were linked to ICF participation codes according to the International Classification of Functioning, Disability and Health (ICF) linking rules. Dilemmas in everyday life were experienced in domestic life, interpersonal interactions and relationships, community, social and civic life. Most dilemmas were experienced in domestic life, including participation restrictions in, e.g. gardening, repairing houses, shovelling snow, watering pot plants, sewing or walking the dog. Also many dilemmas were experienced related to recreation and leisure within the domain community, social and civic life. The different dilemmas were often related to each other. For instance, dilemmas related to community life were combined with dilemmas within mobility, such as lifting and carrying objects. Participation restrictions in today's RA patients are complex. Our results underline that the health care needs to be aware of the patients' own preferences and goals to support the early multi-professional interventions in clinical practice. Implications of Rehabilitation Today's rheumatoid arthritis (RA) patients experience participation restrictions in activities not included in International Classification of Functioning, Disability and Health (ICF) core set for RA or in traditionally questionnaires with predefined activities. The health care need to be aware of the patients' own preferences and goals to meet the individual needs and optimize the rehabilitation in early RA in clinical practice.

Discordant inflammation and pain in early and established rheumatoid arthritis: Latent Class Analysis of Early Rheumatoid Arthritis Network and British Society for Rheumatology Biologics Register data.

PubMed

McWilliams, Daniel F; Ferguson, Eamonn; Young, Adam; Kiely, Patrick D W; Walsh, David A

2016-12-13

Rheumatoid arthritis (RA) disease activity is often measured using the 28-joint Disease Activity Score (DAS28). We aimed to identify and independently verify subgroups of people with RA that may be discordant with respect to self-reported and objective disease state, with potentially different clinical needs. Data were derived from three cohorts: (1) the Early Rheumatoid Arthritis Network (ERAN) and the British Society for Rheumatology Biologics Register (BSRBR), (2) those commencing tumour necrosis factor (TNF)-α inhibitors and (3) those using non-biologic drugs. In latent class analysis, we used variables related to pain, central pain mechanisms or inflammation (pain, vitality, mental health, erythrocyte sedimentation rate, swollen joint count, tender joint count, visual analogue scale of general health). Clinically relevant outcomes were examined. Five, four and four latent classes were found in the ERAN, BSRBR TNF inhibitor and non-biologic cohorts, respectively. The proportions of people assigned with >80% probability into latent classes were 76%, 58% and 72% in the ERAN, TNF inhibitor and non-biologic cohorts, respectively. The latent classes displayed either concordance between measures indicative of mild, moderate or severe disease activity; discordantly worse patient-reported measures despite less markedly elevated inflammation; or discordantly less severe patient-reported measures despite elevated inflammation. Latent classes with discordantly worse patient-reported measures represented 12%, 40% and 21% of the ERAN, TNF inhibitor and non-biologic cohorts, respectively; contained more females; and showed worse function. In those latent classes with worse scores at baseline, DAS28 and function improved over 1 year (p < 0.001 for all comparisons), and scores differed less at follow-up than at baseline. Discordant latent classes can be identified in people with RA, and these findings are robust across three cohorts with varying disease duration and

Longitudinal study of clinical prognostic factors in patients with early rheumatoid arthritis: the PREDICT study.

PubMed

Bird, Paul; Nicholls, Dave; Barrett, Rina; de Jager, Julien; Griffiths, Hedley; Roberts, Lynden; Tymms, Kathleen; McCloud, Philip; Littlejohn, Geoffrey

2017-04-01

To assess the association between baseline clinical prognostic factors and subsequent Disease Activity Score of 28 joints (DAS28) remission in early rheumatoid arthritis (RA). Data were collected using point of care clinical software from participating rheumatology centres. Patients aged 18 years or over whose date of clinical onset of RA was within the previous 12-24 months, who had at least 6 months of follow-up data and a DAS28-ESR (erythrocyte sedimentation rate) score recorded between 12 and 24 months from first being seen for RA were included. Data collected included baseline demographics, mode of disease onset, pattern of joint involvement at onset, smoking status, DAS28, rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), time from symptom onset to presentation and disease activity at baseline. Univariate and multivariate logistic regression of DAS28-ESR remission between 12 and 24 months after first assessment were performed. Data from 1017 patients were analyzed: 70% female; mean age 60 years (SD: 14.7); 70% RF-positive, 58% ACPA-positive. The strongest age and sex adjusted baseline predictors of DAS28-ESR remission at 12-24 months were remission at baseline (odds ratio [OR]: 4.49, 95% CI: 2.17-9.29, P < 0.001), being male (OR: 2.42, 95% CI: 1.46-4.01, P < 0.001), abstaining from alcohol (P < 0.001) and being lower weight (OR: 0.98, 95% CI: 0.97-1.00, P = 0.015). There was no statistically significant association between joint onset patterns, mode of onset, RF, ACPA or smoking status. In this observational study, patients with early RA at risk of not achieving remission include those with high disease activity at baseline, women, those who drink alcohol and those with higher body weight. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

[Financial cost of early rheumatoid arthritis in the first year of medical attention: three clinical scenarios in a third-tier university hospital in Colombia].

PubMed

Mora, Claudia; González, Andrés; Díaz, Jorge; Quintana, Gerardo

2009-03-01

In Colombia, the cost burden of chronic diseases is not well known, either globally or in localized areas of the health system. Rheumatoid arthritis is one of most common chronic diseases, and represents a high cost for the health system. The direct medical costs were estimated for rheumatoid arthritis patients in the in the first year of diagnosis at a level 3 university hospital in Colombia. Three therapy settings for early rheumatoid arthritis patients were established in the first year of diagnosis according to national and international guidelines. Each setting included treatment with disease-modifying anti-rheumatic drugs or biologic therapy based on disease severity as measured by Disease Activity Score 28. All direct medical costs were included: specialized medical care, diagnostic tests and drugs. Cost information was obtained from the Central Military Hospital finance department in Bogotá and the national manual of drug prices based on the "Farmaprecios" 2007 guide, a reference in general use by health institutions. Results. The average of cost of medical care in patients with mild, moderate and severe disease was US $1689, $1805 and $23,441 respectively. The recommended retail prices of the medicines published in "Farmaprecios" was US $1418, $1821 and $31,931. When the charges levied by several major health institutions were compared, substantial increases were noted, US $4936, $7716 and $123,661, respectively. Drug costs represented 86% of total cost, laboratory costs were 10% and medical attention was only 4%. Drugs costs were the principal component of the total direct medical cost, and it increased 40 times when a biological therapy is used. Complete economic evaluation studies are necesary to estimate the viability and clinical relevance of biological therapy for early rheumatoid arthritis.

Comparison of composite measures of disease activity in an early seropositive rheumatoid arthritis cohort

PubMed Central

Ranganath, Veena K; Yoon, Jeonglim; Khanna, Dinesh; Park, Grace S; Furst, Daniel E; Elashoff, David A; Jawaheer, Damini; Sharp, John T; Gold, Richard H; Keystone, Edward C; Paulus, Harold E

2007-01-01

Objective To evaluate concordance and agreement of the original DAS44/ESR‐4 item composite disease activity status measure with nine simpler derivatives when classifying patient responses by European League of Associations for Rheumatology (EULAR) criteria, using an early rheumatoid factor positive (RF+) rheumatoid arthritis (RA) patient cohort. Methods Disease‐modifying anti‐rheumatic drug‐naïve RF+ patients (n = 223; mean duration of symptoms, 6 months) were categorised as ACR none/20/50/70 responders. One‐way analysis of variance and two‐sample t tests were used to investigate the relationship between the ACR response groups and each composite measure. EULAR reached/change cut‐point scores were calculated for each composite measure. EULAR (good/moderate/none) responses for each composite measure and the degree of agreement with the DAS44/ESR‐4 item were calculated for 203 patients. Results Patients were mostly female (78%) with moderate to high disease activity. A centile‐based nomogram compared equivalent composite measure scores. Changes from baseline in the composite measures in patients with ACRnone were significantly less than those of ACR20/50/70 responders, and those for ACR50 were significantly different from those for ACR70. EULAR reached/change cut‐point scores for our cohort were similar to published cut‐points. When compared with the DAS44/ESR‐4 item, EULAR (good/moderate/none) percentage agreements were 92 with the DAS44/ESR‐3 item, 74 with the Clinical Disease Activity Index, and 80 with the DAS28/ESR‐4 item, the DAS28/CRP‐4 item and the Simplified Disease Activity Index. Conclusion The relationships of nine different RA composite measures against the DAS44/ESR‐4 item when applied to a cohort of seropositive patients with early RA are described. Each of these simplified status and response measures could be useful in assessing patients with RA, but the specific measure selected should be pre‐specified and

Role of erosions typical of rheumatoid arthritis in the 2010 ACR/EULAR rheumatoid arthritis classification criteria: results from a very early arthritis cohort.

PubMed

Brinkmann, Gina Hetland; Norli, Ellen S; Bøyesen, Pernille; van der Heijde, Désirée; Grøvle, Lars; Haugen, Anne J; Nygaard, Halvor; Bjørneboe, Olav; Thunem, Cathrine; Kvien, Tore K; Mjaavatten, Maria D; Lie, Elisabeth

2017-11-01

To determine how the European League Against Rheumatism (EULAR) definition of erosive disease (erosion criterion) contributes to the number of patients classified as rheumatoid arthritis (RA) according to the 2010 American College of Rheumatology/EULAR RA classification criteria (2010 RA criteria) in an early arthritis cohort. Patients from the observational study Norwegian Very Early Arthritis Clinic with joint swelling ≤16 weeks, a clinical diagnosis of RA or undifferentiated arthritis, and radiographs of hands and feet were included. Erosive disease was defined according to the EULAR definition accompanying the 2010 RA criteria. We calculated the additional number of patients being classified as RA based on the erosion criteria at baseline and during follow-up. Of the 289 included patients, 120 (41.5%) fulfilled the 2010 RA criteria, whereas 15 (5.2%) fulfilled only the erosion criterion at baseline. 118 patients had radiographic follow-up at 2 years, of whom 6.8% fulfilled the 2010 RA criteria and only one patient fulfilled solely the erosion criterion during follow-up. Few patients with early arthritis were classified as RA based on solely the erosion criteria, and of those who did almost all did so at baseline. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Rheumatoid arthritis

MedlinePlus

... this page: //medlineplus.gov/ency/article/000431.htm Rheumatoid arthritis To use the sharing features on this page, please enable JavaScript. Rheumatoid arthritis (RA) is a long-term disease. It leads ...

The combination of three autoantibodies, ACPA, RF and anti-CarP antibodies is highly specific for rheumatoid arthritis: implications for very early identification of individuals at risk to develop rheumatoid arthritis.

PubMed

Verheul, Marije K; Böhringer, Stefan; van Delft, Myrthe A M; Jones, Jonathan D; Rigby, William F C; Gan, Ryan W; Holers, V Michael; Edison, Jess D; Deane, Kevin D; Janssen, Koen M J; Westra, Johanna; Brink, Mikael; Rantapää-Dahlqvist, Solbritt; Huizinga, Tom W J; van der Helm-van Mil, Annette H M; van der Woude, Diane; Toes, Rene E M; Trouw, Leendert A

2018-05-21

In rheumatoid arthritis(RA), the autoantibodies anti-citrullinated protein antibodies(ACPA) and rheumatoid factor(RF) are commonly used to aid RA diagnosis. Although these autoantibodies are mainly found in RA, their specificity is not optimal. It is therefore difficult to identify RA patients, especially in very early disease, based on the presence of ACPA and RF alone. Also, anti-carbamylated protein(anti-CarP) antibodies have diagnostic and prognostic value as the presence of anti-CarP antibodies associates with joint damage in RA patients and with future RA development in arthralgia patients. Therefore, we aimed to investigate the value of combined antibody testing in relation to prediction and diagnosis of (early) RA. A literature search resulted in twelve studies, consisting of RA patients, pre-RA individuals, disease controls, healthy first-degree relatives of RA patients or healthy controls, in which data on RF, ACPA and anti-CarP antibody-status was available. Random effects meta-analyses were carried out for several antibody combinations. The individual antibodies are highly prevalent in RA(34%-80%) compared to the control groups, but are also present in non-RA controls(0%-23%). To classify most people correctly as RA or non-RA, the combination of ACPA and/or RF often performs well(specificity:65-100, sensitivity:59-88). However, triple positivity for ACPA, RF and anti-CarP antibodies results in a higher specificity(98-100) (accompanied by a lower sensitivity(11-39)). As the rheumatology field is moving towards very early identification of RA and possible screening for individuals at maximum risk in populations with a low pre-test probability, triple positivity provides interesting information on individuals at risk to develop RA. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Rheumatoid Arthritis

MedlinePlus

Rheumatoid arthritis (RA) is a form of arthritis that causes pain, swelling, stiffness and loss of function in ... wrist and fingers. More women than men get rheumatoid arthritis. It often starts in middle age and is ...

Rheumatoid meningitis.

PubMed

Nihat, Akin; Chinthapalli, Krishna; Bridges, Leslie; Johns, Paul; Sofat, Nidhi; Moynihan, Barry

2016-08-01

Rheumatoid meningitis is a rare, potentially treatable condition that can mimic a wide range of neurological conditions, including vascular syndromes and encephalopathies. Despite a concurrent history of rheumatoid arthritis, patients often have no active synovitis. Here we describe a patient with rheumatoid meningitis who presented to a hyperacute stroke unit with dysarthria on waking and transient facial droop. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Rheumatoid Cachexia Revisited: A Metabolic Co-Morbidity in Rheumatoid Arthritis

PubMed Central

Masuko, Kayo

2014-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, play a crucial role. The chronic inflammation, combined with reduced physical activity, leads to muscle wasting whereas fat mass would be maintained; the resulting abnormal metabolic state is described as rheumatoid cachexia. Since the loss of muscle volume would be compensated by the increased fat mass, body mass index (BMI) is reported not to reflect the nutritional status in RA patients. The implication of rheumatoid cachexia for cardiovascular risk and clinical prognosis is not clearly understood, however, adequate control of disease activity in combination with appropriate physical exercise could be the most important strategy to control rheumatoid cachexia and related metabolic problems. PMID:25988122

Treating to the target of remission in early rheumatoid arthritis is cost-effective: results of the DREAM registry.

PubMed

Vermeer, Marloes; Kievit, Wietske; Kuper, Hillechiena H; Braakman-Jansen, Louise M A; Bernelot Moens, Hein J; Zijlstra, Theo R; den Broeder, Alfons A; van Riel, Piet L C M; Fransen, Jaap; van de Laar, Mart A F J

2013-12-13

Where health economic studies are frequently performed using modelling, with input from randomized controlled trials and best guesses, we used real-life data to analyse the cost-effectiveness and cost-utility of a treatment strategy aiming to the target of remission compared to usual care in early rheumatoid arthritis (RA). We used real-life data from comparable cohorts in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry: the DREAM remission induction cohort (treat-to-target, T2T) and the Nijmegen early RA inception cohort (usual care, UC). Both cohorts were followed prospectively using the DREAM registry methodology. All patients fulfilled the American College of Rheumatology criteria for RA and were included in the cohort at the time of diagnosis. The T2T cohort was treated according to a protocolised strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6). The UC cohort was treated without DAS28-guided treatment decisions. EuroQol-5D utility scores were estimated from the Health Assessment Questionnaire. A health care perspective was adopted and direct medical costs were collected. The incremental cost effectiveness ratio (ICER) per patient in remission and incremental cost utility ratio (ICUR) per quality-adjusted life year (QALY) gained were calculated over two and three years of follow-up. Two year data were available for 261 T2T patients and 213 UC patients; an extended follow-up of three years was available for 127 and 180 patients, respectively. T2T produced higher remission percentages and a larger gain in QALYs than UC. The ICER was € 3,591 per patient in remission after two years and T2T was dominant after three years. The ICUR was € 19,410 per QALY after two years and T2T was dominant after three years. We can conclude that treating to the target of remission in early RA is cost-effective compared with UC. The data suggest that in the third year, T2T becomes cost-saving.

Emerging trends in diagnosis and treatment of rheumatoid arthritis.

PubMed

Birch, James T; Bhattacharya, Shelley

2010-12-01

Rheumatoid arthritis is an inflammatory disease of the joints causing pain and stiffness, pathologically characterized by chronic synovitis. Without proper treatment, it progresses to cause joint deformity that results in significant loss of function. Extra-articular disease can also occur, which exacerbates morbidity and mortality associated with the disease. Patients from all age groups can acquire the disease, hence the additional categories of juvenile onset and elderly onset rheumatoid arthritis. Disease-modifying antirheumatic drugs are the mainstay of therapy, and should be initiated as early as possible in the course of the disease in consultation with a rheumatologist. Copyright © 2010 Elsevier Inc. All rights reserved.

Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients.

PubMed

Taylor, John C; Bongartz, Tim; Massey, Jonathan; Mifsud, Borbala; Spiliopoulou, Athina; Scott, Ian C; Wang, Jianmei; Morgan, Michael; Plant, Darren; Colombo, Marco; Orchard, Peter; Twigg, Sarah; McInnes, Iain B; Porter, Duncan; Freeston, Jane E; Nam, Jackie L; Cordell, Heather J; Isaacs, John D; Strathdee, Jenna L; Arnett, Donna; de Hair, Maria J H; Tak, Paul P; Aslibekyan, Stella; van Vollenhoven, Ronald F; Padyukov, Leonid; Bridges, S Louis; Pitzalis, Costantino; Cope, Andrew P; Verstappen, Suzanne M M; Emery, Paul; Barnes, Michael R; Agakov, Felix; McKeigue, Paul; Mushiroda, Taisei; Kubo, Michiaki; Weinshilboum, Richard; Barton, Anne; Morgan, Ann W; Barrett, Jennifer H

2018-05-25

Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10 -7 for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous.

Effective Treatment for Rapid Improvement of Both Disease Activity and Self-Reported Physical Activity in Early Rheumatoid Arthritis.

PubMed

Konijn, Nicole P C; van Tuyl, Lilian H D; Boers, Maarten; den Uyl, Debby; Ter Wee, Marieke M; Kerstens, Pit; Voskuyl, Alexandre E; Nurmohamed, Michael; van Schaardenburg, Dirkjan; Lems, Willem F

2016-02-01

To investigate the longitudinal relationship between disease activity and self-reported physical activity (PA) in patients with early rheumatoid arthritis during the first year of treatment with combination therapy. PA was measured with the Short Questionnaire to Assess Health-Enhancing Physical Activity at baseline, 13 weeks, 26 weeks, and 52 weeks after start of treatment in the context of the Combinatietherapie Bij Reumatoïde Artritis-Light trial. The reported PA classified patients as meeting or not meeting the World Health Organization (WHO) PA guideline (cutoff: 150 minutes of moderate-to-intense activity per week). Other measurements included the Disease Activity Score (DAS). Since both treatment arms showed equal treatment effect, these were analyzed as 1 group with simple before-after analyses and generalized estimating equations (GEE). In these analyses, 140 patients (86% of the trial population, 66% women, mean age 52 years) with complete data were included. At entry, 69% of the patients met the WHO PA guideline, increasing to 90% at week 13, and remaining stable at 89% after 1 year (P < 0.001). Mean DAS improved from 4.0 to 1.8 during the first year of treatment (P < 0.001). In GEE analyses, DAS decreases were significantly associated with PA increases (P = 0.008). Patients with clinically relevant responses (expressed as DAS remission, European League Against Rheumatism good response or American College of Rheumatology criteria for 70% improvement response) showed higher PA levels compared to nonresponders, regardless of the definition of response, for both the WHO and Dutch PA guideline. Early rheumatoid arthritis patients using combination therapy improved both disease activity and PA, a beneficial effect persisting for at least 1 year. © 2016, American College of Rheumatology.

Rheumatoid arthritis (image)

MedlinePlus

Rheumatoid arthritis is an autoimmune disease in which the body's immune system attacks itself. The pattern of joints ... other joints and is worse in the morning. Rheumatoid arthritis is also a systemic disease, involving other body ...

Serum Biomarkers for Discrimination between Hepatitis C-Related Arthropathy and Early Rheumatoid Arthritis.

PubMed

Siloşi, Isabela; Boldeanu, Lidia; Biciuşcă, Viorel; Bogdan, Maria; Avramescu, Carmen; Taisescu, Citto; Padureanu, Vlad; Boldeanu, Mihail Virgil; Dricu, Anica; Siloşi, Cristian Adrian

2017-06-19

In the present study, we aimed to estimate the concentrations of cytokines (interleukin 6, IL-6, tumor necrosis factor-α, TNF-α) and auto-antibodies (rheumatoid factor IgM isotype, IgM-RF, antinuclear auto-antibodies, ANA, anti-cyclic citrullinated peptide antibodies IgG isotype, IgG anti-CCP3.1, anti-cardiolipin IgG isotype, IgG anti-aCL) in serum of patients with eRA (early rheumatoid arthritis) and HCVrA (hepatitis C virus-related arthropathy) and to assess the utility of IL-6, TNF-α together with IgG anti-CCP and IgM-RF in distinguishing between patients with true eRA and HCVrA, in the idea of using them as differential immunomarkers. Serum samples were collected from 54 patients (30 diagnosed with eRA-subgroup 1 and 24 with HCVrA-subgroup 2) and from 28 healthy control persons. For the evaluation of serum concentrations of studied cytokines and auto-antibodies, we used immunoenzimatique techniques. The serum concentrations of both proinflammatory cytokines were statistically significantly higher in patients of subgroup 1 and subgroup 2, compared to the control group ( p < 0.0001). Our study showed statistically significant differences of the mean concentrations only for ANA and IgG anti-CCP between subgroup 1 and subgroup 2. We also observed that IL-6 and TNF-α better correlated with auto-antibodies in subgroup 1 than in subgroup 2. In both subgroups of patients, ROC curves indicated that IL-6 and TNF-α have a higher diagnostic utility as markers of disease. In conclusion, we can say that, due to high sensitivity for diagnostic accuracy, determination of serum concentrations of IL-6 and TNF-α, possibly in combination with auto-antibodies, could be useful in the diagnosis and distinguishing between patients with true eRA and HCV patients with articular manifestation and may prove useful in the monitoring of the disease course.

Genetics Home Reference: rheumatoid arthritis

MedlinePlus

... Email Facebook Twitter Home Health Conditions Rheumatoid arthritis Rheumatoid arthritis Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Rheumatoid arthritis is a disease that causes chronic abnormal inflammation, ...

Rheumatoid Arthritis Educational Video Series

MedlinePlus Videos and Cool Tools

... Corner / Patient Webcasts / Rheumatoid Arthritis Educational Video Series Rheumatoid Arthritis Educational Video Series This series of five videos was designed to help you learn more about Rheumatoid Arthritis (RA). You will learn how the diagnosis of ...

A Systematic Review of Serum Biomarkers Anti-Cyclic Citrullinated Peptide and Rheumatoid Factor as Tests for Rheumatoid Arthritis

PubMed Central

Taylor, Peter; Gartemann, Juliane; Hsieh, Jeanie; Creeden, James

2011-01-01

This systematic review assesses the current status of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) tests in the diagnosis and prognosis of rheumatoid arthritis (RA). We reviewed publications on tests and biomarkers for early diagnosis of RA from English-language MEDLINE-indexed journals and non-MEDLINE-indexed sources. 85 publications were identified and reviewed, including 68 studies from MEDLINE and 17 non-MEDLINE sources. Anti-CCP2 assays provide improved sensitivity over anti-CCP assays and RF, but anti-CCP2 and RF assays in combination demonstrate a positive predictive value (PPV) nearing 100%, greater than the PPV of either of the tests alone. The combination also appears to be able to distinguish between patients whose disease course is expected to be more severe and both tests are incorporated in the 2010 ACR Rheumatoid Arthritis Classification Criteria. While the clinical value of anti-CCP tests has been established, differences in cut-off values, sensitivities and specificities exist between first-, second- and third-generation tests and harmonization efforts are under way. Anti-CCP and RF are clinically valuable biomarkers for the diagnosis and prognosis of RA patients. The combination of the two biomarkers in conjunction with other clinical measures is an important tool for the diagnosis and management of RA patients. PMID:21915375

Current concepts regarding pharmacologic treatment of rheumatoid and osteoarthritis.

PubMed

Wildy, K S; Wasko, M C

2001-05-01

Treating patients with osteoarthritis (OA) and rheumatoid arthritis (RA) remains challenging; however, new agents offer the chance for an improved quality of life. As an alternative to traditional nonsteroidal anti-inflammatories, cyclooxygenase-2 inhibitors provide pain relief for OA and RA patients with possible fewer side effects. Otherwise, OA patients may opt for topical agents, injections, or supplements. Rheumatoid arthritis research has led to an improved understanding of the inflammatory cascade and an appreciation of the early tissue destruction. A new treatment philosophy has thus emerged along with the development of new biologic agents; the latter, along with combination therapy and a new disease modifying antirheumatic drug, leflunomide, have greatly expanded the chances for disease control in RA patients.

Early Psoriatic Arthritis Versus Early Seronegative Rheumatoid Arthritis: Role of Dermoscopy Combined with Ultrasonography for Differential Diagnosis.

PubMed

Zabotti, Alen; Errichetti, Enzo; Zuliani, Francesca; Quartuccio, Luca; Sacco, Stefania; Stinco, Giuseppe; De Vita, Salvatore

2018-05-01

Exclusion of psoriatic skin/nail lesions is important in differentiating early seronegative rheumatoid arthritis (ERA) from early polyarticular psoriatic arthritis (EPsA) and such manifestations may go unnoticed in atypical or minimally expressed cases. The aim of this study is to assess the usefulness of integrated rheumatological-dermatological evaluation in highlighting dermatological lesions missed on rheumatological examination and to investigate the role of ultrasonography (US) and dermoscopy in improving the recognition of subclinical psoriatic findings. Patients with a new diagnosis of seropositive or seronegative ERA and EPsA with prevalent hands involvement were recruited. All were reassessed for the presence of psoriatic lesions during an integrated rheumatological-dermatological clinical evaluation and underwent hands US and proximal nailfold dermoscopy. Seventy-three consecutive subjects were included in the study: 25 with seropositive ERA, 23 with seronegative ERA, and 25 with EPsA. One-fourth of the subjects initially diagnosed as seronegative ERA presented cutaneous or nail psoriasis on integrated rheumatological-dermatological evaluation, thereby being reclassified as EPsA. The presence of at least 1 extrasynovial feature on hand US and dotted vessels on proximal nailfold dermoscopy was significantly associated with EPsA, with a sensitivity of 68.0% and 96.0% and a specificity of 88.1% and 83.3% for US and dermoscopy, respectively. When used together, specificity for PsA diagnosis raised to 90.5%. Integrated rheumatological-dermatological clinical evaluation may be helpful in identifying patients with EPsA misclassified as seronegative ERA. Additionally, US and dermoscopy may be used as supportive tools in identifying subclinical psoriatic features, which may come in handy in distinguishing EPsA from ERA.

Review article: moving towards common therapeutic goals in Crohn's disease and rheumatoid arthritis.

PubMed

Allen, P B; Olivera, P; Emery, P; Moulin, D; Jouzeau, J-Y; Netter, P; Danese, S; Feagan, B; Sandborn, W J; Peyrin-Biroulet, L

2017-04-01

Crohn's disease (CD) and rheumatoid arthritis are chronic, progressive and disabling conditions that frequently lead to structural tissue damage. Based on strategies originally developed for rheumatoid arthritis, the treatment goal for CD has recently moved from exclusively controlling symptoms to both clinical remission and complete mucosal healing (deep remission), with the final aim of preventing bowel damage and disability. To review the similarities and differences in treatment goals between CD and rheumatoid arthritis. This review examined manuscripts from 1982 to 2016 that discussed and/or proposed therapeutic goals with their supportive evidence in CD and rheumatoid arthritis. Proposed therapeutic strategies to improve outcomes in both rheumatoid arthritis and CD include: (i) evaluation of musculoskeletal or organ damage and disability, (ii) tight control, (iii) treat-to-target, (iv) early intervention and (v) disease modification. In contrast to rheumatoid arthritis, there is a paucity of disease-modification trials in CD. Novel therapeutic strategies in CD based on tight control of objective signs of inflammation are expected to change disease course and patients' lives by halting progression or, ideally, preventing the occurrence of bowel damage. Most of these strategies require validation in prospective studies, whereas several disease-modification trials have addressed these issues in rheumatoid arthritis over the last decade. The recent approval of new drugs in CD such as vedolizumab and ustekinumab should facilitate initiation of disease-modification trials in CD in the near future. © 2017 John Wiley & Sons Ltd.

Prevalence of Asymptomatic Arterial Hypertension and Its Correlation with Inflammatory Activity in Early Rheumatoid Arthritis.

PubMed

Bajraktari, Ismet H; Rexhepi, Sylejman; Berisha, Idriz; Lahu, Ali; Kryeziu, Avni; Durmishi, Bastri; Bajraktari, Halit; Bahtiri, Elton

2017-08-15

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that worsens during the course of the disease and can cause disability. Early RA refers to the onset of symptoms within the past 3 months. In RA, increased levels of mediators of inflammation may cause arterial stiffness consequently leading to arterial hypertension. The aim of this cross-sectional study was to assess the prevalence of asymptomatic arterial hypertension in early RA patients as well as the correlation with parameters of inflammation. One hundred and seventy-nine early RA patients diagnosed in agreement with ACR/EULAR (American College of Rheumatology/ European League against Rheumatism) 2010 criteria were consecutively included in the study. CRP (C-reactive protein) and anti CCP (Antibodies to cyclic citrullinated peptides) serum levels, WBC (white blood cells) count and ESR (Erythrocyte sedimentation rate), likewise DAS-28 (28-joint disease activity score) were determined in all included patients. Parametric tests were used to compare the characteristics of the groups and to test the correlation of the variables. Statistical data analysis revealed that a majority of the patients were females (n = 141; 78.7%); the mean age at RA onset was 49.13 ± 12.13 years. Overall prevalence of hypertension was 44.13 % (n = 79). In comparison with the normotensive patients, the hypertensive patients were older and had significantly higher values of CRP, ESR, anti-CCP and DAS-28. A highly significant positive correlation between all the study parameters and systolic and diastolic blood pressure was observed. Presence of significantly higher values of CRP, ESR, anti-CCP and DAS-28 in hypertensive patients indicate that inflammation is associated with an increased risk of hypertension. In this context, early screening for arterial hypertension and adequate therapeutic measures should be considered in early RA patients.

Prevalence of Asymptomatic Arterial Hypertension and Its Correlation with Inflammatory Activity in Early Rheumatoid Arthritis

PubMed Central

Bajraktari, Ismet H.; Rexhepi, Sylejman; Berisha, Idriz; Lahu, Ali; Kryeziu, Avni; Durmishi, Bastri; Bajraktari, Halit; Bahtiri, Elton

2017-01-01

BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that worsens during the course of the disease and can cause disability. Early RA refers to the onset of symptoms within the past 3 months. In RA, increased levels of mediators of inflammation may cause arterial stiffness consequently leading to arterial hypertension. AIM: The aim of this cross-sectional study was to assess the prevalence of asymptomatic arterial hypertension in early RA patients as well as the correlation with parameters of inflammation. METHODS: One hundred and seventy-nine early RA patients diagnosed in agreement with ACR/EULAR (American College of Rheumatology/ European League against Rheumatism) 2010 criteria were consecutively included in the study. CRP (C-reactive protein) and anti CCP (Antibodies to cyclic citrullinated peptides) serum levels, WBC (white blood cells) count and ESR (Erythrocyte sedimentation rate), likewise DAS-28 (28-joint disease activity score) were determined in all included patients. Parametric tests were used to compare the characteristics of the groups and to test the correlation of the variables. RESULTS: Statistical data analysis revealed that a majority of the patients were females (n = 141; 78.7%); the mean age at RA onset was 49.13 ± 12.13 years. Overall prevalence of hypertension was 44.13 % (n = 79). In comparison with the normotensive patients, the hypertensive patients were older and had significantly higher values of CRP, ESR, anti-CCP and DAS-28. A highly significant positive correlation between all the study parameters and systolic and diastolic blood pressure was observed. CONCLUSION: Presence of significantly higher values of CRP, ESR, anti-CCP and DAS-28 in hypertensive patients indicate that inflammation is associated with an increased risk of hypertension. In this context, early screening for arterial hypertension and adequate therapeutic measures should be considered in early RA patients. PMID:28932306

Cardiovascular disease risk scores in the current practice: which to use in rheumatoid arthritis?

PubMed

Purcarea, A; Sovaila, S; Gheorghe, A; Udrea, G; Stoica, V

2014-01-01

Cardiovascular disease (CVD) is the highest prevalence disease in the general population (GP) and it accounts for 20 million deaths worldwide each year. Its prevalence is even higher in rheumatoid arthritis. Early detection of subclinical disease is critical and the use of cardiovascular risk prediction models and calculators is widely spread. The impact of such techniques in the GP was previously studied. Despite their common background and similarities, some disagreement exists between most scores and their importance in special high-risk populations like rheumatoid arthritis (RA), having a low level of evidence. The current article aims to single out those predictive models (models) that could be most useful in the care of rheumatoid arthritis patients.

Cardiovascular disease risk scores in the current practice: which to use in rheumatoid arthritis?

PubMed Central

Purcarea, A; Sovaila, S; Gheorghe, A; Udrea, G; Stoica, V

2014-01-01

Cardiovascular disease (CVD) is the highest prevalence disease in the general population (GP) and it accounts for 20 million deaths worldwide each year. Its prevalence is even higher in rheumatoid arthritis. Early detection of subclinical disease is critical and the use of cardiovascular risk prediction models and calculators is widely spread. The impact of such techniques in the GP was previously studied. Despite their common background and similarities, some disagreement exists between most scores and their importance in special high-risk populations like rheumatoid arthritis (RA), having a low level of evidence. The current article aims to single out those predictive models (models) that could be most useful in the care of rheumatoid arthritis patients. PMID:25713603

Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components

PubMed Central

Dougados, M.; Combe, B.; Cantagrel, A.; Goupille, P.; Olive, P.; Schattenkirchner, M.; Meusser, S; Paimela, L; Rau, R.; Zeidler, H.; Leirisalo-Repo, M.; Peldan, K.

1999-01-01

OBJECTIVES—To investigate the potential clinical benefit of a combination therapy.
METHODS—205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying anti-rheumatoid drugs previously, with an early (⩽1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68).
RESULTS—The mean changes in the DAS during the one year follow up of the study was −1.15, −0.87, −1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007).
CONCLUSION—This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.

 Keywords: rheumatoid arthritis; combination therapy; sulphasalazine; methotrexate PMID:10364900

Do Genetic Susceptibility Variants Associate with Disease Severity in Early Active Rheumatoid Arthritis?

PubMed

Scott, Ian C; Rijsdijk, Frühling; Walker, Jemma; Quist, Jelmar; Spain, Sarah L; Tan, Rachael; Steer, Sophia; Okada, Yukinori; Raychaudhuri, Soumya; Cope, Andrew P; Lewis, Cathryn M

2015-07-01

Genetic variants affect both the development and severity of rheumatoid arthritis (RA). Recent studies have expanded the number of RA susceptibility variants. We tested the hypothesis that these associated with disease severity in a clinical trial cohort of patients with early, active RA. We evaluated 524 patients with RA enrolled in the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trials. We tested validated susceptibility variants - 69 single-nucleotide polymorphisms (SNP), 15 HLA-DRB1 alleles, and amino acid polymorphisms in 6 HLA molecule positions - for their associations with progression in Larsen scoring, 28-joint Disease Activity Scores, and Health Assessment Questionnaire (HAQ) scores over 2 years using linear mixed-effects and latent growth curve models. HLA variants were associated with joint destruction. The *04:01 SNP (rs660895, p = 0.0003), *04:01 allele (p = 0.0002), and HLA-DRβ1 amino acids histidine at position 13 (p = 0.0005) and valine at position 11 (p = 0.0012) significantly associated with radiological progression. This association was only significant in anticitrullinated protein antibody (ACPA)-positive patients, suggesting that while their effects were not mediated by ACPA, they only predicted joint damage in ACPA-positive RA. Non-HLA variants did not associate with radiograph damage (assessed individually and cumulatively as a weighted genetic risk score). Two SNP - rs11889341 (STAT4, p = 0.0001) and rs653178 (SH2B3-PTPN11, p = 0.0004) - associated with HAQ scores over 6-24 months. HLA susceptibility variants play an important role in determining radiological progression in early, active ACPA-positive RA. Genome-wide and HLA-wide analyses across large populations are required to better characterize the genetic architecture of radiological progression in RA.

Cellular and molecular perspectives in rheumatoid arthritis.

PubMed

Veale, Douglas J; Orr, Carl; Fearon, Ursula

2017-06-01

Synovial immunopathology in rheumatoid arthritis is complex involving both resident and infiltrating cells. The synovial tissue undergoes significant neovascularization, facilitating an influx of lymphocytes and monocytes that transform a typically acellular loose areolar membrane into an invasive tumour-like pannus. The microvasculature proliferates to form straight regularly-branching vessels; however, they are highly dysfunctional resulting in reduced oxygen supply and a hypoxic microenvironment. Autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are found at an early stage, often before arthritis has developed, and they have been implicated in the pathogenesis of RA. Abnormal cellular metabolism and mitochondrial dysfunction thus ensue and, in turn, through the increased production of reactive oxygen species actively induce inflammation. Key pro-inflammatory cytokines, chemokines and growth factors and their signalling pathways, including nuclear factor κB, Janus kinase-signal transducer, are highly activated when immune cells are exposed to hypoxia in the inflamed rheumatoid joint show adaptive survival reactions by activating. This review attempts to highlight those aberrations in the innate and adaptive immune systems including the role of genetic and environmental factors, autoantibodies, cellular alterations, signalling pathways and metabolism that are implicated in the pathogenesis of RA and may therefore provide an opportunity for therapeutic intervention.

Serodiagnosis and immune profile in rheumatoid arthritis.

PubMed

Chakraborty, P; Bhattacharya, S; Chakraborty, M; Pal, B

1997-11-01

One hundred and seventy-five cases of clinically diagnosed rheumatoid arthritis, 82 non-rheumatoid cases suffering from various other diseases and 40 healthy normal controls were investigated for detection of rheumatoid factor, quantitation of serum immunoglobulin, demonstration of antinuclear antibody (ANA) and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid factor (RF) showed 64% positivity in rheumatoid group and 1.2% positivity in non-rheumatoid group. All three immunoglobulins (IgG, IgM, IgA) were found to be raised in serum of patients with rheumatoid arthritis, whereas only IgA level was elevated in serum of patients with non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 3.4% and 2.8% cases respectively in cases of clinically diagnosed rheumatoid arthritis who had been suffering from severe active rheumatoid arthritis. In non-rheumatoid group RF was positive in significant titre in only one case of leprosy. Synovial fluid and synovium were found to be heavily infiltrated by plasma cells and lymphocytes. RF appears first in synovial fluid and then in serum. Hence RF titre in blood may not attain significant level for the first several months.

Serology and immunoglobulin profile in rheumatoid arthritis.

PubMed

Adhya, S; Chakraborty, G; Hajra, B; Bhattacharya, S; Sikdar, P K; Sinha, S; Banerjee, P P; Ghosh, E; Chakraborty, P

1998-01-01

One hundred and twenty cases of clinically diagnosed rheumatoid arthritis, 80 non-rheumatoid cases suffering from various other diseases and 40 healthy individuals were investigated for the presence of rheumatoid factor, quantitation of serum immunoglobulin, demonstration of ANA and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid factor showed 56.6% positivity in rheumatoid group and 3.7% positivity in non-rheumatoid group. All three serum immunoglobulins (IgG, IgM, IgA) were raised in serum in significant titre in cases of rheumatoid arthritis, whereas only IgA lever was elevated in the group of non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 11.7% and 4.4% cases of rheumatoid arthritis who had severe underlying disease. In non-rheumatoid group, only one of 6 cases of systemic lupus erythematosus showed rheumatoid factor and that too in an insignificant titre (less than 1:20). Synovium and synovial fluid contained plenty of plasma cells and lymphocytes. It has been observed that RF appears first in synovial fluid and it may take several months to a year to attain detectable level in serum.

Production of Human Monoclonal Rheumatoid Factor Secreting Hybridomas Derived from Rheumatoid Synovial Cells

DTIC Science & Technology

1989-01-01

lymphocytes obtained from patients with other We were then interested to see whether AD7 RF had types of arthritis who were seronegative were also...seropositive rheumatoid anhrius patients and from synowal cells in arthritis patients seroneganve for rheumatoidfactor. 1.0 Patients No. of hybridso 1gM RF...Production of human monoclonal rheumatoid factor secreting hybridomas derived from rheumatoid s’inovial cells 12. PEFTONAL AUTVOR(S) Robbins DL, Kenny

Refractory rheumatoid vasculitis

PubMed Central

Kumar, Ashok; Goel, Anshul; Lapsiwala, Mehul; Singhal, Suman

2016-01-01

Systemic rheumatoid vasculitis (SRV) can develop in rheumatoid arthritis of long duration and high disease activity. It most commonly manifests as cutaneous vasculitis and mononeuritis multiplex. This can involve any organ of the body and carries very high mortality. We report a case of a young male who had rheumatoid arthritis for the past 15 years and became refractory to standard drugs and anti-TNF agents. He subsequently developed SRV, which started as mononeuritis multiplex. Disease progressed to result in gangrene of hands and feet despite receiving intravenous cyclophosphamide. Intravenous immunoglobulin and rituximab also could not provide any response. Prolonged ICU stay resulted in critical care neuromyopathy. Central nervous system vasculitis developed even after repeated infusions of intravenous immunoglobulins and at last he died of complications. In this case report, we have presented rare and chronic protracted presentation of rheumatoid vasculitis involving skin, nerves, brain and testis, which was refractory to the recommended therapies. PMID:28031844

STAT4 and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus

PubMed Central

Remmers, Elaine F.; Plenge, Robert M.; Lee, Annette T.; Graham, Robert R.; Hom, Geoffrey; Behrens, Timothy W.; de Bakker, Paul I.W.; Le, Julie M.; Lee, Hye-Soon; Batliwalla, Franak; Li, Wentian; Masters, Seth L.; Booty, Matthew G.; Carulli, John P.; Padyukov, Leonid; Alfredsson, Lars; Klareskog, Lars; Chen, Wei V.; Amos, Christopher I.; Criswell, Lindsey A.; Seldin, Michael F.; Kastner, Daniel L.

2009-01-01

BACKGROUND Rheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q. METHODS We tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. We then performed fine mapping of the STAT1-STAT4 region in a total of 1620 case patients with established rheumatoid arthritis and 2635 controls, all from North America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus. RESULTS A SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P = 2.81×10-7; odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P = 0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P = 1.87×10-9; odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis. CONCLUSIONS A haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway

STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus.

PubMed

Remmers, Elaine F; Plenge, Robert M; Lee, Annette T; Graham, Robert R; Hom, Geoffrey; Behrens, Timothy W; de Bakker, Paul I W; Le, Julie M; Lee, Hye-Soon; Batliwalla, Franak; Li, Wentian; Masters, Seth L; Booty, Matthew G; Carulli, John P; Padyukov, Leonid; Alfredsson, Lars; Klareskog, Lars; Chen, Wei V; Amos, Christopher I; Criswell, Lindsey A; Seldin, Michael F; Kastner, Daniel L; Gregersen, Peter K

2007-09-06

Rheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q. We tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. We then performed fine mapping of the STAT1-STAT4 region in a total of 1620 case patients with established rheumatoid arthritis and 2635 controls, all from North America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus. A SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P=2.81x10(-7); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P=0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P=1.87x10(-9); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis. A haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses. Copyright 2007

Rheumatoid arthritis and pseudo-vesicular skin plaques: rheumatoid neutrophilic dermatosis.

PubMed

Manriquez, Juan; Giesen, Laura; Puerto, Constanza Del; Gonzalez, Sergio

2016-01-01

A 54 year-old woman with a 3-year history of rheumatoid arthritis (RA) consulted us because of weight loss, fever and skin eruption. On physical examination, erythematous plaques with a pseudo-vesicular appearance were seen on the back of both shoulders. Histological examination was consistent with rheumatoid neutrophilic dermatosis (RND). After 3 days of prednisone treatment, the skin eruption resolved. RND is a rare cutaneous manifestation of seropositive RA, characterized by asymptomatic, symmetrical erythematous plaques with a pseudo-vesicular appearance. Histology characteristically reveals a dense, neutrophilic infiltrate with leucocitoclasis but without other signs of vasculitis. Lesions may resolve spontaneously or with RA treatment. This case illustrates an uncommon skin manifestation of active rheumatoid arthritis.

Rheumatoid myositis leading to acute lower extremity compartment syndrome: a case-based review.

PubMed

Jo, Daniel; Pompa, Tiffany; Khalil, Ambreen; Kong, Frank; Wetz, Robert; Goldstein, Mark

2015-10-01

Muscle pain and weakness in a rheumatoid arthritis (RA) patient has a broad differential, and myositis should be considered early in the disease course as serious limb and life-threatening sequelae may occur. A 55-year-old woman with a past medical history of methotrexate-controlled RA presented with right leg pain for 4 days. The patient suffered sensory loss in the right foot and decreased strength in the toes. Lab tests revealed elevated creatine kinase, ESR, and anti-rheumatoid factor antibody titers. CT scan revealed myositis of posterior compartment muscles. Progressive edema, pain, and neuromuscular deficits persisted despite steroid and antibiotic therapy, so the patient was taken for urgent fasciotomy for acute compartment syndrome. The muscle biopsy showed diffuse mononuclear cell infiltration as well as perivascular and perineural involvement consistent with rheumatoid myositis (RM). The patient did well post-op on a prednisone taper. This case underlines the systemic nature of RA and exemplifies the severity of inflammation that may lead to grave consequences such as compartment syndrome. The histopathology is diagnostic when there is evidence of mononuclear cell infiltration; however, this is not entirely specific. Early, aggressive therapy with immunosuppressives is warranted in such patients. RM has not, to our knowledge, been recorded to cause acute compartment syndrome. Clinicians should be aware of this uncommon manifestation of RA keeping the various presentations of rheumatoid disease in mind when faced with these patients.

A randomised controlled trial of occupational therapy for people with early rheumatoid arthritis.

PubMed

Hammond, A; Young, A; Kidao, R

2004-01-01

Occupational therapy (OT) aims at improving performance of daily living tasks, facilitating successful adjustments in lifestyle, and preventing losses of function. To evaluate the effects of a pragmatic, comprehensive OT programme on self management and health status of people with early rheumatoid arthritis (RA) (<2.5 years). A randomised, controlled "assessor blinded" trial was conducted with assessments made at entry, 6, 12, and 24 months. Main outcomes were AIMS2: physical function (PF), pain visual analogue scale (VAS), and Arthritis Self-Efficacy Scale (ASES). Groups had similar disease duration (9 months OT (n = 162) v 10 months control (n = 164)). The OT group received 7.57 (SD 3.04) hours of therapy. Self management significantly increased in the OT group. Otherwise, there were no significant differences in any outcome measures, or between groups, by ACR functional class: AIMS2: PF (F = 0.04; p = 0.96); pain VAS (F = 0.29; p = 0.74); total ASES score (F = 0.93; p = 0.39). OT improved self management but not health status in early RA. Functional ability remains reasonably good for many in the first five years, so preventive benefits of self management may not yet be apparent and longer follow up is needed. Although many considered the education and therapy useful, insufficient numbers in the OT group used self management sufficiently to make a difference. Behavioural approaches can improve adherence and, potentially, the long term benefits. Future research should evaluate OT as a complex intervention and develop programmes from a theoretical and evidence base.

Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early stage of rheumatoid arthritis

PubMed Central

Yeo, L; Adlard, N; Juarez, M; Smallie, T; Snow, M; Buckley, C D; Raza, K; Filer, A; Scheel-Toellner, D

2016-01-01

Background and objectives For our understanding of the pathogenesis of rheumatoid arthritis (RA), it is important to elucidate the mechanisms underlying early stages of synovitis. Here, synovial cytokine production was investigated in patients with very early arthritis. Methods Synovial biopsies were obtained from patients with at least one clinically swollen joint within 12 weeks of symptom onset. At an 18-month follow-up visit, patients who went on to develop RA, or whose arthritis spontaneously resolved, were identified. Biopsies were also obtained from patients with RA with longer symptom duration (>12 weeks) and individuals with no clinically apparent inflammation. Synovial mRNA expression of 117 cytokines was quantified using PCR techniques and analysed using standard and novel methods of data analysis. Synovial tissue sections were stained for CXCL4, CXCL7, CD41, CD68 and von Willebrand factor. Results A machine learning approach identified expression of mRNA for CXCL4 and CXCL7 as potentially important in the classification of early RA versus resolving arthritis. mRNA levels for these chemokines were significantly elevated in patients with early RA compared with uninflamed controls. Significantly increased CXCL4 and CXCL7 protein expression was observed in patients with early RA compared with those with resolving arthritis or longer established disease. CXCL4 and CXCL7 co-localised with blood vessels, platelets and CD68+ macrophages. Extravascular CXCL7 expression was significantly higher in patients with very early RA compared with longer duration RA or resolving arthritis Conclusions Taken together, these observations suggest a transient increase in synovial CXCL4 and CXCL7 levels in early RA. PMID:25858640

Phrasing of the patient global assessment in the rheumatoid arthritis ACR/EULAR remission criteria: an analysis of 967 patients from two databases of early and established rheumatoid arthritis patients.

PubMed

Gossec, Laure; Kirwan, John Richard; de Wit, Maarten; Balanescu, Andra; Gaujoux-Viala, Cecile; Guillemin, Francis; Rat, Anne-Christine; Saraux, Alain; Fautrel, Bruno; Kvien, Tore K; Dougados, Maxime

2018-06-01

The ACR/EULAR Boolean remission criteria for rheumatoid arthritis (RA) include a strict cutoff for patient global assessment (PGA, value ≤ 1/10). Near-remission corresponds to remission for joint counts and C-reactive protein but with PGA > 1. The objective was to explore whether the contribution of PGA to remission and near-remission varied according to the wording of the PGA and in relation to disease duration. In patients with early arthritis (N = 731, French ESPOIR cohort) or established RA (N = 236 patients from across Europe), frequency of remission versus near-remission was assessed according to the phrasing used for PGA (global health versus disease activity). In 967 patients (mean [standard deviation] age 49.7 [12.7] years, 76.7% women), remission was infrequent: range 12.9-16.7% (according to wording of PGA) in early RA and 6.8-7.2% in established RA. Near-remission was more frequent: 13.0-16.8% in early RA and 13.1-13.6% in established RA. The ratio of remission to near-remission was higher in the early arthritis cohort (0.8-1.3 versus 0.5-0.5 in established RA). Using the disease activity PGA led to more remission and less near-remission than the global health PGA in the early arthritis cohort (12.9 vs 16.7% near-remission, respectively, p = 0.047) but not in established RA. The proportion of patients who can be classified as remission or near-remission differs in early RA compared to establish RA and depends upon the formulation of the PGA question. PGA referring to disease activity and not global health may be preferred in early disease, if the objective is more alignment with inflammation assessment.

Brief Report: Predicting Functional Disability: One-Year Results From the Scottish Early Rheumatoid Arthritis Inception Cohort.

PubMed

Kronisch, Caroline; McLernon, David J; Dale, James; Paterson, Caron; Ralston, Stuart H; Reid, David M; Tierney, Ann; Harvie, John; McKay, Neil; Wilson, Hilary E; Munro, Robin; Saunders, Sarah; Richmond, Ruth; Baxter, Derek; McMahon, Mike; Kumar, Vinod; McLaren, John; Siebert, Stefan; McInnes, Iain B; Porter, Duncan; Macfarlane, Gary J; Basu, Neil

2016-07-01

To identify baseline prognostic indicators of disability at 1 year within a contemporary early inflammatory arthritis inception cohort and then develop a clinically useful tool to support early patient education and decision-making. The Scottish Early Rheumatoid Arthritis (SERA) inception cohort is a multicenter, prospective study of patients with newly presenting RA or undifferentiated arthritis. SERA data were analyzed to determine baseline predictors of disability (defined as a Health Assessment Questionnaire [HAQ] score of ≥1) at 1 year. Clinical and psychosocial baseline exposures were entered into a forward stepwise logistic regression model. The model was externally validated using newly accrued SERA data and subsequently converted into a prediction tool. Of the 578 participants (64.5% female), 36.7% (n = 212) reported functional disability at 1 year. Functional disability was independently predicted by baseline disability (odds ratio [OR] 2.67 [95% confidence interval (95% CI) 1.98, 3.59]), depression (OR 2.52 [95% CI 1.18, 5.37]), anxiety (OR 2.37 [95% CI 1.33, 4.21]), being in paid employment with absenteeism during the last week (OR 1.19 [95% CI 0.63, 2.23]), not being in paid employment (OR 2.36 [95% CI 1.38, 4.03]), and being overweight (OR 1.61 [95% CI 1.04, 2.50]). External validation (using 113 newly acquired patients) evidenced good discriminative performance with a C statistic of 0.74, and the calibration slope showed no evidence of model overfit (P = 0.31). In the context of modern early inflammatory arthritis treatment paradigms, predictors of disability at 1 year appear to be dominated by psychosocial rather than more traditional clinical measures. This indicates the potential benefit of early access to nonpharmacologic interventions targeting key psychosocial factors, such as mental health and work disability. © 2016, American College of Rheumatology.

[Significance of glucose-6-phosphate isomerase assay in early diagnosis of rheumatoid arthritis].

PubMed

Xu, J; Liu, J; Zhu, L; Zhang, X W; Li, Z G

2016-12-18

To explore the titer of glucose-6-phosphate isomerase (GPI) for early diagnosis of the outpatient with rheumatoid arthritis (RA) in real life, and to analyze its relationship with disease activity. In the study, 1 051 patients with arthritis were collected in the group who had joints tender and swelling, and 90 cases of healthy people as a control group. ELISA method was used to detect the serum level of GPI, and according to clinical features and laboratory test, all the patients including 525 RA patients, the other patients including osteoarthritis (OA), 134 cases of seronegative spine joint disease (SpA), 104 cases of systemic lupus erythematosus (SLE), 31 cases of primary Sjogren syndrome (pSS), 24 cases of gout arthritis (GA), 22 cases of other connective tissue diseases (including polymyalgia rheumatica, dermatomyositis, systemic sclerosis, adult Still disease) and 46 cases of other diseases (including 165 cases of osteoporosis, avascular necrosis of the femoral head, traumatic osteomyelitis, bone and joint disease, juvenile rheumatoid arthritis, tumor). The diagnostic values of GPI were assessed, and the differences between the GPI positive and negative groups of the RA patients in clinical characteristics, disease activity, severity and inflammatory index analyzed. The positive rate of serum GPI in the patients with RA was 55.4%, contrasting to other autoimmune diseases (14.3%) and healthy controls (7.78%)(P<0.001). Compared with the OA and SpA patients, the RA group was increased more significantly, and the difference was statistically significant (P<0.001). The diagnostic value of GPI alone for RA was 0.39 mg/L, the sensitivity was 54.2%, and specificity was 87.3%. The positive rate of GPI in RF negative patients was 36.1%; the positive rate of GPI in anti-CCP antibody negative patients was 34.2%; the positive rate of GPI in RF and anti-CCP antibody negative patients was 24.1%. The level of GPI had positive correlation (P<0.05) with ESR, RF, anti

Clinical and serological predictors of remission in rheumatoid arthritis are dependent on treatment regimen.

PubMed

Ma, Margaret H Y; Scott, Ian C; Dahanayake, Chanaka; Cope, Andrew P; Scott, David L

2014-07-01

Early intensive treatment is now the cornerstone for the management of rheumatoid arthritis (RA). In the era of personalized medicine, when treatment is becoming more individualized, it is unclear from the current literature whether all patients with RA benefit equally from such intensive therapies. We investigated the benefit of different treatment regimens on remission rates when stratified to clinical and serological factors. The Combination Anti-rheumatic Drugs in Early Rheumatoid Arthritis (CARDERA) trial recruited patients with RA of less than 2 years' duration who had active disease. The trial compared 4 treatment regimens: methotrexate monotherapy, 2 different double therapy regimens (methotrexate and cyclosporine or methotrexate and prednisolone) and 3-drug therapy. Clinical predictors included age, male sex, and tender joint count (TJC) and serological biomarkers included rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA). Patients who were male, over 50 years, had ≥ 6 TJC, were RF-IgM-positive, or ACPA-positive were more likely to achieve remission at 24 months using 3-drug therapy compared to monotherapy (OR 2.99, 4.95, 2.71, 2.54, and 3.52, respectively). There were no differences in response to monotherapy and 3-drug therapy if patients were female, under 50 years, had < 6 TJC, or were seronegative. Early intensive regimens have become the gold standard in the treatment of early RA. Our study suggests that this intensive approach is only superior to monotherapy in certain subsets of patients. Although these are unlikely to be the only predictors of treatment response, our study brings us a step closer to achieving personalized medicine in RA.

Genomics, transcriptomics and proteomics to elucidate the pathogenesis of rheumatoid arthritis.

PubMed

Song, Xinqiang; Lin, Qingsong

2017-08-01

Rheumatoid arthritis is an autoimmune disease that affects several organs and tissues, predominantly the synovial joints. The pathogenesis of this disease is not completely understood, which maybe involved in the genomic variations, gene expression, protein translation and post-translational modifications. These system variations in genomics, transcriptomics and proteomics are dynamic in nature and their crosstalk is overwhelmingly complex, thus analyzing them separately may not be very informative. However, various '-omics' techniques developed in recent years have opened up new possibilities for clarifying disease pathways and thereby facilitating early diagnosis and specific therapies. This review examines how recent advances in the fields of genomics, transcriptomics and proteomics have contributed to our understanding of rheumatoid arthritis.

Citrullinated Chemokines in Rheumatoid Arthritis

DTIC Science & Technology

2015-10-01

1 AWARD NUMBER: W81XWH-13-1-0210 TITLE: Citrullinated Chemokines in Rheumatoid Arthritis PRINCIPAL INVESTIGATOR: David A. Fox CONTRACTING...CONTRACT NUMBER Citrullinated Chemokines in Rheumatoid Arthritis 5b. GRANT NUMBER W81XWH-13-1-0210 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) David A. Fox...citrulline, which contributes to the pathogenesis of rheumatoid arthritis (RA). We show that citrullinated epithelial- derived neutrophil-activating peptide 78

Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early stage of rheumatoid arthritis.

PubMed

Yeo, L; Adlard, N; Biehl, M; Juarez, M; Smallie, T; Snow, M; Buckley, C D; Raza, K; Filer, A; Scheel-Toellner, D

2016-04-01

For our understanding of the pathogenesis of rheumatoid arthritis (RA), it is important to elucidate the mechanisms underlying early stages of synovitis. Here, synovial cytokine production was investigated in patients with very early arthritis. Synovial biopsies were obtained from patients with at least one clinically swollen joint within 12 weeks of symptom onset. At an 18-month follow-up visit, patients who went on to develop RA, or whose arthritis spontaneously resolved, were identified. Biopsies were also obtained from patients with RA with longer symptom duration (>12 weeks) and individuals with no clinically apparent inflammation. Synovial mRNA expression of 117 cytokines was quantified using PCR techniques and analysed using standard and novel methods of data analysis. Synovial tissue sections were stained for CXCL4, CXCL7, CD41, CD68 and von Willebrand factor. A machine learning approach identified expression of mRNA for CXCL4 and CXCL7 as potentially important in the classification of early RA versus resolving arthritis. mRNA levels for these chemokines were significantly elevated in patients with early RA compared with uninflamed controls. Significantly increased CXCL4 and CXCL7 protein expression was observed in patients with early RA compared with those with resolving arthritis or longer established disease. CXCL4 and CXCL7 co-localised with blood vessels, platelets and CD68(+) macrophages. Extravascular CXCL7 expression was significantly higher in patients with very early RA compared with longer duration RA or resolving arthritis Taken together, these observations suggest a transient increase in synovial CXCL4 and CXCL7 levels in early RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Rheumatoid Arthritis: Can It Affect the Eyes?

MedlinePlus

Rheumatoid arthritis: Can it affect the eyes? Can rheumatoid arthritis affect the eyes? Answers from April Chang-Miller, M.D. Rheumatoid arthritis is a chronic inflammatory disease that primarily affects ...

Rheumatoid Arthritis: Can It Affect the Lungs?

MedlinePlus

Rheumatoid arthritis: Can it affect the lungs? Can rheumatoid arthritis affect your lungs? Answers from April Chang-Miller, M.D. Although rheumatoid arthritis primarily affects joints, it sometimes causes lung disease ...

Cost-Effectiveness of Triple Therapy Versus Etanercept Plus Methotrexate in Early Aggressive Rheumatoid Arthritis.

PubMed

Jalal, Hawre; O'Dell, James R; Bridges, S Louis; Cofield, Stacey; Curtis, Jeffrey R; Mikuls, Ted R; Moreland, Larry W; Michaud, Kaleb

2016-12-01

To evaluate the cost-effectiveness of all 4 interventions in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) clinical trial: immediate triple (IT), immediate etanercept (IE), step-up triple (ST), and step-up etanercept (SE). Step-up interventions started with methotrexate and added either etanercept or sulfasalazine plus hydroxychloroquine to patients with persistent disease activity. We built a Markov cohort model that uses individual-level data from the TEAR trial, published literature, and supplemental clinical data. Costs were in US dollars, benefits in quality-adjusted life years (QALYs), perspective was societal, and the time horizon was 5 years. The immediate strategies were more efficacious than step-up strategies. SE and IE were more costly than ST and IT, primarily due to treatment cost differences. In addition, IT was the least expensive and most effective strategy when the time horizon was 1 and 2 years. When the time horizon was 5 years, IE was marginally more effective than IT (3.483 versus 3.476 QALYs), but IE was substantially more expensive than IT ($148,800 versus $52,600), producing an incremental cost-effectiveness ratio of $12.5 million per QALY. These results were robust to both one-way deterministic and joint probabilistic sensitivity analyses. IT was highly cost-effective in the majority of scenarios. Although IE was more effective in 5 years, a substantial reduction in the cost of biologic agents was required in order for IE to become cost-effective in early aggressive RA under willingness-to-pay thresholds that most health care settings may find acceptable. © 2016, American College of Rheumatology.

Aggressive treatment of early rheumatoid arthritis: recognizing the window of opportunity and treating to target goals.

PubMed

Resman-Targoff, Beth H; Cicero, Marco P

2010-11-01

Evidence supports the use of aggressive therapy for patients with early rheumatoid arthritis (RA). Clinical outcomes in patients with early RA can improve with a treat-to-target approach that sets the goal at disease remission. The current selection of antirheumatic therapies, including conventional and biologic disease-modifying antirheumatic drugs (DMARDs), has made disease remission a realistic target for patients with early RA. The challenge is selecting the optimal antirheumatic drug or combination of drugs for initial and subsequent therapy to balance the clinical benefits, risks, and economic considerations. In some cases, the use of biologic agents as part of the treatment regimen has shown superior results compared with conventional DMARDs alone in halting the progression of disease, especially in reducing radiographic damage. However, the use of biologic agents as initial therapy is challenged by cost-effectiveness analyses, which favor the use of conventional DMARDs. The use of biologic agents may be justified in certain patients with poor prognostic factors or those who experience an inadequate response to conventional DMARDs as a means to slow or halt disease progression and its associated disability. In these cases, the higher cost of treatment with biologic agents may be offset by decreased societal costs, such as lost work productivity, and increased health-related quality of life. Further research is needed to understand optimal strategies for balancing costs, benefits, and risks of antirheumatic drugs. Some key questions are (1) when biologic agents are appropriate for initial therapy, and (2) when to conclude that response to conventional DMARDs is inadequate and biologic agents should be initiated.

Amyloid arthropathy mimicking seronegative rheumatoid arthritis in multiple myeloma: case reports and review of the literature.

PubMed

Alpay, Nilüfer; Artim-Esen, Bahar; Kamali, Sevil; Gül, Ahmet; Kalayoğlu-Beşişik, Sevgi

2009-12-01

We report two patients who suffered from symmetrical polyarthritis simulating rheumatoid arthritis. Acute phase response was almost within normal limits, and autoantibodies including rheumatoid factor were negative. Both of them were diagnosed as having amyloid arthropathy (AmyA) secondary to kappa multiple myeloma based on deposition of kappa-light chain-immunoreactive amyloid in biopsied tissue and Bence Jones protein in urine. Systemic AL amyloidosis may be important in the differential diagnosis of chronic polyarthralgia.

The Impact of Low-Dose Disease-modifying Anti-rheumatics Drugs (DMARDs) on Bone Mineral Density of Premenopausal Women in Early Rheumatoid Arthritis.

PubMed

Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan; Boshnjaku, Shkumbin

2016-04-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical polyarthritis and multisystemic involvement. The aim of this study was to assess the impact of low dose of methotrexate on bone mineral density (BMD) in patients with early rheumatoid arthritis (RA). This paper follows a retrospective study, which involves 60 female patients with early onset RA diagnosed according to the American Rheumatism Association Criteria (ACR/EULAR 2010). The patients were divided into two groups group I was composed of thirty patients treated with dose of 7.5 mg/weekly methotrexate (MTX), while group II included thirty patients treated with dose of 2 g/daily sulfasalazine (SSZ). The Disease Activity was measured by a combination of Erythrocyte Sedimentation Rate (ESR) and Disease Activity Score (DAS-28). Bone mineral density of the lumbar spine (L2-4), and femoral neck, was measured by dual energy X-ray absorptiometry (DEXA) (Stratos 800). Laboratory findings included: In this study, we found no negative effect on BMD in RA patients treated with low dose MTX in comparison to patients treated with SSZ. There was not observed significant difference in BMD of the lumbar spine, femur neck or trochanter, of MTX and SSZ patients in the pretreatment phase, nor after 12 months of treatment. No significant change in the biochemical parameters of the both groups. Based on the results of our study, low dose of methotrexate has no negative effect on BMD in premenopausal RA patients. We believe that these results might provide new insights and that further longitudinal studies with larger groups of premenopausal RA patients are required.

The Impact of Low-Dose Disease-modifying Anti-rheumatics Drugs (DMARDs) on Bone Mineral Density of Premenopausal Women in Early Rheumatoid Arthritis

PubMed Central

Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan; Boshnjaku, Shkumbin

2016-01-01

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical polyarthritis and multisystemic involvement. Objective: The aim of this study was to assess the impact of low dose of methotrexate on bone mineral density (BMD) in patients with early rheumatoid arthritis (RA). Materials and methods: This paper follows a retrospective study, which involves 60 female patients with early onset RA diagnosed according to the American Rheumatism Association Criteria (ACR/EULAR 2010). The patients were divided into two groups group I was composed of thirty patients treated with dose of 7.5 mg/weekly methotrexate (MTX), while group II included thirty patients treated with dose of 2 g/daily sulfasalazine (SSZ). The Disease Activity was measured by a combination of Erythrocyte Sedimentation Rate (ESR) and Disease Activity Score (DAS-28). Bone mineral density of the lumbar spine (L2–4), and femoral neck, was measured by dual energy X-ray absorptiometry (DEXA) (Stratos 800). Laboratory findings included: In this study, we found no negative effect on BMD in RA patients treated with low dose MTX in comparison to patients treated with SSZ. There was not observed significant difference in BMD of the lumbar spine, femur neck or trochanter, of MTX and SSZ patients in the pretreatment phase, nor after 12 months of treatment. No significant change in the biochemical parameters of the both groups. Conclusion: Based on the results of our study, low dose of methotrexate has no negative effect on BMD in premenopausal RA patients. We believe that these results might provide new insights and that further longitudinal studies with larger groups of premenopausal RA patients are required. PMID:27147781

Age at onset determines severity and choice of treatment in early rheumatoid arthritis: a prospective study

PubMed Central

2014-01-01

Introduction Disease activity, severity and comorbidity contribute to increased mortality in patients with rheumatoid arthritis (RA). We evaluated the impact of age at disease onset on prognostic risk factors and treatment in patients with early disease. Methods In this study, 950 RA patients were followed regularly from the time of inclusion (<12 months from symptom onset) for disease activity (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender and/or swollen joints, Visual Analogue Scale pain and global scores, and Disease Activity Score in 28 joints (DAS28)) and function (Health Assessment Questionnaire (HAQ)). Disease severity, measured on the basis of radiographs of the hands and feet (erosions based on Larsen score), extraarticular disease, nodules, and comorbidities and treatment (disease-modifying antirheumatic drugs (DMARDs), corticosteroids, biologics and nonsteroidal anti-inflammatory drugs) were recorded at the time of inclusion and at 5 years. Autoantibodies (rheumatoid factor, antinuclear antibodies and antibodies against cyclic citrullinated peptides (ACPAs)) and genetic markers (human leucocyte antibody (HLA) shared epitope and protein tyrosine phosphatase nonreceptor type 22 (PTPN22)) were analysed at the time of inclusion. Data were stratified as young-onset RA (YORA) and late-onset RA (LORA), which were defined as being below or above the median age at the time of onset of RA (58 years). Results LORA was associated with lower frequency of ACPA (P < 0.05) and carriage of PTPN22-T variant (P < 0.01), but with greater disease activity at the time of inclusion measured on the basis of ESR (P < 0.001), CRP (P < 0.01) and accumulated disease activity (area under the curve for DAS28 score) at 6 months (P < 0.01), 12 months (P < 0.01) and 24 months (P < 0.05), as well as a higher HAQ score (P < 0.01) compared with YORA patients. At baseline and 24 months, LORA was more often associated with erosions (P < 0.01 for both) and higher

[Rheumatoid arthritis and multiple neoplasms].

PubMed

Ivorra, J; Massutí, B; Román, J; Balañá, C; Portilla, J; Pascual, E

1991-09-28

In patients with rheumatoid arthritis the appearance of neoplastic disease has been fundamentally described of lymphoproliferative origin. The case of a 59 year old woman with rheumatoid arthritis of a 4 year evolution is reported. The patient was treated with gold salts and methotrexate and presented successively a bronchogenic carcinoma and a non-Hodgkin lymphoma. The epidemiologic studies in the relation of rheumatoid arthritis-neoplasia are discussed and the pathogenic hypotheses to the immune alterations as well as the treatments employed are described.

Analysis of peripheral blood lymphocytes using flow cytometry in polymyalgia rheumatica, RS3PE and early rheumatoid arthritis.

PubMed

Shimojima, Y; Matsuda, M; Ishii, W; Gono, T; Ikeda, S

2008-01-01

Clinical pictures of poly-myalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) are often indistinguishable from those of early rheumatoid arthritis (RA). To investigate whether there is a difference in immunological aspects among these 3 disorders, we performed a phenotypic analysis of peripheral blood lymphocytes. Eleven patients with early RA, 14 with PMR and 11 with RS3PE were enrolled in this study. After separation of mononuclear cells from peripheral blood using the Ficoll-Hypaque method, surface markers and intracellular cytokines of lymphocytes were analyzed by 2- or 3-color flow cytometry. Both PMR and RS3PE showed a significant decrease in CD8⁺CD25⁺ cells (p<0.05), and significant increases in CD4⁺IFN-gamma⁺IL-4- (p<0.05), CD8⁺IFN-gamma⁺IL-4- (p<0.05 and p<0.01, respectively) and CD4⁺TNF-alpha⁺ cells (p<0.05) compared with early RA. CD3⁺CD4⁺ cells were higher in PMR than in RS3PE (p<0.01), but there were no significant differences in any other phenotypes between these disorders. A decrease in activated cytotoxic/suppressor T cells and increases in circulating Th1 and Tc1 cells may be common characteristics of PMR and RS3PE in comparison with early RA. Both disorders are clearly different from early RA, and probably belong to the same disease entity with regard to phenotypes of peripheral blood lymphocytes.

Utility of different cardiovascular disease prediction models in rheumatoid arthritis.

PubMed

Purcarea, A; Sovaila, S; Udrea, G; Rezus, E; Gheorghe, A; Tiu, C; Stoica, V

2014-01-01

Rheumatoid arthritis comes with a 30% higher probability for cardiovascular disease than the general population. Current guidelines advocate for early and aggressive primary prevention and treatment of risk factors in high-risk populations but this excess risk is under-addressed in RA in real life. This is mainly due to difficulties met in the correct risk evaluation. This study aims to underline the differences in results of the main cardiovascular risk screening models in the real life rheumatoid arthritis population. In a cross-sectional study, patients addressed to a tertiary care center in Romania for an biannual follow-up of rheumatoid arthritis and the ones who were considered free of any cardiovascular disease were assessed for subclinical atherosclerosis. Clinical, biological and carotidal ultrasound evaluations were performed. A number of cardiovascular disease prediction scores were performed and differences between tests were noted in regard to subclinical atherosclerosis as defined by the existence of carotid intima media thickness over 0,9 mm or carotid plaque. In a population of 29 Romanian rheumatoid arthritis patients free of cardiovascular disease, the performance of Framingham Risk Score, HeartSCORE, ARIC cardiovascular disease prediction score, Reynolds Risk Score, PROCAM risk score and Qrisk2 score were compared. All the scores under-diagnosed subclinical atherosclerosis. With an AUROC of 0,792, the SCORE model was the only one that could partially stratify patients in low, intermediate and high-risk categories. The use of the EULAR recommended modifier did not help to reclassify patients. The only score that showed a statistically significant prediction capacity for subclinical atherosclerosis in a Romanian rheumatoid arthritis population was SCORE. The additional calibration or the use of imaging techniques in CVD risk prediction for the intermediate risk category might be warranted.

Utility of different cardiovascular disease prediction models in rheumatoid arthritis

PubMed Central

Purcarea, A; Sovaila, S; Udrea, G; Rezus, E; Gheorghe, A; Tiu, C; Stoica, V

2014-01-01

Background. Rheumatoid arthritis comes with a 30% higher probability for cardiovascular disease than the general population. Current guidelines advocate for early and aggressive primary prevention and treatment of risk factors in high-risk populations but this excess risk is under-addressed in RA in real life. This is mainly due to difficulties met in the correct risk evaluation. This study aims to underline the differences in results of the main cardiovascular risk screening models in the real life rheumatoid arthritis population. Methods. In a cross-sectional study, patients addressed to a tertiary care center in Romania for an biannual follow-up of rheumatoid arthritis and the ones who were considered free of any cardiovascular disease were assessed for subclinical atherosclerosis. Clinical, biological and carotidal ultrasound evaluations were performed. A number of cardiovascular disease prediction scores were performed and differences between tests were noted in regard to subclinical atherosclerosis as defined by the existence of carotid intima media thickness over 0,9 mm or carotid plaque. Results. In a population of 29 Romanian rheumatoid arthritis patients free of cardiovascular disease, the performance of Framingham Risk Score, HeartSCORE, ARIC cardiovascular disease prediction score, Reynolds Risk Score, PROCAM risk score and Qrisk2 score were compared. All the scores under-diagnosed subclinical atherosclerosis. With an AUROC of 0,792, the SCORE model was the only one that could partially stratify patients in low, intermediate and high-risk categories. The use of the EULAR recommended modifier did not help to reclassify patients. Conclusion. The only score that showed a statistically significant prediction capacity for subclinical atherosclerosis in a Romanian rheumatoid arthritis population was SCORE. The additional calibration or the use of imaging techniques in CVD risk prediction for the intermediate risk category might be warranted. PMID:25713628

Arthritis of the hand - Rheumatoid

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... Therapist? Media Find a Hand Surgeon Home Anatomy Rheumatoid Arthritis Email to a friend * required fields From * To * ... debilitating when it affects the hands and fingers. Rheumatoid arthritis is one of the most common forms of ...

Hepcidin plasma levels are not associated with changes in haemoglobin in early rheumatoid arthritis patients.

PubMed

Østgård, R D; Glerup, H; Jurik, A G; Kragstrup, T W; Stengaard-Pedersen, K; Hetland, M L; Hørslev-Petersen, K; Junker, P; Deleuran, B W

2017-11-01

A reduction in haemoglobin level is a frequent complication among rheumatoid arthritis (RA) patients. Hepcidin has been linked to disturbed erythropoiesis. The objective of this study was to investigate the longitudinal changes in hepcidin in patients with early RA. Hepcidin plasma concentrations were measured by enzyme-linked immunosorbent assay in patients with early RA (n = 80) and healthy volunteers (HV, n = 40). Haemoglobin and other iron-related proteins were also measured. At baseline, all patients had active disease and were treatment naïve. Patients were treated with disease-modifying anti-rheumatic drugs (DMARDs) and with additional adalimumab (ADA, n = 42) or placebo (PLA, n = 38) during 52 weeks, using a treat-to-target strategy, aiming for a 28-joint Disease Activity Score (DAS28) < 3.2. At baseline, hepcidin levels [median (interquartile range)] were 9.7 ng/mL (5.2-19.4 ng/mL) in DMARD + ADA and 11.3 ng/mL (5.9-19.1 ng/mL) in DMARD + PLA. Both were significantly higher than seen in HV (6.0 ng/mL (3.3-9.3 ng/mL) (p < 0.001). After 12 months, both treatment regimens resulted in normalization of hepcidin. DAS28 correlated with hepcidin at baseline (r = 0.48, p < 0.001). No correlation was observed between levels of haemoglobin and hepcidin at baseline or during the 52 week follow-up. No change in haemoglobin levels was seen as a function of hepcidin changes. In a mixed statistical model, no single factor was connected with the regulation of haemoglobin in early RA. The changes in hepcidin were not associated with changes in haemoglobin levels. Thus, hepcidin could not be used as a prognostic marker in patients with early RA.

LOW BONE MINERAL DENSITY AMONG PATIENTS WITH NEWLY DIAGNOSED RHEUMATOID ARTHRITIS.

PubMed

Arain, Shafique Rehman; Riaz, Amir; Nazir, Lubna; Umer, Tahira Perveen; Rasool, Tabe

2016-01-01

Osteoporosis is an early and common feature in rheumatoid arthritis. Apart from other manifestations, Osteoporosis is an extra-articular manifestation of rheumatoid arthritis whichmay result in increased risk of fractures, morbidity mortality, and associated healthcare costs. This study evaluates bone mineral density changes in patients withrheumatoid arthritis of recent-onset. This cross sectional descriptive study was conducted in the Rheumatology Department of a tertiary care hospital in Karachi. Data was collected from 76 patients presenting with seropositive or seronegative rheumatoid arthritis. Bone mineral density of these patients measured at lumbar spine and hip by using dual energy x-ray absorptiometrys can. Variables like age, gender, BMI, menstrual status, disease duration, erythrocyte sedimentation rate, vitamin D level, clinical disease activity index and seropositivity for rheumatoid arthritis were measured along with outcome variables. A total of 104 patients fulfilling inclusion criteria were registered with 28 excluded from study. A mong the remaining 76 patients, 68 (89.50%) were female, with mean age of patients (with low bone mineral density) as 50.95 ± 7.87 years. Nineteen (25%) patients had low bone mineral density, 68.52% had low BMD at spine while 10.52% at hip and 21.05% at spine and hip both. Low bone mineral density was found higher in patients with seronegative 7 (50%) as compared to seropositive patients 12 (19.4%) (p-value 0.017), whereas low bone mineral d ensity was found higher 12 (70.6%) among post-menopausal women. Low BMD was found in 25% of patients at earlier stage of the rheumatoid arthritis with seropositivity, age and menopausal status as significant risk factors.

Triple DMARD treatment in early rheumatoid arthritis modulates synovial T cell activation and plasmablast/plasma cell differentiation pathways

PubMed Central

Wechalekar, Mihir D.; Guo, Yanxia; Yin, Xuefeng; Weedon, Helen; Proudman, Susanna M.; Smith, Malcolm D.; Nagpal, Sunil

2017-01-01

Objectives This study sought to investigate the genome-wide transcriptional effects of a combination of disease modifying anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine and hydroxychloroquine) in synovial tissues obtained from early rheumatoid arthritis (RA) patients. While combination DMARD strategies have been investigated for clinical efficacy, very little data exists on the potential molecular mechanism of action. We hypothesized that tDMARD would impact multiple biological pathways, but the specific pathways were unknown. Methods Paired synovial biopsy samples from early RA patients before and after 6 months of tDMARD therapy were collected by arthroscopy (n = 19). These biopsies as well as those from subjects with normal synovium (n = 28) were profiled by total RNA sequencing. Results Large differences in gene expression between RA and control biopsies (over 5000 genes) were identified. Despite clinical efficacy, the expression of a restricted set of less than 300 genes was reversed after 6 months of treatment. Many genes remained elevated, even in patients who achieved low disease activity. Interestingly, tDMARD downregulated genes included those involved in T cell activation and signaling and plasmablast/plasma cell differentiation and function. Conclusions We have identified transcriptomic signatures that characterize synovial tissue from RA patients with early disease. Analysis after 6 months of tDMARD treatment highlight consistent alterations in expression of genes related to T cell activation and plasmablast/plasma cell differentiation. These results provide novel insight into the biology of early RA and the mechanism of tDMARD action and may help identify novel drug targets to improve rates of treatment-induced disease remission. PMID:28863153

Triple DMARD treatment in early rheumatoid arthritis modulates synovial T cell activation and plasmablast/plasma cell differentiation pathways.

PubMed

Walsh, Alice M; Wechalekar, Mihir D; Guo, Yanxia; Yin, Xuefeng; Weedon, Helen; Proudman, Susanna M; Smith, Malcolm D; Nagpal, Sunil

2017-01-01

This study sought to investigate the genome-wide transcriptional effects of a combination of disease modifying anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine and hydroxychloroquine) in synovial tissues obtained from early rheumatoid arthritis (RA) patients. While combination DMARD strategies have been investigated for clinical efficacy, very little data exists on the potential molecular mechanism of action. We hypothesized that tDMARD would impact multiple biological pathways, but the specific pathways were unknown. Paired synovial biopsy samples from early RA patients before and after 6 months of tDMARD therapy were collected by arthroscopy (n = 19). These biopsies as well as those from subjects with normal synovium (n = 28) were profiled by total RNA sequencing. Large differences in gene expression between RA and control biopsies (over 5000 genes) were identified. Despite clinical efficacy, the expression of a restricted set of less than 300 genes was reversed after 6 months of treatment. Many genes remained elevated, even in patients who achieved low disease activity. Interestingly, tDMARD downregulated genes included those involved in T cell activation and signaling and plasmablast/plasma cell differentiation and function. We have identified transcriptomic signatures that characterize synovial tissue from RA patients with early disease. Analysis after 6 months of tDMARD treatment highlight consistent alterations in expression of genes related to T cell activation and plasmablast/plasma cell differentiation. These results provide novel insight into the biology of early RA and the mechanism of tDMARD action and may help identify novel drug targets to improve rates of treatment-induced disease remission.

Disease Characteristics and Rheumatoid Arthritis Development in Patients with Early Undifferentiated Arthritis: A 2-year Followup Study.

PubMed

Brinkmann, Gina H; Norli, Ellen S; Kvien, Tore K; Haugen, Anne J; Grøvle, Lars; Nygaard, Halvor; Bjørneboe, Olav; Thunem, Cathrine; Mjaavatten, Maria D; Lie, Elisabeth

2017-02-01

To examine the 2-year disease course in patients with undifferentiated arthritis (UA) focusing on fulfillment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) classification criteria. Data were provided by the Norwegian Very Early Arthritis Clinic study, which included patients presenting with ≥ 1 swollen joint of ≤ 16 weeks' duration. UA was defined as patients not fulfilling the 2010 ACR/EULAR RA criteria and who did not have a clinical diagnosis other than RA at baseline. The main outcome was fulfillment of the 2010 RA criteria. Secondary outcomes were disease-modifying antirheumatic drug (DMARD) use, resolution of synovitis without use of DMARD during followup, and final clinical diagnosis. We included 477 patients with UA of whom 47 fulfilled the 2010 ACR/EULAR RA criteria during followup (UA-RA) and 430 did not (UA-non-RA). Of the UA-RA patients, 70% fulfilled the criteria within the first 6 months. UA-RA patients were older, more often positive for rheumatoid factor and anticitrullinated protein antibodies, female, and ever smokers, and they more often presented with polyarticular arthritis, small joint involvement, and a swollen shoulder joint. During followup, 53% of UA-RA patients vs 13% of UA-non-RA patients used DMARD (p < 0.001). Overall, 71% of patients with UA achieved absence of clinical synovitis at final followup without use of DMARD. The most frequent final clinical diagnosis was UA (61%). Only 9.8% of patients with UA fulfilled the 2010 RA criteria during 2-year followup. Small joint involvement and swollen shoulder joint were among the factors associated with RA development. In two-thirds of patients with UA, the arthritis resolved without use of DMARD.

A tumor endoprosthesis is useful in elderly rheumatoid arthritis patient with acute intercondylar fracture of the distal femur.

PubMed

Wakabayashi, Hiroki; Naito, Yohei; Hasegawa, Masahiro; Nakamura, Tomoki; Sudo, Akihiro

2012-05-01

The purpose of this paper is to report the use of total knee arthroplasty using a tumor prosthesis in the treatment of elderly patients with an intercondylar fracture of the distal femur. Supracondylar fractures of the femur in patients with rheumatoid arthritis are difficult to treat due to joint deformity. We present outcomes for treating intercondylar fractures of the distal femur in rheumatoid arthritis patient using a tumor endoprosthesis. This technique allows early mobilization of the patient, with restoration of a good range of knee motion. A tumor prosthesis appears to be a viable treatment option for intercondylar femoral fractures in elderly patients. It is well tolerated and permits early ambulation and return to activities of daily living.

[Morphologic festures of cardiac lesions in rheumatoid arthritis].

PubMed

Kop'eva, T N

1976-11-01

Morphological examinations of the heart in cases of articulo-visceral rheumatoid arthritis revealed in 20 of the 35 conducted observations certain changes attributable to the underlying disease. The following groups of changes were revealed: 1) endocarditis; 2) myocarditis; 3) pericarditis; 4) rheumatoid nodules; 5) valvular sclerosis and mural endocarditis; 6) cardiosclerosis; 7) amyloidosis; 8) coronaritis and coronary sclerosis; 9) adhesions in the pericardial cavity. The severity of cardiac leasion in rheumatoid arthritis is determined by the involvement of the serosa into the pathological process. Inflammatory and sclerotic changes in the myocardium are predimonantly of a subepicardial and subendocardial nature, usually non-accompanied by any clear clinical symptoms, or taking a latent course. Rheumatoid nodules typical of rheumatoid arthritis, and deposits of amyloid masses in the walls of the coronary arteries are noted rarely. Changes in the heart are observed mostly in "septic", subacute rheumatoid arthritis and in Still's disease. Cardiac lesions in rheumatoid arthritis are connected with microcirculatory disorders caused by immunopathological processes.

Women's accounts of help-seeking in early rheumatoid arthritis from symptom onset to diagnosis.

PubMed

Townsend, Anne; Backman, Catherine L; Adam, Paul; Li, Linda C

2014-12-01

As interest in gender and health grows, the notion that women are more likely than men to consult doctors is increasingly undermined as more complex understandings of help seeking and gender emerge. While men's reluctance to seek help is associated with practices of masculinities, there has been less consideration of women's help-seeking practices. Rheumatoid arthritis (RA) is a chronic disease that predominantly affects women and requires prompt treatment but considerable patient-based delays persist along the care pathway. This paper examines women's accounts of help seeking in early RA from symptom onset to diagnosis. We conducted in-depth interviews with 37 women with RA <12 months in Canada. Analysis was based on a constant comparison, thematic approach informed by narrative analysis. The women's accounts featured masculine practices associated with men's help-seeking. The women presented such behaviours as relational, e.g. rooted in family socialisation and a determination to maintain roles and 'normal' life. Our findings raise questions about how far notions of gender operate to differentiate men and women's help seeking and may indicate more similarities than differences. Recognising this has implications for policy and practice initiatives for both men and women. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

[Progress on rheumatoid arthritis in elderly].

PubMed

Wang, Xin; Zhao, Qin; Deng, Zhao-da; Wang, Xiao-Yuan; Zhang, Si-Gong; Shen, Hai-Li

2017-06-25

During choosing non-steroidal anti-inflammatory drugs(NSAIDs), risk factors should be evaluated in elder patients with rheumatoid arthritis. The present study focused on biological therapies, and elderly patients should be more concerned about the risk of infection when used it. Traditional Chinese medicine has advantages of obvious curative effect, especially for tripterygium wilfordii, large clinical trial on western and Chinese medical accurate drug strategies for old patients with rheumatoid arthritis. Old patients are easier to suffer from cardiac diseases and interstitial lung disease, rheumatoid arthritis could be controlled along with the treatment for coexistent disease. The incidence of rheumatoid arthritis in old patients is the same with other RA, and need to treat to target based on the aim of relieve pain and reduce activity of diseases, while the clinical charteristic and treatment target in elder patients with rheumatoid arthritis were not similar with other aged patient, so treatment standard target would vary with aging. Resent clinical studies excluded old patients, lead to lack of evidence-based medicine data. Clinical study for elder patients with rheumatoid arthritis are energetically carrying out, and could provide base and guide for clinical treatment. Copyright© 2017 by the China Journal of Orthopaedics and Traumatology Press.

Are rheumatoid arthritis patients discernible from other early arthritis patients using 1.5T extremity magnetic resonance imaging? a large cross-sectional study.

PubMed

Stomp, Wouter; Krabben, Annemarie; van der Heijde, Désirée; Huizinga, Tom W J; Bloem, Johan L; van der Helm-van Mil, Annette H M; Reijnierse, Monique

2014-08-01

Magnetic resonance imaging (MRI) is increasingly used in rheumatoid arthritis (RA) research. A European League Against Rheumatism (EULAR) task force recently suggested that MRI can improve the certainty of RA diagnosis. Because this recommendation may reflect a tendency to use MRI in daily practice, thorough studies on the value of MRI are required. Thus far no large studies have evaluated the accuracy of MRI to differentiate early RA from other patients with early arthritis. We performed a large cross-sectional study to determine whether patients who are clinically classified with RA differ in MRI features compared to patients with other diagnoses. In our study, 179 patients presenting with early arthritis (median symptom duration 15.4 weeks) underwent 1.5T extremity MRI of unilateral wrist, metacarpophalangeal, and metatarsophalangeal joints according to our arthritis protocol, the foot without contrast. Images were scored according to OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) by 2 independent readers. Tenosynovitis was also assessed. The main outcome was fulfilling the 1987 American College of Rheumatology (ACR) criteria for RA. Test characteristics and areas under the receiver-operator-characteristic curves (AUC) were evaluated. In subanalyses, the 2010 ACR/EULAR criteria were used as outcome, and analyses were stratified for anticitrullinated protein antibodies (ACPA). The ACR 1987 criteria were fulfilled in 43 patients (24.0%). Patients with RA had higher scores for synovitis, tenosynovitis, and bone marrow edema (BME) than patients without RA (p < 0.05). ACPA-positive patients had more BME (median scores 6.5 vs. 4.25, p = 0.016) than ACPA-negative patients. For all MRI features, the predictive value for the presence of RA was low (< 50%). For all MRI features the AUC were < 0.70. Patients who fulfilled ACR/EULAR 2010 criteria but not ACR87 criteria for RA had less synovitis than patients who were positive for RA according to

Pathogenesis and Prediction of Rheumatoid Arthritis

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-13-1-0408 TITLE: Pathogenesis and Prediction of Rheumatoid Arthritis PRINCIPAL INVESTIGATOR: Kevin D. Deane, MD/PhD...NUMBER W81XWH-13-1-0408 Pathogenesis and Prediction of Rheumatoid Arthritis 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...there is a preclinical period of rheumatoid arthritis (RA) development that is characterized by abnormalities of the immune system prior to the onset of

Subchondral pseudocysts in rheumatoid arthritis.

PubMed

Rennell, C; Mainzer, F; Multz, C V; Genant, H K

1977-12-01

Subchondral cyst formation (geode) is a not uncommon manifestation of rheumatoid arthritis which may at times impede correct radiologic interpretation. Four patients with rheumatoid arthritis who demonstrated striking subarticular cystic erosive disease are described. These cases emphasize the nature and appearance of this interesting finding.

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...

Management of Early- and Late-Stage Rheumatoid Arthritis: Are Physiotherapy Students' Intended Behaviours Consistent with Canadian Best Practice Guidelines?

PubMed Central

Lineker, Sydney C.; Hallett, Christina; Tumber, Jake; Fernando, Nalin; Hul, Magdalena

2012-01-01

ABSTRACT Purpose: This study examined whether physiotherapy students in a problem-based learning (PBL) curriculum intend to implement best practices for management of clients with rheumatoid arthritis (RA). Method: Physiotherapy students (n=49) completed a subsection of the ACREU Primary Care Survey to evaluate the concordance between intended behaviours and Canadian best practices for early- and late-stage RA, before and after completing the relevant PBL content. Changes in scores were assessed using McNemar's test for dependent proportions. Results: Most students indicated that they would recommend treatments or referrals for physiotherapy/exercise, education, and occupational therapy or joint protection pre- and post-PBL (>83% and >95%, respectively). Post-PBL, more students recommended referral to a rheumatologist and disease-modifying anti-rheumatic drugs (DMARDs) for both early and late RA; however, the increase was significant only for early RA (p=0.013 and 0.031 for referral to rheumatologist and DMARDs, respectively). More students recommended psychosocial support at both stages of RA post-PBL (early RA: p<0.001; late RA: p=0.031). Although more students recommended DMARDs post-PBL, only 8 students in total made this recommendation (16%), and fewer students considered use of non-steroidal anti-inflammatory drugs. Most students (94%) did not recommend referral to a surgeon for early or late RA. Conclusion: Intended behaviour of physiotherapy students was more consistent with Canadian best practice guidelines for managing clients with early- and late-stage RA following the PBL curriculum. Further study is required to determine whether the students were less aware of best practices related to pharmacologic interventions and timely referral to appropriate specialists, or whether they considered these issues to be outside their scope of practice. PMID:23729962

The foot as a barrier in patients with early rheumatoid arthritis - an interview study among Swedish women and men.

PubMed

Björk, Mathilda; Thyberg, Ingrid; Valtersson, Eva; Östlund, Gunnel; Stenström, Birgitta; Sverker, Annette

2017-12-01

Foot impairments are related to reduced mobility and participation restrictions in daily activities in patients with established rheumatoid arthritis (RA). The new biological medications are effective and reduce disease activity, but not disability to the same extent. Foot impairments are assumed to be related to participation restrictions also in patients with early RA, diagnosed after the introduction of biological medications. The knowledge of foot impairments needs to be more explored after the introduction of biological disease-modifying drugs (bDMARDs). The aim of this study was to explore the patients' perspective of foot impairments related to early RA. The sample included 59 patients (20-63 years) who were interviewed about participation dilemmas in daily life using the Critical Incident Technique. The interviews were audio-recorded and transcribed. Data related to foot impairments were extracted and analyzed thematically. A research partner validated the analysis. The study was approved by the Regional Ethics Committee. Patients with early RA described a variety of participation restrictions related to foot impairments: 1) foot hindrances in domestic life, 2) foot impairments influencing work, 3) leisure activities restricted by one's feet 4) struggling to be mobile 5) foot impairments as an early sign of rheumatic disease. There is a need to focus on foot impairments related to early RA, and for health care professionals to understand these signs. A suggestion for future research is to conduct a longitudinal follow-up of foot impairment related to medication, disease activity and disability in patients diagnosed after the introduction of bDMARDs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Transcriptional signature associated with early rheumatoid arthritis and healthy individuals at high risk to develop the disease

PubMed Central

Macías-Segura, N.; Bastian, Y.; Santiago-Algarra, D.; Castillo-Ortiz, J. D.; Alemán-Navarro, A. L.; Jaime-Sánchez, E.; Gomez-Moreno, M.; Saucedo-Toral, C. A.; Lara-Ramírez, Edgar E.; Zapata-Zuñiga, M.; Enciso-Moreno, L.; González-Amaro, R.; Ramos-Remus, C.; Enciso-Moreno, J. A.

2018-01-01

Background Little is known regarding the mechanisms underlying the loss of tolerance in the early and preclinical stages of autoimmune diseases. The aim of this work was to identify the transcriptional profile and signaling pathways associated to non-treated early rheumatoid arthritis (RA) and subjects at high risk. Several biomarker candidates for early RA are proposed. Methods Whole blood total RNA was obtained from non-treated early RA patients with <1 year of evolution as well as from healthy first-degree relatives of patients with RA (FDR) classified as ACCP+ and ACCP- according to their antibodies serum levels against cyclic citrullinated peptides. Complementary RNA (cRNA) was synthetized and hybridized to high-density microarrays. Data was analyzed in Genespring Software and functional categories were assigned to a specific transcriptome identified in subjects with RA and FDR ACCP positive. Specific signaling pathways for genes associated to RA were identified. Gene expression was evaluated by qPCR. Receiver operating characteristic (ROC) analysis was used to evaluate these genes as biomarkers. Results A characteristic transcriptome of 551 induced genes and 4,402 repressed genes were identified in early RA patients. Bioinformatics analysis of the data identified a specific transcriptome in RA patients. Moreover, some overlapped transcriptional profiles between patients with RA and ACCP+ were identified, suggesting an up-regulated distinctive transcriptome from the preclinical stages up to progression to an early RA state. A total of 203 pathways have up-regulated genes that are shared between RA and ACCP+. Some of these genes show potential to be used as progression biomarkers for early RA with area under the curve of ROC > 0.92. These genes come from several functional categories associated to inflammation, Wnt signaling and type I interferon pathways. Conclusion The presence of a specific transcriptome in whole blood of RA patients suggests the activation

Rheumatoid Arthritis

MedlinePlus

... condition? What if my symptoms come back? Other organizations National Institute of Arthritis and Musculoskeletal and Skin Diseases Citations Diagnosis and Management of Rheumatoid Arthritis by JA Rindfleisch, ...

Complement activating properties of complexes containing rheumatoid factor in synovial fluids and sera from patients with rheumatoid arthritis.

PubMed Central

Elson, C J; Carter, S D; Cottrell, B J; Scott, D G; Bacon, P A; Wallington, T B

1985-01-01

The relationship between complexes containing rheumatoid factor and complexes activating complement was examined in synovial fluids and sera from patients with rheumatoid arthritis (RA). In each case this was performed by quantifying the amount of rheumatoid factor bound by solid phase Fab'2 anti-C3 and/or solid phase conglutinin. Both anti-C3 coated and conglutinin coated microtitre plates bound high levels of complexes containing rheumatoid factor from sera of RA patients with vasculitis. Unexpectedly, these complexes were detected in synovial fluids from only a minority of RA patients with synovitis. However, RA synovial fluids did contain other complexes as shown by the presence of complement consuming activity, C1q binding material and immunoglobulin attaching to conglutinin. It is considered that in RA synovial fluids the complexes containing RF and those activating complement are not necessarily the same whilst in vasculitic sera the complexes containing rheumatoid factor also activate complement. PMID:3978872

Treatment of very early rheumatoid arthritis with symptomatic therapy, disease-modifying antirheumatic drugs, or biologic agents: a cost-effectiveness analysis.

PubMed

Finckh, Axel; Bansback, Nick; Marra, Carlo A; Anis, Aslam H; Michaud, Kaleb; Lubin, Stanley; White, Marc; Sizto, Sonia; Liang, Matthew H

2009-11-03

Long-term control or remission of rheumatoid arthritis (RA) may be possible with very early treatment. However, no optimal first therapeutic strategy has been determined. To assess the potential cost-effectiveness of major therapeutic strategies for very early RA. Decision analytic model with probabilistic sensitivity analyses. Published data, the National Data Bank for Rheumatic Diseases, and actual 2007 hospital costs. U.S. adults with very early RA (symptom duration early DMARD therapy with methotrexate; and early therapy with biologics and methotrexate. Cost per quality-adjusted life-year (QALY) gained. By reducing the progression of joint erosions and subsequent functional disability, both early intervention strategies increase quality-adjusted life more than the pyramid strategy and save long-term costs. When the cost of very early intervention is factored in, the cost-effectiveness ratio of the early DMARD strategy is $4849 per QALY (95% CI, $0 to $16 354 per QALY) compared with the pyramid strategy, whereas the benefits gained through the early biologic strategy come at a substantial incremental cost. The early DMARD strategy maximizes the effectiveness of early DMARDs and reserves the use of biologics for patients with more treatment-resistant disease of longer duration, for which the incremental benefit of biologics is greater. The early biologic strategy becomes more cost-effective if drug prices are reduced, risk for death is permanently lowered through biologic therapy, patients experience drug-free remission, responders can be selected before therapy initiation, or effective alternative antirheumatic agents are available for

Detection of rheumatoid arthritis using infrared imaging

NASA Astrophysics Data System (ADS)

Frize, Monique; Adéa, Cynthia; Payeur, Pierre; Di Primio, Gina; Karsh, Jacob; Ogungbemile, Abiola

2011-03-01

Rheumatoid arthritis (RA) is an inflammatory disease causing pain, swelling, stiffness, and loss of function in joints; it is difficult to diagnose in early stages. An early diagnosis and treatment can delay the onset of severe disability. Infrared (IR) imaging offers a potential approach to detect changes in degree of inflammation. In 18 normal subjects and 13 patients diagnosed with Rheumatoid Arthritis (RA), thermal images were collected from joints of hands, wrists, palms, and knees. Regions of interest (ROIs) were manually selected from all subjects and all parts imaged. For each subject, values were calculated from the temperature measurements: Mode/Max, Median/Max, Min/Max, Variance, Max-Min, (Mode-Mean), and Mean/Min. The data sets did not have a normal distribution, therefore non parametric tests (Kruskal-Wallis and Ranksum) were applied to assess if the data from the control group and the patient group were significantly different. Results indicate that: (i) thermal images can be detected on patients with the disease; (ii) the best joints to image are the metacarpophalangeal joints of the 2nd and 3rd fingers and the knees; the difference between the two groups was significant at the 0.05 level; (iii) the best calculations to differentiate between normal subjects and patients with RA are the Mode/Max, Variance, and Max-Min. We concluded that it is possible to reliably detect RA in patients using IR imaging. Future work will include a prospective study of normal subjects and patients that will compare IR results with Magnetic Resonance (MR) analysis.

Rheumatoid arthritis of the cervical spine: current techniques for management.

PubMed

Casey, Adrian T H; Crockard, H Alan; Pringle, Jean; O'Brien, Michael F; Stevens, John M

2002-04-01

The incidence of rheumatoid arthritis in the European and North American population is significant. Rheumatoid arthritis can result in serious damage to the cervical spine and the central neuraxis, ranging from mild instability to myelopathy and death. Aggressive conservative care should be established early. The treating physician should not be lulled into a false sense of security by reports suggesting that cervical subluxations are typically asymptomatic [76-78]. Gradual spinal cord compression can result in severe neurologic deficits that may be irreversible despite appropriate surgical intervention when applied too late. [figure: see text] The treatment of rheumatoid disease in the cervical spine is challenging. Many details must be considered when diagnosing and attempting to institute a treatment plan, particularly surgical treatment. The pathomechanics may result in either instability or ankylosis. The superimposed deformities may be either fixed or mobile. The algorithm suggested by the authors can be used to navigate through the numerous details that must be considered to formulate a reasonable surgical plan. Although these patients are [figure: see text] frail, an "aggressive" surgical solution applied in a timely fashion yields better results than an incomplete or inappropriate surgical solution applied too late. When surgical intervention is anticipated, it should be performed before the development of severe myelopathy. Patients who progress to a Ranawat III-B status have a much higher morbidity and mortality rate associated with surgical intervention than do patients who ambulate. Although considered aggressive by some, "prophylactic" stabilization and fusion of a [figure: see text] relatively flexible, moderately deformed spine before the onset of severe neurologic symptoms may be reasonable. This approach ultimately may serve the patient better than "observation" if the patient is slowly drifting into a severe spinal deformity or shows signs of

Causes and consequences of fatigue in rheumatoid arthritis.

PubMed

Katz, Patricia

2017-05-01

To review current information on the causes, treatments, and consequences of fatigue in rheumatoid arthritis. Disease activity (inflammation, pain, joint symptoms) is associated with greater fatigue. However, disease activity per se accounts for only a small portion of fatigue, and rheumatoid arthritis medications that reduce disease activity have small effects on fatigue. Instead, factors outside the direct effects of rheumatoid arthritis, such as obesity, physical inactivity, sleep disturbance, and depression, explain the majority of variation in fatigue. Some of these factors may be indirect effects of disease (e.g. pain can lead to sleep disturbance). Rheumatoid arthritis has significant effects on the quality of life of individuals with rheumatoid arthritis. The most effective approaches to reducing rheumatoid arthritis fatigue appear to be behavioral, such as increasing physical activity, or cognitive, such as cognitive behavioral interventions. Fatigue in rheumatoid arthritis appears to be largely because of factors outside the direct effects of the disease, such as behavioral and psychological factors. In spite of the tremendous impact of fatigue on patient health and quality of life, effective treatments remain elusive, but existing data show that behavioral and cognitive approaches may be most effective.

Expression of the Inherently Autoreactive Idiotope 9G4 on Autoantibodies to Citrullinated Peptides and on Rheumatoid Factors in Patients with Early and Established Rheumatoid Arthritis

PubMed Central

Cambridge, Geraldine; Moura, Rita A.; Santos, Tania; Khawaja, Akif A.; Polido-Pereira, Joaquim; Canhão, Helena; Leandro, Maria J.; Fonseca, João E.

2014-01-01

Background The pre-symptomatic stage of Rheumatoid arthritis (RA) is associated with pro-inflammatory cytokines and autoantibodies. High levels and epitope spread by Rheumatoid factors (RhF) and autoantibodies to citrullinated proteins signify progression towards disease expression. In established RA, the persistence of high autoantibody levels reflects production by both long-lived plasma cells and short-lived plasmablasts. Neither the relative contributions to pathogenesis by autoantibodies from either source, nor the factors responsible for deciding the fate of autoantigen specific ‘parent’ B-cells, is understood. Phenotypic markers identifying subsets of autoreactive B-cells are therefore of interest in understanding the origin and perpetuation of the autoimmune response in RA. One such phenotypic marker is the rat monoclonal antibody, 9G4, which recognises an idiotope on immunoglobuins derived from the inherently autoreactive VH-gene, VH4-34. We therefore investigated whether the 9G4 idiotope was expressed on autoantibodies in patients with RA. Methodology/Principal Findings Sera from 19 patients with established RA and those with <1year history of untreated polyarthritis either resolving into RA (n = 42) or non-RA diagnosis (n = 31) were included. Autoantibodies to cyclic citrullinated peptides (CCP), RhF and co-expression of the 9G4 idiotope were measured by ELISA. 9G4 recognised a population of anti-CCP antibodies in the majority of sera from patients with established disease and also in samples from patients with early disaese. 9G4+RhF levels were generally lower and not associated with positivity for, or levels of 9G4+CCP. Conclusions/Significance The persistence of 9G4+ immunoglobulins, of any isotype, in serum is rare. We describe here the novel finding of 9G4 expression on anti-CCP antibodies in patients from the earliest symptoms of RA through to established disease. Our results suggest that 9G4 expression on anti-CCP autoantibodies was

Oral Metagenomic Biomarkers in Rheumatoid Arthritis

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-15-1-0320 TITLE: Oral Metagenomic Biomarkers in Rheumatoid Arthritis PRINCIPAL INVESTIGATOR: Edward K Chan CONTRACTING...Biomarkers in Rheumatoid Arthritis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0320 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Edward K Chan 5d...significant difference in the oral  microbiome at the subspecies level of individuals with  rheumatoid   arthritis  (RA). The goal is to test the

Serum levels of macrophage migration inhibitory factor are associated with rheumatoid arthritis course.

PubMed

Llamas-Covarrubias, Mara Anaís; Valle, Yeminia; Navarro-Hernández, Rosa Elena; Guzmán-Guzmán, Iris Paola; Ramírez-Dueñas, María Guadalupe; Rangel-Villalobos, Héctor; Estrada-Chávez, Ciro; Muñoz-Valle, José Francisco

2012-08-01

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unknown etiology. Many cytokines have been found to be associated with RA pathogenesis and among them is macrophage migration inhibitory factor (MIF). The aim of this study was to determine whether MIF serum levels are associated with RA course, clinical activity, and clinical biomarkers of the disease. MIF levels were determined in serum samples of 54 RA patients and 78 healthy subjects (HS) by enzyme-linked immunosorbent assay (ELISA). Disease activity was evaluated using the DAS28 score. Patients were subgrouped according to disease activity and years of evolution of disease. Statistical analysis was carried out by SPSS 10.0 and GraphPad Prism 5 software. RA patients presented increased levels of MIF as compared to HS. MIF levels were raised on early stages of RA and tend to decrease according to years of evolution. Moreover, MIF levels positively correlated with rheumatoid factor in RA patients and with C reactive protein in all individuals studied. Our findings suggest that MIF plays a role in early stages of RA.

Functional disability and health-related quality of life in South Africans with early rheumatoid arthritis.

PubMed

Hodkinson, B; Musenge, E; Ally, M; Meyer, P W A; Anderson, R; Tikly, M

2012-10-01

The severity and predictors of functional disability and health-related quality of life (HRQoL) in a cohort of South Africans with early rheumatoid arthritis (RA) were investigated. Changes in the Health Assessment Questionnaire Disability Index (HAQ) and the 36-Item Short Form Health Survey (SF-36) following 12 months of traditional disease-modifying anti-rheumatic drugs (DMARDs) were studied in previously DMARD-naïve adults with disease duration ≤ 2 years. The majority of the 171 patients were female (82%), Black Africans (89%) with a mean (SD) symptom duration of 11.6 (7.0) months. In the 134 patients seen at 12 months, there were significant improvements in the HAQ and all domains of the SF-36 but 92 (69%) still had substantial functional disability (HAQ > 0.5) and 89 (66%) had suboptimal mental health [SF-36 mental composite score (MCS) < 66.6]. Multivariate analysis showed that female sex (p = 0.05) and high baseline HAQ score (p < 0.01) predicted substantial functional disability at 12 months. Unemployment (p = 0.03), high baseline pain (p = 0.02), and HAQ score (p = 0.04) predicted suboptimal mental health, with a trend towards a low level of schooling being significant (p = 0.08). Early RA has a broad impact on HRQoL in indigent South Africans, with a large proportion of patients still showing substantial functional disability and suboptimal mental health despite 12 months of DMARD therapy. Further research is needed to establish the role of interventions including psychosocial support, rehabilitation programmes, and biological therapy to improve physical function and HRQoL in this population.

Preclinical carotid atherosclerosis in patients with rheumatoid arthritis.

PubMed

Roman, Mary J; Moeller, Elfi; Davis, Adrienne; Paget, Stephen A; Crow, Mary K; Lockshin, Michael D; Sammaritano, Lisa; Devereux, Richard B; Schwartz, Joseph E; Levine, Daniel M; Salmon, Jane E

2006-02-21

Rheumatoid arthritis is associated with increased morbidity and mortality because of cardiovascular disease, independent of traditional risk factors. To determine the prevalence of preclinical atherosclerosis in patients with rheumatoid arthritis and to identify clinical and biological markers for atherosclerotic disease in this patient population. Matched, cross-sectional study. Hospital for Special Surgery in New York City. 98 consecutive outpatients with rheumatoid arthritis who were followed by rheumatologists and 98 controls matched on age, sex, and ethnicity. Cardiovascular risk factor ascertainment and carotid ultrasonography in all participants; disease severity, disease treatment, and inflammatory markers in patients with rheumatoid arthritis. Despite a more favorable risk factor profile, patients with rheumatoid arthritis had a 3-fold increase in carotid atherosclerotic plaque (44% vs. 15%; P < 0.001). The relationship between rheumatoid arthritis and carotid atherosclerotic plaque remained after accounting for age, serum cholesterol levels, smoking history, and hypertensive status; adjusted predicted prevalence was 7.4% (95% CI, 3.4% to 15.2%) for the control group and 38.5% (CI, 25.4% to 53.5%) for patients with rheumatoid arthritis. Age (P < 0.001) and current cigarette use (P < 0.014) were also significantly associated with carotid atherosclerotic plaque. Among patients with rheumatoid arthritis, atherosclerosis was related to age, hypertension status, and use of tumor necrosis factor-alpha inhibitors (a possible marker of disease severity). The study had a cross-sectional design, and inflammatory markers were determined only once. Patients with rheumatoid arthritis have a high prevalence of preclinical atherosclerosis independent of traditional risk factors, suggesting that chronic inflammation and, possibly, disease severity are atherogenic in this population.

Hearing status in patients with rheumatoid arthritis.

PubMed

Ahmadzadeh, A; Daraei, M; Jalessi, M; Peyvandi, A A; Amini, E; Ranjbar, L A; Daneshi, A

2017-10-01

Rheumatoid arthritis is thought to induce conductive hearing loss and/or sensorineural hearing loss. This study evaluated the function of the middle ear and cochlea, and the related factors. Pure tone audiometry, speech reception thresholds, speech discrimination scores, tympanometry, acoustic reflexes, and distortion product otoacoustic emissions were assessed in rheumatoid arthritis patients and healthy volunteers. Pure tone audiometry results revealed a higher bone conduction threshold in the rheumatoid arthritis group, but there was no significant difference when evaluated according to the sensorineural hearing loss definition. Distortion product otoacoustic emissions related prevalence of conductive or mixed hearing loss, tympanometry values, acoustic reflexes, and speech discrimination scores were not significantly different between the two groups. Sensorineural hearing loss was significantly more prevalent in patients who used azathioprine, cyclosporine and etanercept. Higher bone conduction thresholds in some frequencies were detected in rheumatoid arthritis patients that were not clinically significant. Sensorineural hearing loss is significantly more prevalent in refractory rheumatoid arthritis patients.

Negative interference by rheumatoid factor in alpha-fetoprotein chemiluminescent microparticle immunoassay.

PubMed

Wang, Hui; Bi, Xiaohui; Xu, Lei; Li, Yirong

2017-01-01

Background Rheumatoid factor causes positive interference in multiple immunoassays. Recently, negative interference has also been found in immunoassays in the presence of rheumatoid factor. The chemiluminescent microparticle immunoassay is widely used to determine serum alpha-fetoprotein. However, it is not clear whether the presence of rheumatoid factor in the serum causes interference in the chemiluminescent microparticle immunoassay of alpha-fetoprotein. Methods Serum alpha-fetoprotein was determined using the ARCHITECT alpha-fetoprotein assay. The estimation of alpha-fetoprotein recovery was carried out in samples prepared by diluting high-concentration alpha-fetoprotein serum with rheumatoid factor-positive or rheumatoid factor-negative serum. Paramagnetic microparticles coated with hepatitis B surface antigen-anti-HBs complexes were used to remove rheumatoid factor from the serum. Results The average recovery of alpha-fetoprotein was 88.4% and 93.8% in the rheumatoid factor-positive and rheumatoid factor-negative serum samples, respectively. The recovery of alpha-fetoprotein was significantly lower in the rheumatoid factor-positive serum samples than in the rheumatoid factor-negative serum samples. In two of five rheumatoid factor-positive samples, a large difference was found (9.8%) between the average alpha-fetoprotein recoveries in the serially diluted and initial recoveries. Fourteen rheumatoid factor-positive serum samples were pretreated with hepatitis B surface antigen-anti-HBs complex-coated paramagnetic microparticles. The alpha-fetoprotein concentrations measured in the pretreated samples increased significantly. Conclusions It was concluded that the alpha-fetoprotein chemiluminescent microparticle immunoassay is susceptible to interference by rheumatoid factor, leading to significantly lower results. Eliminating the incidence of negative interference from rheumatoid factor should be an important goal for immunoassay providers. In the meantime

Women’s accounts of help-seeking in early rheumatoid arthritis from symptom onset to diagnosis

PubMed Central

Townsend, Anne; Backman, Catherine L; Adam, Paul; Li, Linda C

2018-01-01

Background As interest in gender and health grows, the notion that women are more likely than men to consult doctors is increasingly undermined as more complex understandings of help seeking and gender emerge. While men’s reluctance to seek help is associated with practices of masculinities, there has been less consideration of women’s help-seeking practices. Rheumatoid arthritis (RA) is a chronic disease that predominantly affects women and requires prompt treatment but considerable patient-based delays persist along the care pathway. This paper examines women’s accounts of help seeking in early RA from symptom onset to diagnosis. Methods We conducted in-depth interviews with 37 women with RA <12 months in Canada. Analysis was based on a constant comparison, thematic approach informed by narrative analysis. Results The women’s accounts featured masculine practices associated with men’s help-seeking. The women presented such behaviours as relational, e.g. rooted in family socialisation and a determination to maintain roles and ‘normal’ life. Discussion Our findings raise questions about how far notions of gender operate to differentiate men and women’s help seeking and may indicate more similarities than differences. Recognising this has implications for policy and practice initiatives for both men and women. PMID:24567194

Altered Natural Killer Cell Subsets in Seropositive Arthralgia and Early Rheumatoid Arthritis Are Associated with Autoantibody Status.

PubMed

Chalan, Paulina; Bijzet, Johan; Kroesen, Bart-Jan; Boots, Annemieke M H; Brouwer, Elisabeth

2016-06-01

The role of natural killer (NK) cells in the immunopathogenesis of rheumatoid arthritis (RA) is unclear. Therefore, numerical and functional alterations of CD56(dim) and CD56(bright) NK cells in the early stages of RA development were studied. Whole blood samples from newly diagnosed, treatment-naive, seropositive (SP) and seronegative (SN) patients with RA (SP RA, n = 45 and SN RA, n = 12), patients with SP arthralgia (n = 30), and healthy controls (HC, n = 41) were assessed for numbers and frequencies of T cells, B cells, and NK cells. SP status was defined as positive for anticyclic citrullinated peptide antibodies (anti-CCP) and/or rheumatoid factor (RF). Peripheral blood mononuclear cells were used for further analysis of NK cell phenotype and function. Total NK cell numbers were decreased in SP RA and SP arthralgia but not in SN RA. Also, NK cells from SP RA showed a decreased potency for interferon-γ (IFN-γ) production. A selective decrease of CD56(dim), but not CD56(bright), NK cells in SP RA and SP arthralgia was observed. This prompted investigation of CD16 (FcγRIIIa) triggering in NK cell apoptosis and cytokine expression. In vitro, CD16 triggering induced apoptosis of CD56(dim) but not CD56(bright) NK cells from HC. This apoptosis was augmented by adding interleukin 2 (IL-2). Also, CD16 triggering in the presence of IL-2 stimulated IFN-γ and tumor necrosis factor-α expression by CD56(dim) NK cells. The decline of CD56(dim) NK cells in SP arthralgia and SP RA and the in vitro apoptosis of CD56(dim) NK cells upon CD16 triggering suggest a functional role of immunoglobulin G-containing autoantibody (anti-CCP and/or RF)-immune complexes in this process. Moreover, CD16-triggered cytokine production by CD56(dim) NK cells may contribute to systemic inflammation as seen in SP arthralgia and SP RA.

Arthroscopic Synovectomy of Wrist in Rheumatoid Arthritis.

PubMed

Shim, Jae Woo; Park, Min Jong

2017-11-01

Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting multiple joints. Wrist involvement is common. Patients with persistent symptoms despite medical management are candidates for surgery. Synovectomy can provide pain relief and functional improvement for rheumatoid wrist. Arthroscopic synovectomy is a safe and reliable method, with minimal postoperative morbidity. This article reviews the role, technique, and results of arthroscopic synovectomy in the rheumatoid wrist. Copyright © 2017 Elsevier Inc. All rights reserved.

Pathogenesis and Prediction of Future Rheumatoid Arthritis

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-13-1-0408 TITLE: Pathogenesis and Prediction of Future Rheumatoid Arthritis PRINCIPAL INVESTIGATOR: Kevin D. Deane, MD/PhD...SUBTITLE 5a. CONTRACT NUMBER Pathogenesis and Prediction of Rheumatoid Arthritis 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...preclinical period of rheumatoid arthritis (RA) development that is characterized by abnormalities of the immune system prior to the onset of the

Crescentic glomerular nephritis associated with rheumatoid arthritis: a case report.

PubMed

Balendran, K; Senarathne, L D S U; Lanerolle, R D

2017-07-21

negative. Her erythrocyte sedimentation rate was 110 mm in the first hour, and her C-reactive protein level was 45 mg/dl. Her liver profile showed hypoalbuminemia of 28 g/dl. She was treated with immunomodulators and had a good recovery of her renal function. This case illustrates a rare presentation of antineutrophil cytoplasmic antibody-negative crescentic glomerular nephritis in a patient with rheumatoid arthritis, awareness of which would facilitate early appropriate investigations and treatment.

Tsunami Early Warning via a Physics-Based Simulation Pipeline

NASA Astrophysics Data System (ADS)

Wilson, J. M.; Rundle, J. B.; Donnellan, A.; Ward, S. N.; Komjathy, A.

2017-12-01

Through independent efforts, physics-based simulations of earthquakes, tsunamis, and atmospheric signatures of these phenomenon have been developed. With the goal of producing tsunami forecasts and early warning tools for at-risk regions, we join these three spheres to create a simulation pipeline. The Virtual Quake simulator can produce thousands of years of synthetic seismicity on large, complex fault geometries, as well as the expected surface displacement in tsunamigenic regions. These displacements are used as initial conditions for tsunami simulators, such as Tsunami Squares, to produce catalogs of potential tsunami scenarios with probabilities. Finally, these tsunami scenarios can act as input for simulations of associated ionospheric total electron content, signals which can be detected by GNSS satellites for purposes of early warning in the event of a real tsunami. We present the most recent developments in this project.

Oral Metagenomic Biomarkers in Rheumatoid Arthritis

DTIC Science & Technology

2017-09-01

AWARD NUMBER: W81XWH-15-1-0320 TITLE: Oral Metagenomic Biomarkers in Rheumatoid Arthritis PRINCIPAL INVESTIGATOR: Edward K Chan CONTRACTING... Rheumatoid Arthritis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0320 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Edward K Chan 5d. PROJECT NUMBER...individuals with  rheumatoid   arthritis  (RA). The goal is to test the  hypothesis that oral microbiome and metagenomic analyses will allow us to identify new

Variability in depression prevalence in early rheumatoid arthritis: a comparison of the CES-D and HAD-D Scales

PubMed Central

Covic, Tanya; Pallant, Julie F; Tennant, Alan; Cox, Sally; Emery, Paul; Conaghan, Philip G

2009-01-01

Background Depression is common in rheumatoid arthritis (RA), however reported prevalence varies considerably. Two frequently used instruments to identify depression are the Center for Epidemiological Studies Depression (CES-D) scale, and the Hospital Anxiety and Depression Scale (HADS). The objectives of this study were to test if the CES-D and HADS-D (a) satisfy current modern psychometric standards for unidimensional measurement in an early RA sample; (b) measure the same construct (i.e. depression); and (c) identify similar levels of depression. Methods Data from the two scales completed by patients with early RA were fitted to the Rasch measurement model to show that (a) each scale satisfies the criteria of fit to the model, including strict unidimensionality; (b) that the scales can be co-calibrated onto a single underlying continuum of depression and to (c) examine the location of the cut points on the underlying continuum as indication of the prevalence of depression. Results Ninety-two patients with early RA (62% female; mean age = 56.3, SD = 13.7) gave 141 sets of paired CES-D and HAD-D data. Fit of the data from the CES-D was found to be poor, and the scale had to be reduced to 13 items to satisfy Rasch measurement criteria whereas the HADS-D met model expectations from the outset. The 20 items combined (CES-D13 and HADS-D) satisfied Rasch model expectations. The CES-D gave a much higher prevalence of depression than the HADS-D. Conclusion The CES-D in its present form is unsuitable for use in patients with early RA, and needs to be reduced to a 13-item scale. The HADS-D is valid for early RA and the two scales measure the same underlying construct but their cut points lead to different estimates of the level of depression. Revised cut points on the CES-D13 provide comparative prevalence rates. PMID:19200388

Inter- relationship between rheumatoid arthritis and periodontitis.

PubMed

Rajkarnikar, J; Thomas, B S; Rao, S K

2013-01-01

Periodontal medicine defines a rapidly emerging branch of Periodontology focusing on establishing a strong relationship between periodontal health and systemic health. It is speculated that the major common dysregulation which links Periodontitis with Rheumatoid arthritis (RA) is being played by the mediators of immune inflammatory response. To determine whether there is any relationship between periodontal disease and Rheumatoid arthritis. A total of 100 patients were included for the present study which was divided into two groups: one group (cases) included 50 patients attending the Department of Orthopedics, Kasturba Medical College, Manipal who were diagnosed of Rheumatoid arthritis. Another subject population included 50 patients as controls attending the Department of Oral Medicine, Manipal College of Dental Sciences, Manipal with age and gender matched with those of rheumatoid arthritis group. Specific measures for periodontitis included plaque index, gingival index, number of missing teeth, and radiographic alveolar bone loss scores. Measures of rheumatoid arthritis included health assessment questionaires, levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Various periodontal parameters were compared between the cases and controls. The average alveolar bone loss was statistically more severe in Rheumatoid arthritis (RA) group than in the controls although there were similar plaque index in both the groups. The gingival index was statistically higher in the RA group. The Erythrocyte Sedimentation Rate (ESR) and C- Reactive Protein (CRP) levels of RA patients were also significantly associated with the severity of periodontal disease. There was a significant association between Rheumatoid arthritis and Periodontitis which may be due to a common underlying deregulation of the inflammatory response in these individuals.

Near-infrared Fluorescence Optical Imaging in Early Rheumatoid Arthritis: A Comparison to Magnetic Resonance Imaging and Ultrasonography.

PubMed

Krohn, Michaela; Ohrndorf, Sarah; Werner, Stephanie G; Schicke, Bernd; Burmester, Gerd-Rüdiger; Hamm, Bernd; Backhaus, Marina; Hermann, Kay-Geert A

2015-07-01

Near-infrared fluorescence optical imaging (FOI) is a novel imaging technology in the detection and evaluation of different arthritides. FOI was validated in comparison to magnetic resonance imaging (MRI), greyscale ultrasonography (GSUS), and power Doppler ultrasonography (PDUS) in patients with early rheumatoid arthritis (RA). Hands of 31 patients with early RA were examined by FOI, MRI, and US. In each modality, synovitis of the wrist, metacarpophalangeal joints (MCP) 2-5, and proximal interphalangeal joints (PIP) 2-5 were scored on a 4-point scale (0-3). Sensitivity and specificity of FOI were analyzed in comparison to MRI and US as reference methods, differentiating between 3 phases of FOI enhancement (P1-3). Intraclass correlation coefficients (ICC) were calculated to evaluate the agreement of FOI with MRI and US. A total of 279 joints (31 wrists, 124 MCP and 124 PIP joints) were evaluated. With MRI as the reference method, overall sensitivity/specificity of FOI was 0.81/0.00, 0.49/0.84, and 0.86/0.38 for wrist, MCP, and PIP joints, respectively. Under application of PDUS as reference, sensitivity was even higher, while specificity turned out to be low, except for MCP joints (0.88/0.15, 0.81/0.76, and 1.00/0.27, respectively). P2 appears to be the most sensitive FOI phase, while P1 showed the highest specificity. The best agreement of FOI was shown for PDUS, especially with regard to MCP and PIP joints (ICC of 0.57 and 0.53, respectively), while correlation with MRI was slightly lower. FOI remains an interesting diagnostic tool for patients with early RA, although this study revealed limitations concerning the detection of synovitis. Further research is needed to evaluate its full diagnostic potential in rheumatic diseases.

Understanding Rheumatoid Arthritis (RA): Treatment and Causes

MedlinePlus

... this page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Treatment and Causes Past Issues / Summer 2014 Table of Contents How Is Rheumatoid Arthritis Treated? Doctors have many ways to treat this ...

Early development of Xenopus embryos is affected by simulated gravity

NASA Technical Reports Server (NTRS)

Yokota, Hiroki; Neff, Anton W.; Malacinski, George M.

1994-01-01

Early amphibian (Xenopus laevis) development under clinostat-simulated weightlessness and centrifuge-simulated hypergravity was studied. The results revealed significant effects on (i) 'morphological patterning' such as the cleavage furrow pattern in the vegetal hemisphere at the eight-cell stage and the shape of the dorsal lip in early gastrulae and (ii) 'the timing of embryonic events' such as the third cleavage furrow completion and the dorsal lip appearance. Substantial variations in sensitivity to simulated force fields were observed, which should be considered in interpreting spaceflight data.

Monetary value of lost productivity over a five year follow up in early rheumatoid arthritis estimated on the basis of official register data on patients' sickness absence and gross income: experience from the FIN-RACo trial.

PubMed

Puolakka, K; Kautiainen, H; Pekurinen, M; Möttönen, T; Hannonen, P; Korpela, M; Hakala, M; Arkela-Kautiainen, M; Luukkainen, R; Leirisalo-Repo, M

2006-07-01

To explore the monetary value of rheumatoid arthritis related loss of productivity in patients with early active disease. In a prospective cohort substudy of the FIN-RACo Trial, 162 patients with recent onset rheumatoid arthritis, aged 18 to 65 years and available to the workforce, were followed up for five years. Loss of work productivity in euros 2002 was estimated by data on absence for sickness and on income (human capital approach) from official databases. Treatment responses were evaluated by area under the curve (AUC) of the ACR-N measure and by increase in number of erosions in radiographs of hands and feet. The health assessment questionnaire (HAQ) at six months was linked to the International Classification of Functioning, Disability and Health (ICF). In all, 120 (75%) patients, women more often (82%) than men (61%) (p=0.002), lost work days. The mean lost productivity per patient-year was euro7217 (95% confidence interval (CI), 5561 to 9148): for women, euro6477 (4858 to 8536) and for men, euro8443 (5389 to 12,898). There was an inverse correlation with improvement: euro1101 (323 to 2156) and euro14 952 (10,662 to 19,852) for the highest and lowest quartiles of AUC of ARC-N, respectively. Lost productivity was associated with increase in the number of erosions and with disability in "changing and maintaining body position" subcategory of the ICF. Despite remission targeted treatment with disease modifying antirheumatic drugs, early rheumatoid arthritis results in substantial loss of productivity. A good improvement in the disease reduces the loss markedly.

Rotator cuff surgery in patients with rheumatoid arthritis: clinical outcome comparable to age, sex and tear size matched non-rheumatoid patients.

PubMed

Lim, S J; Sun, J-H; Kekatpure, A L; Chun, J-M; Jeon, I-H

2017-09-01

Aims This study aimed to compare the clinical outcomes of rotator cuff repair in patients with rheumatoid arthritis with those of patients who have no known history of the disease. We hypothesised that the functional outcomes are comparable between patients and without rheumatoid arthritis and may be affected by the level of disease activity, as assessed from C-reactive protein (CRP) level and history of systemic steroid intake. Patients and methods We conducted a retrospective review of the institutional surgical database from May 1995 to April 2012. Twenty-nine patients with rheumatoid arthritis who had rotator cuff repair were enrolled as the study group. Age, sex, and tear size matched patients with no disease who were selected as the control group. The mean duration of follow-up was 46 months (range 24-92 months). Clinical outcomes were assessed with the American Shoulder and Elbow Surgeons (ASES) questionnaire, Constant score and visual analogue scale (VAS). All data were recorded preoperatively and at regular postoperative follow-up visits. CRP was measured preoperatively as the disease activity marker for rheumatoid arthritis. Medication history was thoroughly reviewed in the study group. Results In patients with rheumatoid arthritis, all shoulder functional scores improved after surgery (ASES 56.1-78.1, Constant 50.8-70.5 and VAS 5.2-2.5; P < 0.001). The functional outcome of surgery in patients with rheumatoid arthritis was comparable to that of the control group (difference with control: ASES 78.1 vs. 85.5, P = 0.093; Constant 70.5 vs. 75.9, P = 0.366; VAS 2.5 vs. 1.8, P = 0.108). Patients with rheumatoid arthritis who had an elevated CRP level (> 1 mg/dl) showed inferior clinical outcomes than those with normal CRP levels. Patients with a history of systemic steroid intake showed inferior functional outcomes than those who had not taken steroids. Conclusions Surgical intervention for rotator cuff tear in patients with rheumatoid arthritis

MRI evidence of persistent joint inflammation and progressive joint damage despite clinical remission during treatment of early rheumatoid arthritis.

PubMed

Forslind, K; Svensson, B

2016-01-01

To determine the value of magnetic resonance imaging (MRI) of bones and joints in patients with recent-onset rheumatoid arthritis (RA) treated for 2 years from diagnosis with disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticoids. Thirteen patients with early RA were treated according to clinical practice and followed with MRI, radiographs, and Disease Activity Score calculated on 28 joints (DAS28) at inclusion (baseline) and after 1, 4, 7, 13, and 25 months. MRI of the dominant wrist and metacarpophalangeal (MCP) joints were assessed for synovitis, bone oedema, and erosions using the RA MRI Score (RAMRIS) and for tenosynovitis by an MRI tenosynovitis scoring method. Radiographs were assessed by the van der Heijde modified Sharp score (SHS). Clinical remission was defined by a DAS28 < 2.6. MRI at baseline detected inflammation in joints and tendons in all patients as well as erosions in 10 out of 13 patients. Over time, the erosion score increased while the synovitis and tenosynovitis scores remained almost unchanged. Bone oedema strongly correlated with synovitis. Synovitis and tenosynovitis correlated well with the erosion score at baseline but not thereafter. The MRI changes showed that joint damage started early and continued in the presence of persistent synovial and tenosynovial inflammation. The observations made in this small study suggest that the treatment goal of 'clinical remission' should be supplemented by a 'joint remission' goal. To this end, MRI is an appropriate tool. Further studies are needed to evaluate the optimal use of MRI in early RA.

Early BHs: simulations and observations

NASA Astrophysics Data System (ADS)

Cappelluti, Nico; di-Matteo, Tiziana; Schawinski, Kevin; Fragos, Tassos

We report recent investigations in the field of Early Black Holes. We summarize recent theoretical and observational efforts to understand how Black Holes formed and eventually evolved into Super Massive Black Holes at high-z. This paper makes use of state of the art computer simulations and multiwavelength surveys. Although non conclusive, we present results and hypothesis that pose exciting challenges to modern astrophysics and to future facilities.

Mortality of rheumatoid arthritis in Japan: a longitudinal cohort study.

PubMed

Hakoda, M; Oiwa, H; Kasagi, F; Masunari, N; Yamada, M; Suzuki, G; Fujiwara, S

2005-10-01

To determine the mortality risk of Japanese patients with rheumatoid arthritis, taking into account lifestyle and physical factors, including comorbidity. 91 individuals with rheumatoid arthritis were identified during screening a cohort of 16 119 Japanese atomic bomb survivors in the period 1958 to 1966. These individuals and the remainder of the cohort were followed for mortality until 1999. Mortality risk of the rheumatoid patients was estimated by the Cox proportional hazards model. In addition to age and sex, lifestyle and physical factors such as smoking status, alcohol consumption, blood pressure, and comorbidity were included as adjustment factors for the analysis of total mortality and for analysis of mortality from each cause of death. 83 of the rheumatoid patients (91.2%) and 8527 of the non-rheumatoid controls (52.9%) died during mean follow up periods of 17.8 and 28.0 years, respectively. The age and sex adjusted hazard ratio for mortality in the rheumatoid patients was 1.60 (95% confidence interval, 1.29 to 1.99), p < 0.001. Multiple adjustments, including for lifestyle and physical factors, resulted in a similar mortality hazard ratio of 1.57 (1.25 to 1.94), p < 0.001. Although mortality risk tended to be higher in male than in female rheumatoid patients, the difference was not significant. Pneumonia, tuberculosis, and liver disease were significantly increased as causes of death in rheumatoid patients. Rheumatoid arthritis is an independent risk factor for mortality. Infectious events are associated with increased mortality in rheumatoid arthritis.

Early use of simulation in medical education.

PubMed

Owen, Harry

2012-04-01

An oft-cited belief that, until recently, simulators used in education of health care professionals were simple models is wrong. Hundreds of years ago and, in one instance, thousands of years ago, intricate models were used to help teach anatomy and physiology and in training in obstetrics and many surgical disciplines. Simulators were used to learn skills before performing them on patients and in high-stakes assessment.The newest technologies were often used in simulators to improve fidelity. In the 18th century, obstetric simulators could leak amniotic fluid, and blood were used to train midwives and obstetricians to recognize and manage complications of childbirth. Italy was the major source of simulators early in the 18th century, but in the 19th century, dominance in clinical simulation moved to France, Britain, and then Germany. In comparison, much of the 20th century was a "dark age" for simulation.

Prognostic factors in juvenile rheumatoid arthritis: a case-control study revealing early predictors and outcome after 14.9 years.

PubMed

Flatø, Berit; Lien, Gunhild; Smerdel, Anna; Vinje, Odd; Dale, Knut; Johnston, Virginia; Sørskaar, Dag; Moum, Torbjørn; Ploski, Rafal; Førre, Øystein

2003-02-01

To describe the physical and psychosocial outcome in patients with juvenile rheumatoid arthritis (JRA), compared with subjects in the general population, and to determine patient characteristics, HLA alleles, and disease variables within the first 6 months of disease onset that predict persistent disease, joint erosions, and physical disability. A cohort of 268 (85%) of 316 patients with JRA first admitted to the hospital between 1980 and 1985 were examined after a median of 14.9 years (range 11.7-25.1) of disease duration. Controls matched for age, sex, and geographic region were randomly selected from the general population. Patients' medical records were retrospectively reviewed. Clinical examinations and radiographs of the hips, ankles, and affected joints were obtained. HLA-DRB1 and DPB1 alleles were determined by genotyping and HLA-B27 by serologic testing. Physical and psychosocial health status was assessed using the Short-Form Health Survey (SF-36) and the Health Assessment Questionnaire (HAQ). At followup, 133 patients with JRA (50%) were in remission, 63 (24%) had developed joint erosions, and 93 (36%) had impaired physical functioning (HAQ > 0.0). Patients had greater disability, more bodily pain, and poorer general health than controls. Comparable levels of education, social function, and mental health were found, but the patients had higher rates of unemployment than controls (19% vs 7%; p < 0.001). Predictors of persistent disease and joint erosions were: young onset age and large numbers of affected joints, long duration of elevated erythrocyte sedimentation rate (ESR), and positive IgM rheumatoid factor (RF) within the first 6 months. Additionally, persistent disease was predicted by the presence of DRB1*08, and joint erosions were predicted by symmetric arthritis and DRB1*08 and HLA-B27 in combination. DRB1*01 was a predictor of joint erosions in the pauciarticular onset type (n = 163). Predictors of physical disability were: female sex, symmetric

Visceral leishmaniasis in a rheumatoid arthritis patient receiving methotrexate.

PubMed

Reina, Delia; Cerdà, Dacia; Güell, Elena; Martínez Montauti, Joaquín; Pineda, Antonio; Corominas, Hèctor

Patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs are susceptible to severe infections such as leishmaniasis. As L. infantum is endemic in the Mediterranean region, it is necessary to rule this infectious process out in any RA patient presenting with fever and pancytopenia. An early diagnosis based on a high suspicion can prevent a fatal outcome. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

What People with Rheumatoid Arthritis Need to Know about Osteoporosis

MedlinePlus

... People With Rheumatoid Arthritis Need to Know About Osteoporosis What Is Rheumatoid Arthritis? Rheumatoid arthritis is an ... Management Strategies Resources For Your Information What Is Osteoporosis? Osteoporosis is a condition in which the bones ...

Living with persistent rheumatoid arthritis: a BARFOT study.

PubMed

Bala, Sidona-Valentina; Samuelson, Karin; Hagell, Peter; Fridlund, Bengt; Forslind, Kristina; Svensson, Björn; Thomé, Bibbi

2017-09-01

To describe and understand the meaning of living with persistent rheumatoid arthritis. A considerable number of patients with rheumatoid arthritis live with an ongoing active and symptomatic illness despite access to potent antirheumatic treatment. There is, however, a lack of knowledge about the meaning of living with this severe long-term illness, defined as persistent rheumatoid arthritis. A descriptive design based on a hermeneutic phenomenological method was used. Ten adults with persistent rheumatoid arthritis and at least five years disease duration were interviewed. The interviews were analysed according to van Manen's method. Living with persistent rheumatoid arthritis revealed four overall themes: an existence dominated by painful symptoms and treatment, radical changes and limitations in one's life, a continual struggle to cope with one's life and to master the illness, and a dependency on those who are close by and the world around. The lifeworld was affected to a varying extent and in various ways by the illness but also by the dependence on its treatment and care that was not experienced as sufficiently meeting needs in terms of security, access to and coordination of care as well as team and rehabilitation services. Persistent rheumatoid arthritis and its treatment entail a radical effect on the person's life and quality of life. Current ordinary rheumatology care does not seem to meet the individual needs of the person with persistent rheumatoid arthritis in an optimal way. A greater knowledge about and understanding of the person who lives with persistent rheumatoid arthritis is important for facilitating the development of care and the relief of suffering. A holistic alternative to conventional clinical practice, such as person-centred care, could be tested as an innovative model of care. Our findings might serve as material for educational and counselling purposes for healthcare professionals. © 2016 John Wiley & Sons Ltd.

Why are Dutch rheumatologists reluctant to use the COBRA treatment strategy in early rheumatoid arthritis?

PubMed Central

van Tuyl, Lilian H D; Plass, Anne Marie C; Lems, Willem F; Voskuyl, Alexandre E; Dijkmans, Ben A C; Boers, Maarten

2007-01-01

Background The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial has proved that combination therapy with prednisolone, methotrexate and sulphasalazine is superior to sulphasalazine monotherapy in suppressing disease activity and radiological progression of early rheumatoid arthritis (RA). In addition, 5 years of follow‐up proved that COBRA therapy results in sustained reduction of the rate of radiological progression. Despite this evidence, Dutch rheumatologists seem reluctant to prescribe COBRA therapy. Objective To explore the reasons for the reluctance in Dutch rheumatologists to prescribe COBRA therapy. Methods A short structured questionnaire based on social–psychological theories of behaviour was sent to all Dutch rheumatologists (n = 230). Results The response rate was 50%. COBRA therapy was perceived as both effective and safe, but complex to administer. Furthermore, rheumatologists expressed their concern about the large number of pills that had to be taken, the side effects of high‐dose prednisolone and the low dose of methotrexate. Although the average attitude towards the COBRA therapy was slightly positive (above the neutral point), the majority of responding rheumatologists had a negative intention (below the neutral point) to prescribe COBRA therapy in the near future. Conclusion The reluctance of Dutch rheumatologists to prescribe effective COBRA therapy may be due to perceptions of complexity of the treatment schedule and negative patient‐related consequences of the therapy. PMID:17392349

Toxic epidermal necrolysis due to therapy with cyclophosphamide and mesna. A case report of a patient with seronegative rheumatoid arthritis and rheumatoid vasculitis.

PubMed

Chowdhury, A C; Misra, D P; Patro, P S; Agarwal, V

2016-03-01

Rheumatoid vasculitis usually occurs on the background of seropositive rheumatoid arthritis, although in rare cases the patients can be seronegative. We report a woman with seronegative rheumatoid arthritis with rheumatoid vasculitis who developed toxic epidermal necrolysis involving most of her body surface area, while on therapy with intravenous cyclophosphamide and mesna. After withdrawal of suspected offending agents, administration of intravenous immunoglobulin, and supportive therapy, she had a favorable outcome. Such an occurrence is rare and serves to educate about a potentially life-threatening adverse event associated with a commonly used immunosuppressive agent.

Conversion to seronegative status after abatacept treatment in patients with early and poor prognostic rheumatoid arthritis is associated with better radiographic outcomes and sustained remission: post hoc analysis of the AGREE study.

PubMed

Jansen, Diahann T S L; Emery, Paul; Smolen, Josef S; Westhovens, Rene; Le Bars, Manuela; Connolly, Sean E; Ye, June; Toes, René E M; Huizinga, Tom W J

2018-01-01

To evaluate the effects of the T-cell costimulation blocker abatacept on anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) in early rheumatoid arthritis (RA), and associations between changes in serological status and clinical response. Post hoc analysis of the phase III AGREE study in methotrexate (MTX)-naïve patients with early RA and poor prognostic factors. Patients were randomised to abatacept (~10 mg/kg intravenously according to weight range) or placebo, plus MTX over 12 months followed by open-label abatacept plus MTX for 12 months. Autoantibody titres were determined by ELISA at baseline and months 6 and 12 (double-blind phase). Conversion to seronegative status and its association with clinical response were assessed at months 6 and 12. Abatacept plus MTX was associated with a greater decrease in ACPA (but not RF) titres and higher rates of both ACPA and RF conversion to seronegative status versus MTX alone. More patients converting to ACPA seronegative status receiving abatacept plus MTX achieved remission according to Disease Activity Score in 28 joints (C-reactive protein) or Clinical Disease Activity Index than patients who remained ACPA seropositive. Patients who converted to ACPA seronegative status treated with abatacept plus MTX had a greater probability of achieving sustained remission and less radiographic progression than MTX alone or patients who remained ACPA seropositive (either treatment). Treatment with abatacept plus MTX was more likely to induce conversion to ACPA/RF seronegative status in patients with early, erosive RA. Conversion to ACPA seronegative status was associated with better clinical and radiographic outcomes. NCT00122382.

Fatigue and sleep quality in rheumatoid arthritis patients during hospital admission.

PubMed

Szady, Paulina; Bączyk, Grażyna; Kozłowska, Katarzyna

2017-01-01

Rheumatoid arthritis (RA) is a systemic disease of connective tissue characterised by chronic course with periods of exacerbation and remission. Even in the early stages of the disease patients report the occurrence of fatigue and sleep disorders. Reduced sleep quality and chronic fatigue are common among patients with rheumatoid arthritis. The aim of the research was to evaluate the severity of fatigue and sleep quality assessment among patients hospitalised with rheumatoid arthritis and to determine the relation between the level of symptoms of fatigue and sleep quality and variables such as: age, gender, disease duration, marital status, applied pharmacological treatment, and pain intensity. The study involved 38 patients (12 men and 26 women) hospitalised in the Rheumatologic Ward of the Orthopaedics and Rehabilitation Hospital of the University of Medical Sciences. The average age of the entire group was 56.26 years. Fatigue was evaluated with use of Polish version of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), while in order to evaluate sleep quality within the examined group of patients the Pittsburgh Sleep Quality Index (PSQI) was used. Patients with rheumatoid arthritis in the analysed group have lower sleep quality, and within subjects with such a diagnosis the fatigue is present. The relation was found between fatigue and such variables as: age, illness duration, marital status, applied pharmacological treatment, and severity of pain. Sleep quality within patients with RA is correlated by such variables as: age, gender, applied pharmaceutical treatment, and severity of pain. It was identified that patients with lower sleep quality experience increased levels of fatigue. There is a need to clarify which factors determine the level of fatigue and sleep quality in patients suffering from RA in future population-based research and to indicate to doctors, nurses, psychologists, and physiotherapists the significance and importance of

Rheumatoid Arthritis Pain: Tips for Protecting Your Joints

MedlinePlus

Rheumatoid arthritis pain: Tips for protecting your joints Use these joint protection techniques to help you stay in control of your rheumatoid arthritis pain. By Mayo Clinic Staff Joint protection is ...

Rationale of Cruciate Retaining Design in Rheumatoid Arthritis: A Review of Clinical Analysis and its Role in Rheumatoid Arthritis.

PubMed

Ashraf, Munis; Sharma, Om Prakash; Priyavadhana, Sruthi; Sambandam, Senthil Nathan; Mounasamy, Varatharaj

2017-01-01

Over the years, proponents of total knee designs (cruciate retaining and posterior stabilised) have conducted several long-term studies to claim the potential of these designs in several subsets of patients. Total knee arthroplasty (TKA) in patients with rheumatoid arthritis has also been one such domain where numerous studies were conducted in the past. A general perception among majority of arthroplasty surgeons is that, posterior stabilised (PS) is the implanted design of choice among patients with Rheumatoid arthritis (RA). However, with the available literature there is a significant disparity related to the selection of implants in patients with rheumatoid RA. In this review of literature, an attempt is made to identify the clinical performance and role of one such implant design, the cruciate retaining (CR) prosthesis in rheumatoid arthritis. The review was conducted after a series of advanced search in the following medical databases; Pub med, Biomed central, Cochrane and Google scholar for articles related to long term follow up studies of cruciate retaining total knee arthroplasty in rheumatoid arthritis using the keywords cruciate retaining prosthesis, total knee arthroplasty, rheumatoid arthritis. The available data demonstrate that the CR design is attributed with an excellent long term survivorship and functional outcome even in follow up studies up to twenty-five years. The advantages of using a CR design are long term survivorship, controlled femoral roll back and preservation of bone stock. Thus, the data gathered in this review lead to a consideration that the CR design is an implant design on par with PS design in patients with RA.

[Possible association of gynecological cancer and rheumatoid arthritis].

PubMed

Mercado, Ulises

2012-06-01

The association between rheumatoid arthritis and cancer is controversial. Previous studies have shown a correlation between rheumatoid arthritis and the development of lymphoma. Describe a case of rheumatoid arthritis and associated breast cancer plus the identification of the clinical features of a set of cases in which arthritis and cancer go along. This is a retrospective clinical series study. A database of Hospital General ISSSTECALI of Mexicali, Mexico, containing information on patients suffering from both rheumatoid arthritis and cancer until 2012 was checked. The medical files confirmed the diagnoses. The data available included age, date of arthritis diagnosis, date of cancer diagnosis, related conditions, results of serological tests, type of cancer, treatments used and follow-up information. Fifteen cases of women suffering from both rheumatoid arthritis and cancer were identified on the database of the Hospital General ISSSTECALI in Mexicali. The case described here is the number four on that list. The average age was 54 years and the average time between arthritis and cancer diagnoses was four years. Ten patients were administered methotrexate. Nine patients (60%) suffered from breast cancer and six more from cervical cancer. Three patients suffered from cervical dysplasia. These cases emphasize the need of strict follow-up on patients suffering from inflammatory rheumatoid condition. If cancer follows chronic inflammation, immunosuppression, or it is pure coincidence, is still a matter of debate.

Leprosy and rheumatoid arthritis: consequence or association?

PubMed

Henriques, Celia Coelho; Lopéz, Begoña; Mestre, Tiago; Grima, Bruno; Panarra, António; Riso, Nuno

2012-08-13

Leprosy or Hansen's disease is a chronic granulomatous infectious disease caused by Mycobacterium leprae with a high prevalence in some developing countries however, it is rarely seen in non-endemic regions. Arthritis has been described in all types of Hansen's disease. Chronic arthritis is known to exist even in paucibacillary forms, resolved or treated disease and in patients without reaction, suggesting a perpetuated inflammatory process. In these cases leprosy can mimic some autoimmune diseases such as rheumatoid arthritis. When a patient with a history of leprosy presents with a symmetric, distal, polyarthritis the diagnosis may not be linear. Possibly it is a rheumatoid-like leprous arthritis with M leprae acting as the trigger element for the chronic process or it is an overlap condition, with a concomitant rheumatoid arthritis? A case report of a patient with a chronic inflammatory arthritis with 10 years of evolution is presented. The differential diagnosis between leprous and rheumatoid arthritis is discussed.

Evaluation of clinical and cytogenetic parameters in rheumatoid arthritis patients for effective diagnosis.

PubMed

Chandirasekar, R; Kumar, B Lakshman; Jayakumar, R; Uthayakumar, V; Jacob, Raichel; Sasikala, K

2015-01-15

Rheumatoid arthritis is the commonest inflammatory joint disease, affecting nearly 1% of the adult population worldwide. Early and accurate diagnosis and prognosis of rheumatoid arthritis (RA) have become increasingly important. In the present study, we aimed to elucidate the relationships between hematological, biochemical, immunological and cytogenetic parameters in rheumatoid arthritis patients and healthy normal controls. The study group comprised of 126 RA patients and equal number of healthy normal control subjects. The blood was collected and analyzed for biochemical, immunological, enzymatic and cytogenetic parameters. Results of the present study indicated that 20% of RA patient's hematological, 31% of biochemical and 70% immunological parameters had a significant difference from the controls and reference range. The RF and anti-CCP antibody levels were also positive in 70% of RA patients. A significant increase in minor chromosomal abnormalities was also observed in patients as compared to controls. The knowledge about autoimmune diseases is very low among the South Indian population. The present study has thus helped in understanding the RA disease in a better way based on a pattern of various clinical markers of the disease condition which might help in planning therapeutic intervention strategies and create awareness about the disease management among RA patients of the population studied. Copyright © 2014. Published by Elsevier B.V.

A study on relationship among apoptosis rates, number of peripheral T cell subtypes and disease activity in rheumatoid arthritis.

PubMed

Ji, Lanlan; Geng, Yan; Zhou, Wei; Zhang, Zhuoli

2016-02-01

Rheumatoid arthritis is characterized by type 17 helper T cell (Th17)/regulatory T cell (Treg) imbalance. The objective of this article is to study whether insufficient apoptosis contributes to the imbalance of Th17/Treg in rheumatoid arthritis. Twenty-one rheumatoid arthritis patients and eight healthy volunteers were involved in this study. The percentage of CD4(+) interleukin (IL)-17(+) T cells and CD4(+) transcription factor-forkhead box protein 3 (Foxp3)(+) T cells were measured by flow cytometry, and active caspase-3 labeling was used to detect early apoptosis. The number of T cell subtypes in peripheral blood between the two groups was compared, as well as the apoptotic ratio. Neither the number of Th17 nor Treg cells was significantly different between rheumatoid arthritis patients and healthy controls. However, the number of regulatory T cells positively correlated with erythrocyte sedimentation rate, Disease Activity Score of 28 joints and rheumatoid factor. For the apoptosis of T cell subtypes, the percentage of apoptotic Th17 cells was higher in peripheral blood of rheumatoid arthritis patients compared to controls. Furthermore, peripheral Th17 cells were more sensitive to apoptosis than Treg cells, but there was no difference between rheumatoid arthritis patients and controls. It seemed that there was no relationship between the number and apoptosis ratio of peripheral Th17/Treg cells. But the number of Treg cells positively correlated with disease activity. Furthermore, Th17 cells are more sensitive to apoptosis after freezing, especially in RA patients. This serendipitous finding may provide new areas for the further study of these two cell populations. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Social support as a moderator of functional disability's effect on depressive feelings in early rheumatoid arthritis: a four-year prospective study.

PubMed

Benka, Jozef; Nagyova, Iveta; Rosenberger, Jaroslav; Calfova, Anna; Macejova, Zelmira; Lazurova, Ivica; van Dijk, Jitse P; Groothoff, Johan W

2014-02-01

To examine associations of depressive feelings with disease-related variables and explore the moderating effect of social support on depressive feelings in individuals with early rheumatoid arthritis (RA) prospectively over 4 years. Data were collected annually over 4 years. The sample consisted of 124 individuals with diagnosed RA (85.5% women; mean age 47.9 years; mean disease duration 22.2 months). The strength of cross-sectional and prospective associations of sociodemographic, disease-related variables and the direct and moderating effects of social support on depression were tested using correlations, multilevel models, and hierarchical linear regressions. The study showed that emotional support moderated the influence of functional disability on depressive feelings in individuals with RA. This was not detected for instrumental support. Further prospective associations between functional status, marital status, and depressive feelings were also found. Overall, the strongest association was found between initial depressive feelings and depressive feelings over time. Initial depression seemed to be a risk factor in explaining later depressive feelings, but emotional support might be prospectively beneficial, especially for individuals with higher levels of disability. Early detection of individuals at risk for depression and providing interventions aimed at the specific functions of social support might help to decrease mental health problems. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Pauci-immune necrotizing glomerulonephritis complicating rheumatoid arthritis.

PubMed

Qarni, M U; Kohan, D E

2000-07-01

Necrotizing glomerulonephritis associated with rheumatoid arthritis typically occurs in the setting of frankly apparent systemic vasculitic signs and symptoms. We report two recent cases that differed from this paradigm. Both patients had rheumatoid arthritis and deteriorating renal function due to P-ANCA positive pauci-immune necrotizing crescentic glomerulonephritis, but minimal systemic symptoms. Delay in diagnosis and institution of appropriate therapy may have contributed to the dialysis dependence of one of these patients. We suggest that heightened suspicion of an aggressive necrotizing glomerulonephritis should be maintained in all patients with rheumatoid arthritis who present with acute renal insufficiency even in the absence of frank vasculitis.

Rationale of Cruciate Retaining Design in Rheumatoid Arthritis: A Review of Clinical Analysis and its Role in Rheumatoid Arthritis

PubMed Central

Ashraf, Munis; Sharma, Om Prakash; Priyavadhana, Sruthi; Sambandam, Senthil Nathan; Mounasamy, Varatharaj

2017-01-01

Background: Over the years, proponents of total knee designs (cruciate retaining and posterior stabilised) have conducted several long-term studies to claim the potential of these designs in several subsets of patients. Total knee arthroplasty (TKA) in patients with rheumatoid arthritis has also been one such domain where numerous studies were conducted in the past. A general perception among majority of arthroplasty surgeons is that, posterior stabilised (PS) is the implanted design of choice among patients with Rheumatoid arthritis (RA). However, with the available literature there is a significant disparity related to the selection of implants in patients with rheumatoid RA. In this review of literature, an attempt is made to identify the clinical performance and role of one such implant design, the cruciate retaining (CR) prosthesis in rheumatoid arthritis. Method: The review was conducted after a series of advanced search in the following medical databases; Pub med, Biomed central, Cochrane and Google scholar for articles related to long term follow up studies of cruciate retaining total knee arthroplasty in rheumatoid arthritis using the keywords cruciate retaining prosthesis, total knee arthroplasty, rheumatoid arthritis. Results: The available data demonstrate that the CR design is attributed with an excellent long term survivorship and functional outcome even in follow up studies up to twenty-five years. Conclusion: The advantages of using a CR design are long term survivorship, controlled femoral roll back and preservation of bone stock. Thus, the data gathered in this review lead to a consideration that the CR design is an implant design on par with PS design in patients with RA. PMID:29114338

Reduction in Serum Uric Acid May Be Related to Methotrexate Efficacy in Early Rheumatoid Arthritis: Data from the Canadian Early Arthritis Cohort (CATCH)

PubMed Central

Lee, Jason J.; Bykerk, Vivian P.; Dresser, George K.; Boire, Gilles; Haraoui, Boulos; Hitchon, Carol; Thorne, Carter; Tin, Diane; Jamal, Shahin; Keystone, Edward C.; Pope, Janet E.

2016-01-01

OBJECTIVES The mechanism of action of methotrexate in rheumatoid arthritis (RA) is complex. It may increase adenosine levels by blocking its conversion to uric acid (UA). This study was done to determine if methotrexate lowers UA in early RA (ERA). METHODS Data were obtained from Canadian Early Arthritis Cohort, an incident ERA cohort. All ERA patients with serial UA measurements were included, comparing those with methotrexate use vs. no methotrexate exposure (controls). Analyses were exploratory. Patients with concomitant gout or taking UA-lowering therapies were excluded. RESULTS In total, 49 of the 2,524 ERA patients were identified with data available for both pre-methotrexate UA levels and post-methotrexate UA levels (300 µmol/L and 273 µmol/L, respectively; P = 0.035). The control group not taking methotrexate had a mean baseline UA level of 280 µmol/L and a follow-up level of 282 µmol/L (P = 0.448); mean change in UA with methotrexate was −26.8 µmol/L vs. 2.3 µmol/L in the no methotrexate group (P = 0.042). Methotrexate users with a decrease in UA had a disease activity score of 2.37 for 28 joints when compared with the controls (3.26) at 18 months (P = 0.042). Methotrexate users with decreased UA had a lower swollen joint count (SJC) of 0.9 at 18 months, whereas methotrexate users without lowering of UA had an SJC of 4.5 (P = 0.035). Other analyses were not significant. CONCLUSIONS Methotrexate response is associated with lowering of serum UA in ERA compared to nonusers. This may be due to changes in adenosine levels. Methotrexate response is associated with lower UA and fewer swollen joints compared to nonresponders. PMID:27081318

Rheumatoid factor (RF)

MedlinePlus

... Firestein's Textbook of Rheumatology . 10th ed. Philadelphia, PA: Elsevier; 2017:chap 56. Chernecky CC, Berger BJ. Rheumatoid ... and Diagnostic Procedures . 6th ed. St Louis, MO: Elsevier Saunders; 2013:985-986. Hoffmann M, Lundberg K, ...

[Management of rheumatoid arthritis].

PubMed

Fiehn, C; Krüger, K

2016-11-01

Rheumatoid arthritis is the most common inflammatory rheumatic disease. Due to the destruction of joints in the course of the disease it leads to significant morbidity in affected patients. The quality of life and even life expectancy can be severely impaired. Early diagnosis and early initiation of treatment is a decisive step towards a more benign course of the disease. New classification criteria have been published in order to help in early diagnosis. Methods of imaging, such as ultrasound and magnetic resonance imaging help in the detection of synovitis, which is the major pathomorphological manifestation of arthritis and should be identified without any doubt. Treatment follows the rule of treat to target with the aim of achieving remission or if this is not realistic, at least the lowest possible level of disease activity. The first and perhaps most important step in therapy is the initiation of methotrexate or if contraindications are present, another disease-modifying antirheumatic drug (DMARD) as soon as the diagnosis is made. Initial addition of glucocorticoids is recommended, which should be reduced in dose and terminated as soon as possible. Furthermore, either the combination of different DMARDs or the start of biologic DMARDs, such as tumor necrosis factor alpha (TNF-alpha) inhibitors or second generation biologic DMARDs is possible as a treatment option. The treatment follows the rule of shared decision-making and is the standard to treat comorbidities, the use an interdisciplinary approach and to treat functional deficits by rehabilitation measures, such as physiotherapy.

Late onset rheumatoid arthritis an observational study.

PubMed

Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Rexhepi, Blerta; Bahtiri, Elton; Mahmutaj, Vigan

Rheumatoid arthritis (RA) may have an onset at older age. The onset of the disease at the age of 60 and over is called late-onset rheumatoid arthritis (LORA). The aim of this study was to analyze the clinical, laboratory, radiological, and treatment characteristics of patients with LORA compared to those with early-onset RA (EaORA), provided that all the patients had an approximately equal duration of the disease. This is an observational single-center study, which involved 120 patients with an established diagnosis of RA, of which 60 patients had LORA, and 60 patients EaORA. The disease activity, measured by the Disease Activity Score 28 (DAS28-ESR), was significantly higher in the LORA group compared to the EaORA group (p<0.05). Significantly more patients with LORA had involvement of the shoulders (LORA vs. EaORA, 30% vs. 15%; p <0.05) and knees (LORA vs. EaORA, 46.7% vs. 16.7%; p <0.05). Radiological erosive changes were significantly more frequent in the LORA group in comparison with EaORA (p <0.05). There was no difference between the groups regarding rheumatoid factor (RF) positivity (p>0.05), while the number of patients positive for anti-citrullinated protein antibody (ACPA) was signifi cantly greater in the EaORA group (p<0.05). The values of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were significantly higher in the LORA than in the EaORA group. Hemoglobin levels were lower in the LORA group (11.96±1.64 g/dL) than in the EaORA group (12.18±1.56 g/dL). The most used disease-modifying antirheumatic drugs (DMARDs) were methotrexate and sulfasalazine, while biological drugs were not used. In conclusion, based on the results of our study, LORA has some features that distinguish it from EaORA, such as higher disease activity, more frequent involvement of large joints, and more pronounced structural damage. This should be taken in account in clinical practice, especially regarding treatment choices.

Successful leukocytapheresis therapy in a patient with rheumatoid arthritis on maintenance hemodialysis.

PubMed

Maeshima, Keisuke; Torigoe, Masataka; Iwakura, Mikako; Yamanaka, Kunitoshi; Ishii, Koji

2015-01-01

We report the case of a 44-year-old female undergoing maintenance hemodialysis in whom early-phase rheumatoid arthritis (RA) was successfully treated by leukocytapheresis (LCAP). The effects of prednisone, tacrolimus, and etanercept were limited, but LCAP was highly effective and its efficacy continued even after cessation of LCAP. Moreover, remission was maintained for 2 years after discontinuation of medication. LCAP may be an important treatment option for RA patients with end-stage renal failure who are on hemodialysis.

A probable case of rheumatoid arthritis from the middle Anglo-Saxon period.

PubMed

Mckinnon, Katie; Van Twest, Melanie S; Hatton, Martin

2013-06-01

We present here a case of erosive polyarthropathy in an incomplete skeleton from a middle-Saxon period (c. AD 650-900) cemetery site in Sedgeford, Norfolk, England. After a differential diagnosis that includes erosive osteoarthritis and psoriatic arthritis, we believe rheumatoid arthritis (RA) to be the most probable cause. This example may therefore add to the evidence for an early date for the appearance of RA in Europe. Copyright © 2013 Elsevier Inc. All rights reserved.

A Case Report Describing a Rare Presentation of Simultaneous Occurrence of MPO-ANCA-Associated Vasculitis and Rheumatoid Arthritis.

PubMed

Foray, Nathalie; Hudali, Tamer; Papireddy, Muralidhar; Gao, John

2016-01-01

Background . Renal-limited myeloperoxidase vasculitis with simultaneous rheumatoid arthritis is reported as a rare occurrence. Review of literature suggests that most patients had a diagnosis of rheumatoid arthritis for several years prior to presenting with renal failure from myeloperoxidase vasculitis. Case Presentation . A 58-year-old Caucasian male presented to the hospital experiencing malaise, fevers, decreased oral intake, nausea, and vomiting for one week duration. His past medical history consisted of newly diagnosed but untreated rheumatoid arthritis, hypertension, and non-insulin-dependent diabetes mellitus. He was found to have acute renal failure, proteinuria, and hypoglycemia. Standard therapy, including intravenous fluids, did not improve his acute renal failure. A vasculitis workup resulted in a positive myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA). Renal biopsy revealed crescentic glomerulonephritis (GN) pauci-immune type, suggestive of MPO-ANCA-associated vasculitis (MPO-AAV). Treatment consisted of prednisone, cyclophosphamide, and seven cycles of plasmapheresis, in addition to hemodialysis for uremia. Upon discharge, he received hemodialysis for another week and continued treatment with cyclophosphamide and prednisone. Conclusion . Patients with longstanding rheumatoid arthritis may develop renal failure due to nonsteroidal anti-inflammatory medication use and AA type amyloidosis; however, necrotizing glomerulonephritis with crescent formation has been rarely reported. This stresses the importance of early recognition and swift initiation of treatment.

Predictors of satisfactory improvements in pain for patients with early rheumatoid arthritis in a treat-to-target study.

PubMed

Ten Klooster, Peter M; Vonkeman, Harald E; Oude Voshaar, Martijn A H; Siemons, Liseth; van Riel, Piet L C M; van de Laar, Mart A F J

2015-06-01

The aim of this study was to identify baseline predictors of achieving patient-perceived satisfactory improvement (PPSI) in pain after 6 months of treat to target in patients with early RA. Baseline and 6 month data were used from patients included in the Dutch Rheumatoid Arthritis Monitoring remission induction cohort study. Simple and multivariable logistic regression analyses were used to identify significant predictors of achieving an absolute improvement of 30 mm or a relative improvement of 50% on a visual analogue scale for pain. At 6 months, 125 of 209 patients (59.8%) achieved an absolute PPSI and 130 patients (62.2%) achieved a relative PPSI in pain. Controlling for baseline pain, having symmetrical arthritis was the strongest independent predictor of achieving an absolute [odds ratio (OR) 3.17, P = 0.03] or relative (OR 3.44, P = 0.01) PPSI. Additionally, anti-CCP positivity (OR 2.04, P = 0.04) and having ≤12 tender joints (OR 0.29, P = 0.01) were predictive of achieving a relative PPSI. The total explained variance of baseline predictors was 30% for absolute and 18% for relative improvements, respectively. Symmetrical joint involvement, anti-CCP positivity and fewer tender joints at baseline are prognostic signs for achieving satisfactory improvement in pain after 6 months of treat to target in patients with early RA. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Conversion to seronegative status after abatacept treatment in patients with early and poor prognostic rheumatoid arthritis is associated with better radiographic outcomes and sustained remission: post hoc analysis of the AGREE study

PubMed Central

Emery, Paul; Smolen, Josef S; Westhovens, Rene; Le Bars, Manuela; Connolly, Sean E; Ye, June; Toes, René E M; Huizinga, Tom W J

2018-01-01

Objective To evaluate the effects of the T-cell costimulation blocker abatacept on anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) in early rheumatoid arthritis (RA), and associations between changes in serological status and clinical response. Methods Post hoc analysis of the phase III AGREE study in methotrexate (MTX)-naïve patients with early RA and poor prognostic factors. Patients were randomised to abatacept (~10 mg/kg intravenously according to weight range) or placebo, plus MTX over 12 months followed by open-label abatacept plus MTX for 12 months. Autoantibody titres were determined by ELISA at baseline and months 6 and 12 (double-blind phase). Conversion to seronegative status and its association with clinical response were assessed at months 6 and 12. Results Abatacept plus MTX was associated with a greater decrease in ACPA (but not RF) titres and higher rates of both ACPA and RF conversion to seronegative status versus MTX alone. More patients converting to ACPA seronegative status receiving abatacept plus MTX achieved remission according to Disease Activity Score in 28 joints (C-reactive protein) or Clinical Disease Activity Index than patients who remained ACPA seropositive. Patients who converted to ACPA seronegative status treated with abatacept plus MTX had a greater probability of achieving sustained remission and less radiographic progression than MTX alone or patients who remained ACPA seropositive (either treatment). Conclusions Treatment with abatacept plus MTX was more likely to induce conversion to ACPA/RF seronegative status in patients with early, erosive RA. Conversion to ACPA seronegative status was associated with better clinical and radiographic outcomes. Trial registration number NCT00122382 PMID:29657830

Rheumatoid arthritis in Saudi Arabia

PubMed Central

Almoallim, Hani M.; Alharbi, Laila A.

2014-01-01

The status of rheumatoid arthritis (RA) in Saudi Arabia (SA) was examined from various perspectives based on a systematic literature review and the authors’ personal experiences. In this regard, database and journal search were conducted to identify studies on RA in SA, yielding a total of 43 articles. Although efforts have been made to promote RA research in SA, current studies mostly represent only a few centers and may not accurately portray the national status of RA care. Notably, biological therapies were introduced early for almost all practicing rheumatologists in SA (government and private). However, no national guidelines regarding the management of RA have been developed based on local needs and regulations. Also, while efforts were made to establish RA data registries, they have not been successful. Taken together, this analysis can contribute to the planning of future guidelines and directives for RA care in SA. PMID:25491208

Quadriparesis in a young female suffering from rheumatoid arthritis.

PubMed

Gupta, A K; Agarwal, N; Yadava, R K; Jain, S K

2003-07-01

Cervical spine is involved in a significant proportion of patients suffering from rheumatoid arthritis. Although cervical spine disease may often be 'benign', neurological complications are not uncommon. Patients of rheumatoid arthritis should be screened for cervical spine involvement and appropriately treated with combination of anti-rheumatic drugs. We report a case of quadriparesis secondary to subluxation and disc herniation at C4-C5 level in a young woman with rheumatoid arthritis of short duration.

Periodontitis in early and chronic rheumatoid arthritis: a prospective follow-up study in Finnish population

PubMed Central

Äyräväinen, Leena; Leirisalo-Repo, Marjatta; Kuuliala, Antti; Ahola, Kirsi; Koivuniemi, Riitta; Meurman, Jukka H; Heikkinen, Anna Maria

2017-01-01

Objectives To investigate the association between rheumatoid arthritis (RA) and periodontitis with special emphasis on the role of antirheumatic drugs in periodontal health. Design Prospective follow-up study. Patients with early untreated RA and chronic active RA were examined at baseline and 16 months later. Controls were examined once. Settings and participants The study was conducted in Finland from September 2005 to May 2014 at the Helsinki University Hospital. Overall, 124 participants were recruited for dental and medical examinations: 53 were patients with early disease-modifying antirheumatic drug (DMARD) naїve RA (ERA), 28 were patients with chronic RA (CRA) with insufficient response to conventional DMARDs. After baseline examination, patients with ERA started treatment with synthetic DMARDs and patients with CRA with biological DMARDs. Controls were 43 age-matched, gender-matched and community-matched participants. Outcome measures Degree of periodontitis (defined according to the Center for Disease Control and Prevention and the American Academy of Periodontology). Prevalence of periodontal bacteria (analysed from plaque samples), clinical rheumatological status by Disease Activity Score, 28-joint count (DAS28), function by Health Assessment Questionnaire (HAQ) and treatment response by European League Against Rheumatism (EULAR) criteria. Results Moderate periodontitis was present in 67.3% of patients with ERA, 64.3% of patients with CRA and 39.5% of control participants (p=0.001). Further, patients with RA had significantly more periodontal findings compared with controls, recorded with common periodontal indexes. In the re-examination, patients with RA still showed poor periodontal health in spite of treatment with DMARDs after baseline examination. The prevalence of Porphyromonas gingivalis was higher in patients with ERA with periodontal probing depth ≥4 mm compared with patients with CRA and controls. Antirheumatic medication did not seem

Update on ibuprofen for rheumatoid arthritis.

PubMed

Ward, J R

1984-07-13

In doses of 1,200 mg/day or more, ibuprofen is as effective as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis. The tolerability and safety of ibuprofen are superior to those of aspirin and compare favorably with those of other NSAIDs. Although additional controlled trials are indicated to determine optimal dose, ibuprofen's excellent therapeutic index establishes it as a useful drug in the treatment of rheumatoid arthritis.

A population-based study on the association between rheumatoid arthritis and voice problems.

PubMed

Hah, J Hun; An, Soo-Youn; Sim, Songyong; Kim, So Young; Oh, Dong Jun; Park, Bumjung; Kim, Sung-Gyun; Choi, Hyo Geun

2016-07-01

The objective of this study was to investigate whether rheumatoid arthritis increases the frequency of organic laryngeal lesions and the subjective voice complaint rate in those with no organic laryngeal lesion. We performed a cross-sectional study using the data from 19,368 participants (418 rheumatoid arthritis patients and 18,950 controls) of the 2008-2011 Korea National Health and Nutrition Examination Survey. The associations between rheumatoid arthritis and organic laryngeal lesions/subjective voice complaints were analyzed using simple/multiple logistic regression analysis with complex sample adjusting for confounding factors, including age, sex, smoking status, stress level, and body mass index, which could provoke voice problems. Vocal nodules, vocal polyp, and vocal palsy were not associated with rheumatoid arthritis in a multiple regression analysis, and only laryngitis showed a positive association (adjusted odds ratio, 1.59; 95 % confidence interval, 1.01-2.52; P = 0.047). Rheumatoid arthritis was associated with subjective voice discomfort in a simple regression analysis, but not in a multiple regression analysis. Participants with rheumatoid arthritis were older, more often female, and had higher stress levels than those without rheumatoid arthritis. These factors were associated with subjective voice complaints in both simple and multiple regression analyses. Rheumatoid arthritis was not associated with organic laryngeal diseases except laryngitis. Rheumatoid arthritis did not increase the odds ratio for subjective voice complaints. Voice problems in participants with rheumatoid arthritis originated from the characteristics of the rheumatoid arthritis group (higher mean age, female sex, and stress level) rather than rheumatoid arthritis itself.

Men, rheumatoid arthritis, psychosocial impact and self-management: A narrative review.

PubMed

Flurey, Caroline A; Hewlett, Sarah; Rodham, Karen; White, Alan; Noddings, Robert; Kirwan, John

2016-10-01

Rheumatoid arthritis is a chronic disease affecting fewer men than women. We systematically reviewed the literature on impact and self-management of rheumatoid arthritis in men. A total of 28 papers were included and grouped into two categories: psychosocial impact of rheumatoid arthritis, and coping and self-management. This review finds gender differences relating to quality of life, work, distress, self-management, coping and support. We conclude that there is a dearth of literature focussing on rheumatoid arthritis in men only, and mixed gender studies include insufficient men to draw strong conclusions about men. Thus, further research is needed to understand the support needs of men with rheumatoid arthritis in depth. © The Author(s) 2015.

Ghrelin gene polymorphisms in rheumatoid arthritis.

PubMed

Ozgen, Metin; Koca, Suleyman Serdar; Etem, Ebru Onalan; Yuce, Huseyin; Aydin, Suleyman; Isik, Ahmet

2011-07-01

Ghrelin, an endogenous orexigenic peptide, has anti-inflammatory effects, down-regulates pro-inflammatory cytokines, and its altered levels are reported in various inflammatory diseases. The human preproghrelin (ghrelin/obestatin) gene shows several single nucleotide polymorphisms (SNPs) including Arg51Gln, Leu72Met, Gln90Leu, and A-501C. The aim of this study was to investigate the frequency, and clinical significance, of these four SNPs in a small cohort of Turkish patients with rheumatoid arthritis (RA). The study included 103 patients with RA and 103 healthy controls. In the RA group, disease activity and disease-related damage were assessed using the Disease Activity Score-28 (DAS-28), and the modified Larsen scoring (MLS) methods. In all the participants, genomic DNA was isolated and genotyped by polymerase chain reaction and restriction fragment length polymorphism analysis. The frequencies of ghrelin gene SNPs were 82.5 and 79.6% in the RA and control groups, respectively, and there were no significant differences in terms of genotype distributions and allele frequencies for these four SNPs between the groups. However, the A-501C SNP was found to be associated with early disease onset, and Gln90Leu SNP with less frequent rheumatoid factor positivity, in the RA group. A-501C SNP is associated with earlier onset of RA suggesting that genetic variations in the ghrelin gene may have an impact on RA. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Emotions related to participation restrictions as experienced by patients with early rheumatoid arthritis: a qualitative interview study (the Swedish TIRA project).

PubMed

Östlund, Gunnel; Björk, Mathilda; Thyberg, Ingrid; Thyberg, Mikael; Valtersson, Eva; Stenström, Birgitta; Sverker, Annette

2014-01-01

Psychological distress is a well-known complication in rheumatoid arthritis (RA), but knowledge regarding emotions and their relationship to participation restrictions is scarce. The objective of the study was to explore emotions related to participation restrictions by patients with early RA. In this study, 48 patients with early RA, aged 20-63 years, were interviewed about participation restrictions using the critical incident technique. Information from transcribed interviews was converted into dilemmas and linked to International Classification of Functioning, Disability, and Health (ICF) participation codes. The emotions described were condensed and categorized. Hopelessness and sadness were described when trying to perform daily activities such as getting up in the mornings and getting dressed, or not being able to perform duties at work. Sadness was experienced in relation to not being able to continue leisure activities or care for children. Examples of fear descriptions were found in relation to deteriorating health and fumble fear, which made the individual withdraw from activities as a result of mistrusting the body. Anger and irritation were described in relation to domestic and employed work but also in social relations where the individual felt unable to continue valued activities. Shame or embarrassment was described when participation restrictions became visible in public. Feelings of grief, aggressiveness, fear, and shame are emotions closely related to participation restrictions in everyday life in early RA. Emotions related to disability need to be addressed both in clinical settings in order to optimize rehabilitative multi-professional interventions and in research to achieve further knowledge.

Tissue factor expression in rheumatoid synovium: a potential role in pannus invasion of rheumatoid arthritis.

PubMed

Chen, Lujun; Lu, Yahua; Chu, Yang; Xie, Jun; Ding, Wen'ge; Wang, Fengming

2013-09-01

Angiogenesis, as well as pannus formation within the joint, plays an important role in the erosion of articular cartilage and bone in the pathological process of rheumatoid arthritis (RA). Tissue factor (TF), an essential initiator of the extrinsic pathway of blood coagulation, is also involved in the angiogenesis and the pannus formation of RA progression. In the present study, we used immunofluorescence and confocal scanning methods to characterize TF immunolocalization in RA synovium. We showed that positive staining of TF could be immunolocalized in synoviocytes, CD19(+) B cells and CD68(+) macrophages, whereas weak or negative staining of tissue factor could be found in CD34(+) endothelial cells of neo-vessels, CD3(+) T cells and CD14(+) monocytes in RA synovium tissues. Our study demonstrates a detailed local expression of TF in the rheumatoid synovium, and supports the notion that TF, expressed not only by the synoviocytes themselves, but also the infiltrating CD19(+) B cells and CD68(+) macrophages, is involved in the pannus invasion in the progression of rheumatoid arthritis. Copyright © 2013 Elsevier GmbH. All rights reserved.

The role of anti-cyclic citrullinated peptide antibodies in predicting rheumatoid arthritis.

PubMed

Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Tafaj, Argjend; Izairi, Remzi; Rexhepi, Blerta

2011-01-01

The study presents the results of predicting role of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis, compared to rheumatoid factor. 32 patients with rheumatoid arthritis were identified from a retrospective chart review. The results of our study show that presence of the rheumatoid factor has less diagnostic and prognostic significance than the anti-cyclic citrullinated peptide, and suggests its superiority in predicting an erosive disease course.

Hypereosinophilia and seroconversion of rheumatoid arthritis.

PubMed

Rosenstein, Rachel K; Panush, Richard S; Kramer, Neil; Rosenstein, Elliot D

2014-11-01

At the intersection of atopy and autoimmunity, we present a patient with seronegative rheumatoid arthritis (RA) who developed hypereosinophilia, without evidence of other etiologies, as she became rheumatoid factor (RF) positive. Although the magnitude of eosinophilia in patients with RA has been thought to reflect the severity or activity of the RA, in our patient, eosinophilia developed at a time when the patient's synovitis was well controlled. Although eosinophilia may reflect associated drug hypersensitivity, discontinuation of the medications utilized to control our patient's disease, adalimumab and methotrexate, did not promote clinical improvement. Probably the most curious aspect of our patient was the concomitant development of rheumatoid factor seropositivity in the setting of previously seronegative RA. The temporal relationship between the development of peripheral eosinophilia and seroconversion suggests a possible connection between these events. We speculate that the T cell cytokine production that can induce eosinophilia may simultaneously activate RF production.

Current treatment of juvenile rheumatoid arthritis.

PubMed

Ilowite, Norman T

2002-01-01

Prognostic factors in juvenile rheumatoid arthritis (JRA) include polyarticular onset, polyarticular disease course, and rheumatoid factor positivity; in the systemic onset subtype, persistence of systemic features at 6 months after onset confers a worse prognosis. Timely diagnosis and appropriate aggressive treatment of patients with poor prognostic features improve quality of life and outcome. After nonsteroidal anti-inflammatory drugs, methotrexate is the most commonly used second-line agent. However, approximately one third of patients do not respond to methotrexate adequately. Randomized, placebo-controlled, clinical trials in patients with JRA are few, but one such trial with the tumor necrosis factor inhibitor etanercept shows that this drug is effective and well-tolerated. Other recently approved agents for rheumatoid arthritis, including infliximab, leflunomide, celecoxib, and rofecoxib, have not been adequately studied in pediatric patients, and the role of these agents in children with JRA remains to be determined.

Insufficiency fractures of the distal tibia misdiagnosed as cellulitis in three patients with rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Straaton, K.V.; Lopez-Mendez, A.; Alarcon, G.S.

We describe 3 patients with rheumatoid arthritis who presented with diffuse pain, swelling, and erythema of the distal aspect of the lower extremity, suggestive of either cellulitis or thrombophlebitis, but were found to have insufficiency fractures of the distal tibia. The value of technetium-99m diphosphonate bone scintigraphy in the early recognition of these fractures and a possible explanation for the associated inflammatory symptoms are discussed.

Assessing Medication Adherence in Patients with Rheumatoid Arthritis (RA)

DTIC Science & Technology

2017-04-26

REV1E\\\\’ER 50. "E PFlEV101JS EOmC»lS ARE C . E1E ?~e 3 01 3 FlIll!!S D ~.!!fitt Assessing Medication Adherence in Patients with Rheumatoid Arthritis (RA...Background • Rheumatoid arthritis - Affecting 1-3 million Americans - Seventy percent are women - Associated with higher risk of heart disease and stroke...and Objectives Purpose: Assess medication adherence in patients with rheumatoid arthritis Objectives: 1. Primary: Assess whether there is a correlation

Sleep Loss Exacerbates Fatigue, Depression, and Pain in Rheumatoid Arthritis

PubMed Central

Irwin, Michael R.; Olmstead, Richard; Carrillo, Carmen; Sadeghi, Nina; FitzGerald, John D.; Ranganath, Veena K.; Nicassio, Perry M.

2012-01-01

Study Objectives: Disturbances of sleep are hypothesized to contribute to pain. However, experimental data are limited to healthy pain-free individuals. This study evaluated the effect of sleep loss during part of the night on daytime mood symptoms and pain perceptions in patients with rheumatoid arthritis in comparison with control subjects. Design: A between-groups laboratory study with assessment of mood symptoms and pain perception before and after partial night sleep deprivation (PSD; awake 23:00 hr to 03:00 hr). Setting: General clinical research center. Participants: Patients with rheumatoid arthritis (n = 27) and volunteer comparison control subjects (n = 27). Measurements: Subjective reports of sleep, mood symptoms and pain, polysomnographic assessment of sleep continuity, and subjective and objective assessment of rheumatoid arthritis-specific joint pain. Results: PSD induced differential increases in self-reported fatigue (P < 0.09), depression (P < 0.04), anxiety (P < 0.04), and pain (P < 0.01) in patients with rheumatoid arthritis compared with responses in control subjects, in whom differential increases of self-reported pain were independent of changes in mood symptoms, subjective sleep quality, and objective measures of sleep fragmentation. In the patients with rheumatoid arthritis, PSD also induced increases in disease-specific activity as indexed by self-reported pain severity (P < 0.01) and number of painful joints (P < 0.02) as well as clinician-rated joint counts (P < 0.03). Conclusion: This study provides the first evidence of an exaggerated increase in symptoms of mood and pain in patients with rheumatoid arthritis after sleep loss, along with an activation of rheumatoid arthritis-related joint pain. Given the reciprocal relationship between sleep disturbances and pain, clinical management of pain in patients with rheumatoid arthritis should include an increased focus on the prevention and treatment of sleep disturbance in this clinical

Elevated Ratio of Th17 Cell-Derived Th1 Cells (CD161(+)Th1 Cells) to CD161(+)Th17 Cells in Peripheral Blood of Early-Onset Rheumatoid Arthritis Patients.

PubMed

Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

2016-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161(+)Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161(+)Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase.

Elevated Ratio of Th17 Cell-Derived Th1 Cells (CD161+Th1 Cells) to CD161+Th17 Cells in Peripheral Blood of Early-Onset Rheumatoid Arthritis Patients

PubMed Central

Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

2016-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161+Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161+Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase. PMID:27123445

Dynamics Determine Signaling in a Multicomponent System Associated with Rheumatoid Arthritis.

PubMed

Lindgren, Cecilia; Tyagi, Mohit; Viljanen, Johan; Toms, Johannes; Ge, Changrong; Zhang, Naru; Holmdahl, Rikard; Kihlberg, Jan; Linusson, Anna

2018-05-24

Strategies that target multiple components are usually required for treatment of diseases originating from complex biological systems. The multicomponent system consisting of the DR4 major histocompatibility complex type II molecule, the glycopeptide CII259-273 from type II collagen, and a T-cell receptor is associated with development of rheumatoid arthritis (RA). We introduced non-native amino acids and amide bond isosteres into CII259-273 and investigated the effect on binding to DR4 and the subsequent T-cell response. Molecular dynamics simulations revealed that complexes between DR4 and derivatives of CII259-273 were highly dynamic. Signaling in the overall multicomponent system was found to depend on formation of an appropriate number of dynamic intramolecular hydrogen bonds between DR4 and CII259-273, together with the positioning of the galactose moiety of CII259-273 in the DR4 binding groove. Interestingly, the system tolerated modifications at several positions in CII259-273, indicating opportunities to use analogues to increase our understanding of how rheumatoid arthritis develops and for evaluation as vaccines to treat RA.

Health assessment questionnaire score is the best predictor of 5-year quality of life in early rheumatoid arthritis.

PubMed

Cohen, Jean-David; Dougados, Maxime; Goupille, Philippe; Cantagrel, Alain; Meyer, Olivier; Sibilia, Jean; Daurès, Jean-Pierre; Combe, Bernard

2006-10-01

To evaluate and determine prognostic factors of 5-year quality of life in patients with early rheumatoid arthritis (RA). A cohort of 191 patients with RA and disease duration < 1 year was prospectively followed over 5 years. The outcome measure was quality of life as assessed by the Arthritis Impact Measurement Scales 2 (AIMS2). Univariate analysis, then stepwise multiple logistic regression, was used to find independent baseline prognostic variables. After accounting for death, loss of followup, and missing data, 158 patients (82.72%) were included in the analysis. The mean AIMS2 physical, symptom, psychological, social interaction, and work scores after 5 years were 1.6 (range 0-6.88), 4.0 (0-10), 3.48 (0-9.22), 4.06 (0-8.69), and 1.87 (0-8.13), respectively. The AIMS2 physical component was significantly correlated with Health Assessment Questionnaire (HAQ) score at 5 years. Logistic regression analysis revealed that the baseline values able to predict the 5-year physical, psychological, symptom, social interaction, and work status were, respectively: HAQ score and erythrocyte sedimentation rate (ESR), body mass index (BMI), HAQ; erosion score and sex, HAQ; ESR and anti-perinuclear antibody; matrix metalloproteinase-3 (MMP3) level, joint space narrowing, and tender joint scores; HAQ score and age. The multidimensional structure of the AIMS2 allowed us to assess the 5-year health-related quality of life in early RA. Using this instrument as an outcome variable, prognostic factors were selected and varied widely depending on the evaluated domain. The baseline HAQ score was the best predictive factor of 4 of the 5 domains of the AIMS2.

Hypochlorhydria and hypergastrinaemia in rheumatoid arthritis.

PubMed Central

de Witte, T J; Geerdink, P J; Lamers, C B; Boerbooms, A M; van der Korst, J K

1979-01-01

In order to evaluate the incidence and aetiology of hypergastrinaemia 53 patients with seropositive rheumatoid arthritis were examined for gastric acid secretion, fasting serum gastrin concentration, circulating parietal cell antibodies, and some parameters of the activity of inflammation of rheumatoid arthritis. The basal and maximum acid output was found to be subnormal in this group (P less than 0.01), and in 11 of these patients (23%) the fasting serum gastrin levels were raised (P less than 0.05). This hypergastrinaemia correlated strongly with maximum acid output. Only in cases of achlorhydria or hypochlorhydria (maximum acid output less than 2 mmol/l) was the serum gastrin level markedly raised. Two out of 5 patients with achlorhydria were found to have circulating parietal cell antibodies, and 1 had decreased absorption of vitamin B12. No relationship was found between serum gastrin and duration or activity of rheumatoid arthritis; nor was there a relationship between basal serum gastrin and the various antirheumatic drugs administered. PMID:434940

Postoperative Surgical Infection After Spinal Surgery in Rheumatoid Arthritis.

PubMed

Koyama, Kensuke; Ohba, Tetsuro; Ebata, Shigeto; Haro, Hirotaka

2016-05-01

Individuals with rheumatoid arthritis are at higher risk for infection than the general population, and surgical site infection after spinal surgery in this population can result in clinically significant complications. The goal of this study was to identify risk factors for acute surgical site infection after spinal surgery in patients with rheumatoid arthritis who were treated with nonbiologic (conventional) disease-modifying antirheumatic drugs (DMARDs) alone or with biologic DMARDs. All patients treated with biologic agents were treated with nonbiologic agents as well. The authors performed a retrospective, single-center review of 47 consecutive patients with rheumatoid arthritis who underwent spinal surgery and had follow-up of 3 months or longer. The incidence of surgical site infection was examined, and multivariate logistic regression analysis was performed to test the association of surgical site infection with putative risk factors, including the use of biologic agents, methotrexate, and prednisolone, as well as the duration of rheumatoid arthritis, the presence of diabetes, patient age, length of surgery, and number of operative levels. After spinal surgery, 14.89% (7 of 47) of patients had surgical site infection. Use of methotrexate and/or prednisolone, patient age, diabetes, duration of rheumatoid arthritis, length of surgery, number of operative levels, and use of biologic DMARDs did not significantly increase the risk of infection associated with spinal surgery. All patients who had surgical site infection had undergone spinal surgery with instrumentation. The findings show that greater attention to preventing surgical site infection may be needed in patients with rheumatoid arthritis who undergo spinal surgery with instrumentation. To the authors' knowledge, this is the first study to show that the use of biologic agents did not increase the incidence of surgical site infection after spinal surgery in patients with rheumatoid arthritis

Rheumatoid arthritis and work: The impact of rheumatoid arthritis on absenteeism and presenteeism.

PubMed

Verstappen, Suzanne M M

2015-06-01

For patients with rheumatoid arthritis (RA), being in paid work is very important, and it increases self-esteem and financial independence. Although the management of RA has changed in the last 15 years to early aggressive treatment and the introduction of biologic treatments, many patients still have to take sick leave or even stop working because of their RA (i.e., absenteeism). For those remaining in paid work, patients may experience problems due to RA resulting in productivity loss while at work (i.e., presenteeism). The costs attributed to absenteeism and presenteeism (i.e., indirect costs) have been estimated to be very high, and they even exceed direct costs. However, there is no consensus on how to calculate these costs. This manuscript examines the relationship between the use of biologic therapy and absenteeism, with a focus on sick leave, and on presenteeism, and it provides an overview of indirect costs of absenteeism and presenteeism in those treated with biologic therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Glucocorticoid Receptor-Mediated Repression of Pro-Inflammatory Genes in Rheumatoid Arthritis

DTIC Science & Technology

2015-10-01

1 AWARD NUMBER: W81XWH-14-1-0314 TITLE: Glucocorticoid Receptor-Mediated Repression of Pro-Inflammatory Genes in Rheumatoid Arthritis ...19 Sep 2015 4. TITLE AND SUBTITLE Glucocorticoid Receptor-Mediated Repression of Pro- Inflammatory Genes in Rheumatoid Arthritis 5a. CONTRACT NUMBER...SUBJECT TERMS Rheumatoid arthritis , inflammation and autoimmunity, macrophages, glucocorticoid receptor, transcriptional regulation, coactivators and

Rheumatoid arthritis phenotype at presentation differs depending on the number of autoantibodies present.

PubMed

Derksen, V F A M; Ajeganova, S; Trouw, L A; van der Helm-van Mil, A H M; Hafström, I; Huizinga, T W J; Toes, R E M; Svensson, B; van der Woude, D

2017-04-01

In rheumatoid arthritis (RA), seropositive and seronegative disease may be two entities with different underlying pathophysiological mechanisms, long-term outcomes and disease presentations. However, the effect of the conjoint presence of multiple autoantibodies, as proxy for a more pronounced humoral autoimmune response, on clinical phenotype remains unclear. Therefore, this study investigates the association between the number of autoantibodies and initial clinical presentation in two independent cohorts of patients with early RA. Autoantibody status (rheumatoid factor, anticitrullinated protein antibodies and anticarbamylated protein antibodies) was determined at baseline in the Leiden Early Arthritis Cohort (n=828) and the Swedish BARFOT (Better Anti-Rheumatic Farmaco-Therapy, n=802) study. The association between the number of autoantibodies and baseline clinical characteristics was investigated using univariable and multivariable ordinal regression. In both cohorts, the following independent associations were found in multivariable analysis: patients with a higher number of RA-associated antibodies were younger, more often smokers, had a longer symptom duration and a higher erythrocyte sedimentation rate at presentation compared with patients with few autoantibodies. The number of autoantibodies, reflecting the breadth of the humoral autoimmune response, is associated with the clinical presentation of RA. Predisease pathophysiology is thus reflected by the initial clinical phenotype. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Anticardiolipin antibodies in rheumatoid arthritis.

PubMed

Keane, A; Woods, R; Dowding, V; Roden, D; Barry, C

1987-10-01

Anticardiolipin antibody (ACA) was present in the sera of 49% of 90 consecutive patients with rheumatoid arthritis (RA). The ACA was absent in 30 control patients with osteoarthritis. C-reactive protein levels equal to or exceeding 7 mg/dl were found in 10 patients all of whom were ACA positive. ACA was present in a larger proportion of rheumatoid factor (RF) positive than of RF negative patients. Male sex and extra-articular manifestations of RA were both more common in ACA positive than ACA negative patients. In the ACA positive group the lupus anticoagulant and VDRL tests were negative. However, a small number of patients had evidence of vascular events.

A five-year model to assess the early cost-effectiveness of new diagnostic tests in the early diagnosis of rheumatoid arthritis.

PubMed

Buisman, Leander R; Luime, Jolanda J; Oppe, Mark; Hazes, Johanna M W; Rutten-van Mölken, Maureen P M H

2016-06-10

There is a lack of information about the sensitivity, specificity and costs new diagnostic tests should have to improve early diagnosis of rheumatoid arthritis (RA). Our objective was to explore the early cost-effectiveness of various new diagnostic test strategies in the workup of patients with inflammatory arthritis (IA) at risk of having RA. A decision tree followed by a patient-level state transition model, using data from published literature, cohorts and trials, was used to evaluate diagnostic test strategies. Alternative tests were assessed as add-on to or replacement of the ACR/EULAR 2010 RA classification criteria for all patients and for intermediate-risk patients. Tests included B-cell gene expression (sensitivity 0.60, specificity 0.90, costs €150), MRI (sensitivity 0.90, specificity 0.60, costs €756), IL-6 serum level (sensitivity 0.70, specificity 0.53, costs €50) and genetic assay (sensitivity 0.40, specificity 0.85, costs €750). Patients with IA at risk of RA were followed for 5 years using a societal perspective. Guideline treatment was assumed using tight controlled treatment based on DAS28; if patients had a DAS28 >3.2 at 12 months or later patients could be eligible for starting biological drugs. The outcome was expressed in incremental cost-effectiveness ratios (€2014 per quality-adjusted life year (QALY) gained) and headroom. The B-cell test was the least expensive strategy when used as an add-on and as replacement in intermediate-risk patients, making it the dominant strategy, as it has better health outcomes and lower costs. As add-on for all patients, the B-cell test was also the most cost-effective test strategy. When using a willingness-to-pay threshold of €20,000 per QALY gained, the IL-6 and MRI strategies were not cost-effective, except as replacement. A genetic assay was not cost-effective in any strategy. Probabilistic sensitivity analysis revealed that the B-cell test was consistently superior in all strategies. When

Low prevalence of work disability in early inflammatory arthritis (EIA) and early rheumatoid arthritis at enrollment into a multi-site registry: results from the catch cohort.

PubMed

Mussen, Lauren; Boyd, Tristan; Bykerk, Vivian; de Leon, Faye; Li, Lihua; Boire, Gilles; Hitchon, Carol; Haraoui, Boulos; Thorne, J Carter; Pope, Janet

2013-02-01

We determined the prevalence of work disability in early rheumatoid arthritis (ERA) and undifferentiated early inflammatory arthritis (EIA) patients at first enrollment into the Canadian Early Arthritis Cohort (CATCH) who met the 2010 ACR criteria versus those not meeting criteria, to determine the impact of meeting new criteria on work disability status. Data at first visit into the cohort were analyzed. Descriptive statistics and logistic regression analyses were performed to investigate the association of other variables in our database with work disability. 1,487 patients were enrolled in the CATCH study, a multi-site observational, prospective cohort of patients with EIA. 934 patients were excluded (505 based on missing criteria for ACR 2010 classification, as anti-CCP was absent, and 429 were not working for other reasons). Of the 553 patients included, 71 % were female with mean disease duration of 6.4 months. 524 (94.8 %) were employed while 29 (5.2 %) reported work disability at first visit. There were no differences between those meeting 2010 ACR criteria versus those who did not. Baseline characteristics associated with work disability were male gender, age, education, income, HAQ, and positive RF status. The mean HAQ score in work disabled patients was 1.4 versus 0.9 in those who were working (p < 0.001). Disease activity score (DAS28) was not associated with work disability (p = 0.069), nor was tender joint count, swollen joint count, anti-CCP, patient global assessment, or SF-12v2. In the regression model, work disability was associated with lower income levels (p = 0.01) and worse HAQ scores (OR 2.33; p = 0.001), but not significantly associated with male gender (p = 0.08), older age (>50 years; p = 0.3), lower education (p = 0.3) or RF positivity (p = 0.6). We found rates of work disability to be low at entry into this EIA cohort compared to previous studies. There may be potential for intervention in ERA to prevent the development of work

Tumor necrosis factor-α inhibitor treatment and the risk of incident cardiovascular events in patients with early rheumatoid arthritis: a nested case-control study.

PubMed

Desai, Rishi J; Rao, Jaya K; Hansen, Richard A; Fang, Gang; Maciejewski, Matthew; Farley, Joel

2014-11-01

To compare the risk of cardiovascular (CV) events between use of tumor necrosis factor-α inhibitors (TNFi) and nonbiologic disease-modifying antirheumatic drugs (DMARD) in patients with early rheumatoid arthritis (RA). A nested case-control study was conducted using data from Truven's MarketScan commercial and Medicare claims database for patients with early RA who started treatment with either a TNFi or a nonbiologic DMARD between January 1, 2008, and December 31, 2010. Date of CV event diagnosis for cases was defined as the event date, and 12 age-matched and sex-matched controls were sampled using incidence density sampling. Drug exposure was defined into the following mutually exclusive categories hierarchically: (1) current use of TNFi (with or without nonbiologics), (2) past use of TNFi (with or without nonbiologics), (3) current use of nonbiologics only, and (4) past use of nonbiologics only. Current use was defined as any use in the period 90 days prior to the event date. Conditional logistic regression models were used to derive incidence rate ratios (IRR). From the cohort of patients with early RA, 279 cases of incident CV events and 3348 matched controls were identified. The adjusted risk of CV events was not significantly different between current TNFi users and current nonbiologic users (IRR 0.92, 95% CI 0.59-1.44). However, past users of nonbiologics showed significantly higher risk compared to current nonbiologic users (IRR 1.47, 95% CI 1.04-2.08). No differences in the CV risk were found between current TNFi and current nonbiologic DMARD treatment in patients with early RA.

Coexisting ankylosing spondylitis and rheumatoid arthritis: a case report with literature review.

PubMed

Guo, Ying-Ying; Yang, Li-Li; Cui, Hua-Dong; Zhao, Shuai; Zhang, Ning

2011-10-01

A 30-year-old female patient with coexisting ankylosing spondylitis and rheumatoid arthritis was diagnosed and treated. The human leukocyte antigen (HLA)-B27 is a predisposing factor of ankylosing spondylitis and HLA-DR4 is a predisposing factor of rheumatoid arthritis. This patient was HLA-B27 and HLA-DR4 positive, and ankylosing spondylitis manifested before rheumatoid arthritis. After disease modifying anti-rheumatic drugs successfully arrested ankylosing spondylitis activity the patient conceived and delivered a healthy baby. One year later, she developed peripheral polyarthritis and was diagnosed with rheumatoid arthritis. We hypothesized that pregnancy may be one of the environmental factors that can activate rheumatoid arthritis, and that disease modifying anti-rheumatic drugs play an important role in keeping the disease under control.

Periodontitis in early and chronic rheumatoid arthritis: a prospective follow-up study in Finnish population.

PubMed

Äyräväinen, Leena; Leirisalo-Repo, Marjatta; Kuuliala, Antti; Ahola, Kirsi; Koivuniemi, Riitta; Meurman, Jukka H; Heikkinen, Anna Maria

2017-01-31

To investigate the association between rheumatoid arthritis (RA) and periodontitis with special emphasis on the role of antirheumatic drugs in periodontal health. Prospective follow-up study. Patients with early untreated RA and chronic active RA were examined at baseline and 16 months later. Controls were examined once. The study was conducted in Finland from September 2005 to May 2014 at the Helsinki University Hospital. Overall, 124 participants were recruited for dental and medical examinations: 53 were patients with early disease-modifying antirheumatic drug (DMARD) naїve RA (ERA), 28 were patients with chronic RA (CRA) with insufficient response to conventional DMARDs. After baseline examination, patients with ERA started treatment with synthetic DMARDs and patients with CRA with biological DMARDs. Controls were 43 age-matched, gender-matched and community-matched participants. Degree of periodontitis (defined according to the Center for Disease Control and Prevention and the American Academy of Periodontology). Prevalence of periodontal bacteria (analysed from plaque samples), clinical rheumatological status by Disease Activity Score, 28-joint count (DAS28), function by Health Assessment Questionnaire (HAQ) and treatment response by European League Against Rheumatism (EULAR) criteria. Moderate periodontitis was present in 67.3% of patients with ERA, 64.3% of patients with CRA and 39.5% of control participants (p=0.001). Further, patients with RA had significantly more periodontal findings compared with controls, recorded with common periodontal indexes. In the re-examination, patients with RA still showed poor periodontal health in spite of treatment with DMARDs after baseline examination. The prevalence of Porphyromonas gingivalis was higher in patients with ERA with periodontal probing depth ≥4 mm compared with patients with CRA and controls. Antirheumatic medication did not seem to affect the results. Moderate periodontitis was more frequent in

Early non-response to certolizumab pegol in rheumatoid arthritis predicts treatment failure at one year. Data from a randomised phase III clinical trial.

PubMed

Berenbaum, Francis; Pham, Thao; Claudepierre, Pascal; de Chalus, Thibault; Joubert, Jean-Michel; Saadoun, Carine; Riou França, Lionel; Fautrel, Bruno

2018-01-01

To compare different early clinical criteria of non-response determined at three months as predictors of clinical failure at one year in patients with rheumatoid arthritis starting therapy with certolizumab pegol. Data were derived from a randomised Phase III clinical trial in patients with rheumatoid arthritis who failed to respond to methotrexate monotherapy. Patients included in this post-hoc analysis were treated with certolizumab pegol (400mg qd reduced to 200mg qd after one month) and with methotrexate. The study duration was twelve months. Response at three months was determined with the American College of Rheumatology-50, Disease Assessment Score-28 ESR, Health Assessment Questionnaire and the Clinical Disease Activity Index. The performance of these measures at predicting treatment failure at twelve months defined by the American College of Rheumatology-50 criteria was determined, using the positive predictive values as the principal evaluation criterion. Three hundred and eighty two patients were available for analysis and 225 completed the twelve-month follow-up. At Week 52, 149 (38.1%) patients met the American College of Rheumatology-50 response criterion. Positive predictive values ranged from 81% for a decrease in Health Assessment Questionnaire- Disability index score since baseline >0.22 to 95% for a decrease in Disease Assessment Score-28 score since baseline≥1.2. Sensitivity was≤70% in all cases. Performance of these measures was similar irrespective of the definition of treatment failure at 12months. Simple clinical measures of disease activity can predict future treatment failure reliably and are appropriate for implementing treat-to-target treatment strategies in everyday practice. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Comorbidity of gout and rheumatoid arthritis in a large population database.

PubMed

Merdler-Rabinowicz, Rona; Tiosano, Shmuel; Comaneshter, Doron; Cohen, Arnon D; Amital, Howard

2017-03-01

Coexistence of rheumatoid arthritis and gout is considered to be unusual. The current study was designed as a population-based cross-sectional study, utilizing the medical database of Clalit Health Services, the largest healthcare provider organization in Israel. Data of adult patients who were previously diagnosed with rheumatoid arthritis was retrieved. For each patient, five age- and sex-matched control patients were randomly selected. Different parameters including BMI, socioeconomic status, and existence of gout as well as smoking and hypertension were examined for both groups. The study included 11,540 patients with rheumatoid arthritis and 56,763 controls. The proportion of gout in the study group was high compared to controls (1.61 vs. 0.92%, P < 0.001). In a multivariate analysis, rheumatoid arthritis was associated with gout (OR = 1.72, 95% CI 1.45-2.05, P = 0.00). The proportion of gout in rheumatoid arthritis patients is not lower than in the general population.

Early rheumatoid disease. II. Patterns of joint involvement.

PubMed Central

Fleming, A; Benn, R T; Corbett, M; Wood, P H

1976-01-01

Data from the first research clinic visit (Fleming and others, 1976) have been subjected to factor analysis to identify early patterns of joint involvement. Nine patterns emerged. Two patterns, if present early, were found to have prognostic significance. An eventually more severe disease was associated with a pattern of large joint involvement (shoulder, elbow, wrist, knee) and a pattern based on metatarsophalangeal joints I and III. PMID:970995

Longterm Work Productivity Costs Due to Absenteeism and Permanent Work Disability in Patients with Early Rheumatoid Arthritis: A Nationwide Register Study of 7831 Patients.

PubMed

Martikainen, Janne A; Kautiainen, Hannu; Rantalaiho, Vappu; Puolakka, Kari T

2016-12-01

To estimate the development and potential disproportional distribution of longterm productivity costs (PC) and their determinants leading to work absenteeism and permanent work disability in working-aged patients with early rheumatoid arthritis (RA). A cohort of subjects with early RA was created by identifying the new cases of RA from the national drug reimbursement register that had been granted a special reimbursement for their antirheumatic medications for RA from 2000-2007. The dataset was enriched by cross-linking with other national registries detailing work absenteeism days and permanent disability pensions. In the base case, the human capital approach was applied to estimate PC based on subjects' annual number of absenteeism days and incomes. Hurdle regression analysis was applied to study the determinants of PC. Among the 7831 subjects with early RA, the mean (bootstrapped 95% CI) annual PC per person-observation year was €4800 (4547-5070). The annual PC declined after the first year of RA diagnosis, but increased significantly in subsequent years. In addition, the PC was heavily disproportionally concentrated in a small fraction of patients with RA, because only around 20% of patients accounted for the majority of total annual PC. The initiation of active drug treatment during the first 3 months after RA diagnosis significantly reduced the cumulative PC when compared with no drug treatment. The longterm PC increased significantly in parallel with years elapsing after RA diagnosis. Further, the majority of these PC are incurred by a small proportion of patients.

Folate-targeted nanoparticles for rheumatoid arthritis therapy.

PubMed

Nogueira, Eugénia; Gomes, Andreia C; Preto, Ana; Cavaco-Paulo, Artur

2016-05-01

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. Although the cause of RA remains unknown, the complex interaction between immune mediators (cytokines and effector cells) is responsible for the joint damage that begins at the synovial membrane. Activated macrophages are critical in the pathogenesis of RA and showed specifically express a receptor for the vitamin folic acid (FA), folate receptor β (FRβ). This particular receptor allows internalization of FA-coupled cargo. In this review we will address the potential of nanoparticles as an effective drug delivery system for therapies that will directly target activated macrophages. Special attention will be given to stealth degree of the nanoparticles as a strategy to avoid clearance by macrophages of the mononuclear phagocytic system (MPS). This review summarizes the application of FA-target nanoparticles as drug delivery systems for RA and proposes prospective future directions. Rheumatoid arthritis is a debilitating autoimmune disease of the joints which affects many people worldwide. Up till now, there is a lack of optimal therapy against this disease. In this review article, the authors outlined in depth the current mechanism of disease for rheumatoid arthritis and described the latest research in using folic acid-targeted nanoparticles to target synovial macrophages in the fight against rheumatoid arthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

Response of human rheumatoid arthritis osteoblasts and osteoclasts to adiponectin.

PubMed

Krumbholz, Grit; Junker, Susann; Meier, Florian M P; Rickert, Markus; Steinmeyer, Jürgen; Rehart, Stefan; Lange, Uwe; Frommer, Klaus W; Schett, Georg; Müller-Ladner, Ulf; Neumann, Elena

2017-01-01

Adiponectin is an effector molecule in the pathophysiology of rheumatoid arthritis, e.g. by inducing cytokines and matrix degrading enzymes in synovial fibroblasts. There is growing evidence that adiponectin affects osteoblasts and osteoclasts although the contribution to the aberrant bone metabolism in rheumatoid arthritis is unclear. Therefore, the adiponectin effects on rheumatoid arthritis-derived osteoblasts and osteoclasts were evaluated. Adiponectin and its receptors were examined in bone tissue. Primary human osteoblasts and osteoclasts were stimulated with adiponectin and analysed using realtime polymerase chain-reaction and immunoassays. Effects on matrix-production by osteoblasts and differentiation and resorptive activity of osteoclasts were examined. Immunohistochemistry of rheumatoid arthritis bone tissue showed adiponectin expression in key cells of bone remodelling. Adiponectin altered gene expression and cytokine release in osteoblasts and increased IL-8 secretion by osteoclasts. Adiponectin inhibited osterix and induced osteoprotegerin mRNA in osteoblasts. In osteoclasts, MMP-9 and tartrate resistant acid phosphatase expression was increased. Accordingly, mineralisation capacity of osteoblasts decreased whereas resorptive activity of osteoclasts increased. The results confirm the proinflammatory potential of adiponectin and support the idea that adiponectin influences rheumatoid arthritis bone remodelling through alterations in osteoblast and osteoclast.

Secular Changes in Clinical Features at Presentation of Rheumatoid Arthritis: Increase in Comorbidity But Improved Inflammatory States.

PubMed

Nikiphorou, Elena; Norton, Sam; Carpenter, Lewis; Dixey, Josh; Andrew Walsh, David; Kiely, Patrick; Young, Adam

2017-01-01

To examine secular trends in demographics, clinical manifestations, and comorbidity on first presentation of rheumatoid arthritis (RA) prior to disease-modifying antirheumatic drug treatment. A total of 2,701 patients were recruited over 25 years to 2 UK-based RA inception cohorts: the Early Rheumatoid Arthritis Study (9 centers; 1986-2001) and the Early Rheumatoid Arthritis Network (23 centers; 2002-2012). Trends in demographic and baseline clinical/laboratory and radiographic variables and comorbidities were estimated using mixed-effects models, including random effects for recruitment center. Age at onset increased from 53.2 to 57.7 years in 1990 and 2010, respectively (2.6 months/year; 95% confidence interval [95% CI] 1.2, 4.1). Sex ratio, the proportion living in deprived areas, and smoking status were unchanged (P > 0.05) and there were no changes in the proportion seropositive or erosive at baseline (P > 0.05). After controlling for treatment at the time of assessment, erythrocyte sedimentation rate decreased and hemoglobin increased over time (P > 0.05); however, the Health Assessment Questionnaire (HAQ), the Disease Activity Score (DAS), the DAS in 28 joints, and joint counts were unchanged (P > 0.05). The overall prevalence of comorbidity increased from 29.0% in 1990 to 50.7% in 2010, mainly due to cardiovascular and non-cardiac vascular conditions, including hypertension. There was a significant increase in body mass index (0.15 units/year; 95% CI 0.11, 0.18), resulting in an increase in the prevalence of obesity from 13.3% in 1990 to 33.6% in 2010. Age at onset and comorbidity burden, especially obesity, have increased at RA presentation over 25 years, reflecting wider demographic trends at the population level. In contrast, there were no accompanying changes in disease severity assessed by composite markers of disease activity, radiographic erosions, seropositivity, or HAQ at presentation. Treatment strategies in early RA should take

Rheumatoid arthritis in a rural South African Negro population.

PubMed Central

Beighton, P; Solomon, L; Valkenburg, H A

1975-01-01

(1) An epidemiological study of a rural African community has been carried out in the Western Transvaal. Altogether 801 respondents over 15 years old were examined; radiographs of the hands and feet were obtained in all these individuals. Serological tests for rheumatoid factor were carried out on 516 blood samples. (2) The diagnosis of inflammatory polyarthritis was based on a modification of the Rome Criteria of 1961. Two categories were defined: 'definite' and 'probable' rheumatoid arthritis. (3) In this population inflammatory polyarthritis was much less common and much milder in its manifestations than in European and American peoples. The prevalence of 'definite' rheumatoid arthritis was 0.12% and of 'definite' and 'probable' rheumatoid arthritis combined, 0.87. Such changes as were encountered on clinical and radiological examination were invariably mild; no respondent in the entire survey had clinical features that would have been accepted in the ordinary way as those of rheumatoid arthritis. (4) The latex fixation test (LFT) was positive in 8.9% of the sera tested; the modified LFT aftaer inactivation of the serum at 56 degrees C was positive in 15.1% of cases. Similar findings in West African populations have been explained on the basis of alteration of the immune response by widespread parasitic infections. No obvious aetiological factor of this type was found in the present survey. PMID:1137440

Chinese Registry of rheumatoid arthritis (CREDIT): II. prevalence and risk factors of major comorbidities in Chinese patients with rheumatoid arthritis.

PubMed

Jin, Shangyi; Li, Mengtao; Fang, Yongfei; Li, Qin; Liu, Ju; Duan, Xinwang; Liu, Yi; Wu, Rui; Shi, Xiaofei; Wang, Yongfu; Jiang, Zhenyu; Wang, Yanhong; Yu, Chen; Wang, Qian; Tian, Xinping; Zhao, Yan; Zeng, Xiaofeng

2017-11-15

Rheumatoid arthritis patients are at higher risk of developing comorbidities. The main objective of this study was to evaluate the prevalence of major comorbidities in Chinese rheumatoid arthritis patients. We also aimed to identify factors associated with these comorbidities. Baseline demographic, clinical characteristics and comorbidity data from RA patients enrolled in the Chinese Registry of rhEumatoiD arthrITis (CREDIT) from Nov 2016 to August 2017 were presented and compared with those from five other registries across the world. Possible factors related to three major comorbidities (cardiovascular disease, fragility fracture and malignancy) were identified using multivariate logistic regression analyses. A total of 13,210 RA patients were included (80.6% female, mean age 52.9 years and median RA duration 4.0 years). Baseline prevalence rates of major comorbidities were calculated: CVD, 2.2% (95% CI 2.0-2.5%); fragility fracture, 1.7% (95% CI 1.5-1.9%); malignancy, 0.6% (95% CI 0.5-0.7%); overall major comorbidities, 4.2% (95% CI 3.9-4.6%). Advanced age was associated with all comorbidities. Male gender and disease duration were positively related to CVD. Female sex and longer disease duration were potential risk factors for fragility fractures. Ever use of methotrexate (MTX) was negatively related to baseline comorbidities. Patients with rheumatoid arthritis in China have similar prevalence of comorbidities with other Asian countries. Advanced age and long disease duration are possible risk factors for comorbidities. On the contrary, MTX may protect RA patients from several major comorbidities, supporting its central role in the management of rheumatoid arthritis.

Dialysis treatment in patients with rheumatoid arthritis.

PubMed

Hezemans, R L; Krediet, R T; Arisz, L

1995-07-01

The results of dialysis treatment in 24 rheumatoid arthritis patients, 20 chronic rheumatoid arthritis (RA) and 4 juvenile rheumatoid arthritis (JRA), were analysed. Presence of secondary amyloidosis, renal function, morbidity and survival were examined. Amyloidosis was present in 13 patients. Especially among amyloidosis patients, renal function declined rapidly in the last year before dialysis started. On average, 63 days per patient-year were spent in the hospital, 58% was dialysis-related, mainly due to vascular access problems. Hospitalization was even more widespread in amyloidosis patients (79 days, 72% dialysis-related). Median survival in RA patients with amyloidosis was 11 months; in RA patients without amyloidosis this was 29 months. Two-year survival was only 1 out of 10 for the RA amyloidosis patients; for the RA non-amyloidosis patients this was 5 out of 6 (p < 0.01). Cardiovascular causes of death were most frequent. In conclusion, high morbidity and low survival make RA patients with amyloidosis a high-risk group on renal replacement therapy.

Disease-modifying antirheumatic drugs other than methotrexate in rheumatoid arthritis and seronegative arthritis.

PubMed

Nandi, Pradip; Kingsley, Gabrielle H; Scott, David L

2008-05-01

To outline recent research findings with nonmethotrexate disease-modifying antirheumatic drugs in rheumatoid arthritis and seronegative arthritis spanning systematic reviews, randomized controlled trials, observational clinical practice trials and assessments of adverse effects. Systematic reviews show no important differences between methotrexate, leflunomide and sulfasalazine monotherapies; early disease-modifying antirheumatic drug therapy reduces erosive progression. Observational studies show that nonmethotrexate disease-modifying antirheumatic drugs are widely prescribed; their usage has increased in the biologic era. A systemic review also showed patients who failed monotherapy benefited from disease-modifying antirheumatic drug combinations without excess toxicity. Randomized controlled trials of intensive initial disease-modifying antirheumatic drug combinations showed they reduce synovitis and erosive damage, especially when used with steroids. The subsequent sequence of disease-modifying antirheumatic drugs and the value of changing disease-modifying antirheumatic drug monotherapies or stepping-up to combination disease-modifying antirheumatic drugs are, however, unresolved. The adverse risks of nonmethotrexate disease-modifying antirheumatic drugs have been evaluated, including infections and lung disease; patient-related risks seem more important than drug-related risks, though several disease-modifying antirheumatic drugs increase both types of adverse reactions. Two limitations of nonmethotrexate disease-modifying antirheumatic drugs are reduced impact on comorbidities like cardiovascular disease and reduced patient and clinician preferences for these treatments. Nonmethotrexate disease-modifying antirheumatic drugs are effective, relatively well tolerated and widely used. Their role in intensive treatment strategies in early rheumatoid arthritis appears of crucial importance.

IL-6-driven STAT signalling in circulating CD4+ lymphocytes is a marker for early anticitrullinated peptide antibody-negative rheumatoid arthritis.

PubMed

Anderson, Amy E; Pratt, Arthur G; Sedhom, Mamdouh A K; Doran, John Paul; Routledge, Christine; Hargreaves, Ben; Brown, Philip M; Lê Cao, Kim-Anh; Isaacs, John D; Thomas, Ranjeny

2016-02-01

A previously identified signal transduction and activator of transcription-3 (STAT3) target-enriched gene signature in circulating CD4+ T cells of patients with early rheumatoid arthritis (RA) was prominent in autoantibody-negative individuals. Here, interleukin (IL)-6-mediated STAT signalling was investigated in circulating lymphocytes of an independent early arthritis patient cohort, seeking further insight into RA pathogenesis and biomarkers of potential clinical utility. Constitutive and IL-6-induced expression of phosphorylated STAT1 (pSTAT1) and pSTAT3 was determined in T and B cells using Phosflow cytometric analysis in patients with RA and controls. Contemporaneous levels of serum cytokines were measured by immunoassay. Induced gene expression was measured in cultured CD4+T cells by quantitative real-time PCR. Among circulating lymphocytes of 187 patients with early arthritis, constitutive pSTAT3 correlated with serum IL-6 levels maximally in CD4+ T cells. Increased constitutive pSTAT3, but not pSTAT1, was observed in circulating CD4+ T cells of patients with early anticitrullinated peptide autoantibody (ACPA)-negative RA compared with disease controls, and these levels decreased alongside markers of disease activity with IL-6R-targeted treatment. Among patients presenting with seronegative undifferentiated arthritis (UA) the ratio of constitutive pSTAT3:pSTAT1 in CD4+ T cells contributed substantially to an algorithm for predicting progression to classifiable RA during a median of 20 months follow-up (area under receiver operator characteristic curve=0.84; p<0.001). Our findings support a particular role for IL-6-driven CD4+ T cell activation via STAT3 during the induction of RA, particularly as a feature of ACPA-negative disease. CD4+ T cell pSTAT measurements show promise as biomarkers of UA-RA progression and now require independent validation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

Current treatment paradigms in rheumatoid arthritis.

PubMed

Fries, J F

2000-06-01

Rheumatoid arthritis (RA) has traditionally been treated using the pyramid approach, in which non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment and disease-modifying anti-rheumatic drugs (DMARDs) are introduced relatively late in the disease. This approach is no longer valid. Previously regarded as a benign disease, RA is now recognized as causing substantial morbidity and mortality, as do the NSAIDs used in treatment. DMARDs are more effective in controlling the pain and disability of RA than NSAIDs, and are often no more toxic. The current treatment paradigm emphasizes early, consistent use of DMARDs. A 'sawtooth' strategy of DMARD use has been proposed, in which a rising but low level of disability triggers a change in therapy. Determining the most clinically useful DMARD combinations and the optimal sequence of DMARD use requires effectiveness studies, Bayesian approaches and analyses of long-term outcomes. Such approaches will allow optimization of multiple drug therapies in RA, and should substantially improve the long-term outcome for many patients.

Preliminary clinical results: an analyzing tool for 2D optical imaging in detection of active inflammation in rheumatoid arthritis

NASA Astrophysics Data System (ADS)

Adi Aizudin Bin Radin Nasirudin, Radin; Meier, Reinhard; Ahari, Carmen; Sievert, Matti; Fiebich, Martin; Rummeny, Ernst J.; No"l, Peter B.

2011-03-01

Optical imaging (OI) is a relatively new method in detecting active inflammation of hand joints of patients suffering from rheumatoid arthritis (RA). With the high number of people affected by this disease especially in western countries, the availability of OI as an early diagnostic imaging method is clinically highly relevant. In this paper, we present a newly in-house developed OI analyzing tool and a clinical evaluation study. Our analyzing tool extends the capability of existing OI tools. We include many features in the tool, such as region-based image analysis, hyper perfusion curve analysis, and multi-modality image fusion to aid clinicians in localizing and determining the intensity of inflammation in joints. Additionally, image data management options, such as the full integration of PACS/RIS, are included. In our clinical study we demonstrate how OI facilitates the detection of active inflammation in rheumatoid arthritis. The preliminary clinical results indicate a sensitivity of 43.5%, a specificity of 80.3%, an accuracy of 65.7%, a positive predictive value of 76.6%, and a negative predictive value of 64.9% in relation to clinical results from MRI. The accuracy of inflammation detection serves as evidence to the potential of OI as a useful imaging modality for early detection of active inflammation in patients with rheumatoid arthritis. With our in-house developed tool we extend the usefulness of OI imaging in the clinical arena. Overall, we show that OI is a fast, inexpensive, non-invasive and nonionizing yet highly sensitive and accurate imaging modality.-

NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis

PubMed Central

Khandpur, Ritika; Carmona-Rivera, Carmelo; Vivekanandan-Giri, Anuradha; Gizinski, Alison; Yalavarthi, Srilakshmi; Knight, Jason S.; Friday, Sean; Li, Sam; Patel, Rajiv M.; Subramanian, Venkataraman; Thompson, Paul; Chen, Pojen; Fox, David A.; Pennathur, Subramaniam; Kaplan, Mariana J.

2013-01-01

The early events leading to the development of rheumatoid arthritis (RA) remain unclear but formation of autoantibodies to citrullinated antigens (ACPA) is considered a key pathogenic phenomenon. Neutrophils isolated from patients with various autoimmune diseases display enhanced extracellular trap formation (NETs), a phenomenon that externalizes autoantigens and immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and synovial fluid RA neutrophils, compared to neutrophils from healthy controls and from patients with osteoarthritis. Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. During NETosis, neutrophils externalized citrullinated autoantigens implicated in RA pathogenesis, whereas anti-citrullinated vimentin antibodies potently induced NET formation. The inflammatory cytokines IL-17A and TNF-α induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease. PMID:23536012

The Role of IL-17 in the Angiogenesis of Rheumatoid Arthritis

DTIC Science & Technology

2015-06-01

AWARD NUMBER: W81XWH-10-1-0102 TITLE: The Role of IL-17 in the Angiogenesis of Rheumatoid Arthritis PRINCIPAL INVESTIGATOR: Shiva Shahrara...NUMBER W81XWH-10-1-0102 The Role of IL-17 in the Angiogenesis of Rheumatoid Arthritis 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S... rheumatoid arthritis (RA) joint vascularization. However, less is known about the pro-angiogenic factors downstream of IL-17 cascade that could indirectly

Economics of non-adherence to biologic therapies in rheumatoid arthritis.

PubMed

De Vera, Mary A; Mailman, Jonathan; Galo, Jessica S

2014-11-01

Adherence to biologic therapies among patients with rheumatoid arthritis is sub-optimal, with the proportion of adherent patients reported to be as low as 11 %. We found few studies evaluating economic outcomes, including health care costs, associated with non-adherence with biologic therapies. Findings suggest that while higher pharmacy costs drive total health care costs among adherent patients, non-adherent patients incur greater health care utilization including inpatient, outpatient, and laboratory services. Finally, economic factors are important determinants of adherence to biologics in patients with rheumatoid arthritis. Evidence to date has shown that higher out-of-pocket payments have a negative association with adherence to biologics. Furthermore, cost-related non-adherence is a highly prevalent problem in rheumatoid arthritis. Given the high costs of biologics and continued expansion of use in rheumatoid arthritis, there is need for more research to understand the economic implications of adherence to these therapies.

Subacromial bursitis with giant rice bodies as initial presentation of rheumatoid arthritis.

PubMed

Subramaniam, Ramesh; Tan, Justina Wei Lyn; Chau, Cora Yuk Ping; Lee, Keng Thiam

2012-10-01

Rice body formation is a nonspecific response to chronic synovial inflammation associated with tuberculous arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, seronegative inflammatory arthritis, and even osteoarthritis. Such bodies were termed rice bodies because of their close resemblance to grains of polished white rice. We present a case report of a middle-aged woman with right shoulder subacromial/subdeltoid bursitis with giant rice body formation as her initial presentation of rheumatoid arthritis. Her right shoulder symptoms resolved after subacromial and subdeltoid bursectomy and removal of the rice bodies. She subsequently developed inflammatory arthritis of other joints, met the criteria for rheumatoid arthritis, and has been treated medically.

Thrombokinetics in patients with rheumatoid arthritis treated with D-penicillamine.

PubMed Central

Thomas, D; Gallus, A S; Brooks, P M; Tampi, R; Geddes, R; Hill, W

1984-01-01

The mechanism of D-penicillamine induced thrombocytopenia in rheumatoid arthritis was investigated by measuring platelet life-span and platelet production rate in 2 groups of rheumatoid arthritis patients treated with 250-750 mg/day D-penicillamine, 14 with a normal platelet count and 9 with thrombocytopenia (platelet count 50-130 X 10(9)/1). Age matched control patients not treated with D-penicillamine included 14 with rheumatoid arthritis and 9 with osteoarthritis. The platelet life-span was normal, but platelet production rate was significantly reduced in the thrombocytopenic patients, suggesting that D-penicillamine causes thrombocytopenia through bone marrow suppression. PMID:6742902

Methotrexate: the emerging drug of choice for serious rheumatoid arthritis.

PubMed

Salach, R H; Cash, J M

1994-01-01

The recently recognized high morbidity and unexpected mortality associated with rheumatoid arthritis (RA) has spurred new interest in more aggressive, early treatment of this disease. Methotrexate (MTX) has rapidly become the rheumatologist's drug of choice for serious RA because of its favorable efficacy to toxicity ratio and rapid onset of action compared with other second-line agents. The initial concerns about hepatic fibrosis and cirrhosis in psoriatic patients has subsided somewhat as long-term liver toxicity data are accumulating in patients with RA. Routine liver biopsy with incremental doses of MTX is no longer recommended. Potential for severe lung, hematologic, and infectious complications exists, mandating careful monitoring of RA patients taking MTX.

Radiographic Severity of Rheumatoid Arthritis in African-Americans: Results from the CLEAR Registry

PubMed Central

Bridges, S. Louis; Causey, Zenoria L.; Burgos, Paula I.; Huynh, B. Quynh N.; Hughes, Laura B.; Danila, Maria I.; van Everdingen, Amalia; Ledbetter, Stephanie; Conn, Doyt L.; Tamhane, Ashutosh; Westfall, Andrew O.; Jonas, Beth L.; Callahan, Leigh F.; Smith, Edwin A.; Brasington, Richard; Moreland, Larry W.; Alarcón, Graciela S.; van der Heijde, Désirée M.

2010-01-01

Objective To describe radiographic changes in African-Americans with rheumatoid arthritis (RA) from the CLEAR (Consortium for the Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis) Registry, a multicenter observational study. Methods Self-declared African-American patients, were enrolled in CLEAR I, a longitudinal cohort of early RA (disease duration <2 years) from 2000 to 2005; or in CLEAR II, a cross-sectional cohort (any disease duration), from 2006 to the present. Demographic and clinical data were obtained, and sets of hand/wrist and foot radiographs were scored using the modified Sharp/van der Heijde scoring system. Results A total of 357 and 418 patients, respectively, have been enrolled into CLEAR I and CLEAR II. We report here an interim analysis of radiographic severity in these patients. For the CLEAR I cohort, 294 patients had a mean radiographic score of 2.89 at the baseline visit; 32.0% showed either erosions (25.9%) or joint space narrowing (JSN) (19.4%). At the 36-month visit the mean score was 5.65; 44.2% had erosions, 41.5% JSN and 55.4% had either. Among those patients without radiographic damage at baseline, 18.9% had progressed at the 36-month visit, compared to 57.1% of those with baseline damage (p<0.0001). For the CLEAR II cohort, 167 patients with RA of any duration, 65.3% exhibited joint erosions, 65.3% JSN and 74.8% exhibited either. The mean radiographic score was 33.42. Conclusion This is the largest radiographic study of African American RA patients. Damage occurs early in the disease and is associated with radiographic progression at 3 years of disease duration. The CLEAR Registry will provide a valuable resource for future analyses of genetic, clinical, and environmental factors associated with radiographic severity of RA in African-Americans. PMID:20461784

Should tumour necrosis factor antagonist safety information be applied from patients with rheumatoid arthritis to psoriasis? Rates of serious adverse events in the prospective rheumatoid arthritis BIOBADASER and psoriasis BIOBADADERM cohorts.

PubMed

García-Doval, I; Hernández, M V; Vanaclocha, F; Sellas, A; de la Cueva, P; Montero, D

2017-03-01

Information on the safety of tumour necrosis factor (TNF) antagonists frequently arises from their use in rheumatic diseases, their first approved indications, and is later applied to psoriasis. Whether the risk of biological therapy is similar in psoriasis and rheumatoid arthritis has been considered a priority research question. To compare the safety profile of anti-TNF drugs in patients with rheumatoid arthritis and psoriasis. We compared two prospective safety cohorts of patients with rheumatoid arthritis and psoriasis that share methods (BIOBADASER and BIOBADADERM). There were 1248 serious or mortal adverse events in 16 230 person-years of follow-up in the rheumatoid arthritis cohort (3171 patients), and 124 in the 2760 person-years of follow-up of the psoriasis cohort (946 patients). Serious and mortal adverse events were less common in patients with psoriasis than in rheumatoid arthritis (incidence rate ratio of serious adverse events in psoriasis/rheumatoid arthritis: 0·6, 95% confidence interval 0·5-0·7). This risk remained after adjustment for sex, age, treatment, disease, hypertension, diabetes, hypercholesterolaemia and simultaneous therapy with methotrexate (hazard ratio 0·54, 95% confidence interval 0·47-0·61), and after excluding patients receiving corticosteroids. Patients with rheumatoid arthritis showed a higher rate of infections, cardiac disorders, respiratory disorders and infusion-related reactions, whereas patients with psoriasis had more skin and subcutaneous tissue disorders and hepatobiliary disorders. Patients with rheumatoid arthritis clinical practice have almost double the risk of serious adverse events compared with patients with psoriasis, with a different pattern of adverse events. Safety data from rheumatoid arthritis should not be fully extrapolated to psoriasis. These differences are likely to apply to other immune-mediated inflammatory diseases. © 2016 British Association of Dermatologists.

The Effect of Reduced or Withdrawn Etanercept-methotrexate Therapy on Patient-reported Outcomes in Patients with Early Rheumatoid Arthritis.

PubMed

Wiland, Piotr; Dudler, Jean; Veale, Douglas; Tahir, Hasan; Pedersen, Ron; Bukowski, Jack; Vlahos, Bonnie; Williams, Theresa; Gaylord, Stefanie; Kotak, Sameer

2016-07-01

An analysis of a clinical trial to assess the effects of treatment reduction and withdrawal on patient-reported outcomes (PRO) in patients with early, moderate to severe rheumatoid arthritis (RA) who achieved 28-joint Disease Activity Score (DAS28) low disease activity (LDA) or remission with etanercept (ETN) plus methotrexate (MTX) therapy. During treatment induction, patients received open-label ETN 50 mg weekly plus MTX for 52 weeks. In the reduced-treatment phase, patients with DAS28-erythrocyte sedimentation rate (ESR) ≤ 3.2 at Week 39 and DAS28-ESR < 2.6 at Week 52 in the open-label phase were randomized to double-blind treatment with ETN 25 mg plus MTX, MTX, or placebo (PBO) for 39 weeks (weeks 0-39). In the third phase, patients who achieved DAS28 remission (DAS28-ESR < 2.6) or LDA (2.6 ≤ DAS28-ESR ≤ 3.2) at Week 39 in the double-blind phase had all treatment withdrawn and were observed for an additional 26 weeks (weeks 39-65). Of the 306 patients enrolled, 193 were randomized in the double-blind phase and 131 participated in the treatment-withdrawal phase. After reduction or withdrawal of ETN 50 mg/MTX, patients reduced to ETN 25 mg/MTX experienced slight, nonsignificant declines in the majority of PRO measures, whereas switching to PBO or MTX alone caused significant declines. Presenteeism and activity impairment scores were significantly better in the ETN reduced-dose group versus MTX monotherapy and PBO at Week 39 (p ≤ 0.05). In patients with early RA who achieved remission while receiving full-dose ETN/MTX, continuing combination therapy at a lower dose did not cause a significant worsening of PRO response, but switching to MTX alone or PBO did. ClinicalTrials.gov identifier: NCT00913458.

A case of scleritis associated rheumatoid arthritis accompanying an intraocular elevated lesion.

PubMed

Kobayashi, Takatoshi; Takai, Nanae; Tada, Rei; Shoda, Hiromi; Kida, Teruyo; Ikeda, Tsunehiko; Ozaki, Takurou; Makino, Shigeki

2018-05-30

Scleritis and/or uveitis sometimes accompanies patients who suffer from rheumatoid arthritis. However, few studies have reported scleritis and/or uveitis accompanying a fundus elevated lesion, such as an intraocular tumor. In this study, we report a case of rheumatoid uveitis associated with an intraocular elevated lesion. A 66-year-old female visited another eye clinic and was diagnosed as bilateral anterior uveitis, and was prescribed steroid eye drops for treatment. She had previously been diagnosed as rheumatoid arthritis at the age of 30 years. Due to vitreous opacity that appeared in her right eye, we increased the instillation of steroid eye drops and the amount of oral prednisolone. Although the inflammation had improved, anterior uveitis relapsed, and an intraocular whitish elevated lesion resembling an intraocular tumor at the superior nasal retina appeared. We speculated this lesion to be a granuloma complicated with rheumatoid arthritis. Thus, we increased the amount of prednisolone administration, and the lesion began to shrink and ultimately fully disappeared. We strongly believe that our case's lesion was a subretinal granuloma related with rheumatoid arthritis, as it disappeared by increased corticosteroid treatment. Our findings show that we should consider rheumatoid arthritis in a differential diagnosis of such types of fundus elevated lesions.

Socioeconomic status and the risk of developing rheumatoid arthritis: results from the Swedish EIRA study

PubMed Central

Bengtsson, C; Nordmark, B; Klareskog, L; Lundberg, I; Alfredsson, L; the, E

2005-01-01

Objective: To study whether formal education and occupational class are associated with incidence of rheumatoid arthritis overall and with the incidence of the two major subgroups of rheumatoid arthritis—seropositive (RF+) and seronegative (RF–) disease. Methods: 930 cases and 1126 controls participated in a population based case–control study using incident cases of rheumatoid arthritis, carried out in Sweden during the period May 1996 to June 2001. The relative risk (RR) of developing rheumatoid arthritis with 95% confidence interval (CI) was calculated for different levels of formal education compared with university degree and for different occupational classes compared with higher non-manual employees. Results: Subjects without a university degree had an increased risk of rheumatoid arthritis compared with those with a university degree (RR = 1.4 (95% CI, 1.2 to 1.8)). For manual employees, assistant and intermediate non-manual employees together, the risk of developing rheumatoid arthritis was about 20% more than for non-manual employees. These increased risks were more pronounced for RF+ than for RF– rheumatoid arthritis and were mainly confined to women. Smoking could not of its own explain the observed associations between risk of rheumatoid arthritis in different socioeconomic groups in Sweden. Conclusions: There was an association between high socioeconomic status and lower risk of rheumatoid arthritis in a population based investigation that was representative for the Swedish population. The study shows that as yet unexplained environmental or lifestyle factors, or both, influence the risk of rheumatoid arthritis, even in the relatively egalitarian Swedish society. PMID:15843455

Pelvic radiotherapy in the setting of rheumatoid arthritis: Refining the paradigm.

PubMed

Felefly, T; Mazeron, R; Huertas, A; Canova, C H; Maroun, P; Kordahi, M; Morice, P; Deutsch, É; Haie-Méder, C; Chargari, C

2017-04-01

Conflicting results concerning the toxicity of radiotherapy in the setting of rheumatoid arthritis were reported in literature. This work describes the toxicity profiles of patients with rheumatoid arthritis undergoing pelvic radiotherapy for gynecologic malignancies at our institution. Charts of patients with rheumatoid arthritis who underwent pelvic radiotherapy for cervical or endometrial cancer in a curative intent at the Gustave-Roussy Cancer Campus between 1990 and 2015 were reviewed for treatment-related toxicities. Acute and late effects were graded as per the Common Terminology Criteria for Adverse Events version 4.0 scoring system. Eight patients with cervical cancer and three with endometrial cancer were identified. Median follow-up was 56 months. Median external beam radiotherapy dose was 45Gy. All patients received a brachytherapy boost using either pulse- or low-dose rate technique. Concomitant chemotherapy was used in seven cases. Median time from rheumatoid arthritis diagnosis to external beam radiation therapy was 5 years. No severe acute gastrointestinal or genitourinary toxicity was reported. One patient had grade 3 dermatitis. Any late toxicity occurred in 7 /11 patients, and one patient experienced severe late toxicities. One patient with overt systemic rheumatoid arthritis symptoms at the time of external beam radiation therapy experienced late grade 3 ureteral stenosis, enterocolitis and lumbar myelitis. Pelvic radiotherapy, in the setting of rheumatoid arthritis, appears to be feasible, with potentially slight increase in low grade late events compared to other anatomic sites. Patients with overt systemic rheumatoid arthritis manifestation at the time of radiotherapy might be at risk of potential severe toxicities. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Exploring simulated early star formation in the context of the ultrafaint dwarf galaxies

NASA Astrophysics Data System (ADS)

Corlies, Lauren; Johnston, Kathryn V.; Wise, John H.

2018-04-01

Ultrafaint dwarf galaxies (UFDs) are typically assumed to have simple, stellar populations with star formation ending at reionization. Yet as the observations of these galaxies continue to improve, their star formation histories (SFHs) are revealed to be more complicated than previously thought. In this paper, we study how star formation, chemical enrichment, and mixing proceed in small, dark matter haloes at early times using a high-resolution, cosmological, hydrodynamical simulation. The goals are to inform the future use of analytic models and to explore observable properties of the simulated haloes in the context of UFD data. Specifically, we look at analytic approaches that might inform metal enrichment within and beyond small galaxies in the early Universe. We find that simple assumptions for modelling the extent of supernova-driven winds agree with the simulation on average, whereas inhomogeneous mixing and gas flows have a large effect on the spread in simulated stellar metallicities. In the context of the UFDs, this work demonstrates that simulations can form haloes with a complex SFH and a large spread in the metallicity distribution function within a few hundred Myr in the early Universe. In particular, bursty and continuous star formation are seen in the simulation and both scenarios have been argued from the data. Spreads in the simulated metallicities, however, remain too narrow and too metal-rich when compared to the UFDs. Future work is needed to help reduce these discrepancies and advance our interpretation of the data.

Radiographic estimation in seropositive and seronegative rheumatoid arthritis

PubMed Central

Sahatçiu-Meka, Vjollca; Rexhepi, Sylejman; Manxhuka-Kërliu, Suzana; Rexhepi, Mjellma

2011-01-01

Long since it have been suggested that a subpopulation of patients with rheumatoid arthritis, diagnosed with negative rheumatoid factor tests, represents a clinical entity quite distinct from that of seropositive rheumatoid arthritis (RA). Our aim was to establish a scientific comparative analysis between seronegative and seropositive rheumatoid arthritis, regarding some radiological and clinical parameters, applied for the first time on patients from Kosovo. Two hundred fifty patients with rheumatoid arthritis according to the American College of Rheumatology criteria were retrospectively studied by analysis the radiographic damage and clinical parameters of the disease, using a data base. All examinees were between 25-60 years of age (Xb=49.96, SD=10.37) with disease duration between 1-27 years (Xb = 6.41, SD=6.47). All patients underwent a standardised evaluation radiographs. Baseline standardised poster anterior radiographs of hands and feet and radiographs of other joints, depending on indications, were assessed. Erythrocyte sedimentation rate values correlated with the radiological damages and statistical difference was found for seronegative subset (r=0.24, p<0.01). Longer duration of the disease resulted in the increase of radiological changes in both subsets (r=0.66, p<0.01) seronegative, (r=0.49, p<0.01) seropositive. Anatomic changes of IInd and IIIrd level were nearly equally distributed in both subsets, 76 (60.8%) seronegative, 75 (60%) seropositive. Radiological damages are nearly equal in both subsets, elevate in relation to the duration of the disease and correlate with ESR values. Regarding the sero-status, differences within sex, with some exceptions, are not relevant. Although there are some definite quantitative and qualitative differences regarding sero-status, obviously there is a great deal of overlap between the two groups. PMID:21875421

Radiographic estimation in seropositive and seronegative rheumatoid arthritis.

PubMed

Sahatçiu-Meka, Vjollca; Rexhepi, Sylejman; Manxhuka-Kërliu, Suzana; Rexhepi, Mjellma

2011-08-01

Long since it have been suggested that a subpopulation of patients with rheumatoid arthritis, diagnosed with negative rheumatoid factor tests, represents a clinical entity quite distinct from that of seropositive rheumatoid arthritis (RA). Our aim was to establish a scientific comparative analysis between seronegative and seropositive rheumatoid arthritis, regarding some radiological and clinical parameters, applied for the first time on patients from Kosovo. Two hundred fifty patients with rheumatoid arthritis according to the American College of Rheumatology criteria were retrospectively studied by analysis the radiographic damage and clinical parameters of the disease, using a data base. All examinees were between 25-60 years of age (Xb=49.96, SD=10.37) with disease duration between 1-27 years (Xb = 6.41, SD=6.47). All patients underwent a standardised evaluation radiographs. Baseline standardised poster anterior radiographs of hands and feet and radiographs of other joints, depending on indications, were assessed. Erythrocyte sedimentation rate values correlated with the radiological damages and statistical difference was found for seronegative subset (r=0.24, p<0.01). Longer duration of the disease resulted in the increase of radiological changes in both subsets (r=0.66, p<0.01) seronegative, (r=0.49, p<0.01) seropositive. Anatomic changes of IInd and IIIrd level were nearly equally distributed in both subsets, 76 (60.8%) seronegative, 75 (60%) seropositive. Radiological damages are nearly equal in both subsets, elevate in relation to the duration of the disease and correlate with ESR values. Regarding the sero-status, differences within sex, with some exceptions, are not relevant. Although there are some definite quantitative and qualitative differences regarding sero-status, obviously there is a great deal of overlap between the two groups.

The Role of the Interferon-Gamma-Jak/STAT Pathway in Rheumatoid Arthritis

DTIC Science & Technology

2017-09-01

AWARD NUMBER: W81XWH-16-1-0537 TITLE: The Role of the Interferon-Gamma-Jak/STAT Pathway in Rheumatoid Arthritis PRINCIPAL INVESTIGATOR: Stanley...Sep 2016 - 31 Aug 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER The Role of the Interferon-Gamma-Jak/STAT Pathway in Rheumatoid Arthritis 5b...subsets that likely counteracts IL-2 regulator activity and contribute to the pathogenesis of RA. 15. SUBJECT TERMS Rheumatoid arthritis ; Autoimmunity; T

Plasma zinc and its relationship to clinical symptoms and drug treatment in rheumatoid arthritis.

PubMed Central

Balogh, Z; El-Ghobarey, A F; Fell, G S; Brown, D H; Dunlop, J; Dick, W C

1980-01-01

Total plasma zinc levels in patients with rheumatoid arthritis on different therapeutic treatments were determined in conjunction with total serum proteins, serum albumin and globulin, and articular index of joint tenderness, erythrocyte sedimentation rate, rheumatoid factor, serum copper, and serum iron. There were significantly lower zinc levels in patients with rheumatoid arthritis on nonsteroidal anti-inflammatory drugs than in patients on levamisole and penicillamine. Zinc levels correlated positively with serum albumin, and there was an inverse correlation between zinc levels and both ESR and globulin concentration in all rheumatoid patients. However, the correlation coefficient varied in the different treatment groups. The results of this study support the hypothesis that low plasma zinc level in rheumatoid arthritis is one of the nonspecific features of inflammation. PMID:7436558

Regression of an atlantoaxial rheumatoid pannus following posterior instrumented fusion.

PubMed

Bydon, Mohamad; Macki, Mohamed; Qadi, Mohamud; De la Garza-Ramos, Rafael; Kosztowski, Thomas A; Sciubba, Daniel M; Wolinsky, Jean-Paul; Witham, Timothy F; Gokaslan, Ziya L; Bydon, Ali

2015-10-01

Rheumatoid patients may develop a retrodental lesion (atlantoaxial rheumatoid pannus) that may cause cervical instability and/or neurological compromise. The objective is to characterize clinical and radiographic outcomes after posterior instrumented fusion for atlantoaxial rheumatoid pannus. We retrospectively reviewed all patients who underwent posterior fusions for an atlantoaxial rheumatoid pannus at a single institution. Both preoperative and postoperative imaging was available for all patients. Anterior or circumferential operations, non-atlantoaxial panni, or prior C1-C2 operations were excluded. Primary outcome measures included Nurick score, Ranawat score (neurologic status in patients with rheumatoid arthritis), pannus regression, and reoperation. Pannus volume was determined with axial and sagittal views on both preoperative and postoperative radiological images. Thirty patients surgically managed for an atlantoaxial rheumatoid pannus were followed for a mean of 24.43 months. Nine patients underwent posterior instrumented fusion alone, while 21 patients underwent posterior decompression and instrumented fusion. Following a posterior instrumented fusion in all 30 patients, the pannus statistically significantly regressed by 44.44%, from a mean volume of 1.26cm(3) to 0.70cm(3) (p<0.001), over 8.02 months. The Nurick score significantly improved from 2.40 to 0.60 (p<0.001), but the marginal improvement of 0.20 in the Ranawat score did not reach significance (p=0.312). Six patients (20%) required reoperations over a mean of 13.18 months. Reoperations were indicated for C1 instrumentation failure in four patients and pseudoarthrosis in two patients. Following posterior instrumented fusion, the pannus radiographically regressed by 44.44% over a mean of 8.02 months, and patients clinically improved per the Nurick score. The Ranawat score did not improve, and 20% of patients required reoperation over a mean of 13.18 months. The annualized reoperation rate was

A rheumatoid arthritis study by Fourier transform infrared spectroscopy

NASA Astrophysics Data System (ADS)

Carvalho, Carolina S.; Silva, Ana Carla A.; Santos, Tatiano J. P. S.; Martin, Airton A.; dos Santos Fernandes, Ana Célia; Andrade, Luís E.; Raniero, Leandro

2012-01-01

Rheumatoid arthritis is a systemic inflammatory disease of unknown causes and a new methods to identify it in early stages are needed. The main purpose of this work is the biochemical differentiation of sera between normal and RA patients, through the establishment of a statistical method that can be appropriately used for serological analysis. The human sera from 39 healthy donors and 39 rheumatics donors were collected and analyzed by Fourier Transform Infrared Spectroscopy. The results show significant spectral variations with p<0.05 in regions corresponding to protein, lipids and immunoglobulins. The technique of latex particles, coated with human IgG and monoclonal anti-CRP by indirect agglutination known as FR and CRP, was performed to confirm possible false-negative results within the groups, facilitating the statistical interpretation and validation of the technique.

Web-based rehabilitation interventions for people with rheumatoid arthritis: A systematic review.

PubMed

Srikesavan, Cynthia; Bryer, Catherine; Ali, Usama; Williamson, Esther

2018-01-01

Background Rehabilitation approaches for people with rheumatoid arthritis include joint protection, exercises and self-management strategies. Health interventions delivered via the web have the potential to improve access to health services overcoming time constraints, physical limitations, and socioeconomic and geographic barriers. The objective of this review is to determine the effects of web-based rehabilitation interventions in adults with rheumatoid arthritis. Methods Randomised controlled trials that compared web-based rehabilitation interventions with usual care, waiting list, no treatment or another web-based intervention in adults with rheumatoid arthritis were included. The outcomes were pain, function, quality of life, self-efficacy, rheumatoid arthritis knowledge, physical activity and adverse effects. Methodological quality was assessed using the Cochrane Risk of Bias tool and quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation approach. Results Six source documents from four trials ( n = 567) focusing on self-management, health information or physical activity were identified. The effects of web-based rehabilitation interventions on pain, function, quality of life, self-efficacy, rheumatoid arthritis knowledge and physical activity are uncertain because of the very low quality of evidence mostly from small single trials. Adverse effects were not reported. Conclusion Large, well-designed trials are needed to evaluate the clinical and cost-effectiveness of web-based rehabilitation interventions in rheumatoid arthritis.

Angiopoietin-like 4: A molecular link between insulin resistance and rheumatoid arthritis.

PubMed

Masuko, Kayo

2017-05-01

Recent evidence suggests that common factor(s) or molecule(s) might regulate lipid and glucose metabolism, inflammation, and bone and cartilage degeneration. These findings may be particularly relevant for cases of rheumatoid arthritis, in which chronic inflammation occurs in an autoimmune context and causes the degradation of articular joints as well as insulin resistance and cardiovascular complications. Candidates for this common regulatory system include signals mediated by peroxisome proliferator-activated regulator and its response factor, angiopoietin-like 4. The expression and bioactivity of angiopoietin-like 4, an adipocytokine that was originally reported to have an angiogenic function, have been detected not only in the vascular system and adipose tissue but also in rheumatoid joints. An essential role for angiopoietin-like 4 has been established in dyslipidemia, and recent reports indicate that it may modulate bone and cartilage catabolism in rheumatoid arthritis. The enhanced expression of angiopoietin-like 4 in rheumatoid arthritis may explain the occurrence of insulin resistance, cardiovascular risk, and joint destruction, thereby suggesting that this molecule could be a potential target for anti-rheumatoid arthritis strategies. This review describes recent research on the role of angiopoietin-like 4 in chronic inflammatory conditions and rheumatoid arthritis, as well as potential therapeutic candidates. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:939-943, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Moderate alcohol consumption is associated with increased radiological progression in women, but not in men, with early rheumatoid arthritis: results from the ESPOIR cohort (Étude et Suivi des Polyarthrites Indifférenciées Récentes).

PubMed

Sageloli, F; Quesada, J L; Fautrel, B; Salliot, C; Gaudin, P; Baillet, A

2018-05-18

We conducted this study to determine whether alcohol consumption influences radiological progression in early rheumatoid arthritis (RA). Patients fulfilling the European League Against Rheumatism/American College of Rheumatology 2010 criteria in the early arthritis cohort ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes) were included in this study. Alcohol consumption was collected at baseline and at each visit. We classified alcohol consumption into three groups: abstinent (0 g/day), moderate (≤ 20 g/day for women, ≤ 30 g/day for men), and abuse (> 20 g/day for women, > 30 g/day for men). The primary outcome was the occurrence of radiological progression, defined as an increase ≥ 5 points in the total Sharp/van der Heijde score. We investigated whether alcohol consumption is predictive of radiological progression at 1, 3, and 5 years by univariate and multivariate analysis adjusted for age, baseline erosion, rheumatoid factor, anti-citrullinated peptide antibody, smoking status, body mass index, and treatment with leflunomide or methotrexate and biologics. The study included 596 patients. When considering the influence of gender on the interaction between alcohol consumption and radiological progression, we showed a deleterious effect of moderate consumption in women [odds ratio (OR) = 1.73, 95% confidence interval (CI) 1.01; 2.96, p = 0.045] and a trend towards a protective effect of moderate consumption in men (OR = 0.50, 95% CI 0.21; 1.16, p = 0.106) in multivariate analysis. Our data suggest a deleterious effect of moderate consumption of alcohol on radiological progression in women, but not in men, with early RA.

Evaluation of human serum of severe rheumatoid arthritis by confocal Raman spectroscopy

NASA Astrophysics Data System (ADS)

Carvalho, C. S.; Raniero, L.; Santo, A. M. E.; Pinheiro, M. M.; Andrade, L. E. C.; Cardoso, M. A. G.; Junior, J. S.; Martin, A. A.

2010-02-01

Rheumatoid Arthritis is a systemic chronic inflammatory disease, recurrent and systemic, initiated by autoantibodies and maintained by inflammatory mechanisms cellular applicants. The evaluation of this disease to promote early diagnosis, need an associations of many tools, such as clinical, physical examination and thorough medical history. However, there is no satisfactory consensus due to its complexity. In the present work, confocal Raman spectroscopy was used to evaluate the biochemical composition of human serum of 40 volunteers, 24 patients with rheumatoid arthritis presenting clinical signs and symptoms, and 16 healthy donors. The technique of latex agglutination for the polystyrene covered with human immunoglobulin G and PCR (protein c-reactive) was performed for confirmation of possible false-negative results within the groups, facilitating the statistical interpretation and validation of the technique. This study aimed to verify the changes for the characteristics Raman peaks of biomolecules such as immunoglobulins amides and protein. The results were highly significant with a good separation between groups mentioned. The discriminant analysis was performed through the principal components and correctly identified 92% of the donors. Based on these results, we observed the behavior of arthritis autoimmune, evident in certain spectral regions that characterize the serological differences between the groups.

78 FR 32667 - Draft Guidance for Industry on Rheumatoid Arthritis: Developing Drug Products for Treatment...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-31

...] Draft Guidance for Industry on Rheumatoid Arthritis: Developing Drug Products for Treatment... support the approval of drug products for the treatment of patients with rheumatoid arthritis (RA). It... Drugs, Devices, and Biological Products for the Treatment of Rheumatoid Arthritis (RA),'' published in...

Assessment of global DNA methylation in peripheral blood cell subpopulations of early rheumatoid arthritis before and after methotrexate.

PubMed

de Andres, María C; Perez-Pampin, Eva; Calaza, Manuel; Santaclara, Francisco J; Ortea, Ignacio; Gomez-Reino, Juan J; Gonzalez, Antonio

2015-08-29

DNA methylation is an epigenetic mechanism regulating gene expression that has been insufficiently studied in the blood of rheumatoid arthritis (RA) patients, as only T cells and total peripheral blood mononuclear cells (PBMCs) from patients with established RA have been studied and with conflicting results. Five major blood cell subpopulations: T, B and NK cells, monocytes, and polymorphonuclear leukocytes, were isolated from 19 early RA patients and 17 healthy controls. Patient samples were taken before and 1 month after the start of treatment with methotrexate (MTX). Analysis included DNA methylation with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring (HPLC-ESI-MS/MS-SRM) and expression levels of seven methylation-specific enzymes by quantitative polymerase chain reaction (qPCR). Disease-modifying anti-rheumatic drug (DMARD)-naïve early RA patients showed global DNA hypomethylation in T cells and monocytes, together with a lower expression of DNA methyltrasnferase 1 (DNMT1), the maintenance DNA methyltransferase, which was also decreased in B cells. Furthermore, significantly increased expression of ten-eleven translocation1 (TET1), TET2 and TET3, enzymes involved in demethylation, was found in monocytes and of TET2 in T cells. There was also modest decreased expression of DNMT3A in B cells and of growth arrest and DNA-damage-inducible protein 45A (GADD45A) in T and B cells. Treatment with MTX reverted hypomethylation in T cells and monocytes, which were no longer different from controls, and increased global methylation in B cells. In addition, DNMT1 and DNMT3A showed a trend to reversion of their decreased expression. Our results confirm global DNA hypomethylation in patients with RA with specificity for some blood cell subpopulations and their reversal with methotrexate treatment. These changes are accompanied by parallel changes in the levels of enzymes involved in methylation, suggesting

In-Depth Analysis of Citrulline-Specific CD4 T-Cells in Rheumatoid Arthritis

DTIC Science & Technology

2016-01-01

1 AWARD NUMBER: W81XWH-15-1-0004 TITLE: In-Depth Analysis of Citrulline-Specific CD4 T-Cells in Rheumatoid Arthritis PRINCIPAL INVESTIGATOR...present in rheumatoid arthritis (RA) patients exhibit a distinct cell surface phenotype and transcriptional signature that could be used to predict...and are on track to achieve our Year 2 goals 15. SUBJECT TERMS Rheumatoid arthritis ; CD4 T cells; citrulline; HLA class II tetramers; RNAseq

Genetic association of CCR5 promoter single nucleotide polymorphism in seronegative and seropositive rheumatoid arthritis.

PubMed

Lima, Guadalupe; Furuzawa-Carballeda, Janette; Ramos-Bello, Dolores; Jakez-Ocampo, Juan; Pascual-Ramos, Virginia; Núñez-Alvarez, Carlos A; Granados, Julio; Llorente, Luis

2012-06-01

The aim of this study was to investigate the possible role of the CCR5 59029 A→G promoter point mutation polymorphism in determining the susceptibility to rheumatoid factor-positive and rheumatoid factor-negative rheumatoid arthritis. This polymorphism was assessed in 85 seropositive and 39 seronegative rheumatoid arthritis patients and in 126 healthy individuals of the same geographic and ethnic origin. We found an increase in the genetic frequency of the A allele in the 59029 A→G promoter region of the CCR5 receptor in patients with rheumatoid arthritis compared with healthy controls (p = 0.01; OR = 1.5, 95% CI (1.0-2.2). Likewise, the homozygous state for the A allele was found to be more frequent in rheumatoid arthritis patients, again when compared with healthy controls (p = 0.03; OR = 1.8, 95% CI 1.0-3.0). The increased frequency of the A allele was more evident in the more benign, seronegative rheumatoid arthritis group when compared with controls (p = 0.003; OR 2.4 95% CI 1.3-4.4), and when combining the A homozygous and the AG heterozygous patients compared with healthy subjects. These results suggest that this CCR5 promoter polymorphism seems to play an important role in determining different clinical courses in both forms of rheumatoid arthritis.

Fibromyalgia complicating disease management in rheumatoid arthritis.

PubMed

Abbasi, Lubna; Haidri, Fakhir Raza

2014-06-01

To evaluate frequency of fibromyalgia in rheumatoid arthritis and its effect on disease activity score. Cross-sectional study. The Indus Hospital, Karachi, from December 2010 to May 2011. All adult patients of either gender diagnosed as rheumatoid arthritis on the basis of clinical, laboratory and X-ray criteria were included in the study. The sample data was separated into two groups depending on presence or absence of fibromyalgia and 28 joint disease activity score (DAS-28) value was evaluated. There were 31 (25.83%) patients with rheumatoid arthritis and fibromyalgia (RAFM) out of the total 120. The median (IQR) age of patients was 40 (32 - 51) years. All were females. The overall female frequency was 79 (88.8%). The median (IQR) DAS-28 score in RA group was 4.9 (3.66 - 5.71), while the median (IQR) DAS-28 score in RAFM was 7.04 (6.62 - 7.64) [p < 0.0001]. The number of patient getting combination therapy of DMARD in RAFM group was 61.3% while in RA group was 42.7%. DAS-28 was found to be significantly higher in RAFM patients probably because of higher perception of pain.

Quantification of joint inflammation in rheumatoid arthritis by time-resolved diffuse optical spectroscopy and tracer kinetic modeling

NASA Astrophysics Data System (ADS)

Ioussoufovitch, Seva; Morrison, Laura B.; Lee, Ting-Yim; St. Lawrence, Keith; Diop, Mamadou

2015-03-01

Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation, which can cause progressive joint damage and disability. Diffuse optical spectroscopy (DOS) and imaging have the potential to become potent monitoring tools for RA. We devised a method that combined time-resolved DOS and tracer kinetics modeling to rapidly and reliably quantify blood flow in the joint. Preliminary results obtained from two animals show that the technique can detect joint inflammation as early as 5 days after onset.

Effect of Treat-to-target Strategies Aiming at Remission of Arterial Stiffness in Early Rheumatoid Arthritis: A Randomized Controlled Study.

PubMed

Tam, Lydia Ho-Pui; Shang, Qing; Li, Edmund Kwok-Ming; Wong, Priscilla Ching-Han; Kwok, Kitty Yan; Kun, Emily Wai-Lin; Yim, Isaac Cheuk-Wan; Lee, Violet Ka-Lai; Yip, Ronald Man-Lung; Pang, Steve Hin-Ting; Lao, Virginia Weng-Nga; Mak, Queenie Wah-Yan; Cheng, Isaac Tsz-Ho; Lau, Xerox Sze-Lok; Li, Tena Ka-Yan; Zhu, Tracy Yaner; Lee, Alex Pui-Wai; Tam, Lai-Shan

2018-05-15

To determine the efficacy of 2 tight control treatment strategies aiming at Simplified Disease Activity Score (SDAI) remission (SDAI ≤ 3.3) compared to 28-joint count Disease Activity Score (DAS28) remission (DAS28 < 2.6) in the prevention of arterial stiffness in patients with early rheumatoid arthritis (RA). This was an open-label study in which 120 patients with early RA were randomized to receive 1 year of tight control treatment. Group 1 (n = 60) aimed to achieve SDAI ≤ 3.3 and Group 2 (n = 60), DAS28 < 2.6. Pulse wave velocity (PWV) and augmentation index (AIx) were measured at baseline and 12 months. A posthoc analysis was also performed to ascertain whether achieving sustained remission could prevent progression in arterial stiffness. The proportions of patients receiving methotrexate monotherapy were significantly lower in Group 1 throughout the study period. At 12 months, the proportions of patients achieving DAS28 and SDAI remission, and the change in PWV and AIx, were comparable between the 2 groups. In view of the lack of differences between the 2 groups, a posthoc analysis was performed at Month 12, including all 110 patients with PWV, to elucidate the independent predictors associated with the change in PWV. Multivariate analysis revealed that achieving sustained DAS28 remission at months 6, 9, and 12 and a shorter disease duration were independent explanatory variables associated with less progression of PWV. With limited access to biologic disease-modifying antirheumatic drugs, treatment efforts toward DAS28 and SDAI remission had similar effects in preventing the progression of arterial stiffness at 1 year. However, achieving sustained DAS28 remission was associated with a significantly greater improvement in PWV. [Clinical Trial registration: Clinicaltrial.gov NCT01768923.].

Outcome of orthoses intervention in the rheumatoid foot.

PubMed

Kavlak, Yasemin; Uygur, Fatma; Korkmaz, Cengiz; Bek, Nilgün

2003-06-01

This study was carried out to determine the effect of foot orthoses on pain, gait, and energy expenditure in patients with rheumatoid arthritis. Eighteen patients were evaluated for these parameters. Each patient was given a foot insert or shoe modification suitable for his or her foot deformity. Following 3 months of orthosis use, a significant difference was found in regards to pain (p < .05), step length and stride length (p < .05), and physiological cost index (p < .05). The results suggest that foot orthoses are an important feature in the rehabilitation of the rheumatoid foot.

Pathogenesis of rheumatoid arthritis and the immune response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scheinberg, M.A.

1983-08-01

The interrelationship among lymphocytes, macrophages, and neutrophils appears to be an important aspect of the synovial inflammation that is characteristic of rheumatoid arthritis. In a study comparing gold sodium aurothiomalate (GST) with auranofin (Au), an orally absorbed compound, both appeared to inhibit the disease process and no difference between parenteral and oral administration was observed. Another study involved two groups of nine patients with severe rheumatoid arthritis. One group underwent plasmapheresis. The second group underwent total lymphoid irradiation. Both agents appeared to inhibit the disease process. Plasmapheresis was better tolerated that irradiation.

In-Depth Analysis of Citrulline-Specific CD4 T Cells in Rheumatoid Arthritis

DTIC Science & Technology

2016-01-01

1 AWARD NUMBER: W81XWH-15-1-0003 TITLE: In-Depth Analysis of Citrulline-Specific CD4 T Cells in Rheumatoid Arthritis PRINCIPAL INVESTIGATOR...Annual 3. DATES COVERED 10 Dec 2014 – 09 Dec 2015 4. TITLE AND SUBTITLE In-Depth Analysis of Citrulline-Specific CD4 T Cells in Rheumatoid Arthritis ...cells present in rheumatoid arthritis (RA) patients exhibit a distinct cell surface phenotype and transcriptional signature that could be used to

Large-scale linkage analysis of 1302 affected relative pairs with rheumatoid arthritis

PubMed Central

Hamshere, Marian L; Segurado, Ricardo; Moskvina, Valentina; Nikolov, Ivan; Glaser, Beate; Holmans, Peter A

2007-01-01

Rheumatoid arthritis is the most common systematic autoimmune disease and its etiology is believed to have both strong genetic and environmental components. We demonstrate the utility of including genetic and clinical phenotypes as covariates within a linkage analysis framework to search for rheumatoid arthritis susceptibility loci. The raw genotypes of 1302 affected relative pairs were combined from four large family-based samples (North American Rheumatoid Arthritis Consortium, United Kingdom, European Consortium on Rheumatoid Arthritis Families, and Canada). The familiality of the clinical phenotypes was assessed. The affected relative pairs were subjected to autosomal multipoint affected relative-pair linkage analysis. Covariates were included in the linkage analysis to take account of heterogeneity within the sample. Evidence of familiality was observed with age at onset (p << 0.001) and rheumatoid factor (RF) IgM (p << 0.001), but not definite erosions (p = 0.21). Genome-wide significant evidence for linkage was observed on chromosome 6. Genome-wide suggestive evidence for linkage was observed on chromosomes 13 and 20 when conditioning on age at onset, chromosome 15 conditional on gender, and chromosome 19 conditional on RF IgM after allowing for multiple testing of covariates. PMID:18466440

The Influence of Simulations on Family Engagement--Prospective Early Childhood Educators' Perceptions

ERIC Educational Resources Information Center

Paz-Albo Prieto, Jesús

2018-01-01

Nurturing experiences in preparation for prospective early childhood educators' work with families during their training are critical for establishing empowering relationships. This article details a qualitative case study of 77 prospective early childhood educators engaged with the Parent, Family and Community Engagement Simulation. An electronic…

Three Dimensional Volcanic Plume Simulations on Early Mars

NASA Astrophysics Data System (ADS)

Fisher, M. A.; Kobs-Nawotniak, S. E.

2016-12-01

Current explosive volcanic plume models for early Mars are thought to overestimate plume height by tens of kilometers. They are based on 1D empirical terrestrial plume models, which determine plume rise using Morton-style convection. Not only do these models fail to account for turbulent mixing processes, but the Martian versions also violate assumptions regarding the speed of sound, radial expansion, and availability of ambient air for entrainment. Since volcanically derived volatiles are hypothesized to have increased early Martian warming, it is vital to understand how high these volatiles can be injected into the atmosphere. Active Tracer High-resolution Atmospheric Model (ATHAM; Oberhuber et al., 1998) is a 3D plume simulator that circumvents the underlying assumptions of the current Martian plume models by solving the Navier-Stokes equations. Martian-ATHAM (M-ATHAM) simulates Martian volcanic eruptions by replacing terrestrial planetary and atmospheric conditions with those appropriate for early Mars. In particular we evaluate three different atmospheric compositions with unique temperature and density profiles: 99.5% CO2/0.5% SO2 and 85% CO2/15% H2 representing a "warm and wet" climate and 100% CO2 representing a "cold and wet" climate. We evaluated for mass eruption rates from 10^3 kg/s to 10^10 kg/s using the Idaho National Laboratory's supercomputer Falcon in order determine what conditions produced stable eruption columns. Of the three different atmospheric compositions, 100% CO2 and 99.5% CO2/0.5% SO2 produced stable plumes for the same mass eruption rates whereas the 85% CO2/15% H2 atmosphere produced stable plumes for a slightly higher range of mass eruption rates. The tallest plumes were produced by 85% CO2/15% H2 atmosphere, producing plumes 5% taller than the revised empirical models, suggesting closer agreement than previously assumed under certain conditions. In comparison to terrestrial plumes, all early Martian plumes needed higher mass

Tofacitinib in Rheumatoid Arthritis: Lack of Early Change in Disease Activity Predicts a Low Probability of Achieving Low Disease Activity at Month 6.

PubMed

Van Vollenhoven, Ronald F; Lee, Eun Bong; Fallon, Lara; Zwillich, Samuel H; Wilkinson, Bethanie; Chapman, Douglass; Demasi, Ryan; Keystone, Edward

2018-04-26

Optimal targeted treatment in rheumatoid arthritis requires early identification of failure to respond. This post-hoc analysis explored the relationship between early disease activity changes and achievement of low disease activity (LDA) and remission targets with tofacitinib. Data were from two randomized, double-blind, Phase 3 studies. In ORAL Start (NCT01039688), methotrexate (MTX)-naïve patients received tofacitinib 5 or 10 mg BID, or MTX, for 24 months. In placebo-controlled ORAL Standard (NCT00853385), MTX-inadequate responder (MTX-IR) patients received tofacitinib 5 or 10 mg BID or adalimumab 40 mg Q2W, with MTX, for 12 months. Probabilities of achieving LDA (CDAI ≤10; DAS28-4[ESR] ≤3.2) at months 6 and 12 were calculated, given failure to achieve threshold improvement from baseline (change in CDAI ≥6; DAS28-4[ESR] ≥1.2) at month 1 or 3. In ORAL Start, 7.2% and 5.4% of patients receiving tofacitinib 5 and 10 mg BID, respectively, failed to improve CDAI ≥6 at month 3; of those who failed, 3.8% and 28.6%, respectively, achieved month 6 CDAI-defined LDA. In ORAL Standard, 18.8% and 17.5% of patients receiving tofacitinib 5 and 10 mg BID, respectively, failed to improve CDAI ≥6 at month 3; of those who failed, 0% and 2.9%, respectively, achieved month 6 CDAI-defined LDA. Findings were similar when considering month 1 improvements or DAS28-4(ESR) thresholds. In MTX-IR patients, lack of response to tofacitinib after 1 or 3 months predicted low probability of achieving LDA at month 6. Lack of early response may be considered when deciding whether to continue treatment with tofacitinib. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Increased serum concentrations of Nɛ-carboxymethyllysine are related to the presence and the severity of rheumatoid arthritis.

PubMed

Knani, Ines; Bouzidi, Hassan; Zrour, Saoussen; Bergaoui, Naceur; Hammami, Mohamed; Kerkeni, Mohsen

2018-07-01

Background There are limited data regarding the contribution of advanced glycation end products in the presence of rheumatoid arthritis. We investigated whether serum N ɛ -carboxymethyllysine and pentosidine were related to the presence and the severity of rheumatoid arthritis. Methods Eighty patients with rheumatoid arthritis and 30 control subjects were included in a cross-sectional study. The severity of rheumatoid arthritis was assessed using the disease activity score for 28 joints. Serum N ɛ -carboxymethyllysine and pentosidine were measured by enzyme-linked immunosorbent assay. Results Serum N ɛ -carboxymethyllysine and pentosidine concentrations were significantly higher in patients with rheumatoid arthritis vs. control subjects ( P < 0.001). Serum N ɛ -carboxymethyllysine and pentosidine concentrations were significantly higher in rheumatoid arthritis patients with high disease activity vs. rheumatoid arthritis patients with moderate disease activity ( P < 0.001, P = 0.019, respectively). A multiple logistic regression analysis demonstrated that N ɛ -carboxymethyllysine was independently associated with the presence of rheumatoid arthritis (OR = 1.21, 95% CI: 1.05-1.39, P = 0.006). Furthermore, in a multivariate stepwise regression analysis, N ɛ -carboxymethyllysine was independently correlated with disease activity score for 28 joints (standardized β = 0.43, P = 0.001). Conclusion Serum N ɛ -carboxymethyllysine and pentosidine were increased during rheumatoid arthritis, and N ɛ -carboxymethyllysine was independently associated with the presence and the severity of rheumatoid arthritis.

Using Big Data to Evaluate the Association between Periodontal Disease and Rheumatoid Arthritis.

PubMed

Grasso, Michael A; Comer, Angela C; DiRenzo, Dana D; Yesha, Yelena; Rishe, Naphtali D

2015-01-01

An association between periodontal disease and rheumatoid arthritis is believed to exist. Most investigations into a possible relationship have been case-control studies with relatively low sample sizes. The advent of very large clinical repositories has created new opportunities for data-driven research. We conducted a retrospective cohort study to measure the association between periodontal disease and rheumatoid arthritis in a population of 25 million patients. We demonstrated that subjects with periodontal disease were roughly 1.4 times more likely to have rheumatoid arthritis. These results compare favorably with those of previous studies on smaller cohorts. Additional work is needed to identify the mechanisms behind this association and to determine if aggressive treatment of periodontal disease can alter the course of rheumatoid arthritis.

In-Depth Analysis of Citrulline Specific CD4 T-Cells in Rheumatoid Arthritis

DTIC Science & Technology

2017-01-01

AWARD NUMBER: W81XWH-15-1-0004 TITLE: In-Depth Analysis of Citrulline-Specific CD4 T-Cells in Rheumatoid Arthritis PRINCIPAL INVESTIGATOR...2016 4. TITLE AND SUBTITLE In-Depth Analysis of Citrulline-Specific CD4 T Cells in Rheumatoid Arthritis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH...NOTES 14. ABSTRACT The goal of this project is to test the hypothesis that cit-specific CD4 T cells present in rheumatoid arthritis (RA) patients

[The role of the human microbiom in the pathogenesis of rheumatoid arthritis - a literature review].

PubMed

Krajewska-Włodarczyk, Magdalena

Rheumatoid arthritis is a chronic, progressive, autoimmune disease with numerous articular, extra-articular and systemic manifestations. The cause of rheumatoid arthritis is multifactorial including genetic and environmental factors. Recent advantages in sequencing techniques have allowed the deep characterization of the human microbiota. Available evidence confirms the existence of an association between dysbiosis and rheumatoid arthritis but it still remains unclear whether alterations in the microbiome are a pathogenic cause or an effect of autoimmune disease. In patients with rheumatoid arthritis the most supported association between disease and microbiota is with the oral dysbiosis usually observed in patients with periodontitis. Given the strong variability and abundance of microbes living in close relation with human host, it becomes a difficult task to define what should be considered the favorable microbiome. There is need for broader studies to establish how the human microbiome contributes to disease susceptibility, and to characterize the role of microbial diversity in the pathogenesis of rheumatoid arthritis, disease manifestation, and progression. The identification of dysbiosis specific for rheumatoid arthritis and the understanding of the dynamic interaction between microbiota and their host may help in establishing an individualized management for each patient with rheumatoid arthritis, and achieve a better efficacy of the therapy.

Cachexia and adiposity in rheumatoid arthritis. Relevance for disease management and clinical outcomes.

PubMed

Challal, Salima; Minichiello, Emeline; Boissier, Marie-Christophe; Semerano, Luca

2016-03-01

Altered body composition is a frequent finding in rheumatoid arthritis and is associated with the two major outcomes of the disease: disability and cardiovascular mortality. It is estimated that up to two thirds of patients may be affected by loss of lean mass, the so-called rheumatoid cachexia. Hence, body weight being equal, the relative amount of lean mass is lower and that of body fat is higher in rheumatoid arthritis patients vs. healthy controls. Both disease-related factors and other factors, like drug treatments, physical activity and nutrition contribute to modify body composition in rheumatoid arthritis. The effect of pharmacological treatments, and notably of anti-TNF drugs, on body composition is controversial. Conversely, training programs to stimulate muscle growth can restore lean mass and reduce adiposity. There is good evidence that amelioration of body composition ameliorates function and reduces disability. Currently, there is no evidence that interventions that modify body composition can reduce cardiovascular morbidity and mortality in rheumatoid arthritis. Copyright © 2015. Published by Elsevier SAS.

Cyclocurcumin, a curcumin derivative, exhibits immune-modulating ability and is a potential compound for the treatment of rheumatoid arthritis as predicted by the MM-PBSA method.

PubMed

Fu, Min; Chen, Lihui; Zhang, Limin; Yu, Xiao; Yang, Qingrui

2017-05-01

The control and treatment of rheumatoid arthritis is a challenge in today's world. Therefore, the pursuit of natural disease-modifying antirheumatic drugs (DMRDs) remains a top priority in rheumatology. The present study focused on curcumin and its derivatives in the search for new DMRDs. We focused on prominent p38 mitogen-activated protein (MAP) kinase p38α which is a prime regulator of tumor necrosis factor-α (TNF-α), a key mediator of rheumatoid arthritis. In the present study, we used the X-ray crystallographic structure of p38α for molecular docking simulations and molecular dynamic simulations to study the binding modes of curcumin and its derivatives with the active site of p38α. The ATP-binding domain was used for evaluating curcumin and its derivatives. Molecular docking simulation results were used to select 4 out of 8 compounds. These 4 compounds were simulated using GROMACS molecular simulation platform; the results generated were subjected to molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) calculations. The results showed cyclocurcumin as a potential natural compound for development of a potent DMRD. These data were further supported by inhibition of TNF-α release from lipopolysaccharide (LPS)-stimulated human macrophages following cyclocurcumin treatment.

Chronobiology and the treatment of rheumatoid arthritis.

PubMed

Cutolo, Maurizio

2012-05-01

As circadian rhythms and biological signaling occur in a complex network with cyclical 24-h period interactions (chronobiology) between the central and the autonomic nervous systems, the endocrine glands and the immune system, this review will explore the involvement of this emerging network in the disease pathophysiology and management. Recent advances regarding nocturnal hormones such as melatonin and prolactin that activate the nighttime immune response, and the successive rise of cortisol that dowregulates the ongoing immune reactivity very early in the morning, will be discussed within the circadian neuroendocrine immune network. In addition, the role of sleep and the daily distribution of body energy, which are important factors for the homoeostatic regulation of circadian physiological/pathological processes of the immune network will be reviewed.In chronic immune/inflammatory conditions such as rheumatoid arthritis (RA), stiffness and functional disability are evident in the early morning hours as under the chronic stress of the disease the nighttime adrenal cortisol production becomes insufficient to inhibit ongoing nocturnal immune/inflammatory activity. Currently, the most advanced approach to optimizing the risk-benefit ratio for long-term glucocorticoid treatment in RA seems to be low-dose chronotherapy with modified nighttime release prednisone (release at 3 a.m.). A similar chronotherapeutical approach could also be effective with disease-modifying antirheumatic drugs such as methotrexate.

In-Depth Analysis of Citrulline-Specific CD4 T Cells in Rheumatoid Arthritis

DTIC Science & Technology

2017-01-01

AWARD NUMBER: W81XWH-15-1-0003 TITLE: In-Depth Analysis of Citrulline-Specific CD4 T Cells in Rheumatoid Arthritis PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE In-Depth Analysis of Citrulline-Specific CD4 T Cells in Rheumatoid Arthritis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0003...NOTES 14. ABSTRACT The goal of this project is to test the hypothesis that cit-specific CD4 T cells present in rheumatoid arthritis (RA) patients

Coeliac Disease With Rheumatoid Arthritis: An Unusual Association.

PubMed

Warjri, Synrang Batngen; Ete, Tony; Beyong, Taso; Barman, Bhupen; Lynrah, Kyrshanlang G; Nobin, Hage; Perme, Obang

2015-02-01

Coeliac disease has a significant association with many autoimmune disorders. It shares many common genetic and immunological features with other autoimmune diseases. Gluten, a gut-derived antigen, is the driver of the autoimmunity seen in coeliac disease. The altered intestinal permeability found in coeliac patients, coupled with a genetic predisposition and altered immunological response, may result in a systemic immune response that is directed against sites other than the gut. Gut-derived antigens may have a role in the pathogenesis of other autoimmune disorders including rheumatoid arthritis. Here we report a case of adult coeliac disease associated with rheumatoid arthritis.

Ocular manifestations of rheumatoid arthritis and their correlation with anti-cyclic citrullinated peptide antibodies.

PubMed

Vignesh, Ammapati Paul Pandian; Srinivasan, Renuka

2015-01-01

To study the ocular manifestations of rheumatoid arthritis and to correlate the role of anti-cyclic citrullinated peptide antibody (anti-CCP antibody) with the ocular manifestations. Three-hundred and ninety-two eyes of the 196 rheumatoid arthritis patients who attended the ophthalmology outpatient department underwent a detailed ocular examination using slit lamp biomicroscopy and ophthalmoscopy. The tear function of all the patients was assessed using Schirmer's test, tear film break-up time and ocular surface staining. The anti-CCP antibody titers for all the rheumatoid arthritis patients were estimated using enzyme-linked immunosorbent assay tests. Seventy-seven patients (135 eyes, 39%) out of the 196 patients studied had ocular manifestations typical of rheumatoid arthritis. Dry eye was the most common manifestation (28%, 54 patients). Of the patients, 78% was females (60 patients). The mean duration of rheumatoid arthritis in patients with ocular manifestations was 5.4±2.7 years and without ocular manifestations was 2.1±1.6years. Three percent of the patients had episcleritis (six patients). Scleritis was present in 2% of the patients (four patients). Peripheral ulcerative keratitis and sclerosing keratitis was present in 1% of the population each (two patients each). Eighty-five percent (66 patients) had bilateral manifestations 15% (eleven patients) had unilateral manifestations. There was a strong association between the presence of anti-CCP antibodies and ocular manifestations of rheumatoid arthritis which was shown by the statistically significant P-value of <0.0001. Ocular manifestations are a significant part of the extra-articular manifestation of rheumatoid arthritis. Dry eye was the most common ocular manifestation. There was a statistically significant association between the presence of anti-CCP antibodies specific to rheumatoid arthritis and the ocular manifestations.

Treatment of rheumatoid arthritis: a global perspective on the use of antirheumatic drugs

PubMed Central

Envalds, Minja; Pincus, Theodore

2008-01-01

Modern therapy for rheumatoid arthritis (RA) is based on knowledge of the severity of the natural history of the disease. RA patients are approached with early and aggressive treatment strategies, methotrexate as an anchor drug, biological targeted therapies in those with inadequate response to methotrexate, and “tight control,” aiming for remission and low disease activity according to quantitative monitoring. This chapter presents a rationale for current treatment strategies for RA with antirheumatic drugs, a review of published reports concerning treatments in clinical cohorts outside of clinical trials, and current treatments at 61 sites in 21 countries in the QUEST-RA database. PMID:18437286

Rheumatoid arthritis clinical features and management strategies at an urban tertiary facility in Pakistan.

PubMed

Rais, Rehan; Saeed, Mohammad; Haider, Rimsha; Jassani, Zahra; Riaz, Amir; Perveen, Tahira

2014-12-01

To determine the presentation patterns, biologically vulnerable patient groups and treatment strategies of rheumatoid arthritis. The retrospective study was conducted at the Rheumatology Clinic of Liaquat National Hospital and Medical College, Karachi, and comprised data of rheumatology patients who presented between September 2006 and September 2012. After screening all the files, rheumatoid arthritis cases were identified. Data collection was done using a questionnaire that included patient demographics, co-morbidities, clinical manifestations and drug therapy. SPSS 13 was used for statistical analysis. Of the 2300 files screened, 500(21.7%) related to patients of rheumatoid arthritis. The mean age at presentation of these 500 patients was 41±15 years. There were 367(73.4%) women and they presented at an earlier age compared to men (p<0.024). Erosions were present in 198(40%) patients on X-rays and 22(4.4%) had joint deformities. Seropositive rheumatoid arthritis was associated with higher erythrocyte sedimentation rate levels (p<0.014), but did not differ from seronegative rheumatoid arthritis in terms of Disease Activity Score-28 levels (p<0.21). The skewed gender distribution was likely an effect of rheumatoid arthritis biology rather than due to issues of healthcare accessibility. Seronegative RA is likely to present late though it is as destructive as the seropositive disease.

Studying the Immunomodulatory Effects of Small Molecule Ras Inhibitors in Animal Models of Rheumatoid Arthritis

DTIC Science & Technology

2016-10-01

2016 4. TITLE AND SUBTITLE Studying the Immunomodulatory Effects of Small Molecule Ras-Inhibitors in Animal Models of Rheumatoid Arthritis 5a...TERMS Ras GTPases; Rheumatoid Arthritis (RA); Farnesylthiosalicylic acid (FTS); T helper cells, disease-modifying antirheumatic drugs (DMARDs...anergy and to restore IL-2 production. Importantly, T cells from patients with Rheumatoid Arthritis (RA) display augmented activation of the Ras

Studying the Immunomodulatory Effects of Small Molecule Ras-Inhibitors in Animal Models of Rheumatoid Arthritis

DTIC Science & Technology

2016-10-01

Studying the Immunomodulatory Effects of Small Molecule Ras-Inhibitors in Animal Models of Rheumatoid Arthritis 5a. CONTRACT NUMBER 5b. GRANT... Rheumatoid Arthritis (RA); Farnesylthiosalicylic acid (FTS); T helper cells, disease-modifying antirheumatic drugs (DMARDs); targeted synthetic DMARDs 16...active Ras was shown to reverse anergy and to restore IL-2 production. Importantly, T cells from patients with Rheumatoid Arthritis (RA) display

Health Assessment Questionnaire disability progression in early rheumatoid arthritis: Systematic review and analysis of two inception cohorts

PubMed Central

Norton, Sam; Fu, Bo; Scott, David L.; Deighton, Chris; Symmons, Deborah P.M.; Wailoo, Allan J.; Tosh, Jonathan; Lunt, Mark; Davies, Rebecca; Young, Adam; Verstappen, Suzanne M.M

2014-01-01

Objective The Health Assessment Questionnaire is widely used for patients with inflammatory polyarthritis (IP) and its subset, rheumatoid arthritis (RA). In this study, we evaluated the progression of HAQ scores in RA (i) by systematically reviewing the published literature on the methods used to assess changes in functional disability over time and (ii) to study in detail HAQ progression in two large prospective observational studies from the UK. Methods Data from two large inception cohorts, ERAS and NOAR, were studied to determine trajectories of HAQ progression over time by applying latent class growth models (LCGMs) to each dataset separately. Age, sex, baseline DAS28, symptom duration, rheumatoid factor, fulfilment of the 1987 ACR criteria and socio-economic status (SES) were included as potential predictors of HAQ trajectory subgroup membership. Results The literature search identified 49 studies showing that HAQ progression has mainly been based on average changes in the total study population. In the HAQ progression study, a LCGM with four HAQ trajectory subgroups was selected as providing the best fit in both cohorts. In both the cohorts, older age, female sex, longer symptom duration, fulfilment of the 1987 ACR criteria, higher DAS28 and lower SES were associated with increased likelihood of membership of subgroups with worse HAQ progression. Conclusion Four distinct HAQ trajectory subgroups were derived from the ERAS and NOAR cohorts. The fact that the subgroups identified were nearly identical supports their validity. Identifying distinct groups of patients who are at risk of poor functional outcome may help to target therapy to those who are most likely to benefit. PMID:24925692

Influence of periodontal treatment on rheumatoid arthritis: a systematic review and meta-analysis.

PubMed

Calderaro, Débora Cerqueira; Corrêa, Jôice Dias; Ferreira, Gilda Aparecida; Barbosa, Izabela Guimarães; Martins, Carolina Castro; Silva, Tarcília Aparecida; Teixeira, Antônio Lúcio

To evaluate the influence of periodontal treatment on rheumatoid arthritis activity. MEDLINE/PUBMED, The Cochrane Library, Clinical Trials, SciELO and LILACS were searched for studies published until December 2014. Included articles were: prospective studies; including patients older than 18 years, diagnosed with periodontitis and rheumatoid arthritis submitted to non-surgical periodontal treatment; with a control group receiving no periodontal treatment; with outcomes including at least one marker of rheumatoid arthritis activity. Methodological quality of the studies was assessed using PEDro scale. Quantitative data were pooled in statistical meta-analysis using Review Manager 5. Four articles were included. Non-surgical periodontal treatment was associated with a significant reduction of DAS28 (OR: -1.18; 95% CI: -1.43, -0.93; p<0.00001). Erythrocyte sedimentation rate, C-reactive protein, patient's assessment of rheumatoid activity using visual analogical scale, tender and swollen joint counts showed a trend toward reduction (not statistically significant). The reduction of DAS 28 in patients with rheumatoid arthritis after periodontal treatment suggests that the improvement of periodontal condition is beneficial to these patients. Further randomized controlled clinical trials are necessary to confirm this finding. Copyright © 2016. Published by Elsevier Editora Ltda.

Influence of periodontal treatment on rheumatoid arthritis: a systematic review and meta-analysis.

PubMed

Calderaro, Débora Cerqueira; Corrêa, Jôice Dias; Ferreira, Gilda Aparecida; Barbosa, Izabela Guimarães; Martins, Carolina Castro; Silva, Tarcília Aparecida; Teixeira, Antônio Lúcio

2016-11-26

To evaluate the influence of periodontal treatment on rheumatoid arthritis activity. MEDLINE/PUBMED, The Cochrane Library, Clinical Trials, SciELO and LILACS were searched for studies published until December 2014. Included articles were: prospective studies; including patients older than 18 years, diagnosed with periodontitis and rheumatoid arthritis submitted to non-surgical periodontal treatment; with a control group receiving no periodontal treatment; with outcomes including at least one marker of rheumatoid arthritis activity. Methodological quality of the studies was assessed using PEDro scale. Quantitative data were pooled in statistical meta-analysis using Review Manager 5. Four articles were included. Non-surgical periodontal treatment was associated with a significant reduction of DAS28 (OR: -1.18; 95% CI: -1.43, -0.93; p <0.00001). Erythrocyte sedimentation rate, C-reactive protein, patient's assessment of rheumatoid activity using visual analogical scale, tender and swollen joint counts showed a trend towards reduction (not statistically significant). The reduction of DAS 28 in patients with rheumatoid arthritis after periodontal treatment suggests that the improvement of periodontal condition is beneficial to these patients. Further randomized controlled clinical trials are necessary to confirm this finding. Copyright © 2016. Published by Elsevier Editora Ltda.

Long-term outcomes of destructive seronegative (rheumatoid) arthritis - description of four clinical cases.

PubMed

Nikiphorou, Elena; Sjöwall, Christopher; Hannonen, Pekka; Rannio, Tuomas; Sokka, Tuulikki

2016-06-03

Seronegative rheumatoid arthritis is associated with a milder course of progression compared to seropositive disease. However, long-term follow-up data of the clinical course of seronegative rheumatoid arthritis are sparse. Here we describe four cases with a rare disease entity of aggressive destructive seronegative (rheumatoid) arthritis with 20-35 years of follow-up. The four cases are women with an initial presentation of seronegative rheumatoid arthritis in 1980-1996 and have received disease-modifying anti-rheumatic drugs since the diagnosis. In all cases, the condition has been refractory to treatments and evolved into a severe disease with destructions of the wrists, sub-talar and ankle joints, as well as large joints but not small joints of fingers and toes. All cases are negative with regard to rheumatoid factor, anti-cyclic citrullinated peptide antibodies and antibodies against carbamylated proteins. This report adds to the existing literature, making the reader aware of this sub-type of inflammatory arthritis which despite being seronegative, can have devastating disease consequences. The report highlights the need for further research into this field in order to better understand this disease sub-type, the pathogenesis, disease course and outcomes.

Self-limiting arthritis among patients fulfilling the 2010 ACR/EULAR classification criteria for rheumatoid arthritis in a very early arthritis cohort.

PubMed

Norli, Ellen Sauar; Brinkmann, Gina H; Kvien, Tore K; Bjørneboe, Olav; Haugen, Anne J; Nygaard, Halvor; Thunem, Cathrine; Lie, Elisabeth; Mjaavatten, Maria D

2016-12-01

To study occurrence of and factors associated with self-limiting arthritis among patients fulfilling the 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA) (2010 RA criteria) in patients with ≤16 weeks׳ duration of joint swelling. We applied the 2010 RA criteria in 1118 patients included in a 2-year longitudinal cohort. In all, 256 patients fulfilled the 2010 RA criteria at baseline; outcome was defined as either "self-limiting arthritis" (no DMARD use during follow-up, no swollen joints at last assessment, and no final clinical diagnosis of RA) or "persistent disease." The associations between baseline characteristics, including the components of the 2010 RA criteria score, and outcomes were studied. In total, 36 of 256 patients (14.1%) classified as having RA had self-limiting arthritis. These patients differed from patients with persistent disease according to ACPA positivity (11.1% vs. 65.0%, p < 0.001), duration of joint swelling (median = 47.5 vs. 66.0 days, p = 0.002), 2010 RA criteria points (median = 6.0 vs. 7.0, p < 0.001), and ever smoking (52.8% vs. 74.5%, p = 0.01). Having no serology points and no duration points were independent predictors of self-limiting arthritis. The rate of self-limiting arthritis was 2.7% vs. 29.4% among ACPA positive vs. ACPA negative patients (p < 0.001), and 32.5% when duration of joint swelling was <4 weeks vs. 10.6% with longer duration (p < 0.001). Negative ACPA status, short duration of joint swelling and being a never smoker were factors associated with self-limiting arthritis in early arthritis patients classified as having RA at presentation. Our findings contribute to identify patients who potentially do not need DMARDs and who should not be included in early RA clinical drug trials. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Fatigue, Older Age, Higher Body Mass Index, and Female Sex on Disability in Early Rheumatoid Arthritis in the Treatment-to-Target Era.

PubMed

Twigg, Sarah; Hensor, Elizabeth M A; Freeston, Jane; Tan, Ai Lyn; Emery, Paul; Tennant, Alan; Morgan, Ann W

2018-03-01

To compare disease activity and disability over 2 years in early rheumatoid arthritis (RA) before and after implementation of treat-to-target therapy and identify predictors of adverse outcome. The Yorkshire Early Arthritis Register (YEAR) recruited 725 patients with early RA between 2002 and 2009, treated with a step-up approach. The Inflammatory Arthritis Continuum study (IACON) recruited cases between 2010 and 2014 and treated to target. A total of 384 IACON cases met 2010 American College of Rheumatology/European League Against Rheumatism criteria. Latent growth curves of change in Disease Activity Score in 28 joints (DAS28) and the Health Assessment Questionnaire (HAQ) were compared between YEAR and IACON. Latent class growth analysis identified trajectories of change. Baseline predictors of trajectories were identified using logistic regression. The mean DAS28 over 2 years was lower in IACON than in YEAR. Latent trajectories of HAQ change in YEAR were high stable (21% of cohort), moderate reducing (35%), and low reducing (44%). Only moderate reducing (66%) and low reducing (34%) were seen in IACON. In both cohorts, female sex and fatigue predicted adverse HAQ trajectories (high stable and moderate reducing). Odds ratios (ORs) for moderate reducing compared to low reducing for women were 2.58 (95% confidence interval [95% CI] 1.69, 4.49) in YEAR and 5.81 (95% CI 2.44, 14.29) in IACON. ORs per centimeter fatigue visual analog score were 1.13 (95% CI 1.07, 1.20) in YEAR and 1.16 (95% CI 1.12, 1.20) in IACON. Treat-to-target therapy gave more favorable trajectories of change in DAS28 and HAQ, but adverse HAQ trajectory was more likely in women with greater fatigue, suggesting such patients would benefit from interventions to improve function as well as reduce inflammation. © 2017, American College of Rheumatology.

Two-dimensional electrophoretic analysis of human leukocyte proteins from patients with rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willard, K.E.; Thorsrud, A.K.; Munthe, E.

Human leukocyte proteins from more than 150 patients with rheumatoid arthritis, together with age- and sex-matched controls, were analyzed by use of the ISO-DALT technique of two-dimensional polyacrylamide gel electrophoresis. Patients with ankylosing spondylitis, polymyalgia rheumatica, psoriatic arthritis, calcium tendinitis, post-infectious arthritis, and asymmetrical seronegative arthritis were also included as positive controls. Synthesis of several proteins, referred to by number as members of the Rheuma set, is shown to increase in the leukocyte preparations from patients with classical rheumatoid arthritis. Several of these proteins are specific to monocytes or granulocytes; others are of unknown cellular origin, but appear to bemore » unique to rheumatoid arthritis. The Rheuma proteins appear to be indicators of disease activity, because their increased synthesis can be correlated with sedimentation rate and other clinical indices of rheumatoid disease activity.« less

[Dyslipidemia and atherogenic risk in patients with rheumatoid arthritis].

PubMed

Batún Garrido, José Antonio de Jesús; Olán, Francisco; Hernández Núñez, Éufrates

2016-01-01

Dyslipidaemia is one of the main risk factors for atherosclerotic cardiovascular disease. Patients with rheumatoid arthritis have 2-3 times more cardiovascular risk, which is partly due to the pattern of lipids which increase the atherogenic index. A descriptive, cross-sectional, observational and prospective study was conducted on 82 patients, selected for their lipid profile. Variables associated with the disease and the drugs used were recorded. Atherogenic risk was calculated, with Chi square being used for categorical variables, and the Mann-Whitney test for the continuous ones. The dyslipidaemia frequency was 54.9%. The most frequent age range of dyslipidaemia was between 51 and 60 years. Patients with type i obesity had a higher frequency of dyslipidaemia. Less dyslipidaemia was found with a lower rate of disease activity. Patients with cyclic citrullinated anti-peptide antibodies and positive rheumatoid factor, erythrocyte sedimentation rate>13mm or CRP>2mg/L had a higher frequency of dyslipidaemia. The mean Castelli atherogenic index was 4.36, the index of Kannel was 2.59, and triglycerides/HDL-c ratio was 3.83.Patients with dyslipidaemia showed a higher frequency of positive rheumatoid factor (P=.0008), and those patients who were taking hydroxychloroquine had a lower frequency of dyslipidaemia P=.03. Patients with rheumatoid arthritis have a pro-atherogenic lipid profile. It is important to know this and treat it to reduce cardiovascular risk. Copyright © 2016 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Course and prognosis in seropositive and seronegative rheumatoid arthritis.

PubMed

Sahatçiu-Meka, Vjollca; Rexhepi, Sylejman; Kukeli, Anton; Manxhuka-Kërliu, Suzana; Pallaskas, Kelmend; Murtezani, Ardiana; Rexhepi, Mjellma; Rexhepi, Blerta

2013-01-01

Long since it have been suggested that a subpopulation of patients with rheumatoid arthritis (RA), diagnosed with negative rheumatoid factor (RF) tests, represents a clinical entity quite distinct from that of seropositive rheumatoid arthritis. The aim of the study was to establish a scientific comparative analysis between RA seronegative and seropositive, regarding course and prognoses of the disease. Two hundred fifty patients with rheumatoid arthritis according to the (American College of Rheumatology) criteria were retrospectively studied by analysis the course and prognoses of disease. All examinees were between 25-60 years of age (Xb=49.9, SD=10.3) with disease duration between 1-27 years (Xbox=6.41, SD=6.47). Course of the disease with "remissions and exacerbations", progressive continual course and bad prognoses, were more presented in seropositive group ofpatients. Partial remission was more common in seronegative patients but according to serostatus and gender has not shown statistically significant difference. Duration of the disease was a specific prognostic sign for both subsets [(r=0.32, p<0.01) seronegative, (r=0.22, p<0.05) seropositive], while age was only a specific prognostic sign for the seropositive subset [(r=0.01, p>0.05) seronegative, (r=0.18, p<0.05) seropositive]. Seropositive and seronegative RA distinguish in course and prognostic feature, but not enough to differentiate them in two different forms of the disease. Regarding the sero-status, differences within sex, with some exceptions, are not relevant.

Studying the Immunomodulatory Effects of Small Molecule Ras-Inhibitors in Animal Models of Rheumatoid Arthritis

DTIC Science & Technology

2015-10-01

Models of Rheumatoid Arthritis PRINCIPAL INVESTIGATOR: Yoel Kloog RECIPIENT: Tel Aviv University TEL AVIV 69978 Israel REPORT DATE: October...TITLE AND SUBTITLE Studying the Immunomodulatory Effects of Small Molecule Ras- Inhibitors in Animal Models of Rheumatoid Arthritis 5a. CONTRACT NUMBER... Rheumatoid Arthritis (RA) display augmented activation of the Ras/Raf/MEK/ERK1/2 signaling pathway, and accordingly overexpression of active K-RAS in

Early Validation of Failure Detection, Isolation, and Recovery Design Using Heterogeneous Modelling and Simulation

NASA Astrophysics Data System (ADS)

van der Plas, Peter; Guerriero, Suzanne; Cristiano, Leorato; Rugina, Ana

2012-08-01

Modelling and simulation can support a number of use cases across the spacecraft development life-cycle. Given the increasing complexity of space missions, the observed general trend is for a more extensive usage of simulation already in the early phases. A major perceived advantage is that modelling and simulation can enable the validation of critical aspects of the spacecraft design before the actual development is started, as such reducing the risk in later phases.Failure Detection, Isolation, and Recovery (FDIR) is one of the areas with a high potential to benefit from early modelling and simulation. With the increasing level of required spacecraft autonomy, FDIR specifications can grow in such a way that the traditional document-based review process soon becomes inadequate.This paper shows that FDIR modelling and simulation in a system context can provide a powerful tool to support the FDIR verification process. It is highlighted that FDIR modelling at this early stage requires heterogeneous modelling tools and languages, in order to provide an adequate functional description of the different components (i.e. FDIR functions, environment, equipment, etc.) to be modelled.For this reason, an FDIR simulation framework is proposed in this paper. This framework is based on a number of tools already available in the Avionics Systems Laboratory at ESTEC, which are the Avionics Test Bench Functional Engineering Simulator (ATB FES), Matlab/Simulink, TASTE, and Real Time Developer Studio (RTDS).The paper then discusses the application of the proposed simulation framework to a real case-study, i.e. the FDIR modelling of a satellite in support of actual ESA mission. Challenges and benefits of the approach are described. Finally, lessons learned and the generality of the proposed approach are discussed.

Rheumatoid arthritis and pulmonary nodules: An unexpected final diagnosis.

PubMed

Zurita Prada, Pablo Antonio; Urrego Laurín, Claudia Lía; Assyaaton Bobo, Sow; Faré García, Regina; Estrada Trigueros, Graciliano; Gallardo Romero, José Manuel; Borrego Pintado, Maria Henar

We report the case of a 50-year-old female smoker with an 11-year history of seropositive rheumatoid arthritis (rheumatoid factor and anti-cyclic citrullinated peptide antibodies) receiving triple therapy. She developed pulmonary nodules diagnosed as Langerhans cell histiocytosis by lung biopsy. We found no reported cases of the coexistence of these two diseases. Smoking abstinence led to radiologic resolution without modifying the immunosuppressive therapy. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Subendocardial viability ratio in patients with rheumatoid arthritis: comparison with healthy controls and identification of prognostic factors.

PubMed

Anyfanti, Panagiota; Triantafyllou, Areti; Gkaliagkousi, Eugenia; Triantafyllou, Georgios; Koletsos, Nikolaos; Chatzimichailidou, Sophia; Panagopoulos, Panagiotis; Botis, Ioannis; Aslanidis, Spyros; Douma, Stella

2017-06-01

Cardiac involvement is common in rheumatoid arthritis. Subendocardial viability ratio (SEVR) is a non-invasive measure of microvascular coronary perfusion, yet it remains unclear whether it is affected in rheumatoid arthritis patients. We additionally sought predictors of SEVR in rheumatoid arthritis among a wide range of disease-related parameters, cardiac and hemodynamic factors, and markers of atherosclerosis, arteriosclerosis, and endothelial dysfunction. SEVR was estimated in rheumatoid arthritis patients and healthy controls by applanation tonometry, which was also used to evaluate arterial stiffness (pulse wave velocity and augmentation index). In the rheumatoid arthritis group, carotid intima-media thickness (cIMT) was additionally estimated by ultrasound, cardiac and hemodynamic parameters by impedance cardiography, and endothelial dysfunction by measurement of asymmetric dimethylarginine (ADMA). In a total of 122 participants, SEVR was lower among 91 patients with rheumatoid arthritis compared to 31 controls (141.4 ± 21.9 vs 153.1 ± 18.7%, p = 0.009) and remained so among 29 rheumatoid arthritis patients without hypertension, diabetes, or cardiovascular diseases, compared to the control group (139.7 ± 21.7 vs 153.1 ± 18.7%, p = 0.013). SEVR did not significantly correlate with arterial stiffness, cIMT, ADMA, or disease-related parameters. Multivariate analysis revealed gender (p = 0.007), blood pressure (p = 0.028), heart rate (p = 0.025), cholesterol levels (p = 0.008), cardiac index (p < 0.001) and left ventricular ejection time (p = 0.004) as independent predictors of SEVR among patients with rheumatoid arthritis. Patients with rheumatoid arthritis exhibit lower values of SEVR compared to healthy individuals. Cardiac and hemodynamic parameters, rather than functional indices of endothelial and macrovascular dysfunction, may be useful as predictors of myocardial perfusion in rheumatoid arthritis.

Rheumatoid cachexia and other nutritional alterations in rheumatologic diseases.

PubMed

Hurtado-Torres, Gilberto Fabián; González-Baranda, Lourdes Larisa; Abud-Mendoza, Carlos

2015-01-01

The prevalence of nutritional alterations in rheumatologic diseases ranges from 4 to 95%, depending on the detection method used. Formerly described as the single term rheumatoid cachexia, nutritional alterations can currently be grouped and subdivided based on the physiopathological mechanisms involved: chronic disease-related inflammatory conditions (cachexia), malnutrition associated to acute malnutrition inflammatory conditions (protein-caloric malnutrition) and starvation-related malnutrition. Clinical manifestations of malnutrition associated to rheumatic diseases vary from the patient with low weight or overweight and obesity; with lean body mass depletion as well as functional repercussions, and impact of quality of life as a common denominator. Additionally, the associated increase in body fat mass increases the risk for cardiovascular morbidity. A multidisciplinary approach towards rheumatic diseases should include aspects oriented towards prevention, early identification, diagnosis and correction of nutritional alterations. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Cost-utility of COBRA-light versus COBRA therapy in patients with early rheumatoid arthritis: the COBRA-light trial

PubMed Central

ter Wee, Marieke M; Coupé, Veerle MH; den Uyl, Debby; Blomjous, Birgit S; Kooijmans, Esmee; Kerstens, Pit JSM; Nurmohamed, Mike T; van Schaardenburg, Dirkjan; Voskuyl, Alexandre E; Boers, Maarten; Lems, Willem F

2017-01-01

Objective To evaluate if COmbinatie therapie Bij Reumatoïde Artritis (COBRA)-light therapy is cost-effective in treating patients with early rheumatoid arthritis (RA) compared with COBRA therapy. Methods This economic evaluation was performed next to the open-label, randomised non-inferiority COBRA-light trial in 164 patients with early RA. Non-responders to COBRA or COBRA-light received etanercept (50 mg/week) for 3–6 months. The societal perspective analysis took medical direct, non-medical direct and indirect costs into account. Costs were measured with patient cost diaries for the follow-up period of 52 weeks. Bootstrapping techniques estimated uncertainty around the cost-effectiveness ratios, presented in cost-effectiveness planes. Results 164 patients were randomised to either COBRA or COBRA-light strategy. At week 52, COBRA-light proved to be non-inferior to COBRA therapy on all clinical outcome measures. The results of the base-case cost-utility analysis (intention-to-treat analyses) revealed that COBRA-light strategy is more expensive (k€9.3 (SD 0.9) compared with COBRA (k€7.2 (SD 0.8)), but the difference in costs were not significant (k€2.0; 95% CI –0.3 to 4.4). Also, both strategies produced similar quality-adjusted life-years (QALYs). The sensitivity analyses showed robustness of these results. In a per-protocol sensitivity analysis, in which costs of etanercept were assumed to be provided as prescribed according to protocol, both arms had much higher costs: COBRA-light: k€11.5 (8.3) compared with k€8.5 (6.8) for COBRA, and the difference in costs was significant (k€2.9; 0.6 to 5.3). Conclusions In the base-case cost-utility analysis, the two strategies produced similar QALYs for similar costs. But it is anticipated that if protocol had been followed correctly, the COBRA-light strategy would have been more costly due to additional etanercept costs, for a limited health gain. Given the limited added benefit and high costs of starting

Cost-utility of COBRA-light versus COBRA therapy in patients with early rheumatoid arthritis: the COBRA-light trial.

PubMed

Ter Wee, Marieke M; Coupé, Veerle Mh; den Uyl, Debby; Blomjous, Birgit S; Kooijmans, Esmee; Kerstens, Pit Jsm; Nurmohamed, Mike T; van Schaardenburg, Dirkjan; Voskuyl, Alexandre E; Boers, Maarten; Lems, Willem F

2017-01-01

To evaluate if COmbinatie therapie Bij Reumatoïde Artritis (COBRA)-light therapy is cost-effective in treating patients with early rheumatoid arthritis (RA) compared with COBRA therapy. This economic evaluation was performed next to the open-label, randomised non-inferiority COBRA-light trial in 164 patients with early RA. Non-responders to COBRA or COBRA-light received etanercept (50 mg/week) for 3-6 months. The societal perspective analysis took medical direct, non-medical direct and indirect costs into account. Costs were measured with patient cost diaries for the follow-up period of 52 weeks. Bootstrapping techniques estimated uncertainty around the cost-effectiveness ratios, presented in cost-effectiveness planes. 164 patients were randomised to either COBRA or COBRA-light strategy. At week 52, COBRA-light proved to be non-inferior to COBRA therapy on all clinical outcome measures. The results of the base-case cost-utility analysis (intention-to-treat analyses) revealed that COBRA-light strategy is more expensive (k€9.3 (SD 0.9) compared with COBRA (k€7.2 (SD 0.8)), but the difference in costs were not significant (k€2.0; 95% CI -0.3 to 4.4). Also, both strategies produced similar quality-adjusted life-years (QALYs). The sensitivity analyses showed robustness of these results. In a per-protocol sensitivity analysis, in which costs of etanercept were assumed to be provided as prescribed according to protocol, both arms had much higher costs: COBRA-light: k€11.5 (8.3) compared with k€8.5 (6.8) for COBRA, and the difference in costs was significant (k€2.9; 0.6 to 5.3). In the base-case cost-utility analysis, the two strategies produced similar QALYs for similar costs. But it is anticipated that if protocol had been followed correctly, the COBRA-light strategy would have been more costly due to additional etanercept costs, for a limited health gain. Given the limited added benefit and high costs of starting etanercept in the presence of low disease

Obesity is the main determinant of insulin resistance more than the circulating pro-inflammatory cytokines levels in rheumatoid arthritis patients.

PubMed

Castillo-Hernandez, Jesus; Maldonado-Cervantes, Martha Imelda; Reyes, Juan Pablo; Patiño-Marin, Nuria; Maldonado-Cervantes, Enrique; Solorzano-Rodriguez, Claudia; de la Cruz Mendoza, Esperanza; Alvarado-Sanchez, Brenda

Systemic blockade of TNF-α in Rheumatoid arthritis with insulin resistance seems to produce more improvement in insulin sensitivity in normal weight patients with Rheumatoid arthritis than in obese patients with Rheumatoid arthritis, suggesting that systemic-inflammation and obesity are independent risk factors for insulin resistance in Rheumatoid arthritis patients. To evaluate the insulin resistance in: normal weight patients with Rheumatoid arthritis, overweight patients with Rheumatoid arthritis, obese Rheumatoid arthritis patients, and matched control subjects with normal weight and obesity; and its association with major cytokines involved in the pathogenesis of the disease. Assessments included: body mass index, insulin resistance by Homeostasis Model Assessment, ELISA method, and enzymatic colorimetric assay. Outstanding results from these studies include: (1) In Rheumatoid arthritis patients, insulin resistance was well correlated with body mass index, but not with levels of serum cytokines. In fact, levels of cytokines were similar in all Rheumatoid arthritis patients, regardless of being obese, overweight or normal weight (2) Insulin resistance was significantly higher in Rheumatoid arthritis with normal weight than in normal weight (3) No significant difference was observed between insulin resistances of Rheumatoid arthritis with obesity and obesity (4) As expected, levels of circulating cytokines were significantly higher in Rheumatoid arthritis patients than in obesity. Obesity appears to be a dominant condition above inflammation to produce IR in RA patients. The dissociation of the inflammation and obesity components to produce IR suggests the need of an independent therapeutic strategy in obese patients with RA. Copyright © 2017. Published by Elsevier Editora Ltda.

Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity.

PubMed

Curtis, Jeffrey R; van der Helm-van Mil, Annette H; Knevel, Rachel; Huizinga, Tom W; Haney, Douglas J; Shen, Yijing; Ramanujan, Saroja; Cavet, Guy; Centola, Michael; Hesterberg, Lyndal K; Chernoff, David; Ford, Kerri; Shadick, Nancy A; Hamburger, Max; Fleischmann, Roy; Keystone, Edward; Weinblatt, Michael E

2012-12-01

Quantitative assessment of disease activity in rheumatoid arthritis (RA) is important for patient management, and additional objective information may aid rheumatologists in clinical decision making. We validated a recently developed multibiomarker disease activity (MBDA) test relative to clinical disease activity in diverse RA cohorts. Serum samples were obtained from the Index for Rheumatoid Arthritis Measurement, Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study, and Leiden Early Arthritis Clinic cohorts. Levels of 12 biomarkers were measured and combined according to a prespecified algorithm to generate the composite MBDA score. The relationship of the MBDA score to clinical disease activity was characterized separately in seropositive and seronegative patients using Pearson's correlations and the area under the receiver operating characteristic curve (AUROC) to discriminate between patients with low and moderate/high disease activity. Associations between changes in MBDA score and clinical responses 6-12 weeks after initiation of anti-tumor necrosis factor or methotrexate treatment were evaluated by the AUROC. The MBDA score was significantly associated with the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) in both seropositive (AUROC 0.77, P < 0.001) and seronegative (AUROC 0.70, P < 0.001) patients. In subgroups based on age, sex, body mass index, and treatment, the MBDA score was associated with the DAS28-CRP (P < 0.05) in all seropositive and most seronegative subgroups. Changes in the MBDA score at 6-12 weeks could discriminate both American College of Rheumatology criteria for 50% improvement responses (P = 0.03) and DAS28-CRP improvement (P = 0.002). Changes in the MBDA score at 2 weeks were also associated with subsequent DAS28-CRP response (P = 0.02). Our findings establish the criterion and discriminant validity of a novel multibiomarker test as an objective measure of RA disease activity to aid

Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity

PubMed Central

Curtis, Jeffrey R; van der Helm-van Mil, Annette H; Knevel, Rachel; Huizinga, Tom W; Haney, Douglas J; Shen, Yijing; Ramanujan, Saroja; Cavet, Guy; Centola, Michael; Hesterberg, Lyndal K; Chernoff, David; Ford, Kerri; Shadick, Nancy A; Hamburger, Max; Fleischmann, Roy; Keystone, Edward; Weinblatt, Michael E

2012-01-01

Objective Quantitative assessment of disease activity in rheumatoid arthritis (RA) is important for patient management, and additional objective information may aid rheumatologists in clinical decision making. We validated a recently developed multibiomarker disease activity (MBDA) test relative to clinical disease activity in diverse RA cohorts. Methods Serum samples were obtained from the Index for Rheumatoid Arthritis Measurement, Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study, and Leiden Early Arthritis Clinic cohorts. Levels of 12 biomarkers were measured and combined according to a prespecified algorithm to generate the composite MBDA score. The relationship of the MBDA score to clinical disease activity was characterized separately in seropositive and seronegative patients using Pearson's correlations and the area under the receiver operating characteristic curve (AUROC) to discriminate between patients with low and moderate/high disease activity. Associations between changes in MBDA score and clinical responses 6–12 weeks after initiation of anti–tumor necrosis factor or methotrexate treatment were evaluated by the AUROC. Results The MBDA score was significantly associated with the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) in both seropositive (AUROC 0.77, P < 0.001) and seronegative (AUROC 0.70, P < 0.001) patients. In subgroups based on age, sex, body mass index, and treatment, the MBDA score was associated with the DAS28-CRP (P < 0.05) in all seropositive and most seronegative subgroups. Changes in the MBDA score at 6–12 weeks could discriminate both American College of Rheumatology criteria for 50% improvement responses (P = 0.03) and DAS28-CRP improvement (P = 0.002). Changes in the MBDA score at 2 weeks were also associated with subsequent DAS28-CRP response (P = 0.02). Conclusion Our findings establish the criterion and discriminant validity of a novel multibiomarker test as an

Angiopoietin-2 serum levels correlate with severity, early onset and cardiovascular disease in patients with rheumatoid arthritis.

PubMed

López-Mejías, Raquel; Corrales, Alfonso; Genre, Fernanda; Hernández, José L; Ochoa, Rodrigo; Blanco, Ricardo; González-Juanatey, Carlos; Martín, Javier; Llorca, Javier; González-Gay, Miguel A

2013-01-01

Rheumatoid arthritis (RA) is an inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular (CV) disease. Angiopoietin-2 (Angpt-2), a marker of endothelial cell activation, has been proposed as a mediator of angiogenesis, which might play an important role in the regulation of endothelial integrity and inflammation. Therefore, the aim of this study was to determine whether Angpt-2 is related to severity and CV disease in RA patients. Angpt-2 serum levels were measured by enzyme linked immunosorbent assay (ELISA) in 290 patients with RA. A control group of 100 individuals frequency matched by age and sex and classic CV risk factors and CV disease was also assessed. Eighty-four patients with RA (28.9%) had experienced CV events. Also, extra-articular manifestations were present in 41 (14%) of these patients. Although there were not significant differences between patients and controls, a correlation between age at the time of disease onset and Angpt-2 was observed in RA patients (r=-0.31; p=0.02). Angpt-2 serum levels also correlated positively with extra-articular disease (mean±standard deviation in RA patients with and without extra-articular manifestations were 2476±1716 pg/ml and 1897±1228 pg/ml, respectively; p=0.01). Moreover, after adjustment for sex, age at RA diagnosis and CV risk factors, Angpt-2 levels were higher in RA patients with CV disease than in RA patients without CV complications (2472±1826 pg/ml vs. 1875±1101 pg/ml; p=0.05). Angpt-2 serum levels remained significantly higher in RA patients with CV disease compared to those without CV disease after additional adjustment for extra-articular manifestations (p=0.04). Our results show that Angpt-2 serum levels correlate with disease severity, early onset and CV disease in RA patients.

Rheumatoid hand surgery: differing perceptions amongst surgeons, rheumatologists and therapists in the UK.

PubMed

Burke, F D; Miranda, S M; Owen, V M F; Bradley, M J; Sinha, S

2011-10-01

Rheumatoid arthritis is a systemic disease that requires coordinated management by rheumatologists, surgical specialists and therapists working in a multidisciplinary team. Differences of opinion within the team may adversely affect patient care. Our aim was to assess differences in perception about rheumatoid hand surgery between rheumatologists, hand surgeons and hand therapists in the UK. We used a postal questionnaire to assess commonly performed rheumatoid hand operations. For each procedure, respondents rated the most important indication for surgery and scored effectiveness at reducing pain, improving function and aesthetics, and preventing deformity. Statistically significant differences were found between all three groups with regards to expected outcome and main indications for surgery. We concluded that significant differences do exist in the perceptions of rheumatologists, surgeons and therapists. Rheumatoid hand operations require more detailed study, clarifying indications and outcome to allow consistent advice to patients from all members of the multidisciplinary team.

Symmetrical primary cutaneous marginal zone lymphoma associated with rheumatoid arthritis.

PubMed

Yildirim, Fatma Elif; Karaduman, Ayşen; Hürmüz, Pervin; Ozyar, Enis; Barişta, Ibrahim; Sağlam, Arzu

2010-05-01

Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is an indolent low grade B cell lymphoma of the skin, with lack of extracutaneous involvement at the time of diagnosis. Herein we report the case of a patient with rheumatoid arthritis (RA) who developed symmetrical PCMZL lesions on both ear lobes. Lesions occurring symmetrically on ear lobes are more specific for cutaneous lymphoid hyperplasia (CLH) and this kind of symmetrical localization hasn't been reported for PCMZL before. PCMZL is considered to arise from a background of reactive lymphoid hyperplasia and this case point out the concept of CLH and PCMZL spectrum. Association of marginal zone lymphoma with rheumatoid arthritis and resolution of lesions together with the resolution of symptoms due to rheumatoid arthritis after rituximab therapy is another interesting point for this case. To the best of our knowledge PCMZL associated with RA has not been reported previously.

[Subclinical sensorineural hearing loss in female patients with rheumatoid arthritis].

PubMed

Treviño-González, José Luis; Villegas-González, Mario Jesús; Muñoz-Maldonado, Gerardo Enrique; Montero-Cantu, Carlos Alberto; Nava-Zavala, Arnulfo Hernán; Garza-Elizondo, Mario Alberto

2015-01-01

The rheumatoid arthritis is a clinical entity capable to cause hearing impairment that can be diagnosed promptly with high frequencies audiometry. To detect subclinical sensorineural hearing loss in patients with rheumatoid arthritis. Cross-sectional study on patients with rheumatoid arthritis performing high frequency audiometry 125Hz to 16,000Hz and tympanometry. The results were correlated with markers of disease activity and response to therapy. High frequency audiometry was performed in 117 female patients aged from 19 to 65 years. Sensorineural hearing loss was observed at a sensitivity of pure tones from 125 to 8,000 Hz in 43.59%, a tone threshold of 10,000 to 16,000Hz in 94.02% patients in the right ear and in 95.73% in the left ear. Hearing was normal in 8 (6.84%) patients. Hearing loss was observed in 109 (93.16%), and was asymmetric in 36 (30.77%), symmetric in 73 (62.37%), bilateral in 107 (91.45%), unilateral in 2 (1.71%), and no conduction and/or mixed hearing loss was encountered. Eight (6.83%) patients presented vertigo, 24 (20.51%) tinnitus. Tympanogram type A presented in 88.90% in the right ear and 91.46% in the left ear, with 5.98 to 10.25% type As. Stapedius reflex was present in 75.3 to 85.2%. Speech discrimination in the left ear was significantly different (p = 0.02)in the group older than 50 years. No association was found regarding markers of disease activity, but there was an association with the onset of rheumatoid arthritis disease. Patients with rheumatoid arthritis had a high prevalence of sensorineural hearing loss for high and very high frequencies. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Anti-citrullinated protein antibody and rheumatoid factor in patients with end-stage renal disease.

PubMed

Romic, Zeljko; Unic, Adriana; Derek, Lovorka; Zivkovic, Marcela; Marijancevic, Domagoj; Kes, Petar; Pehar, Mario

2009-01-01

Patients with end-stage renal disease (ESRD) and on hemodialysis (HD) are at increased risk for developing rheumatoid arthritis (RA), as a result of defective immunity. Our aim was to examine if ESRD and the length of HD treatment impact the clinical utility of antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factor (RF) as diagnostic tools for RA. We included 94 subjects in our study: 37 healthy volunteers and 57 patients with ESRD who had been undergoing HD for 1-12 years, and without confirmed RA. In order to test our hypothesis, we measured and correlated anti-CCP and RF as laboratory markers of RA. Our study showed that there is no significant difference between values for anti-CCP (p=0.11) and RF (p=0.98) in control subjects as well as in patients undergoing HD, regardless of the length of time that patients had been undergoing HD treatment. Our study indicates that HD does not impair the specificity of anti-CCP and RF for RA in patients where the disease has not yet developed. Future prospective studies may show whether there is any use in determinating RF, and especially anti-CCP, as early predictors of RA in patients with ESRD who are at greater risk of developing this condition.

Incidence of Rheumatoid Arthritis in the Southern part of Denmark from 1995 to 2001

PubMed Central

Pedersen, Jens K; Svendsen, Anders J; Hørslev-Petersen, Kim

2007-01-01

We estimated the incidence of rheumatoid arthritis in the southern part of Denmark from 1995 to 2001. At a rheumatology hospital serving a population of about 200 000 people over the age of 15, medical records were scrutinized. As case definition we used the tree and list format of 1987 American College of Rheumatology criteria for rheumatoid arthritis. The mean annual incidence rate per 100 000 person years was 40 in females, 21 in males, and 31 in females and males combined. The incidence of rheumatoid arthritis in Denmark is in accordance with recent studies from North America, the UK, and Northern European countries. The aetiology of rheumatoid arthritis is unknown but this study indicates that in these populations the exposure to non-genetic host and environmental aetiological factors is similar. PMID:19088896

The Future of Rheumatoid Arthritis and Hand Surgery - Combining Evolutionary Pharmacology and Surgical Technique

PubMed Central

M, Malahias; H, Gardner; S, Hindocha; A, Juma; Khan, W

2012-01-01

Rheumatoid arthritis is a systemic autoimmune disease of uncertain aetiology, which is characterized primarily by synovial inflammation with secondary skeletal destructions. Rheumatoid Arthritis is diagnosed by the presence of four of the seven diagnostic criteria, defined by The American College of Rheumatology. Approximately half a million adults in the United Kingdom suffer from rheumatoid arthritis with an age prevalence between the second and fourth decades of life; annually approximately 20,000 new cases are diagnosed. The management of Rheumatoid Arthritis is complex; in the initial phase of the disease it primarily depends on pharmacological management. With disease progression, surgical input to correct deformity comes to play an increasingly important role. The treatment of this condition is also intimately coupled with input from both the occupational therapists and physiotherapy. PMID:22423304

A Clinical Update and Global Economic Burden of Rheumatoid Arthritis.

PubMed

Fazal, Syed Ali; Khan, Mohammad; Nishi, Shamima E; Alam, Fahmida; Zarin, Nowshin; Bari, Mohammad T; Ashraf, Ghulam Md

2018-02-13

Rheumatoid arthritis (RA) is a predominant inflammatory autoimmune disorder. The incidence and prevalence of RA is increasing with considerable morbidity and mortality worldwide. The pathophysiology of RA has become clearer due to many significant research outputs during the last two decades. Many inflammatory cytokines involved in RA pathophysiology and the presence of autoantibodies are being used as potential biomarkers via the use of effective diagnostic techniques for the early diagnosis of RA. Currently, several disease-modifying anti-rheumatic drugs are being prescribed targeting RA pathophysiology, which have shown significant contributions in improving the disease outcomes. Even though innovations in treatment strategies and monitoring are helping the patients to achieve early and sustained clinical and radiographic remission, the high cost of drugs and limited health care budgets are restricting the easy access of RA treatment. Both direct and indirect high cost of treatment are creating economic burden for the patients and affecting their quality of life. The aim of this review is to describe the updated concept of RA pathophysiology and highlight current diagnostic tools used for the early detection as well as prognosis - targeting several biomarkers of RA. Additionally, we explored the updated treatment options with side effects besides discussing the global economic burden. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Cystic Rheumatoid Arthritis--case report].

PubMed

Mourão, Ana Filipa; Santos, Fernando Pimentel; Falcão, Sandra; Pinto, Teresa Laura; Barros, Rita; de Matos, António Alves; Branco, Jaime Cunha

2007-01-01

Among the many radiological findings seen in Rheumatoid Arthritis RA small subchondral geodes and erosions are typical. Large geodes are far less common abnormalities and their presence may indicate diagnostic and therapeutic difficulties. We present a case report of a 55-year old woman with seronegative RA that developed a large geode in the knee with extensive joint destruction.

Dendritic cells provide a potential link between smoking and inflammation in rheumatoid arthritis

PubMed Central

2012-01-01

smoking on inflamed rheumatoid synovial tissue involves activation of the AHR pathway. A subset of synovial DCs is important in the response to cigarette smoke. The potential for smoking to affect DC behaviour in joint tissues has relevance to both early and late phases of RA pathogenesis and warrants further investigation. PMID:23036591

Severity indices in rheumatoid arthritis: A systematic review.

PubMed

Toledano, Esther; García de Yébenes, M Jesús; González-Álvaro, Isidoro; Carmona, Loreto

2017-08-11

To identify tools designed to evaluate the severity of patients with rheumatoid arthritis (RA) in order to use them in the investigation of prognostic markers in early arthritis. We conducted a systematic review of studies that developed/validated an index for RA disease severity. They were analyzed using the COSMIN checklist to assess their methodological quality. In addition, all the variables included were evaluated for their clarity of definition, feasibility and probability of being present in each outcome during the first 2 years of the disease course. To estimate redundancy, variables were grouped by domains. After reviewing 3,519 articles, 3 studies were included. The first study, the PAS, assessed whether current and lifetime treatment with disease-modifying antirheumatic drugs and/or biologics accurately predicted RA severity, as measured by the patient-reported PAS. Treatment variables did not fully distinguish patients in the highest and lowest quartiles of PAS scores. Another severity index, the Claims-Based Index for RA Severity (CIRAS), included the variables age, sex, Felty's syndrome, number of rehabilitation and rheumatology visits, test for inflammatory markers, number of chemistry panels/platelet counts ordered and rheumatoid factor test. The correlation was low (r=0.56) with an index previously validated by the same research group, the RA medical records-based index of severity (RARBIS), with Disease Activity Score-C-reactive protein (DAS28-PCR) (r=0.07) and Multidimensional Health Assessment Questionnaire (MD-HAQ) (r=0.008). Finally, the RARBIS, used to validate the CIRAS, was devised as an RA severity index based on medical records. It includes as domains surgery, radiology, extra-articular manifestations, clinical and laboratory variables, previously chosen by an expert panel. RARBIS had a weak correlation with treatment intensity (r=0.35) and with DAS28 (r=0.41). There is no index to assess the severity of RA based on the course of the

Periodontal disease and rheumatoid arthritis: the evidence accumulates for complex pathobiologic interactions

PubMed Central

Bingham, Clifton O.; Moni, Malini

2015-01-01

Purpose of review This review was conducted to focus on the recent clinical and translational research related to the associations between periodontal disease and rheumatoid arthritis. Recent findings There is a growing interest in the associations between oral health and autoimmune and inflammatory diseases. A number of epidemiologic studies have described associations between rheumatoid arthritis and periodontal disease. Recent clinical studies continue to support these reports, and are increasingly linked with biological assessments to better understand the nature of these relationships. A number of recent studies have evaluated the periopathogenic roles of Porphyromonas gingivalis, the oral microbiome, and mechanisms of site-specific and substrate-specific citrullination. These are helping to further elucidate the interactions between these two inflammatory disease processes. Summary Studies of clinical oral health parameters, the gingival microenvironment, autoantibodies and biomarkers, and rheumatoid arthritis disease activity measures are providing a better understanding of the potential mechanisms responsible for rheumatoid arthritis and periodontal disease associations. The cumulative results and ongoing studies have the promise to identify novel mechanisms and interventional strategies to improve patient outcomes for both conditions. PMID:23455329

The glutathione defense system in the pathogenesis of rheumatoid arthritis.

PubMed

Hassan, M Q; Hadi, R A; Al-Rawi, Z S; Padron, V A; Stohs, S J

2001-01-01

In order to assess a possible role of the natural glutathione defense system in the pathogenesis of rheumatoid arthritis (RA), serum reduced glutathione levels (GSH), glutathione reductase (GSR), glutathione S-transferase (GST), glutathione peroxidase (GSH-Px) and alkaline phosphatase (ALP) activities, lipid peroxidation (MDA content) and indexes of inflammation were evaluated in 58 rheumatic patients. Rheumatoid athritis was associated with significant depletion (ca. 50%) in GSH levels compared with normal control subjects. Serum levels of the detoxifying enzymes GSR and GSH-Px decreased by ca. 50% and 45%, respectively, whereas a threefold increase in the activity of GST was observed. A 1.2-fold increase in ALP was observed in patients with RA. These effects were accompanied by a 3.1-fold increase in serum MDA content. The MDA content was higher in RA patients who were seropositive for rheumatoid factor as well as positive for C-reactive proteins. The erythrocyte sedimentation rate for all patients with RA was approximately 13.8-fold higher than for the control group, and was higher among RA patients who were positive for C-reactive proteins and exhibited seropositivity for rheumatoid factor. Patients with RA receiving gold therapy exhibited significantly lower MDA levels whereas all other factors that were measured were not effected. The results support a hypothesis that defense mechanisms against reactive oxygen species are impaired in RA. Copyright 2001 John Wiley & Sons, Ltd.

Anticitrullinated protein antibodies and rheumatoid factor are associated with increased mortality but with different causes of death in patients with rheumatoid arthritis: a longitudinal study in three European cohorts.

PubMed

Ajeganova, S; Humphreys, J H; Verheul, M K; van Steenbergen, H W; van Nies, J A B; Hafström, I; Svensson, B; Huizinga, T W J; Trouw, L A; Verstappen, S M M; van der Helm-van Mil, A H M

2016-11-01

Patients with rheumatoid arthritis (RA)-related autoantibodies have an increased mortality rate. Different autoantibodies are frequently co-occurring and it is unclear which autoantibodies associate with increased mortality. In addition, association with different causes of death is thus far unexplored. Both questions were addressed in three early RA populations. 2331 patients with early RA included in Better Anti-Rheumatic Farmaco-Therapy cohort (BARFOT) (n=805), Norfolk Arthritis Register (NOAR) (n=678) and Leiden Early Arthritis Clinic cohort (EAC) (n=848) were studied. The presence of anticitrullinated protein antibodies (ACPA), rheumatoid factor (RF) and anticarbamylated protein (anti-CarP) antibodies was studied in relation to all-cause and cause-specific mortality, obtained from national death registers. Cox proportional hazards regression models (adjusted for age, sex, smoking and inclusion year) were constructed per cohort; data were combined in inverse-weighted meta-analyses. During 26 300 person-years of observation, 29% of BARFOT patients, 30% of NOAR and 18% of EAC patients died, corresponding to mortality rates of 24.9, 21.0 and 20.8 per 1000 person-years. The HR for all-cause mortality (95% CI) was 1.48 (1.22 to 1.79) for ACPA, 1.47 (1.22 to 1.78) for RF and 1.33 (1.11 to 1.60) for anti-CarP. When including all three antibodies in one model, RF was associated with all-cause mortality independent of other autoantibodies, HR 1.30 (1.04 to 1.63). When subsequently stratifying for death cause, ACPA positivity associated with increased cardiovascular death, HR 1.52 (1.04 to 2.21), and RF with increased neoplasm-related death, HR 1.64 (1.02 to 2.62), and respiratory disease-related death, HR 1.71 (1.01 to 2.88). The presence of RF in patients with RA associates with an increased overall mortality rate. Cause-specific mortality rates differed between autoantibodies: ACPA associates with increased cardiovascular death and RF with death related to neoplasm

Autoantibodies to two novel peptides in seronegative and early rheumatoid arthritis.

PubMed

De Winter, Liesbeth M; Hansen, Wendy L J; van Steenbergen, Hanna W; Geusens, Piet; Lenaerts, Jan; Somers, Klaartje; Stinissen, Piet; van der Helm-van Mil, Annette H M; Somers, Veerle

2016-08-01

Despite recent progress in biomarker discovery for RA diagnostics, still over one-third of RA patients-and even more in early disease-present without RF or ACPA. The aim of this study was to confirm the presence of previously identified autoantibodies to novel Hasselt University (UH) peptides in early and seronegative RA. Screening for antibodies against novel UH peptides UH-RA.1, UH-RA.9, UH-RA.14 and UH-RA.21, was performed in two large independent cohorts. Peptide ELISAs were developed to screen for the presence of antibodies to UH-RA peptides. First, 292 RA patients (including 39 early patients), 90 rheumatic and 97 healthy controls from UH were studied. Antibody reactivity to two peptides (UH-RA.1 and UH-RA.21) was also evaluated in 600 RA patients, 309 patients with undifferentiated arthritis and 157 rheumatic controls from the Leiden Early Arthritis Clinic cohort. In both cohorts, 38% of RA patients were seronegative for RF and ACPA. Testing for autoantibodies to UH-RA.1 and UH-RA.21 reduced the serological gap from 38% to 29% in the UH cohort (P = 0.03) and from 38% to 32% in the Leiden Early Arthritis Clinic cohort (P = 0.01). Furthermore, 19-33% of early RA patients carried antibodies to these peptides. Specificities in rheumatic controls ranged from 82 to 96%. Whereas antibodies against UH-RA.1 were related to remission, anti-UH-RA.21 antibodies were associated with inflammation, joint erosion and higher tender and swollen joint counts. This study validates the presence of antibody reactivity to novel UH-RA peptides in seronegative and early RA. This might reinforce current diagnostics and improve early diagnosis and intervention in RA. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Workplace impacts of anti-TNF therapies in rheumatoid arthritis: review of the literature.

PubMed

Birnbaum, Howard; Shi, Lizheng; Pike, Crystal; Kaufman, Rebecca; Sun, Peter; Cifaldi, Mary

2009-02-01

Rheumatoid arthritis (RA) causes pain and serious functional impacts and substantially affects patients' daily lives, including their ability to work. This review examines recent studies of patients with RA treated with TNF antagonists and the impacts these therapies have on the workplace. A total of 133 articles and 14 poster abstracts were reviewed that matched specific criteria. The results of early studies of TNF antagonists varied regarding their effects on patients with RA in the workplace. However, recent studies of adalimumab showed positive impacts across a range of workplace burdens. Treatments such as adalimumab may help employees with RA to remain in the workforce and lead to reduced workplace costs to the employers and employees.

Is remitting seronegative symmetrical synovitis with pitting edema (RS3PE) a subset of rheumatoid arthritis?

PubMed

Yao, Qingping; Su, Xiangqian; Altman, Roy D

2010-08-01

To contrast and compare the spectrum of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) with rheumatoid arthritis (RA) using an illustrative case. The relevant English literature of RS3PE was searched using the keywords "RS3PE" alone and in combination with terms such as neoplasia and rheumatic disease. Original and review articles were reviewed and the clinical setting was exemplified with a case report. RS3PE initially was reported to represent a form of RA. However, RS3PE has clinical features that are different from both early- and late-onset RA, such as lack of bony erosions and rheumatoid factor. RS3PE is thought to involve vascular endothelial growth factor, suggesting an infectious etiology, generally has an excellent prognosis, and is associated with neoplasia not commonly seen in RA, and the RA associated human leukocyte antigen (HLA) DRB1 genotype is absent. Based on the clinical, laboratory, suspected infectious etiology, genetic differences, and types of associated malignancies, RS3PE appears to be a distinct entity rather than a subset of RA. Copyright 2010 Elsevier Inc. All rights reserved.

Studying the Immunomodulatory Effects of Small Molecule Ras-Inhibitors in Animal Models of Rheumatoid Arthritis

DTIC Science & Technology

2015-10-01

Studying the Immunomodulatory Effects of Small Molecule Ras-Inhibitors in Animal Models of Rheumatoid Arthritis 5a. CONTRACT NUMBER 5b. GRANT NUMBER...Importantly, T cells from patients with Rheumatoid Arthritis (RA) display augmented activation of the Ras/Raf/MEK/ERK1/2 signaling pathway, and...analysis. The proposed project is highly relevant to the FY13 PRMRP topic area of Rheumatoid Arthritis (RA). The short-term impact of our research will

Early Remission Is a Realistic Target in a Majority of Patients with DMARD-naive Rheumatoid Arthritis.

PubMed

Rannio, Tuomas; Asikainen, Juha; Kokko, Arto; Hannonen, Pekka; Sokka, Tuulikki

2016-04-01

We analyzed remission rates at 3 and 12 months in patients with rheumatoid arthritis (RA) who were naive for disease-modifying antirheumatic drugs (DMARD) and who were treated in a Finnish rheumatology clinic from 2008 to 2011. We compared remission rates and drug treatments between patients with RA and patients with undifferentiated arthritis (UA). Data from all DMARD-naive RA and UA patients from the healthcare district were collected using software that includes demographic and clinical characteristics, disease activity, medications, and patient-reported outcomes. Our rheumatology clinic applies the treat-to-target principle, electronic monitoring of patients, and multidisciplinary care. Out of 409 patients, 406 had data for classification by the 2010 RA criteria of the American College of Rheumatology/European League Against Rheumatism. A total of 68% were female, and mean age (SD) was 58 (16) years. Respectively, 56%, 60%, and 68% were positive for anticyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), and RF/anti-CCP, and 19% had erosive disease. The median (interquartile range) duration of symptoms was 6 (4-12) months. A total of 310 were classified as RA and 96 as UA. The patients with UA were younger, had better functional status and lower disease activity, and were more often seronegative than the patients with RA. The 28-joint Disease Activity Score (3 variables) remission rates of RA and UA patients at 3 months were 67% and 58% (p = 0.13), and at 12 months, 71% and 79%, respectively (p = 0.16). Sustained remission was observed in 57%/56% of RA/UA patients. Patients with RA used more conventional synthetic DMARD combinations than did patients with UA. None used biological DMARD at 3 months, and only 2.7%/1.1% of the patients (RA/UA) used them at 12 months (p = 0.36). Remarkably high remission rates are achievable in real-world DMARD-naive patients with RA or UA.

Early Changes of the Cortical Micro-Channel System in the Bare Area of the Joints of Patients With Rheumatoid Arthritis.

PubMed

Werner, David; Simon, David; Englbrecht, Matthias; Stemmler, Fabian; Simon, Christoph; Berlin, Andreas; Haschka, Judith; Renner, Nina; Buder, Thomas; Engelke, Klaus; Hueber, Axel J; Rech, Jürgen; Schett, Georg; Kleyer, Arnd

2017-08-01

To characterize the specific structural properties of the erosion-prone bare area of the human joint, and to search for early microstructural changes in this region during rheumatoid arthritis (RA). In the initial part of the study, human cadaveric hand joints were examined for exact localization of the bare area of the metacarpal heads, followed by detection of cortical micro-channels (CoMiCs) in this region by high-resolution peripheral quantitative computed tomography (HR-pQCT) and, after anatomic dissection, validation of the presence of CoMiCs by micro-computed tomography (micro-CT). In the second part of the study, the number and distribution of CoMiCs were analyzed in 107 RA patients compared to 105 healthy individuals of similar age and sex distribution. Investigation by HR-pQCT combined with adaptive thresholding allowed the detection of CoMiCs in the bare area of human cadaveric joints. The existence of CoMiCs in the bare area was additionally validated by micro-CT. In healthy individuals, the number of CoMiCs increased with age. RA patients showed significantly more CoMiCs compared to healthy individuals (mean ± SD 112.9 ± 54.7/joint versus 75.2 ± 41.9/joint; P < 0.001), with 20-49-year-old RA patients exhibiting similar numbers of CoMiCs as observed in healthy individuals older than age 65 years. Importantly, CoMiCs were already found in RA patients very early in their disease course, with enrichment in the erosion-prone radial side of the joint. CoMiCs represent a new form of structural change in the joints of patients with RA. Although the number of CoMiCs increases with age, RA patients develop CoMiCs much earlier in life, and such changes can even occur at the onset of the disease. CoMiCs therefore represent an interesting new opportunity to assess structural changes in RA. © 2017, American College of Rheumatology.

Once-daily treatment of rheumatoid arthritis with choline magnesium trisalicylate.

PubMed

Mann, C C; Boyer, J T

1984-01-01

A pilot study evaluated once-daily treatment of rheumatoid arthritis with choline magnesium trisalicylate (CMT) in patients diagnosed as having classical or definite rheumatoid arthritis, with morning stiffness as a major complaint. Twenty patients were selected who, in an earlier phase of the study, had found twice-daily treatment with CMT effective and tolerable. Efficacy was evaluated in 15 of these patients and safety was evaluated in all 20. Comparisons were made with the twice-daily regimen and with previous nonsteroidal anti-inflammatory drug (NSAID) therapy. Changes in clinical indicators (numbers of painful and swollen joints and the duration of morning stiffness) showed that once-daily treatment with CMT was as effective as twice-daily treatment with CMT or as treatment with other prior NSAIDs in controlling signs and symptoms of rheumatoid arthritis. Side effects in both the twice-daily and the once-daily treatment regimens were similar in incidence and nature.

Epidemiological evaluation quality of life in patients suffering from early rheumatoid arthritis: a pragmatic, prospective, randomized, blind allocation controlled of a modular program group intervention.

PubMed

Yousefi, Hadi; Chopra, Arvind; Farrokhseresht, Reza; Sarmukaddam, Sanjeev; Noghabi, Fariba Asadi; Bedekar, Nilima; Madani, Abdolhosain

2015-01-01

Epidemiology has taken on new roles in the management of health care services. In this study, we developed a non-pharmacological self-management modular program group intervention and evaluated its efficacy as an adjunct therapy in patients suffering from early rheumatoid arthritis (RA). Patients were randomized to either participate in a non-equivalent intervention group along with the standard of care or only receive standard-of-care treatment at a community rheumatology center. The outcomes measured were a pain visual analog scale (VAS), patient general health (GH) on a VAS, and the Short Form 36 Health Survey version 2 scale measuring quality of life. These parameters were evaluated in the first week to obtain baseline values, and at 20, 32, 48, and 60 weeks to evaluate the efficacy of the intervention group. The patients were randomized, with 100 patients in the intervention group and 106 in the control group. The intervention and control groups were similar with regard to the percentage of women (86% vs. 89.6%), tobacco usage (25% vs. 19.8%), mean age (42.6±13.2 years vs. 46.6±10.9 years), and disease duration (15.3±6.7 months vs. 14.5±6.6 months). The mean outcomes were significantly different between the two groups, and post-hoc pairwise analysis demonstrated significant deterioration in the control group in contrast to improvement in the intervention group at the second, third, fourth, and fifth evaluations. Improvements were often seen as early as the 12-week and 24-week follow-up visits. Epidemiology contributes to the evaluation of how well specific therapies or other health interventions prevent or control health problems. The modular program group intervention implemented in this study appears to be a suitable and feasible method to facilitate much more comprehensive management of early RA in socioeconomically challenged communities.

Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kitahara, Kanako; Department of Immunology, Toho University School of Medicine, Tokyo; Kusunoki, Natsuko

The adipokines are linked not only to metabolic regulation, but also to immune responses. Adiponectin, but not leptin or resistin induced interleukin-8 production from rheumatoid synovial fibroblasts (RSF). The culture supernatant of RSF treated with adiponectin induced chemotaxis, although adiponectin itself had no such effect. Addition of antibody against adiponectin, and inhibition of adiponectin receptor gene decreased adiponectin-induced IL-8 production. Nuclear translocation of nuclear factor-kappa B was increased by adiponectin. The induction of interleukin-8 was inhibited by mitogen-activated protein kinase inhibitors. These findings suggest that adiponectin contributes to the pathogenesis of rheumatoid arthritis.

Benefits of Exercise in Rheumatoid Arthritis

PubMed Central

Cooney, Jennifer K.; Law, Rebecca-Jane; Matschke, Verena; Lemmey, Andrew B.; Moore, Jonathan P.; Ahmad, Yasmeen; Jones, Jeremy G.; Maddison, Peter; Thom, Jeanette M.

2011-01-01

This paper aims to highlight the importance of exercise in patients with rheumatoid arthritis (RA) and to demonstrate the multitude of beneficial effects that properly designed exercise training has in this population. RA is a chronic, systemic, autoimmune disease characterised by decrements to joint health including joint pain and inflammation, fatigue, increased incidence and progression of cardiovascular disease, and accelerated loss of muscle mass, that is, “rheumatoid cachexia”. These factors contribute to functional limitation, disability, comorbidities, and reduced quality of life. Exercise training for RA patients has been shown to be efficacious in reversing cachexia and substantially improving function without exacerbating disease activity and is likely to reduce cardiovascular risk. Thus, all RA patients should be encouraged to include aerobic and resistance exercise training as part of routine care. Understanding the perceptions of RA patients and health professionals to exercise is key to patients initiating and adhering to effective exercise training. PMID:21403833

Early rheumatoid arthritis 6 years after diagnosis is still associated with high direct costs and increasing loss of productivity: the Swedish TIRA project.

PubMed

Hallert, E; Husberg, M; Kalkan, A; Skogh, T; Bernfort, L

2014-01-01

To calculate total costs over 6 years after diagnosis of early rheumatoid arthritis (RA). In the longitudinal prospective multicentre TIRA study, 239 patients from seven units, diagnosed in 1996-98, reported regularly on health-care utilization and the number of days lost from work. Costs were obtained from official databases and calculated using unit costs (Swedish kronor, SEK) from 2001. Indirect costs were calculated using the human capital approach (HCA). Costs were inflation adjusted to Euro June 2012, using the Swedish Consumer Price Index and the exchange rate of June 2012. Statistical analyses were based on linear mixed models (LMMs) for changes over time. The mean total cost per patient was EUR 14,768 in year 1, increasing to EUR 18,438 in year 6. Outpatient visits and hospitalization decreased but costs for surgery increased from EUR 92/patient in year 1 to EUR 444/patient in year 6. Drug costs increased from EUR 429/patient to EUR 2214/patient, mainly because of the introduction of biologics. In year 1, drugs made up for 10% of direct costs, and increased to 49% in year 6. Sick leave decreased during the first years but disability pensions increased, resulting in unchanged indirect costs. Over the following years, disability pensions increased further and indirect costs increased from EUR 10,284 in year 1 to EUR 13,874 in year 6. LMM analyses showed that indirect costs were unchanged whereas direct costs, after an initial fall, increased over the following years, leading to increasing total costs. In the 6 years after diagnosis of early RA, drug costs were partially offset by decreasing outpatient visits but indirect costs remained unchanged and total costs increased.

Rheumatoid Arthritis and Complementary Medicine: In Depth

MedlinePlus

... Rheumatology International . 2010;30(5):571–586. Setty AR, Sigal LH. Herbal medications commonly used in the ... 4):185–192. Balneotherapy Anain JM Jr, Bojrab AR, Rhinehart FC. Conservative treatments for rheumatoid arthritis in ...

Gage for evaluating rheumatoid hands

NASA Technical Reports Server (NTRS)

Houge, J. C.; Plautz, K. A.

1981-01-01

Two-axis goniometer accurately measures movements of fingers about knuckle joints, diagnosing hands structurally changed by rheumatoid arthritis. Instrument measures lateral movement which is small in normal knuckles but increased in diseased joints. Goniometer is two connected protractors that simultaneously measure angles in perpindicular planes. Dials are offset to clear bony protuberances; extension and offset adjustments span any hand size.

The impact of rheumatoid arthritis on the burden of disease in urban China.

PubMed

Langley, Paul C; Mu, Rong; Wu, Michael; Dong, Peng; Tang, Boxiong

2011-01-01

The aim of this study is to assess the burden of disease associated with the impact of rheumatoid arthritis in urban China. Burden of disease is considered from four perspectives: (i) health-related quality-of-life (HRQoL); (ii) health status; (iii) employment status; and (iv) absenteeism and presenteeism. Data are from the 2009 National Health and Wellness Survey (NHWS) of urban China. This is an internet-based survey and details the health experience of 13,007 respondents. The survey is representative of the urban China population at 18 years of age and over (18.1% of the total population). Of those responding to the survey, a total of 353 reported that they had been diagnosed with rheumatoid arthritis--an unweighted estimate of 2.65%. The sample design allows a comparison of those reporting rheumatoid arthritis with those not reporting this disease and, hence, a quantitative assessment of the burden of disease. Estimates of the quantitative impact of the presence of rheumatoid arthritis are through a series of generalized linear regression models. HRQoL is evaluated through the SF-12 instrument together with responses to the first item of the SF-12, self-reported health status. The SF-12 instrument generates three measures of HRQoL: the physical component summary (PCS), the mental component summary (MCS) and SF-6D utilities. Health status is captured as a self-report on a 5-point scale. Employment status is considered in terms of self-reported labor force participation, while absenteeism and presenteeism are estimated from the Work Productivity Activity Index (WPAI). Apart from a binary variable capturing the presence or absence of rheumatoid arthritis, control variables were included to capture the impact of other potential determinants of HRQoL and health status. The presence of rheumatoid arthritis in urban China has a significant deficit impact on HRQoL as measured by the PCS and MCS components of the SF-12, SF-6D absolute utilities and on self

Efficacy of tocilizumab on MRI-determined bone oedema in rheumatoid arthritis.

PubMed

Bensaoud, Nada; Rostom, Samira; Bahiri, Rachid; Hajjaj-Hassouni, Najia

2015-06-01

The aim of this study was to assess the impact of tocilizumab on bone oedema in rheumatoid arthritis (RA) as shown by magnetic resonance imaging (MRI). In this longitudinal study, patients with rheumatoid arthritis according to the American College of Rheumatology (ACR) 2009 criteria with inadequate response or intolerance to disease-modifying anti-rheumatic drugs (DMARDs), treated with tocilizumab, were included. Sociodemographic characteristics and clinical and laboratory data for the disease were collected at baseline (M0) and 06 months (M6) of treatment. Disease activity was assessed using disease activity score in 28 joints (DAS28), simplified disease activity index (SDAI) and clinical disease activity index (CDAI). MRI of the dominant hand was performed at baseline and M6 of treatment. The primary outcome measure was the assessment of bone oedema by rheumatoid arthritis MRI scoring system (RAMRIS) bone oedema. Secondary outcomes included RAMRIS synovitis, DAS28, C-reactive protein (CRP) and SDAI at baseline and M6. Twenty-two patients with RA were included, 19 females (86.4 %), with a mean of age 42 ± 13.7. The mean disease duration was 8 ± 5.2 years. The mean DAS28 was 5.78 ± 0.87. The median CRP was 16 mg/l (6.7 to 36.3). The average SDAI was 90 ± 34. Three patients were excluded from the study for serious side effects. At baseline, bone oedema was present in 41 % of patients (N = 9), with a median bone oedema RAMRIS 0 (0 to 7.2). At M6, bone oedema decreased or disappeared in 32 % (N = 7) with a significant improvement in the RAMRIS bone oedema score (p = 0.04). Moreover, there is a significant improvement in RAMRIS synovitis (p < 0.0001) as well as in activity parameters: DAS28 (p < 0.0001), CRP (p < 0.0001) and SDAI (p < 0.0001). This study suggests that tocilizumab is associated with a significant improvement on MRI-determined bone oedema in the short term. This improvement in bone oedema is correlated

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

PubMed

Martin, Naomi H; Ibrahim, Fowzia; Tom, Brian; Galloway, James; Wailoo, Allan; Tosh, Jonathan; Lempp, Heidi; Prothero, Louise; Georgopoulou, Sofia; Sturt, Jackie; Scott, David L

2017-12-08

Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen

The impact of dietary habits on the pathogenesis of rheumatoid arthritis: a case-control study.

PubMed

Rambod, Masoume; Nazarinia, Mohammadali; Raieskarimian, Farahnaz

2018-05-22

It has not been clear what kinds and how much nutrients could be harmful, preventive, or healthful for development of rheumatoid arthritis. This study aimed to determine the impact of dietary habits on the pathogenesis of rheumatoid arthritis. This case-control study was conducted on a total of 500 rheumatoid arthritis patients and 500 healthy controls refereed to three clinics of Shiraz University of Medical Sciences in 2015-2016. Convenience sampling was used for data collection in both case and control groups. An approved valid and reliable questionnaire including information about the intake of different kinds of beverages, and nutritious and non-nutritious diet was used. Data were analyzed by SPSS, version 20, using t test, chi-square and Multiple Logistic Regression model. The associations between rheumatoid arthritis development and variables including drinking 1-7 cups of coffee (OR = .44, CI .25-.76), ≥ 8 cups of coffee (OR = .50, CI .28-.90), full-fat milk (OR = 1.01, CI 1.003-1.03) per month, and intake of green tea (OR = .65, CI .45-.93) and solid oils (OR = 2.29, CI:1.57-3.34) were significant. Based on the findings, coffee consumption more than one cup per month and green tea might have preventive effects on developing rheumatoid arthritis. On the other hand, patients who consumed more full-fat milk per month and solid oil might be at risk of development of rheumatoid arthritis. Therefore, modification of diet based on these findings is suggested. Performing a cohort study to determine the causality effect of dietary habits and development and prevention of rheumatoid arthritis is recommended.

Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms.

PubMed

Paulin, Francisco; Doyle, Tracy J; Fletcher, Elaine A; Ascherman, Dana P; Rosas, Ivan O

2015-01-01

The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

The effects of the Mediterranean diet on rheumatoid arthritis prevention and treatment: a systematic review of human prospective studies.

PubMed

Forsyth, Casuarina; Kouvari, Matina; D'Cunha, Nathan M; Georgousopoulou, Ekavi N; Panagiotakos, Demosthenes B; Mellor, Duane D; Kellett, Jane; Naumovski, Nenad

2018-05-01

Rheumatoid arthritis is a progressive autoimmune disease characterised by severely swollen and painful joints. To compliment pharmacotherapy, people living with rheumatoid arthritis often turn to dietary interventions such as the Mediterranean diet. The aim of the present systematic review is to discuss the effects of the Mediterranean diet on the management and prevention of rheumatoid arthritis in human prospective studies. Four studies met the inclusion criteria, including two intervention studies reporting improvement in the pain visual analogue scale (p < 0.05) and a decrease in the health assessment questionnaire for rheumatoid arthritis score (p < 0.05) in the Mediterranean diet groups. Only one study reported a reduction in the 28 joint count disease activity score for rheumatoid arthritis for the Mediterranean diet group (p < 0.05). This review has identified beneficial effects of the Mediterranean diet in reducing pain and increasing physical function in people living with rheumatoid arthritis. However, there is currently insufficient evidence to support widespread recommendation of the Mediterranean diet for prevention of rheumatoid arthritis.

Vocational Rehabilitation for Persons with Rheumatoid Arthritis.

ERIC Educational Resources Information Center

Allaire, Saralynn H.

1998-01-01

Useful vocational rehabilitation strategies for persons with rheumatoid arthritis include (1) management of symptoms and reduction of energy demand; (2) reasonable job accommodations; (3) identification of suitable jobs and necessary training; and (4) enhancement of self-advocacy skills. (SK)

Outcome of Joint-Preserving Arthroplasty for Rheumatoid Forefoot Deformities.

PubMed

Fukushi, Jun-ichi; Nakashima, Yasuharu; Okazaki, Ken; Yamada, Hisakata; Mawatari, Taro; Ohishi, Masanobu; Oyamada, Akiko; Akasaki, Yukio; Iwamoto, Yukihide

2016-03-01

Along with the recent advances in the pharmacological management of rheumatoid arthritis, there is a trend toward the use of joint-preserving surgery in the treatment of rheumatoid forefoot deformities. However, the clinical outcomes of joint-preserving surgery for rheumatoid forefoot deformities have not been assessed in comparison to resection arthroplasty. We retrospectively evaluated 23 feet in 17 patients with rheumatoid forefoot deformities who underwent surgery between January 2010 and December 2013. The patients included 1 male (1 foot) and 16 females (22 feet), with a mean age of 62 years. The mean length of follow-up was 28 months. The patients were treated by 3 surgeons. One surgeon performed joint-preserving procedures (JP group) to the feet in which (1) no pain with motion existed, and (2) the range of motion in the first metatarsophalangeal (MTP) joint was greater than 30 degrees (n = 10); otherwise, resection arthroplasty with arthrodesis of the first MTP joint was performed (n = 3). The other surgeons performed resection arthroplasty in all cases (n = 10) (RA group, n = 13 in total). The clinical outcomes of the patients were evaluated using the Japanese Society for Surgery of the Foot (JSSF) hallux and lesser toe scales. There were no significant differences in the preoperative total JSSF scores for either the hallux (54.5 and 61.4 points) or the lesser toe (45.2 and 57.4 points) between the RA and JP groups, respectively. Postoperatively, the total JSSF scores for both the hallux (79.4 and 88.2 points) and lesser toes (73.6 and 87.7 points) showed significant improvement in both the RA and JP groups, respectively; however, the JP group showed a greater postoperative improvement. The scores relating to the function category on the hallux scale and the alignment category on the lesser toe scale were significantly higher in the JP group. With regard to the function of the hallux and the alignment of the lesser toes, the joint-preserving procedures

Rheumatoid arthritis in an urban South African Negro population.

PubMed Central

Solomon, L; Robin, G; Valkenburg, H A

1975-01-01

(1) An epidemiological study of an urban South African Negro community has been carried out in Johannesburg. Altogether 964 respondents were examined and in each case radiographs of the hands and feet were obtained. Rheumatoid factor tests were carried out on 404 serum samples. (2) Rheumatoid arthritis (RA) was graded 'definite' or 'probable' on the basis of a modification of the Rome criteria (Kellgren, Jeffrey, and Ball, 1963a). (3) In marked contrast to the findings in rural Africans the prevalence of RA in this community was similar to that in Caucasian populations. Five respondents (all elderly women) had 'definite' RA, giving a prevalence of 1.4% of the females and 0.9% of the total population sample over 15 years old. The prevalence of 'definite' and 'probable' RA combined was 2.6% for males, 3.7% for females, and 3.3% for all individuals over 15 years old. Prevalence increased with age, reaching a maximum in the 65- to 74-year cohort. (4) The form and severity of the clinical and radiological features were unlike the mild manifestations seen in rural African peoples and closely resembled the usual clinical picture of rheumatoid disease. (5) The latex fixation test was positive in 12.1% of the sera tested, which is similar to the high titres found in other African populations. No obvious cause for this phenomenon was found. (6) Several reasons for the marked difference in prevalence of RA between this urban African population and a rural African population are considered. Marked intraracial differences such as this point to the importance of sociological and environmental factors in the pathogenesis of rheumatoid arthritis. PMID:1137439

Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis

PubMed Central

Zhao, Xiaoyan; Okeke, Nwora Lance; Sharpe, Orr; Batliwalla, Franak M; Lee, Annette T; Ho, Peggy P; Tomooka, Beren H; Gregersen, Peter K; Robinson, William H

2008-01-01

Introduction There is increasing evidence that autoantibodies and immune complexes (ICs) contribute to synovitis in rheumatoid arthritis (RA), yet the autoantigens incorporated in ICs in RA remain incompletely characterised. Methods We used the C1q protein to capture ICs from plasma derived from human RA and control patients. Antibodies specific for immunoglobulin were used to detect ICs, and fibrinogen antibodies were used to detect fibrinogen-containing ICs. RA and control plasma were separated by liquid chromatography, and fractions then characterised by ELISA, immunoblotting and mass spectrometry. Immunohistochemical staining was performed on rheumatoid synovial tissue. Results C1q-immunoassays demonstrated increased levels of IgG (p = 0.01) and IgM (p = 0.0002) ICs in plasma derived from RA patients possessing anti-cyclic citrullinated peptide (CCP+) autoantibodies as compared with healthy controls. About one-half of the anti-CCP+ RA possessed circulating ICs containing fibrinogen (p = 0.0004). Fractionation of whole RA plasma revealed citrullinated fibrinogen in the high molecular weight fractions that contained ICs. Positive correlations were observed between fibrinogen-containing ICs and anti-citrullinated fibrinogen autoantibodies, anti-CCP antibody, rheumatoid factor and certain clinical characteristics. Immunohistochemical staining demonstrated co-localisation of fibrinogen, immunoglobulin and complement component C3 in RA pannus tissue. Mass spectrometry analysis of immune complexes immunoprecipitated from RA pannus tissue lysates demonstrated the presence of citrullinated fibrinogen. Conclusion Circulating ICs containing citrullinated fibrinogen are present in one-half of anti-CCP+ RA patients, and these ICs co-localise with C3 in the rheumatoid synovium suggesting that they contribute to synovitis in a subset of RA patients. PMID:18710572

Spleen and liver enlargement in a patient with rheumatoid arthritis.

PubMed

Bedoya, María Eugenia; Ceccato, Federico; Paira, Sergio

2015-01-01

We describe the case of a 51-year-old woman with a seropositive, erosive, and non-nodular rheumatoid arthritis of 15 year of evolution. The patient had poor compliance with medical visits and treatment. She came to the clinic with persistent pancytopenia and spleen and liver enlargement. Liver and bone marrow biopsies were carried out and amyloidosis, neoplasias and infections were ruled out. We discuss the differential diagnosis of pancytopenia and spleen and liver enlargement in a long-standing rheumatoid arthritis patient. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

The role of exercise in the management of rheumatoid arthritis.

PubMed

Metsios, George S; Stavropoulos-Kalinoglou, Antonis; Kitas, George D

2015-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with significant functional impairment and increased risk for cardiovascular disease. Along with pharmacological therapy, exercise seems to be a very promising intervention to improve disease-related outcomes, including functional ability and systemic manifestations, such as the increased cardiovascular risk. In this review, we discuss the physiological mechanisms by which exercise improves inflammation, cardiovascular risk and psychological health in patients with rheumatoid arthritis (RA) and describe in detail how exercise can be incorporated in the management of this disease using real examples from our clinical practice.

Knowledge and perception of cardiovascular disease risk among patients with rheumatoid arthritis.

PubMed

Boo, Sunjoo; Oh, Hyunjin; Froelicher, Erika S; Suh, Chang-Hee

2017-01-01

Patients with rheumatoid arthritis are at increased risk for cardiovascular disease. The prerequisites for reducing the risk of cardiovascular disease are adequate levels of knowledge and being aware of the risk. In this study, the levels of knowledge about cardiovascular disease among patients with rheumatoid arthritis and the perception were evaluated in relation to their actual 10-year risk of cardiovascular disease. This cross-sectional study of 200 patients with rheumatoid arthritis was conducted in a university-affiliated hospital in South Korea. The patients' actual risk of cardiovascular disease was estimated using the Framingham Risk Score. The most common risk factor was physical inactivity, with 77% of the patients not engaging in regular exercise. The patients lacked knowledge about the effects of physical inactivity and anti-inflammatory medication on the development of cardiovascular disease. Misperceptions about the risk of cardiovascular disease were common, i.e., 19.5% of the patients underestimated their risk and 41% overestimated. Hypertension, diabetes, obesity, and smoking were the most prevalent among the patients who underestimated their risk, and these same patients had the lowest level of knowledge about cardiovascular disease. This study demonstrated the rheumatoid arthritis patients' lack of knowledge about the effects of physical inactivity and anti-inflammatory medications on the development of cardiovascular disease, and their misperception of cardiovascular risk was common. As a preventive measure, educational programs about cardiovascular disease should be tailored specifically for patients with rheumatoid arthritis, and behavioral interventions, including routine exercise, should be made available at the time of diagnosis.

Improving healthcare consumer effectiveness: an Animated, Self-serve, Web-based Research Tool (ANSWER) for people with early rheumatoid arthritis.

PubMed

Li, Linda C; Adam, Paul; Townsend, Anne F; Stacey, Dawn; Lacaille, Diane; Cox, Susan; McGowan, Jessie; Tugwell, Peter; Sinclair, Gerri; Ho, Kendall; Backman, Catherine L

2009-08-20

People with rheumatoid arthritis (RA) should use DMARDs (disease-modifying anti-rheumatic drugs) within the first three months of symptoms in order to prevent irreversible joint damage. However, recent studies report the delay in DMARD use ranges from 6.5 months to 11.5 months in Canada. While most health service delivery interventions are designed to improve the family physician's ability to refer to a rheumatologist and prescribe treatments, relatively little has been done to improve the delivery of credible, relevant, and user-friendly information for individuals to make treatment decisions. To address this care gap, the Animated, Self-serve, Web-based Research Tool (ANSWER) will be developed and evaluated to assist people in making decisions about the use of methotrexate, a type of DMARD. The objectives of this project are: 1) to develop ANSWER for people with early RA; and 2) to assess the extent to which ANSWER reduces people's decisional conflict about the use of methotrexate, improves their knowledge about RA, and improves their skills of being 'effective healthcare consumers'. Consistent with the International Patient Decision Aid Standards, the development process of ANSWER will involve: 1.) creating a storyline and scripts based on the best evidence on the use of methotrexate and other management options in RA, and the contextual factors that affect a patient's decision to use a treatment as found in ERAHSE; 2.) using an interactive design methodology to create, test, analyze and refine the ANSWER prototype; 3.) testing the content and user interface with health professionals and patients; and 4.) conducting a pilot study with 51 patients, who are diagnosed with RA in the past 12 months, to assess the extent to which ANSWER improves the quality of their decisions, knowledge and skills in being effective consumers. We envision that the ANSWER will help accelerate the dissemination of knowledge and skills necessary for people with early RA to make informed

Organic brain syndrome in rheumatoid arthritis following corticosteroid withdrawal.

PubMed

Gupta, V P; Ehrlich, G E

1976-01-01

Six patients with seropositive nodule-forming rheumatoid arthritis developed severe central nervous system manifestations consistent with a diagnosis of organic brain syndrome. Organic brain syndrome occurred while 5 of these patients were undergoing corticosteroid withdrawal after prolonged administration. Neuropsychiatric symptoms rapidly cleared, responding to reinstitution of oral or parenteral corticosteroids in large doses in 4 patients, to increase in dosage in 1 patient, and to no drug therapy in the remaining 1. Marked reduction in rheumatoid factor in sera and demonstration of IgM deposits in the choroid plexus in 1 of the patients raised the possibility of immune complex-mediated central nervous system vasculitis.

Juggling identities of rheumatoid arthritis, motherhood and paid work - a grounded theory study.

PubMed

Feddersen, Helle; Mechlenborg Kristiansen, Tine; Tanggaard Andersen, Pernille; Hørslev-Petersen, Kim; Primdahl, Jette

2018-02-01

To explore how women with rheumatoid arthritis manage their illness, motherhood, and work life. A constructivist, grounded theory approach based on individual interviews and participant observations with 20 women with rheumatoid arthritis who participated in work life and had children living at home or were pregnant. After initial and focused coding Goffman's concepts of social identity were applied. A core category: "Juggling meaningful identities" and three conceptual categories were developed: (1) Work life as the strongest identity marker; (2) Motherhood: a two-sided act; (3) Living with rheumatoid arthritis as an identity? Paid work, motherhood, and illness are linked to the women's social identities. The women construct and change their identities in interactions with children, partners, other parents, colleagues, and employers. The women attribute the highest priority to their professional identity, spending the majority of their time and energy in an effort to appear as "good stable workers". The disease is seen as a hindrance in this regard, and the illness identity is almost completely rejected. In motherhood, the women prioritize close interaction with their children, and deprioritize external activities. Extended outbreaks of the disease and issues regarding the children force the women to deprioritize working life. Implications for rehabilitation Juggling meaningful identities of rheumatoid arthritis, motherhood, and paid work challenge women in managing their everyday lives. Therefore, rehabilitation professionals should support individuals to develop new strategies to manage the challenges they experience regarding juggling motherhood and work ability. Work is a dominant identity marker for women with rheumatoid arthritis therefore, rehabilitation professionals have an important role to play in investigating possible ways for the individual to maintain employment or return to work. Living with rheumatoid arthritis and being a paid worker challenge

Robust regression and posterior predictive simulation increase power to detect early bursts of trait evolution.

PubMed

Slater, Graham J; Pennell, Matthew W

2014-05-01

A central prediction of much theory on adaptive radiations is that traits should evolve rapidly during the early stages of a clade's history and subsequently slowdown in rate as niches become saturated--a so-called "Early Burst." Although a common pattern in the fossil record, evidence for early bursts of trait evolution in phylogenetic comparative data has been equivocal at best. We show here that this may not necessarily be due to the absence of this pattern in nature. Rather, commonly used methods to infer its presence perform poorly when when the strength of the burst--the rate at which phenotypic evolution declines--is small, and when some morphological convergence is present within the clade. We present two modifications to existing comparative methods that allow greater power to detect early bursts in simulated datasets. First, we develop posterior predictive simulation approaches and show that they outperform maximum likelihood approaches at identifying early bursts at moderate strength. Second, we use a robust regression procedure that allows for the identification and down-weighting of convergent taxa, leading to moderate increases in method performance. We demonstrate the utility and power of these approach by investigating the evolution of body size in cetaceans. Model fitting using maximum likelihood is equivocal with regards the mode of cetacean body size evolution. However, posterior predictive simulation combined with a robust node height test return low support for Brownian motion or rate shift models, but not the early burst model. While the jury is still out on whether early bursts are actually common in nature, our approach will hopefully facilitate more robust testing of this hypothesis. We advocate the adoption of similar posterior predictive approaches to improve the fit and to assess the adequacy of macroevolutionary models in general.

Aerobic Exercise Prescription for Rheumatoid Arthritics.

ERIC Educational Resources Information Center

Evans, Blanche W.; Williams, Hilda L.

The use of exercise as a general treatment for rheumatoid arthritics (RA) has included range of motion, muscular strength, water exercise and rest therapy while virtually ignoring possible benefits of aerobic exercise. The purposes of this project were to examine the guidelines for exercise prescription in relation to this special population and…

Antibody to the rheumatoid arthritis nuclear antigen. Its relationship to in vivo Epstein-Barr virus infection.

PubMed

Catalano, M A; Carson, D A; Niederman, J C; Feorino, P; Vaughan, J H

1980-05-01

Most patients with seropositive rheumatoid arthritis, and a variable but lesser percentage of normal subjects, have precipitating antibodies to a nuclear antigen, rheumatoid arthritis nuclear antigen, present in Epstein-Barr virus-infected human B lymphoblastoid cells. We have used a sensitive indirect immunofluorescence assay for antibody to rheumatoid arthritis nuclear antigen in a study of patients with infectious mononucleosis and healthy control subjects. Of 110 sera from normal, college-age cadets, 58 were from individuals without prior Epstein-Barr virus infection, as indicated by the lack of antibody to viral capsid antigen. All of these also lacked activity to rheumatoid arthritis nuclear antigen. 52 sera were positive for antibody to viral capsid antigen, and antibody to rheumatoid arthritis nuclear antigen was present in 26 (50%) of these. In 67 sequential sera from 11 college-age students with infectious mononucleosis who became positive for antibody to rheumatoid arthritis nuclear antigen, only 2 were positive during the 1 mo. Thereafter the incidence and titers increased progressively through the 1st yr after infection. This time-course resembled that for the development of antibody to Epstein-Barr nuclear antigen, another transformation antigen in Epstein-Barr virus-infected B lymphocytes. The development of positivity for both was much later than that of antibody to the structural viral capsid antigen, which in the current study was always positive by 1 wk. Thus, antibody to rheumatoid arthritis nuclear antigen is present in a large proportion of normal individuals and can now be clearly ascribed, from both in vivo and in vitro studies, to prior infection with Epstein-Barr virus.

Ratio of Circulating IFNγ (+) "Th17 Cells" in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project.

PubMed

Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

2016-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17(+)Th17 cells, and IFNγ (+)Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ (+)Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies.

Understanding emerging treatment paradigms in rheumatoid arthritis

PubMed Central

2011-01-01

Treatment strategies for rheumatoid arthritis (RA) will continue to evolve as new drugs are developed, as new data become available, and as our potential to achieve greater and more consistent outcomes becomes more routine. Many patients will find both symptom relief and modest control of their disease with disease-modifying antirheumatic drugs (DMARDs), yet this course of therapy is clearly not effective in all patients. In fact, despite strong evidence that intensive treatment in the early stages of RA can slow or stop disease progression and may prevent disability, many patients continue to be managed in a stepwise manner and are treated with an ongoing monotherapy regimen with DMARDs. There is now a large body of evidence demonstrating the success of treating RA patients with anti-TNF therapy, usually in combination with methotrexate. As a result of the increased use of anti-TNF therapy, treatment paradigms have changed – and our practice is beginning to reflect this change. In the present review, we summarize the salient points of several recently proposed and emerging treatment paradigms with an emphasis on how these strategies may impact future practice. PMID:21624182

Understanding emerging treatment paradigms in rheumatoid arthritis.

PubMed

Breedveld, Ferdinand C; Combe, Bernard

2011-05-25

Treatment strategies for rheumatoid arthritis (RA) will continue to evolve as new drugs are developed, as new data become available, and as our potential to achieve greater and more consistent outcomes becomes more routine. Many patients will find both symptom relief and modest control of their disease with disease-modifying antirheumatic drugs (DMARDs), yet this course of therapy is clearly not effective in all patients. In fact, despite strong evidence that intensive treatment in the early stages of RA can slow or stop disease progression and may prevent disability, many patients continue to be managed in a stepwise manner and are treated with an ongoing monotherapy regimen with DMARDs. There is now a large body of evidence demonstrating the success of treating RA patients with anti-TNF therapy, usually in combination with methotrexate. As a result of the increased use of anti-TNF therapy, treatment paradigms have changed - and our practice is beginning to reflect this change. In the present review, we summarize the salient points of several recently proposed and emerging treatment paradigms with an emphasis on how these strategies may impact future practice.

Effect of rocker shoes on pain, disability and activity limitation in patients with rheumatoid arthritis.

PubMed

Bagherzadeh Cham, Masumeh; Ghasemi, Mohammad Sadegh; Forogh, Bijan; Sanjari, Mohammad Ali; Zabihi Yeganeh, Mozdeh; Eshraghi, Arezoo

2014-08-01

Rheumatoid arthritis is a chronic inflammatory joint disease which affects the joints and soft tissues of the foot and ankle. Rocker shoes may be prescribed for the symptomatic foot in rheumatoid arthritis; however, there is a limited evidence base to support the use of rocker shoes in these patients. The aim of this study was to evaluate the effectiveness of heel-to-toe rocker shoes on pain, disability, and activity limitation in patients with rheumatoid arthritis. Clinical trial. Seventeen female patients with rheumatoid arthritis of 1 year or more duration, disease activity score of less than 2.6, and foot and ankle pain were recruited. Heel-to-toe rocker shoe was made according to each patient's foot size. All the patients were evaluated immediately, 7 and 30 days after their first visit. Foot Function Index values were recorded at each appointment. With the use of rocker shoes, Foot Function Index values decreased in all subscales. This reduction was noted in the first visit and was maintained throughout the trials. Rocker shoe can improve pain, disability, and activity limitation in patients with rheumatoid foot pain. All the subjects reported improved comfort levels. The results of this study showed that high-top, heel-to-toe rocker shoe with wide toe box was effective at reducing foot and ankle pain. It was also regarded as comfortable and acceptable footwear by the patients with rheumatoid foot problems. © The International Society for Prosthetics and Orthotics 2013.

Clinical and serological characteristics of Ecuadorian patients with rheumatoid arthritis

PubMed Central

Ríos, Carlos; Maldonado, Génessis; Paredes, Carlos; Ferro, Christian; Moreno, Mario; Vera, Claudia; Vargas, Sara; Calapaqui, Wendy; Vallejo, Carlos

2017-01-01

Background Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, wherein late diagnosis and treatment leads to deformities and disability. Objective The aim of the study was to assess and describe the clinical and immunological characteristics, activity status of the disease, and functional capacity in a cohort of Ecuadorian patients with RA. Methods This is a cross-sectional, descriptive study conducted on a population of patients with prediagnosed RA from public and private Ecuadorian rheumatology clinics. This study investigated 400 patients with a mean age of 50 years, 353 (82.25%) of which were female. Results The study showed that 44.3%, 83.5%, 60.3%, 41.8%, 37.5%, and 11.5% had an acute onset of the disease, symmetrical polyarthritis, morning stiffness exceeding 1 h, dry eyes, dry mouth, and rheumatoid nodules, respectively. A total of 89.7% presented with positive rheumatoid factor, and 96.5% were anti-citrullinated protein antibody positive. Conclusion This is the largest Ecuadorian cohort of patients with RA; clinical features are similar to those of other Latin American populations. PMID:28652830

Clinical and serological characteristics of Ecuadorian patients with rheumatoid arthritis.

PubMed

Ríos, Carlos; Maldonado, Génessis; Paredes, Carlos; Ferro, Christian; Moreno, Mario; Vera, Claudia; Vargas, Sara; Calapaqui, Wendy; Vallejo, Carlos

2017-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, wherein late diagnosis and treatment leads to deformities and disability. The aim of the study was to assess and describe the clinical and immunological characteristics, activity status of the disease, and functional capacity in a cohort of Ecuadorian patients with RA. This is a cross-sectional, descriptive study conducted on a population of patients with prediagnosed RA from public and private Ecuadorian rheumatology clinics. This study investigated 400 patients with a mean age of 50 years, 353 (82.25%) of which were female. The study showed that 44.3%, 83.5%, 60.3%, 41.8%, 37.5%, and 11.5% had an acute onset of the disease, symmetrical polyarthritis, morning stiffness exceeding 1 h, dry eyes, dry mouth, and rheumatoid nodules, respectively. A total of 89.7% presented with positive rheumatoid factor, and 96.5% were anti-citrullinated protein antibody positive. This is the largest Ecuadorian cohort of patients with RA; clinical features are similar to those of other Latin American populations.

Autoantibodies to Posttranslational Modifications in Rheumatoid Arthritis

PubMed Central

Burska, Agata N.; Hunt, Laura; Strollo, Rocky; Ryan, Brent J.; Vital, Ed; Nissim, Ahuva; Winyard, Paul G.; Emery, Paul; Ponchel, Frederique

2014-01-01

Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases (AIDs). Rheumatoid factor (RF) is known since the late 1930s to be associated with rheumatoid arthritis (RA). The discovery of anticitrullinated protein antibodies in the last century has changed this and other posttranslational modifications (PTM) relevant to RA have since been described. Such PTM introduce neoepitopes in proteins that can generate novel autoantibody specificities. The recent recognition of these novel specificities in RA provides a unique opportunity to understand human B-cell development in vivo. In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation. With the advancement of research methodologies it should be expected that other autoantibodies against PTM proteins could be discovered in patients with autoimmune diseases. Many of such autoantibodies may provide significant biomarker potential. PMID:24782594

Cartilage and bone damage in rheumatoid arthritis

PubMed Central

Maśliński, Włodzimierz; Prochorec-Sobieszek, Monika; Nieciecki, Michał; Sudoł-Szopińska, Iwona

2018-01-01

Rheumatoid arthritis (RA), which is a chronic inflammatory disease with a multifactorial aetiology, leads to partial or permanent disability in the majority of patients. It is characterised by persistent synovitis and formation of pannus, i.e. invasive synovial tissue, which ultimately leads to destruction of the cartilage, subchondral bone, and soft tissues of the affected joint. Moreover, inflammatory infiltrates in the subchondral bone, which can lead to inflammatory cysts and later erosions, play an important role in the pathogenesis of RA. These inflammatory infiltrates can be seen in magnetic resonance imaging (MRI) as bone marrow oedema (BME). BME is observed in 68–75% of patients in early stages of RA and is considered a precursor of rapid disease progression. The clinical significance of synovitis and bone marrow oedema as precursors of erosions is well established in daily practice, and synovitis, BME, cysts, hyaline cartilage defects and bone erosions can be detected by ultrasonography (US) and MRI. A less explored subject is the inflammatory and destructive potential of intra- and extra-articular fat tissue, which can also be evaluated in US and MRI. Finally, according to certain hypotheses, hyaline cartilage damage may trigger synovitis and lead to irreversible joint damage, and MRI may be used for preclinical detection of cartilage biochemical abnormalities. This review discusses the pathomechanisms that lead to articular cartilage and bone damage in RA, including erosion precursors such as synovitis and osteitis and panniculitis, as well as the role of imaging techniques employed to detect early cartilage damage and bone erosions. PMID:29853727

RAACFDb: Rheumatoid arthritis ayurvedic classical formulations database.

PubMed

Mohamed Thoufic Ali, A M; Agrawal, Aakash; Sajitha Lulu, S; Mohana Priya, A; Vino, S

2017-02-02

In the past years, the treatment of rheumatoid arthritis (RA) has undergone remarkable changes in all therapeutic modes. The present newfangled care in clinical research is to determine and to pick a new track for better treatment options for RA. Recent ethnopharmacological investigations revealed that traditional herbal remedies are the most preferred modality of complementary and alternative medicine (CAM). However, several ayurvedic modes of treatments and formulations for RA are not much studied and documented from Indian traditional system of medicine. Therefore, this directed us to develop an integrated database, RAACFDb (acronym: Rheumatoid Arthritis Ayurvedic Classical Formulations Database) by consolidating data from the repository of Vedic Samhita - The Ayurveda to retrieve the available formulations information easily. Literature data was gathered using several search engines and from ayurvedic practitioners for loading information in the database. In order to represent the collected information about classical ayurvedic formulations, an integrated database is constructed and implemented on a MySQL and PHP back-end. The database is supported by describing all the ayurvedic classical formulations for the treatment rheumatoid arthritis. It includes composition, usage, plant parts used, active ingredients present in the composition and their structures. The prime objective is to locate ayurvedic formulations proven to be quite successful and highly effective among the patients with reduced side effects. The database (freely available at www.beta.vit.ac.in/raacfdb/index.html) hopefully enables easy access for clinical researchers and students to discover novel leads with reduced side effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Understanding the information needs of women with rheumatoid arthritis concerning pregnancy, post-natal care and early parenting: A mixed-methods study.

PubMed

Ackerman, Ilana N; Jordan, Joanne E; Van Doornum, Sharon; Ricardo, Margaret; Briggs, Andrew M

2015-08-19

Although women with rheumatoid arthritis (RA) face a number of challenges in negotiating the journey to parenthood, no studies have explored the information needs of women with RA in relation to their childbearing years. This study aimed to determine the need for (and preferred mode/s of delivery of) information regarding pregnancy, post-natal care and early parenting among women with RA. Interviews and focus groups were conducted with 27 women with RA who were pregnant in the last 5 years, currently pregnant or planning pregnancy. Verbatim transcripts were analysed using both inductive and deductive approaches. Two validated instruments were used to quantify information needs and preferences: the Educational Needs Assessment Tool (ENAT, range 0-156, higher scores indicate higher educational needs) and the Autonomy Preference Index (API, range 0-100, higher scores indicate stronger preferences). Lack of information about medication safety, access to physical/emotional support services and practical strategies for coping with daily challenges related to parenting were the most prominent of the six key themes identified. Rheumatologists were the primary source for information regarding treatment decisions while arthritis consumer organisations were perceived as critical 'resource hubs'. There was strong preference for information delivered electronically, especially among rural participants. Quantitative outcomes supported the qualitative findings; on average, participants reported high educational needs (mean ENAT score 97.2, SD 30.8) and API scores indicated that desire for information (mean 89.8, SD 5.6) was greater than the need for involvement in treatment decision-making (mean 68.4, SD 8.2). Many women with RA struggle to find adequate information on pregnancy planning, pregnancy and early parenting in relation to their chronic condition, and there is a clear need to develop accessible information that is consumer-focused and evidence-based. Although most

High density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

PubMed Central

Eyre, Steve; Bowes, John; Diogo, Dorothée; Lee, Annette; Barton, Anne; Martin, Paul; Zhernakova, Alexandra; Stahl, Eli; Viatte, Sebastien; McAllister, Kate; Amos, Christopher I.; Padyukov, Leonid; Toes, Rene E.M.; Huizinga, Tom W.J.; Wijmenga, Cisca; Trynka, Gosia; Franke, Lude; Westra, Harm-Jan; Alfredsson, Lars; Hu, Xinli; Sandor, Cynthia; de Bakker, Paul I.W.; Davila, Sonia; Khor, Chiea Chuen; Heng, Khai Koon; Andrews, Robert; Edkins, Sarah; Hunt, Sarah E; Langford, Cordelia; Symmons, Deborah; Concannon, Pat; Onengut-Gumuscu, Suna; Rich, Stephen S; Deloukas, Panos; Gonzalez-Gay, Miguel A.; Rodriguez-Rodriguez, Luis; Ärlsetig, Lisbeth; Martin, Javier; Rantapää-Dahlqvist, Solbritt; Plenge, Robert; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter K; Worthington, Jane

2012-01-01

Summary Using the Immunochip custom single nucleotide polymorphism (SNP) array, designed for dense genotyping of 186 genome wide association study (GWAS) confirmed loci we analysed 11,475 rheumatoid arthritis cases of European ancestry and 15,870 controls for 129,464 markers. The data were combined in meta-analysis with GWAS data from additional independent cases (n=2,363) and controls (n=17,872). We identified fourteen novel loci; nine were associated with rheumatoid arthritis overall and 5 specifically in anti-citrillunated peptide antibody positive disease, bringing the number of confirmed European ancestry rheumatoid arthritis loci to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at six loci and association to low frequency variants (minor allele frequency <0.05) at 4 loci. Bioinformatic analysis of the data generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations. PMID:23143596

Epstein-Barr virus and rheumatoid arthritis: is there a link?

PubMed

Costenbader, Karen H; Karlson, Elizabeth W

2006-01-01

Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic, destructive, debilitating arthritis. Its etiology is unknown; it is presumed that environmental factors trigger development in the genetically predisposed. Epstein-Barr virus, a nearly ubiquitous virus in the human population, has generated great interest as a potential trigger. This virus stimulates polyclonal lymphocyte expansion and persists within B lymphocytes for the host's life, inhibited from reactivating by the immune response. In latent and replicating forms, it has immunomodulating actions that could play a role in the development of this autoimmune disease. The evidence linking Epstein-Barr virus and rheumatoid arthritis is reviewed.

Rheumatoid arthritis antigens homocitrulline and citrulline are generated by local myeloperoxidase and peptidyl arginine deiminases 2, 3 and 4 in rheumatoid nodule and synovial tissue.

PubMed

Turunen, Sanna; Huhtakangas, Johanna; Nousiainen, Tomi; Valkealahti, Maarit; Melkko, Jukka; Risteli, Juha; Lehenkari, Petri

2016-10-20

Seropositive rheumatoid arthritis (RA) is characterized by autoantibodies binding to citrullinated and homocitrullinated proteins. We wanted to study the expression patterns of these disease-associated protein forms and if the rheumatoid nodule and synovial tissue itself contain biologically active levels of citrullinating peptidyl arginine deiminases 2, 3 and 4 and homocitrullination-facilitating neutrophil enzyme myeloperoxidase. Total of 195 synovial samples from metatarsal joints from five ACPA/RF-positive RA patients (n = 77), synovial samples from knees of eight seropositive RA (n = 60), seven seronegative RA (n = 33) and five osteoarthritis (n = 25) patients were analyzed for citrulline and homocitrulline contents using HPLC. The location of citrulline- and homocitrulline-containing proteins, PAD 2, 3, 4 and myeloperoxidase were shown by immunostaining. Myeloperoxidase and citrulline- or homocitrulline-containing proteins were stained on Western blot. Overall, necrosis was frequent in metatarsals of seropositive RA and absent in seronegative RA and osteoarthritis patients. In histological analysis, there was a significant local patterning and variation in the citrulline and homocitrulline content and it was highest in metatarsal synovial tissues of seropositive RA patients. We found peptidyl arginine deiminase 2, 3 and 4 in the lining and sublining layers of intact synovial tissue. Myeloperoxidase was found locally around necrotic areas. The tissues with necrosis contained the highest levels of citrulline and homocitrulline. Rheumatoid nodules and synovia contain significant amount of PAD2, 3 and 4 and myeloperoxidase enzymes. These enzymes could explain the levels of citrulline and homocitrulline in seropositive RA synovial and rheumatoid nodule tissues especially around necrotic tissue.

Higher serum levels of rheumatoid factor and anti-nuclear antibodies in helicobacter pylori-infected peptic ulcer patients.

PubMed

Jafarzadeh, Abdollah; Nemati, Maryam; Rezayati, Mohammad Taghi; Nabizadeh, Mansooreh; Ebrahimi, Medhi

2013-07-01

H. pylori infection has been associated with some autoimmune disorders. The aim of this study was to evaluate the serum concentrations of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected peptic ulcer patients, H. pylori-infected asymptomatic carriers and a healthy control group. A Total of 100 H. pylori-infected peptic ulcer patients, 65 asymptomatic carriers and 30 healthy H. pylori-negative subjects (as a control group) were enrolled into study. Serum samples of participants tested for the levels of rheumatoid factor and anti-nuclear antibodies by use of ELISA. The mean serum levels of rheumatoid factor and anti-nuclear antibodies in peptic ulcer group was significantly higher in comparison to the control group (p<0.05). Although, the mean serum levels of rheumatoid factor and anti-nuclear antibodies in the asymptomatic carriers group was higher than those in the control group, the difference was not statistically significant. No significant differences were observed between peptic ulcer patients and asymptomatic carriers groups regarding the mean serum levels of rheumatoid factor and anti-nuclear antibodies. The mean serum levels of rheumatoid factor in men with peptic ulcer was significantly higher compared to the group of healthy men (p<0.05). Although in female of peptic ulcer patients or asymptomatic carriers groups, the mean serum levels of rheumatoid factor was higher than that in healthy women, but the differences were not statistically significant. Also, no significant differences were observed between men and women with peptic ulcer, asymptomatic carriers control groups based on the serum levels of anti-nuclear antibodies. The results showed higher serum levels of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected patients with peptic ulcer disease which represent the H. pylori-related immune disturbance in these patients. Additional follow-up studies are necessary to clarify the clinical significance of these

Bilateral Cricoarytenoid Arthritis: A Cause of Recurrent Upper Airway Obstruction in Rheumatoid Arthritis

PubMed Central

Pradhan, Pradeep; Bhardwaj, Abhishek; Venkatachalam, VP

2016-01-01

We report a case of bilateral cricoarytenoid joint arthritis with history of rheumatoid arthritis, presented with stridor to the outpatient department. Endolaryngoscopy revealed adducted vocal cords and a nodule over left arytenoid which later confirmed to be rheumatoid nodule on histopathologic examination. Initially, although patient responded well to medical treatment, recurrence was noticed after 6 months follow-up. PMID:27418875

Chronic comorbidity in patients with early rheumatoid arthritis: a descriptive study.

PubMed

Kroot, E J; van Gestel, A M; Swinkels, H L; Albers, M M; van de Putte, L B; van Riel, P L

2001-07-01

To study the presence of chronic coexisting diseases in patients with rheumatoid arthritis (RA) and its effect on RA treatment, disease course, and outcome during the first years of the disease. From January 1985 to December 1990, 186 patients with recent onset RA were enrolled in a prospective longitudinal study. Between January 1991 and November 1992 patients were interviewed on the basis of a comorbidity questionnaire. For analysis the diseases were coded according to the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) medical diagnoses. Disease activity during the period of followup was measured by the Disease Activity Score. Outcome in terms of physical disability (Health Assessment Questionnaire) and radiological damage (Sharp's modified version) over 3 and 6 year periods was determined. In the group of 186 patients, with mean disease duration of 4.3 years at January 1991, 50 patients (27%) reported at least one chronic coexisting disease. The most frequently reported coexisting diseases were of cardiovascular (29%), respiratory (18%), or dermatological (11%) origin. For the major part (66%) chronic coexisting diseases were already present before onset of RA. No statistically significant differences in use of disease modifying antirheumatic drugs or corticosteroids were observed between RA patients with and without chronic coexisting diseases. No statistically significant differences were found in disease activity or in outcome in terms of physical disability and radiological damage over 3 and 6 year periods between the 2 groups with RA. The results showed that about 27% of patients with RA in this inception cohort had at least one chronic coexisting disease. Treatment, disease course, and outcome did not differ between patients with and without chronic coexisting diseases during the first years of the disease.

Ratio of Circulating IFNγ + “Th17 Cells” in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project

PubMed Central

Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

2016-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17+Th17 cells, and IFNγ +Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ +Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies. PMID:27294146

Simulating a Dynamic Antarctic Ice Sheet in the Early to Middle Miocene

NASA Astrophysics Data System (ADS)

Gasson, E.; DeConto, R.; Pollard, D.; Levy, R. H.

2015-12-01

There are a variety of sources of geological data that suggest major variations in the volume and extent of the Antarctic ice sheet during the early to middle Miocene. Simulating such variability using coupled climate-ice sheet models is problematic due to a strong hysteresis effect caused by height-mass balance feedback and albedo feedback. This results in limited retreat of the ice sheet once it has reached the continental size, as likely occurred prior to the Miocene. Proxy records suggest a relatively narrow range of atmospheric CO2 during the early to middle Miocene, which exacerbates this problem. We use a new climate forcing which accounts for ice sheet-climate feedbacks through an asynchronous GCM-RCM coupling, which is able to better resolve the narrow Antarctic ablation zone in warm climate simulations. When combined with recently suggested mechanisms for retreat into subglacial basins due to ice shelf hydrofracture and ice cliff failure, we are able to simulate large-scale variability of the Antarctic ice sheet in the Miocene. This variability is equivalent to a seawater oxygen isotope signal of ~0.5 ‰, or a sea level equivalent change of ~35 m, for a range of atmospheric CO2 between 280 - 500 ppm.

A comparison of rural and urban rheumatoid arthritis populations.

PubMed

Basu, N; Steven, M

2009-02-01

There is evidence to suggest that remote populations have poorer clinical outcomes in certain disease processes such as asthma and cancer. This study looks to identify any disparities in the management of patients with rheumatoid arthritis in the context of rurality. A retrospective observational study was performed on all 1314 patients with a diagnosis of rheumatoid arthritis who have been under the care of the principal rheumatologist at Raigmore Hospital, Inverness, between the years 1994 and 2004 inclusive. Rurality was defined according to the Scottish Household Survey. Populations were assessed in terms of age; sex; duration of diagnosis; number of years of Disease Modifying AntiRheumatic Drugs (DMARD) therapy, prednisolone use and the number of musculoskeletal practical interventions undertaken (eg joint aspiration or replacement). Two thirds of patients were considered rural dwellers. No significant difference was established between the populations with regards to management. DMARD therapy had been prescribed in 77% of rural patients vs 70% of their city counterparts for a mean 5.4 and 4.0 years respectively. The proportion of patients exposed to prednisolone therapy and who underwent musculoskeletal procedures were equivalent. Rural dwellers, with rheumatoid arthritis in the Highlands of Scotland, do not appear to be disadvantaged in regards to their disease management in comparison to the urban population.

Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery: combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds

PubMed Central

Nikiphorou, Elena; Norton, Sam; Young, Adam; Carpenter, Lewis; Dixey, Josh; Walsh, David Andrew; Kiely, Patrick

2016-01-01

Objectives To examine the association between disease activity in early rheumatoid arthritis (RA), functional limitation and long-term orthopaedic episodes. Methods Health Assessment Questionnaire (HAQ) disability scores were collected from two longitudinal early RA inception cohorts in routine care; Early Rheumatoid Arthritis Study and Early Rheumatoid Arthritis Network from 1986 to 2012. The incidence of major and intermediate orthopaedic surgical episodes over 25 years was collected from national data sets. Disease activity was categorised by mean disease activity score (DAS28) annually between years 1 and 5; remission (RDAS≤2.6), low (LDAS>2.6–3.2), low-moderate (LMDAS≥3.2–4.19), high-moderate (HMDAS 4.2–5.1) and high (HDAS>5.1). Results Data from 2045 patients were analysed. Patients in RDAS showed no HAQ progression over 5 years, whereas there was a significant relationship between rising DAS28 category and HAQ at 1 year, and the rate of HAQ progression between years 1 and 5. During 27 986 person-years follow-up, 392 intermediate and 591 major surgeries were observed. Compared with the RDAS category, there was a significantly increased cumulative incidence of intermediate surgery in HDAS (OR 2.59 CI 1.49 to 4.52) and HMDAS (OR 1.8 CI 1.05 to 3.11) categories, and for major surgery in HDAS (OR 2.48 CI 1.5 to 4.11), HMDAS (OR 2.16 CI 1.32 to 3.52) and LMDAS (OR 2.07 CI 1.28 to 3.33) categories. There was no significant difference in HAQ progression or orthopaedic episodes between RDAS and LDAS categories. Conclusions There is an association between disease activity and both poor function and long-term orthopaedic episodes. This illustrates the far from benign consequences of persistent moderate disease activity, and supports European League Against Rheumatism treat to target recommendations to secure low disease activity or remission in all patients. PMID:26979104

Preclinical Rheumatoid Arthritis (Autoantibodies): An Updated Review

PubMed Central

Deane, Kevin D.

2014-01-01

Multiple studies demonstrate that there is a period of development of rheumatoid arthritis (RA) during which there are elevations of disease-related biomarkers, including autoantibodies, in the absence of and prior to the development of RA; this period can be termed ‘preclinical RA’. These ‘preclinical’ autoantibodies including rheumatoid factor and antibodies to citrullinated protein antigens, and more recent studies have also identified a wider variety of autoantibodies and a wide range of inflammatory biomarkers. These findings in conjunction with established and emerging data about genetic and environmental risk factors for RA support a model of disease development where certain factors lead to an initial triggering of RA-related autoimmunity that expands over time to the point where symptomatic arthritis classifiable as RA develops. Herein will be reviewed updates in the field, as well as a discussion of current limitations of our understanding of preclinical RA, and potential future directions for study. PMID:24643396

Finite element simulation of ultrasonic waves in corroded reinforced concrete for early-stage corrosion detection

NASA Astrophysics Data System (ADS)

Tang, Qixiang; Yu, Tzuyang

2017-04-01

In reinforced concrete (RC) structures, corrosion of steel rebar introduces internal stress at the interface between rebar and concrete, ultimately leading to debonding and separation between rebar and concrete. Effective early-stage detection of steel rebar corrosion can significantly reduce maintenance costs and enable early-stage repair. In this paper, ultrasonic detection of early-stage steel rebar corrosion inside concrete is numerically investigated using the finite element method (FEM). Commercial FEM software (ABAQUS) was used in all simulation cases. Steel rebar was simplified and modeled by a cylindrical structure. 1MHz ultrasonic elastic waves were generated at the interface between rebar and concrete. Two-dimensional plain strain element was adopted in all FE models. Formation of surface rust in rebar was modeled by changing material properties and expanding element size in order to simulate the rust interface between rebar and concrete and the presence of interfacial stress. Two types of surface rust (corroded regions) were considered. Time domain and frequency domain responses of displacement were studied. From our simulation result, two corrosion indicators, baseline (b) and center frequency (fc) were proposed for detecting and quantifying corrosion.

Extra-articular manifestations of seronegative and seropositive rheumatoid arthritis.

PubMed

Sahatciu-Meka, Vjollca; Rexhepi, Sylejman; Manxhuka-Kerliu, Suzana; Rexhepi, Mjellma

2010-02-01

Although considered a "joint disease," rheumatoid arthritis is associated with the involvement of extra-articular manifestations. The aim of the study is the investigation and comparison of frequency and type of extra-articular manifestations in a well defined community based cohort of patients with seropositive and seronegative rheumatoid arthritis. Using the ACR (1987) criteria for rheumatoid arthritis, patients have been classified into the 2nd and 3rd functional class (ARA). The studied group consisted of 125 seronegative patients with titters lower than 1:64 as defined by Rose-Waaler test, whereas the control group consisted of 125 seropositive patients with titters of 1:64 or higher. All patients were between 25-60 years of age (Xb=49,96), with disease duration between 1-27 years (Xb=6,41). In order to present the findings of the study, the structure, prevalence, arithmetic mean (Xb), standard deviation (SB), variation quotient (QV%) and variation interval (Rmax-Rmin) have been used. Probability level has been expressed by p<0,01 and p<0,05. Correlation between the number of extra-articular manifestations and duration of the disease has been calculated by means of Pearson linear correlation. Higher presence of diffuse lung fibrosis, central and peripheral nervous system damages have been confirmed in the seropositive group, and osteoporosis in the seronegative; however, no statistical difference has been found. In extra-articular manifestations, "rheumatoid core" in the seropositive subset (chi2=4,80, p<0,05) presented significant statistical difference. Rheumatoid nodules were more frequent in seropositive subset (12%:16%), in both sexes; however, they were not of significant statistical difference. Neuropathy and lung diseases were also frequently present in seropositive group, but no statistical difference has been found regarding the statistical difference. Longer duration of the disease resulted in an increase of the number of extra

Occupational therapy during the first 10 years of rheumatoid arthritis.

PubMed

Malcus-Johnson, Pia; Carlqvist, Carin; Sturesson, Anna-Lena; Eberhardt, Kerstin

2005-01-01

To describe disease development and occupational therapy during the first 10 years of rheumatoid arthritis (RA), and to assess patients' experiences of occupational therapy and comprehensive care. A total of 168 early RA patients with variable disease severity were followed up with regular team visits. The occupational therapist evaluated hand function and activity and performed the necessary interventions. These were recorded and the number of visits generating interventions was calculated. Semi-structured interview of 11 patients regarding their views of occupational therapy and team contact was performed. Impairments of hand function were in general mild to moderate and remained fairly unchanged over time. Activity limitations increased slowly. Half of the follow-up visits generated interventions. Most common were prescriptions of assistive devices and orthoses, hand-training instructions and patient education. The patients interviewed were positive regarding occupational therapy and felt safe with comprehensive care. RA patients in all stages of the disease benefit from regular contact with an occupational therapist and team care.

Fears and Beliefs in Rheumatoid Arthritis and Spondyloarthritis: A Qualitative Study

PubMed Central

Berenbaum, Francis; Chauvin, Pierre; Hudry, Christophe; Mathoret-Philibert, Florence; Poussiere, Maud; De Chalus, Thibault; Dreuillet, Caroline; Russo-Marie, Françoise; Joubert, Jean-Michel; Saraux, Alain

2014-01-01

Objectives To explore beliefs and apprehensions about disease and its treatment in patients with rheumatoid arthritis and spondyloarthritis. Methods 25 patients with rheumatoid arthritis and 25 with spondyloarthritis participated in semi-structured interviews about their disease and its treatment. The interviews were performed by trained interviewers in participants' homes. The interviews were recorded and the main themes identified by content analysis. Results Patients differentiated between the underlying cause of the disease, which was most frequently identified as a hereditary or individual predisposition. In patients with rheumatoid arthritis, the most frequently cited triggering factor for disease onset was a psychological factor or life-event, whereas patients with spondyloarthritis tended to focus more on an intrinsic vulnerability to disease. Stress and overexertion were considered important triggering factors for exacerbations, and relaxation techniques were frequently cited strategies to manage exacerbations. The unpredictability of the disease course was a common source of anxiety. Beliefs about the disease and apprehensions about the future tended to evolve over the course of the disease, as did treatment expectations. Conclusions Patients with rheumatoid arthritis and spondyloarthritis hold a core set of beliefs and apprehensions that reflect their level of information about their disease and are not necessarily appropriate. The physician can initiate discussion of these beliefs in order to dispel misconceptions, align treatment expectations, provide reassurance to the patient and readjust disease management. Such a dialogue would help improve standards of care in these chronic and incapacitating diseases. PMID:25474157

Relationship between toxic metals exposure via cigarette smoking and rheumatoid arthritis.

PubMed

Afridi, Hassan Imran; Kazi, Tasneem Gul; Talpur, Farah Naz; Naher, Sumsun; Brabazon, Dermot

2014-01-01

The incidence of Rheumatoid Arthritis (RA) has increased among people who smoke tobacco. In the present study, the association between toxic metals exposure via cigarette smoking and rheumatoid arthritis incidence in the population living in Dublin, Ireland, is investigated. The different brands of cigarettes (filler tobacco, filter and ash) consumed by the population studied were analysed for Cd, Ni, and Pb. The concentrations of toxic elements in biological samples and different components of cigarettes were measured by inductively coupled plasma atomic emission spectrophotometer after microwave-assisted acid digestion. The validity and accuracy of the methodology were checked using certified reference materials. The filler tobacco of different branded cigarettes contain Cd, Ni, and Pb concentrations in the ranges of 1.73-2.02, 0.715-1.52, and 0.378-1.16 μg/cigarette, respectively. The results of this study showed that the mean values of cadmium nickel, and lead were significantly higher in scalp hair and blood samples of rheumatoid arthritis patients when related to healthy controls, while the difference was significant in the case of smoker patients (p < 0.001). The levels of all three toxic metals were 2- to 3-fold higher in scalp hair and blood samples of non arthritis smoker subjects as compared to nonsmoker controls. The high exposure of toxic metals as a result of cigarette smoking may be synergistic with risk factors associated with rheumatoid arthritis.

Herpes zoster risk factors in a national cohort of veterans with rheumatoid arthritis

PubMed Central

McDonald, Jay R.; Zeringue, Angelique L.; Caplan, Liron; Ranganathan, Prabha; Xian, Hong; Burroughs, Thomas E.; Fraser, Victoria J; Cunningham, Fran; Eisen, Seth A.

2009-01-01

Background Herpes zoster occurs more commonly in patients taking immunosuppressive medications, though the risk associated with different medications is poorly understood. Methods Retrospective cohort study including 20,357 patients who were followed in the Veterans Affairs healthcare system and treated for rheumatoid arthritis from October 1998 through June 2005. Cox proportional hazards regression was used to determine risk factors for herpes zoster, and herpes zoster-free survival. Chart review was performed to validate the diagnosis of herpes zoster. Results The incidence of herpes zoster was 9.96 per 1000 patient-years. In time-to-event analysis, patients receiving medications used to treat mild rheumatoid arthritis were less likely to have an episode of herpes zoster than patients receiving medications used to treat moderate and severe rheumatoid arthritis (p<0.001). Independent risk factors for herpes zoster included older age, prednisone use, medications used to treat moderate and severe rheumatoid arthritis, malignancy, chronic lung disease, renal failure, and liver disease. Among patients receiving tumor necrosis factor-alpha antagonists, etanercept (HR 0.62) and adalimumab (HR 0.53) were associated with lower risk of herpes zoster. There was excellent agreement between ICD-9-CM diagnosis of herpes zoster and diagnosis by chart review (kappa = 0.92). Conclusions Risk factors for herpes zoster included older age, prednisone use, medications used to treat moderate and severe rheumatoid arthritis, and several comorbid medical conditions. These results demonstrate that the Department of Veterans Affairs’ national administrative databases can be used to study rare adverse drug events. PMID:19368499

Emerging immunotherapies for rheumatoid arthritis

PubMed Central

Reynolds, Gary; Cooles, Faye AH; Isaacs, John D; Hilkens, Catharien MU

2014-01-01

Novel treatments in development for rheumatoid arthritis target 3 broad areas: cytokines, cells, and signaling pathways. Therapies from each domain share common advantages (for example previously demonstrated efficacy, potential long-term immunomodulation, and oral administration respectively) that have stimulated research in each area but also common obstacles to their development. In this review recent progress in each area will be discussed alongside the factors that have impeded their path to clinical use. PMID:24535556

Application of Synchrotron Radiation Imaging for Non-destructive Monitoring of Mouse Rheumatoid Arthritis Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Chang-Hyuk; Kim, Hong-Tae; Choe, Jung-Yoon

This study was performed to observe microstructures of the rheumatoid arthritis induced mouse feet using a synchrotron radiation beam and to compare findings with histological observations. X-ray refraction images from ex-vivo rheumatoid arthritis induced mouse feet were obtained with an 8KeV white (unmonochromatic) beam and 20 micron thick CsI(Tl) scintillation crystal. The visual image was magnified using a x 10 microscope objective and captured using digital CCD camera. Experiments were performed at 1B2 bending magnet beamline of the Pohang Accelerator Laboratory (PAL) in Korea. Obtained images were compared with histopathologic findings from same sample. Cartilage destruction and thickened joint capsulemore » with joint space narrowing were clearly identified at each grade of rheumatoid model with spatial resolution of as much as 1.2 micron and these findings were directly correlated with histopathologic findings. The results suggest that x-ray microscopy study of the rheumatoid arthritis model using synchrotron radiation demonstrates the potential for clinically relevant micro structure of mouse feet without sectioning and fixation.« less

The development of a questionnaire to evaluate rheumatoid arthritis patient's knowledge about methotrexate.

PubMed

Fayet, Françoise; Savel, Carine; Rodere, Malory; Pereira, Bruno; Abdi, Dihya; Mathieu, Sylvain; Tournadre, Anne; Soubrier, Martin; Dubost, Jean-Jacques

2016-03-01

Assess knowledge concerning methotrexate in rheumatoid arthritis patients by means of a questionnaire. Methotrexate is the standard drug for rheumatoid arthritis treatment. It has potentially serious side effects that can be largely prevented by making sure that patients are well informed and comply with prescription guidelines. Cross-sectional survey. A questionnaire on methotrexate (mode of action, administration, drug interactions), side effects, monitoring and lifestyle implications was offered to all the rheumatoid arthritis patients treated with the drug seen between March and September 2013 in a large hospital in France. One hundred and eighty-three patients (143 women), mean age 60 (13·5) years, with a median disease duration of 12 years [7-20] and treated with methotrexate for eight years [5-13] took part. Methotrexate was identified as a disease-modifying antirheumatic drug by 78% of the patients. The weekly administration method was well assimilated (97%); 67% indicated that the rationale for folic acid was to reduce treatment toxicity. Only 21% knew that trimethoprim was contraindicated. Half were aware of the haematologic risk and 36% were aware of the risk of hypersensitivity pneumonitis. There was knowledge concerning laboratory testing (80%), but 54% thought they were only being monitored for rheumatoid arthritis activity. Only 13% of the men, but 90% of the women, of childbearing age knew that contraception was essential, and 75% indicated that alcohol consumption should be limited. A low knowledge score correlated significantly with age and low educational level. It was independent of sex, duration of treatment for rheumatoid arthritis. Rheumatoid arthritis patient's knowledge concerning methotrexate is poor, particularly for the most serious side effects (haematologic and hypersensitivity pneumonitis), interactions with trimethoprim, and in men, the need for contraception. Patient knowledge concerning methotrexate should be regularly checked and

Epistatic interaction between FCRL3 and NFκB1 genes in Spanish patients with rheumatoid arthritis

PubMed Central

Martínez, A; Sánchez, E; Valdivia, A; Orozco, G; López‐Nevot, M A; Pascual‐Salcedo, D; Balsa, A; Fernández‐Gutiérrez, B; de la Concha, E G; García‐Sánchez, A; Koeleman, B P C; Urcelay, E; Martín, J

2006-01-01

Background A Japanese study has described a strong association between rheumatoid arthritis and several polymorphisms located in the Fc receptor‐like 3 (FCRL3) gene, a member of a family of genes related to Fc receptors located on chromosome 1q21–23. Objectives To evaluate the association between rheumatoid arthritis and FCLR3 polymorphisms in a large cohort of Caucasian patients with rheumatoid arthritis and healthy controls of Spanish origin. Owing to the described functional link between the FCRL3 polymorphisms and the transcription factor nuclear factor κB (NFκB), a functional polymorphism located in the NFκB1 gene was included. Methods 734 patients with rheumatoid arthritis from Madrid and Granada, Spain, were included in the study, along with 736 healthy controls. Polymorphisms in the FCRL3 gene were studied by TaqMan technology. The −94ins/delATTG NFκB1 promoter polymorphism was analysed by fragment analysis after polymerase chain reaction with labelled primers. Genotypes were compared using 3×2 contingency tables and χ2 values. Results No overall differences were found in any of the FCRL3 polymorphisms and in the NFκB1 promoter polymorphism when patients were compared with controls. However, when stratified according to NFκB1 genotypes, a susceptibility effect of FCRL3 polymorphisms was observed in patients who were heterozygotes for NFκB1 (pc = 0.003). Conclusions The FCRL3 polymorphisms associated with rheumatoid arthritis in a Japanese population are not associated per se with rheumatoid arthritis in a Spanish population. A genetic interaction was found between NFκB1 and FCRL3 in Spanish patients with rheumatoid arthritis. These findings may provide a general rationale for divergent genetic association results in different populations. PMID:16476711

Measures of rheumatoid arthritis disease activity in Australian clinical practice.

PubMed

Taylor, Andrew; Bagga, Hanish

2011-01-01

Objectives. To investigate which rheumatoid arthritis (RA) disease activity measures are being collected in patients receiving glucocorticoids, non-biologic or biologic disease-modifying antirheumatic drugs (DMARDs) in Australian rheumatology practice. Methods. A retrospective audit of medical records was conducted from eight rheumatology practices around Australia. Each rheumatologist recruited 30 consecutive eligible patients into the review, 10 of whom must have been receiving a biological agent for rheumatoid arthritis. Disease activity measures and radiographic assessments were collected from each patient's last consultation. For biologic patients, disease activity measures were also collected from when the patient was first initiated on the biological agent. Results. At last consultation, the disease measures that were recorded most often were ESR (89.2%), haemoglobin (87.5%), and CRP (84.2%). DAS28 was infrequently recorded (16.3%). The rate of recording disease activity measures for patients receiving biologic DMARDs decreased over time (mean 27 months). Conclusion. This review has shown inconsistency of RA activity measures being recorded in Australian rheumatology clinical practice. An accurate assessment of the disease process is necessary to effectively target rheumatoid arthritis patients to treat in order to achieve optimal outcomes.

The utility of clinical decision tools for diagnosing osteoporosis in postmenopausal women with rheumatoid arthritis

PubMed Central

Brand, Caroline; Lowe, Adrian; Hall, Stephen

2008-01-01

Background Patients with rheumatoid arthritis have a higher risk of low bone mineral density than normal age matched populations. There is limited evidence to support cost effectiveness of population screening in rheumatoid arthritis and case finding strategies have been proposed as a means to increase cost effectiveness of diagnostic screening for osteoporosis. This study aimed to assess the performance attributes of generic and rheumatoid arthritis specific clinical decision tools for diagnosing osteoporosis in a postmenopausal population with rheumatoid arthritis who attend ambulatory specialist rheumatology clinics. Methods A cross-sectional study of 127 ambulatory post-menopausal women with rheumatoid arthritis was performed. Patients currently receiving or who had previously received bone active therapy were excluded. Eligible women underwent clinical assessment and dual-energy-xray absorptiometry (DXA) bone mineral density assessment. Clinical decision tools, including those specific for rheumatoid arthritis, were compared to seven generic post-menopausal tools to predict osteoporosis (defined as T score < -2.5). Sensitivity, specificity, positive predictive and negative predictive values and area under the curve were assessed. The diagnostic attributes of the clinical decision tools were compared by examination of the area under the receiver-operator-curve. Results One hundred and twenty seven women participated. The median age was 62 (IQR 56–71) years. Median disease duration was 108 (60–168) months. Seventy two (57%) women had no record of a previous DXA examination. Eighty (63%) women had T scores at femoral neck or lumbar spine less than -1. The area under the ROC curve for clinical decision tool prediction of T score <-2.5 varied between 0.63 and 0.76. The rheumatoid arthritis specific decision tools did not perform better than generic tools, however, the National Osteoporosis Foundation score could potentially reduce the number of unnecessary DXA

Rheumatoid-like arthritis associated with a colonic carcinoma.

PubMed

Simon, R D; Ford, L E

1980-05-01

A 76-year-old woman with rapidly progressive athritis associated with a rising rheumatoid factor, acute joint effusion, and fever had remission of her symptoms and return of her laboratory values to normal following removal of a colonic carcinoma.

Epstein–Barr virus and rheumatoid arthritis: is there a link?

PubMed Central

Costenbader, Karen H; Karlson, Elizabeth W

2006-01-01

Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic, destructive, debilitating arthritis. Its etiology is unknown; it is presumed that environmental factors trigger development in the genetically predisposed. Epstein–Barr virus, a nearly ubiquitous virus in the human population, has generated great interest as a potential trigger. This virus stimulates polyclonal lymphocyte expansion and persists within B lymphocytes for the host's life, inhibited from reactivating by the immune response. In latent and replicating forms, it has immunomodulating actions that could play a role in the development of this autoimmune disease. The evidence linking Epstein–Barr virus and rheumatoid arthritis is reviewed. PMID:16542469

Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial

PubMed Central

Aga, Anna-Birgitte; Olsen, Inge Christoffer; Lillegraven, Siri; Hammer, Hilde B; Uhlig, Till; Fremstad, Hallvard; Madland, Tor Magne; Lexberg, Åse Stavland; Haukeland, Hilde; Rødevand, Erik; Høili, Christian; Stray, Hilde; Noraas, Anne; Hansen, Inger Johanne Widding; Bakland, Gunnstein; Nordberg, Lena Bugge; van der Heijde, Désirée; Kvien, Tore K

2016-01-01

clinical tight control arm reached the primary endpoint (mean difference 3.3%, 95% confidence interval −7.1% to 13.7%). Secondary endpoints (disease activity, physical function, and joint damage) were similar between the two groups. Six (5%) patients in the ultrasound tight control arm and seven (6%) patients in the conventional arm had serious adverse events. Conclusions The systematic use of ultrasound in the follow-up of patients with early rheumatoid arthritis treated according to current recommendations is not justified on the basis of the ARCTIC results. The findings highlight the need for randomised trials assessing the clinical application of medical technology. Trial registration Clinical trials NCT01205854. PMID:27530741

Health-related quality of life for patients with rheumatoid arthritis foot involvement.

PubMed

Wickman, Amy M; Pinzur, Michael S; Kadanoff, Ruth; Juknelis, Dainius

2004-01-01

Rheumatoid arthritis is a common disabling form of arthritis that frequently affects the hands and feet. With time, the majority of affected individuals will become disabled. Sixty-nine consecutively selected mild to moderately affected individuals with rheumatoid arthritis provided demographic data and agreed to complete the Short Musculoskeletal Function Assessment (SFMA) instrument. Focus group subjects selectively used minimally adaptive nonprescription footwear. Control subjects had similar disease expression, but did not alter their choice of footwear due to their disease. Adult patients with rheumatoid arthritis demonstrate a significant negative impact on their quality of life with mild or moderate disease expression, as evidenced by poor scores in all six domains of the SFMA. Subjects who used even mildly adaptive nonprescription footwear demonstrated a statistically significant negative impact in mobility (p < .044) and functional index (p < .052) domains as compared with the control population having similar overall disease expression. Focus subjects also demonstrated a trend to less favorable scores in the arm and hand domain. Mean scores of the daily activity, emotional status, and bother index domains fared worse than population norms, but there was no statistical difference between subjects using, or not using, adaptive footwear. Individuals affected with mild to moderate rheumatoid arthritis are disabled as compared with the general population. There is a severe negative impact on mobility and functional capacity when the disease process begins to affect their feet.

Total fixation of cricoarytenoid joint of a patient with rheumatoid arthritis and Hashimoto thyroiditis.

PubMed

Stojanović, Stevan P; Zivić, Ljubica; Stojanović, Jasmina; Belić, Branislav

2010-01-01

The incidence of cricoarytenoid joint fixation in case of rheumatoid arthritis is 17 to 33%. In later stages of rheumatoid arthritis, a gradual fixation of cricoarytenoid joint develops and both halves of the larynx become less movable which calls for endotracheal intubation; while total fixation of this joint demands surgical tracheotomy. Hashimoto thyroiditis can display symptoms which are difficult to distinguish from the ones present in total fixation of cricoarytenoid joint caused by rheumatoid arthritis. A 60-year-old woman in terminal stage of rheumatoid arthritis and Hashimoto thyroiditis, diagnosed after clinical and other examinations. She was treated for strident breathing with surgical tracheotomy. The microscopic examination of the larynx with the use of laryngoscopic pincers suggested the immovability of the right and very limited movability of the left arytenoid cartilage. A computerized endovideostroboscopy showed only passive vertical vibrating movements of the right vocal cord and irregular vibrations of the left vocal cord. Total fixation of the cricoarytenoid joint can be caused by many pathological processes, but so far references have shown no case of rheumatoid arthritis and Hashimoto thyroiditis. In differential diagnostics, one of many examinations is the microscopic examination of the larynx, but it is very important to determine the movability of the arytenoid cartilage with the use of appropriate instruments in total endotracheal anaesthesia while the patient is fully relaxed. Movements in cricoarytenoid joints in patients with Hashimoto thyroiditis and the same conditions are preserved.

Epidemiological evaluation quality of life in patients suffering from early rheumatoid arthritis: a pragmatic, prospective, randomized, blind allocation controlled of a modular program group intervention

PubMed Central

2015-01-01

OBJECTIVES: Epidemiology has taken on new roles in the management of health care services. In this study, we developed a non-pharmacological self-management modular program group intervention and evaluated its efficacy as an adjunct therapy in patients suffering from early rheumatoid arthritis (RA). METHODS: Patients were randomized to either participate in a non-equivalent intervention group along with the standard of care or only receive standard-of-care treatment at a community rheumatology center. The outcomes measured were a pain visual analog scale (VAS), patient general health (GH) on a VAS, and the Short Form 36 Health Survey version 2 scale measuring quality of life. These parameters were evaluated in the first week to obtain baseline values, and at 20, 32, 48, and 60 weeks to evaluate the efficacy of the intervention group. RESULTS: The patients were randomized, with 100 patients in the intervention group and 106 in the control group. The intervention and control groups were similar with regard to the percentage of women (86% vs. 89.6%), tobacco usage (25% vs. 19.8%), mean age (42.6±13.2 years vs. 46.6±10.9 years), and disease duration (15.3±6.7 months vs. 14.5±6.6 months). The mean outcomes were significantly different between the two groups, and post-hoc pairwise analysis demonstrated significant deterioration in the control group in contrast to improvement in the intervention group at the second, third, fourth, and fifth evaluations. Improvements were often seen as early as the 12-week and 24-week follow-up visits. CONCLUSIONS: Epidemiology contributes to the evaluation of how well specific therapies or other health interventions prevent or control health problems. The modular program group intervention implemented in this study appears to be a suitable and feasible method to facilitate much more comprehensive management of early RA in socioeconomically challenged communities. PMID:26552423

Could early rheumatoid arthritis resolve after periodontitis treatment only?: case report and review of the literature.

PubMed

Salemi, Simonetta; Biondo, Michela I; Fiorentino, Chiara; Argento, Giuseppe; Paolantonio, Michele; Di Murro, Carlo; Malagnino, Vito A; Canzoni, Marco; Diamanti, Andrea Picchianti; D'Amelio, Raffaele

2014-12-01

Rheumatoid arthritis (RA) is an immune-mediated polyarthritis; currently no pathogenic agent has been identified as a disease trigger. A patient with RA, presumably caused by periodontal infection, whose remission has been observed after periodontitis treatment in absence of specific RA therapy, is reported here for the first time, to our knowledge. A 61-year-old male patient presented migrant arthritis associated with antibodies against citrullinated protein antigens positivity. The clinical features allowed to make RA diagnosis according to the 2010 European League against Rheumatism/American College of Rheumatology RA classification criteria. X-ray of the second upper molar showed chronic apical periodontitis. After its treatment, arthritis remission has been observed in the absence of specific RA therapy. It has been suggested that periodontitis may have a trigger role in RA pathogenesis. This could be explained by the enzymatic action of Porphyromonas gingivalis, probably leading to break tolerance to collagen. The identification and subsequent treatment of periodontitis should therefore be considered pivotal in RA prophylaxis and management.

Update of the Mexican College of Rheumatology guidelines for the pharmacologic treatment of rheumatoid arthritis.

PubMed

Cardiel, Mario H; Díaz-Borjón, Alejandro; Vázquez del Mercado Espinosa, Mónica; Gámez-Nava, Jorge Iván; Barile Fabris, Leonor A; Pacheco Tena, César; Silveira Torre, Luis H; Pascual Ramos, Virginia; Goycochea Robles, María Victoria; Aguilar Arreola, Jorge Enrique; González Díaz, Verónica; Alvarez Nemegyei, José; González-López, Laura del Carmen; Salazar Páramo, Mario; Portela Hernández, Margarita; Castro Colín, Zully; Xibillé Friedman, Daniel Xavier; Alvarez Hernández, Everardo; Casasola Vargas, Julio; Cortés Hernández, Miguel; Flores-Alvarado, Diana E; Martínez Martínez, Laura A; Vega-Morales, David; Flores-Suárez, Luis Felipe; Medrano Ramírez, Gabriel; Barrera Cruz, Antonio; García González, Adolfo; López López, Susana Marisela; Rosete Reyes, Alejandra; Espinosa Morales, Rolando

2014-01-01

The pharmacologic management of rheumatoid arthritis has progressed substantially over the past years. It is therefore desirable that existing information be periodically updated. There are several published international guidelines for the treatment of rheumatoid arthritis that hardly adapt to the Mexican health system because of its limited healthcare resources. Hence, it is imperative to unify the existing recommendations and to incorporate them to a set of clinical, updated recommendations; the Mexican College of Rheumatology developed these recommendations in order to offer an integral management approach of rheumatoid arthritis according to the resources of the Mexican health system. To review, update and improve the available evidence within clinical practice guidelines on the pharmacological management of rheumatoid arthritis and produce a set of recommendations adapted to the Mexican health system, according to evidence available through December 2012. The working group was composed of 30 trained and experienced rheumatologists with a high quality of clinical knowledge and judgment. Recommendations were based on the highest quality evidence from the previously established treatment guidelines, meta-analysis and controlled clinical trials for the adult population with rheumatoid arthritis. During the conformation of this document, each working group settled the existing evidence from the different topics according to their experience. Finally, all the evidence and decisions were unified into a single document, treatment algorithm and drug standardization tables. This update of the Mexican Guidelines for the Pharmacologic Treatment of Rheumatoid Arthritis provides the highest quality information available at the time the working group undertook this review and contextualizes its use for the complex Mexican health system. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Early medication use in new-onset rheumatoid arthritis may delay joint replacement: results of a large population-based study.

PubMed

Moura, Cristiano S; Abrahamowicz, Michal; Beauchamp, Marie-Eve; Lacaille, Diane; Wang, Yishu; Boire, Gilles; Fortin, Paul R; Bessette, Louis; Bombardier, Claire; Widdifield, Jessica; Hanly, John G; Feldman, Debbie; Maksymowych, Walter; Peschken, Christine; Barnabe, Cheryl; Edworthy, Steve; Bernatsky, Sasha

2015-08-03

Use of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) may prevent joint damage and potentially reduce joint replacement surgeries. We assessed the association between RA drug use and joint replacement in Quebec, Canada. A cohort of new-onset RA patients was identified from Quebec's physician billing and hospitalization databases from 2002-2011. The outcome was defined using procedure codes submitted by orthopedic surgeons. Medication use was obtained from pharmacy databases. We used alternative Cox regression models with time-dependent variables measuring the cumulative effects of past use during different time windows (one model focussing on the first year after cohort entry) for methotrexate (MTX), and other DMARDs. Models were adjusted for baseline sociodemographics, co-morbidity and prior health service use, time-dependent cumulative use of other drugs (anti-tumor necrosis factor [anti-TNF] agents, other biologics, cyclooxygenase-2 inhibitors [COXIBs], nonselective nonsteroidal antiinflammatory drugs [NSAIDs], and systemic steroids), and markers of disease severity. During follow-up, 608 joint replacements occurred among 11,333 patients (median follow-up: 4.6 years). The best-fitting model relied on the cumulative early use (within the first year after cohort entry) of MTX and of other DMARDs, with an interaction between MTX and other DMARDs. In this model, greater exposure within the first year, to either MTX (adjusted hazard ratio, HR = 0.95 per 1 month, 95% confidence interval, 95% CI 0.93-0.97) or other DMARDs (HR = 0.97, 95% CI 0.95-0.99) was associated with longer time to joint replacement. Our results suggest that longer exposure to either methotrexate (MTX) or other DMARDs within the first year after RA diagnosis is associated with longer time to joint replacement surgery.

Geode development and multiple fractures in rheumatoid arthritis.

PubMed

Lowthian, P J; Calin, A

1985-02-01

The radiological development from normal bone of geodes and subsequent fractures in phalanges of two adjacent fingers is described in a patient with classical rheumatoid arthritis. Presentation was as a septic, discharging focus, but infection was excluded; the pathology is described.

High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.

PubMed

Eyre, Steve; Bowes, John; Diogo, Dorothée; Lee, Annette; Barton, Anne; Martin, Paul; Zhernakova, Alexandra; Stahl, Eli; Viatte, Sebastien; McAllister, Kate; Amos, Christopher I; Padyukov, Leonid; Toes, Rene E M; Huizinga, Tom W J; Wijmenga, Cisca; Trynka, Gosia; Franke, Lude; Westra, Harm-Jan; Alfredsson, Lars; Hu, Xinli; Sandor, Cynthia; de Bakker, Paul I W; Davila, Sonia; Khor, Chiea Chuen; Heng, Khai Koon; Andrews, Robert; Edkins, Sarah; Hunt, Sarah E; Langford, Cordelia; Symmons, Deborah; Concannon, Pat; Onengut-Gumuscu, Suna; Rich, Stephen S; Deloukas, Panos; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Ärlsetig, Lisbeth; Martin, Javier; Rantapää-Dahlqvist, Solbritt; Plenge, Robert M; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter K; Worthington, Jane

2012-12-01

Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.

Pain Behavior in Rheumatoid Arthritis Patients: Identification of Pain Behavior Subgroups

PubMed Central

Waters, Sandra J.; Riordan, Paul A.; Keefe, Francis J.; Lefebvre, John C.

2008-01-01

This study used Ward’s minimum variance hierarchical cluster analysis to identify homogeneous subgroups of rheumatoid arthritis patients suffering from chronic pain who exhibited similar pain behavior patterns during a videotaped behavior sample. Ninety-two rheumatoid arthritis patients were divided into two samples. Six motor pain behaviors were examined: guarding, bracing, active rubbing, rigidity, grimacing, and sighing. The cluster analysis procedure identified four similar subgroups in Sample 1 and Sample 2. The first subgroup exhibited low levels of all pain behaviors. The second subgroup exhibited a high level of guarding and low levels of other pain behaviors. The third subgroup exhibited high levels of guarding and rigidity and low levels of other pain behaviors. The fourth subgroup exhibited high levels of guarding and active rubbing and low levels of other pain behaviors. Sample 1 contained a fifth subgroup that exhibited a high level of active rubbing and low levels of other pain measures. The results of this study suggest that there are homogeneous subgroups within rheumatoid arthritis patient populations who differ in the motor pain behaviors they exhibit. PMID:18358682

Validating and assessing the sensitivity of the Health Assessment Questionnaire-Disability Index-derived Short Form-6D in patients with early aggressive rheumatoid arthritis.

PubMed

Amjadi, Sogol S; Maranian, Paul M; Paulus, Harold E; Kaplan, Robert M; Ranganath, Veena K; Furst, Daniel E; Khanna, Puja P; Khanna, Dinesh

2009-06-01

New methodologies allow the scores for the Health Assessment Questionnaire-Disability Index (HAQ-DI) to be translated into preferences/utility scores. We evaluated the construct validity of the HAQ-DI-derived Short Form-6D (SF-6D) score and assessed its responsiveness to change over 6- and 12-month followup periods in patients with early aggressive rheumatoid arthritis (RA). Patients (n=277) participating in an RA observational study completed self-reported measures of symptoms and the HAQ-DI at baseline and at 6 and 12 months. Total Sharp scores, C-reactive protein, and erythrocyte sedimentation rate were assessed along with clinical data. Construct validity was assessed by examining the association between SF-6D score and patient-reported and clinical measures using Spearman correlation coefficients. The responsiveness of SF-6D to change was assessed using patient and physician assessments of the disease as clinical anchors. The magnitude of responsiveness was calculated using SF-6D effect size (ES). Mean SF-6D scores were 0.690, 0.720, and 0.723 at baseline and 6 and 12-month followup, respectively. Baseline patient-reported measures had moderate to high correlations with baseline SF-6D (r=0.43 to 0.52); whereas clinical measures had negligible to low correlations with SF-6D (r=0.001 to 0.32). ES was moderate for the groups that were deemed to have improved (ES 0.63-0.75) but negligible to small for those that did not (ES 0.13-0.46). Our data support the validity and responsiveness of the HAQ-DI derived SF-6D score in an early RA cohort. These results support the use of the HAQ-DI derived SF-6D in RA cohorts and clinical trials lacking preference-based measures.

Outcome of total ankle arthroplasty in patients with rheumatoid arthritis and noninflammatory arthritis. A multicenter cohort study comparing clinical outcome and safety.

PubMed

Pedersen, Elizabeth; Pinsker, Ellie; Younger, Alastair S E; Penner, Murray J; Wing, Kevin J; Dryden, Peter J; Glazebrook, Mark; Daniels, Timothy R

2014-11-05

Patients with rheumatoid arthritis often have degeneration of the ankle and ipsilateral hindfoot joints. Patients with rheumatoid arthritis undergoing total ankle arthroplasty have a higher risk of wound breakdown and infection. We compared intermediate-term clinical outcomes after total ankle arthroplasty in patients with rheumatoid arthritis and patients with noninflammatory arthritis. Fifty patients with rheumatoid arthritis were compared with fifty patients with noninflammatory arthritis (the control group), matched for age within ten years, prosthesis type, and follow-up time. All patients underwent total ankle arthroplasty. Revisions and major complications were noted. Outcome scores included the Ankle Osteoarthritis Scale (AOS) and Short Form-36 (SF-36) Health Survey. The groups were similar with respect to body mass index and length of follow-up (mean, 63.8 months for the rheumatoid arthritis group and 65.6 months for noninflammatory arthritis group); the rheumatoid arthritis group was younger (mean, 58.5 years compared with 61.2 years). The mean AOS pain scores were significantly different in the rheumatoid arthritis and noninflammatory arthritis groups preoperatively (p < 0.01), but were similar following total ankle arthroplasty (mean and standard deviation, 18.5 ± 17.8 for the rheumatoid arthritis group and 19.7 ± 16.5 for the noninflammatory arthritis group; p = 0.93). Both groups showed significant improvement (p < 0.05) with regard to the AOS scores for pain and disability and SF-36 physical component summary scores following surgery. Postoperatively, AOS disability and SF-36 physical component summary scores were better for patients with noninflammatory arthritis. There were seven revisions in the rheumatoid arthritis group and five in noninflammatory arthritis group. There was one major wound complication in the rheumatoid arthritis cohort and none in the control cohort. Patients with rheumatoid arthritis benefit from total ankle arthroplasty and

Early Career Teacher Professional Development: Bridging Simulation Technology with Evidence-Based Behavior Management

ERIC Educational Resources Information Center

Shernoff, Elisa; Frazier, Stacy; Lisetti, Christine; Buche, Cedric; Lunn, Stephanie; Brown, Claire; Delmarre, Alban; Chou, Tommy; Gabbard, Joseph; Morgan, Emily

2018-01-01

Early career teachers working in high poverty schools face of overwhelming challenges navigating disruptive behaviors with studies highlighting behavior problems as one of the strongest predictors of turnover (Ingersoll & Smith, 2003). Simulation-based technology leverages important pedagogical strengths (e.g., realistic training context,…

Geode of the femur: an uncommon manifestation potentially reflecting the pathogenesis of rheumatoid arthritis.

PubMed

Lee, Wonuk; Terk, Michael R; Hu, Bing; Garber, Elayne K; Weisman, Michael H

2006-12-01

Geodes are noted frequently in rheumatoid arthritis (RA), but large geodes of the femur are uncommon. We describe a patient with RA and a large geode in his femur; histological findings were consistent with a rheumatoid nodule and chronically inflamed synovium. We review the literature of large femoral geodes and what this particular manifestation may reflect about the pathogenesis of RA.

Serum ghrelin in female patients with rheumatoid arthritis during treatment with infliximab.

PubMed

Magiera, Michal; Kopec-Medrek, Magdalena; Widuchowska, Małgorzata; Kotulska, Anna; Dziewit, Tomasz; Ziaja, Damian; Kucharz, Eugene J; Logiewa-Bazger, Beata; Mazur, Wlodzimierz

2013-06-01

Ghrelin is a gastric hormone that posses multiple functions, including induction of growth hormone release, regulation of proinflammatory cytokines and control of food intake and energy homeostasis. A few reports on serum ghrelin level in chronic inflammatory states revealed contradictory results. The study was undertaken to determine ghrelin in patients with rheumatoid arthritis receiving infliximab, a TNF-α blocking agent. Serum ghrelin was determined in 18 female rheumatoid patients before the treatment with infliximab, 1 week after the first infusion and after 53 weeks of medication and compared with 15 age-matched healthy women. Serum ghrelin level was shown to be increased in the patients. A decrease in serum ghrelin level was found after the first infusion of infliximab and similarly decreased ghrelin level but still higher than in the control was shown in the 53rd week of medication. The obtained results suggest that ghrelin level is related to inflammation, and its serum level in patients with severe rheumatoid arthritis behaves similarly to acute-phase reactants.

Heterophilic antibody interference affecting multiple hormone assays: Is it due to rheumatoid factor?

PubMed

Mongolu, Shiva; Armston, Annie E; Mozley, Erin; Nasruddin, Azraai

2016-01-01

Assay interference with heterophilic antibodies has been well described in literature. Rheumatoid factor is known to cause similar interference leading to falsely elevated hormone levels when measured by immunometric methods like enzyme-linked immunosorbent assay (ELISA) or multiplex immunoasays (MIA). We report a case of a 60-year-old male patient with a history of rheumatoid arthritis referred to our endocrine clinic for investigation of hypogonadism and was found to have high serum levels of LH, FSH, SHBG, Prolactin, HCG and TSH. We suspected assay interference and further tests were performed. We used Heteroblock tubes and PEG precipitation to eliminate the interference and the hormone levels post treatment were in the normal range. We believe the interference was caused by high serum levels of rheumatoid factor. Although he was treated with thyroxine for 3 years, we believe he may have been treated inappropriately as his Free T4 level was always normal despite high TSH due to assay interference. Our case illustrates the phenomenon of heterophilic antibody interference likely due to high levels of rheumatoid factor. It is essential for clinicians and endocrinologists in particular to be aware of this possibility when making treatment decisions in these groups of patients.

Inhibition of GSK-3β Alleviates Collagen II-Induced Rheumatoid Arthritis in Rats.

PubMed

Zhou, Haiyan; Liu, Jun; Zeng, Jiashun; Hu, Bailong; Fang, Xiuyi; Li, Long

2016-03-31

Glycogen synthase kinase-3β (GSK-3β) inhibitor is a serine/threonine kinase with an inhibitory role in glycogen synthesis, which is essential in inflammatory and immunological diseases. The purpose of our study was to determine if TDZD-8 can alleviate collagen II-induced rheumatoid arthritis in rats. Twenty collagen II-induced rheumatoid arthritis rats were treated with selective GSK-3β inhibitor. The effects of GSK-3β inhibition on collagen II-induced rheumatoid arthritis in the rats were evaluated by paw edema, histological examination of arthritic synovium, radiographic examination of knee joint, and the level of inflammation mediators such as prostaglandin E2, 5-hydroxytryptamin, and histamine. The level of cytokines such as IL-6, IL-12, IL-10, and TNF-α, was examined by Elisa. GSK-3β inhibitor significantly reduced the development of rheumatoid arthritis in rats. The levels of inflammation mediators such as prostaglandin E2, 5-hydroxytryptamin, and histamine were decreased in the TDZD-8 group. Serum levels of IL-6, IL-12, and TNF-α were significantly reduced in the TDZD-8 group compared with the RA group. Treatment with GSK-3β inhibitor suppressed inflammatory response in RA rats. These findings suggest that the inhibition of GSK-3β can be an effective treatment for RA.

Estimating the cost-effectiveness of 54 weeks of infliximab for rheumatoid arthritis.

PubMed

Wong, John B; Singh, Gurkirpal; Kavanaugh, Arthur

2002-10-01

To estimate the cost-effectiveness of infliximab plus methotrexate for active, refractory rheumatoid arthritis. We projected the 54-week results from a randomized controlled trial of infliximab into lifetime economic and clinical outcomes using a Markov computer simulation model. Direct and indirect costs, quality of life, and disability estimates were based on trial results; Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) database outcomes; and published data. Results were discounted using the standard 3% rate. Because most well-accepted medical therapies have cost-effectiveness ratios below $50,000 to $100,000 per quality-adjusted life-year (QALY) gained, results below this range were considered to be "cost-effective." At 3 mg/kg, each infliximab infusion would cost $1393. When compared with methotrexate alone, 54 weeks of infliximab plus methotrexate decreased the likelihood of having advanced disability from 23% to 11% at the end of 54 weeks, which projected to a lifetime marginal cost-effectiveness ratio of $30,500 per discounted QALY gained, considering only direct medical costs. When applying a societal perspective and including indirect or productivity costs, the marginal cost-effectiveness ratio for infliximab was $9100 per discounted QALY gained. The results remained relatively unchanged with variation of model estimates over a broad range of values. Infliximab plus methotrexate for 54 weeks for rheumatoid arthritis should be cost-effective with its clinical benefit providing good value for the drug cost, especially when including productivity losses. Although infliximab beyond 54 weeks will likely be cost-effective, the economic and clinical benefit remains uncertain and will depend on long-term results of clinical trials.

Clinical and radiological features of rheumatoid arthritis in British black Africans.

PubMed

Ravindran, Vinod; Seah, May-Ai; Elias, David A; Choy, Ernest H; Scott, David L; Gordon, Patrick A

2008-01-01

The objective of this study was to determine whether radiographic damage is different in British black African patients with rheumatoid arthritis compared to Caucasian patients. Data on demographics, disease- and disability-related variables were obtained from all black African patients and their age-, gender- and disease-duration-matched Caucasian controls. After all features identifying the patients were concealed, X-rays of hands and feet were scored by using the Sharp/van der Heijde method. Data were analysed using Mann-Whitney U test, t test and chi (2) test. Sixty-four patients (32 in each ethnic group) were studied. The median age was 52 years and median disease duration 6 years. Seventy-two percent of patients were female. Black Africans and Caucasians did not differ significantly in rheumatoid factor positivity, disease-modifying anti-rheumatic drugs and biological treatment use. British black African patients had significantly more tender joints and disability. Joint space narrowing was significantly greater in Caucasian patients [48 (27-85) vs 56 (34-107), p = 0.01]. Caucasian patients had more number of erosions (172 vs 220) and higher erosion score; however, the difference in the erosion scores was not statistically significant [2 (0-48) vs 4.5 (0-46), p = 0.17]. Radiographic damage was less severe in black African patients with rheumatoid arthritis compared to their age-, gender- and disease-duration-matched Caucasian controls. A large prospective study is required to confirm the findings of this study and to establish the factors which might be accountable for any differences in the expression of rheumatoid arthritis in this ethnic group.

Psoriasis, psoriatic arthritis, and rheumatoid arthritis: Is all inflammation the same?

PubMed

Coates, Laura C; FitzGerald, Oliver; Helliwell, Philip S; Paul, Carle

2016-12-01

To review the pathophysiology, co-morbidities, and therapeutic options for psoriasis, psoriatic arthritis and rheumatoid arthritis in order to further understand the similarities and differences in treatment paradigms in the management of each disease. New targets for individualized therapeutic decisions are also identified with the aim of improving therapeutic outcome and reducing toxicity. Using the PubMed database, we searched literature published from 2000 to 2015 using combinations of the key words "psoriasis," "psoriatic arthritis," "rheumatoid arthritis," "pathogenesis," "immunomodulation," and "treatment." This was a non-systematic review and there were no formal inclusion and exclusion criteria. Abstracts identified in the search were screened for relevance and articles considered appropriate evaluated further. References within these selected articles were also screened. Information was extracted from 198 articles for inclusion in this report. There was no formal data synthesis. Articles were reviewed and summarized according to disease area (psoriasis, psoriatic arthritis, and rheumatoid arthritis). The pathophysiology of psoriasis, psoriatic arthritis, and rheumatoid arthritis involves chronic inflammation mediated by pro-inflammatory cytokines. Dysfunction in integrated signaling pathways affecting different constituents of the immune system result in varying clinical features in the three diseases. Co-morbidities, including cardiovascular disease, malignancies, and non-alcoholic fatty liver disease are increased. Increased understanding of the immunopathogenesis allowed development of targeted treatments; however, despite a variety of potentially predictive genetic, protein and cellular biomarkers, there is still significant unmet need in these three inflammatory disorders. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Rheumatoid arthritis: identifying and characterising polymorphisms using rat models

PubMed Central

2016-01-01

ABSTRACT Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this disease. Genome-wide association studies have identified ∼100 new loci associated with rheumatoid arthritis, in addition to the already known locus within the major histocompatibility complex II region. However, together, these loci account for only a modest fraction of the genetic variance associated with this disease and very little is known about the pathogenic roles of most of the risk loci identified. Here, we discuss how rat models of rheumatoid arthritis are being used to detect quantitative trait loci that regulate different arthritic traits by genetic linkage analysis and to positionally clone the underlying causative genes using congenic strains. By isolating specific loci on a fixed genetic background, congenic strains overcome the challenges of genetic heterogeneity and environmental interactions associated with human studies. Most importantly, congenic strains allow functional experimental studies be performed to investigate the pathological consequences of natural genetic polymorphisms, as illustrated by the discovery of several major disease genes that contribute to arthritis in rats. We discuss how these advances have provided new biological insights into arthritis in humans. PMID:27736747

Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women

PubMed Central

Arleevskaya, Marina I.; Shafigullina, Albina Z.; Filina, Yulia V.; Lemerle, Julie; Renaudineau, Yves

2017-01-01

To evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ). In the eRA group, clinical [disease activity score (DAS28), health assessment questionnaire] and biological parameters associated with inflammation (erythrocyte sedimentation rate, C-reactive protein) or with RA [rheumatoid factor, anticyclic citrullinated peptide (anti-CCP2) antibodies] were evaluated. An elevated incidence of infection events in the previous year characterized the eRA and relative groups. In addition, a history of herpes simplex virus (HSV) episodes was associated with disease activity, while an elevated incidence of anti-CCP2 autoantibody characterized eRA patients with a history of viral upper respiratory tract infection symptoms (V-URI). Granulocyte ROS activity in eRA patients was quantitatively [STZ peak and its area under the curve (AUC)] and qualitatively (STZ time of peak) altered, positively correlated with disease activity, and parameters were associated with viral symptoms including HSV exacerbation/recurrence, and V-URI. In conclusion, our study provides arguments to consider a history of increased viral infection symptoms in RA at the early stage and such involvement needs to be studied further. PMID:29259607

Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women.

PubMed

Arleevskaya, Marina I; Shafigullina, Albina Z; Filina, Yulia V; Lemerle, Julie; Renaudineau, Yves

2017-01-01

To evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ). In the eRA group, clinical [disease activity score (DAS28), health assessment questionnaire] and biological parameters associated with inflammation (erythrocyte sedimentation rate, C-reactive protein) or with RA [rheumatoid factor, anticyclic citrullinated peptide (anti-CCP2) antibodies] were evaluated. An elevated incidence of infection events in the previous year characterized the eRA and relative groups. In addition, a history of herpes simplex virus (HSV) episodes was associated with disease activity, while an elevated incidence of anti-CCP2 autoantibody characterized eRA patients with a history of viral upper respiratory tract infection symptoms (V-URI). Granulocyte ROS activity in eRA patients was quantitatively [STZ peak and its area under the curve (AUC)] and qualitatively (STZ time of peak) altered, positively correlated with disease activity, and parameters were associated with viral symptoms including HSV exacerbation/recurrence, and V-URI. In conclusion, our study provides arguments to consider a history of increased viral infection symptoms in RA at the early stage and such involvement needs to be studied further.

[The golden age of rheumatoid arthritis treatment].

PubMed

Mercado, Ulises

2014-01-01

Today, we enjoy the golden age of rheumatology. In the 1970s, the paradigm for treating rheumatoid arthritis consisted in a pyramid. In the decade of the 1980s, and shortly after began a revolution in the understanding and treatment of rheumatic diseases. Methotrexate and tumor necrosis factor-blockers came on the scene.

Rheumatoid Arthritis-Associated Interstitial Lung Disease: Current Concepts.

PubMed

Brito, Yoel; Glassberg, Marilyn K; Ascherman, Dana P

2017-11-09

Among the many extra-articular complications of rheumatoid arthritis (RA), interstitial lung disease (ILD) contributes significantly to morbidity and mortality. Prevalence estimates for RA-ILD vary widely depending on the specific clinical, radiographic, and functional criteria used to establish the diagnosis. A key unresolved issue is whether early, subclinical forms of RA-ILD represent a precursor to end stage, fibrotic lung disease. Based on uncertainties surrounding the natural history of RA-ILD, incomplete understanding of underlying disease pathogenesis, and lack of controlled clinical trials, evidence-based therapeutic strategies remain largely undefined. Correlative clinico-epidemiological studies have identified key risk factors for disease progression. Complementing these findings, the identification of specific molecular and serological markers of RA-ILD has improved our understanding of disease pathogenesis and established the foundation for predictive biomarker profiling. Experience from case series and cohort studies suggests that newer biological agents such as rituximab may be viable treatment options. RA-ILD continues to have a major impact on "disease intrinsic" morbidity and mortality. Increased understanding of disease pathogenesis and the natural history of subclinical RA-ILD will promote the development of more refined therapeutic strategies.

[Gold salt alveolitis in 3 patients with rheumatoid arthritis].

PubMed

Music, E; Tomsic, M; Logar, D

1995-06-01

When the characteristic symptoms for an interstitial pulmonary disease arise in patients with rheumatoid arthritis, a drug-induced alveolitis should be considered in the differential diagnosis. In such cases, the administration of the drug and gold salts should be stopped. The cases of three patients with rheumatoid arthritis (RA) who had been treated with gold salts for 2 months (A), 23 months (B), and 36 months (C) are presented. The total dose of sodium aureothiomalate amounted to 280 mg for patient A, 1150 mg for patient B, and 2190 mg for patient C. Clinical signs, X-rays of the lungs, pulmonary function tests, and laboratory tests were evaluated for the three patients while, for patient A BAL as well as provocation tests were additionally performed before and after therapy. In this case, the histological picture of the lungs is presented; biopsies were taken during the first BAL. The clinical complaints of all 3 patients were similar, with the alveolitis being observed as diffuse in one case and above all in the upper regions in two cases on radiology. This led to differing degrees of diffusion disorders in the lungs. In patient A, the diagnosis was made in the stage of progressive fibrotic alveolitis and was treated with D-penicillamine. All 3 patients received steroids over 3-6 months and the gold salts were stopped. Because of the long duration and doubtful differential diagnosis for patient A with either rheumatoid lung or gold salt alveolitis, a provocation test with sodium aureothiomalate was performed. All 3 patients had blood eosinophilia while, in case A, a thrombopenia was also found. A gold salt alveolitis can occur as a side effect of gold salts in addition to skin vasculitis and hematological disorders. When the gold salt administration is not stopped a fibrotic alveolitis can develop. The provocation test can be diagnostically useful to distinguish between a rheumatoid lung and gold salt alveolitis.

Rheumatoid arthritis vaccine therapies: perspectives and lessons from therapeutic ligand epitope antigen presentation system vaccines for models of rheumatoid arthritis

PubMed Central

Rosenthal, Kenneth S.; Mikecz, Katalin; Steiner, Harold L.; Glant, Tibor T.; Finnegan, Alison; Carambula, Roy E.; Zimmerman, Daniel H.

2016-01-01

The current status of therapeutic vaccines for autoimmune diseases is reviewed with rheumatoid arthritis as the focus. Therapeutic vaccines for autoimmune diseases must regulate or subdue responses to common self-antigens. Ideally, such a vaccine would initiate an antigen-specific modulation of the T-cell immune response that drives the inflammatory disease. Appropriate animal models and types of T helper cells and signature cytokine responses that drive autoimmune disease are also discussed. Interpretation of these animal models must be done cautiously because the means of initiation, autoantigens, and even the signature cytokine and T helper cell (Th1 or Th17) responses that are involved in the disease may differ significantly from those in humans. We describe ligand epitope antigen presentation system vaccine modulation of T-cell autoimmune responses as a strategy for the design of therapeutic vaccines for rheumatoid arthritis, which may also be effective in other autoimmune conditions. PMID:25787143

Heat shock proteins: the missing link between hormonal and reproductive factors and rheumatoid arthritis?

PubMed

da Silva, J A

1991-10-01

Epidemiologic data suggest a strong link between hormonal and reproductive factors and the incidence of rheumatoid arthritis. Of interest is a possible protective effect of oral contraceptives or estrogen replacement therapy against the development of rheumatoid arthritis. At least 1 pregnancy also appears to reduce the risk of this disease. It has been hypothesized that hormonal contraceptive use and pregnancy elicit the production of higher amounts of endogenous heat shock proteins, which, in turn, induce immunotolerance to subsequent exposure to the actual triggering agent of rheumatoid arthritis. A related possibility is that pregnant women are exposed to specific types of heat shock proteins produced by the fetus in high concentrations. Heat shock proteins are known to be the predominant antigens related to the induction of reactive arthritis. The production of some such proteins is dependent on sex hormones in a tissue-specific way and their concentrations are raised dramatically by stimulation with estrogen and progesterone. A possible mechanism for heat protein-induced immunotolerance would be the predominant stimulation of a suppressor T cell clone. More research on the pathogenesis of rheumatic diseases and the activity of sex hormones could result in the development of a vaccine against rheumatoid arthritis.

Rheumatoid Arthritis and Incidence of Twelve Initial Presentations of Cardiovascular Disease: A Population Record-Linkage Cohort Study in England.

PubMed

Pujades-Rodriguez, Mar; Duyx, Bram; Thomas, Sara L; Stogiannis, Dimitris; Rahman, Anisur; Smeeth, Liam; Hemingway, Harry

2016-01-01

While rheumatoid arthritis is an established risk factor for cardiovascular disease (CVD), our knowledge of how the pattern of risk varies for different cardiovascular phenotypes is incomplete. The association between rheumatoid arthritis and the initial presentation of 12 types of CVDs were examined in a contemporary population of men and women of a wide age range. CALIBER data, which links primary care, hospital and mortality data in England, was analysed. A cohort of people aged ≥18 years and without history of CVD was assembled and included all patients with prospectively recorded rheumatoid arthritis from January 1997, until March 2010, matched with up to ten people without rheumatoid arthritis by age, sex and general practice. The associations between rheumatoid arthritis and the initial presentation of 12 types of CVDs were estimated using multivariable random effects Poisson regression models. The analysis included 12,120 individuals with rheumatoid arthritis and 121,191 comparators. Of these, 2,525 patients with and 18,146 without rheumatoid arthritis developed CVDs during a median of 4.2 years of follow-up. Patients with rheumatoid arthritis had higher rates of myocardial infarction (adjusted incidence ratio [IRR] = 1.43, 95%CI 1.21-1.70), unheralded coronary death (IRR = 1.60, 95%CI 1.18-2.18), heart failure (IRR = 1.61, 95%CI 1.43-1.83), cardiac arrest (HR = 2.26, 95%CI 1.69-3.02) and peripheral arterial disease (HR = 1.36, 95%CI 1.14-1.62); and lower rates of stable angina (HR = 0.83, 95%CI 0.73-0.95). There was no evidence of association with cerebrovascular diseases, abdominal aortic aneurysm or unstable angina, or of interactions with sex or age. The observed associations with some but not all types of CVDs inform both clinical practice and the selection of cardiovascular endpoints for trials and for the development of prognostic models for patients with rheumatoid arthritis.

Generation mechanism of RANKL(+) effector memory B cells: relevance to the pathogenesis of rheumatoid arthritis.

PubMed

Ota, Yuri; Niiro, Hiroaki; Ota, Shun-Ichiro; Ueki, Naoko; Tsuzuki, Hirofumi; Nakayama, Tsuyoshi; Mishima, Koji; Higashioka, Kazuhiko; Jabbarzadeh-Tabrizi, Siamak; Mitoma, Hiroki; Akahoshi, Mitsuteru; Arinobu, Yojiro; Kukita, Akiko; Yamada, Hisakata; Tsukamoto, Hiroshi; Akashi, Koichi

2016-03-16

The efficacy of B cell-depleting therapies for rheumatoid arthritis underscores antibody-independent functions of effector B cells such as cognate T-B interactions and production of pro-inflammatory cytokines. Receptor activator of nuclear factor κB ligand (RANKL) is a key cytokine involved in bone destruction and is highly expressed in synovial fluid B cells in patients with rheumatoid arthritis. In this study we sought to clarify the generation mechanism of RANKL(+) effector B cells and their impacts on osteoclast differentiation. Peripheral blood and synovial fluid B cells from healthy controls and patients with rheumatoid arthritis were isolated using cell sorter. mRNA expression of RANKL, osteoprotegerin, tumor necrosis factor (TNF)-α, and Blimp-1 was analyzed by quantitative real-time polymerase chain reaction. Levels of RANKL, CD80, CD86, and CXCR3 were analyzed using flow cytometry. Functional analysis of osteoclastogenesis was carried out in the co-culture system using macrophage RAW264 reporter cells. RANKL expression was accentuated in CD80(+)CD86(+) B cells, a highly activated B-cell subset more abundantly observed in patients with rheumatoid arthritis. Upon activation via B-cell receptor and CD40, switched-memory B cells predominantly expressed RANKL, which was further augmented by interferon-γ (IFN-γ) but suppressed by interleukin-21. Strikingly, IFN-γ also enhanced TNF-α expression, while it strongly suppressed osteoprotegerin expression in B cells. IFN-γ increased the generation of CXCR3(+)RANKL(+) effector B cells, mimicking the synovial B cell phenotype in patients with rheumatoid arthritis. Finally, RANKL(+) effector B cells in concert with TNF-α facilitated osteoclast differentiation in vitro. Our current findings have shed light on the generation mechanism of pathogenic RANKL(+) effector B cells that would be an ideal therapeutic target for rheumatoid arthritis in the future.

[Bone structure in rheumatoid arthritis].

PubMed

Ono, Kumiko; Ohashi, Satoru; Tanaka, Sakae; Matsumoto, Takuya

2013-07-01

In rheumatoid arthritis (RA) , the osteoclast pathway is activated by abnormal immune conditions accompanied by chronic inflammation, resulting in periarticular osteoporosis and local bone destruction around joints. In addition, multiple factors, including reduced physical activity and pharmacotherapies such as steroids, lead to systemic osteoporosis. These conditions cause decreasing bone mineral density and deterioration of bone quality, and expose patients to increased risk of fracture. Understanding the bone structures of RA and evaluating fracture risk are central to the treatment of RA.

Heparan Sulfate Differences in Rheumatoid Arthritis versus Healthy Sera

PubMed Central

López-Hoyos, Marcos; Seo, Youjin; Andaya, Armann; Leary, Julie A.

2015-01-01

Heparan sulfate (HS) is a complex and highly variable polysaccharide, expressed ubiquitously on the cell surface as HS proteoglycans (HSPGs), and found in the extracellular matrix as free HS fragments. Its heterogeneity due to various acetylation and sulfation patterns endows a multitude of functions. In animal tissues, HS interacts with a wide range of proteins to mediate numerous biological activities; given its multiple roles in inflammation processes, characterization of HS in human serum has significant potential for elucidating disease mechanisms. Historically, investigation of HS was limited by its low concentration in human serum, together with the complexity of the serum matrix. In this study, we used a modified mass spectrometry method to examine HS disaccharide profiles in the serum of 50 women with rheumatoid arthritis (RA), and compared our results to 51 sera from healthy women. Using various purification methods and online LC-MS/MS, we discovered statistically significant differences in the sulfation and acetylation patterns between populations. Since early diagnosis of RA is considered important in decelerating the disease's progression, identification of specific biomolecule characterizations may provide crucial information towards developing new therapies for suppressing the disease in its early stages. This is the first report of potential glycosaminoglycan biomarkers for RA found in human sera, while acknowledging the obvious fact that a larger population set, and more stringent collection parameters, will need to be investigated in the future. PMID:25217862

Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity

PubMed Central

2013-01-01

Introduction It remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA. Methods A cohort of 71 consecutive patients with early RA starting treatment with disease-modifying antirheumatic drugs (DMARDs) was recruited. Disease activity at baseline and after 21 to 24 weeks of follow-up was measured using the Disease Activity Score in 28 joints (DAS28). Immune response profiling was performed by analyzing multi-cytokine production from peripheral blood cells following incubation with a panel of stimuli, including a mixture of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates. Profiles identified via principal components analysis (PCA) for each stimulus were then correlated with the ΔDAS28 from baseline to follow-up. A clinically meaningful improvement in the DAS28 was defined as a decrease of ≥1.2. Results A profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12, and IFN-γ) produced in response to CMV/EBV was found to correlate with the ΔDAS28 from baseline to follow-up. At baseline, a higher magnitude of the CMV/EBV immune response profile predicted inadequate DAS28 improvement (mean PCA-1 scores: 65.6 versus 50.2; P = 0.029). The baseline CMV/EBV response was particularly driven by IFN-γ (P = 0.039) and IL-4 (P = 0.027). Among patients who attained clinically meaningful DAS28 improvement, the CMV/EBV PCA-1 score increased from baseline to follow-up (mean +11.6, SD 25.5), whereas among patients who responded inadequately to DMARD therapy, the CMV/EBV PCA-1 score decreased (mean -12.8, SD 25.4; P = 0.002). Irrespective of the ΔDAS28, methotrexate use was associated with up-regulation of the CMV/EBV response. The CMV/EBV profile was associated with positive CMV IgG (P <0.001), but not EBV IgG (P = 0.32), suggesting this response was related to

Geode development and multiple fractures in rheumatoid arthritis.

PubMed Central

Lowthian, P J; Calin, A

1985-01-01

The radiological development from normal bone of geodes and subsequent fractures in phalanges of two adjacent fingers is described in a patient with classical rheumatoid arthritis. Presentation was as a septic, discharging focus, but infection was excluded; the pathology is described. Images PMID:3977410

The role of autoantibodies in the pathophysiology of rheumatoid arthritis.

PubMed

Derksen, V F A M; Huizinga, T W J; van der Woude, D

2017-06-01

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. The presence of autoantibodies in the sera of RA patients has provided many clues to the underlying disease pathophysiology. Based on the presence of several autoantibodies like rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies (anti-CarP), and more recently anti-acetylated protein antibodies RA can be subdivided into seropositive and seronegative disease. The formation of these autoantibodies is associated with both genetic and environmental risk factors for RA, like specific human leukocyte antigen (HLA) alleles and smoking. Autoantibodies can be detected many years before disease onset in a subset of patients, suggesting a sequence of events in which the first autoantibodies develop in predisposed hosts, before an inflammatory response ensues leading to clinically apparent arthritis. Research on the characteristics and effector functions of these autoantibodies might provide more insight in pathophysiological processes underlying arthritis in RA. Recent data suggests that ACPA might play a role in perpetuating inflammation once it has developed. Furthermore, pathophysiological mechanisms have been discovered supporting a direct link between the presence of ACPA and both bone erosions and pain in RA patients. In conclusion, investigating the possible pathogenic potential of autoantibodies might lead to improved understanding of the underlying pathophysiological processes in rheumatoid arthritis.

Collagen‐induced arthritis as an animal model of rheumatoid cachexia

PubMed Central

Alabarse, Paulo V.G.; Lora, Priscila S.; Silva, Jordana M.S.; Santo, Rafaela C.E.; Freitas, Eduarda C.; de Oliveira, Mayara S.; Almeida, Andrelise S.; Immig, Mônica; Teixeira, Vivian O.N.; Filippin, Lidiane I.

2018-01-01

Abstract Background Rheumatoid arthritis is characterized by chronic polyarticular synovitis and presents systemic changes that impact quality of life, such as impaired muscle function, seen in up to 66% of the patients. This can progress to severely debilitating state known as rheumatoid cachexia—without loss of fat mass and body weight—for which there is little consensus in terms of diagnosis or treatment. This study aims to evaluate whether the collagen‐induced arthritis (CIA) animal model also develops clinical and functional features characteristic of rheumatoid cachexia. Methods Male DBA1/J mice were randomly divided into 2 groups: healthy animals (CO, n = 11) and CIA animals (n = 13). The clinical score and edema size, animal weight and food intake, free exploratory locomotion, grip strength, and endurance exercise performance were tested 0, 18, 35, 45, 55, and 65 days after disease induction. After euthanasia, several organs, visceral and brown fat, and muscles were dissected and weighed. Muscles were used to assess myofiber diameter. Ankle joint was used to assess arthritis severity by histological score. Statistical analysis were performed using one‐way and two‐way analyses of variance followed by Tukey's and Bonferroni's test or t‐test of Pearson and statistical difference were assumed for a P value under 0.05. Results The CIA had significantly higher arthritis scores and larger hind paw edema volumes than CO. The CIA had decreased endurance exercise performance total time (fatigue; 23, 22, 24, and 21% at 35, 45, 55, and 65 days, respectively), grip strength (27, 55, 63, 60, and 66% at 25, 35, 45, 55, and 65 days, respectively), free locomotion (43, 57, 59, and 66% at 35, 45, 55, and 65 days, respectively), and tibialis anterior and gastrocnemius muscle weight (25 and 24%, respectively) compared with CO. Sarcoplasmic ratios were also reduced in CIA (TA: 23 and GA: 22% less sarcoplasmic ratio), confirming the atrophy of skeletal muscle

Comparative study of the detection of joint injury in early-stage rheumatoid arthritis by magnetic resonance imaging of the wrist and finger joints and physical examination.

PubMed

Tamai, Mami; Kawakami, Atsushi; Iwamoto, Naoki; Kawashiri, Shin-Ya; Fujikawa, Keita; Aramaki, Toshiyuki; Kita, Junko; Okada, Akitomo; Koga, Tomohiro; Arima, Kazuhiko; Kamachi, Makoto; Yamasaki, Satoshi; Nakamura, Hideki; Ida, Hiroaki; Origuchi, Tomoki; Takao, Shoichiro; Aoyagi, Kiyoshi; Uetani, Masataka; Eguchi, Katsumi

2011-03-01

To verify whether magnetic resonance imaging (MRI)-proven joint injury is sensitive as compared with joint injury determined by physical examination. MRI of the wrist and finger joints of both hands was examined in 51 early-stage rheumatoid arthritis (RA) patients by both plain and gadolinium diethylenetriaminepentaacetic acid-enhanced MRI. Synovitis, bone edema, and bone erosion (the latter two included as bone lesions at the wrist joints); metacarpophalangeal joints; and proximal interphalangeal joints were considered as MRI-proven joint injury. Japan College of Rheumatology-certified rheumatologists had given a physical examination just before the MRI study. The presence of tender and/or swollen joints in the same fields as MRI was considered as joint injury on physical examination. The association of MRI-proven joint injury with physical examination-proven joint injury was examined. A total of 1,110 sites were available to be examined. MRI-proven joint injury was found in 521 sites, whereas the other 589 sites were normal. Physical examination-proven joint injury was found in 305 sites, which was significantly low as compared with MRI-proven joint injury (P = 1.1 × 10(-12) versus MRI). Joint injury on physical examination was not found in 81.5% of the sites where MRI findings were normal. Furthermore, an association of the severity of MRI-proven joint injury with that of joint injury on physical examination was clearly demonstrated (P = 1.6 × 10(-15), r(s) = 0.469). Our present data suggest that MRI is not only sensitive but accurately reflects the joint injury in patients with early-stage RA. Copyright © 2011 by the American College of Rheumatology.

[Homeostasis and Disorder of Musculoskeletal System.Progress in the treatment of rheumatoid arthritis.

PubMed

Tanaka, Yoshiya

Rheumatoid arthritis is a systemic autoimmune disease characterized by inflammation and joint damage that causes significant morbidity and mortality. Rapid and appropriate intervention using disease-modifying anti-rheumatic drugs(DMARDs)is prerequisite to halt joint destruction and long-term functional disabilities. Recent progress in the treatment strategy has brought about paradigm shift for the management of the disease, namely, the combined use of methotrexate, a synthetic DMARD, and a biologic DMARD targeting TNF, IL-6 and T cells has revolutionized treatment of rheumatoid arthritis. Clinical remission is now realistic targets for the treatment, achieved by a large proportion of rheumatoid arthritis patients, which leads to structural remission without damage in bone and cartilage as well as functional remission. Furthermore, orally available small but strong molecules targeting Janus kinase(JAK)are emerging. When DMARDs are prescribed, appropriate selection of DMARDs, adequate screening, regular monitoring and systemic management are required.

A Case of Disseminated Histoplasmosis in a Patient with Rheumatoid Arthritis on Abatacept.

PubMed

Jain, Nina; Doyon, Jeffrey B; Lazarus, Jacob E; Schaefer, Inga-Marie; Johncilla, Melanie E; Agoston, Agoston T; Dalal, Anuj K; Velásquez, Gustavo E

2018-05-01

Biologic agents are effective treatments for rheumatoid arthritis but are associated with important risks, including severe infections. Tumor Necrosis Factor (TNF) α inhibitors are known to increase the risk of systemic fungal infections such as disseminated histoplasmosis. Abatacept is a biologic agent with a mechanism different from that of TNFα inhibitors: It suppresses cellular immunity by competing for the costimulatory signal on antigen-presenting cells. The risk of disseminated histoplasmosis for patients on abatacept is not known. We report a case of abatacept-associated disseminated histoplasmosis and review the known infectious complications of abatacept. While the safety of resuming biologic agents following treatment for disseminated histoplasmosis is also not known, abatacept is recommended over TNFα inhibitors for rheumatoid arthritis patients with a prior serious infection. We discuss the evidence supporting this recommendation and discuss alternative treatments for rheumatoid arthritis patients with a history of a serious infection.

[The laser therapy of rheumatoid arthritis].

PubMed

Soroka, N F

1989-01-01

About 300 patients with rheumatoid arthritis (RA) underwent multimodality treatment including laser radiation of varying wavelengths. Use was made of helium-neon, infrared, argon and helium-cadmium lasers. A new method of combined laser therapy by radiation of helium-cadmium and helium-neon lasers is described. A scheme of optimal parameters and types of laser radiation recommended for the treatment of different clinical varieties of RA is provided.

The Plasticity of Th17 Cells in the Pathogenesis of Rheumatoid Arthritis.

PubMed

Kotake, Shigeru; Yago, Toru; Kobashigawa, Tsuyoshi; Nanke, Yuki

2017-07-10

Helper T (Th) cells play an important role in the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). It has been revealed that Th17 cells can shift to Th1 cells (i.e., "nonclassic Th1 cells"), which are reported to be more pathogenic than Th17 cells per se . Thus, the association of Th cells in the pathogenesis of autoimmune disease has become more complicated. We recently reported using peripheral blood from untreated and early-onset RA patients that the ratio of CD161+Th1 cells (i.e., Th17-derived Th1 cells to CD161+Th17 cells) is elevated and that levels of interferon-γ (IFNγ)+Th17 cells are inversely correlated with levels of anti-CCP antibodies. Here, we review the plasticity of Th17 cells in the pathogenesis of RA, suggesting possible implications for novel therapies.

The Plasticity of Th17 Cells in the Pathogenesis of Rheumatoid Arthritis

PubMed Central

Kotake, Shigeru; Kobashigawa, Tsuyoshi; Nanke, Yuki

2017-01-01

Helper T (Th) cells play an important role in the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). It has been revealed that Th17 cells can shift to Th1 cells (i.e., “nonclassic Th1 cells”), which are reported to be more pathogenic than Th17 cells per se. Thus, the association of Th cells in the pathogenesis of autoimmune disease has become more complicated. We recently reported using peripheral blood from untreated and early-onset RA patients that the ratio of CD161+Th1 cells (i.e., Th17-derived Th1 cells to CD161+Th17 cells) is elevated and that levels of interferon-γ (IFNγ)+Th17 cells are inversely correlated with levels of anti-CCP antibodies. Here, we review the plasticity of Th17 cells in the pathogenesis of RA, suggesting possible implications for novel therapies. PMID:28698517

Sequential high-content profiling of the IgG-autoantibody repertoire reveals novel antigens in rheumatoid arthritis.

PubMed

Vordenbäumen, Stefan; Lueking, Angelika; Budde, Petra; Zucht, Hans-Dieter; Goehler, Heike; Brinks, Ralph; Fischer-Betz, Rebecca; Richter, Jutta; Bleck, Ellen; Detert, Jacqueline; Langer, Hans-Eckhard; Sörgel, Anne; Burmester, Gerd-Rüdiger; Schulz-Knappe, Peter; Schneider, Matthias

2016-10-12

The aim was to identify novel diagnostic autoantibody candidates for rheumatoid arthritis (RA) by comprehensive screening for autoreactivity. We incubated 5892 recombinant proteins coupled to fluorescent beads, with patients' sera for the detection of IgG-autoantibodies in three independent patient cohorts: A (n = 72 patients with established RA); B/B- (n = 116 patients with early RA (B) and n = 51 CCP-negative patients with early RA from B (B-)); and C (n = 184 patients with early seronegative RA), in comparison to matched healthy controls. Intersects of significantly increased autoantibodies as determined by the Mann-Whitney test were sought. Screening of 5892 antigens in RA cohorts A and B, or the seronegative cohorts B- and C revealed intersects of 23 and 13 significantly increased autoantibodies, respectively. Reactivity to three antigens was increased in all cohorts tested: N-acetylglucosamine-1-phosphate transferase, gamma subunit (GNPTG), heterogeneous nuclear ribonucleoprotein A1-like 2 (HNRNPA1), and insulin-like growth factor binding protein 2 (IGFBP2). Comprehensive sequential screening for autoantibodies reveals novel candidates for diagnostic markers in both seropositive and seronegative RA and suggests new fields of research into the pathogenesis of RA.

Life stories of people with rheumatoid arthritis who retired early: how gender and other contextual factors shaped their everyday activities, including paid work.

PubMed

Stamm, T A; Machold, K P; Smolen, J; Prodinger, B

2010-06-01

The aim of the present study was to explore how contextual factors affect the everyday activities of women and men with rheumatoid arthritis (RA), as evident in their life stories. Fifteen people with RA, who had retired early due to the disease, were interviewed up to three times, according to a narrative biographic interview style. The life stories of the participants, which were reconstructed from the biographical data and from the transcribed 'told story' were analysed from the perspective of contextual factors, including personal and environmental factors. The rigour and accuracy of the analysis were enhanced by reflexivity and peer-review of the results. The life stories of the participants in this study reflected how contextual factors (such as gender, the healthcare system, the support of families and social and cultural values) shaped their everyday activities. In a society such as in Austria, which is based on traditional patriarchal values, men were presented with difficulties in developing a non-paid-work-related role. For women, if paid work had to be given up, they were more likely to engage in alternative challenging activities which enabled them to develop reflective skills, which in turn contributed to a positive and enriching perspective on their life stories. Health professionals may thus use some of the women's strategies to help men. Interventions by health professionals in people with RA may benefit from an approach sensitive to personal and environmental factors.

Opposing effects of rheumatoid arthritis and low dose prednisolone on arginine metabolomics.

PubMed

Radhakutty, Anjana; Mangelsdorf, Brenda L; Drake, Sophie M; Rowland, Andrew; Smith, Malcolm D; Mangoni, Arduino A; Thompson, Campbell H; Burt, Morton G

2017-11-01

The effects of low dose prednisolone on circulating markers of endothelial function, the arginine metabolites asymmetric dimethyl arginine (ADMA), mono methyl arginine (MMA), and homoarginine, are uncertain. We assessed whether patients with rheumatoid arthritis have perturbations in arginine metabolite concentrations that are reversed by low dose prednisolone. Eighteen rheumatoid arthritis patients who had not taken prednisolone for >6 months (non-glucocorticoid (GC) users), 18 rheumatoid arthritis patients taking continuous oral prednisolone (6.5 ± 1.8 mg/day) for >6 months (GC users) and 20 healthy controls were studied. Fasting plasma concentrations of ADMA, MMA, and homoarginine were measured by ultra-performance liquid-chromatography. Baseline data from non-GC users were compared with healthy controls to assess the effect of rheumatoid arthritis. The change in arginine metabolites in non-GC users after 7 days of prednisolone (6 mg/day) was used to assess the acute effects of prednisolone. Baseline data from non-GC users were compared with GC users to assess the chronic effects of prednisolone. Non-GC users had higher ADMA (0.59 ± 0.03 vs. 0.47 ± 0.01 μM, p = 0.004) and MMA concentrations (0.10 ± 0.01 vs. 0.05 ± 0.00 μM, p < 0.001) than controls. The only change with acute prednisolone was a reduction in homoarginine (1.23 ± 0.06 vs. 1.08 ± 0.06 μM, p = 0.04) versus baseline. GC users had lower concentrations of ADMA (0.51 ± 0.02 vs. 0.59 ± 0.03 μM, p = 0.03) than non-GC users. Rheumatoid arthritis patients have higher concentrations of ADMA and MMA, inhibitors of endothelial function. Chronic, but not acute, prednisolone therapy is associated with a lower ADMA concentration, suggesting a salutary effect of long-term glucocorticoid treatment on endothelial function. Copyright © 2017 Elsevier B.V. All rights reserved.

Sexual dysfunction and its determinants in Malaysian women with rheumatoid arthritis.

PubMed

Shahar, Mohammad A; Hussein, Heselynn; Sidi, Hatta; Shah, Shamsul A; Mohamed Said, Mohd S

2012-10-01

To determine the prevalence of sexual dysfunction (FSD) among women with rheumatoid arthritis attending the Rheumatology Clinic in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and Hospital Putrajaya, Malaysia, and to determine its associations with potential clinical and disease activity factors. This was a cross-sectional study involving women with rheumatoid arthritis between the ages of 20 and 60 years. A validated Malay Version Female Sexual Function Index (MVFSFI) was administered to diagnose FSD. Sociodemographic and disease activity profiles were obtained and those who had and did not have FSD were compared. Among 63 respondents, 51 patients were included in the analysis for FSD. The prevalence of FSD in women with rheumatoid arthritis attending UKMMC and Hospital Putrajaya Rheumatology Clinic was 29.4%. Erythrocyte sedimentation rate (ESR) and Disease Activity Score in 28 joints (DAS28-ESR) correlates with MVFSFI score with r=-0.364 (P=0.009) and r=-0.268 (P=0.057), respectively. Sociodemographic factors that correlate with MVFSFI score were: patient's age (r=0.520, P<0.001); duration of marriage (r=-0.355, P=0.001); husband's age (r=-0.460, P=0.001); age of oldest child (r=-0.449, P=0.001); and age of youngest child (r=-0.627, P<0.001). We found in this study that the prevalence of FSD in rheumatoid arthritis in our centers was 29.4%. Age and family dynamics appear to be more important predictors compared to disease activity. © 2012 The Authors International Journal of Rheumatic Diseases © 2012 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Conceptual Design of Simulation Models in an Early Development Phase of Lunar Spacecraft Simulator Using SMP2 Standard

NASA Astrophysics Data System (ADS)

Lee, Hoon Hee; Koo, Cheol Hea; Moon, Sung Tae; Han, Sang Hyuck; Ju, Gwang Hyeok

2013-08-01

The conceptual study for Korean lunar orbiter/lander prototype has been performed in Korea Aerospace Research Institute (KARI). Across diverse space programs around European countries, a variety of simulation application has been developed using SMP2 (Simulation Modelling Platform) standard related to portability and reuse of simulation models by various model users. KARI has not only first-hand experience of a development of SMP compatible simulation environment but also an ongoing study to apply the SMP2 development process of simulation model to a simulator development project for lunar missions. KARI has tried to extend the coverage of the development domain based on SMP2 standard across the whole simulation model life-cycle from software design to its validation through a lunar exploration project. Figure. 1 shows a snapshot from a visualization tool for the simulation of lunar lander motion. In reality, a demonstrator prototype on the right-hand side of image was made and tested in 2012. In an early phase of simulator development prior to a kick-off start in the near future, targeted hardware to be modelled has been investigated and indentified at the end of 2012. The architectural breakdown of the lunar simulator at system level was performed and the architecture with a hierarchical tree of models from the system to parts at lower level has been established. Finally, SMP Documents such as Catalogue, Assembly, Schedule and so on were converted using a XML(eXtensible Mark-up Language) converter. To obtain benefits of the suggested approaches and design mechanisms in SMP2 standard as far as possible, the object-oriented and component-based design concepts were strictly chosen throughout a whole model development process.

Preserved cardiorespiratory function and NT-proBNP levels before and during exercise in patients with recent onset of rheumatoid arthritis: the clinical challenge of stratifying the patient cardiovascular risks.

PubMed

Zoli, A; Bosello, S; Comerci, G; Galiano, N; Forni, A; Loperfido, F; Ferraccioli, G F

2017-01-01

Rheumatoid arthritis (RA) is associated with an increased risk of myocardial infarction and congestive heart failure. In RA patients, elevated NT-proBNP levels have been reported to be a prognostic marker of left ventricular dysfunction. In this study, we evaluated cardiorespiratory functional capacity and NT-proBNP levels before and during cardiopulmonary exercise test in early RA (ERA) patients. Twenty ERA patients and 10 healthy controls were studied by color Doppler echocardiography to evaluate ventricular systolic and diastolic function. Arterial stiffness and wave reflections were quantified non-invasively using applanation tonometry of the radial artery. Cardiopulmonary treadmill test was performed to measure peak VO 2 and VE/VCO 2 parameters. NT-proBNP plasma levels were measured before and at the exercise peak during cardiopulmonary exercise. The peak oxygen uptake [VO 2 (ml/min/kg)], the ventilatory equivalents for carbon dioxide (EqCO 2 ), respiratory exchange ratio and arterial stiffness were similar between patients and controls during cardiopulmonary exercise test. Basal and peak cardiopulmonary exercise NT-proBNP plasma levels were comparable in ERA patients with respect to healthy controls. When we analyzed patients according to disease characteristics and cardiovascular risk factors, ERA patients with high disease activity, BMI > 25 kg/m 2 and ACPA positivity presented significantly higher baseline and exercise peak NT-proBNP levels. Cardiorespiratory function is preserved in patients with recent onset of rheumatoid arthritis. The increased basal and exercise peak NT-proBNP plasma levels in patients with negative disease prognostic factors represent a possible marker to stratify the cardiovascular risk in patients with early rheumatoid arthritis.

Is Male Rheumatoid Arthritis an Occupational Disease? A Review

PubMed Central

Murphy, Dan; Hutchinson, David

2017-01-01

Background: Rheumatoid arthritis (RA) is a systemic, inflammatory disease with an estimated global prevalence of 0.3–1.0%. An unexplained association exists between low formal education and the development of RA independent of smoking. It is established that RA is initiated in the lungs and that various occupations associated with dust, fume and metal inhalation can increase the risk of RA development. Objective: The objective of this review is to evaluate published clinical reports related to occupations associated with RA development. We highlight the concept of a “double-hit” phenomenon involving adsorption of toxic metals from cigarette smoke by dust residing in the lung as a result of various work exposures. We discuss the relevant pathophysiological consequences of these inhalational exposures in relation to RA associated autoantibody production. Method: A thorough literature search was performed using available databases including Pubmed, Embase, and Cochrane database to cover all relative reports, using combinations of keywords: rheumatoid arthritis, rheumatoid factor, anti-citrullinated peptide antibody silica, dust, fumes, metals, cadmium, cigarette smoking, asbestos, mining, bronchial associated lymphoid tissue, heat shock protein 70, and adsorption. Conclusion: We postulate that the inhalation of dust, metals and fumes is a significant trigger factor for RA development in male patients and that male RA should be considered an occupational disease. To the best of our knowledge, this is the first review of occupations as a risk factor for RA in relation to the potential underlying pathophysiology. PMID:28932330

Discrete Element Model for Simulations of Early-Life Thermal Fracturing Behaviors in Ceramic Nuclear Fuel Pellets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hai Huang; Ben Spencer; Jason Hales

2014-10-01

A discrete element Model (DEM) representation of coupled solid mechanics/fracturing and heat conduction processes has been developed and applied to explicitly simulate the random initiations and subsequent propagations of interacting thermal cracks in a ceramic nuclear fuel pellet during initial rise to power and during power cycles. The DEM model clearly predicts realistic early-life crack patterns including both radial cracks and circumferential cracks. Simulation results clearly demonstrate the formation of radial cracks during the initial power rise, and formation of circumferential cracks as the power is ramped down. In these simulations, additional early-life power cycles do not lead to themore » formation of new thermal cracks. They do, however clearly indicate changes in the apertures of thermal cracks during later power cycles due to thermal expansion and shrinkage. The number of radial cracks increases with increasing power, which is consistent with the experimental observations.« less

3D simulations of early blood vessel formation

NASA Astrophysics Data System (ADS)

Cavalli, F.; Gamba, A.; Naldi, G.; Semplice, M.; Valdembri, D.; Serini, G.

2007-08-01

Blood vessel networks form by spontaneous aggregation of individual cells migrating toward vascularization sites (vasculogenesis). A successful theoretical model of two-dimensional experimental vasculogenesis has been recently proposed, showing the relevance of percolation concepts and of cell cross-talk (chemotactic autocrine loop) to the understanding of this self-aggregation process. Here we study the natural 3D extension of the computational model proposed earlier, which is relevant for the investigation of the genuinely three-dimensional process of vasculogenesis in vertebrate embryos. The computational model is based on a multidimensional Burgers equation coupled with a reaction diffusion equation for a chemotactic factor and a mass conservation law. The numerical approximation of the computational model is obtained by high order relaxed schemes. Space and time discretization are performed by using TVD schemes and, respectively, IMEX schemes. Due to the computational costs of realistic simulations, we have implemented the numerical algorithm on a cluster for parallel computation. Starting from initial conditions mimicking the experimentally observed ones, numerical simulations produce network-like structures qualitatively similar to those observed in the early stages of in vivo vasculogenesis. We develop the computation of critical percolative indices as a robust measure of the network geometry as a first step towards the comparison of computational and experimental data.

[Education of patients with rheumatoid arthritis. Assessment of a survey of interests].

PubMed

Pacheco, D; Berdichevsky, R; Ballesteros, F; Jérez, J; Sobarzo, E; Fuentealba, C; Pino, C; Sanhueza, R; Estefan, M E; Medina, C

1998-02-01

The congruence of interests between health care providers and clients is essential if subjects with chronic diseases will be educated. To assess, in patients with rheumatoid arthritis, those fields in which they would like to receive education. Eighty eight patients with rheumatoid arthritis were surveyed about the topics in which they would like to be educated. The inquiry included medical aspects, handicap overcoming, social issues and labor aspects. Eighty two percent of patients were interested in medical aspects, 77% in social issues and 71% in handicap overcoming. Eighty three percent of patients with greater handicaps preferred handicap overcoming, 75% social aspects and 74% medical aspects. Younger patients had a greater interest in labor aspects, those with a recently diagnosed disease were interested in their legal rights and those with a prolonged disease wanted information about self help groups. The greater educational interests of patients with rheumatoid arthritis were on medical aspects. However, those impaired by the disease were interested in handicap overcoming. Age and duration of the disease also influenced the educational interests of patients. Thus, education in these patients must be individualized.

High Prevalence of Gallstone Disease in Rheumatoid Arthritis: A New Comorbidity Related to Dyslipidemia?

PubMed

García-Gómez, María Carmen; de Lama, Eugenia; Ordoñez-Palau, Sergi; Nolla, Joan Miquel; Corbella, Emili; Pintó, Xavier

2017-08-01

To assess the prevalence of gallstone disease and identify associated risk factors in rheumatoid arthritis (RA) patients compared to the general population. Eighty-four women with rheumatoid arthritis were included in the study. Each patient was assessed via a structured interview, physical examination, abdominal ultrasound and blood test including lipid profile. The prevalence of gallstone disease in rheumatoid arthritis was compared with data from a study of the Spanish population matched by age groups. Twenty-eight of the 84 women had gallstone disease (33.3%). RA women with and without gallstone disease were similar in most of the variables assessed, except for older age and menopausal status in the former. A greater prevalence of gallstone disease was seen in rheumatoid arthritis patients compared to the general population of the same age; however, the differences were significant only in women aged 60 or older (45.5% versus 23.1% respectively, P-value .008). The age-adjusted OR of developing gallstone disease in RA women compared with general population women was 2,3 (95% CI: 1.3-4.1). A significantly higher HDL3-c subfraction and higher apoA-I/HDL and HDL3-c/TC ratios were observed in patients with gallstone disease. Women with rheumatoid arthritis may have a predisposition to gallstones that can manifest in middle or older age compared with women in the general population. This situation could be related to chronic inflammation and HDL metabolism. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Explanatory factors and predictors of fatigue in persons with rheumatoid arthritis: A longitudinal study.

PubMed

Feldthusen, Caroline; Grimby-Ekman, Anna; Forsblad-d'Elia, Helena; Jacobsson, Lennart; Mannerkorpi, Kaisa

2016-04-28

To investigate the impact of disease-related aspects on long-term variations in fatigue in persons with rheumatoid arthritis. Observational longitudinal study. Sixty-five persons with rheumatoid arthritis, age range 20-65 years, were invited to a clinical examination at 4 time-points during the 4 seasons. Outcome measures were: general fatigue rated on visual analogue scale (0-100) and aspects of fatigue assessed by the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire. Disease-related variables were: disease activity (erythrocyte sedimentation rate), pain threshold (pressure algometer), physical capacity (six-minute walk test), pain (visual analogue scale (0-100)), depressive mood (Hospital Anxiety and Depression scale, depression subscale), personal factors (age, sex, body mass index) and season. Multivariable regression analysis, linear mixed effects models were applied. The strongest explanatory factors for all fatigue outcomes, when recorded at the same time-point as fatigue, were pain threshold and depressive mood. Self-reported pain was an explanatory factor for physical aspects of fatigue and body mass index contributed to explaining the consequences of fatigue on everyday living. For predicting later fatigue pain threshold and depressive mood were the strongest predictors. Pain threshold and depressive mood were the most important factors for fatigue in persons with rheumatoid arthritis.

Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trentham, D.E.; Belli, J.A.; Anderson, R.J.

Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly after a year after the completion of irradiation and was paralleled by a restitutionmore » of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.« less

Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trentham, D.E.; Belli, J.A.Anderson, R.J.; Buckley, J.A.

Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly before a year after the completion of irradiation and was paralleled by a restitutionmore » of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.« less

Increased concentration of two different advanced glycation end-products detected by enzyme immunoassays with new monoclonal antibodies in sera of patients with rheumatoid arthritis.

PubMed

Vytásek, Richard; Sedová, Liliana; Vilím, Vladimír

2010-05-03

Levels of pentosidine (representative of advanced glycation end-products) in sera of patients with rheumatoid arthritis are increased when compared with sera of other diagnoses or healthy controls. These levels have been reported to correlate with clinical indices of rheumatoid arthritis activity and with laboratory markers of inflammation. The purpose of this study was to find out if these findings pertain to other advanced glycation end-products. We have developed two immunoassays based on new monoclonal antibodies to advanced glycation end-products. Antibody 103-E3 reacts with an unidentified antigen, formed in the reaction of proteins with ribose, while antibody 8-C1 responds to Nepsilon-(carboxyethyl)lysine. We have used these monoclonal antibodies to measure levels of advanced glycation end-products in sera of patients with rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and healthy controls. We calculated the correlations between advanced glycation end-product levels in rheumatoid arthritis sera and the Disease Activity Score 28 (DAS28), age, disease duration, CRP, anti-CCP, rheumatoid factor and treatment with corticosteroids, respectively. Levels of both glycation products were significantly higher in sera of patients with rheumatoid arthritis when compared with sera of patients with systemic lupus erythematosus, osteoarthritis, or the healthy controls. Neither the level of Nepsilon-(carboxyethyl)lysine nor the level of the 103-E3 antigen in rheumatoid arthritis sera correlated with the DAS28-scored rheumatoid arthritis activity. The levels of both antigens in rheumatoid arthritis sera did not correlate with age, gender, corticosteroid treatment, or levels of CRP, anti-CCP antibodies, and rheumatoid factor in sera. We report highly specific increases in the levels of two advanced glycation end-products in sera of patients with rheumatoid arthritis. This increase could be explained neither by rheumatoid arthritis activity nor by

Does tocilizumab contribute to elevation of rheumatoid factor and induction of paradoxical syaloadenitis in rheumatoid arthritis patients?

PubMed

Martinović Kaliterna, Dušanka; Aljinović, Jure; Perković, Dijana; Marasović Krstulović, Daniela; Marinović, Ivanka; Vlak, Tonko

2014-02-01

A 56-year-old woman, treated with tocilizumab (TCZ) for 8 months for severe rheumatoid arthritis (RA), was admitted to the hospital due to the swelling and tenderness of parotid glands. The patient was diagnosed with seropositive erosive RA in 1988, and treated with different disease modifying antirheumatic drugs (DMARDs) that were used together with a low dosage of glucocorticoides, followed by biologic therapy with infliximab and adalimumab which also proved to be inefficient. The patient had an excellent initial response on TCZ therapy. After 8 months, she was presented with an extreme enlargement of parotid glands. Bacterial, viral, and granulomatous diseases were excluded. A spectrum of autoantibodies including anti-Ro and anti-La showed normal values, expect for slightly elevated anti-cyclic citrullinated peptide (anti-CCP) and extreme elevation of the rheumatoid factor (RF) to 10,100 IU/ml. The biopsy of salivary glands was done and histological specimen showed limphoplasmocytic syaloadenitis. Tocilizumab therapy was stopped and the dosage of glucocorticoids and methotrexate (MTX) was raised. After 6 weeks, the patient was in better condition with slightly lower levels of RF (9,010 IU/ml). We hypothesise that in this patient, TCZ stimulated RF hyper production which can induce a paradoxical secondary syaloadenitis in RA.

Metabolic Syndrome in Rheumatoid Arthritis

PubMed Central

Ferraz-Amaro, Iván; González-Juanatey, Carlos; López-Mejias, Raquel; Riancho-Zarrabeitia, Leyre; González-Gay, Miguel A.

2013-01-01

Insulin resistance is an essential feature of the metabolic syndrome that has been linked to rheumatoid arthritis (RA). Understanding how inflammation arising in one tissue affects the physiology and pathology of other organs remains an unanswered question with therapeutic implications for chronic conditions including obesity, diabetes mellitus, atherosclerosis, and RA. Adipokines may play a role in the development of atherogenesis in patients with RA. Biologic therapies, such as TNF-α antagonists, that block proinflammatory cytokines have beneficial effects on the insulin resistance that is often observed in patients with RA. PMID:23431244

Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis.

PubMed

Crofford, L J; Kalogeras, K T; Mastorakos, G; Magiakou, M A; Wells, J; Kanik, K S; Gold, P W; Chrousos, G P; Wilder, R L

1997-04-01

Systemic symptoms in rheumatoid arthritis (RA) are mediated, at least in part, by elevated levels of circulating interleukin (IL)-6, and this cytokine is also a potent stimulus of the hypothalamic-pituitary-adrenal axis. To evaluate the 24-h circadian secretory dynamics of ACTH, cortisol, and IL-6 and their interactions in patients with early untreated RA, we recruited and studied five newly diagnosed, untreated RA patients early in the course of their disease and five age-, gender-, and race-matched control subjects. We collected serial blood samples over 24 h and measured plasma ACTH and cortisol every 30 min and IL-6 every hour. The 24-h collection was followed by administration of ovine CRH (oCRH) and post-oCRH serial blood samples over 2 h. We analyzed the 24-h overall levels of these hormones and their circadian variations and performed time-lagged cross-correlation analyses among them. The untreated RA patients had 24 h time-integrated plasma ACTH, plasma cortisol levels, and urinary free cortisol excretion that were not significantly different from control subjects, in spite of their disease activity. However, an earlier morning surge of plasma ACTH and cortisol in the patients was suggested. Plasma ACTH and cortisol responses to oCRH were similar in RA patients and controls. IL-6 levels were significantly increased in the RA patients compared with control subjects during the early morning hours (P < 0.05). There was pronounced circadian variation of plasma Il-6 levels. In the RA patients, we detected a positive temporal correlation between plasma levels of IL-6 and ACTH/cortisol, with elevated levels of IL-6 before the elevations of ACTH and cortisol by 1 and 2 h, respectively. In the same patients, we detected a negative effect of cortisol upon IL-6 exerted with a delay of 5 h. The data presented here suggest that although endogenous IL-6 may stimulate secretion of ACTH and cortisol, overall activity of the hypothalamic-pituitary-adrenal axis remains

Flurbiprofen in the symptomatic management of rheumatoid arthritis: a valuable alternative.

PubMed

Richy, F; Rabenda, V; Mawet, A; Reginster, J-Y

2007-08-01

The withdrawal of certain cyclooxygenase-2 selective drugs and the availability of over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) have increased the pressure for researching and prescribing conventional NSAIDs with a favourable efficacy/tolerance ratio in inflammatory diseases, particularly rheumatoid arthritis. The aim of this comprehensive meta-analysis was to evaluate the absolute and relative efficacy and safety of flurbiprofen in the management of rheumatoid arthritis. A systematic and exhaustive bibliographic research of published literature has been performed. The inclusion criteria are summarised as follows: randomised trial and rheumatoid arthritis and flurbiprofen and oral administration and anti-inflammatory doses from 100 to 300 mg and (placebo or aspirin or indomethacin or naproxen or ibuprofen or ketoprofen) and (articular pain or stiffness or swelling or mobility or patient/physician reported efficacy or tolerance or gastrointestinal (GI) tolerance). Studies were conducted from January 1975 to January 2006. Analyses have been stratified by comparisons and outcomes. Publication bias and robustness have been extensively investigated. Fourteen studies, accounting for 1103 patient-years, have been included in the quantitative review. The mean daily doses administrated were 200 mg flurbiprofen, 4000 mg aspirin, 150 indomethacin, 750 mg naproxen and 1800 mg ibuprofen. Flurbiprofen was superior to placebo for all outcomes, and superior to three of four other NSAIDs in terms of formal symptomatic measures (pain, stiffness and swelling). Several patients or physicians reported the efficacy of flurbiprofen as superior to indomethacin and naproxen, while its safety, and particularly its GI tolerance were better compared with aspirin and indomethacin. Sensitivity analyses have reported a sufficient robustness against systematic publication bias assumptions. This meta-analysis has shown that flurbiprofen is an interesting alternative to commonly

Whipple's disease mimicking rheumatoid arthritis can cause misdiagnosis and treatment failure.

PubMed

Glaser, Cornelia; Rieg, Siegbert; Wiech, Thorsten; Scholz, Christine; Endres, Dominique; Stich, Oliver; Hasselblatt, Peter; Geißdörfer, Walter; Bogdan, Christian; Serr, Annerose; Häcker, Georg; Voll, Reinhard E; Thiel, Jens; Venhoff, Nils

2017-05-25

Whipple's disease, a rare chronic infectious disorder caused by Tropheryma whipplei, may present with predominant joint manifestations mimicking rheumatoid arthritis (RA). A retrospective single-center cohort study of seven patients was performed. Clinical symptoms were assessed by review of medical charts and Whipple's disease was diagnosed by periodic-acid-Schiff-stain and/or Tropheryma whipplei-specific polymerase-chain-reaction. Median age at disease onset was 54 years, six patients were male. Median time to diagnosis was 5 years. All patients presented with polyarthritis with a predominantly symmetric pattern. Three had erosive arthritis. Affected joints were: wrists (5/7), metacarpophalangeal joints (MCPs) (5/7), knees (5/7), proximal interphalangeal joints (PIPs) (3/7), hips (2/7), elbow (2/7), shoulder (2/7). All patients had increased C-reactive-protein concentrations, while rheumatoid factor and anti-CCP-antibodies were absent, and were initially (mis)classified as RA-patients according to EULAR/ACR-criteria (median DAS28 4.3). Six patients received antirheumatic treatment consisting of prednisone with methotrexate and/or leflunomide, three were additionally treated with at least one biologic agent (abatacept, adalimumab, etanercept, rituximab, tocilizumab). Most patients showed insufficient treatment response. In all patients Tropheryma whipplei was detected in synovial fluid by polymerase-chain-reaction; in three patients the diagnosis of Whipple's disease was further ascertained by periodic-acid-Schiff-staining. Gastrointestinal symptoms and other extra-articular manifestations were absent, mild or non-specific. Treatment was initiated with trimethoprin/sulfamethoxazole in five and doxycycline/hydroxychloroquine in two patients and had to be adapted in five patients. Finally, all patients had good treatment responses with improvement of arthritis and extra-articular manifestations. Whipple's disease is rare and can mimic rheumatoid arthritis

Studies of the antibody nature of the rheumatoid factor

PubMed Central

Aho, K.; Harboe, M.; Leikola, J.

1964-01-01

The reaction of the rheumatoid factor (RF) with 7S γ-globulin antibodies of nine persons immunized with sheep erythrocytes was studied. All of a panel of rheumatoid sera with high Waaler-Rose titres agglutinated sheep cells sensitized with the human anti-sheep cell antibodies and O Rh positive cells sensitized with the `diagnostic' anti-CD serum Ripley. The RF measurable with these systems could be absorbed to diphtheria toxoid—human antitoxin precipitate, whereas the absorption with egg albumin—rabbit anti-egg albumin precipitate did not result in any appreciable titre reduction. However, the eluate from the rabbit precipitate was highly active in these systems, whereas Rh positive cells sensitized with anti-Rh sera suitable for Gm(a) typing were not regularly agglutinated. A markedly greater concentration of native than of heat-aggregated γ-globulin was needed for inhibition of the agglutination by the RF of cells heavily sensitized with the human anti-sheep cell antibodies. No appreciable difference in this respect was seen when using lightly sensitized cells. Only the heavily sensitized cells fixed complement. The `natural' 7S γ-globulin antibodies against sheep cells were neither suited for demonstration of RF nor did they fix complement. Sheep cells coated with 7S γ-globulin antibodies of a Gm(a+) person were agglutinated by a non-rheumatoid anti-Gm(a) serum, and this system was well suited for Gm(a) typing, whereas cells coated with antibodies of a Gm(a-) person were not agglutinated. Rheumatoid anti-Gm(a) sera agglutinated cells sensitized with antibodies of both Gm(a+) and Gm(a-) persons. Using cells coated with Gm(a+) antibodies, some distinction between Gm(a+) and Gm(a-) sera could be obtained under carefully controlled conditions. The use of a Gm(a-) coat resulted in a slight difference in the inhibiting capacity, which had no relation to the serum's Gm(a) type. The results suggest that the reaction of the RF with sheep cells heavily sensitized

Advances in the treatment of rheumatoid arthritis: old versus new therapies.

PubMed

Saravanan, Vadivelu; Hamilton, Jennifer

2002-07-01

Rheumatoid arthritis (RA) is a common cause of disability in the western population, with an annual incidence of 0.05% and a prevalence of 1%. Although a small percentage of patients go into natural remission, the untreated disease progresses to cause disability, morbidity and early mortality. Unravelling of the cytokine network in the pathogenesis of RA has led to the development of drugs that target these cytokines and prevent joint damage. Three biological anticytokine agents, etanercept, infliximab and anakinra, are now available for use in RA. More experience will quantify their safety and benefits. The potency of the older disease-modifying antirheumatic drugs (DMARDs), such as methotrexate and sulfasalazine, is also being realised, especially when used early in the disease process and in combination. Leflunomide is a new DMARD with efficacy similar to methotrexate and sulfasalazine. Symptomatic treatment of RA with nonsteroidal anti-inflammatory drugs has also undergone a revolution with the availability of a new class of COX-2-specific inhibitors. These drugs control inflammation and provide pain relief with less GI toxicity. Management of comorbid conditions associated with RA and its treatment (i.e., osteoporosis, cardiovascular and lung disease) has also become a priority for the rheumatologist. It is hoped that more aggressive use of conventional DMARDs and biological agents will result in less disability and a higher proportion of patients achieving remission.

Association of anti-cyclic citrullinated peptide antibodies, anti-citrullin antibodies, and IgM and IgA rheumatoid factors with serological parameters of disease activity in rheumatoid arthritis.

PubMed

Greiner, Alexander; Plischke, Herbert; Kellner, Herbert; Gruber, Rudolf

2005-06-01

We evaluated the association of anti-cyclic citrullinated peptide (CCP) antibody titers with serological markers of disease activity. We also compared three different anti-CCP antibody ELISAs with an anti-citrullin ELISA and the IgM and the IgA rheumatoid factor (RF) in their performance of discriminating between rheumatoid arthritis (RA) and other rheumatic diseases. Sera from 333 consecutive patients of the Rheumaeinheit der Medizinischen Poliklinik Munchen, an outpatient clinic for rheumatic diseases, were collected and tested. Anti-CCP antibodies were assayed with three different commercially available ELISAs. Antifilaggrin antibodies were tested with a commercially available ELISA using in vitro deiminated recombinant rat filaggrin. IgA-RF was analyzed with an ELISA, whereas IgM-RF was measured by latex-enhanced turbidimetry. Rheumatoid arthritis (RA) was diagnosed in 87 patients according to the revised classification criteria of the American College of Rheumatology (ACR), probable RA was diagnosed in 23 patients in an early phase not (yet) fulfilling the ACR criteria, and 223 patients had other rheumatic diseases. Differences in sensitivity and specificity were calculated using McNemar's test. A measure of agreement (kappa statistic) was used to examine whether the tests tended to identify the same patients as positive or negative. Correlations between CCP titers and other tests were analyzed by Spearman nonparametric rank correlation. No significant differences in sensitivity and specificity were found between the tested CCP assays (80.0-80.9% and 97.3-98.1%, respectively). All three CCP tests were slightly but not significantly more sensitive and specific than the anti-citrullin assay (77% and 92%, respectively), comparably sensitive but significantly more specific compared with the IgM-RF (86% and 82%, respectively), and significantly more sensitive but comparably specific compared with the IgA-RF (63% and 94.4%, respectively) in detecting the patients

[Sub-maximal aerobic capacity and quality of life of patients with rheumatoid arthritis].

PubMed

Lataoui, S; Belghali, S; Zeglaoui, H; Bouajina, E; Ben Saad, H

2017-01-01

Studies about sub-maximal aerobic capacity of patients with rheumatoid arthritis are scarce. To assess the sub-maximal aerobic capacity of these patients through the 6-min walk test, estimated age of the "muscular and cardiorespiratory" chain. Thirty-seven consecutive patients (aged 20 to 60 years) with newly diagnosed rheumatoid arthritis will be included. Non-inclusion criteria will be: use of drugs (e.g.; methotrexate, beta-blockers), orthopaedic or rheumatologic conditions (other than rheumatoid arthritis) that may alter walking ability and recent infections. Exclusion criteria will be: 6-min walking test contra-indications and imperfect performance of the required lung function and walking maneuvers. Signs of walking intolerance will be: test interruption, distance ≤lower limit of normal, dyspnea score ≥5/10 (visual analogue scale) at the end of the test, haemoglobin oxygen saturation (SpO 2 ) drop ≥5%, cardiac frequency at the end of the test ≤60% of maximum predicted. An estimated "muscular and cardiorespiratory chain" age higher than the chronological one will be considered as a sign of accelerated ageing. A high percentage of patients suffering from rheumatoid arthritis would show evidences of walking limitation and accelerated "muscular and cardiorespiratory chain" ageing. There would be a significant correlation between the walking test and clinical, biological, radiological and pulmonary function data and the patients' quality-of-life status. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Bone mineral density level by dual energy X-ray absorptiometry in rheumatoid arthritis.

PubMed

Makhdoom, Asadullah; Rahopoto, Muhammad Qasim; Awan, Shazia; Tahir, Syed Muhammad; Memon, Shazia; Siddiqui, Khaleeque Ahmed

2017-01-01

To observe the level of bone mineral density by Dual Energy X-ray Absorptiometry in rheumatoid arthritis patients. The observational study was conducted at Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan, from January 2011 to December 2014. Bone mineral density was measured from the femoral neck, ward's triangle and lumbar spine, in patients 25-55 years of age, who were diagnosed with rheumatoid arthritis. All the cases were assessed for bone mineral density from appendicular as well as axial skeleton. Data was collected through a designed proforma and analysis was performed using SPSS 21. Of the 229 rheumatoid arthritis patients, 33(14.4%) were males. Five (15.1%) males had normal bone density, 14(42.4%) had osteopenia and 14(42.4%) had osteoporosis. Of the 196(85.5%) females, 45(29.9%) had normal bone density, 72 (37.7%) had osteopenia and 79(40.30%) had osteoporosis. Of the 123(53.7%) patients aged 30-50 years, 38(30.9%) had normal bone density, 59(48.0%) had osteopenia, and 26(21.1%) had osteoporosis. Of the 106(46.3%) patients over 50 years, 12(11.3%) had normal bone density, 27 (25.5%) had osteopenia and 67(63.2%) had osteoporosis. Osteoporosis and osteopenia were most common among rheumatoid arthritis patients. Assessment of bone mineral density by Dual Energy X-ray Absorptiometry can lead to quick relief in the clinical symptoms with timely therapy.

Twenty‐Year Outcome and Association Between Early Treatment and Mortality and Disability in an Inception Cohort of Patients With Rheumatoid Arthritis: Results From the Norfolk Arthritis Register

PubMed Central

Gwinnutt, James M.; Symmons, Deborah P. M.; MacGregor, Alexander J.; Chipping, Jacqueline R.; Marshall, Tarnya; Lunt, Mark

2017-01-01

Objective To describe the outcome in patients with rheumatoid arthritis (RA) over 20 years from symptom onset, and to assess the association between early treatment (with disease‐modifying antirheumatic drugs/steroids) and mortality and disability during follow‐up. Methods Patients recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 1994 who met the 2010 American College of Rheumatology/European League Against Rheumatism RA criteria at baseline were included in this analysis. Demographic and clinical variables were collected at baseline and at years 1–3, 5, 7, 10, 15, and 20. Disease activity (swollen joint count [SJC]/tender joint count [TJC]), disability (Health Assessment Questionnaire disability index [HAQ DI]), and mortality over 20 years were determined. Associations between treatment group (early treatment [ET], treatment ≤6 months after symptom onset; late treatment [LT], treatment >6 months after symptom onset; never treatment [NT], no treatment) and mortality and disability were assessed using weighted pooled logistic regression and weighted multilevel mixed‐effects linear regression, respectively. Inverse weights were used to account for confounding by indication and censoring. Results This study included 602 patients with RA (median age 56 years [interquartile range 44–68 years]; 65.9% women). The median SJCs and TJCs were low during the follow‐up period (1–3 swollen joints and 3–6 tender joints). The median HAQ DI score increased after year 1 but remained at low/moderate levels (median 1.25 after year 10). The risk of mortality was reduced in the ET and LT groups compared with that in the NT group. The ET group and the NT group had comparable HAQ DI scores during the follow‐up period (β = 0.03, 95% confidence interval [95% CI] −0.06, 0.12), while the HAQ DI score was increased in the LT group (for LT versus NT, β = 0.10 [95% CI 0.02, 0.17]). Conclusion The results of this study indicate the importance of

Examining the role of fluctuations in the early stages of homogenous polymer crystallization with simulation and statistical learning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Welch, Jr., Paul Michael

Here, we propose a relationship between the dynamics in the amorphous and crystalline domains during polymer crystallization: the fluctuations of ordering-rate about a material-specific value in the amorphous phase drive those fluctuations associated with the increase in percent crystallinity. This suggests a differential equation that satisfies the three experimentally observed time regimes for the rate of crystal growth. To test this postulated expression, we applied a suite of statistical learning tools to molecular dynamics simulations to extract the relevant phenomenology. This study shows that the proposed relationship holds in the early time regime. It illustrates the effectiveness of soft computingmore » tools in the analysis of coarse-grained simulations in which patterns exist, but may not easily yield to strict quantitative evaluation. This ability assists us in characterizing the critical early time molecular arrangement during the primary nucleation phase of polymer melt crystallization. In addition to supporting the validity of the proposed kinetics expression, the simulations show that (i) the classical nucleation and growth mechanism is active in the early stages of ordering; (ii) the number of nuclei and their masses grow linearly during this early time regime; and (iii) a fixed inter-nuclei distance is established.« less

Examining the role of fluctuations in the early stages of homogenous polymer crystallization with simulation and statistical learning

DOE PAGES

Welch, Jr., Paul Michael

2017-01-23

Here, we propose a relationship between the dynamics in the amorphous and crystalline domains during polymer crystallization: the fluctuations of ordering-rate about a material-specific value in the amorphous phase drive those fluctuations associated with the increase in percent crystallinity. This suggests a differential equation that satisfies the three experimentally observed time regimes for the rate of crystal growth. To test this postulated expression, we applied a suite of statistical learning tools to molecular dynamics simulations to extract the relevant phenomenology. This study shows that the proposed relationship holds in the early time regime. It illustrates the effectiveness of soft computingmore » tools in the analysis of coarse-grained simulations in which patterns exist, but may not easily yield to strict quantitative evaluation. This ability assists us in characterizing the critical early time molecular arrangement during the primary nucleation phase of polymer melt crystallization. In addition to supporting the validity of the proposed kinetics expression, the simulations show that (i) the classical nucleation and growth mechanism is active in the early stages of ordering; (ii) the number of nuclei and their masses grow linearly during this early time regime; and (iii) a fixed inter-nuclei distance is established.« less

Pain Coping Strategies and Depression in Rheumatoid Arthritis.

ERIC Educational Resources Information Center

Brown, Gregory K.; And Others

1989-01-01

Examined role of pain episodes and active and passive pain coping strategies in predicting depression in 287 patients with rheumatoid arthritis (RA). Findings revealed pain, passive coping, and interaction between the 2 accounted for higher depression. Results also indicated that frequent use of passive pain coping strategies in face of high pain…

A randomized controlled trial examining Iyengar yoga for young adults with rheumatoid arthritis: a study protocol

PubMed Central

2011-01-01

Background Rheumatoid arthritis is a chronic, disabling disease that can compromise mobility, daily functioning, and health-related quality of life, especially in older adolescents and young adults. In this project, we will compare a standardized Iyengar yoga program for young people with rheumatoid arthritis to a standard care wait-list control condition. Methods/Design Seventy rheumatoid arthritis patients aged 16-35 years will be randomized into either the 6-week Iyengar yoga program (12 - 1.5 hour sessions twice weekly) or the 6-week wait-list control condition. A 20% attrition rate is anticipated. The wait-list group will receive the yoga program following completion of the first arm of the study. We will collect data quantitatively, using questionnaires and markers of disease activity, and qualitatively using semi-structured interviews. Assessments include standardized measures of general and arthritis-specific function, pain, mood, and health-related quality of life, as well as qualitative interviews, blood pressure/resting heart rate measurements, a medical exam and the assessment of pro-inflammatory cytokines. Data will be collected three times: before treatment, post-treatment, and two months following the treatment. Discussion Results from this study will provide critical data on non-pharmacologic methods for enhancing function in rheumatoid arthritis patients. In particular, results will shed light on the feasibility and potential efficacy of a novel intervention for rheumatoid arthritis symptoms, paving the way for a larger clinical trial. Trial Registration ClinicalTrials.gov NCT01096823 PMID:21255431

Collagen-induced arthritis as an animal model of rheumatoid cachexia.

PubMed

Alabarse, Paulo V G; Lora, Priscila S; Silva, Jordana M S; Santo, Rafaela C E; Freitas, Eduarda C; de Oliveira, Mayara S; Almeida, Andrelise S; Immig, Mônica; Teixeira, Vivian O N; Filippin, Lidiane I; Xavier, Ricardo M

2018-03-25

Rheumatoid arthritis is characterized by chronic polyarticular synovitis and presents systemic changes that impact quality of life, such as impaired muscle function, seen in up to 66% of the patients. This can progress to severely debilitating state known as rheumatoid cachexia-without loss of fat mass and body weight-for which there is little consensus in terms of diagnosis or treatment. This study aims to evaluate whether the collagen-induced arthritis (CIA) animal model also develops clinical and functional features characteristic of rheumatoid cachexia. Male DBA1/J mice were randomly divided into 2 groups: healthy animals (CO, n = 11) and CIA animals (n = 13). The clinical score and edema size, animal weight and food intake, free exploratory locomotion, grip strength, and endurance exercise performance were tested 0, 18, 35, 45, 55, and 65 days after disease induction. After euthanasia, several organs, visceral and brown fat, and muscles were dissected and weighed. Muscles were used to assess myofiber diameter. Ankle joint was used to assess arthritis severity by histological score. Statistical analysis were performed using one-way and two-way analyses of variance followed by Tukey's and Bonferroni's test or t-test of Pearson and statistical difference were assumed for a P value under 0.05. The CIA had significantly higher arthritis scores and larger hind paw edema volumes than CO. The CIA had decreased endurance exercise performance total time (fatigue; 23, 22, 24, and 21% at 35, 45, 55, and 65 days, respectively), grip strength (27, 55, 63, 60, and 66% at 25, 35, 45, 55, and 65 days, respectively), free locomotion (43, 57, 59, and 66% at 35, 45, 55, and 65 days, respectively), and tibialis anterior and gastrocnemius muscle weight (25 and 24%, respectively) compared with CO. Sarcoplasmic ratios were also reduced in CIA (TA: 23 and GA: 22% less sarcoplasmic ratio), confirming the atrophy of skeletal muscle mass in these animals than in CO. Myofiber

[Current concepts of pharmacotherapy in rheumatoid arthritis].

PubMed

Balabanova, R M

2003-01-01

Although there were essential achievements in understanding the pathogenesis of rheumatoid arthritis (RA), the mentioned pathologies still remain one of the most complicated problems in practical medicine. Rheumatologists arrived, during the last decade, at a conclusion on a need in an early aggressive therapy, because the destructive changes develop in joints yet during the first 4 months starting from the onset of initial RA clinical signs. The approach towards treatment by non-steroid anti-inflammatory drugs changed with respect to the risk factors related with the onset of potential complications and to choosing the safest drugs, which became possible owing to the development of drugs, whose action is aimed at suppression of cyclo-oxygenase-2 (COG-2). The group of "disease-modifying antirheumatic drugs" (DMARD) was added two new cytotoxic drugs, i.e. cyclosporin A and leflunomid. A concept of combined therapy by 2 or 3 DMARD was elaborated to ensure an effect in case of tolerance to monotherapy. The feasibility and safety of therapy by glucocorticosteroids both with small daily doses and with pulse therapy in extra aggressive RA variations were proven. The use of biological agents, i.e. of monoclonal antibodies to TNF alpha and IL-4 or of their receptors antagonists, is an absolutely new trend in RA treatment. Treatment safety is in the focus of attention; monitoring methods were designed to ensure such safety.

Genetic Markers of Cardiovascular Disease in Rheumatoid Arthritis

PubMed Central

Rodríguez-Rodríguez, Luis; López-Mejías, Raquel; García-Bermúdez, Mercedes; González-Juanatey, Carlos; González-Gay, Miguel A.; Martín, Javier

2012-01-01

Cardiovascular (CV) disease is the most common cause of premature mortality in patients with rheumatoid arthritis (RA). It is the result of an accelerated atherosclerotic process. Both RA and atherosclerosis are complex polygenic diseases. Besides traditional CV risk factors and chronic inflammation, a number of studies have confirmed the role of genetic factors in the development of the atherogenesis observed in RA. In this regard, besides a strong association between the HLA-DRB1∗04 shared epitope alleles and both endothelial dysfunction, an early step in the atherosclerotic process, and clinically evident CV disease, other polymorphisms belonging to genes implicated in inflammatory and metabolic pathways, located inside and outside the HLA region, such as the 308 variant (G > A, rs1800629) of the TNFA locus, the rs1801131 polymorphism (A > C; position + 1298) of the MTHFR locus, or a deletion of 32 base pairs on the CCR5 gene, seem to be associated with the risk of CV disease in patients with RA. Despite considerable effort to decipher the genetic basis of CV disease in RA, further studies are required to better establish the genetic influence in the increased risk of CV events observed in patients with RA. PMID:22927710

Rheumatoid Arthritis Complicated by Pseudochylothorax Without Pleural Thickening: A Diagnostic Challenge for Clinicians.

PubMed

Agrawal, Anand; Chandermani; Madaan, Himanshu; Yadav, Sarita

2016-01-01

A 60-year-old female who was known to have rheumatoid arthritis for the preceding two-and-half years presented with difficulty in breathing associated with chest pain over the right hemithorax of two months duration. She was found to have a right-sided mild to moderate pleural effusion; there was no evidence of pleural thickening. The pleural fluid was pale yellow in appearance and diagnostic work-up confirmed it to be a pseudochylous pleural effusion. The present case highlights the rare occurrence of pseudochylothorax without pleural thickening as a complication of rheumatoid arthritis.

Prevalence of dry eye syndrome and Sjogren's syndrome in patients with rheumatoid arthritis.

PubMed

Kosrirukvongs, Panida; Ngowyutagon, Panotsom; Pusuwan, Pawana; Koolvisoot, Ajchara; Nilganuwong, Surasak

2012-04-01

Rheumatoid arthritis has manifestations in various organs including ophthalmic involvement. The present study evaluates prevalence of dry eye and secondary Sjogren's syndrome using salivary scintigraphy which has not been used in previous reports. To evaluate the prevalence of secondary Sjogren's syndrome in patients with rheumatoid arthritis, including clinical characteristics and dry eye, compared with non-Sjogren's syndrome. Descriptive cross sectional study Sixty-one patients with rheumatoid arthritis were recruited at Siriraj Hospital during March 2009-September 2010 and filled in the questionnaires about dry eye for Ocular Surface Disease Index (OSDI) with a history taking of associated diseases, medications, duration of symptoms of dry eyes and dry mouth. The Schirmer I test without anesthesia, tear break-up time, rose bengal staining score, severity of keratitis and salivary scintigraphy were measured and analyzed. Prevalence of secondary Sjogren's syndrome and dry eye were 22.2% (95% CI 15.4 to 30.9) and 46.7% (95% CI 38.0 to 55.6), respectively. Dry eye interpreted from OSDI, Schirmer 1 test, tear break-up time and rose bengal staining was 16.4%, 46.7%, 82% and 3.3% respectively. Fifty-two percent of patients had a history of dry eye and dry mouth with mean duration 27.4 and 29.8 months, respectively. Superficial punctate keratitis and abnormal salivary scintigraphy were found in 58.2% and 77.8%. Duration of rheumatoid arthritis, erythrocyte sedimentation rate were not correlated with secondary Sjogren's syndrome. Dry eye from OSDI with secondary Sjogren's syndrome (33.3%) compared with non-Sjogren's syndrome (9.5%) was significant difference (p = 0.008). Adjusted odds ratio for secondary Sjogren's syndrome in OSDIL score > 25 was 13.8 (95% CI 2.6 to 73.8, p = 0.002) compared to OSDI score < 25. Awareness and detection of dry eye syndrome and secondary Sjogren's syndrome in rheumatoid arthritis was crucial for evaluation of their severity and proper

Evidence for increased chylomicron remnants in rheumatoid arthritis.

PubMed

Burggraaf, Benjamin; van Breukelen-van der Stoep, Deborah F; van Zeben, Jendé; van der Meulen, Noelle; van de Geijn, Gert-Jan M; Liem, Anho; Valdivielso, Pedro; Rioja Villodres, José; Ramírez-Bollero, José; van der Zwan, Ellen; Castro Cabezas, Manuel

2018-02-01

Levels of apolipoprotein (apo) B48 may be increased in conditions associated with systemic inflammation and increased cardiovascular disease (CVD) risk such as rheumatoid arthritis (RA). We aimed to evaluate apo B48 levels in patients with RA in relation to subclinical atherosclerosis. Patients with RA (without CVD) and controls without RA but with high CVD risk (based on the presence of diabetes mellitus or a history of CVD) and healthy controls were included in this cross-sectional study. Carotid intima-media thickness (cIMT) was measured as a surrogate for vascular damage. In total, 312 patients with RA, 65 controls with high CVD risk and 36 healthy controls were included. Patients with RA had the highest mean apo B48 (10.00 ± 6.65 mg/L) compared to controls with high CVD risk and healthy controls (8.37 ± 5.16 and 5.22 ± 2.46, P < .001). Triglycerides levels were comparable with controls. In RA, apo B48 correlated positively with triglycerides (r = .645; P < .001) but not with cIMT. However, in RA subjects not using lipid or blood pressure lowering medication, a weak correlation was found with cIMT (r = .157; P = .014). RA patients in the highest apo B48 tertile were more often rheumatoid factor positive and anti-CCP positive compared to the lowest tertile. Rheumatoid arthritis patients have higher levels of apo B48 compared to controls with high CVD risk and healthy controls, with normal levels of triglycerides. This accumulation of atherogenic chylomicron remnants may contribute to the elevated CVD risk in RA patients. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

Labial salivary gland biopsy assessment in rheumatoid vasculitis.

PubMed

Flipo, R M; Janin, A; Hachulla, E; Houvenagel, E; Foulet, A; Cardon, T; Desbonnet, A; Grardel, B; Duquesnoy, B; Delcambre, B

1994-10-01

To assess the vascular involvement in labial salivary gland (LSG) from patients with rheumatoid vasculitis (RV). Forty seven patients with rheumatoid arthritis (RA) took part in a prospective study. Among them, 12 had proven RV. LSG biopsy was performed after local anaesthesia. Histological appearance of inflammatory vascular damage was observed in all but one patient with proven RV (92%). Inflammatory vascular involvement was also identified in LSG biopsy of seven patients with RA (20%) and only one patient in the control group (8%). A second specimen of LSG was studied after a mean treatment period of six months and failed to show any feature of inflammatory vascular involvement in three of the five cases that were analysed. The study emphasises the high incidence of immunopathological features of microvascular damage in patients with RV. LSG biopsy is minimally invasive and may be a potential useful tool for the diagnosis of RV especially when skin lesions are absent or impossible to biopsy. The assessment of the predictive value of positive LSG biopsy in RA requires a long term prospective study.

Risk of autism spectrum disorder in children born to mothers with systemic lupus erythematosus and rheumatoid arthritis in Taiwan.

PubMed

Tsai, Ping-Han; Yu, Kuang-Hui; Chou, I-Jun; Luo, Shue-Fen; Tseng, Wen-Yi; Huang, Lu-Hsiang; Kuo, Chang-Fu

2017-11-26

To determine whether offspring of Taiwanese mothers with systemic lupus erythematosus or rheumatoid arthritis have a higher risk of autism spectrum disorder. Using the National Health Insurance database and National Birth Registry, we identified a cohort of all live births in Taiwan between 2001 and 2012. Children born to mothers with systemic lupus erythematosus or rheumatoid arthritis were identified and matched with up to 8 controls by maternal age, 1-minute Apgar score, 5-minute Apgar score, mode of delivery, sex of the child, gestational age, birth weight and place of residence. Marginal Cox proportional hazard models were used to estimate relative risk (RR) with 95% confidence intervals (CI) for ASD in offspring. Of 1,893,244 newborns, 0.08% (n=1594) were born to systemic lupus erythematosus mothers, and 0.04% (n=673) were born to rheumatoid arthritis mothers. Overall, 5 of 673 (0.74%) offspring of rheumatoid arthritis mothers, 7 of 1594 (0.44%) offspring of systemic lupus erythematosus mothers and 10,631 of 1,893,244 (0.56%) offspring of all mothers developed autism spectrum disorder. Autism spectrum disorder incidence (per 100,000 person-years) was 140.39 (95% CI, 45.58-327.62) for the rheumatoid arthritis group and 76.19 (95% CI, 30.63-156.97) for the systemic lupus erythematosus group. Autism spectrum disorder risk was not significantly higher for children born to mothers with rheumatoid arthritis (HR, 1.42; 95% CI, 0.60-3.40) or systemic lupus erythematosus (HR, 0.76; 95% CI, 0.36-1.59). Children born to women with systemic lupus erythematosus or rheumatoid arthritis do not have a higher risk of autism spectrum disorder. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

The revised Bristol Rheumatoid Arthritis Fatigue measures and the Rheumatoid Arthritis Impact of Disease scale: validation in six countries

PubMed Central

Kirwan, John; Bode, Christina; Cramp, Fiona; Carmona, Loreto; Dures, Emma; Englbrecht, Matthias; Fransen, Jaap; Greenwood, Rosemary; Hagel, Sofia; van de Laar, Maart; Molto, Anna; Nicklin, Joanna; Petersson, Ingemar F; Redondo, Marta; Schett, Georg; Gossec, Laure

2018-01-01

Abstract Objective To evaluate the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ), the revised Bristol Rheumatoid Arthritis Numerical Rating Scales (BRAF-NRS V2) and the Rheumatoid Arthritis Impact of Disease (RAID) scale in six countries. Methods We surveyed RA patients in France, Germany, The Netherlands, Spain, Sweden and the UK, including the HAQ, 36-item Short Form Health Survey (SF-36) and potential revisions of the BRAF-NRS coping and Spanish RAID coping items. Factor structure and internal consistency were examined by factor analysis and Cronbach’s α and construct validity by Spearman’s correlation. Results A total of 1276 patients participated (76% female, 25% with a disease duration <5 years, median HAQ 1.0). The original BRAF-MDQ four-factor structure and RAID single-factor structure were confirmed in every country with ⩾66% of variation in items explained by each factor and all item factor loadings of 0.71–0.98. Internal consistency for the BRAF-MDQ total and subscales was a Cronbach’s α of 0.75–0.96 and for RAID, 0.93–0.96. Fatigue construct validity was shown for the BRAF-MDQ and BRAF-NRS severity and effect scales, correlated internally with SF-36 vitality and with RAID fatigue (r = 0.63–0.93). Broader construct validity for the BRAFs and RAID was shown by correlation with each other, HAQ and SF-36 domains (r = 0.46–0.82), with similar patterns in individual countries. The revised BRAF-NRS V2 Coping item had stronger validity than the original in all analyses. The revised Spanish RAID coping item performed as well as the original. Conclusion Across six European countries, the BRAF-MDQ identifies the same four aspects of fatigue, and along with the RAID, shows strong factor structure and internal consistency and moderate–good construct validity. The revised BRAF-NRS V2 shows improved construct validity and replaces the original. PMID:29087507

The revised Bristol Rheumatoid Arthritis Fatigue measures and the Rheumatoid Arthritis Impact of Disease scale: validation in six countries.

PubMed

Hewlett, Sarah; Kirwan, John; Bode, Christina; Cramp, Fiona; Carmona, Loreto; Dures, Emma; Englbrecht, Matthias; Fransen, Jaap; Greenwood, Rosemary; Hagel, Sofia; van de Laar, Maart; Molto, Anna; Nicklin, Joanna; Petersson, Ingemar F; Redondo, Marta; Schett, Georg; Gossec, Laure

2018-02-01

To evaluate the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ), the revised Bristol Rheumatoid Arthritis Numerical Rating Scales (BRAF-NRS V2) and the Rheumatoid Arthritis Impact of Disease (RAID) scale in six countries. We surveyed RA patients in France, Germany, The Netherlands, Spain, Sweden and the UK, including the HAQ, 36-item Short Form Health Survey (SF-36) and potential revisions of the BRAF-NRS coping and Spanish RAID coping items. Factor structure and internal consistency were examined by factor analysis and Cronbach's α and construct validity by Spearman's correlation. A total of 1276 patients participated (76% female, 25% with a disease duration <5 years, median HAQ 1.0). The original BRAF-MDQ four-factor structure and RAID single-factor structure were confirmed in every country with ⩾66% of variation in items explained by each factor and all item factor loadings of 0.71-0.98. Internal consistency for the BRAF-MDQ total and subscales was a Cronbach's α of 0.75-0.96 and for RAID, 0.93-0.96. Fatigue construct validity was shown for the BRAF-MDQ and BRAF-NRS severity and effect scales, correlated internally with SF-36 vitality and with RAID fatigue (r = 0.63-0.93). Broader construct validity for the BRAFs and RAID was shown by correlation with each other, HAQ and SF-36 domains (r = 0.46-0.82), with similar patterns in individual countries. The revised BRAF-NRS V2 Coping item had stronger validity than the original in all analyses. The revised Spanish RAID coping item performed as well as the original. Across six European countries, the BRAF-MDQ identifies the same four aspects of fatigue, and along with the RAID, shows strong factor structure and internal consistency and moderate-good construct validity. The revised BRAF-NRS V2 shows improved construct validity and replaces the original. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Explanatory Style in Patients with Rheumatoid Arthritis: An Unrecognized Predictor of Mortality

PubMed Central

Crowson, Aaron D.; Colligan, Robert C.; Matteson, Eric L.; Davis, John M.; Crowson, Cynthia S.

2016-01-01

Objective To determine whether pessimistic explanatory style altered the risk for and mortality of rheumatoid arthritis (RA) patients. Methods The study included subjects from a population-based cohort with incident RA and non-RA comparison cohort who completed the Minnesota Multiphasic Personality Inventory (MMPI). Results Among 148 RA and 135 non-RA subjects, pessimism was associated with development of rheumatoid factor positive (RF+) RA. Pessimism was associated with an increased risk of mortality (hazard ratio [HR]:2.88 with similar magnitude to RF+ (HR:2.28). Conclusion Pessimistic explanatory style was associated with an increased risk of developing RA and increased mortality rate in patients with RA. PMID:28148754

High-Density Genotyping of Immune Loci in Koreans and Europeans Identifies Eight New Rheumatoid Arthritis Risk Loci

PubMed Central

Kim, Kwangwoo; Bang, So-Young; Lee, Hye-Soon; Cho, Soo-Kyung; Choi, Chan-Bum; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Yoo, Dae Hyun; Kang, Young Mo; Kim, Seong-Kyu; Suh, Chang-Hee; Shim, Seung-Cheol; Lee, Shin-Seok; Lee, Jisoo; Chung, Won Tae; Choe, Jung-Yoon; Shin, Hyoung Doo; Lee, Jong-Young; Han, Bok-Ghee; Nath, Swapan K.; Eyre, Steve; Bowes, John; Pappas, Dimitrios A.; Kremer, Joel M.; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Ärlestig, Lisbeth; Okada, Yukinori; Diogo, Dorothée; Liao, Katherine P.; Karlson, Elizabeth W.; Raychaudhuri, Soumya; Rantapää-Dahlqvist, Solbritt; Martin, Javier; Klareskog, Lars; Padyukov, Leonid; Gregersen, Peter K.; Worthington, Jane; Greenberg, Jeffrey D.; Plenge, Robert M.; Bae, Sang-Cheol

2015-01-01

Objective A highly polygenic etiology and high degree of allele-sharing between ancestries have been well-elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. Methods We analyzed Korean rheumatoid arthritis case-control samples using the Immunochip and GWAS array to search for new risk alleles of rheumatoid arthritis with anti-citrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data, for a total sample size of 9,299 Korean and 45,790 European case-control samples. Results We identified 8 new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1–FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5×10−8), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the 7 new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of SNPs that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. Conclusion This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases. PMID:24532676

High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci.

PubMed

Kim, Kwangwoo; Bang, So-Young; Lee, Hye-Soon; Cho, Soo-Kyung; Choi, Chan-Bum; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Yoo, Dae Hyun; Kang, Young Mo; Kim, Seong-Kyu; Suh, Chang-Hee; Shim, Seung-Cheol; Lee, Shin-Seok; Lee, Jisoo; Chung, Won Tae; Choe, Jung-Yoon; Shin, Hyoung Doo; Lee, Jong-Young; Han, Bok-Ghee; Nath, Swapan K; Eyre, Steve; Bowes, John; Pappas, Dimitrios A; Kremer, Joel M; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Ärlestig, Lisbeth; Okada, Yukinori; Diogo, Dorothée; Liao, Katherine P; Karlson, Elizabeth W; Raychaudhuri, Soumya; Rantapää-Dahlqvist, Solbritt; Martin, Javier; Klareskog, Lars; Padyukov, Leonid; Gregersen, Peter K; Worthington, Jane; Greenberg, Jeffrey D; Plenge, Robert M; Bae, Sang-Cheol

2015-03-01

A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data for a total sample size of 9299 Korean and 45,790 European case-control samples. We identified eight new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1-FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5×10(-8)), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the seven new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of single nucleotide polymorphisms (SNPs) that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Raised serum alkaline phosphatase and aspartate transaminase levels in two rheumatoid patients treated with sulphasalazine.

PubMed Central

Farr, M; Symmons, D P; Bacon, P A

1985-01-01

Hepatotoxicity is a rare complication of sulphasalazine therapy in ulcerative colitis. This report describes two rheumatoid patients in whom raised serum levels of liver enzymes occurred soon after starting sulphasalazine treatment for their arthritis. In both cases the serum enzyme levels returned to normal after stopping the drug. Drug-induced hepatotoxicity should be considered in patients with rheumatoid arthritis (RA) who develop raised serum levels of liver enzymes while taking sulphasalazine. PMID:2865931

Indium-111 leukocyte imaging in patients with rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uno, K.; Matsui, N.; Nohira, K.

1986-03-01

This study evaluates the usefulness of labeled leukocyte imaging in patients with rheumatoid arthritis. In 33 patients, the incidence of pain and swelling in 66 wrist joints and 66 knee joints was compared with the accumulation of (/sup 111/In)leukocytes. No accumulation of (/sup 111/In)leukocytes was seen in any of the patients' wrists (0/12) or knee joints (0/14) when both pain and swelling were absent. In contrast, 93% (25/27) of wrist joints and 80% (24/30) of knee joints with both pain and swelling were positive by (/sup 111/In)leukocyte scintigraphy. There was little correlation between the stage of the disease, as determinedmore » by radiography, and (/sup 111/In)leukocyte accumulation. This study suggests that (/sup 111/In)leukocyte imaging may be a reliable procedure for monitoring the activity of rheumatoid arthritis, especially for confirming the lack of an ongoing inflammatory response.« less

Treatment of Rheumatoid Arthritis with Fenoprofen: Comparison with Aspirin

PubMed Central

Huskisson, E. C.; Wojtulewski, J. A.; Berry, H.; Scott, Jane; Hart, F. Dudley; Balme, H. W.

1974-01-01

Fenoprofen, a compound with analgesic, anti-inflammatory, and antipyretic properties in animals, has been compared with placebo in a double-blind cross-over trial in 60 patients with rheumatoid arthritis. There was a statistically highly significant reduction in pain, duration of morning stiffness, analgesic requirements, and articular index, with increase in grip strength. There was no significant reduction in joint size or temperature. In a subsequent double-blind group-comparative study fenoprofen proved to be as effective as aspirin in relieving the symptoms of rheumatoid arthritis, with strikingly fewer side effects. Almost half of the patients taking aspirin were unable to tolerate the drug in adequate dosage for six months. The remainder were able to take on average only 4 g daily, and at this dose almost half still complained of tinnitus and deafness. Fenoprofen is likely to be useful for patients who cannot tolerate aspirin and other more toxic anti-inflammatory drugs or whose disease is not of sufficient severity to justify their use. PMID:4590669

[Rheumatoid arthritis among mapuche aborigines. A 16 years experience in the IX Region of the Chile].

PubMed

Kaliski, S; Bustos, L; Artigas, C; Alarcón, C; Vega, M A; Cárdenas, C

2001-03-01

Mapuche, Chilean natives, represent approximately 9.8% of Chilean population and in the IX region of the country, they account for 18.4% of population over 15 years old. They preserve some socio-cultural characteristics that make them different to the rest of the population. To describe the epidemiological characteristics rheumatoid arthritis among Mapuche natives. Retrospective review of patients of Mapuche origin with rheumatoid arthritis, seen at Temuco Hospital between 1980 and 1996. Among 308 cases gathered, only 106 (93 women, aged 55 +/- 10 years old) complied with 1987 American College of Rheumatology (ACR) criteria for rheumatoid arthritis. The disease began between 29 and 52 years old in 73% of patients and the mean delay in diagnosis was 4.4 years. At diagnosis, 99% had symmetric poliarthritis, 28.3% had either fatigue, fever or weight loss, and 46.9% were in class III or in class IV of ACR-1991. Fifty three percent of patients developed Sicca syndrome, 36% developed nodules, 23% developed Raynaud phenomenon, 11% developed pulmonary involvement, 7% developed vasculitis, 5% developed neurological manifestations and 19% developed ophthalmologic involvement. Rheumatoid factor was positive in 78% and 73% had erosions. HLA DR4 was (+) in 60% of 30 patients. Thirty percent required 3 or more disease modifying drugs and prednisone over 10 mg/day. There was no correlation between functional capacity and several other features of the disease. Mapuche rheumatoid arthritis patients are detected late and have a poor functional capacity at the time of diagnosis. They also have a higher proportion of extraarticular manifestations, more erosions and require more aggressive treatments.

A review on interleukins: The key manipulators in rheumatoid arthritis.

PubMed

Sharma, Jatin; Bhar, Sutonuka; Devi, C Subathra

2017-09-01

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with weakening of bones and joint pain. It primarily involves autoimmunity, matrix destruction, osteoclastogenesis, inflammation, and angiogenesis. Numerous cellular and humoral components of the immune system are involved in the etiology of diseases; however, the cardinal part is played by the inter-cellular signaling messengers called cytokines. Interleukins is a vaguely defined sub-class of cytokines that are abundantly found in the RA patients. The multifariousness and diversity in the function of the interleukins make them very likely to be associated with the pathogenesis in multiple ways. Nonetheless, the variety in opinions of researchers globally has led to contentious inferences. Ergo, in this review we have amalgamated the views of researchers from the past two decades till date to provide a comprehensive report about the role of interleukins in rheumatoid arthritis.

The future role of anti-tumour necrosis factor (TNF) products in the treatment of rheumatoid arthritis.

PubMed

Camussi, G; Lupia, E

1998-05-01

Tumour necrosis factor-alpha (TNF alpha) is a pleiotropic cytokine which is overproduced in rheumatoid joints primarily by macrophages. This cytokine has a potential pathogenic role in the establishment of rheumatoid synovitis, in the formation of pannus tissue and in the process of joint destruction, as it increases synoviocyte proliferation and triggers a cascade of secondary mediators involved in the recruitment of inflammatory cells, in neo-angiogenesis and in the process of joint destruction. These findings made TNF alpha a potential target for anticytokine therapy. Experimental studies have shown that TNF alpha blockade by monoclonal antibodies or by soluble TNF receptor reduced the extent and severity of arthritis both in collagen-induced arthritis in mice and in transgenic mice overexpressing TNF alpha, which develop a rheumatoid-like destructive arthritis. Clinical studies based on the use of anti-TNF alpha antibodies or soluble receptors have suggested a potential beneficial effect of TNF alpha-blocking therapy in inducing amelioration of inflammatory parameters in patients with long-standing active disease. In these patients anti-TNF alpha therapy induces a rapid improvement in multiple clinical assessment of disease activity, including morning stiffness, pain score, Ritchie articular index and swollen joint count. The clinical benefits are associated with an improvement in some serological parameters, such as C-reactive protein and serum amyloid-A, erythrocyte sedimentation rate, blood cytokine levels, haemoglobin, white cells and platelet counts, rheumatoid factor titre and histological features of the synovium. However, it remains to be determined whether anti-TNF alpha therapy may be useful in the long term management of rheumatoid patients and in the achievement of better outcomes of disease. Because TNF alpha production also serves a specific function in host defence against infections and tumours, the adverse effects of long term anti-TNF alpha

The history of bacteriologic concepts of rheumatic fever and rheumatoid arthritis.

PubMed

Benedek, Thomas G

2006-10-01

Review of the development of etiologic and pathogenetic concepts of rheumatic fever (RF) and rheumatoid arthritis (RA) from the beginning of clinical bacteriology to the discovery of antibiotics. Analysis of English and German language publications pertaining to bacteriology and "rheumatism" between the 1870s and 1940s. Early in the 20th century there was a widely held belief that a microbial cause would eventually be found for most diseases. This encouraged pursuit of the intermittent findings of positive blood and synovial fluid cultures in cases of RF and RA. Development of a streptococcal agglutination test supported the erroneous belief that RA is a streptococcal infection, while the simultaneous development of other immunologic tests for streptococci suggested that a hemolytic streptococcus was etiologic in RF. Table 1 provides a chronology of major events supporting and retarding resolutions. Much of the conflicting data and inferences regarding the etiology of RF and RA can be attributed to the absence or inadequacy of controls in observations of clinical cohorts and laboratory experiments.

Effects of a biologic agent in a patient with rheumatoid arthritis after treatment for methotrexate-associated B-cell lymphoma: a case report.

PubMed

Kuroda, Takeshi; Sato, Hiroe; Nakatsue, Takeshi; Wada, Yoko; Murakami, Shuichi; Nakano, Masaaki; Narita, Ichiei

2014-04-11

Several studies have suggested an increased risk of malignant tumor in patients with rheumatoid arthritis. It has been also reported that rheumatoid arthritis patients have a high incidence of lymphoma compared with the general population, and that patients receiving methotrexate, which is the anchor drug for rheumatoid arthritis treatment, can develop lymphoproliferative disease. Nevertheless, management of rheumatoid arthritis after treatment for methotrexate-associated lymphoma has not been fully investigated. We here report a patient with rheumatoid arthritis who developed malignant lymphoma associated with methotrexate therapy. Moreover, we describe the use of a biologic agent for a rheumatoid arthritis patient after treatment for lymphoma associated with methotrexate. A 60-year-old Japanese man with a 20-year history of rheumatoid arthritis was admitted to our hospital with a left inguinal tumor. Open biopsy was performed and a biopsy specimen revealed diffuse large B-cell lymphoma. As our patient had received methotrexate for 4 years, we diagnosed the lymphoproliferative disease as being methotrexate-related. This lymphoma was not associated with Epstein- Barr virus by Epstein-Barr virus-encoded ribonucleic acid in-situ hybridization, but this patient was an Epstein-Barr virus carrier, regarding serological testing. The lymphoma went into complete remission after 6 courses of rituximab plus cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone/prednisolone therapy. Two years later, however, rheumatoid arthritis activity gradually increased and was not controlled with salazosulfapyridine. Etanercept was administered in view of its possible effect on B-cells, and this reduced the level of disease activity without recurrence of lymphoma. The management of rheumatoid arthritis after treatment for methotrexate-associated lymphoma has not been fully investigated yet. Etanercept appeared to be safe because of its B-cell effect, but further observation

Rheumatoid arthritis: Recent advances on its etiology, role of cytokines and pharmacotherapy.

PubMed

Alam, Javaid; Jantan, Ibrahim; Bukhari, Syed Nasir Abbas

2017-08-01

An autoimmune disease is defined as a clinical syndrome resulted from an instigation of both T cell and B cell or individually, in the absence of any present infection or any sort of distinguishable cause. Clonal deletion of auto reactive cells remains the central canon of immunology for decades, keeping the role of T cell and B cell aside, which are actually the guards to recognize the entry of foreign body. According to NIH, 23.5 million Americans are all together affected by these diseases. They are rare, but with the exception of RA. Rheumatoid arthritis is chronic and systemic autoimmune response to the multiple joints with unknown ethology, progressive disability, systemic complications, early death and high socioeconomic costs. Its ancient disease with an old history found in North American tribes since 1500 BCE, but its etiology is yet to be explored. Current conventional and biological therapies used for RA are not fulfilling the need of the patients but give only partial responses. There is a lack of consistent and liable biomarkers of prognosis therapeutic response, and toxicity. Rheumatoid arthritis is characterized by hyperplasic synovium, production of cytokines, chemokines, autoantibodies like rheumatoid factor (RF) and anticitrullinated protein antibody (ACPA), osteoclastogensis, angiogenesis and systemic consequences like cardiovascular, pulmonary, psychological, and skeletal disorders. Cytokines, a diverse group of polypeptides, play critical role in the pathogenesis of RA. Their involvement in autoimmune diseases is a rapidly growing area of biological and clinical research. Among the proinflammatory cytokines, IL-1α/β and TNF-α trigger the intracellular molecular signalling pathway responsible for the pathogenesis of RA that leads to the activation of mesenchymal cell, recruitment of innate and adaptive immune system cells, activation of synoviocytes which in term activates various mediators including tumour necrosis factor-alpha (TNF

Coexistence of bronchiectasis and rheumatoid arthritis: revisited.

PubMed

Wilczynska, Maria M; Condliffe, Alison M; McKeon, Damian J

2013-04-01

The presence of bronchiectasis (BR) in patients with rheumatoid arthritis (RA) has been recognized for many decades; nevertheless, little research has been undertaken in this area. It is important to recognize that BR coexistent with RA differs from the other types of BR. The purpose of this descriptive review was to delineate the epidemiology, etiology, risk factors, pulmonary function testing, imaging, prognosis and management of concomitant BR and RA. To inform our study we searched the PubMed, EMBASE, CINAHL, and MEDLINE databases, using combinations of the following key words: computed tomography, lung function tests, rheumatoid arthritis, bronchiectasis, biological agents, and interstitial lung disease. The number of published papers covering this topic is limited, but several relevant conclusions can be drawn. Patients with concomitant RA and BR have worse obstructive airways disease, increased susceptibility to recurrent pulmonary infections, faster lung function decline, and higher mortality, compared with subjects with either RA or BR alone. The use of disease-modifying anti-rheumatic drugs (both biological and non-biological) for RA in RA-BR patients imparts a further challenge in managing these patients. Although there are not any published guidelines on the management of coexisting RA-BR, we have attempted to provide such recommendations, based on the literature review and our experience.

Leflunomide in active rheumatoid arthritis: a prospective study in daily practice.

PubMed

Van Roon, E N; Jansen, T L Th A; Mourad, L; Houtman, P M; Bruyn, G A W; Griep, E N; Wilffert, B; Tobi, H; Brouwers, J R B J

2004-08-01

We prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. In this prospective case series study, a standard dataset was collected from outpatient medical records, including patient and disease characteristics, data on leflunomide use and adverse drug reactions. During the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow-up duration was 317 (11-911) days. Sixty-five percent of patients experienced at least one adverse drug reaction related to leflunomide. During follow-up 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS(28)) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow-up, respectively. Within a 12-month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS(28) response criteria. In the setting of care-as-usual rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within 1 year of starting leflunomide treatment, mainly because of adverse drug reactions.

Lack of pharmacokinetic interaction between rofecoxib and methotrexate in rheumatoid arthritis patients.

PubMed

Schwartz, J I; Agrawal, N G; Wong, P H; Bachmann, K A; Porras, A G; Miller, J L; Ebel, D L; Sack, M R; Holmes, G B; Redfern, J S; Gertz, B J

2001-10-01

Rofecoxib is a highly selective and potent inhibitor of cyclooxgenase-2 (COX-2). Methotrexate is a disease-modifying agent with a narrow therapeutic index frequently prescribed for the management of rheumatoid arthritis. The objective of this study was to investigate the influence of clinical doses of rofecoxib on the pharmacokinetics of methotrexate in patients with rheumatoid arthritis. This was a randomized, double-blind, placebo-controlled study in 25 rheumatoid arthritis patients on stable doses of methotrexate. Patients received oral methotrexate (7.5 to 20 mg) on days -1, 7, 14, and 21. Nineteen patients received rofecoxib 12.5, 25, and 50 mg once daily on days 1 to 7, 8 to 14, and 15 to 21, respectively. Six patients received placebo on days 1 to 21 only to maintain a double-blinded design for assessment of adverse experiences. Plasma and urine samples were analyzed for methotrexate and its major although inactive metabolite, 7-hydroxymethotrexate. The AUC(0-infinity) geometric mean ratios (GMR) and their 90% confidence intervals (90% CI) (rofecoxib + methotrexate/methotrexate alone) for day 7/day -1, day 14/day -1, and day 21/day -1, for rofecoxib 12.5, 25, and 50 mg, were 1.03 (0.93, 1.14), 1.02 (0.92, 1.12), and 1.06 (0.96, 1.17), respectively (p > 0.2 for all comparisons to day -1). All AUC(0-infinity), GMR and Cmax GMR 90% CIs fell within the predefined comparability limits of (0.80, 1.25). Similar results were observed for renal clearance of methotrexate and 7-hydroxymethotrexate at the highest dose of rofecoxib tested (50 mg). It was concluded that rofecoxib at doses of 12.5, 25, and 50 mg once daily has no effect on the plasma concentrations or renal clearance (tested at the highest dose of rofecoxib) of methotrexate in rheumatoid arthritis patients.

Osteoprotegerin CGA Haplotype Protection against Cerebrovascular Complications in Anti-CCP Negative Patients with Rheumatoid Arthritis

PubMed Central

Castañeda, Santos; González-Juanatey, Carlos; Llorca, Javier; Corrales, Alfonso; Ubilla, Begoña; Miranda-Filloy, José A.; Pina, Trinitario; Gómez-Vaquero, Carmen; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, Benjamín; Balsa, Alejandro; Pascual-Salcedo, Dora; López-Longo, Francisco J.; Carreira, Patricia; Blanco, Ricardo; González-Álvaro, Isidoro; Martín, Javier; González-Gay, Miguel A.

2014-01-01

Introduction Rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG) has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis. Methods Three OPG gene variants (rs3134063, rs2073618 and rs3134069) were genotyped by TaqMan assays in 2027 Spanish patients with rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing was positive in 997 of 1714 tested. Also, 18.3% of the whole series had experienced cardiovascular events, including 5.4% with cerebrovascular accidents. The relationship between OPG variants and cardiovascular events was assessed using Cox regression. Results No association between OPG gene variants and cardiovascular disease was observed in the whole group of rheumatoid arthritis patients or in anti-CCP positive patients. Nevertheless, a protective effect of CGA haplotype on the risk of cardiovascular disease in general, and specifically in the risk of cerebrovascular complications after adjusting for sex, age at disease diagnosis and traditional cardiovascular risk factors was disclosed in anti-CCP negative patients (HR = 0.54; 95%CI: 0.31–0.95; p = 0.032 and HR = 0.17; 95%CI: 0.04–0.78; p = 0.022, respectively). Conclusion Our results indicate a protective effect of the OPG CGA haplotype on cardiovascular risk, mainly due to a protective effect against cerebrovascular events in anti-CCP negative rheumatoid arthritis patients. PMID:25184828

Analysis of pulmonary sounds for the diagnosis of interstitial lung diseases secondary to rheumatoid arthritis.

PubMed

Pancaldi, Fabrizio; Sebastiani, Marco; Cassone, Giulia; Luppi, Fabrizio; Cerri, Stefania; Della Casa, Giovanni; Manfredi, Andreina

2018-05-01

The diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis is fundamental to improving their survival rate. In particular, the average survival time of patients affected by rheumatoid arthritis with pulmonary implications is approximately 3 years. The gold standard for confirming the diagnosis of this disease is computer tomography. However, it is very difficult to raise diagnosis suspicion because the symptoms of the disease are extremely common in elderly people. The detection of the so-called velcro crackle in lung sounds can effectively raise the suspicion of an interstitial disease and speed up diagnosis. However, this task largely relies on the experience of physicians and has not yet been standardized in clinical practice. The diagnosis of interstitial lung diseases based on thorax auscultation still represents an underexplored field in the study of rheumatoid arthritis. In this study, we investigate the problem of the automatic detection of velcro crackle in lung sounds. In practice, the patient is auscultated using a digital stethoscope and the lung sounds are saved to a file. The acquired digital data are then analysed using a suitably developed algorithm. In particular, the proposed solution relies on the empirical observation that the audio bandwidth associated with velcro crackle is larger than that associated with healthy breath sounds. Experimental results from a database of 70 patients affected by rheumatoid arthritis demonstrate that the developed tool can outperform specialized physicians in terms of diagnosing pulmonary disorders. The overall accuracy of the proposed solution is 90.0%, with negative and positive predictive values of 95.0% and 83.3%, respectively, whereas the reliability of physician diagnosis is in the range of 60-70%. The devised algorithm represents an enabling technology for a novel approach to the diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis. Copyright �

Detection of rheumatoid arthritis in humans by fluorescence imaging

NASA Astrophysics Data System (ADS)

Ebert, Bernd; Dziekan, Thomas; Weissbach, Carmen; Mahler, Marianne; Schirner, Michael; Berliner, Birgitt; Bauer, Daniel; Voigt, Jan; Berliner, Michael; Bahner, Malte L.; Macdonald, Rainer

2010-02-01

The blood pool agent indo-cyanine green (ICG) has been investigated in a prospective clinical study for detection of rheumatoid arthritis using fluorescence imaging. Temporal behavior as well as spatial distribution of fluorescence intensity are suited to differentiate healthy and inflamed finger joints after i.v. injection of an ICG bolus.

Total knee arthroplasty in a rheumatoid arthritic knee with large geode: a case report.

PubMed

Shih, H N; Hsu, K Y; Tan, C F; Hsueh, S; Hsu, R W

1997-09-01

Geodes (subchondral cysts) are a well-known manifestation of rheumatoid arthritis. Solitary cysts or cysts larger than 2 cm are not generally found in the knee joint of patients with rheumatoid arthritis (RA). We report a case of RA involving both knees with a giant geode over the right proximal tibia. Surgical treatment was performed including synovectomy, cyst enucleation and packing of autogenous bone chips followed by primary total knee arthroplasty. The postsurgical result was excellent with the knee restored to good function and complete healing of the cystic lesion.

Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis: common target, common therapies

PubMed Central

Hampel, Constanze; Anastasiadis, Panos Z.; Kallakury, Bhaskar; Uren, Aykut; Foley, David W; Brown, Milton L.; Shapiro, Lawrence; Brenner, Michael; Haigh, David; Byers, Stephen W.

2014-01-01

Cadherin-11 (CDH11), associated with epithelial to mesenchymal transformation in development, poor prognosis malignancies and cancer stem cells, is also a major therapeutic target in rheumatoid arthritis (RA). CDH11 expressing basal-like breast carcinomas and other CDH11 expressing malignancies exhibit poor prognosis. We show that CDH11 is increased early in breast cancer and ductal carcinoma in-situ. CDH11 knockdown and antibodies effective in RA slowed the growth of basal-like breast tumors and decreased proliferation and colony formation of breast, glioblastoma and prostate cancer cells. The repurposed arthritis drug celecoxib, which binds to CDH11, and other small molecules designed to bind CDH11 without inhibiting COX-2 preferentially affect the growth of CDH11 positive cancer cells in vitro and in animals. These data suggest that CDH11 is important for malignant progression, and is a therapeutic target in arthritis and cancer with the potential for rapid clinical translation PMID:24681547

The use of chimeric vimentin citrullinated peptides for the diagnosis of rheumatoid arthritis.

PubMed

Malakoutikhah, Morteza; Gómara, María J; Gómez-Puerta, José A; Sanmartí, Raimon; Haro, Isabel

2011-11-10

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and, in many cases, destruction of the joints. To prevent progressive and irreversible structural damage, early diagnosis of RA is of paramount importance. The present study addresses the search of new RA citrullinated antigens that could supplement or complement diagnostic/prognostic existing tests. With this aim, the epitope anticitrullinated vimentin antibody response was mapped using synthetic peptides. To improve the sensitivity/specificity balance, a vimentin peptide that was selected, and its cyclic analogue, were combined with fibrin- and filaggrin-related peptides to render chimeric peptides. Our findings highlight the putative application of these chimeric peptides for the design of RA diagnosis systems and imply that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported here (fibrin, vimentin, filaggrin) has a specific utility in the identification of a particular subset of RA patients.

The simulated early learning of cervical spine manipulation technique utilising mannequins.

PubMed

Chapman, Peter D; Stomski, Norman J; Losco, Barrett; Walker, Bruce F

2015-01-01

Trivial pain or minor soreness commonly follows neck manipulation and has been estimated at one in three treatments. In addition, rare catastrophic events can occur. Some of these incidents have been ascribed to poor technique where the neck is rotated too far. The aims of this study were to design an instrument to measure competency of neck manipulation in beginning students when using a simulation mannequin, and then examine the suitability of using a simulation mannequin to teach the early psychomotor skills for neck chiropractic manipulative therapy. We developed an initial set of questionnaire items and then used an expert panel to assess an instrument for neck manipulation competency among chiropractic students. The study sample comprised all 41 fourth year 2014 chiropractic students at Murdoch University. Students were randomly allocated into either a usual learning or mannequin group. All participants crossed over to undertake the alternative learning method after four weeks. A chi-square test was used to examine differences between groups in the proportion of students achieving an overall pass mark at baseline, four weeks, and eight weeks. This study was conducted between January and March 2014. We successfully developed an instrument of measurement to assess neck manipulation competency in chiropractic students. We then randomised 41 participants to first undertake either "usual learning" (n = 19) or "mannequin learning" (n = 22) for early neck manipulation training. There were no significant differences between groups in the overall pass rate at baseline (χ(2) = 0.10, p = 0.75), four weeks (χ(2) = 0.40, p = 0.53), and eight weeks (χ(2) = 0.07, p = 0.79). This study demonstrates that the use of a mannequin does not affect the manipulation competency grades of early learning students at short term follow up. Our findings have potentially important safety implications as the results indicate that students could initially

An exploratory study to determine whether infliximab modifies levels of rheumatoid factor and antibodies to cyclic citrullinated peptides in rheumatoid arthritis patients.

PubMed

Martínez-Estupiñán, Lina; Hernández-Flórez, Diana; Janta, Iustina; Ovalles-Bonilla, Juan Gabriel; Nieto, Juan Carlos; González-Fernández, Carlos M; Del Río, Tamara; Monteagudo, Indalecio; López-Longo, Francisco Javier; Naredo, Esperanza; Valor, Lara

2018-01-01

The aim of this study was to investigate the relationship between serum infliximab (IFX) levels and changes of RF and ACPA levels in patients with rheumatoid arthritis (RA). Enzyme-linked immunosorbent assays (ELISA) [Promonitor® IFX R1 (version 2) (Progenika Biopharma, Spain)] were used to measure drug levels and antidrug-antibodies (ADAb) in IFX RA-treated patients (n=19). Disease activity was assessed using DAS28. IgM rheumatoid factor (RF) and IgM, IgA and IgG anti-cyclic citrullinated peptide (ACPA) were determined through ELISA. A significant decrease in RF (p=0.01), ACPA IgG (p=0.007), IgM (p=0.01) and IgA (p=0.03) was observed in patients presenting adequate levels of serum IFX. No significant changes to RF or ACPA were observed in patients with undetectable IFX. Data from this study support the hypothesis that the anti-TNF antagonist IFX downregulates autoantibody levels in RA patients when IFX levels are detectable. Larger-scale studies need to be performed to establish RF and ACPA presence as therapeutic response predictive factors.

[Kidney involvement in rheumatoid arthritis].

PubMed

Icardi, A; Araghi, P; Ciabattoni, M; Romano, U; Lazzarini, P; Bianchi, G

2003-01-01

Rheumatoid Arthritis (RA) is a widespread disease and its renal involvement, relatively common, is clinically significant because worsens course and mortality of the primary disease. There is still no agreement on the prevalence of renal disorders in RA: data analysis originates from different sources, as death certificates, autopsies, clinical and laboratory findings and kidney biopsies, each with its limitations. Histoimmunological studies on bioptical specimens of patients with RA and kidney damage, led to clarify prevalent pathologies. In order of frequency: glomerulonephritis and amyloidosis (60-65% and 20-30% respectively), followed by acute or chronic interstitial nephritis. Kidney injury during RA includes secondary renal amyloidosis, nephrotoxic effects of antirheumatic drugs and nephropathies as extra-articular manifestations (rheumatoid nephropathy). Amyloidosis affects survival, increases morbidity and is the main cause of end stage renal disease in patients with RA and nephropathy. Strong association between RA activity and amyloidosis needs the use of immunosuppressive and combined therapies, to prevent this complication and reduce risk of dialysis. Long-lasting and combined RA pharmacotherapy involves various renal side effects. In this review we describe NSAIDs and DMARDs (Disease-Modifying Antirheumatic Drugs) nephrotoxicity, particularly by gold compounds, D-penicillamine, cyclosporine A and methotrexate. Rare cases of IgA glomerulonephritis during immunomodulating therapy with leflunomide and TNF blocking receptor (etanercept) are reported; real clinical significance of this drug-related nephropathy will be established by development of RA treatment. In RA nephropathies, mesangial glomerulonephritis is the most frequent histological lesion (35-60 % out of biopsies from patients with urinary abnormalities and/or kidney impairment), followed by minimal change glomerulopathy (3-14%) and p-ANCA positive necrotizing crescentic glomerulonephritis.